@article {pmid37264211, year = {2023}, author = {Lamolle, G and Simón, D and Iriarte, A and Musto, H}, title = {Main Factors Shaping Amino Acid Usage Across Evolution.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {37264211}, issn = {1432-1432}, abstract = {The standard genetic code determines that in most species, including viruses, there are 20 amino acids that are coded by 61 codons, while the other three codons are stop triplets. Considering the whole proteome each species features its own amino acid frequencies, given the slow rate of change, closely related species display similar GC content and amino acids usage. In contrast, distantly related species display different amino acid frequencies. Furthermore, within certain multicellular species, as mammals, intragenomic differences in the usage of amino acids are evident. In this communication, we shall summarize some of the most prominent and well-established factors that determine the differences found in the amino acid usage, both across evolution and intragenomically.}, } @article {pmid37264002, year = {2023}, author = {Galand, PE and Ruscheweyh, HJ and Salazar, G and Hochart, C and Henry, N and Hume, BCC and Oliveira, PH and Perdereau, A and Labadie, K and Belser, C and Boissin, E and Romac, S and Poulain, J and Bourdin, G and Iwankow, G and Moulin, C and Armstrong, EJ and Paz-García, DA and Ziegler, M and Agostini, S and Banaigs, B and Boss, E and Bowler, C and de Vargas, C and Douville, E and Flores, M and Forcioli, D and Furla, P and Gilson, E and Lombard, F and Pesant, S and Reynaud, S and Thomas, OP and Troublé, R and Zoccola, D and Voolstra, CR and Thurber, RV and Sunagawa, S and Wincker, P and Allemand, D and Planes, S}, title = {Diversity of the Pacific Ocean coral reef microbiome.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3039}, pmid = {37264002}, issn = {2041-1723}, abstract = {Coral reefs are among the most diverse ecosystems on Earth. They support high biodiversity of multicellular organisms that strongly rely on associated microorganisms for health and nutrition. However, the extent of the coral reef microbiome diversity and its distribution at the oceanic basin-scale remains to be explored. Here, we systematically sampled 3 coral morphotypes, 2 fish species, and planktonic communities in 99 reefs from 32 islands across the Pacific Ocean, to assess reef microbiome composition and biogeography. We show a very large richness of reef microorganisms compared to other environments, which extrapolated to all fishes and corals of the Pacific, approximates the current estimated total prokaryotic diversity for the entire Earth. Microbial communities vary among and within the 3 animal biomes (coral, fish, plankton), and geographically. For corals, the cross-ocean patterns of diversity are different from those known for other multicellular organisms. Within each coral morphotype, community composition is always determined by geographic distance first, both at the island and across ocean scale, and then by environment. Our unprecedented sampling effort of coral reef microbiomes, as part of the Tara Pacific expedition, provides new insight into the global microbial diversity, the factors driving their distribution, and the biocomplexity of reef ecosystems.}, } @article {pmid37256696, year = {2023}, author = {Blomme, J and Wichard, T and Jacobs, TB and De Clerck, O}, title = {Ulva: An emerging green seaweed model for systems biology.}, journal = {Journal of phycology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpy.13341}, pmid = {37256696}, issn = {1529-8817}, abstract = {Green seaweeds exhibit a wide range of morphologies and occupy various ecological niches, spanning from freshwater to marine and terrestrial habitats. These organisms, which predominantly belong to the class Ulvophyceae, showcase a remarkable instance of parallel evolution toward complex multicellularity and macroscopic thalli in the Viridiplantae lineage. Within the green seaweeds, several Ulva species ("sea lettuce") are model organisms for studying carbon assimilation, interactions with bacteria, life cycle progression, and morphogenesis. Ulva species are also notorious for their fast growth and capacity to dominate nutrient-rich, anthropogenically disturbed coastal ecosystems during "green tide" blooms. From an economic perspective, Ulva has garnered increasing attention as a promising feedstock for the production of food, feed, and biobased products, also as a means of removing excess nutrients from the environment. We propose that Ulva is poised to further develop as a model in green seaweed research. In this perspective, we focus explicitly on Ulva mutabilis/compressa as a model species and highlight the molecular data and tools that are currently available or in development. We discuss several areas that will benefit from future research or where exciting new developments have been reported in other Ulva species.}, } @article {pmid37256290, year = {2023}, author = {Jiang, P and Kreitman, M and Reinitz, J}, title = {The effect of mutational robustness on the evolvability of multicellular organisms and eukaryotic cells.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.14180}, pmid = {37256290}, issn = {1420-9101}, support = {R01 OD010936/CD/ODCDC CDC HHS/United States ; }, abstract = {Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity and other classes of hierarchical organization on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which individuals with explicit genotype and a hierarchical phenotype representing multicellularity evolve. Robustness is described by a single real number between zero and one which emerges from the genotype-phenotype map. We find that high robustness is favoured in constant environments, and lower robustness is favoured after environmental change. Multicellularity and hierarchical organization severely constrain robustness: peak evolvability occurs at an absolute level of robustness of about 0.99 compared with values of about 0.5 in a classical neutral network model. These constraints result in a sharp peak of evolvability in which the maximum is set by the fact that the fixation of adaptive mutations becomes more improbable as robustness decreases. When robustness is put under genetic control, robustness levels leading to maximum evolvability are selected for, but maximal relative fitness appears to require recombination.}, } @article {pmid37253212, year = {2023}, author = {Hoch, NC}, title = {Tissue specificity of DNA damage and repair.}, journal = {Physiology (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiol.00006.2023}, pmid = {37253212}, issn = {1548-9221}, abstract = {DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution. Nonetheless, the emergence of multicellular organisms led to profound differences in cellular context and physiology, leading to large variations in the predominant sources of DNA damage between different cell types, and in the relative contribution of different DNA repair pathways towards genome maintenance in different tissues. While we continue to make large strides into understanding how individual DNA repair mechanisms operate on a molecular level, much less attention is given to these cell type-specific differences. This short review aims to provide a broad overview of DNA damage and repair mechanism to non-specialists, and to highlight some fundamental open questions in tissue and cell-type-specificity of these processes, which may have profound implications for our understanding of important pathophysiological processes such as cancer, neurodegeneration and aging.}, } @article {pmid37247371, year = {2023}, author = {McCourt, RM and Lewis, LA and Strother, PK and Delwiche, CF and Wickett, NJ and de Vries, J and Bowman, JL}, title = {Green land: Multiple perspectives on green algal evolution and the earliest land plants.}, journal = {American journal of botany}, volume = {110}, number = {5}, pages = {e16175}, doi = {10.1002/ajb2.16175}, pmid = {37247371}, issn = {1537-2197}, abstract = {Green plants, broadly defined as green algae and the land plants (together, Viridiplantae), constitute the primary eukaryotic lineage that successfully colonized Earth's emergent landscape. Members of various clades of green plants have independently made the transition from fully aquatic to subaerial habitats many times throughout Earth's history. The transition, from unicells or simple filaments to complex multicellular plant bodies with functionally differentiated tissues and organs, was accompanied by innovations built upon a genetic and phenotypic toolkit that have served aquatic green phototrophs successfully for at least a billion years. These innovations opened an enormous array of new, drier places to live on the planet and resulted in a huge diversity of land plants that have dominated terrestrial ecosystems over the past 500 million years. This review examines the greening of the land from several perspectives, from paleontology to phylogenomics, to water stress responses and the genetic toolkit shared by green algae and plants, to the genomic evolution of the sporophyte generation. We summarize advances on disparate fronts in elucidating this important event in the evolution of the biosphere and the lacunae in our understanding of it. We present the process not as a step-by-step advancement from primitive green cells to an inevitable success of embryophytes, but rather as a process of adaptations and exaptations that allowed multiple clades of green plants, with various combinations of morphological and physiological terrestrialized traits, to become diverse and successful inhabitants of the land habitats of Earth.}, } @article {pmid37239953, year = {2023}, author = {Kozlov, AP}, title = {Carcino-Evo-Devo, A Theory of the Evolutionary Role of Hereditary Tumors.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, doi = {10.3390/ijms24108611}, pmid = {37239953}, issn = {1422-0067}, abstract = {A theory of the evolutionary role of hereditary tumors, or the carcino-evo-devo theory, is being developed. The main hypothesis of the theory, the hypothesis of evolution by tumor neofunctionalization, posits that hereditary tumors provided additional cell masses during the evolution of multicellular organisms for the expression of evolutionarily novel genes. The carcino-evo-devo theory has formulated several nontrivial predictions that have been confirmed in the laboratory of the author. It also suggests several nontrivial explanations of biological phenomena previously unexplained by the existing theories or incompletely understood. By considering three major types of biological development-individual, evolutionary, and neoplastic development-within one theoretical framework, the carcino-evo-devo theory has the potential to become a unifying biological theory.}, } @article {pmid37233789, year = {2023}, author = {Wu, N and Wei, L and Zhu, Z and Liu, Q and Li, K and Mao, F and Qiao, J and Zhao, X}, title = {Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.}, journal = {Protein & cell}, volume = {}, number = {}, pages = {}, doi = {10.1093/procel/pwad032}, pmid = {37233789}, issn = {1674-8018}, abstract = {Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.}, } @article {pmid37232711, year = {2023}, author = {Wang, X and Zhang, Y and Xie, M and Wang, Z and Qiao, H}, title = {Temperature-Promoted Giant Unilamellar Vesicle (GUV) Aggregation: A Way of Multicellular Formation.}, journal = {Current issues in molecular biology}, volume = {45}, number = {5}, pages = {3757-3771}, doi = {10.3390/cimb45050242}, pmid = {37232711}, issn = {1467-3045}, abstract = {The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.}, } @article {pmid37223732, year = {2023}, author = {Hengge, R and Pruteanu, M and Stülke, J and Tschowri, N and Turgay, K}, title = {Recent advances and perspectives in nucleotide second messenger signaling in bacteria.}, journal = {microLife}, volume = {4}, number = {}, pages = {uqad015}, pmid = {37223732}, issn = {2633-6693}, abstract = {Nucleotide second messengers act as intracellular 'secondary' signals that represent environmental or cellular cues, i.e. the 'primary' signals. As such, they are linking sensory input with regulatory output in all living cells. The amazing physiological versatility, the mechanistic diversity of second messenger synthesis, degradation, and action as well as the high level of integration of second messenger pathways and networks in prokaryotes has only recently become apparent. In these networks, specific second messengers play conserved general roles. Thus, (p)ppGpp coordinates growth and survival in response to nutrient availability and various stresses, while c-di-GMP is the nucleotide signaling molecule to orchestrate bacterial adhesion and multicellularity. c-di-AMP links osmotic balance and metabolism and that it does so even in Archaea may suggest a very early evolutionary origin of second messenger signaling. Many of the enzymes that make or break second messengers show complex sensory domain architectures, which allow multisignal integration. The multiplicity of c-di-GMP-related enzymes in many species has led to the discovery that bacterial cells are even able to use the same freely diffusible second messenger in local signaling pathways that can act in parallel without cross-talking. On the other hand, signaling pathways operating with different nucleotides can intersect in elaborate signaling networks. Apart from the small number of common signaling nucleotides that bacteria use for controlling their cellular "business," diverse nucleotides were recently found to play very specific roles in phage defense. Furthermore, these systems represent the phylogenetic ancestors of cyclic nucleotide-activated immune signaling in eukaryotes.}, } @article {pmid37220133, year = {2023}, author = {Lipińska-Zubrycka, L and Grochowski, M and Bähler, J and Małecki, M}, title = {Pervasive mRNA uridylation in fission yeast is catalysed by both Cid1 and Cid16 terminal uridyltransferases.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0285576}, doi = {10.1371/journal.pone.0285576}, pmid = {37220133}, issn = {1932-6203}, abstract = {Messenger RNA uridylation is pervasive and conserved among eukaryotes, but the consequences of this modification for mRNA fate are still under debate. Utilising a simple model organism to study uridylation may facilitate efforts to understand the cellular function of this process. Here we demonstrate that uridylation can be detected using simple bioinformatics approach. We utilise it to unravel widespread transcript uridylation in fission yeast and demonstrate the contribution of both Cid1 and Cid16, the only two annotated terminal uridyltransferases (TUT-ases) in this yeast. To detect uridylation in transcriptome data, we used a RNA-sequencing (RNA-seq) library preparation protocol involving initial linker ligation to fragmented RNA-an approach borrowed from small RNA sequencing that was commonly used in older RNA-seq protocols. We next explored the data to detect uridylation marks. Our analysis show that uridylation in yeast is pervasive, similarly to the one in multicellular organisms. Importantly, our results confirm the role of the cytoplasmic uridyltransferase Cid1 as the primary uridylation catalyst. However, we also observed an auxiliary role of the second uridyltransferase, Cid16. Thus both fission yeast uridyltransferases are involved in mRNA uridylation. Intriguingly, we found no physiological phenotype of the single and double deletion mutants of cid1 and cid16 and only minimal impact of uridylation on steady-state mRNA levels. Our work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and we demonstrate that it is possible to detect uridylation marks in RNA-seq data without the need for specific methodologies.}, } @article {pmid37219671, year = {2023}, author = {Gmiter, D and Pacak, I and Nawrot, S and Czerwonka, G and Kaca, W}, title = {Genomes comparison of two Proteus mirabilis clones showing varied swarming ability.}, journal = {Molecular biology reports}, volume = {}, number = {}, pages = {}, pmid = {37219671}, issn = {1573-4978}, abstract = {BACKGROUND: Proteus mirabilis is a Gram-negative bacteria most noted for its involvement with catheter-associated urinary tract infections. It is also known for its multicellular migration over solid surfaces, referred to as 'swarming motility'. Here we analyzed the genomic sequences of two P. mirabilis isolates, designated K38 and K39, which exhibit varied swarming ability.

METHODS AND RESULTS: The isolates genomes were sequenced using Illumina NextSeq sequencer, resulting in about 3.94 Mbp, with a GC content of 38.6%, genomes. Genomes were subjected for in silico comparative investigation. We revealed that, despite a difference in swarming motility, the isolates showed high genomic relatedness (up to 100% ANI similarity), suggesting that one of the isolates probably originated from the other.

CONCLUSIONS: The genomic sequences will allow us to investigate the mechanism driving this intriguing phenotypic heterogeneity between closely related P. mirabilis isolates. Phenotypic heterogeneity is an adaptive strategy of bacterial cells to several environmental pressures. It is also an important factor related to their pathogenesis. Therefore, the availability of these genomic sequences will facilitate studies that focus on the host-pathogen interactions during catheter-associated urinary tract infections.}, } @article {pmid37211257, year = {2023}, author = {Fields, C and Levin, M}, title = {Regulative development as a model for origin of life and artificial life studies.}, journal = {Bio Systems}, volume = {}, number = {}, pages = {104927}, doi = {10.1016/j.biosystems.2023.104927}, pmid = {37211257}, issn = {1872-8324}, abstract = {Using the formal framework of the Free Energy Principle, we show how generic thermodynamic requirements on bidirectional information exchange between a system and its environment can generate complexity. This leads to the emergence of hierarchical computational architectures in systems that operate sufficiently far from thermal equilibrium. In this setting, the environment of any system increases its ability to predict system behavior by "engineering" the system towards increased morphological complexity and hence larger-scale, more macroscopic behaviors. When seen in this light, regulative development becomes an environmentally-driven process in which "parts" are assembled to produce a system with predictable behavior. We suggest on this basis that life is thermodynamically favorable and that, when designing artificial living systems, human engineers are acting like a generic "environment".}, } @article {pmid37205856, year = {2023}, author = {Hu, K and Le Vo, KL and Wang, F and Zhang, X and Gu, C and Fang, N and Phan, NTN and Ewing, AG}, title = {Single Exosome Amperometric Measurements Reveal Encapsulation of Chemical Messengers for Intercellular Communication.}, journal = {Journal of the American Chemical Society}, volume = {}, number = {}, pages = {}, doi = {10.1021/jacs.3c02844}, pmid = {37205856}, issn = {1520-5126}, abstract = {In multicellular organisms, cells typically communicate by sending and receiving chemical signals. Chemical messengers involved in the exocytosis of neuroendocrine cells or neurons are generally assumed to only originate from the fusing of intracellular large dense core vesicles (LDCVs) or synaptic vesicles with the cellular membrane following stimulation. Accumulated evidence suggests that exosomes─one of the main extracellular vesicles (EVs)─carrying cell-dependent DNA, mRNA, proteins, etc., play an essential role in cellular communication. Due to experimental limitations, it has been difficult to monitor the real-time release of individual exosomes; this restricts a comprehensive understanding of the basic molecular mechanisms and the functions of exosomes. In this work, we introduce amperometry with microelectrodes to capture the dynamic release of single exosomes from a single living cell, distinguish them from other EVs, and differentiate the molecules inside exosomes and those secreted from LDCVs. We show that, similar to many LDCVs and synaptic vesicles, exosomes released by neuroendocrine cells also contain catecholamine transmitters. This finding reveals a different mode of chemical communication via exosome-encapsulated chemical messengers and a potential interconnection between the two release pathways, changing the canonical view of exocytosis of neuroendocrine cells and possibly neurons. This defines a new mechanism for chemical communication at the fundamental level and opens new avenues in the research of the molecular biology of exosomes in the neuroendocrine and central nervous systems.}, } @article {pmid37202179, year = {2023}, author = {Sobala, ŁF}, title = {Evolution and phylogenetic distribution of endo-α-mannosidase.}, journal = {Glycobiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/glycob/cwad041}, pmid = {37202179}, issn = {1460-2423}, abstract = {While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. It is unique as the only endo-acting mannosidase found in this organelle. Relatively little is known about its origins and evolutionary history; so far it was reported to occur only in vertebrates. In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. The endomannosidase was found to be more widely distributed in animals and other eukaryotes. The protein motif changes in context of the canonical animal enzyme were tracked. Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. Finally, a framework where N-glycosylation co-evolved with complex multicellularity is described. A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. This systematic analysis of the endomannosidase evolution is one step towards this goal.}, } @article {pmid37195672, year = {2023}, author = {Fernandes, J}, title = {Virus-Induced Lysis of Tumor and Other Pathogenic Unicellular Entities and Its Potential to Treat Leishmaniasis.}, journal = {DNA and cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1089/dna.2023.0048}, pmid = {37195672}, issn = {1557-7430}, abstract = {This article is focused on the main pathways used by viruses to achieve infection and lysis of unicellular eukaryotes described as pathogenic for multicellular organisms. In light of the recent discussions on how tumor cells exhibit unicellular behavior, highly malignant cells can be considered as another unicellular pathogenic entity, but with endogenous origin. Thus, a comparative panel of viral lysis of exogenous pathogenic unicellular eukaryotes such as Acanthamoeba sp., yeast, and tumors is presented. The important intracellular parasite Leishmania sp is also presented, which, in contrast, has its virulence improved by viral infections. The possible exploitation of viral-mediated eukaryotic cell lysis to overcome infections of Leishmania sp is discussed.}, } @article {pmid36728830, year = {2023}, author = {Mawaribuchi, S and Shimomura, O and Oda, T and Hiemori, K and Shimizu, K and Yamase, K and Date, M and Tateno, H}, title = {rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma.}, journal = {Glycobiology}, volume = {33}, number = {4}, pages = {342-352}, doi = {10.1093/glycob/cwad009}, pmid = {36728830}, issn = {1460-2423}, abstract = {Early detection is urgently needed to improve the patient's pancreatic ductal adenocarcinoma (PDAC) survival. Previously, we identified a novel tumor-associated glycan, H-type3, which is expressed on PDAC cells and is detected by rBC2LCN (recombinant N-terminal domain of BC2L-C identified from Burkholderia cenocepacia) lectin. Here, we identified that SERPINA3 is an rBC2LCN-reactive glycoprotein (BC2-S3) secreted from PDAC cells into the blood in patients with PDAC by liquid chromatography-tandem mass spectrometry analysis and lectin blotting. In immune staining, BC2-S3 was detected specifically in the tumor but not in normal tissues of PDAC. Lectin-ELISA was then developed to measure the serum level of BC2-S3 in healthy control (HC, n = 99) and patients with PDAC (n = 88). BC2-S3 exhibited higher in patients with PDAC than in those with HC. BC2-S3 showed similar diagnostic performance in all stages of PDAC (stages IA-IV, true positive rate = 76.1%, true negative rate = 81.8%) to CA19-9 (72.7%, 75.8%). Remarkably, BC2-S3 showed a significantly higher detection rate (89.7%) for early stage PDAC (IA-IIA) than CA19-9 (62.1%, P = 0.029). The combination of BC2-S3 and CA19-9 further improved the diagnostic ability for all stages of PDAC (81.8%, 87.9%). In conclusion, BC2-S3 is a glycobiomarker candidate for PDAC.}, } @article {pmid37183897, year = {2023}, author = {Kaucka, M}, title = {Cis-regulatory landscapes in the evolution and development of the mammalian skull.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1880}, pages = {20220079}, doi = {10.1098/rstb.2022.0079}, pmid = {37183897}, issn = {1471-2970}, abstract = {Extensive morphological variation found in mammals reflects the wide spectrum of their ecological adaptations. The highest morphological diversity is present in the craniofacial region, where geometry is mainly dictated by the bony skull. Mammalian craniofacial development represents complex multistep processes governed by numerous conserved genes that require precise spatio-temporal control. A central question in contemporary evolutionary biology is how a defined set of conserved genes can orchestrate formation of fundamentally different structures, and therefore how morphological variability arises. In principle, differential gene expression patterns during development are the source of morphological variation. With the emergence of multicellular organisms, precise regulation of gene expression in time and space is attributed to cis-regulatory elements. These elements contribute to higher-order chromatin structure and together with trans-acting factors control transcriptional landscapes that underlie intricate morphogenetic processes. Consequently, divergence in cis-regulation is believed to rewire existing gene regulatory networks and form the core of morphological evolution. This review outlines the fundamental principles of the genetic code and genomic regulation interplay during development. Recent work that deepened our comprehension of cis-regulatory element origin, divergence and function is presented here to illustrate the state-of-the-art research that uncovered the principles of morphological novelty. This article is part of the theme issue 'The mammalian skull: development, structure and function'.}, } @article {pmid37176080, year = {2023}, author = {Suwannachuen, N and Leetanasaksakul, K and Roytrakul, S and Phaonakrop, N and Thaisakun, S and Roongsattham, P and Jantasuriyarat, C and Sanevas, N and Sirikhachornkit, A}, title = {Palmelloid Formation and Cell Aggregation Are Essential Mechanisms for High Light Tolerance in a Natural Strain of Chlamydomonas reinhardtii.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, doi = {10.3390/ijms24098374}, pmid = {37176080}, issn = {1422-0067}, abstract = {Photosynthetic organisms, such as higher plants and algae, require light to survive. However, an excessive amount of light can be harmful due to the production of reactive oxygen species (ROS), which cause cell damage and, if it is not effectively regulated, cell death. The study of plants' responses to light can aid in the development of methods to improve plants' growth and productivity. Due to the multicellular nature of plants, there may be variations in the results based on plant age and tissue type. Chlamydomonas reinhardtii, a unicellular green alga, has also been used as a model organism to study photosynthesis and photoprotection. Nonetheless, the majority of the research has been conducted with strains that have been consistently utilized in laboratories and originated from the same source. Despite the availability of many field isolates of this species, very few studies have compared the light responses of field isolates. This study examined the responses of two field isolates of Chlamydomonas to high light stress. The light-tolerant strain, CC-4414, managed reactive oxygen species (ROS) slightly better than the sensitive strain, CC-2344, did. The proteomic data of cells subjected to high light revealed cellular modifications of the light-tolerant strain toward membrane proteins. The morphology of cells under light stress revealed that this strain utilized the formation of palmelloid structures and cell aggregation to shield cells from excessive light. As indicated by proteome data, morphological modifications occur simultaneously with the increase in protein degradation and autophagy. By protecting cells from stress, cells are able to continue to upregulate ROS management mechanisms and prevent cell death. This is the first report of palmelloid formation in Chlamydomonas under high light stress.}, } @article {pmid37173684, year = {2023}, author = {Foo, YZ and Lagisz, M and O'Dea, RE and Nakagawa, S}, title = {The influence of immune challenges on the mean and variance in reproductive investment: a meta-analysis of the terminal investment hypothesis.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {107}, pmid = {37173684}, issn = {1741-7007}, abstract = {Finding the optimal balance between survival and reproduction is a central puzzle in life-history theory. The terminal investment hypothesis predicts that when individuals encounter a survival threat that compromises future reproductive potential, they will increase immediate reproductive investment to maximise fitness. Despite decades of research on the terminal investment hypothesis, findings remain mixed. We examined the terminal investment hypothesis with a meta-analysis of studies that measured reproductive investment of multicellular iteroparous animals after a non-lethal immune challenge. We had two main aims. The first was to investigate whether individuals, on average, increase reproductive investment in response to an immune threat, as predicted by the terminal investment hypothesis. We also examined whether such responses vary adaptively on factors associated with the amount of reproductive opportunities left (residual reproductive value) in the individuals, as predicted by the terminal investment hypothesis. The second was to provide a quantitative test of a novel prediction based on the dynamic threshold model: that an immune threat increases between-individual variance in reproductive investment. Our results provided some support for our hypotheses. Older individuals, who are expected to have lower residual reproductive values, showed stronger mean terminal investment response than younger individuals. In terms of variance, individuals showed a divergence in responses, leading to an increase in variance. This increase in variance was especially amplified in longer-living species, which was consistent with our prediction that individuals in longer-living species should respond with greater individual variation due to increased phenotypic plasticity. We find little statistical evidence of publication bias. Together, our results highlight the need for a more nuanced view on the terminal investment hypothesis and a greater focus on the factors that drive individual responses.}, } @article {pmid37165189, year = {2023}, author = {Bozdag, GO and Zamani-Dahaj, SA and Day, TC and Kahn, PC and Burnetti, AJ and Lac, DT and Tong, K and Conlin, PL and Balwani, AH and Dyer, EL and Yunker, PJ and Ratcliff, WC}, title = {De novo evolution of macroscopic multicellularity.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {37165189}, issn = {1476-4687}, abstract = {While early multicellular lineages necessarily started out as relatively simple groups of cells, little is known about how they became Darwinian entities capable of sustained multicellular evolution[1-3]. Here we investigate this with a multicellularity long-term evolution experiment, selecting for larger group size in the snowflake yeast (Saccharomyces cerevisiae) model system. Given the historical importance of oxygen limitation[4], our ongoing experiment consists of three metabolic treatments[5]-anaerobic, obligately aerobic and mixotrophic yeast. After 600 rounds of selection, snowflake yeast in the anaerobic treatment group evolved to be macroscopic, becoming around 2 × 10[4] times larger (approximately mm scale) and about 10[4]-fold more biophysically tough, while retaining a clonal multicellular life cycle. This occurred through biophysical adaptation-evolution of increasingly elongate cells that initially reduced the strain of cellular packing and then facilitated branch entanglements that enabled groups of cells to stay together even after many cellular bonds fracture. By contrast, snowflake yeast competing for low oxygen[5] remained microscopic, evolving to be only around sixfold larger, underscoring the critical role of oxygen levels in the evolution of multicellular size. Together, this research provides unique insights into an ongoing evolutionary transition in individuality, showing how simple groups of cells overcome fundamental biophysical limitations through gradual, yet sustained, multicellular evolution.}, } @article {pmid37160092, year = {2023}, author = {Conlin, PL and Ratcliff, WC}, title = {Evolution: Understanding the origins of facultative multicellular life cycles.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {R356-R358}, doi = {10.1016/j.cub.2023.03.065}, pmid = {37160092}, issn = {1879-0445}, abstract = {Multicellular organisms exhibit a fascinating diversity of life cycles, but little is known about the factors governing life-cycle evolution. New studies of wild yeast and cyanobacteria provide insight into how and why facultative multicellular life cycles arise.}, } @article {pmid37157910, year = {2023}, author = {Pradeu, T and Daignan-Fornier, B and Ewald, A and Germain, PL and Okasha, S and Plutynski, A and Benzekry, S and Bertolaso, M and Bissell, M and Brown, JS and Chin-Yee, B and Chin-Yee, I and Clevers, H and Cognet, L and Darrason, M and Farge, E and Feunteun, J and Galon, J and Giroux, E and Green, S and Gross, F and Jaulin, F and Knight, R and Laconi, E and Larmonier, N and Maley, C and Mantovani, A and Moreau, V and Nassoy, P and Rondeau, E and Santamaria, D and Sawai, CM and Seluanov, A and Sepich-Poore, GD and Sisirak, V and Solary, E and Yvonnet, S and Laplane, L}, title = {Reuniting philosophy and science to advance cancer research.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12971}, pmid = {37157910}, issn = {1469-185X}, abstract = {Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer.}, } @article {pmid37156924, year = {2023}, author = {Levin, M}, title = {Darwin's agential materials: evolutionary implications of multiscale competency in developmental biology.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {80}, number = {6}, pages = {142}, pmid = {37156924}, issn = {1420-9071}, abstract = {A critical aspect of evolution is the layer of developmental physiology that operates between the genotype and the anatomical phenotype. While much work has addressed the evolution of developmental mechanisms and the evolvability of specific genetic architectures with emergent complexity, one aspect has not been sufficiently explored: the implications of morphogenetic problem-solving competencies for the evolutionary process itself. The cells that evolution works with are not passive components: rather, they have numerous capabilities for behavior because they derive from ancestral unicellular organisms with rich repertoires. In multicellular organisms, these capabilities must be tamed, and can be exploited, by the evolutionary process. Specifically, biological structures have a multiscale competency architecture where cells, tissues, and organs exhibit regulative plasticity-the ability to adjust to perturbations such as external injury or internal modifications and still accomplish specific adaptive tasks across metabolic, transcriptional, physiological, and anatomical problem spaces. Here, I review examples illustrating how physiological circuits guiding cellular collective behavior impart computational properties to the agential material that serves as substrate for the evolutionary process. I then explore the ways in which the collective intelligence of cells during morphogenesis affect evolution, providing a new perspective on the evolutionary search process. This key feature of the physiological software of life helps explain the remarkable speed and robustness of biological evolution, and sheds new light on the relationship between genomes and functional anatomical phenotypes.}, } @article {pmid37155901, year = {2023}, author = {Cooney, DB and Levin, SA and Mori, Y and Plotkin, JB}, title = {Evolutionary dynamics within and among competing groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {20}, pages = {e2216186120}, doi = {10.1073/pnas.2216186120}, pmid = {37155901}, issn = {1091-6490}, abstract = {Biological and social systems are structured at multiple scales, and the incentives of individuals who interact in a group may diverge from the collective incentive of the group as a whole. Mechanisms to resolve this tension are responsible for profound transitions in evolutionary history, including the origin of cellular life, multicellular life, and even societies. Here, we synthesize a growing literature that extends evolutionary game theory to describe multilevel evolutionary dynamics, using nested birth-death processes and partial differential equations to model natural selection acting on competition within and among groups of individuals. We analyze how mechanisms known to promote cooperation within a single group-including assortment, reciprocity, and population structure-alter evolutionary outcomes in the presence of competition among groups. We find that population structures most conducive to cooperation in multiscale systems can differ from those most conducive within a single group. Likewise, for competitive interactions with a continuous range of strategies we find that among-group selection may fail to produce socially optimal outcomes, but it can nonetheless produce second-best solutions that balance individual incentives to defect with the collective incentives for cooperation. We conclude by describing the broad applicability of multiscale evolutionary models to problems ranging from the production of diffusible metabolites in microbes to the management of common-pool resources in human societies.}, } @article {pmid37153718, year = {2023}, author = {W B, M and A S, R and P, M and F, B}, title = {Cellular and Natural Viral Engineering in Cognition-Based Evolution.}, journal = {Communicative & integrative biology}, volume = {16}, number = {1}, pages = {2196145}, pmid = {37153718}, issn = {1942-0889}, abstract = {Neo-Darwinism conceptualizes evolution as the continuous succession of predominately random genetic variations disciplined by natural selection. In that frame, the primary interaction between cells and the virome is relegated to host-parasite dynamics governed by selective influences. Cognition-Based Evolution regards biological and evolutionary development as a reciprocating cognition-based informational interactome for the protection of self-referential cells. To sustain cellular homeorhesis, cognitive cells collaborate to assess the validity of ambiguous biological information. That collective interaction involves coordinate measurement, communication, and active deployment of resources as Natural Cellular Engineering. These coordinated activities drive multicellularity, biological development, and evolutionary change. The virome participates as the vital intercessory among the cellular domains to ensure their shared permanent perpetuation. The interactions between the virome and the cellular domains represent active virocellular cross-communications for the continual exchange of resources. Modular genetic transfers between viruses and cells carry bioactive potentials. Those exchanges are deployed as nonrandom flexible tools among the domains in their continuous confrontation with environmental stresses. This alternative framework fundamentally shifts our perspective on viral-cellular interactions, strengthening established principles of viral symbiogenesis. Pathogenesis can now be properly appraised as one expression of a range of outcomes between cells and viruses within a larger conceptual framework of Natural Viral Engineering as a co-engineering participant with cells. It is proposed that Natural Viral Engineering should be viewed as a co-existent facet of Natural Cellular Engineering within Cognition-Based Evolution.}, } @article {pmid37141807, year = {2023}, author = {Tsai, HH and Wang, J and Geldner, N and Zhou, F}, title = {Spatiotemporal control of root immune responses during microbial colonization.}, journal = {Current opinion in plant biology}, volume = {74}, number = {}, pages = {102369}, doi = {10.1016/j.pbi.2023.102369}, pmid = {37141807}, issn = {1879-0356}, abstract = {The entire evolutionary trajectory of plants towards large and complex multi-cellular organisms has been accompanied by incessant interactions with omnipresent unicellular microbes. This led to the evolution of highly complex microbial communities, whose members display the entire spectrum of pathogenic to mutualistic behaviors. Plant roots are dynamic, fractally growing organs and even small Arabidopsis roots harbor millions of individual microbes of diverse taxa. It is evident that microbes at different positions on a root surface could experience fundamentally different environments, which, moreover, rapidly change over time. Differences in spatial scales between microbes and roots compares to humans and the cities they inhabit. Such considerations make it evident that mechanisms of root-microbe interactions can only be understood if analyzed at relevant spatial and temporal scales. This review attempts to provide an overview of the rapid recent progress that has been made in mapping and manipulating plant damage and immune responses at cellular resolution, as well as in visualizing bacterial communities and their transcriptional activities. We further discuss the impact that such approaches will have for a more predictive understanding of root-microbe interactions.}, } @article {pmid37140022, year = {2023}, author = {Krasovec, M and Hoshino, M and Zheng, M and Lipinska, AP and Coelho, SM}, title = {Low spontaneous mutation rate in complex multicellular eukaryotes with a haploid-diploid life cycle.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad105}, pmid = {37140022}, issn = {1537-1719}, abstract = {The spontaneous mutation rate µ is a crucial parameter to understand evolution and biodiversity. Mutation rates are highly variable across species, suggesting that µ is susceptible to selection and drift and that species life cycle and life history may impact its evolution. In particular, asexual reproduction and haploid selection are expected to affect mutation rate, but very little empirical data is available to test this expectation. Here, we sequence 30 genomes of a parent-offspring pedigree in the model brown alga Ectocarpus sp.7, and 137 genomes of an interspecific cross of the closely related brown alga Scytosiphon to have access to the spontaneous mutation rate of representative organisms of a complex multicellular eukaryotic lineage outside animals and plants, and to evaluate the potential impact of life cycle on mutation rate. Brown algae alternate between a haploid and a diploid stage, both multicellular and free living, and utilize both sexual and asexual reproduction. They are therefore excellent models to empirically test expectations of the effect of asexual reproduction and haploid selection on mutation rate evolution. We estimate that Ectocarpus has a base substitution rate of µbs = 4.07 × 10-10 per site per generation, whereas the Scytosiphon interspecific cross had µbs =1.22 × 10-9. Overall, our estimations suggest that these brown algae, despite being multicellular complex eukaryotes, have unusually low mutation rates. In Ectocarpus, effective population size (Ne) could not entirely explain the low µb. We propose that the haploid-diploid life cycle, combined with extensive asexual reproduction may be additional key drivers of mutation rate.}, } @article {pmid37123368, year = {2023}, author = {Nikitin, MA and Romanova, DY and Borman, SI and Moroz, LL}, title = {Amino acids integrate behaviors in nerveless placozoans.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1125624}, pmid = {37123368}, issn = {1662-4548}, abstract = {Placozoans are the simplest known free-living animals without recognized neurons and muscles but a complex behavioral repertoire. However, mechanisms and cellular bases of behavioral coordination are unknown. Here, using Trichoplax adhaerens as a model, we described 0.02-0.002 Hz oscillations in locomotory and feeding patterns as evidence of complex multicellular integration; and showed their dependence on the endogenous secretion of signal molecules. Evolutionary conserved low-molecular-weight transmitters (glutamate, aspartate, glycine, GABA, and ATP) acted as coordinators of distinct locomotory and feeding patterns. Specifically, L-glutamate induced and partially mimicked endogenous feeding cycles, whereas glycine and GABA suppressed feeding. ATP-modified feeding is complex, first causing feeding-like cycles and then suppressing feeding. Trichoplax locomotion was modulated by glycine, GABA, and, surprisingly, by animals' own mucus trails. Mucus triples locomotory speed compared to clean substrates. Glycine and GABA increased the frequency of turns. The effects of the amino acids are likely mediated by numerous receptors (R), including those from ionotropic GluRs, metabotropic GluRs, and GABA-BR families. Eighty-five of these receptors are encoded in the Trichoplax genome, more than in any other animal sequenced. Phylogenetic reconstructions illuminate massive lineage-specific expansions of amino acid receptors in Placozoa, Cnidaria, and Porifera and parallel evolution of nutritional sensing. Furthermore, we view the integration of feeding behaviors in nerveless animals by amino acids as ancestral exaptations that pave the way for co-options of glutamate, glycine, GABA, and ATP as classical neurotransmitters in eumetazoans.}, } @article {pmid37107699, year = {2023}, author = {Grochau-Wright, ZI and Nedelcu, AM and Michod, RE}, title = {The Genetics of Fitness Reorganization during the Transition to Multicellularity: The Volvocine regA-like Family as a Model.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/genes14040941}, pmid = {37107699}, issn = {2073-4425}, abstract = {The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell level to a cell group. This reorganization of fitness occurs by re-allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group: soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life history genes present in the unicellular ancestors of a multicellular lineage. For instance, single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival under stress. Such stress response life history genes can provide the genetic basis for the evolution of cellular differentiation in multicellular lineages. The regA-like gene family in the volvocine green algal lineage provides an excellent model system to study how this co-option can occur. We discuss the origin and evolution of the volvocine regA-like gene family, including regA-the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA-like family a useful template for similar investigations in other lineages.}, } @article {pmid37107559, year = {2023}, author = {Casotti, MC and Meira, DD and Zetum, ASS and Araújo, BC and Silva, DRCD and Santos, EVWD and Garcia, FM and Paula, F and Santana, GM and Louro, LS and Alves, LNR and Braga, RFR and Trabach, RSDR and Bernardes, SS and Louro, TES and Chiela, ECF and Lenz, G and Carvalho, EF and Louro, ID}, title = {Computational Biology Helps Understand How Polyploid Giant Cancer Cells Drive Tumor Success.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/genes14040801}, pmid = {37107559}, issn = {2073-4425}, abstract = {Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"}, } @article {pmid37098330, year = {2023}, author = {Colgren, J and Burkhardt, P}, title = {Evolution: Was the nuclear-to-cytoplasmic ratio a key factor in the origin of animal multicellularity?.}, journal = {Current biology : CB}, volume = {33}, number = {8}, pages = {R298-R300}, doi = {10.1016/j.cub.2023.03.010}, pmid = {37098330}, issn = {1879-0445}, abstract = {The ichthyosporean Sphaeroforma arctica, a protist closely related to animals, displays coenocytic development followed by cellularization and cell release. A new study reveals that the nuclear-to-cytoplasmic ratio drives cellularization in these fascinating organisms.}, } @article {pmid37096591, year = {2023}, author = {Stéger, A and Palmgren, M}, title = {Hypothesis paper: the development of a regulatory layer in P2B autoinhibited Ca[2+]-ATPases may have facilitated plant terrestrialization and animal multicellularization.}, journal = {Plant signaling & behavior}, volume = {18}, number = {1}, pages = {2204284}, doi = {10.1080/15592324.2023.2204284}, pmid = {37096591}, issn = {1559-2324}, abstract = {With the appearance of plants and animals, new challenges emerged. These multicellular eukaryotes had to solve for example the difficulties of multifaceted communication between cells and adaptation to new habitats. In this paper, we are looking for one piece of the puzzle that made the development of complex multicellular eukaryotes possible with a focus on regulation of P2B autoinhibited Ca[2+]-ATPases. P2B ATPases pump Ca[2+] out of the cytosol at the expense of ATP hydrolysis, and thereby maintain a steep gradient between the extra- and intracytosolic compartments which is utilized for Ca[2+]-mediated rapid cell signaling. The activity of these enzymes is regulated by a calmodulin (CaM)-responsive autoinhibitory region, which can be located in either termini of the protein, at the C-terminus in animals and at the N-terminus in plants. When the cytoplasmic Ca[2+] level reaches a threshold, the CaM/Ca[2+] complex binds to a calmodulin-binding domain (CaMBD) in the autoinhibitor, which leads to the upregulation of pump activity. In animals, protein activity is also controlled by acidic phospholipids that bind to a cytosolic portion of the pump. Here, we analyze the appearance of CaMBDs and the phospholipid-activating sequence and show that their evolution in animals and plants was independent. Furthermore, we hypothesize that different causes may have initiated the appearance of these regulatory layers: in animals, it is linked to the appearance of multicellularity, while in plants it co-occurs with their water-to-land transition.}, } @article {pmid37094139, year = {2023}, author = {Ros-Rocher, N and Kidner, RQ and Gerdt, C and Davidson, WS and Ruiz-Trillo, I and Gerdt, JP}, title = {Chemical factors induce aggregative multicellularity in a close unicellular relative of animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {18}, pages = {e2216668120}, doi = {10.1073/pnas.2216668120}, pmid = {37094139}, issn = {1091-6490}, abstract = {Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals' closest unicellular living relatives-the filasterean Capsaspora owczarzaki. We discovered that Capsaspora aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable Capsaspora cells. We also found that this multicellular stage is reversible as depletion of the cues triggers disaggregation, which can be overcome upon reinduction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.}, } @article {pmid37093889, year = {2023}, author = {Kumar, T and Sethuraman, R and Mitra, S and Ravindran, B and Narayanan, M}, title = {MultiCens: Multilayer network centrality measures to uncover molecular mediators of tissue-tissue communication.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1011022}, doi = {10.1371/journal.pcbi.1011022}, pmid = {37093889}, issn = {1553-7358}, abstract = {With the evolution of multicellularity, communication among cells in different tissues and organs became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the "influence" of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and performs well on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer's disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like "Multi-tissue-expanded Gene Ontology" analysis, can enable whole-body yet molecular-level systems investigations in humans.}, } @article {pmid37086724, year = {2023}, author = {Hashimoto, A and Kawamura, N and Tarusawa, E and Takeda, I and Aoyama, Y and Ohno, N and Inoue, M and Kagamiuchi, M and Kato, D and Matsumoto, M and Hasegawa, Y and Nabekura, J and Schaefer, A and Moorhouse, AJ and Yagi, T and Wake, H}, title = {Microglia enable cross-modal plasticity by removing inhibitory synapses.}, journal = {Cell reports}, volume = {}, number = {}, pages = {112383}, doi = {10.1016/j.celrep.2023.112383}, pmid = {37086724}, issn = {2211-1247}, abstract = {Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage.}, } @article {pmid37083675, year = {2023}, author = {Isaksson, H and Brännström, Å and Libby, E}, title = {Minor variations in multicellular life cycles have major effects on adaptation.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1010698}, doi = {10.1371/journal.pcbi.1010698}, pmid = {37083675}, issn = {1553-7358}, abstract = {Multicellularity has evolved several independent times over the past hundreds of millions of years and given rise to a wide diversity of complex life. Recent studies have found that large differences in the fundamental structure of early multicellular life cycles can affect fitness and influence multicellular adaptation. Yet, there is an underlying assumption that at some scale or categorization multicellular life cycles are similar in terms of their adaptive potential. Here, we consider this possibility by exploring adaptation in a class of simple multicellular life cycles of filamentous organisms that only differ in one respect, how many daughter filaments are produced. We use mathematical models and evolutionary simulations to show that despite the similarities, qualitatively different mutations fix. In particular, we find that mutations with a tradeoff between cell growth and group survival, i.e. "selfish" or "altruistic" traits, spread differently. Specifically, altruistic mutations more readily spread in life cycles that produce few daughters while in life cycles producing many daughters either type of mutation can spread depending on the environment. Our results show that subtle changes in multicellular life cycles can fundamentally alter adaptation.}, } @article {pmid37081145, year = {2023}, author = {Cornwallis, CK and Svensson-Coelho, M and Lindh, M and Li, Q and Stábile, F and Hansson, LA and Rengefors, K}, title = {Single-cell adaptations shape evolutionary transitions to multicellularity in green algae.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, pmid = {37081145}, issn = {2397-334X}, abstract = {The evolution of multicellular life has played a pivotal role in shaping biological diversity. However, we know surprisingly little about the natural environmental conditions that favour the formation of multicellular groups. Here we experimentally examine how key environmental factors (predation, nitrogen and water turbulence) combine to influence multicellular group formation in 35 wild unicellular green algae strains (19 Chlorophyta species). All environmental factors induced the formation of multicellular groups (more than four cells), but there was no evidence this was adaptive, as multicellularity (% cells in groups) was not related to population growth rate under any condition. Instead, population growth was related to extracellular matrix (ECM) around single cells and palmelloid formation, a unicellular life-cycle stage where two to four cells are retained within a mother-cell wall after mitosis. ECM production increased with nitrogen levels resulting in more cells being in palmelloids and higher rates of multicellular group formation. Examining the distribution of 332 algae species across 478 lakes monitored over 55 years, showed that ECM and nitrogen availability also predicted patterns of obligate multicellularity in nature. Our results highlight that adaptations of unicellular organisms to cope with environmental challenges may be key to understanding evolutionary routes to multicellular life.}, } @article {pmid37080197, year = {2023}, author = {Cadart, C and Bartz, J and Oaks, G and Liu, MZ and Heald, R}, title = {Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.03.071}, pmid = {37080197}, issn = {1879-0445}, abstract = {Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species and can be manipulated within a species. Here, we show that triploid tadpoles contain fewer, larger cells than diploids and consume oxygen at a lower rate. Drug treatments revealed that the major processes accounting for tadpole energy expenditure include cell proliferation, biosynthesis, and maintenance of plasma membrane potential. While inhibiting cell proliferation did not abolish the oxygen consumption difference between diploids and triploids, treatments that altered cellular biosynthesis or electrical potential did. Combining these results with a simple mathematical framework, we propose that the decrease in total cell surface area lowered production and activity of plasma membrane components including the Na[+]/K[+] ATPase, reducing energy consumption in triploids. Comparison of Xenopus species that evolved through polyploidization revealed that metabolic differences emerged during development when cell size scaled with genome size. Thus, ploidy affects metabolism by altering the cell surface area to volume ratio in a multicellular organism.}, } @article {pmid37073225, year = {2022}, author = {Chen, H and Li, DH and Jiang, AJ and Li, XG and Wu, SJ and Chen, JW and Qu, MJ and Qi, XQ and Dai, J and Zhao, R and Zhang, WJ and Liu, SS and Wu, LF}, title = {Metagenomic analysis reveals wide distribution of phototrophic bacteria in hydrothermal vents on the ultraslow-spreading Southwest Indian Ridge.}, journal = {Marine life science & technology}, volume = {4}, number = {2}, pages = {255-267}, pmid = {37073225}, issn = {2662-1746}, abstract = {UNLABELLED: Deep-sea hydrothermal vents are known as chemosynthetic ecosystems. However, high temperature vents emit light that hypothetically can drive photosynthesis in this habitat. Metagenomic studies have sporadically reported the occurrence of phototrophic populations such as cyanobacteria in hydrothermal vents. To determine how geographically and taxonomically widespread phototrophs are in deep-sea hydrothermal vents, we collected samples from three niches in a hydrothermal vent on the Southwest Indian Ridge and carried out an integrated metagenomic analysis. We determined the typical community structures of microorganisms found in active venting fields and identified populations of known potential chlorophototrophs and retinalophototrophs. Complete chlorophyll biosynthetic pathways were identified in all samples. By contrast, proteorhodopsins were only found in active beehive smoker diffusers. Taxonomic groups possessing potential phototrophy dependent on semiconductors present in hydrothermal vents were also found in these samples. This systematic comparative metagenomic study reveals the widespread distribution of phototrophic bacteria in hydrothermal vent fields. Our results support the hypothesis that the ocean is a seed bank of diverse microorganisms. Geothermal vent light may provide energy and confer a competitive advantage on phototrophs to proliferate in hydrothermal vent ecosystems.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-021-00121-y.}, } @article {pmid37068309, year = {2023}, author = {Xiao, K and Wang, Y and Dong, K and Zhang, S}, title = {SmartGate is a spatial metabolomics tool for resolving tissue structures.}, journal = {Briefings in bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1093/bib/bbad141}, pmid = {37068309}, issn = {1477-4054}, abstract = {Imaging mass spectrometry (IMS) is one of the powerful tools in spatial metabolomics for obtaining metabolite data and probing the internal microenvironment of organisms. It has dramatically advanced the understanding of the structure of biological tissues and the drug treatment of diseases. However, the complexity of IMS data hinders the further acquisition of biomarkers and the study of certain specific activities of organisms. To this end, we introduce an artificial intelligence tool, SmartGate, to enable automatic peak selection and spatial structure identification in an iterative manner. SmartGate selects discriminative m/z features from the previous iteration by differential analysis and employs a graph attention autoencoder model to perform spatial clustering for tissue segmentation using the selected features. We applied SmartGate to diverse IMS data at multicellular or subcellular spatial resolutions and compared it with four competing methods to demonstrate its effectiveness. SmartGate can significantly improve the accuracy of spatial segmentation and identify biomarker metabolites based on tissue structure-guided differential analysis. For multiple consecutive IMS data, SmartGate can effectively identify structures with spatial heterogeneity by introducing three-dimensional spatial neighbor information.}, } @article {pmid37067637, year = {2023}, author = {Ros-Rocher, N and Brunet, T}, title = {What is it like to be a choanoflagellate? Sensation, processing and behavior in the closest unicellular relatives of animals.}, journal = {Animal cognition}, volume = {}, number = {}, pages = {}, pmid = {37067637}, issn = {1435-9456}, support = {EvoMorphoCell 101040745/ERC_/European Research Council/International ; }, abstract = {All animals evolved from a single lineage of unicellular precursors more than 600 million years ago. Thus, the biological and genetic foundations for animal sensation, cognition and behavior must necessarily have arisen by modifications of pre-existing features in their unicellular ancestors. Given that the single-celled ancestors of the animal kingdom are extinct, the only way to reconstruct how these features evolved is by comparing the biology and genomic content of extant animals to their closest living relatives. Here, we reconstruct the Umwelt (the subjective, perceptive world) inhabited by choanoflagellates, a group of unicellular (or facultatively multicellular) aquatic microeukaryotes that are the closest living relatives of animals. Although behavioral research on choanoflagellates remains patchy, existing evidence shows that they are capable of chemosensation, photosensation and mechanosensation. These processes often involve specialized sensorimotor cellular appendages (cilia, microvilli, and/or filopodia) that resemble those that underlie perception in most animal sensory cells. Furthermore, comparative genomics predicts an extensive "sensory molecular toolkit" in choanoflagellates, which both provides a potential basis for known behaviors and suggests the existence of a largely undescribed behavioral complexity that presents exciting avenues for future research. Finally, we discuss how facultative multicellularity in choanoflagellates might help us understand how evolution displaced the locus of decision-making from a single cell to a collective, and how a new space of behavioral complexity might have become accessible in the process.}, } @article {pmid37048099, year = {2023}, author = {Leitner, N and Ertl, R and Gabner, S and Fuchs-Baumgartinger, A and Walter, I and Hlavaty, J}, title = {Isolation and Characterization of Novel Canine Osteosarcoma Cell Lines from Chemotherapy-Naïve Patients.}, journal = {Cells}, volume = {12}, number = {7}, pages = {}, doi = {10.3390/cells12071026}, pmid = {37048099}, issn = {2073-4409}, abstract = {The present study aimed to establish novel canine osteosarcoma cell lines (COS3600, COS3600B, COS4074) and characterize the recently described COS4288 cells. The established D-17 cell line served as a reference. Analyzed cell lines differed notably in their biological characteristics. Calculated doubling times were between 22 h for COS3600B and 426 h for COS4074 cells. COS3600B and COS4288 cells produced visible colonies after anchorage-independent growth in soft agar. COS4288 cells were identified as cells with the highest migratory capacity. All cells displayed the ability to invade through an artificial basement membrane matrix. Immunohistochemical analyses revealed the mesenchymal origin of all COS cell lines as well as positive staining for the osteosarcoma-relevant proteins alkaline phosphatase and karyopherin α2. Expression of p53 was confirmed in all tested cell lines. Gene expression analyses of selected genes linked to cellular immune checkpoints (CD270, CD274, CD276), kinase activity (MET, ERBB2), and metastatic potential (MMP-2, MMP-9) as well as selected long non-coding RNA (MALAT1) and microRNAs (miR-9, miR-34a, miR-93) are provided. All tested cell lines were able to grow as multicellular spheroids. In all spheroids except COS4288, calcium deposition was detected by von Kossa staining. We believe that these new cell lines serve as useful biological models for future studies.}, } @article {pmid37047167, year = {2023}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, doi = {10.3390/ijms24076196}, pmid = {37047167}, issn = {1422-0067}, abstract = {Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the 'atavistic reversal', 'cancer attractor', 'somatic mutation', 'genome chaos', and 'tissue organization field' theories. The 'atavistic reversal' theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called 'gradual atavism', and evidence for the 'serial atavism' model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.}, } @article {pmid37046079, year = {2023}, author = {Li, G and Chen, L and Pang, K and Tang, Q and Wu, C and Yuan, X and Zhou, C and Xiao, S}, title = {Tonian carbonaceous compressions indicate that Horodyskia is one of the oldest multicellular and coenocytic macro-organisms.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {399}, pmid = {37046079}, issn = {2399-3642}, abstract = {Macrofossils with unambiguous biogenic origin and predating the one-billion-year-old multicellular fossils Bangiomorpha and Proterocladus interpreted as crown-group eukaryotes are quite rare. Horodyskia is one of these few macrofossils, and it extends from the early Mesoproterozoic Era to the terminal Ediacaran Period. The biological interpretation of this enigmatic fossil, however, has been a matter of controversy since its discovery in 1982, largely because there was no evidence for the preservation of organic walls. Here we report new carbonaceous compressions of Horodyskia from the Tonian successions (~950-720 Ma) in North China. The macrofossils herein with bona fide organic walls reinforce the biogenicity of Horodyskia. Aided by the new material, we reconstruct Horodyskia as a colonial organism composed of a chain of organic-walled vesicles that likely represent multinucleated (coenocytic) cells of early eukaryotes. Two species of Horodyskia are differentiated on the basis of vesicle sizes, and their co-existence in the Tonian assemblage provides a link between the Mesoproterozoic (H. moniliformis) and the Ediacaran (H. minor) species. Our study thus provides evidence that eukaryotes have acquired macroscopic size through the combination of coenocytism and colonial multicellularity at least ~1.48 Ga, and highlights an exceptionally long range and morphological stasis of this Proterozoic macrofossils.}, } @article {pmid37029839, year = {2023}, author = {Varilla González, JD and Macedo Alves, F and Bagnatori Sartori, ÂL and de Oliveira Arruda, RDC}, title = {Diversity and evolution of leaflet anatomical characters in the Pterocarpus clade (Fabaceae: Papilionoideae).}, journal = {Journal of plant research}, volume = {}, number = {}, pages = {}, pmid = {37029839}, issn = {1618-0860}, abstract = {The Pterocarpus clade includes 23 genera previously attributed to different Fabaceae tribes. The recent rearrangements of many genera in the clade do not recognize morphological synapomorphies. This study aimed to identify new synapomorphies for the Pterocarpus clade, to identify characters supporting inter-generic relationships currently resolved only by molecular data and to identify diagnostic characters at the genus and species levels. Subterminal leaflets of the studied genera were selected and analyzed using light and scanning electron microscopy. Ancestral reconstruction was performed using morphological and anatomical characters of 16 genera of the Pterocarpus clade. The convex epidermal relief in the region of the main vein indicated the relationship among all genera of the group. Anchor-like multicellular trichomes are features shared by Brya and Cranocarpus, which are the sister group to the other genera of the clade. Subepidermal layers are features shared by the Centrolobium, Etaballia, Paramachaerium, Pterocarpus and Tipuana genera, and the sclerenchyma sheath in the leaflet margin is reported in the Discolobium, Riedeliella and Platymiscium genera. Bulbous based glandular trichomes and vesicular glandular trichomes are diagnostic at the species level in Centrolobium and Pterocarpus, respectively. The leaflet characters investigated can be useful for the taxonomic delimitation at both the genus and species levels of the Pterocarpus clade. Our dataset provides new synapomorphies, elucidates the inter-generic relationships and reinforces the phylogenetic classification of the Pterocarpus clade resolved by molecular data.}, } @article {pmid37023182, year = {2023}, author = {Darras, H and Berney, C and Hasin, S and Drescher, J and Feldhaar, H and Keller, L}, title = {Obligate chimerism in male yellow crazy ants.}, journal = {Science (New York, N.Y.)}, volume = {380}, number = {6640}, pages = {55-58}, doi = {10.1126/science.adf0419}, pmid = {37023182}, issn = {1095-9203}, mesh = {Animals ; Male ; *Ants/genetics ; Chimerism ; Semen ; Diploidy ; Reproduction ; }, abstract = {Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.}, } @article {pmid37019107, year = {2023}, author = {Barrere, J and Nanda, P and Murray, AW}, title = {Alternating selection for dispersal and multicellularity favors regulated life cycles.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.03.031}, pmid = {37019107}, issn = {1879-0445}, abstract = {The evolution of complex multicellularity opened paths to increased morphological diversity and organizational novelty. This transition involved three processes: cells remained attached to one another to form groups, cells within these groups differentiated to perform different tasks, and the groups evolved new reproductive strategies.[1][,][2][,][3][,][4][,][5] Recent experiments identified selective pressures and mutations that can drive the emergence of simple multicellularity and cell differentiation,[6][,][7][,][8][,][9][,][10][,][11] but the evolution of life cycles, particularly how simple multicellular forms reproduce, has been understudied. The selective pressure and mechanisms that produced a regular alternation between single cells and multicellular collectives are still unclear.[12] To probe the factors regulating simple multicellular life cycles, we examined a collection of wild isolates of the budding yeast S. cerevisiae.[12][,][13] We found that all these strains can exist as multicellular clusters, a phenotype that is controlled by the mating-type locus and strongly influenced by the nutritional environment. Inspired by this variation, we engineered inducible dispersal in a multicellular laboratory strain and demonstrated that a regulated life cycle has an advantage over constitutively single-celled or constitutively multicellular life cycles when the environment alternates between favoring intercellular cooperation (a low sucrose concentration) and dispersal (a patchy environment generated by emulsion). Our results suggest that the separation of mother and daughter cells is under selection in wild isolates and is regulated by their genetic composition and the environments they encounter and that alternating patterns of resource availability may have played a role in the evolution of life cycles.}, } @article {pmid37011504, year = {2023}, author = {Morehouse, BR}, title = {Phage defense origin of animal immunity.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102295}, doi = {10.1016/j.mib.2023.102295}, pmid = {37011504}, issn = {1879-0364}, abstract = {The innate immune system is the first line of defense against microbial pathogens. Many of the features of eukaryotic innate immunity have long been viewed as lineage-specific innovations, evolved to deal with the challenges and peculiarities of multicellular life. However, it has become increasingly apparent that in addition to evolving their own unique antiviral immune strategies, all lifeforms have some shared defense strategies in common. Indeed, critical fixtures of animal innate immunity bear striking resemblance in both structure and function to the multitude of diverse bacteriophage (phage) defense pathways discovered hidden in plain sight within the genomes of bacteria and archaea. This review will highlight many surprising examples of the recently revealed connections between prokaryotic and eukaryotic antiviral immune systems.}, } @article {pmid37005641, year = {2023}, author = {Guan, X and Zhang, L and Lai, S and Zhang, J and Wei, J and Wang, K and Zhang, W and Li, C and Tong, J and Lei, Z}, title = {Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging.}, journal = {Journal of nanobiotechnology}, volume = {21}, number = {1}, pages = {118}, pmid = {37005641}, issn = {1477-3155}, mesh = {Humans ; Diagnostic Imaging ; *Nanoparticles ; *Quantum Dots ; HeLa Cells ; Water ; }, abstract = {Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.}, } @article {pmid37005419, year = {2023}, author = {Tang, SK and Zhi, XY and Zhang, Y and Makarova, KS and Liu, BB and Zheng, GS and Zhang, ZP and Zheng, HJ and Wolf, YI and Zhao, YR and Jiang, SH and Chen, XM and Li, EY and Zhang, T and Chen, PR and Feng, YZ and Xiang, MX and Lin, ZQ and Shi, JH and Chang, C and Zhang, X and Li, R and Lou, K and Wang, Y and Chang, L and Yin, M and Yang, LL and Gao, HY and Zhang, ZK and Tao, TS and Guan, TW and He, FC and Lu, YH and Cui, HL and Koonin, EV and Zhao, GP and Xu, P}, title = {Cellular differentiation into hyphae and spores in halophilic archaea.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1827}, pmid = {37005419}, issn = {2041-1723}, mesh = {Hyphae/genetics ; Proteomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Streptomyces/genetics ; *Halobacteriaceae/genetics ; Spores ; Cell Differentiation ; Sequence Analysis, DNA ; China ; }, abstract = {Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.}, } @article {pmid37002899, year = {2023}, author = {LeBleu, VS and Dai, J and Tsutakawa, S and MacDonald, BA and Alge, JL and Sund, M and Xie, L and Sugimoto, H and Tainer, J and Zon, LI and Kalluri, R}, title = {Identification of unique α4 chain structure and conserved anti-angiogenic activity of α3NC1 type IV collagen in zebrafish.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {}, number = {}, pages = {}, doi = {10.1002/dvdy.590}, pmid = {37002899}, issn = {1097-0177}, abstract = {BACKGROUND: Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1 to α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.

RESULTS: We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in contrast with its human ortholog, contains an additional cysteine residue and lacks the M93 and K211 residues involved in sulfilimine bond formation between adjacent protomers. This may alter α4 chain interactions with other α chains, as supported by temporal and anatomic expression patterns of collagen IV chains during zebrafish development. Despite the divergence between zebrafish and human α3 NC1 domain (endogenous angiogenesis inhibitor, Tumstatin), the zebrafish α3 NC1 domain exhibits conserved anti-angiogenic activity in human endothelial cells.

CONCLUSIONS: Our work supports type IV collagen is largely conserved between zebrafish and humans, with a possible difference involving the α4 chain. This article is protected by copyright. All rights reserved.}, } @article {pmid37002250, year = {2023}, author = {Jiménez-Marín, B and Rakijas, JB and Tyagi, A and Pandey, A and Hanschen, ER and Anderson, J and Heffel, MG and Platt, TG and Olson, BJSC}, title = {Gene loss during a transition to multicellularity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5268}, pmid = {37002250}, issn = {2045-2322}, mesh = {*Biological Evolution ; Phylogeny ; }, abstract = {Multicellular evolution is a major transition associated with momentous diversification of multiple lineages and increased developmental complexity. The volvocine algae comprise a valuable system for the study of this transition, as they span from unicellular to undifferentiated and differentiated multicellular morphologies despite their genomes being similar, suggesting multicellular evolution requires few genetic changes to undergo dramatic shifts in developmental complexity. Here, the evolutionary dynamics of six volvocine genomes were examined, where a gradual loss of genes was observed in parallel to the co-option of a few key genes. Protein complexes in the six species exhibited novel interactions, suggesting that gene loss could play a role in evolutionary novelty. This finding was supported by gene network modeling, where gene loss outpaces gene gain in generating novel stable network states. These results suggest gene loss, in addition to gene gain and co-option, may be important for the evolution developmental complexity.}, } @article {pmid37000909, year = {2023}, author = {Little, JC and Kaaronen, RO and Hukkinen, JI and Xiao, S and Sharpee, T and Farid, AM and Nilchiani, R and Barton, CM}, title = {Earth Systems to Anthropocene Systems: An Evolutionary, System-of-Systems, Convergence Paradigm for Interdependent Societal Challenges.}, journal = {Environmental science & technology}, volume = {57}, number = {14}, pages = {5504-5520}, doi = {10.1021/acs.est.2c06203}, pmid = {37000909}, issn = {1520-5851}, abstract = {Humans have made profound changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change and impacts, renewable energy, adaptive infrastructure, disasters, pandemics, food insecurity, and biodiversity loss) are complex and systemic, with causes, interactions, and consequences that cascade across a globally connected system of systems. In this Critical Review, we turn to our "origin story" for insight, briefly tracing the formation of the Universe and the Earth, the emergence of life, the evolution of multicellular organisms, mammals, primates, and humans, as well as the more recent societal transitions involving agriculture, urbanization, industrialization, and computerization. Focusing on the evolution of the Earth, genetic evolution, the evolution of the brain, and cultural evolution, which includes technological evolution, we identify a nested evolutionary sequence of geophysical, biophysical, sociocultural, and sociotechnical systems, emphasizing the causal mechanisms that first formed, and then transformed, Earth systems into Anthropocene systems. Describing how the Anthropocene systems coevolved, and briefly illustrating how the ensuing societal challenges became tightly integrated across multiple spatial, temporal, and organizational scales, we conclude by proposing an evolutionary, system-of-systems, convergence paradigm for the entire family of interdependent societal challenges of the Anthropocene.}, } @article {pmid36996815, year = {2023}, author = {Olivetta, M and Dudin, O}, title = {The nuclear-to-cytoplasmic ratio drives cellularization in the close animal relative Sphaeroforma arctica.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.03.019}, pmid = {36996815}, issn = {1879-0445}, abstract = {The ratio of nuclear content to cytoplasmic volume (N/C ratio) is a key regulator driving the maternal-to-zygotic transition in most animal embryos. Altering this ratio often impacts zygotic genome activation and deregulates the timing and outcome of embryogenesis.[1][,][2][,][3] Despite being ubiquitous across animals, little is known about when the N/C ratio evolved to control multicellular development. Such capacity either originated with the emergence of animal multicellularity or was co-opted from the mechanisms present in unicellular organisms.[4] An effective strategy to tackle this question is to investigate the close relatives of animals exhibiting life cycles with transient multicellular stages.[5] Among these are ichthyosporeans, a lineage of protists undergoing coenocytic development followed by cellularization and cell release.[6][,][7][,][8] During cellularization, a transient multicellular stage resembling animal epithelia is generated, offering a unique opportunity to examine whether the N/C ratio regulates multicellular development. Here, we use time-lapse microscopy to characterize how the N/C ratio affects the life cycle of the best-studied ichthyosporean model, Sphaeroforma arctica. We uncover that the last stages of cellularization coincide with a significant increase in the N/C ratio. Increasing the N/C ratio by reducing the coenocytic volume accelerates cellularization, whereas decreasing the N/C ratio by lowering the nuclear content halts it. Moreover, centrifugation and pharmacological inhibitor experiments suggest that the N/C ratio is locally sensed at the cortex and relies on phosphatase activity. Altogether, our results show that the N/C ratio drives cellularization in S. arctica, suggesting that its capacity to control multicellular development predates animal emergence.}, } @article {pmid36996248, year = {2023}, author = {Herold, J and Behle, E and Rosenbauer, J and Ferruzzi, J and Schug, A}, title = {Development of a scoring function for comparing simulated and experimental tumor spheroids.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010471}, doi = {10.1371/journal.pcbi.1010471}, pmid = {36996248}, issn = {1553-7358}, abstract = {Progress continues in the field of cancer biology, yet much remains to be unveiled regarding the mechanisms of cancer invasion. In particular, complex biophysical mechanisms enable a tumor to remodel the surrounding extracellular matrix (ECM), allowing cells to invade alone or collectively. Tumor spheroids cultured in collagen represent a simplified, reproducible 3D model system, which is sufficiently complex to recapitulate the evolving organization of cells and interaction with the ECM that occur during invasion. Recent experimental approaches enable high resolution imaging and quantification of the internal structure of invading tumor spheroids. Concurrently, computational modeling enables simulations of complex multicellular aggregates based on first principles. The comparison between real and simulated spheroids represents a way to fully exploit both data sources, but remains a challenge. We hypothesize that comparing any two spheroids requires first the extraction of basic features from the raw data, and second the definition of key metrics to match such features. Here, we present a novel method to compare spatial features of spheroids in 3D. To do so, we define and extract features from spheroid point cloud data, which we simulated using Cells in Silico (CiS), a high-performance framework for large-scale tissue modeling previously developed by us. We then define metrics to compare features between individual spheroids, and combine all metrics into an overall deviation score. Finally, we use our features to compare experimental data on invading spheroids in increasing collagen densities. We propose that our approach represents the basis for defining improved metrics to compare large 3D data sets. Moving forward, this approach will enable the detailed analysis of spheroids of any origin, one application of which is informing in silico spheroids based on their in vitro counterparts. This will enable both basic and applied researchers to close the loop between modeling and experiments in cancer research.}, } @article {pmid36992628, year = {2023}, author = {Östmans, R and Cortes Ruiz, MF and Rostami, J and Sellman, FA and Wågberg, L and Lindström, SB and Benselfelt, T}, title = {Elastoplastic behavior of anisotropic, physically crosslinked hydrogel networks comprising stiff, charged fibrils in an electrolyte.}, journal = {Soft matter}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2sm01571d}, pmid = {36992628}, issn = {1744-6848}, abstract = {Fibrillar hydrogels are remarkably stiff, low-density networks that can hold vast amounts of water. These hydrogels can easily be made anisotropic by orienting the fibrils using different methods. Unlike the detailed and established descriptions of polymer gels, there is no coherent theoretical framework describing the elastoplastic behavior of fibrillar gels, especially concerning anisotropy. In this work, the swelling pressures of anisotropic fibrillar hydrogels made from cellulose nanofibrils were measured in the direction perpendicular to the fibril alignment. This experimental data was used to develop a model comprising three mechanical elements representing the network and the osmotic pressure due to non-ionic and ionic surface groups on the fibrils. At low solidity, the stiffness of the hydrogels was dominated by the ionic swelling pressure governed by the osmotic ingress of water. Fibrils with different functionality show the influence of aspect ratio, chemical functionality, and the remaining amount of hemicelluloses. This general model describes physically crosslinked hydrogels comprising fibrils with high flexural rigidity - that is, with a persistence length larger than the mesh size. The experimental technique is a framework to study and understand the importance of fibrillar networks for the evolution of multicellular organisms, like plants, and the influence of different components in plant cell walls.}, } @article {pmid36985211, year = {2023}, author = {Li, AQ and Zhang, WJ and Li, XG and Bao, XC and Qi, XQ and Wu, LF and Bartlett, DH}, title = {Piezophilic Phenotype Is Growth Condition Dependent and Correlated with the Regulation of Two Sets of ATPase in Deep-Sea Piezophilic Bacterium Photobacterium profundum SS9.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985211}, issn = {2076-2607}, abstract = {Alteration of respiratory components as a function of pressure is a common strategy developed in deep-sea microorganisms, presumably to adapt to high hydrostatic pressure (HHP). While the electron transport chain and terminal reductases have been extensively studied in deep-sea bacteria, little is known about their adaptations for ATP generation. In this study, we showed that the deep-sea bacterium Photobacterium profundum SS9 exhibits a more pronounced piezophilic phenotype when grown in minimal medium supplemented with glucose (MG) than in the routinely used MB2216 complex medium. The intracellular ATP level varied with pressure, but with opposite trends in the two culture media. Between the two ATPase systems encoded in SS9, ATPase-I played a dominant role when cultivated in MB2216, whereas ATPase-II was more abundant in the MG medium, especially at elevated pressure when cells had the lowest ATP level among all conditions tested. Further analyses of the ΔatpI, ΔatpE1 and ΔatpE2 mutants showed that disrupting ATPase-I induced expression of ATPase-II and that the two systems are functionally redundant in MB2216. Collectively, we provide the first examination of the differences and relationships between two ATPase systems in a piezophilic bacterium, and expanded our understanding of the involvement of energy metabolism in pressure adaptation.}, } @article {pmid36980921, year = {2023}, author = {Han, M and Ren, J and Guo, H and Tong, X and Hu, H and Lu, K and Dai, Z and Dai, F}, title = {Mutation Rate and Spectrum of the Silkworm in Normal and Temperature Stress Conditions.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980921}, issn = {2073-4425}, mesh = {Animals ; *Bombyx/genetics ; Temperature ; Mutation Rate ; Insecta/genetics ; Genome ; }, abstract = {Mutation rate is a crucial parameter in evolutionary genetics. However, the mutation rate of most species as well as the extent to which the environment can alter the genome of multicellular organisms remain poorly understood. Here, we used parents-progeny sequencing to investigate the mutation rate and spectrum of the domestic silkworm (Bombyx mori) among normal and two temperature stress conditions (32 °C and 0 °C). The rate of single-nucleotide mutations in the normal temperature rearing condition was 0.41 × 10[-8] (95% confidence interval, 0.33 × 10[-8]-0.49 × 10[-8]) per site per generation, which was up to 1.5-fold higher than in four previously studied insects. Moreover, the mutation rates of the silkworm under the stresses are significantly higher than in normal conditions. Furthermore, the mutation rate varies less in gene regions under normal and temperature stresses. Together, these findings expand the known diversity of the mutation rate among eukaryotes but also have implications for evolutionary analysis that assumes a constant mutation rate among species and environments.}, } @article {pmid36980213, year = {2023}, author = {Merino, MM and Garcia-Sanz, JA}, title = {Stemming Tumoral Growth: A Matter of Grotesque Organogenesis.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980213}, issn = {2073-4409}, mesh = {Humans ; *Neoplasm Recurrence, Local ; *Organogenesis ; Neoplastic Stem Cells ; Cell Transformation, Neoplastic ; }, abstract = {The earliest metazoans probably evolved from single-celled organisms which found the colonial system to be a beneficial organization. Over the course of their evolution, these primary colonial organisms increased in size, and division of labour among the cells became a remarkable feature, leading to a higher level of organization: the biological organs. Primitive metazoans were the first organisms in evolution to show organ-type structures, which set the grounds for complex organs to evolve. Throughout evolution, and concomitant with organogenesis, is the appearance of tissue-specific stem cells. Tissue-specific stem cells gave rise to multicellular living systems with distinct organs which perform specific physiological functions. This setting is a constructive role of evolution; however, rebel cells can take over the molecular mechanisms for other purposes: nowadays we know that cancer stem cells, which generate aberrant organ-like structures, are at the top of a hierarchy. Furthermore, cancer stem cells are the root of metastasis, therapy resistance, and relapse. At present, most therapeutic drugs are unable to target cancer stem cells and therefore, treatment becomes a challenging issue. We expect that future research will uncover the mechanistic "forces" driving organ growth, paving the way to the implementation of new strategies to impair human tumorigenesis.}, } @article {pmid36964572, year = {2023}, author = {Barrera-Redondo, J and Lotharukpong, JS and Drost, HG and Coelho, SM}, title = {Uncovering gene-family founder events during major evolutionary transitions in animals, plants and fungi using GenEra.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {54}, pmid = {36964572}, issn = {1474-760X}, mesh = {Animals ; Phylogeny ; *Biological Evolution ; *Genomics/methods ; Fungi/genetics ; Plants/genetics ; Evolution, Molecular ; }, abstract = {We present GenEra (https://github.com/josuebarrera/GenEra), a DIAMOND-fueled gene-family founder inference framework that addresses previously raised limitations and biases in genomic phylostratigraphy, such as homology detection failure. GenEra also reduces computational time from several months to a few days for any genome of interest. We analyze the emergence of taxonomically restricted gene families during major evolutionary transitions in plants, animals, and fungi. Our results indicate that the impact of homology detection failure on inferred patterns of gene emergence is lineage-dependent, suggesting that plants are more prone to evolve novelty through the emergence of new genes compared to animals and fungi.}, } @article {pmid36959212, year = {2023}, author = {Nofech-Mozes, I and Soave, D and Awadalla, P and Abelson, S}, title = {Pan-cancer classification of single cells in the tumour microenvironment.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1615}, pmid = {36959212}, issn = {2041-1723}, mesh = {Humans ; Female ; *Tumor Microenvironment ; *Breast Neoplasms/pathology ; Gene Expression Profiling/methods ; Transcriptome ; Stromal Cells/pathology ; }, abstract = {Single-cell RNA sequencing can reveal valuable insights into cellular heterogeneity within tumour microenvironments (TMEs), paving the way for a deep understanding of cellular mechanisms contributing to cancer. However, high heterogeneity among the same cancer types and low transcriptomic variation in immune cell subsets present challenges for accurate, high-resolution confirmation of cells' identities. Here we present scATOMIC; a modular annotation tool for malignant and non-malignant cells. We trained scATOMIC on >300,000 cancer, immune, and stromal cells defining a pan-cancer reference across 19 common cancers and employ a hierarchical approach, outperforming current classification methods. We extensively confirm scATOMIC's accuracy on 225 tumour biopsies encompassing >350,000 cancer and a variety of TME cells. Lastly, we demonstrate scATOMIC's practical significance to accurately subset breast cancers into clinically relevant subtypes and predict tumours' primary origin across metastatic cancers. Our approach represents a broadly applicable strategy to analyse multicellular cancer TMEs.}, } @article {pmid36951905, year = {2023}, author = {Jiao, ZX and Li, XG and Zhang, HH and Xu, J and Bai, SJ and Dai, J and Lin, J and Zhang, WJ and Qi, XQ and Wu, LF}, title = {Crassaminicella indica sp. nov., a novel thermophilic anaerobic bacterium isolated from a deep-sea hydrothermal vent.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {73}, number = {3}, pages = {}, doi = {10.1099/ijsem.0.005725}, pmid = {36951905}, issn = {1466-5034}, mesh = {*Fatty Acids/chemistry ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Base Composition ; *Hydrothermal Vents/microbiology ; Anaerobiosis ; Sequence Analysis, DNA ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Phospholipids/chemistry ; Bacteria, Anaerobic ; }, abstract = {A novel moderately thermophilic heterotrophic bacterium, designated strain 143-21[T], was isolated from a deep-sea hydrothermal chimney sample collected from the Central Indian Ridge at a depth of 2 440 m. Phylogenetic analysis indicated that strain 143-21[T] belongs to the genus Crassaminicella. It was most closely related to Crassaminicella thermophila SY095[T] (96.79 % 16S rRNA gene sequence similarity) and Crassaminicella profunda Ra1766H[T] (96.52 %). Genomic analysis showed that strain 143-21[T] shares 79.79-84.45 % average nucleotide identity and 23.50-29.20 % digital DNA-DNA hybridization with the species of the genus Crassaminicella, respectively. Cells were rod-shaped, non-motile, Gram-positive-staining. Terminal endospores were observed in stationary-phase cells when strain 143-21[T] was grown on Thermococcales rich medium. Strain 143-21[T] was able to grow at 30-60 °C (optimum, 50 °C), pH 6.5-8.5 (optimum, pH 7.0) and in 1.0-7.0 % NaCl (w/v; optimum 2.0 %, w/v). Strain 143-21[T] utilized fructose, glucose, maltose, mannose, ribose, N-acetyl-d-(+)-glucosamine and casamino acids, as well as amino acids including glutamate, lysine, histidine and cysteine. The main fermentation products from glucose were acetate (2.07 mM), H2 and CO2. It did not reduce elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe (III). The predominant cellular fatty acids were C14 : 0 (48.8 %), C16 : 0 (12.9 %), and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 10.2 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, as well as two unidentified phospholipids and four unidentified aminolipids. No respiratory quinones were detected. Based on its phylogenetic analysis and physiological characteristics, strain 143-21[T] is considered to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella indica sp. nov. is proposed. The type strain is strain 143-21[T] (=DSM 114408[T]= MCCC 1K06400[T]).}, } @article {pmid36945744, year = {2023}, author = {Li, Y and Kim, EJ and Voshall, A and Moriyama, EN and Cerutti, H}, title = {Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.}, journal = {The Plant cell}, volume = {}, number = {}, pages = {}, doi = {10.1093/plcell/koad093}, pmid = {36945744}, issn = {1532-298X}, abstract = {Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including three AGOs and three DICER-like (DCL) proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.}, } @article {pmid36915469, year = {2023}, author = {Prieto, I and Barbáchano, A and Rodríguez-Salas, N and Viñal, D and Cortés-Guiral, D and Muñoz, A and Fernández-Barral, A}, title = {Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report.}, journal = {Journal of gastrointestinal oncology}, volume = {14}, number = {1}, pages = {442-449}, pmid = {36915469}, issn = {2078-6891}, abstract = {BACKGROUND: Peritoneal metastasis from colorectal cancer (CRC) has limited therapeutic options and poor prognosis. Systemic chemotherapy combined with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) have yielded initial promising results. However, standard local therapies with oxaliplatin and mitomycin are not optimal and a better individualized management of these patients remains as an unmet clinical need. Patient-derived organoid (PDO) technology allows to culture in three dimensions normal and cancer stem cells (CSC) that self-organize in multicellular structures that recapitulates some of the features of the particular organ or tumor of origin, emerging as a promising tool for drug-testing and precision medicine. This technology could improve the efficacy of systemic and intraperitoneal chemotherapy and avoid unnecessary treatments and side effects to the patient.

CASE DESCRIPTION: Here we report a case of a 45-year-old man with a rectal adenocarcinoma with liver, lymph node and peritoneal metastases. The patient was treated with systemic chemotherapy (FOLFOXIRI plus Bevacizumab) and was subjected to mitomycin-based PIPAC. We generated patient-derived peritoneal carcinomatosis organoids in order to screen the activity of drugs for a personalized treatment. Both 5-FU and SN-38, the active irinotecan derivative, displayed strong cytotoxicity, while the response to oxaliplatin was much lower. Although the development of a colo-cutaneous fistulae prevented from further PIPAC, the patient continued with fluoropirimidine maintenance treatment based on standard clinical practice and the drug-screening test performed on organoids.

CONCLUSIONS: Our results suggest that the peritoneal implant shows chemoresistance to oxaliplatin, while it might still be sensitive to irinotecan and 5-FU, which supports a potential benefit of these two drugs in the local and/or systemic treatment of our patient. This study shows the strength of the utility of the establishment of organoids for drug response assays and thus, for the personalized treatment of colorectal carcinomatosis patients.}, } @article {pmid36912901, year = {2023}, author = {Ebinghaus, M and Dos Santos, MDM and Tonelli, GSSS and Macagnan, D and Carvalho, EA and Dianese, JC}, title = {Raveneliopsis, a new genus of ravenelioid rust fungi on Cenostigma (Caesalpinioideae) from the Brazilian Cerrado and Caatinga.}, journal = {Mycologia}, volume = {115}, number = {2}, pages = {263-276}, doi = {10.1080/00275514.2023.2177048}, pmid = {36912901}, issn = {1557-2536}, mesh = {Brazil ; Phylogeny ; *Basidiomycota/genetics ; *Fabaceae ; }, abstract = {The multicellular discoid convex teliospore heads represent a prominent generic feature of the genus Ravenelia. However, recent molecular phylogenetic work has shown that this is a convergent trait, and that this genus does not represent a natural group. In 2000, a rust fungus infecting the Caesalpinioid species Cenostigma macrophyllum (= C. gardnerianum) was described as Ravenelia cenostigmatis. This species shows some rare features, such as an extra layer of sterile cells between the cysts and the fertile teliospores, spirally ornamented urediniospores, as well as strongly incurved paraphyses giving the telia and uredinia a basket-like appearance. Using freshly collected specimens of Rav. cenostigmatis and Rav. spiralis on C. macrophyllum, our phylogenetic analyses based on the nuc 28S, nuc 18S, and mt CO3 (cytochrome c oxidase subunit 3) gene sequences demonstrated that these two rust fungi belong in a lineage within the Raveneliineae that is distinct from Ravenelia s. str. Besides proposing their recombination into the new genus Raveneliopsis (type species R. cenostigmatis) and briefly discussing their potentially close phylogenetic affiliations, we suggest that five other Ravenelia species that are morphologically and ecologically close to the type species of Raveneliopsis, i.e., Rav. corbula, Rav. corbuloides, Rav. parahybana, Rav. pileolarioides, and Rav. Striatiformis, may be recombined pending new collections and confirmation through molecular phylogenetic analyses.}, } @article {pmid36909237, year = {2023}, author = {Bajgar, A and Krejčová, G}, title = {On the origin of the functional versatility of macrophages.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1128984}, pmid = {36909237}, issn = {1664-042X}, abstract = {Macrophages represent the most functionally versatile cells in the animal body. In addition to recognizing and destroying pathogens, macrophages remove senescent and exhausted cells, promote wound healing, and govern tissue and metabolic homeostasis. In addition, many specialized populations of tissue-resident macrophages exhibit highly specialized functions essential for the function of specific organs. Sometimes, however, macrophages cease to perform their protective function and their seemingly incomprehensible response to certain stimuli leads to pathology. In this study, we address the question of the origin of the functional versatility of macrophages. To this end, we have searched for the evolutionary origin of macrophages themselves and for the emergence of their characteristic properties. We hypothesize that many of the characteristic features of proinflammatory macrophages evolved in the unicellular ancestors of animals, and that the functional repertoire of macrophage-like amoebocytes further expanded with the evolution of multicellularity and the increasing complexity of tissues and organ systems. We suggest that the entire repertoire of macrophage functions evolved by repurposing and diversification of basic functions that evolved early in the evolution of metazoans under conditions barely comparable to that in tissues of multicellular organisms. We believe that by applying this perspective, we may find an explanation for the otherwise counterintuitive behavior of macrophages in many human pathologies.}, } @article {pmid36907967, year = {2023}, author = {Lu, B and Hu, X and Warren, A and Song, W and Yan, Y}, title = {From oral structure to molecular evidence: new insights into the evolutionary phylogeny of the ciliate order Sessilida (Protista, Ciliophora), with the establishment of two new families and new contributions to the poorly studied family Vaginicolidae.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {36907967}, issn = {1869-1889}, abstract = {Ciliated protists represent one of the most primitive and diverse lineages of eukaryotes, with nuclear dimorphism, a distinctive sexual process (conjugation), and extensive genome rearrangements. Among divergent ciliate lineages, the peritrich order Sessilida includes members with a colonial lifestyle, which may hint to an independent evolutionary attempt for multicellularity, although they are still single-celled organisms. To date, the evolution and phylogeny of this group are still far from clear, in part due to the paucity of molecular and/or morphological data for many taxa. In this study, we extend taxon sampling of a loricate group of sessilids by obtaining 69 new rDNA (SSU rDNA, ITS1-5.8S rDNA-ITS2, and LSU rDNA) sequences from 20 well-characterized representative species and analyze the phylogenetic relationships within Sessilida. The main findings are: (i) the genera Rhabdostyla and Campanella each represents a unique taxon at family level, supporting the establishment of two new families, i.e., Rhabdostylidae n. fam. and Campanellidae n. fam., respectively, the former being sister to a morphologically heterogeneous clade comprising Astylozoidae and several incertae sedis species and the latter occupying the basal position within the Sessilida clade; (ii) the structure of infundibular polykinety 3 is likely to be a phylogenetically informative character for resolving evolutionary relationships among sessilids; (iii) differences between sparsely and the densely arranged silverline systems could be a suprageneric taxonomic character; (iv) the monophyly of Vaginicolidae is confirmed, which is consistent with its specialized morphology, i.e., the possession of a typical peritrich lorica which might be an apomorphy for this group; (v) within Vaginicolidae, the monotypic Cothurniopsis sensu Stokes, 1893 is a synonym of Cothurnia Ehrenberg, 1831, and a new combination is created, i.e., Cothurnia valvata nov. comb.; (vi) Vaginicola sensu lato comprises at least two distinctly divergent clades, one affiliated with Thuricola and the other with a systematically puzzling clade represented by Vaginicola tincta.}, } @article {pmid36899423, year = {2023}, author = {Ouyang, X and Wu, B and Yu, H and Dong, B}, title = {DYRK1-mediated phosphorylation of endocytic components is required for extracellular lumen expansion in ascidian notochord.}, journal = {Biological research}, volume = {56}, number = {1}, pages = {10}, pmid = {36899423}, issn = {0717-6287}, mesh = {Animals ; Humans ; *Ciona intestinalis/metabolism ; Notochord/metabolism ; Phosphorylation ; Embryonic Development ; Morphogenesis ; }, abstract = {BACKGROUND: The biological tube is a basal biology structure distributed in all multicellular animals, from worms to humans, and has diverse biological functions. Formation of tubular system is crucial for embryogenesis and adult metabolism. Ascidian Ciona notochord lumen is an excellent in vivo model for tubulogenesis. Exocytosis has been known to be essential for tubular lumen formation and expansion. The roles of endocytosis in tubular lumen expansion remain largely unclear.

RESULTS: In this study, we first identified a dual specificity tyrosine-phosphorylation-regulated kinase 1 (DYRK1), the protein kinase, which was upregulated and required for ascidian notochord extracellular lumen expansion. We demonstrated that DYRK1 interacted with and phosphorylated one of the endocytic components endophilin at Ser263 that was essential for notochord lumen expansion. Moreover, through phosphoproteomic sequencing, we revealed that in addition to endophilin, the phosphorylation of other endocytic components was also regulated by DYRK1. The loss of function of DYRK1 disturbed endocytosis. Then, we demonstrated that clathrin-mediated endocytosis existed and was required for notochord lumen expansion. In the meantime, the results showed that the secretion of notochord cells is vigorous in the apical membrane.

CONCLUSIONS: We found the co-existence of endocytosis and exocytosis activities in apical membrane during lumen formation and expansion in Ciona notochord. A novel signaling pathway is revealed that DYRK1 regulates the endocytosis by phosphorylation that is required for lumen expansion. Our finding thus indicates a dynamic balance between endocytosis and exocytosis is crucial to maintain apical membrane homeostasis that is essential for lumen growth and expansion in tubular organogenesis.}, } @article {pmid36897970, year = {2023}, author = {Davidescu, MR and Romanczuk, P and Gregor, T and Couzin, ID}, title = {Growth produces coordination trade-offs in Trichoplax adhaerens, an animal lacking a central nervous system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {11}, pages = {e2206163120}, doi = {10.1073/pnas.2206163120}, pmid = {36897970}, issn = {1091-6490}, support = {R01 GM097275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Placozoa/physiology ; Body Size ; Central Nervous System ; Biological Evolution ; }, abstract = {How collectives remain coordinated as they grow in size is a fundamental challenge affecting systems ranging from biofilms to governments. This challenge is particularly apparent in multicellular organisms, where coordination among a vast number of cells is vital for coherent animal behavior. However, the earliest multicellular organisms were decentralized, with indeterminate sizes and morphologies, as exemplified by Trichoplax adhaerens, arguably the earliest-diverged and simplest motile animal. We investigated coordination among cells in T. adhaerens by observing the degree of collective order in locomotion across animals of differing sizes and found that larger individuals exhibit increasingly disordered locomotion. We reproduced this effect of size on order through a simulation model of active elastic cellular sheets and demonstrate that this relationship is best recapitulated across all body sizes when the simulation parameters are tuned to a critical point in the parameter space. We quantify the trade-off between increasing size and coordination in a multicellular animal with a decentralized anatomy that shows evidence of criticality and hypothesize as to the implications of this on the evolution hierarchical structures such as nervous systems in larger organisms.}, } @article {pmid36893064, year = {2023}, author = {Garg, A and Nam, W and Wang, W and Vikesland, P and Zhou, W}, title = {In Situ Spatiotemporal SERS Measurements and Multivariate Analysis of Virally Infected Bacterial Biofilms Using Nanolaminated Plasmonic Crystals.}, journal = {ACS sensors}, volume = {8}, number = {3}, pages = {1132-1142}, doi = {10.1021/acssensors.2c02412}, pmid = {36893064}, issn = {2379-3694}, mesh = {*Spectrum Analysis, Raman/methods ; Multivariate Analysis ; Discriminant Analysis ; *Biofilms ; Cluster Analysis ; }, abstract = {In situ spatiotemporal biochemical characterization of the activity of living multicellular biofilms under external stimuli remains a significant challenge. Surface-enhanced Raman spectroscopy (SERS), combining the molecular fingerprint specificity of vibrational spectroscopy with the hotspot sensitivity of plasmonic nanostructures, has emerged as a promising noninvasive bioanalysis technique for living systems. However, most SERS devices do not allow reliable long-term spatiotemporal SERS measurements of multicellular systems because of challenges in producing spatially uniform and mechanically stable SERS hotspot arrays to interface with large cellular networks. Furthermore, very few studies have been conducted for multivariable analysis of spatiotemporal SERS datasets to extract spatially and temporally correlated biological information from multicellular systems. Here, we demonstrate in situ label-free spatiotemporal SERS measurements and multivariate analysis of Pseudomonas syringae biofilms during development and upon infection by bacteriophage virus Phi6 by employing nanolaminate plasmonic crystal SERS devices to interface mechanically stable, uniform, and spatially dense hotspot arrays with the P. syringae biofilms. We exploited unsupervised multivariate machine learning methods, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), to resolve the spatiotemporal evolution and Phi6 dose-dependent changes of major Raman peaks originating from biochemical components in P. syringae biofilms, including cellular components, extracellular polymeric substances (EPS), metabolite molecules, and cell lysate-enriched extracellular media. We then employed supervised multivariate analysis using linear discriminant analysis (LDA) for the multiclass classification of Phi6 dose-dependent biofilm responses, demonstrating the potential for viral infection diagnosis. We envision extending the in situ spatiotemporal SERS method to monitor dynamic, heterogeneous interactions between viruses and bacterial networks for applications such as phage-based anti-biofilm therapy development and continuous pathogenic virus detection.}, } @article {pmid36877741, year = {2023}, author = {Luque, LM and Carlevaro, CM and Llamoza Torres, CJ and Lomba, E}, title = {Physics-based tissue simulator to model multicellular systems: A study of liver regeneration and hepatocellular carcinoma recurrence.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010920}, pmid = {36877741}, issn = {1553-7358}, mesh = {Humans ; *Carcinoma, Hepatocellular ; Liver Regeneration ; *Liver Neoplasms ; Hepatectomy ; Models, Biological ; Neoplasm Recurrence, Local ; Tumor Microenvironment ; }, abstract = {We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.}, } @article {pmid36876435, year = {2023}, author = {Bernardo, N and Crespo, I and Cuppari, A and Meijer, WJJ and Boer, DR}, title = {A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53.}, journal = {Acta crystallographica. Section D, Structural biology}, volume = {79}, number = {Pt 3}, pages = {259-267}, pmid = {36876435}, issn = {2059-7983}, mesh = {Humans ; *Eukaryota ; Tumor Suppressor Protein p53 ; *Bacillus ; Bacillus subtilis ; Transcription Factors ; DNA ; }, abstract = {Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (RcopLS20) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology. In RcopLS20, this tetramerization domain is responsible for inducing DNA looping, a process that involves multiple tetramers. In accordance, it is shown that RcopLS20 can form octamers. This domain was named TetDloop and its occurrence was identified in other Bacillus species. The TetDloop fold was also found in the structure of a transcriptional repressor from Salmonella phage SPC32H. It is proposed that the TetDloop fold has evolved through divergent evolution and that the TetDloop originates from a common ancestor predating the occurrence of multicellular life.}, } @article {pmid36860212, year = {2022}, author = {Du, Q and Schaap, P}, title = {Autophagy of the somatic stalk cells likely nurses the propagating spores of Dictyostelid social amoebas [version 2; peer review: 2 approved, 1 approved with reservations].}, journal = {Open research Europe}, volume = {2}, number = {}, pages = {104}, pmid = {36860212}, issn = {2732-5121}, support = {742288/ERC_/European Research Council/International ; }, abstract = {BACKGROUND: Autophagy (self-feeding) assists survival of starving cells by partial self-digestion, while dormancy as cysts, spores or seeds enables long-term survival. Starving Dictyostelium amoebas construct multicellular fruiting bodies with spores and stalk cells, with many Dictyostelia still able to encyst individually like their single-celled ancestors. While autophagy mostly occurs in the somatic stalk cells, autophagy gene knock-outs in Dictyostelium discoideum (D. discoideum) formed no spores and lacked cAMP induction of prespore gene expression.

METHODS: To investigate whether autophagy also prevents encystation, we knocked-out autophagy genes atg5 and atg7 in the dictyostelid Polysphondylium pallidum, which forms both spores and cysts. We measured spore and cyst differentiation and viability in the knock-out as well as stalk and spore gene expression and its regulation by cAMP. We tested a hypothesis that spores require materials derived from autophagy in stalk cells. Sporulation requires secreted cAMP acting on receptors and intracellular cAMP acting on PKA. We compared the morphology and viability of spores developed in fruiting bodies with spores induced from single cells by stimulation with cAMP and 8Br-cAMP, a membrane-permeant PKA agonist.

RESULTS: Loss of autophagy in P. pallidum reduced but did not prevent encystation. Stalk cells still differentiated but stalks were disorganised. However, no spores were formed at all and cAMP-induced prespore gene expression was lost. D. discoideum spores induced in vitro by cAMP and 8Br-cAMP were smaller and rounder than spores formed multicellularly and while they were not lysed by detergent they germinated not (strain Ax2) or poorly (strain NC4), unlike spores formed in fruiting bodies.

CONCLUSIONS: The stringent requirement of sporulation on both multicellularity and autophagy, which occurs mostly in stalk cells, suggests that stalk cells nurse the spores through autophagy. This highlights autophagy as a major cause for somatic cell evolution in early multicellularity.}, } @article {pmid36856076, year = {2023}, author = {Takeuchi, K and Senda, M and Ikeda, Y and Okuwaki, K and Fukuzawa, K and Nakagawa, S and Sasaki, M and Sasaki, AT and Senda, T}, title = {Functional molecular evolution of a GTP sensing kinase: PI5P4Kβ.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.16763}, pmid = {36856076}, issn = {1742-4658}, support = {R01CA255331/NH/NIH HHS/United States ; R01GM144426/NH/NIH HHS/United States ; R01NS089815/NH/NIH HHS/United States ; }, abstract = {Over 4 billion years of evolution, multiple mutations, including nucleotide substitutions, gene and genome duplications and recombination, have established de novo genes that translate into proteins with novel properties essential for high-order cellular functions. However, molecular processes through which a protein evolutionarily acquires a novel function are mostly speculative. Recently, we have provided evidence for a potential evolutionary mechanism underlying how, in mammalian cells, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) evolved into a GTP sensor from ATP-utilizing kinase. Mechanistically, PI5P4Kβ has acquired the guanine efficient association (GEA) motif by mutating its nucleotide base recognition sequence, enabling the evolutionary transition from an ATP-dependent kinase to a distinct GTP/ATP dual kinase with its KM for GTP falling into physiological GTP concentrations-the genesis of GTP sensing activity. Importantly, the GTP sensing activity of PI5P4Kβ is critical for the manifestation of cellular metabolism and tumourigenic activity in the multicellular organism. The combination of structural, biochemical and biophysical analyses used in our study provides a novel framework for analysing how a protein can evolutionarily acquire a novel activity, which potentially introduces a critical function to the cell.}, } @article {pmid36854987, year = {2023}, author = {Duan, J and Wang, Y}, title = {Modeling nervous system tumors with human stem cells and organoids.}, journal = {Cell regeneration (London, England)}, volume = {12}, number = {1}, pages = {4}, pmid = {36854987}, issn = {2045-9769}, abstract = {Nervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models, such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models, call for the development of novel preclinical cancer models to more faithfully mimic the patient's cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.}, } @article {pmid36854263, year = {2023}, author = {Tang, S and Pichugin, Y and Hammerschmidt, K}, title = {An environmentally induced multicellular life cycle of a unicellular cyanobacterium.}, journal = {Current biology : CB}, volume = {33}, number = {4}, pages = {764-769.e5}, doi = {10.1016/j.cub.2023.01.069}, pmid = {36854263}, issn = {1879-0445}, mesh = {Animals ; *Cyanobacteria ; *Automobile Driving ; Biological Evolution ; Cell Death ; Life Cycle Stages ; }, abstract = {Understanding the evolutionary transition to multicellularity is a key problem in biology.[1][,][2][,][3][,][4] Nevertheless, the ecological conditions driving such transitions are not well understood. The first known transition to multicellularity occurred 2.5 billion years ago in cyanobacteria,[5][,][6][,][7] and today's cyanobacteria are characterized by enormous morphological diversity. They range from unicellular species; unicellular cyanobacteria with packet-like phenotypes, e.g., tetrads; and simple filamentous species to highly differentiated filamentous species.[8][,][9][,][10] The cyanobacterium Cyanothece sp. ATCC 51142, an isolate from the intertidal zone of the U.S. Gulf Coast,[11] was classified as a unicellular species.[12] We report a facultative life cycle of Cyanothece sp. in which multicellular filaments alternate with unicellular stages. In a series of experiments, we identified salinity and population density as environmental factors triggering the phenotypic switch between the two morphologies. Then, we used numerical models to test hypotheses regarding the nature of the environmental cues and the mechanisms underlying filament dissolution. While the results predict that the observed response is likely caused by an excreted compound in the medium, we cannot fully exclude changes in nutrient availability (as in Tuomi et al.[13] and Matz and Jürgens[14]). The best-fit modeling results show a nonlinear effect of the compound, which is characteristic of density-dependent sensing systems.[15][,][16] Furthermore, filament fragmentation is predicted to occur by connection cleavage rather than cell death of each alternating cell, which is supported by fluorescent and scanning electron microscopy results. The switch between unicellular and multicellular morphology constitutes an environmentally dependent life cycle that is likely an important step en route to permanent multicellularity.}, } @article {pmid36849252, year = {2023}, author = {Göbel, T and Goebel, B and Hyprath, M and Lamminger, I and Weisser, H and Angioni, C and Mathes, M and Thomas, D and Kahnt, AS}, title = {Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.}, journal = {Life science alliance}, volume = {6}, number = {5}, pages = {}, pmid = {36849252}, issn = {2575-1077}, mesh = {Humans ; *Arachidonate 5-Lipoxygenase/genetics ; Lipid Metabolism ; *Colonic Neoplasms ; Mechanistic Target of Rapamycin Complex 2 ; Phosphatidylinositol 3-Kinases ; }, abstract = {The leukotriene (LT) pathway is positively correlated with the progression of solid malignancies, but the factors that control the expression of 5-lipoxygenase (5-LO), the central enzyme in LT biosynthesis, in tumors are poorly understood. Here, we report that 5-LO along with other members of the LT pathway is up-regulated in multicellular colon tumor spheroids. This up-regulation was inversely correlated with cell proliferation and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways. Furthermore, we found that E2F1 and its target gene MYBL2 were involved in the repression of 5-LO during cell proliferation. Importantly, we found that this PI3K/mTORC-2- and MEK-1/ERK-dependent suppression of 5-LO is also existent in tumor cells from other origins, suggesting that this mechanism is widely applicable to other tumor entities. Our data show that tumor cells fine-tune 5-LO and LT biosynthesis in response to environmental changes repressing the enzyme during proliferation while making use of the enzyme under cell stress conditions, implying that tumor-derived 5-LO plays a role in the manipulation of the tumor stroma to quickly restore cell proliferation.}, } @article {pmid36830620, year = {2023}, author = {van Oosten-Hawle, P}, title = {Organismal Roles of Hsp90.}, journal = {Biomolecules}, volume = {13}, number = {2}, pages = {}, pmid = {36830620}, issn = {2218-273X}, mesh = {Humans ; Animals ; *HSP90 Heat-Shock Proteins/metabolism ; *Molecular Chaperones/metabolism ; Signal Transduction ; Proteostasis ; Stress, Physiological ; Mammals/metabolism ; }, abstract = {Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that assists in the maturation of many client proteins involved in cellular signal transduction. As a regulator of cellular signaling processes, it is vital for the maintenance of cellular proteostasis and adaptation to environmental stresses. Emerging research shows that Hsp90 function in an organism goes well beyond intracellular proteostasis. In metazoans, Hsp90, as an environmentally responsive chaperone, is involved in inter-tissue stress signaling responses that coordinate and safeguard cell nonautonomous proteostasis and organismal health. In this way, Hsp90 has the capacity to influence evolution and aging, and effect behavioral responses to facilitate tissue-defense systems that ensure organismal survival. In this review, I summarize the literature on the organismal roles of Hsp90 uncovered in multicellular organisms, from plants to invertebrates and mammals.}, } @article {pmid36824942, year = {2023}, author = {Compton, Z and Harris, V and Mellon, W and Rupp, S and Mallo, D and Kapsetaki, SE and Wilmot, M and Kennington, R and Noble, K and Baciu, C and Ramirez, L and Peraza, A and Martins, B and Sudhakar, S and Aksoy, S and Furukawa, G and Vincze, O and Giraudeau, M and Duke, EG and Spiro, S and Flach, E and Davidson, H and Zehnder, A and Graham, TA and Troan, B and Harrison, TM and Tollis, M and Schiffman, JD and Aktipis, A and Abegglen, LM and Maley, CC and Boddy, AM}, title = {Cancer Prevalence Across Vertebrates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.02.15.527881}, pmid = {36824942}, abstract = {Cancer is pervasive across multicellular species. Are there any patterns that can explain differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight and decreases with gestation time, contrary to Peto’s Paradox. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.}, } @article {pmid36822389, year = {2023}, author = {Wang, S and Chan, SY and Deng, Y and Khoo, BL and Chua, SL}, title = {Oxidative stress induced by Etoposide anti-cancer chemotherapy drives the emergence of tumor-associated bacteria resistance to fluoroquinolones.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2023.02.011}, pmid = {36822389}, issn = {2090-1224}, abstract = {INTRODUCTION: Antibiotic-resistant bacterial infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, are prevalent in lung cancer patients, resulting in poor clinical outcomes and high mortality. Etoposide (ETO) is an FDA-approved chemotherapy drug that kills cancer cells by damaging DNA through oxidative stress. However, it is unclear if ETO can cause unintentional side effects on tumor-associated microbial pathogens, such as inducing antibiotic resistance.

OBJECTIVES: We aimed to show that prolonged ETO treatment could unintendedly confer fluoroquinolone antibiotic resistance to P. aeruginosa, and evaluate the effect of tumor-associated P. aeruginosa on tumor progression.

METHODS: We employed experimental evolution assay to treat P. aeruginosa with prolonged ETO exposure, evaluated the ciprofloxacin resistance, and elucidated the gene mutations by DNA sequencing. We also established a lung tumor-P. aeruginosa bacterial model to study the role of ETO-evolved intra-tumoral bacteria in tumor progression using immunostaining and confocal microscopy.

RESULTS: ETO could generate oxidative stress and lead to gene mutations in P. aeruginosa, especially the gyrase (gyrA) gene, resulting in acquired fluoroquinolone resistance. We further demonstrated using a microfluidic-based lung tumor-P. aeruginosa coculture model that bacteria can evolve ciprofloxacin (CIP) resistance in a tumor microenvironment. Moreover, ETO-induced CIP-resistant (EICR) mutants could form multicellular biofilms which protected tumor cells from ETO killing and enabled tumor progression.

CONCLUSION: Overall, our preclinical proof-of-concept provides insights into how anti-cancer chemotherapy could inadvertently allow tumor-associated bacteria to acquire antibiotic resistance mutations and shed new light on the development of novel anti-cancer treatments based on anti-bacterial strategies.}, } @article {pmid36821408, year = {2023}, author = {Baselga-Cervera, B and Jacobsen, KA and Denison, RF and Travisano, M}, title = {Experimental evolution in the cyanobacterium Trichormus variabilis: increases in size and morphological diversity.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/evolut/qpad037}, pmid = {36821408}, issn = {1558-5646}, abstract = {Cyanobacteria morphology has apparently remained almost unchanged for billions of years, exhibiting remarkable evolutionary stasis. Cyanobacteria appear to have reached their maximum morphological complexity in terms of size, modes of multicellularity, and cellular types by ~2 Ga. This contrasts with the increased complexity observed in other multicellular lineages, such as plants. Using experimental evolution, we show that morphological diversity can rapidly evolve in a species of filamentous cyanobacteria. Since size has such significance with regard to organismal complexity, we subjected the heterocyst-forming cyanobacterium Trichornus variabilis (syn. Anabaena variabilis) to selection for larger size. We observed increases in size of more than 30-fold, relative to the ancestral population, after 45 cycles of selection. Two distinguishable nascent morphological elaborations were identified in all the selected populations: Tangle (long, tangled filaments) and Cluster (clusters of short filaments) morphology. Growth from single cells indicates heritability of the evolved Tangle and Cluster morphological phenotypes. Cyanobacteria evolutionary conservatism is ascribed to developmental constraints, slow evolution rates, or ecological flexibility. These results open opportunities to study possibilities and constraints for the evolution of higher integrated biological levels of organization within this lineage.}, } @article {pmid36816026, year = {2023}, author = {Horjales, S and Li Calzi, M and Francia, ME and Cayota, A and Garcia-Silva, MR}, title = {piRNA pathway evolution beyond gonad context: Perspectives from apicomplexa and trypanosomatids.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1129194}, pmid = {36816026}, issn = {1664-8021}, abstract = {piRNAs function as genome defense mechanisms against transposable elements insertions within germ line cells. Recent studies have unraveled that piRNA pathways are not limited to germ cells as initially reckoned, but are instead also found in non-gonadal somatic contexts. Moreover, these pathways have also been reported in bacteria, mollusks and arthropods, associated with safeguard of genomes against transposable elements, regulation of gene expression and with direct consequences in axon regeneration and memory formation. In this Perspective we draw attention to early branching parasitic protozoa, whose genome preservation is an essential function as in late eukaryotes. However, little is known about the defense mechanisms of these genomes. We and others have described the presence of putative PIWI-related machinery members in protozoan parasites. We have described the presence of a PIWI-like protein in Trypanosoma cruzi, bound to small non-coding RNAs (sRNAs) as cargo of secreted extracellular vesicles relevant in intercellular communication and host infection. Herein, we put forward the presence of members related to Argonaute pathways in both Trypanosoma cruzi and Toxoplasma gondii. The presence of PIWI-like machinery in Trypansomatids and Apicomplexa, respectively, could be evidence of an ancestral piRNA machinery that evolved to become more sophisticated and complex in multicellular eukaryotes. We propose a model in which ancient PIWI proteins were expressed broadly and had functions independent of germline maintenance. A better understanding of current and ancestral PIWI/piRNAs will be relevant to better understand key mechanisms of genome integrity conservation during cell cycle progression and modulation of host defense mechanisms by protozoan parasites.}, } @article {pmid36813362, year = {2023}, author = {Samuel, V and Rajeev, T and Ramesh, L and Sundararaman, A}, title = {Integrin receptor trafficking in health and disease.}, journal = {Progress in molecular biology and translational science}, volume = {196}, number = {}, pages = {271-302}, doi = {10.1016/bs.pmbts.2022.09.008}, pmid = {36813362}, issn = {1878-0814}, mesh = {Humans ; Protein Transport/physiology ; *Integrins/metabolism ; Cell Membrane/metabolism ; Signal Transduction ; *Neoplasms/metabolism ; Cell Adhesion/physiology ; Cell Movement/physiology ; }, abstract = {Integrins are a family of 24 different heterodimers that are indispensable for multicellular life. Cell polarity, adhesion and migration are controlled by integrins delivered to the cell surface which in turn is regulated by the exo- and endocytic trafficking of integrins. The deep integration between trafficking and cell signaling determines the spatial and temporal output from any biochemical cue. Integrin trafficking plays a key role in development and many pathological conditions, especially cancer. Several novel regulators of integrin traffic have been discovered in recent times, including a novel class of integrin carrying vesicles, the intracellular nanovesicles (INVs). The tight regulation of trafficking pathways by cell signaling, where kinases phosphorylate key small GTPases in the trafficking pathway enable coordination of cell response to the extracellular milieu. Integrin heterodimer expression and trafficking differ in different tissues and contexts. In this Chapter, we discuss recent studies on integrin trafficking and its contribution to normal physiological and pathophysiological states.}, } @article {pmid36811171, year = {2023}, author = {Furumizu, C and Aalen, RB}, title = {Peptide signaling through leucine-rich repeat receptor kinases: insight into land plant evolution.}, journal = {The New phytologist}, volume = {238}, number = {3}, pages = {977-982}, doi = {10.1111/nph.18827}, pmid = {36811171}, issn = {1469-8137}, mesh = {*Protein Serine-Threonine Kinases/metabolism ; Plant Proteins/metabolism ; Leucine ; Phylogeny ; Signal Transduction/physiology ; Peptides/genetics ; *Embryophyta/genetics/metabolism ; }, abstract = {Multicellular organisms need mechanisms for communication between cells so that they can fulfill their purpose in the organism as a whole. Over the last two decades, several small post-translationally modified peptides (PTMPs) have been identified as components of cell-to-cell signaling modules in flowering plants. Such peptides most often influence growth and development of organs not universally conserved among land plants. PTMPs have been matched to subfamily XI leucine-rich repeat receptor-like kinases with > 20 repeats. Phylogenetic analyses, facilitated by recently published genomic sequences of non-flowering plants, have identified seven clades of such receptors with a history back to the common ancestor of bryophytes and vascular plants. This raises a number of questions: When did peptide signaling arise during land plant evolution? Have orthologous peptide-receptor pairs preserved their biological functions? Has peptide signaling contributed to major innovations, such as stomata, vasculature, roots, seeds, and flowers? Using genomic, genetic, biochemical, and structural data and non-angiosperm model species, it is now possible to address these questions. The vast number of peptides that have not yet found their partners suggests furthermore that we have far more to learn about peptide signaling in the coming decades.}, } @article {pmid36809239, year = {2023}, author = {Lambros, M and Sella, Y and Bergman, A}, title = {Phenotypic pliancy and the breakdown of epigenetic polycomb mechanisms.}, journal = {PLoS computational biology}, volume = {19}, number = {2}, pages = {e1010889}, pmid = {36809239}, issn = {1553-7358}, support = {R01 CA164468/CA/NCI NIH HHS/United States ; R01 DA033788/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; Polycomb-Group Proteins/genetics ; *Drosophila Proteins/metabolism ; Epigenesis, Genetic ; Cell Differentiation ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Epigenetic regulatory mechanisms allow multicellular organisms to develop distinct specialized cell identities despite having the same total genome. Cell-fate choices are based on gene expression programs and environmental cues that cells experience during embryonic development, and are usually maintained throughout the life of the organism despite new environmental cues. The evolutionarily conserved Polycomb group (PcG) proteins form Polycomb Repressive Complexes that help orchestrate these developmental choices. Post-development, these complexes actively maintain the resulting cell fate, even in the face of environmental perturbations. Given the crucial role of these polycomb mechanisms in providing phenotypic fidelity (i.e. maintenance of cell fate), we hypothesize that their dysregulation after development will lead to decreased phenotypic fidelity allowing dysregulated cells to sustainably switch their phenotype in response to environmental changes. We call this abnormal phenotypic switching phenotypic pliancy. We introduce a general computational evolutionary model that allows us to test our systems-level phenotypic pliancy hypothesis in-silico and in a context-independent manner. We find that 1) phenotypic fidelity is an emergent systems-level property of PcG-like mechanism evolution, and 2) phenotypic pliancy is an emergent systems-level property resulting from this mechanism's dysregulation. Since there is evidence that metastatic cells behave in a phenotypically pliant manner, we hypothesize that progression to metastasis is driven by the emergence of phenotypic pliancy in cancer cells as a result of PcG mechanism dysregulation. We corroborate our hypothesis using single-cell RNA-sequencing data from metastatic cancers. We find that metastatic cancer cells are phenotypically pliant in the same manner as predicted by our model.}, } @article {pmid36806172, year = {2023}, author = {Kuang, X and Guan, G and Tang, C and Zhang, L}, title = {MorphoSim: an efficient and scalable phase-field framework for accurately simulating multicellular morphologies.}, journal = {NPJ systems biology and applications}, volume = {9}, number = {1}, pages = {6}, pmid = {36806172}, issn = {2056-7189}, abstract = {The phase field model can accurately simulate the evolution of microstructures with complex morphologies, and it has been widely used for cell modeling in the last two decades. However, compared to other cellular models such as the coarse-grained model and the vertex model, its high computational cost caused by three-dimensional spatial discretization hampered its application and scalability, especially for multicellular organisms. Recently, we built a phase field model coupled with in vivo imaging data to accurately reconstruct the embryonic morphogenesis of Caenorhabditis elegans from 1- to 8-cell stages. In this work, we propose an improved phase field model by using the stabilized numerical scheme and modified volume constriction. Then we present a scalable phase-field framework, MorphoSim, which is 100 times more efficient than the previous one and can simulate over 100 mechanically interacting cells. Finally, we demonstrate how MorphoSim can be successfully applied to reproduce the assembly, self-repairing, and dissociation of a synthetic artificial multicellular system - the synNotch system.}, } @article {pmid36797913, year = {2023}, author = {Leptos, KC and Chioccioli, M and Furlan, S and Pesci, AI and Goldstein, RE}, title = {Phototaxis of Chlamydomonas arises from a tuned adaptive photoresponse shared with multicellular Volvocine green algae.}, journal = {Physical review. E}, volume = {107}, number = {1-1}, pages = {014404}, doi = {10.1103/PhysRevE.107.014404}, pmid = {36797913}, issn = {2470-0053}, support = {207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Chlamydomonas ; Phylogeny ; Phototaxis ; *Chlorophyta ; Biological Evolution ; *Volvox ; }, abstract = {A fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellate Chlamydomonas to multicellular species of Volvox with up to 50,000 Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies of Volvox and Gonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse of micropipette-held Chlamydomonas with 3D tracking of freely swimming cells, we show that such tuning also underlies its phototaxis. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of timescales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive timescales in Volvocine algae are tuned to the organisms' rotational periods across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella of Chlamydomonas, the flagellated edges of Gonium, and the flagellated hemispheres of Volvox.}, } @article {pmid36789784, year = {2023}, author = {Rusin, LY}, title = {Evolution of homology: From archetype towards a holistic concept of cell type.}, journal = {Journal of morphology}, volume = {284}, number = {4}, pages = {e21569}, doi = {10.1002/jmor.21569}, pmid = {36789784}, issn = {1097-4687}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; *Growth and Development ; Cell Lineage ; Phenotype ; }, abstract = {The concept of homology lies in the heart of comparative biological science. The distinction between homology as structure and analogy as function has shaped the evolutionary paradigm for a century and formed the axis of comparative anatomy and embryology, which accept the identity of structure as a ground measure of relatedness. The advent of single-cell genomics overturned the classical view of cell homology by establishing a backbone regulatory identity of cell types, the basic biological units bridging the molecular and phenotypic dimensions, to reveal that the cell is the most flexible unit of living matter and that many approaches of classical biology need to be revised to understand evolution and diversity at the cellular level. The emerging theory of cell types explicitly decouples cell identity from phenotype, essentially allowing for the divergence of evolutionarily related morphotypes beyond recognition, as well as it decouples ontogenetic cell lineage from cell-type phylogeny, whereby explicating that cell types can share common descent regardless of their structure, function or developmental origin. The article succinctly summarizes current progress and opinion in this field and formulates a more generalistic view of biological cell types as avatars, transient or terminal cell states deployed in a continuum of states by the developmental programme of one and the same omnipotent cell, capable of changing or combining identities with distinct evolutionary histories or inventing ad hoc identities that never existed in evolution or development. It highlights how the new logic grounded in the regulatory nature of cell identity transforms the concepts of cell homology and phenotypic stability, suggesting that cellular evolution is inherently and massively network-like, with one-to-one homologies being rather uncommon and restricted to shallower levels of the animal tree of life.}, } @article {pmid36786569, year = {2023}, author = {Cont, A and Vermeil, J and Persat, A}, title = {Material Substrate Physical Properties Control Pseudomonas aeruginosa Biofilm Architecture.}, journal = {mBio}, volume = {}, number = {}, pages = {e0351822}, doi = {10.1128/mbio.03518-22}, pmid = {36786569}, issn = {2150-7511}, abstract = {In the wild, bacteria are most frequently found in the form of multicellular structures called biofilms. Biofilms grow at the surface of abiotic and living materials with wide-ranging mechanical properties. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on indwelling medical devices and on soft tissues, including burn wounds and the airway mucosa. Despite the critical role of substrates in the foundation of biofilms, we still lack a clear understanding of how material mechanics regulate their architecture and the physiology of resident bacteria. Here, we demonstrate that physical properties of hydrogel material substrates define P. aeruginosa biofilm architecture. We show that hydrogel mesh size regulates twitching motility, a surface exploration mechanism priming biofilms, ultimately controlling the organization of single cells in the multicellular community. The resulting architectural transitions increase P. aeruginosa's tolerance to colistin, a last-resort antibiotic. In addition, mechanical regulation of twitching motility affects P. aeruginosa clonal lineages, so that biofilms are more mixed on relatively denser materials. Our results thereby establish material properties as a factor that dramatically affects biofilm architecture, antibiotic efficacy, and evolution of the resident population. IMPORTANCE The biofilm lifestyle is the most widespread survival strategy in the bacterial world. Pseudomonas aeruginosa biofilms cause chronic infections and are highly recalcitrant to antimicrobials. The genetic requirements allowing P. aeruginosa to grow into biofilms are known, but not the physical stimuli that regulate their formation. Despite colonizing biological tissues, investigations of biofilms on soft materials are limited. In this work, we show that biofilms take unexpected forms when growing on soft substrates. The physical properties of the material shape P. aeruginosa biofilms by regulating surface-specific twitching motility. Physical control of biofilm morphogenesis ultimately influences the resilience of biofilms to antimicrobials, linking physical environment with tolerance to treatment. Altogether, our work established that the physical properties of a surface are a critical environmental regulator of biofilm biogenesis and evolution.}, } @article {pmid36786333, year = {2023}, author = {Godfroy, O and Zheng, M and Yao, H and Henschen, A and Peters, AF and Scornet, D and Colin, S and Ronchi, P and Hipp, K and Nagasato, C and Motomura, T and Cock, JM and Coelho, SM}, title = {The baseless mutant links protein phosphatase 2A with basal cell identity in the brown alga Ectocarpus.}, journal = {Development (Cambridge, England)}, volume = {150}, number = {4}, pages = {}, doi = {10.1242/dev.201283}, pmid = {36786333}, issn = {1477-9129}, support = {864038/ERC_/European Research Council/International ; }, mesh = {*Protein Phosphatase 2/genetics/metabolism ; Mutation/genetics ; Gene Expression Profiling ; Protein Processing, Post-Translational ; *Phaeophyta/genetics/metabolism ; }, abstract = {The first mitotic division of the initial cell is a key event in all multicellular organisms and is associated with the establishment of major developmental axes and cell fates. The brown alga Ectocarpus has a haploid-diploid life cycle that involves the development of two multicellular generations: the sporophyte and the gametophyte. Each generation deploys a distinct developmental programme autonomously from an initial cell, the first cell division of which sets up the future body pattern. Here, we show that mutations in the BASELESS (BAS) gene result in multiple cellular defects during the first cell division and subsequent failure to produce basal structures during both generations. BAS encodes a type B″ regulatory subunit of protein phosphatase 2A (PP2A), and transcriptomic analysis identified potential effector genes that may be involved in determining basal cell fate. The bas mutant phenotype is very similar to that observed in distag (dis) mutants, which lack a functional Tubulin-binding co-factor Cd1 (TBCCd1) protein, indicating that TBCCd1 and PP2A are two essential components of the cellular machinery that regulates the first cell division and mediates basal cell fate determination.}, } @article {pmid36781087, year = {2023}, author = {Brown, Y and Hua, S and Tanwar, PS}, title = {Extracellular matrix in high-grade serous ovarian cancer: Advances in understanding of carcinogenesis and cancer biology.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {118}, number = {}, pages = {16-46}, doi = {10.1016/j.matbio.2023.02.004}, pmid = {36781087}, issn = {1569-1802}, mesh = {Female ; Humans ; *Ovarian Neoplasms/genetics ; *Cystadenocarcinoma, Serous/genetics ; Extracellular Matrix/pathology ; Carcinogenesis/genetics ; Biology ; Tumor Microenvironment ; }, abstract = {High-grade serous ovarian cancer (HGSOC) is notoriously known as the "silent killer" of post-menopausal women as it has an insidious progression and is the deadliest gynaecological cancer. Although a dual origin of HGSOC is now widely accepted, there is growing evidence that most cases of HGSOC originate from the fallopian tube epithelium. In this review, we will address the fallopian tube origin and involvement of the extracellular matrix (ECM) in HGSOC development. There is limited research on the role of ECM at the earliest stages of HGSOC carcinogenesis. Here we aim to synthesise current understanding of the contribution of ECM to each stage of HGSOC development and progression, beginning at serous tubal intraepithelial carcinoma (STIC) precursor lesions and proceeding across key events including dissemination of tumourigenic fallopian tube epithelial cells to the ovary, survival of these cells in peritoneal fluid as multicellular aggregates, and colonisation of the ovary. Likewise, as part of the metastatic series of events, serous ovarian cancer cells survive travel in peritoneal fluid, attach to, migrate across the mesothelium and invade into the sub-mesothelial matrix of secondary sites in the peritoneal cavity. Halting cancer at the pre-metastatic stage and finding ways to stop the dissemination of ovarian cancer cells from the primary site is critical for improving patient survival. The development of drug resistance also contributes to poor survival statistics in HGSOC. In this review, we provide an update on the involvement of the ECM in metastasis and drug resistance in HGSOC. Interplay between different cell-types, growth factor gradients as well as evolving ECM composition and organisation, creates microenvironment conditions that promote metastatic progression and drug resistance of ovarian cancer cells. By understanding ECM involvement in the carcinogenesis and chemoresistance of HGSOC, this may prompt ideas for further research for developing new early diagnostic tests and therapeutic strategies for HGSOC with the end goal of improving patient health outcomes.}, } @article {pmid36779552, year = {2023}, author = {Mitchell, RL and Kenrick, P and Pressel, S and Duckett, J and Strullu-Derrien, C and Davies, N and McMahon, WJ and Summerfield, R}, title = {Terrestrial surface stabilisation by modern analogues of the earliest land plants: A multi-dimensional imaging study.}, journal = {Geobiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/gbi.12546}, pmid = {36779552}, issn = {1472-4669}, abstract = {The evolution of the first plant-based terrestrial ecosystems in the early Palaeozoic had a profound effect on the development of soils, the architecture of sedimentary systems, and shifts in global biogeochemical cycles. In part, this was due to the evolution of complex below-ground (root-like) anchorage systems in plants, which expanded and promoted plant-mineral interactions, weathering, and resulting surface sediment stabilisation. However, little is understood about how these micro-scale processes occurred, because of a lack of in situ plant fossils in sedimentary rocks/palaeosols that exhibit these interactions. Some modern plants (e.g., liverworts, mosses, lycophytes) share key features with the earliest land plants; these include uni- or multicellular rhizoid-like anchorage systems or simple roots, and the ability to develop below-ground networks through prostrate axes, and intimate associations with fungi, making them suitable analogues. Here, we investigated cryptogamic ground covers in Iceland and New Zealand to better understand these interactions, and how they initiate the sediment stabilisation process. We employed multi-dimensional and multi-scale imaging, including scanning electron microscopy (SEM) and X-ray Computed Tomography (μCT) of non-vascular liverworts (Haplomitriopsida and complex thalloids) and mosses, with additional imaging of vascular lycopods. We find that plants interact with their substrate in multiple ways, including: (1) through the development of extensive surface coverings as mats; (2) entrapment of sediment grains within and between networks of rhizoids; (3) grain entwining and adherence by rhizoids, through mucilage secretions, biofilm-like envelopment of thalli on surface grains; and (4) through grain entrapment within upright 'leafy' structures. Significantly, μCT imaging allows us to ascertain that rhizoids are the main method for entrapment and stabilisation of soil grains in the thalloid liverworts. This information provides us with details of how the earliest land plants may have significantly influenced early Palaeozoic sedimentary system architectures, promoted in situ weathering and proto-soil development, and how these interactions diversified over time with the evolution of new plant organ systems. Further, this study highlights the importance of cryptogamic organisms in the early stages of sediment stabilisation and soil formation today.}, } @article {pmid36778228, year = {2023}, author = {Feng, X and Zheng, J and Irisarri, I and Yu, H and Zheng, B and Ali, Z and de Vries, S and Keller, J and Fürst-Jansen, JMR and Dadras, A and Zegers, JMS and Rieseberg, TP and Ashok, AD and Darienko, T and Bierenbroodspot, MJ and Gramzow, L and Petroll, R and Haas, FB and Fernandez-Pozo, N and Nousias, O and Li, T and Fitzek, E and Grayburn, WS and Rittmeier, N and Permann, C and Rümpler, F and Archibald, JM and Theißen, G and Mower, JP and Lorenz, M and Buschmann, H and von Schwartzenberg, K and Boston, L and Hayes, RD and Daum, C and Barry, K and Grigoriev, IV and Wang, X and Li, FW and Rensing, SA and Ari, JB and Keren, N and Mosquna, A and Holzinger, A and Delaux, PM and Zhang, C and Huang, J and Mutwil, M and de Vries, J and Yin, Y}, title = {Chromosome-level genomes of multicellular algal sisters to land plants illuminate signaling network evolution.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778228}, abstract = {UNLABELLED: The filamentous and unicellular algae of the class Zygnematophyceae are the closest algal relatives of land plants. Inferring the properties of the last common ancestor shared by these algae and land plants allows us to identify decisive traits that enabled the conquest of land by plants. We sequenced four genomes of filamentous Zygnematophyceae (three strains of Zygnema circumcarinatum and one strain of Z. cylindricum) and generated chromosome-scale assemblies for all strains of the emerging model system Z. circumcarinatum . Comparative genomic analyses reveal expanded genes for signaling cascades, environmental response, and intracellular trafficking that we associate with multicellularity. Gene family analyses suggest that Zygnematophyceae share all the major enzymes with land plants for cell wall polysaccharide synthesis, degradation, and modifications; most of the enzymes for cell wall innovations, especially for polysaccharide backbone synthesis, were gained more than 700 million years ago. In Zygnematophyceae, these enzyme families expanded, forming co-expressed modules. Transcriptomic profiling of over 19 growth conditions combined with co-expression network analyses uncover cohorts of genes that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

HIGHLIGHTS: Genomes of four filamentous algae (Zygnema) sisters to land plants Zygnema are rich in genes for multicellular growth and environmental acclimation: signaling, lipid modification, and transport Cell wall innovations: diversification of hexameric rosette cellulose synthase in ZygnematophyceaeCo-expression networks reveal conserved modules for balancing growth and acclimation.}, } @article {pmid36765079, year = {2023}, author = {Debit, A and Charton, F and Pierre-Elies, P and Bowler, C and Cruz de Carvalho, H}, title = {Differential expression patterns of long noncoding RNAs in a pleiomorphic diatom and relation to hyposalinity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2440}, pmid = {36765079}, issn = {2045-2322}, mesh = {Animals ; *Diatoms/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Gene Expression Profiling ; Transcriptome ; Culture Media/metabolism ; }, abstract = {Long non-coding (lnc)RNAs have been shown to have central roles in stress responses, cell identity and developmental processes in multicellular organisms as well as in unicellular fungi. Previous works have shown the occurrence of lncRNAs in diatoms, namely in Phaeodactylum tricornutum, many of which being expressed under specific stress conditions. Interestingly, P. tricornutum is the only known diatom that has a demonstrated morphological plasticity, occurring in three distinct morphotypes: fusiform, triradiate and oval. Although the morphotypes are interchangeable, the fusiform is the dominant one while both the triradiate and the oval forms are less common, the latter often being associated with stress conditions such as low salinity and solid culture media, amongst others. Nonetheless, the molecular basis underpinning morphotype identity in P. tricornutum remains elusive. Using twelve previously published transcriptomic datasets originating from the three morphotypes of P. tricornutum, we sought to investigate the expression patterns of lncRNAs (lincRNAs and NATs) in these distinct morphotypes, using pairwise comparisons, in order to explore the putative involvement of these noncoding molecules in morphotype identity. We found that differentially expressed lncRNAs cluster according to morphotype, indicating that lncRNAs are not randomly expressed, but rather seem to provide a specific (noncoding) transcriptomic signature of the morphotype. We also present evidence to suggest that the major differences in DE genes (both noncoding and coding) between the stress related oval morphotype and the most common fusiform morphotype could be due, to a large extent, to the hyposaline culture conditions rather than to the morphotype itself. However, several lncRNAs associated to each one of the three morphotypes were identified, which could have a potential role in morphotype (or cell) identity in P. tricornutum, similar to what has been found in both animals and plant development.}, } @article {pmid36756235, year = {2022}, author = {Yang, Q and Sharif, Y and Zhuang, Y and Chen, H and Zhang, C and Fu, H and Wang, S and Cai, T and Chen, K and Raza, A and Wang, L and Zhuang, W}, title = {Genome-wide identification of germin-like proteins in peanut (Arachis hypogea L.) and expression analysis under different abiotic stresses.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {1044144}, pmid = {36756235}, issn = {1664-462X}, abstract = {Peanut is an important food and feed crop, providing oil and protein nutrients. Germins and germin-like proteins (GLPs) are ubiquitously present in plants playing numerous roles in defense, growth and development, and different signaling pathways. However, the GLP members have not been comprehensively studied in peanut at the genome-wide scale. We carried out a genome-wide identification of the GLP genes in peanut genome. GLP members were identified comprehensively, and gene structure, genomic positions, motifs/domains distribution patterns, and phylogenetic history were studied in detail. Promoter Cis-elements, gene duplication, collinearity, miRNAs, protein-protein interactions, and expression were determined. A total of 84 GLPs (AhGLPs) were found in the genome of cultivated peanut. These GLP genes were clustered into six groups. Segmental duplication events played a key role in the evolution of AhGLPs, and purifying selection pressure was underlying the duplication process. Most AhGLPs possessed a well-maintained gene structure and motif organization within the same group. The promoter regions of AhGLPs contained several key cis-elements responsive to 'phytohormones', 'growth and development', defense, and 'light induction'. Seven microRNAs (miRNAs) from six families were found targeting 25 AhGLPs. Gene Ontology (GO) enrichment analysis showed that AhGLPs are highly enriched in nutrient reservoir activity, aleurone grain, external encapsulating structure, multicellular organismal reproductive process, and response to acid chemicals, indicating their important biological roles. AhGLP14, AhGLP38, AhGLP54, and AhGLP76 were expressed in most tissues, while AhGLP26, AhGLP29, and AhGLP62 showed abundant expression in the pericarp. AhGLP7, AhGLP20, and AhGLP21, etc., showed specifically high expression in embryo, while AhGLP12, AhGLP18, AhGLP40, AhGLP78, and AhGLP82 were highly expressed under different hormones, water, and temperature stress. The qRT-PCR results were in accordance with the transcriptome expression data. In short, these findings provided a foundation for future functional investigations on the AhGLPs for peanut breeding programs.}, } @article {pmid36750954, year = {2023}, author = {Zhang, X and Chen, S and Zhao, Z and Ma, C and Liu, Y}, title = {Investigation of B-atp6-orfH79 distributing in Chinese populations of Oryza rufipogon and analysis of its chimeric structure.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {81}, pmid = {36750954}, issn = {1471-2229}, mesh = {DNA, Mitochondrial/genetics/metabolism ; Mitochondria/metabolism ; *Oryza/genetics ; Plant Breeding ; }, abstract = {BACKGROUND: The cytoplasmic male sterility (CMS) of rice is caused by chimeric mitochondrial DNA (mtDNA) that is maternally inherited in the majority of multicellular organisms. Wild rice (Oryza rufipogon Griff.) has been regarded as the ancestral progenitor of Asian cultivated rice (Oryza sativa L.). To investigate the distribution of original CMS source, and explore the origin of gametophytic CMS gene, a total of 427 individuals with seventeen representative populations of O. rufipogon were collected in from Dongxiang of Jiangxi Province to Sanya of Hainan Province, China, for the PCR amplification of atp6, orfH79 and B-atp6-orfH79, respectively.

RESULTS: The B-atp6-orfH79 and its variants (B-atp6-GSV) were detected in five among seventeen populations (i.e. HK, GZ, PS, TL and YJ) through PCR amplification, which could be divided into three haplotypes, i.e., BH1, BH2, and BH3. The BH2 haplotype was identical to B-atp6-orfH79, while the BH1 and BH3 were the novel haplotypes of B-atp6-GSV. Combined with the high-homology sequences in GenBank, a total of eighteen haplotypes have been revealed, only with ten haplotypes in orfH79 and its variants (GSV) that belong to three species (i.e. O. rufipogon, Oryza nivara and Oryza sativa). Enough haplotypes clearly demonstrated the uniform structural characteristics of the B-atp6-orfH79 as follows: except for the conserved sequence (671 bp) composed of B-atp6 (619 bp) and the downstream followed the B-atp6 (52 bp, DS), and GSV sequence, a rich variable sequence (VS, 176 bp) lies between the DS and GSV with five insertion or deletion and more than 30 single nucleotide polymorphism. Maximum likelihood analysis showed that eighteen haplotypes formed three clades with high support rate. The hierarchical analysis of molecular variance (AMOVA) indicated the occurrence of variation among all populations (FST = 1; P < 0.001), which implied that the chimeric structure occurred independently. Three haplotypes (i.e., H1, H2 and H3) were detected by the primer of orfH79, which were identical to the GVS in B-atp6-GVS structure, respectively. All seventeen haplotypes of the orfH79, belonged to six species based on our results and the existing references. Seven existed single nucleotide polymorphism in GSV section can be translated into eleven various amino acid sequences.

CONCLUSIONS: Generally, this study, indicating that orfH79 was always accompanied by the B-atp6, not only provide two original CMS sources for rice breeding, but also confirm the uniform structure of B-atp-orfH79, which contribute to revealing the origin of rice gametophytic CMS genes, and the reason about frequent recombination of mitochondrial DNA.}, } @article {pmid36743469, year = {2023}, author = {Liu, J and Xing, WY and Liu, B and Zhang, CC}, title = {Three-dimensional coordination of cell-division site positioning in a filamentous cyanobacterium.}, journal = {PNAS nexus}, volume = {2}, number = {2}, pages = {pgac307}, pmid = {36743469}, issn = {2752-6542}, abstract = {Bacterial cells mostly divide symmetrically. In the filamentous, multicellular cyanobacterium Anabaena, cell-division planes are aligned vertically relative to the long axis of every single cell. This observation suggests that both the placement and the angle of the division planes are controlled in every single cell so that the filament can grow in one single dimension along the long axis. In this study, we showed that inactivation of patU3 encoding a cell-division inhibitor led cells to divide asymmetrically in two dimensions leading to twisted filaments, indicating that PatU3 controls not only the position but also the angle of the division planes. Deletion of the conserved minC and minD genes affected cell division symmetry, but not the angle of the division planes. Remarkably, when both patU3 and minCD were inactivated, cells could divide asymmetrically over 360° angles in three dimensions across different cellular sections, producing not only cells with irregular sizes, but also branching filaments. This study demonstrated the existence of a system operating in a three-dimensional manner for the control of cell division in Anabaena. Such a regulation may have been evolved to accommodate multicellular behaviors, a hallmark in evolution.}, } @article {pmid36717890, year = {2023}, author = {Piccinini, G and Milani, L}, title = {Germline-related molecular phenotype in Metazoa: conservation and innovation highlighted by comparative transcriptomics.}, journal = {EvoDevo}, volume = {14}, number = {1}, pages = {2}, pmid = {36717890}, issn = {2041-9139}, abstract = {BACKGROUND: In Metazoa, the germline represents the cell lineage devoted to the transmission of genetic heredity across generations. Its functions intuitively evoke the crucial roles that it plays in organism development and species evolution, and its establishment is tightly tied to animal multicellularity itself. The molecular toolkit expressed in germ cells has a high degree of conservation between species, and it also shares many components with the molecular phenotype of some animal totipotent cell lineages, like planarian neoblasts and sponge archaeocytes. The present study stems from these observations and represents a transcriptome-wide comparative analysis between germline-related samples of 9 animal species (7 phyla), comprehending also totipotent lineages classically considered somatic.

RESULTS: Differential expression analyses were performed for each species between germline-related and control somatic tissues. We then compared the different germline-related transcriptional profiles across the species without the need for an a priori set of genes. Through a phylostratigraphic analysis, we observed that the proportion of phylum- and Metazoa-specific genes among germline-related upregulated transcripts was lower than expected by chance for almost all species. Moreover, homologous genes related to proper DNA replication resulted the most common when comparing the considered species, while the regulation of transcription and post-transcriptional mechanisms appeared more variable, showing shared upregulated functions and domains, but very few homologous whole-length sequences.

CONCLUSIONS: Our wide-scale comparative analysis mostly confirmed previous molecular characterizations of specific germline-related lineages. Additionally, we observed a consistent signal throughout the whole data set, therefore comprehending both canonically defined germline samples (germ cells), and totipotent cell lineages classically considered somatic (neoblasts and archaeocytes). The phylostratigraphic analysis supported the less probable involvement of novel molecular factors in the germline-related transcriptional phenotype and highlighted the early origin of such cell programming and its conservation throughout evolution. Moreover, the fact that the mostly shared molecular factors were involved in DNA replication and repair suggests how fidelity in genetic material inheritance is a strong and conserved driver of germline-related molecular phenotype, while transcriptional and post-transcriptional regulations appear differently tuned among the lineages.}, } @article {pmid36717459, year = {2022}, author = {Pandey, T and Ma, DK}, title = {Stress-Induced Phenoptosis: Mechanistic Insights and Evolutionary Implications.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {12}, pages = {1504-1511}, doi = {10.1134/S0006297922120082}, pmid = {36717459}, issn = {1608-3040}, mesh = {Animals ; Humans ; *Caenorhabditis elegans/genetics ; *Apoptosis ; Aging/genetics ; Bacteria ; Signal Transduction ; Biological Evolution ; Mammals ; }, abstract = {Evolution by natural selection results in biological traits that enable organismic adaptation and survival under various stressful environments. External stresses can be sometimes too severe to overcome, leading to organismic death either because of failure in adapting to such stress, or alternatively, through a regulated form of organismic death (phenoptosis). While regulated cell deaths, including apoptosis, have been extensively studied, little is known about the molecular and cellular mechanisms underlying phenoptosis and its evolutionary significance for multicellular organisms. In this article, we review documented phenomena and mechanistic evidence emerging from studies of stress-induced phenoptosis in the multicellular organism C. elegans and stress-induced deaths at cellular levels in organisms ranging from bacteria to mammals, focusing on abiotic and pathogen stresses. Genes and signaling pathways involved in phenoptosis appear to promote organismic death during severe stress and aging, while conferring fitness and immune defense during mild stress and early life, consistent with their antagonistic pleiotropy actions. As cell apoptosis during development can shape tissues and organs, stress-induced phenoptosis may also contribute to possible benefits at the population level, through mechanisms including kin selection, abortive infection, and soma-to-germline resource allocation. Current models can generate experimentally testable predictions and conceptual frameworks with implications for understanding both stress-induced phenoptosis and natural aging.}, } @article {pmid36715204, year = {2023}, author = {Klure, DM and Greenhalgh, R and Parchman, TL and Matocq, MD and Galland, LM and Shapiro, MD and Dearing, MD}, title = {Hybridization in the absence of an ecotone favors hybrid success in woodrats (Neotoma spp.).}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {4}, pages = {959-970}, pmid = {36715204}, issn = {1558-5646}, support = {T32 GM141848/GM/NIGMS NIH HHS/United States ; T32GM141848/NH/NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Sigmodontinae/genetics ; *Hybridization, Genetic ; Nucleic Acid Hybridization ; }, abstract = {Hybridization is a common process that has broadly impacted the evolution of multicellular eukaryotes; however, how ecological factors influence this process remains poorly understood. Here, we report the findings of a 3-year recapture study of the Bryant's woodrat (Neotoma bryanti) and desert woodrat (Neotoma lepida), two species that hybridize within a creosote bush (Larrea tridentata) shrubland in Whitewater, CA, USA. We used a genotype-by-sequencing approach to characterize the ancestry distribution of individuals across this hybrid zone coupled with Cormack-Jolly-Seber modeling to describe demography. We identified a high frequency of hybridization at this site with ~40% of individuals possessing admixed ancestry, which is the result of multigenerational backcrossing and advanced hybrid-hybrid crossing. F1, F2, and advanced generation hybrids had apparent survival rates similar to parental N. bryanti, while parental and backcross N. lepida had lower apparent survival rates and were far less abundant. Compared to bimodal hybrid zones where hybrids are often rare and selected against, we find that hybrids at Whitewater are common and have comparable survival to the dominant parental species, N. bryanti. The frequency of hybridization at Whitewater is therefore likely limited by the abundance of the less common parental species, N. lepida, rather than selection against hybrids.}, } @article {pmid36711609, year = {2023}, author = {Shekhar, S and Guo, H and Colin, SP and Marshall, W and Kanso, E and Costello, JH}, title = {Cooperative hydrodynamics accompany multicellular-like colonial organization in the unicellular ciliate Stentor.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711609}, abstract = {Evolution of multicellularity from early unicellular ancestors is arguably one of the most important transitions since the origin of life [1,2] . Multicellularity is often associated with higher nutrient uptake [3] , better defense against predation, cell specialization and better division of labor [4] . While many single-celled organisms exhibit both solitary and colonial existence [3,5,6] , the organizing principles governing the transition and the benefits endowed are less clear. Using the suspension-feeding unicellular protist Stentor coeruleus , we show that hydrodynamic coupling between proximal neighbors results in faster feeding flows that depend on the separation between individuals. Moreover, we find that the accrued benefits in feeding current enhancement are typically asymmetricâ€" individuals with slower solitary currents gain more from partnering than those with faster currents. We find that colony-formation is ephemeral in Stentor and individuals in colonies are highly dynamic unlike other colony-forming organisms like Volvox carteri [3] . Our results demonstrate benefits endowed by the colonial organization in a simple unicellular organism and can potentially provide fundamental insights into the selective forces favoring early evolution of multicellular organization.}, } @article {pmid36711513, year = {2023}, author = {Pineau, RM and Demory, D and Libby, E and Lac, DT and Day, TC and Bravo, P and Yunker, PJ and Weitz, JS and Bozdag, GO and Ratcliff, WC}, title = {Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.01.19.524803}, pmid = {36711513}, abstract = {The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth’s ecosystems. Yet little is known about how early steps in the evolution of multicellularity transform eco-evolutionary dynamics, e.g., via niche expansion processes that may facilitate coexistence. Using long-term experimental evolution in the snowflake yeast model system, we show that the evolution of multicellularity drove niche partitioning and the adaptive divergence of two distinct, specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subject to selection for rapid growth in rich media, followed by selection favoring larger group size. Both small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations. These small and large sized snowflake yeast lineages specialized on divergent aspects of a trade-off between growth rate and survival, mirroring predictions from ecological theory. Through modeling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically-impactful emergent properties of this evolutionary transition.}, } @article {pmid36698752, year = {2023}, author = {Moriel, A and Wolfenson, H and Bouchbinder, E}, title = {Characteristic energy scales of active fluctuations in adherent cells.}, journal = {Biophysical reports}, volume = {3}, number = {1}, pages = {100099}, pmid = {36698752}, issn = {2667-0747}, abstract = {Cell-matrix and cell-cell adhesion play important roles in a wide variety of physiological processes, from the single-cell level to the large scale, multicellular organization of tissues. Cells actively apply forces to their environment, either extracellular matrix or neighboring cells, as well as sense its biophysical properties. The fluctuations associated with these active processes occur on an energy scale much larger than that of ordinary thermal equilibrium fluctuations, yet their statistical properties and characteristic scales are not fully understood. Here, we compare measurements of the energy scale of active cellular fluctuations-an effective cellular temperature-in four different biophysical settings, involving both single-cell and cell-aggregate experiments under various control conditions, different cell types, and various biophysical observables. The results indicate that a similar energy scale of active fluctuations might characterize the same cell type in different settings, though it may vary among different cell types, being approximately six to eight orders of magnitude larger than the ordinary thermal energy at room temperature. These findings call for extracting the energy scale of active fluctuations over a broader range of cell types, experimental settings, and biophysical observables and for understanding the biophysical origin and significance of such cellular energy scales.}, } @article {pmid36693985, year = {2023}, author = {Trivedi, DD and Dalai, SK and Bakshi, SR}, title = {The Mystery of Cancer Resistance: A Revelation Within Nature.}, journal = {Journal of molecular evolution}, volume = {91}, number = {2}, pages = {133-155}, pmid = {36693985}, issn = {1432-1432}, mesh = {Humans ; Horses ; Animals ; Mice ; *Carcinogens, Environmental ; *Neoplasms/genetics ; Immunity, Innate ; Mole Rats ; Mammals ; Tumor Microenvironment ; }, abstract = {Cancer, a disease due to uncontrolled cell proliferation is as ancient as multicellular organisms. A 255-million-years-old fossilized forerunner mammal gorgonopsian is probably the oldest evidence of cancer, to date. Cancer seems to have evolved by adapting to the microenvironment occupied by immune sentinel, modulating the cellular behavior from cytotoxic to regulatory, acquiring resistance to chemotherapy and surviving hypoxia. The interaction of genes with environmental carcinogens is central to cancer onset, seen as a spectrum of cancer susceptibility among human population. Cancer occurs in life forms other than human also, although their exposure to environmental carcinogens can be different. Role of genetic etiology in cancer in multiple species can be interesting with regard to not only cancer susceptibility, but also genetic conservation and adaptation in speciation. The widely used model organisms for cancer research are mouse and rat which are short-lived and reproduce rapidly. Research in these cancer prone animal models has been valuable as these have led to cancer therapy. However, another rewarding area of cancer research can be the cancer-resistant animal species. The Peto's paradox and G-value paradox are evident when natural cancer resistance is observed in large mammals, like elephant and whale, small rodents viz. Naked Mole Rat and Blind Mole Rat, and Bat. The cancer resistance remains to be explored in other small or large and long-living animals like giraffe, camel, rhinoceros, water buffalo, Indian bison, Shire horse, polar bear, manatee, elephant seal, walrus, hippopotamus, turtle and tortoise, sloth, and squirrel. Indeed, understanding the molecular mechanisms of avoiding neoplastic transformation across various life forms can be potentially having translational value for human cancer management. Adapted and Modified from (Hanahan and Weinberg 2011).}, } @article {pmid36692278, year = {2022}, author = {Forterre, P and Gaïa, M}, title = {[Viruses and the evolution of modern eukaryotic cells].}, journal = {Medecine sciences : M/S}, volume = {38}, number = {12}, pages = {990-998}, doi = {10.1051/medsci/2022164}, pmid = {36692278}, issn = {1958-5381}, mesh = {Humans ; *Eukaryotic Cells ; Phylogeny ; *Viruses/genetics ; Eukaryota/genetics ; Cell Nucleus ; Evolution, Molecular ; Biological Evolution ; }, abstract = {It is now well accepted that viruses have played an important role in the evolution of modern eukaryotes. In this review, we suggest that interactions between ancient eukaryoviruses and proto-eukaryotes also played a major role in eukaryogenesis. We discuss phylogenetic analyses that highlight the viral origin of several key proteins in the molecular biology of eukaryotes. We also discuss recent observations that, by analogy, could suggest a viral origin of the cellular nucleus. Finally, we hypothesize that mechanisms of cell differentiation in multicellular organisms might have originated from mechanisms implemented by viruses to transform infected cells into virocells.}, } @article {pmid36689549, year = {2023}, author = {Tuohinto, K and DiMaio, TA and Kiss, EA and Laakkonen, P and Saharinen, P and Karnezis, T and Lagunoff, M and Ojala, PM}, title = {KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1010753}, pmid = {36689549}, issn = {1553-7374}, support = {R01 CA189986/CA/NCI NIH HHS/United States ; R01 CA217788/CA/NCI NIH HHS/United States ; R21 CA240479/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Sarcoma, Kaposi ; *Herpesvirus 8, Human/genetics ; Endothelial Cells ; Endothelium, Vascular/pathology ; }, abstract = {Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells. We previously identified two types of circulating endothelial colony forming cells (ECFCs), ones that expressed markers of blood endothelium and ones that expressed markers of lymphatic endothelium. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are significantly more susceptible to KSHV infection than the blood ECFCs and maintain the viral episomes during passage in culture while the blood ECFCs lose the viral episome. Only the KSHV-infected lymphatic ECFCs (K-ECFCLY) grew to small multicellular colonies in soft agar whereas the infected blood ECFCs and all uninfected ECFCs failed to proliferate. The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. These data suggest that KSHV-infected lymphatic ECFCs can be utilized as a KSHV infection model for in vivo translational studies to test novel inhibitors representing potential treatment modalities for KS.}, } @article {pmid36688394, year = {2023}, author = {McShea, DW}, title = {Four reasons for scepticism about a human major transition in social individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210403}, pmid = {36688394}, issn = {1471-2970}, mesh = {Animals ; Humans ; *Biological Evolution ; Eukaryota ; *Hominidae ; Selection, Genetic ; Reproduction ; }, abstract = {The 'major transitions in evolution' are mainly about the rise of hierarchy, new individuals arising at ever higher levels of nestedness, in particular the eukaryotic cell arising from prokaryotes, multicellular individuals from solitary protists and individuated societies from multicellular individuals. Some lists include human societies as a major transition, but based on a comparison with the non-human transitions, there are reasons for scepticism. (i) The foundation of the major transitions is hierarchy, but the cross-cutting interactions in human societies undermine hierarchical structure. (ii) Natural selection operates in three modes-stability, growth and reproductive success-and only the third produces the complex adaptations seen in fully individuated higher levels. But human societies probably evolve mainly in the stability and growth modes. (iii) Highly individuated entities are marked by division of labour and commitment to morphological differentiation, but in humans differentiation is mostly behavioural and mostly reversible. (iv) As higher-level individuals arise, selection drains complexity, drains parts, from lower-level individuals. But there is little evidence of a drain in humans. In sum, a comparison with the other transitions gives reasons to doubt that human social individuation has proceeded very far, or if it has, to doubt that it is a transition of the same sort. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688393, year = {2023}, author = {Townsend, C and Ferraro, JV and Habecker, H and Flinn, MV}, title = {Human cooperation and evolutionary transitions in individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210414}, pmid = {36688393}, issn = {1471-2970}, mesh = {Humans ; *Biological Evolution ; *Social Behavior ; Adaptation, Physiological ; Communication ; }, abstract = {A major evolutionary transition in individuality involves the formation of a cooperative group and the transformation of that group into an evolutionary entity. Human cooperation shares principles with those of multicellular organisms that have undergone transitions in individuality: division of labour, communication, and fitness interdependence. After the split from the last common ancestor of hominoids, early hominins adapted to an increasingly terrestrial niche for several million years. We posit that new challenges in this niche set in motion a positive feedback loop in selection pressure for cooperation that ratcheted coevolutionary changes in sociality, communication, brains, cognition, kin relations and technology, eventually resulting in egalitarian societies with suppressed competition and rapid cumulative culture. The increasing pace of information innovation and transmission became a key aspect of the evolutionary niche that enabled humans to become formidable cooperators with explosive population growth, the ability to cooperate and compete in groups of millions, and emergent social norms, e.g. private property. Despite considerable fitness interdependence, the rise of private property, in concert with population explosion and socioeconomic inequality, subverts potential transition of human groups into evolutionary entities due to resurgence of latent competition and conflict. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688387, year = {2023}, author = {Davison, DR and Michod, RE}, title = {Steps to individuality in biology and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210407}, pmid = {36688387}, issn = {1471-2970}, mesh = {Animals ; Humans ; Biological Evolution ; *Hominidae ; *Cultural Evolution ; Biology ; }, abstract = {Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural transition involving integrated groups of cultural traditions and the hominins that create and transmit traditions. We focus primarily on the early Pleistocene and examine hominin carnivory and the cultural change from Oldowan to Acheulean technology. We use Pan behaviour as an outgroup comparison. We summarize the important similarities and differences we find between ETI stages in the biological and cultural realms. As we are not cultural anthropologists, we may overlook or be mistaken in the processes we associate with each step. We hope that by clearly describing these steps to individuality and illustrating them with cultural principles and processes, other researchers may build upon our initial exercise. Our analysis supports the hypothesis that human culture has undergone an ETI beginning with a Pan-like ancestor, continuing during the Pleistocene, and culminating in modern human culture. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36684435, year = {2022}, author = {Cofre, J and Saalfeld, K}, title = {The first embryo, the origin of cancer and animal phylogeny. I. A presentation of the neoplastic process and its connection with cell fusion and germline formation.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {1067248}, pmid = {36684435}, issn = {2296-634X}, abstract = {The decisive role of Embryology in understanding the evolution of animal forms is founded and deeply rooted in the history of science. It is recognized that the emergence of multicellularity would not have been possible without the formation of the first embryo. We speculate that biophysical phenomena and the surrounding environment of the Ediacaran ocean were instrumental in co-opting a neoplastic functional module (NFM) within the nucleus of the first zygote. Thus, the neoplastic process, understood here as a biological phenomenon with profound embryologic implications, served as the evolutionary engine that favored the formation of the first embryo and cancerous diseases and allowed to coherently create and recreate body shapes in different animal groups during evolution. In this article, we provide a deep reflection on the Physics of the first embryogenesis and its contribution to the exaptation of additional NFM components, such as the extracellular matrix. Knowledge of NFM components, structure, dynamics, and origin advances our understanding of the numerous possibilities and different innovations that embryos have undergone to create animal forms via Neoplasia during evolutionary radiation. The developmental pathways of Neoplasia have their origins in ctenophores and were consolidated in mammals and other apical groups.}, } @article {pmid36679107, year = {2023}, author = {Zhou, Y and Li, G and Han, G and Xun, L and Mao, S and Yang, L and Wang, Y}, title = {Developmental Programmed Cell Death Involved in Ontogenesis of Dictamnus dasycarpus Capitate Glandular Hairs.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36679107}, issn = {2223-7747}, abstract = {Plant glandular trichomes have received much attention due to their commercial and biological value. Recent studies have focused on the development of various glands in plants, suggesting that programmed cell death (PCD) may play an important role during the development of plant secretory structures. However, the development processes and cytological characteristics in different types of plant secretory structures differed significantly. This study aims to provide new data on the developmental PCD of the capitate glandular hairs in Dictamnus dasycarpus. Light, scanning, immunofluorescence labeling, and transmission electron microscopy were used to determine the different developmental processes of the capitate glandular hairs from a cytological perspective. Morphologically, the capitate glandular hair originates from one initial epidermal cell and differentiates into a multicellular trichome characterized by two basal cells, two lines of stalk cells, and a multicellular head. It is also histochemically detected by essential oils. TUNEL-positive reactions identified nuclei with diffused fluorescence or an irregular figure by DAPI, and Evans blue staining showed that the head and stalk cells lost their viability. Ultrastructural evidence revealed the developmental process by two possible modes of PCD. Non-autolytic PCD was characterized by buckling cell walls and degenerated nuclei, mitochondria, plastids, multivesicular body (MVB), and end-expanded endoplasmic reticulum in the condensed cytoplasm, which were mainly observed in the head cells. The MVB was detected in the degraded vacuole, a degraded nucleus with condensed chromatin and diffused membrane, and eventual loss of the vacuole membrane integrity exhibited typical evidence of vacuole-mediated autolytic PCD in the stalk cells. Furthermore, protoplasm degeneration coupled with dark oil droplets and numerous micro-dark osmiophilic substances was observed during late stages. The secretion mode of essential oils is also described in this paper.}, } @article {pmid36655713, year = {2023}, author = {Römling, U}, title = {Is biofilm formation intrinsic to the origin of life?.}, journal = {Environmental microbiology}, volume = {25}, number = {1}, pages = {26-39}, doi = {10.1111/1462-2920.16179}, pmid = {36655713}, issn = {1462-2920}, mesh = {Humans ; *Biofilms ; }, abstract = {Biofilms are multicellular, often surface-associated, communities of autonomous cells. Their formation is the natural mode of growth of up to 80% of microorganisms living on this planet. Biofilms refractory towards antimicrobial agents and the actions of the immune system due to their tolerance against multiple environmental stresses. But how did biofilm formation arise? Here, I argue that the biofilm lifestyle has its foundation already in the fundamental, surface-triggered chemical reactions and energy preserving mechanisms that enabled the development of life on earth. Subsequently, prototypical biofilm formation has evolved and diversified concomitantly in composition, cell morphology and regulation with the expansion of prokaryotic organisms and their radiation by occupation of diverse ecological niches. This ancient origin of biofilm formation thus mirrors the harnessing environmental conditions that have been the rule rather than the exception in microbial life. The subsequent emergence of the association of microbes, including recent human pathogens, with higher organisms can be considered as the entry into a nutritional and largely stress-protecting heaven. Nevertheless, basic mechanisms of biofilm formation have surprisingly been conserved and refunctionalized to promote sustained survival in new environments.}, } @article {pmid36650459, year = {2023}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamashita, S and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of two species of the multicellular volvocine green algal genus Astrephomene.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {16}, pmid = {36650459}, issn = {1471-2180}, mesh = {*Chlorophyta/genetics ; Cryopreservation/methods ; Freezing ; Dimethylformamide ; }, abstract = {BACKGROUND: Astrephomene is an interesting green algal genus that, together with Volvox, shows convergent evolution of spheroidal multicellular bodies with somatic cells of the colonial or multicellular volvocine lineage. A recent whole-genome analysis of A. gubernaculifera resolved the molecular-genetic basis of such convergent evolution, and two species of Astrephomene were described. However, maintenance of culture strains of Astrephomene requires rapid inoculation of living cultures, and cryopreserved culture strains have not been established in public culture collections.

RESULTS: To establish cryopreserved culture strains of two species of Astrephomene, conditions for cryopreservation of the two species were investigated using immature and mature vegetative colonies and two cryoprotectants: N,N-dimethylformamide (DMF) and hydroxyacetone (HA). Rates of cell survival of the A. gubernaculifera or A. perforata strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3 and 6%) of DMF and HA and two types of colonies: immature colonies (small colonies newly released from the parent) and mature colonies (large colonies just before daughter colony formation). The highest rate of survival [11 ± 13% (0.36-33%) by the most probable number (MPN) method] of A. gubernaculifera strain NIES-4017 (established in 2014) was obtained when culture samples of immature colonies were subjected to cryogenic treatment with 6% DMF. In contrast, culture samples of mature colonies subjected to 3% HA cryogenic treatment showed the highest "MPN survival" [5.5 ± 5.9% (0.12-12%)] in A. perforata. Using the optimized cryopreservation conditions for each species, survival after freezing in liquid nitrogen was examined for six other strains of A. gubernaculifera (established from 1962 to 1981) and another A. perforata strain maintained in the Microbial Culture Collection at the National Institute for Environmental Studies (MCC-NIES). We obtained ≥0.1% MPN survival of the A. perforata strain. However, only two of the six strains of A. gubernaculifera showed ≥0.1% MPN survival. By using the optimal cryopreserved conditions obtained for each species, five cryopreserved strains of two species of Astrephomene were established and deposited in the MCC-NIES.

CONCLUSIONS: The optimal cryopreservation conditions differed between the two species of Astrephomene. Cryopreservation of long-term-maintained strains of A. gubernaculifera may be difficult; further studies of cryopreservation of these strains are needed.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {8}, number = {2}, pages = {197-203}, pmid = {36646908}, issn = {2058-5276}, mesh = {*Eukaryota ; Anaerobiosis ; *Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Fermentation ; }, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36641836, year = {2023}, author = {Barrenechea Angeles, I and Romero-Martínez, ML and Cavaliere, M and Varrella, S and Francescangeli, F and Piredda, R and Mazzocchi, MG and Montresor, M and Schirone, A and Delbono, I and Margiotta, F and Corinaldesi, C and Chiavarini, S and Montereali, MR and Rimauro, J and Parrella, L and Musco, L and Dell'Anno, A and Tangherlini, M and Pawlowski, J and Frontalini, F}, title = {Encapsulated in sediments: eDNA deciphers the ecosystem history of one of the most polluted European marine sites.}, journal = {Environment international}, volume = {172}, number = {}, pages = {107738}, doi = {10.1016/j.envint.2023.107738}, pmid = {36641836}, issn = {1873-6750}, mesh = {Humans ; Animals ; *Ecosystem ; *Biodiversity ; Biota ; Europe ; Human Activities ; Geologic Sediments ; }, abstract = {The Anthropocene is characterized by dramatic ecosystem changes driven by human activities. The impact of these activities can be assessed by different geochemical and paleontological proxies. However, each of these proxies provides only a fragmentary insight into the effects of anthropogenic impacts. It is highly challenging to reconstruct, with a holistic view, the state of the ecosystems from the preindustrial period to the present day, covering all biological components, from prokaryotes to multicellular eukaryotes. Here, we used sedimentary ancient DNA (sedaDNA) archives encompassing all trophic levels of biodiversity to reconstruct the two century-natural history in Bagnoli-Coroglio (Gulf of Pozzuoli, Tyrrhenian Sea), one of the most polluted marine-coastal sites in Europe. The site was characterized by seagrass meadows and high eukaryotic diversity until the beginning of the 20th century. Then, the ecosystem completely changed, with seagrasses and associated fauna as well as diverse groups of planktonic and benthic protists being replaced by low diversity biota dominated by dinophyceans and infaunal metazoan species. The sedaDNA analysis revealed a five-phase evolution of the area, where changes appear as the result of a multi-level cascade effect of impacts associated with industrial activities, urbanization, water circulation and land-use changes. The sedaDNA allowed to infer reference conditions that must be considered when restoration actions are to be implemented.}, } @article {pmid36637886, year = {2023}, author = {Kuzdzal-Fick, JJ and Moreno, A and Broersma, CME and Cooper, TF and Ostrowski, EA}, title = {From individual behaviors to collective outcomes: fruiting body formation in Dictyostelium as a group-level phenotype.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {3}, pages = {731-745}, doi = {10.1093/evolut/qpac038}, pmid = {36637886}, issn = {1558-5646}, mesh = {*Dictyostelium/genetics ; Phenotype ; Genotype ; Reproduction ; }, abstract = {Collective phenotypes, which arise from the interactions among individuals, can be important for the evolution of higher levels of biological organization. However, how a group's composition determines its collective phenotype remains poorly understood. When starved, cells of the social amoeba Dictyostelium discoideum cooperate to build a multicellular fruiting body, and the morphology of the fruiting body is likely advantageous to the surviving spores. We assessed how the number of strains, as well as their genetic and geographic relationships to one another, impact the group's morphology and productivity. We find that some strains consistently enhance or detract from the productivity of their groups, regardless of the identity of the other group members. We also detect extensive pairwise and higher-order genotype interactions, which collectively have a large influence on the group phenotype. Whereas previous work in Dictyostelium has focused almost exclusively on whether spore production is equitable when strains cooperate to form multicellular fruiting bodies, our results suggest a previously unrecognized impact of chimeric co-development on the group phenotype. Our results demonstrate how interactions among members of a group influence collective phenotypes and how group phenotypes might in turn impact selection on the individual.}, } @article {pmid36637107, year = {2023}, author = {Iyer, J and Pillai, S and Munguia-Lopez, JG and Zhang, Y and Mielkozorova, M and Tran, SD}, title = {Salivary gland bioengineering - yesterday, today, tomorrow!.}, journal = {Histology and histopathology}, volume = {}, number = {}, pages = {18580}, doi = {10.14670/HH-18-580}, pmid = {36637107}, issn = {1699-5848}, abstract = {Salivary glands are specialized structures developed as an extensively compact, arborized design through classical embryogenesis, accompanied by a cascade of events channelized by numerous growth factors and genetic regulatory pathways. Salivary secretions maintain oral homeostasis and, when diminished in certain conditions, present as xerostomia or salivary hypofunction, adversely impacting the patient's quality of life. The current available treatments primarily aim at tackling the immediate symptoms providing temporary relief to the patient. Despite scientific efforts to develop permanent and effective solutions to restore salivation, a significant permanent treatment is yet to be established. Tissue engineering has proven as a promising remedial tool in several diseases, as well as in xerostomia, and aims to restore partial loss of organ function. Recapitulating the physiological cellular microenvironment to in vitro culture conditions is constantly evolving. Replicating the dynamic multicellular interactions, genetic pathways, and cytomorphogenic forces, as displayed during salivary gland development have experienced considerable barriers. Through this review, we endeavour to provide an outlook on the evolution of in vitro salivary gland research, highlighting the key bioengineering advances and the challenges faced with the current therapeutic strategies for salivary hypofunction, with an insight into our team's scientific contributions.}, } @article {pmid36636779, year = {2023}, author = {Gombos, S and Miras, M and Howe, V and Xi, L and Pottier, M and Kazemein Jasemi, NS and Schladt, M and Ejike, JO and Neumann, U and Hänsch, S and Kuttig, F and Zhang, Z and Dickmanns, M and Xu, P and Stefan, T and Baumeister, W and Frommer, WB and Simon, R and Schulze, WX}, title = {A high-confidence Physcomitrium patens plasmodesmata proteome by iterative scoring and validation reveals diversification of cell wall proteins during evolution.}, journal = {The New phytologist}, volume = {238}, number = {2}, pages = {637-653}, doi = {10.1111/nph.18730}, pmid = {36636779}, issn = {1469-8137}, mesh = {*Proteome/metabolism ; *Plasmodesmata/metabolism ; Phylogeny ; Reproducibility of Results ; Cell Wall/metabolism ; }, abstract = {Plasmodesmata (PD) facilitate movement of molecules between plant cells. Regulation of this movement is still not understood. Plasmodesmata are hard to study, being deeply embedded within cell walls and incorporating several membrane types. Thus, structure and protein composition of PD remain enigmatic. Previous studies of PD protein composition identified protein lists with few validations, making functional conclusions difficult. We developed a PD scoring approach in iteration with large-scale systematic localization, defining a high-confidence PD proteome of Physcomitrium patens (HC300). HC300, together with bona fide PD proteins from literature, were placed in Pddb. About 65% of proteins in HC300 were not previously PD-localized. Callose-degrading glycolyl hydrolase family 17 (GHL17) is an abundant protein family with representatives across evolutionary scale. Among GHL17s, we exclusively found members of one phylogenetic clade with PD localization and orthologs occur only in species with developed PD. Phylogenetic comparison was expanded to xyloglucan endotransglucosylases/hydrolases and Exordium-like proteins, which also diversified into PD-localized and non-PD-localized members on distinct phylogenetic clades. Our high-confidence PD proteome HC300 provides insights into diversification of large protein families. Iterative and systematic large-scale localization across plant species strengthens the reliability of HC300 as basis for exploring structure, function, and evolution of this important organelle.}, } @article {pmid36616337, year = {2023}, author = {Wu, X and Liu, X and Zhang, S and Zhou, Y}, title = {Cell Division and Meristem Dynamics in Fern Gametophytes.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36616337}, issn = {2223-7747}, abstract = {One of the most important questions in all multicellular organisms is how to define and maintain different cell fates during continuous cell division and proliferation. Plant meristems provide a unique research system to address this fundamental question because meristems dynamically maintain themselves and sustain organogenesis through balancing cell division and cell differentiation. Different from the gametophytes of seed plants that depend on their sporophytes and lack meristems, the gametophytes of seed-free ferns develop different types of meristems (including apical cell-based meristems and multicellular apical and marginal meristems) to promote independent growth and proliferation during the sexual gametophyte phase. Recent studies combining confocal time-lapse imaging and computational image analysis reveal the cellular basis of the initiation and proliferation of different types of meristems in fern gametophytes, providing new insights into the evolution of meristems in land plants. In this review, we summarize the recent progress in understanding the cell growth dynamics in fern gametophytes and discuss both conserved and diversified mechanisms underlying meristem cell proliferation in seed-free vascular plants.}, } @article {pmid36611928, year = {2022}, author = {von der Heyde, B and Hallmann, A}, title = {Cell Type-Specific Pherophorins of Volvox carteri Reveal Interplay of Both Cell Types in ECM Biosynthesis.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611928}, issn = {2073-4409}, mesh = {*Volvox/genetics/metabolism ; Phylogeny ; Extracellular Matrix/metabolism ; *Chlorophyta/genetics ; Extracellular Matrix Proteins/metabolism ; }, abstract = {The spheroidal green algae Volvox carteri serves as a model system to investigate the formation of a complex, multifunctional extracellular matrix (ECM) in a relatively simple, multicellular organism with cell differentiation. The V. carteri ECM is mainly composed of hydroxyproline-rich glycoproteins (HRGPs) and there are diverse region-specific, anatomically distinct structures in the ECM. One large protein family with importance for ECM biosynthesis stands out: the pherophorins. The few pherophorins previously extracted from the ECM and characterized, were specifically expressed by somatic cells. However, the localization and function of most pherophorins is unknown. Here, we provide a phylogenetic analysis of 153 pherophorins of V. carteri and its unicellular relative Chlamydomonas reinhardtii. Our analysis of cell type-specific mRNA expression of pherophorins in V. carteri revealed that, contrary to previous assumptions, only about half (52%) of the 102 investigated pherophorin-related genes show stronger expression in somatic cells, whereas about one-third (34%) of the genes show significant higher expression in reproductive cells (gonidia). We fused two pherophorin genes that are expressed by different cell types to yfp, stably expressed them in Volvox and studied the tagged proteins by live-cell imaging. In contrast to earlier biochemical approaches, this genetic approach also allows the in vivo analysis of non-extractable, covalently cross-linked ECM proteins. We demonstrate that the soma-specific pherophorin SSG185 is localized in the outermost ECM structures of the spheroid, the boundary zone and at the flagellar hillocks. SSG185:YFP is detectable as early as 1.5 h after completion of embryogenesis. It is then present for the rest of the life cycle. The gonidia-specific pherophorin PhG is localized in the gonidial cellular zone 1 ("gonidial vesicle") suggesting its involvement in the protection of gonidia and developing embryos until hatching. Even if somatic cells produce the main portion of the ECM of the spheroids, ECM components produced by gonidia are also required to cooperatively assemble the total ECM. Our results provide insights into the evolution of the pherophorin protein family and convey a more detailed picture of Volvox ECM synthesis.}, } @article {pmid36598979, year = {2023}, author = {Chuai, M and Serrano Nájera, G and Serra, M and Mahadevan, L and Weijer, CJ}, title = {Reconstruction of distinct vertebrate gastrulation modes via modulation of key cell behaviors in the chick embryo.}, journal = {Science advances}, volume = {9}, number = {1}, pages = {eabn5429}, pmid = {36598979}, issn = {2375-2548}, abstract = {The morphology of gastrulation driving the internalization of the mesoderm and endoderm differs markedly among vertebrate species. It ranges from involution of epithelial sheets of cells through a circular blastopore in amphibians to ingression of mesenchymal cells through a primitive streak in amniotes. By targeting signaling pathways controlling critical cell behaviors in the chick embryo, we generated crescent- and ring-shaped mesendoderm territories in which cells can or cannot ingress. These alterations subvert the formation of the chick primitive streak into the gastrulation modes seen in amphibians, reptiles, and teleost fish. Our experimental manipulations are supported by a theoretical framework linking cellular behaviors to self-organized multicellular flows outlined in detail in the accompanying paper. Together, this suggests that the evolution of gastrulation movements is largely determined by changes in a few critical cell behaviors in the mesendoderm territory across different species and controlled by a relatively small number of signaling pathways.}, } @article {pmid36598184, year = {2023}, author = {Dang, CC and Vinh, LS}, title = {Estimating amino acid substitution models for metazoan evolutionary studies.}, journal = {Journal of evolutionary biology}, volume = {36}, number = {3}, pages = {499-506}, doi = {10.1111/jeb.14147}, pmid = {36598184}, issn = {1420-9101}, mesh = {Animals ; Phylogeny ; *Evolution, Molecular ; Amino Acid Substitution ; Bayes Theorem ; *Proteins ; Models, Genetic ; }, abstract = {Amino acid substitution models represent the substitution rates among amino acids during the evolution of protein sequences. The models are a prerequisite for maximum likelihood or Bayesian methods to analyse the phylogenetic relationships among species based on their protein sequences. Estimating amino acid substitution models requires large protein datasets and intensive computation. In this paper, we presented the estimation of both time-reversible model (Q.met) and time non-reversible model (NQ.met) for multicellular animals (Metazoa). Analyses showed that the Q.met and NQ.met models were significantly better than existing models in analysing metazoan protein sequences. Moreover, the time non-reversible model NQ.met enables us to reconstruct the rooted phylogenetic tree for Metazoa. We recommend researchers to employ the Q.met and NQ.met models in analysing metazoan protein sequences.}, } @article {pmid36587372, year = {2023}, author = {Palmiero, M and Cantarosso, I and di Blasio, L and Monica, V and Peracino, B and Primo, L and Puliafito, A}, title = {Collective directional migration drives the formation of heteroclonal cancer cell clusters.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13369}, pmid = {36587372}, issn = {1878-0261}, abstract = {Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation-independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin-rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.}, } @article {pmid36585440, year = {2022}, author = {Lynch, M and Trickovic, B and Kempes, CP}, title = {Evolutionary scaling of maximum growth rate with organism size.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22586}, pmid = {36585440}, issn = {2045-2322}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Genetic Drift ; Eukaryota/genetics ; Mutation ; Selection, Genetic ; }, abstract = {Data from nearly 1000 species reveal the upper bound to rates of biomass production achievable by natural selection across the Tree of Life. For heterotrophs, maximum growth rates scale positively with organism size in bacteria but negatively in eukaryotes, whereas for phototrophs, the scaling is negligible for cyanobacteria and weakly negative for eukaryotes. These results have significant implications for understanding the bioenergetic consequences of the transition from prokaryotes to eukaryotes, and of the expansion of some groups of the latter into multicellularity. The magnitudes of the scaling coefficients for eukaryotes are significantly lower than expected under any proposed physical-constraint model. Supported by genomic, bioenergetic, and population-genetic data and theory, an alternative hypothesis for the observed negative scaling in eukaryotes postulates that growth-diminishing mutations with small effects passively accumulate with increasing organism size as a consequence of associated increases in the power of random genetic drift. In contrast, conditional on the structural and functional features of ribosomes, natural selection has been able to promote bacteria with the fastest possible growth rates, implying minimal conflicts with both bioenergetic constraints and random genetic drift. If this extension of the drift-barrier hypothesis is correct, the interpretations of comparative studies of biological traits that have traditionally ignored differences in population-genetic environments will require revisiting.}, } @article {pmid36553613, year = {2022}, author = {Kozlov, AP}, title = {The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553613}, issn = {2073-4425}, mesh = {Animals ; Humans ; *Genes, Tumor Suppressor ; Oncogenes ; Cell Differentiation ; *Neoplasms/genetics ; Fishes ; }, abstract = {To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory.}, } @article {pmid36550365, year = {2022}, author = {Bowman, JL}, title = {The origin of a land flora.}, journal = {Nature plants}, volume = {8}, number = {12}, pages = {1352-1369}, pmid = {36550365}, issn = {2055-0278}, mesh = {*Biological Evolution ; Phylogeny ; Plants/genetics ; *Embryophyta/genetics ; }, abstract = {The origin of a land flora fundamentally shifted the course of evolution of life on earth, facilitating terrestrialization of other eukaryotic lineages and altering the planet's geology, from changing atmospheric and hydrological cycles to transforming continental erosion processes. Despite algal lineages inhabiting the terrestrial environment for a considerable preceding period, they failed to evolve complex multicellularity necessary to conquer the land. About 470 million years ago, one lineage of charophycean alga evolved complex multicellularity via developmental innovations in both haploid and diploid generations and became land plants (embryophytes), which rapidly diversified to dominate most terrestrial habitats. Genome sequences have provided unprecedented insights into the genetic and genomic bases for embryophyte origins, with some embryophyte-specific genes being associated with the evolution of key developmental or physiological attributes, such as meristems, rhizoids and the ability to form mycorrhizal associations. However, based on the fossil record, the evolution of the defining feature of embryophytes, the embryo, and consequently the sporangium that provided a reproductive advantage, may have been most critical in their rise to dominance. The long timeframe and singularity of a land flora were perhaps due to the stepwise assembly of a large constellation of genetic innovations required to conquer the terrestrial environment.}, } @article {pmid36547392, year = {2022}, author = {Baselga-Cervera, B and Gettle, N and Travisano, M}, title = {Loss-of-heterozygosity facilitates a fitness valley crossing in experimentally evolved multicellular yeast.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1976}, pages = {20212722}, pmid = {36547392}, issn = {1471-2954}, mesh = {*Adaptation, Physiological/genetics ; *Biological Evolution ; Genotype ; Heterozygote ; *Saccharomyces cerevisiae/genetics ; *Loss of Heterozygosity ; *Genetic Fitness ; }, abstract = {Determining how adaptive possibilities do or do not become evolutionary realities is central to understanding the tempo and mode of evolutionary change. Some of the simplest evolutionary landscapes arise from underdominance at a single locus where the fitness valley consists of only one less-fit genotype. Despite their potential for rapid evolutionary change, few such examples have been investigated. We capitalized on an experimental system in which a significant evolutionary shift, the transition from uni-to-multicellularity, was observed in asexual diploid populations of Saccharomyces cerevisiae experimentally selected for increased settling rates. The multicellular phenotype results from recessive single-locus mutations that undergo loss-of-heterozygosity (LOH) events. By reconstructing the necessary heterozygous intermediate steps, we found that the evolution of multicellularity involves a decrease in size during the first steps. Heterozygous genotypes are 20% smaller in size than genotypes with functional alleles. Nevertheless, populations of heterozygotes give rise to multicellular genotypes more readily than unicellular genotypes with two functional alleles, by rapid LOH events. LOH drives adaptation that may enable rapid evolution in diploid yeast. Together these results show discordance between the phenotypic and genotypic multicellular transition. The evolutionary path to multicellularity, and the adaptive benefits of increased size, requires initial size reductions.}, } @article {pmid36546265, year = {2022}, author = {Liu, J and Zhang, W and He, K and Liu, L and Wang, C and Jiang, Y and Ma, S and Tian, J and Li, Y and Zhang, T and Tian, L and He, F and Paterson, GA and Wei, Y and Pan, Y and Lin, W}, title = {Survival of the magnetotactic bacterium Magnetospirillum gryphiswaldense exposed to Earth's lower near space.}, journal = {Science bulletin}, volume = {67}, number = {13}, pages = {1335-1339}, doi = {10.1016/j.scib.2022.03.005}, pmid = {36546265}, issn = {2095-9281}, mesh = {*Magnetospirillum ; Bacteria, Aerobic ; Gram-Negative Bacteria ; }, } @article {pmid36542495, year = {2023}, author = {Martinez, P and Ustyantsev, K and Biryukov, M and Mouton, S and Glasenburg, L and Sprecher, SG and Bailly, X and Berezikov, E}, title = {Genome assembly of the acoel flatworm Symsagittifera roscoffensis, a model for research on body plan evolution and photosymbiosis.}, journal = {G3 (Bethesda, Md.)}, volume = {13}, number = {2}, pages = {}, pmid = {36542495}, issn = {2160-1836}, mesh = {Animals ; *Platyhelminths/genetics ; Phylogeny ; Base Sequence ; Genome Size ; Transcriptome ; Chromosomes ; }, abstract = {Symsagittifera roscoffensis is a well-known member of the order Acoela that lives in symbiosis with the algae Tetraselmis convolutae during its adult stage. Its natural habitat is the eastern coast of the Atlantic, where at specific locations thousands of individuals can be found, mostly, lying in large pools on the surface of sand at low tide. As a member of the Acoela it has been thought as a proxy for ancestral bilaterian animals; however, its phylogenetic position remains still debated. In order to understand the basic structural characteristics of the acoel genome, we sequenced and assembled the genome of aposymbiotic species S. roscoffensis. The size of this genome was measured to be in the range of 910-940 Mb. Sequencing of the genome was performed using PacBio Hi-Fi technology. Hi-C and RNA-seq data were also generated to scaffold and annotate it. The resulting assembly is 1.1 Gb large (covering 118% of the estimated genome size) and highly continuous, with N50 scaffold size of 1.04 Mb. The repetitive fraction of the genome is 61%, of which 85% (half of the genome) are LTR retrotransposons. Genome-guided transcriptome assembly identified 34,493 genes, of which 29,351 are protein coding (BUSCO score 97.6%), and 30.2% of genes are spliced leader trans-spliced. The completeness of this genome suggests that it can be used extensively to characterize gene families and conduct accurate phylogenomic reconstructions.}, } @article {pmid36542491, year = {2023}, author = {Bonardd, S and Nandi, M and Hernández García, JI and Maiti, B and Abramov, A and Díaz Díaz, D}, title = {Self-Healing Polymeric Soft Actuators.}, journal = {Chemical reviews}, volume = {123}, number = {2}, pages = {736-810}, pmid = {36542491}, issn = {1520-6890}, mesh = {*Polymers/chemistry ; *Hydrogels/chemistry ; Temperature ; }, abstract = {Natural evolution has provided multicellular organisms with sophisticated functionalities and repair mechanisms for surviving and preserve their functions after an injury and/or infection. In this context, biological systems have inspired material scientists over decades to design and fabricate both self-healing polymeric materials and soft actuators with remarkable performance. The latter are capable of modifying their shape in response to environmental changes, such as temperature, pH, light, electrical/magnetic field, chemical additives, etc. In this review, we focus on the fusion of both types of materials, affording new systems with the potential to revolutionize almost every aspect of our modern life, from healthcare to environmental remediation and energy. The integration of stimuli-triggered self-healing properties into polymeric soft actuators endow environmental friendliness, cost-saving, enhanced safety, and lifespan of functional materials. We discuss the details of the most remarkable examples of self-healing soft actuators that display a macroscopic movement under specific stimuli. The discussion includes key experimental data, potential limitations, and mechanistic insights. Finally, we include a general table providing at first glance information about the nature of the external stimuli, conditions for self-healing and actuation, key information about the driving forces behind both phenomena, and the most important features of the achieved movement.}, } @article {pmid36541176, year = {2022}, author = {La Fortezza, M and Velicer, GJ}, title = {Correction to: 'Social selection within aggregative multicellular development drives morphological evolution' (2021) by La Fortezza and Velicer.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1989}, pages = {20222290}, doi = {10.1098/rspb.2022.2290}, pmid = {36541176}, issn = {1471-2954}, } @article {pmid36539037, year = {2023}, author = {Rangarajan, ES and Smith, EW and Izard, T}, title = {The nematode α-catenin ortholog, HMP1, has an extended α-helix when bound to actin filaments.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {2}, pages = {102817}, pmid = {36539037}, issn = {1083-351X}, mesh = {Animals ; *Actin Cytoskeleton/chemistry/metabolism/ultrastructure ; Actins/chemistry/metabolism/ultrastructure ; *alpha Catenin/chemistry/metabolism ; Cadherins/metabolism ; *Caenorhabditis elegans ; Mammals ; Protein Conformation, alpha-Helical ; Protein Domains ; Cryoelectron Microscopy ; Cell Adhesion ; Cell Communication ; }, abstract = {The regulation of cell-cell junctions during epidermal morphogenesis ensures tissue integrity, a process regulated by α-catenin. This cytoskeletal protein connects the cadherin complex to filamentous actin at cell-cell junctions. The cadherin-catenin complex plays key roles in cell physiology, organism development, and disease. While mutagenesis of Caenorhabditis elegans cadherin and catenin shows that these proteins are key for embryonic morphogenesis, we know surprisingly little about their structure and attachment to the cytoskeleton. In contrast to mammalian α-catenin that functions as a dimer or monomer, the α-catenin ortholog from C. elegans, HMP1 for humpback, is a monomer. Our cryogenic electron microscopy (cryoEM) structure of HMP1/α-catenin reveals that the amino- and carboxy-terminal domains of HMP1/α-catenin are disordered and not in contact with the remaining HMP1/α-catenin middle domain. Since the carboxy-terminal HMP1/α-catenin domain is the F-actin-binding domain (FABD), this interdomain constellation suggests that HMP1/α-catenin is constitutively active, which we confirm biochemically. Our perhaps most surprising finding, given the high sequence similarity between the mammalian and nematode proteins, is our cryoEM structure of HMP1/α-catenin bound to F-actin. Unlike the structure of mammalian α-catenin bound to F-actin, binding to F-actin seems to allosterically convert a loop region of the HMP1/α-catenin FABD to extend an HMP1/α-catenin FABD α-helix. We use cryoEM and bundling assays to show for the first time how the FABD of HMP1/α-catenin bundles actin in the absence of force. Collectively, our data advance our understanding of α-catenin regulation of cell-cell contacts and additionally aid our understanding of the evolution of multicellularity in metazoans.}, } @article {pmid36534348, year = {2022}, author = {Nery, MF and Rennó, M and Picorelli, A and Ramos, E}, title = {A phylogenetic review of cancer resistance highlights evolutionary solutions to Peto's Paradox.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3 Suppl 1}, pages = {e20220133}, pmid = {36534348}, issn = {1415-4757}, abstract = {Cancer is a genetic disease present in all complex multicellular lineages. Finding ways to eliminate it is a goal of a large part of the scientific community and nature itself. Early, scientists realized that the cancer incidence at the species level was not related to the number of cells or lifespan, a phenomenon called Peto's Paradox. The interest in resolving this paradox triggered a growing interest in investigating the natural strategies for cancer suppression hidden in the animal's genomes. Here, we gathered information on the main mechanisms that confer resistance to cancer, currently described for lineages that have representatives with extended longevity and large body sizes. Some mechanisms to reduce or evade cancer are common and shared between lineages, while others are species-specific. The diversity of paths that evolution followed to face the cancer challenge involving coding, regulatory, and structural aspects of genomes is astonishing and much yet lacks discovery. Multidisciplinary studies involving oncology, ecology, and evolutionary biology and focusing on nonmodel species can greatly expand the frontiers of knowledge about cancer resistance in animals and may guide new promising treatments and prevention that might apply to humans.}, } @article {pmid36531949, year = {2022}, author = {Nguyen, NM and Merle, T and Broders-Bondon, F and Brunet, AC and Battistella, A and Land, EBL and Sarron, F and Jha, A and Gennisson, JL and Röttinger, E and Fernández-Sánchez, ME and Farge, E}, title = {Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {992371}, pmid = {36531949}, issn = {2296-634X}, abstract = {The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.}, } @article {pmid36531944, year = {2022}, author = {Fisher, LAB and Schöck, F}, title = {The unexpected versatility of ALP/Enigma family proteins.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {963608}, pmid = {36531944}, issn = {2296-634X}, abstract = {One of the most intriguing features of multicellular animals is their ability to move. On a cellular level, this is accomplished by the rearrangement and reorganization of the cytoskeleton, a dynamic network of filamentous proteins which provides stability and structure in a stationary context, but also facilitates directed movement by contracting. The ALP/Enigma family proteins are a diverse group of docking proteins found in numerous cellular milieus and facilitate these processes among others. In vertebrates, they are characterized by having a PDZ domain in combination with one or three LIM domains. The family is comprised of CLP-36 (PDLIM1), Mystique (PDLIM2), ALP (PDLIM3), RIL (PDLIM4), ENH (PDLIM5), ZASP (PDLIM6), and Enigma (PDLIM7). In this review, we will outline the evolution and function of their protein domains which confers their versatility. Additionally, we highlight their role in different cellular environments, focusing specifically on recent advances in muscle research using Drosophila as a model organism. Finally, we show the relevance of this protein family to human myopathies and the development of muscle-related diseases.}, } @article {pmid36529400, year = {2023}, author = {Liu, Y and Cao, M and Yan, X and Cai, X and Li, Y and Li, C and Xue, T}, title = {Genome-wide identification of gap junction (connexins and pannexins) genes in black rockfish (Sebastes schlegelii): Evolution and immune response mechanism following challenge.}, journal = {Fish & shellfish immunology}, volume = {132}, number = {}, pages = {108492}, doi = {10.1016/j.fsi.2022.108492}, pmid = {36529400}, issn = {1095-9947}, mesh = {Animals ; *Connexins/genetics ; Phylogeny ; Gap Junctions/chemistry/metabolism ; *Perciformes/metabolism ; Immunity ; }, abstract = {Cell-to-cell communication through gap junction channels is very important to coordinate the functions of cells in all multicellular biological tissues. It allows the direct exchange of ions and small molecules (including second messengers, such as Ca[2+], IP3, cyclic nucleotides, and oligonucleotides). In this study, a total of 48 members of the gap junction (GJ) protein family were identified from Sebastes schlegelii. In S. schlegelii, GJ proteins were classified into two types, connexin, and pannexin, and then connexins were divided into five subfamilies. The naming of 48 genes was verified through phylogenetic analysis and syntenic analysis. The connexin proteins contained four transmembrane fragments and two extracellular loops, the lengths of the intracellular loop and C-terminal was quite different, and the C-terminal region was highly variable after post-translational modification. PPI analysis showed that GJs interacted with tight junctions, adhesive junctions, and cell adhesions to form a complex network and participated in cell-cell junction organization, ATP binding, ion channel, voltage-gated conduction, wnt signaling pathway, Fc-γ receptor signaling pathway, and DNA replication. In addition, the S. schlegelii GJ protein was highly expressed in intestinal tissues and remarkably regulated after Edwardsiella tarda and Streptococcus iniae infection. The expression of GJs in intestinal cells of S. schlegelii was significantly regulated by LPS and poly (I:C), which was consistent with the results of intestinal tissue stimulation by pathogens. In conclusion, this study can provide valuable information for further research on the function of S. schlegelii GJ proteins.}, } @article {pmid36526191, year = {2023}, author = {Barbosa, FAS and Brait, LAS and Coutinho, FH and Ferreira, CM and Moreira, EF and de Queiroz Salles, L and Meirelles, PM}, title = {Ecological landscape explains aquifers microbial structure.}, journal = {The Science of the total environment}, volume = {862}, number = {}, pages = {160822}, doi = {10.1016/j.scitotenv.2022.160822}, pmid = {36526191}, issn = {1879-1026}, mesh = {Humans ; *Groundwater/chemistry ; Bacteria/metabolism ; Water Quality ; Gram-Negative Bacteria ; *Microbiota ; }, abstract = {Aquifers have significant social, economic, and ecological importance. They supply 30 % of the freshwater for human consumption worldwide, including agricultural and industrial use. Despite aquifers' importance, the relationships between aquifer categories and their inhabiting microbial communities are still unknown. Characterizing variations within microbial communities' function and taxonomy structure at different aquifers could give a panoramic view of patterns that may enable the detection and prediction of environmental impact caused by multiple sources. Using publicly available shotgun metagenomic datasets, we examined whether soil properties, land use, and climate variables would have a more significant influence on the taxonomy and functional structure of the microbial communities than the ecological landscapes of the aquifer (i.e., Karst, Porous, Saline, Geyser, and Porous Contaminated). We found that these categories are stronger predictors of microbial communities' structure than geographical localization. In addition, our results show that microbial richness and dominance patterns are the opposite of those found in multicellular life, where extreme habitats harbour richer functional and taxonomic microbial communities. We found that low-abundant and recently described candidate taxa, such as the chemolithoautotrophic genus Candidatus Altiarcheum and the Candidate phylum Parcubacteria, are the main contributors to aquifer microbial communities' dissimilarities. Genes related to gram-negative bacteria proteins, cell wall structures, and phage activity were the primary contributors to aquifer microbial communities' dissimilarities among the aquifers' ecological landscapes. The results reported in the present study highlight the utility of using ecological landscapes for investigating aquifer microbial communities. In addition, we suggest that functions played by recently described and low abundant bacterial groups need further investigation once they might affect water quality, geochemical cycles, and the effects of anthropogenic disturbances such as pollution and climatic events on aquifers.}, } @article {pmid36523555, year = {2022}, author = {Hogg, DW and Reid, AL and Dodsworth, TL and Chen, Y and Reid, RM and Xu, M and Husic, M and Biga, PR and Slee, A and Buck, LT and Barsyte-Lovejoy, D and Locke, M and Lovejoy, DA}, title = {Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1031264}, pmid = {36523555}, issn = {1664-042X}, abstract = {Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca[2+] signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.}, } @article {pmid36510137, year = {2022}, author = {Hao, J and Liang, Y and Ping, J and Li, J and Shi, W and Su, Y and Wang, T}, title = {Chloroplast gene expression level is negatively correlated with evolutionary rates and selective pressure while positively with codon usage bias in Ophioglossum vulgatum L.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {580}, pmid = {36510137}, issn = {1471-2229}, mesh = {*Genes, Chloroplast ; Codon Usage ; Codon/genetics ; *Genome, Chloroplast/genetics ; Biological Evolution ; }, abstract = {BACKGROUND: Characterization of the key factors determining gene expression level has been of significant interest. Previous studies on the relationship among evolutionary rates, codon usage bias, and expression level mostly focused on either nuclear genes or unicellular/multicellular organisms but few in chloroplast (cp) genes. Ophioglossum vulgatum is a unique fern and has important scientific and medicinal values. In this study, we sequenced its cp genome and transcriptome to estimate the evolutionary rates (dN and dS), selective pressure (dN/dS), gene expression level, codon usage bias, and their correlations.

RESULTS: The correlation coefficients between dN, dS, and dN/dS, and Transcripts Per Million (TPM) average values were -0.278 (P = 0.027 < 0.05), -0.331 (P = 0.008 < 0.05), and -0.311 (P = 0.013 < 0.05), respectively. The codon adaptation index (CAI) and tRNA adaptation index (tAI) were significantly positively correlated with TPM average values (P < 0.05).

CONCLUSIONS: Our results indicated that when the gene expression level was higher, the evolutionary rates and selective pressure were lower, but the codon usage bias was stronger. We provided evidence from cp gene data which supported the E-R (E stands for gene expression level and R stands for evolutionary rate) anti-correlation.}, } @article {pmid36506100, year = {2022}, author = {Wright, BA and Kvansakul, M and Schierwater, B and Humbert, PO}, title = {Cell polarity signalling at the birth of multicellularity: What can we learn from the first animals.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {1024489}, pmid = {36506100}, issn = {2296-634X}, abstract = {The innovation of multicellularity has driven the unparalleled evolution of animals (Metazoa). But how is a multicellular organism formed and how is its architecture maintained faithfully? The defining properties and rules required for the establishment of the architecture of multicellular organisms include the development of adhesive cell interactions, orientation of division axis, and the ability to reposition daughter cells over long distances. Central to all these properties is the ability to generate asymmetry (polarity), coordinated by a highly conserved set of proteins known as cell polarity regulators. The cell polarity complexes, Scribble, Par and Crumbs, are considered to be a metazoan innovation with apicobasal polarity and adherens junctions both believed to be present in all animals. A better understanding of the fundamental mechanisms regulating cell polarity and tissue architecture should provide key insights into the development and regeneration of all animals including humans. Here we review what is currently known about cell polarity and its control in the most basal metazoans, and how these first examples of multicellular life can inform us about the core mechanisms of tissue organisation and repair, and ultimately diseases of tissue organisation, such as cancer.}, } @article {pmid36505058, year = {2022}, author = {Alarcón, ME and Polo, PG and Akyüz, SN and Rafiqi, AM}, title = {Evolution and ontogeny of bacteriocytes in insects.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1034066}, pmid = {36505058}, issn = {1664-042X}, abstract = {The ontogenetic origins of the bacteriocytes, which are cells that harbour bacterial intracellular endosymbionts in multicellular animals, are unknown. During embryonic development, a series of morphological and transcriptional changes determine the fate of distinct cell types. The ontogeny of bacteriocytes is intimately linked with the evolutionary transition of endosymbionts from an extracellular to an intracellular environment, which in turn is linked to the diet of the host insect. Here we review the evolution and development of bacteriocytes in insects. We first classify the endosymbiotic occupants of bacteriocytes, highlighting the complex challenges they pose to the host. Then, we recall the historical account of the discovery of bacteriocytes. We then summarize the molecular interactions between the endosymbiont and the host. In addition, we illustrate the genetic contexts in which the bacteriocytes develop, with examples of the genetic changes in the hosts and endosymbionts, during specific endosymbiotic associations. We finally address the evolutionary origin as well as the putative ontogenetic or developmental source of bacteriocytes in insects.}, } @article {pmid36499258, year = {2022}, author = {Vainshelbaum, NM and Giuliani, A and Salmina, K and Pjanova, D and Erenpreisa, J}, title = {The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499258}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Gene Duplication ; Genome, Plant ; Proteome/genetics ; Evolution, Molecular ; Polyploidy ; Transcriptome ; *Neoplasms/genetics ; Mammals/genetics ; }, abstract = {The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein-protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer-testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma-germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.}, } @article {pmid36497057, year = {2022}, author = {Aktas, RG and Karski, M and Issac, B and Sun, L and Rockowitz, S and Sliz, P and Vakili, K}, title = {Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497057}, issn = {2073-4409}, mesh = {Humans ; Child ; *Organoids ; *Epithelial Cells ; }, abstract = {Organoids have been used to investigate the three-dimensional (3D) organization and function of their respective organs. These self-organizing 3D structures offer a distinct advantage over traditional two-dimensional (2D) culture techniques by creating a more physiologically relevant milieu to study complex biological systems. The goal of this study was to determine the feasibility of establishing organoids from various pediatric liver diseases and characterize the long-term evolution of cholangiocyte organoids (chol-orgs) under a single continuous culture condition. We established chol-orgs from 10 different liver conditions and characterized their multicellular organization into complex epithelial structures through budding, merging, and lumen formation. Immunofluorescent staining, electron microscopy, and single-nucleus RNA (snRNA-seq) sequencing confirmed the cholangiocytic nature of the chol-orgs. There were significant cell population differences in the transcript profiles of two-dimensional and organoid cultures based on snRNA-seq. Our study provides an approach for the generation and long-term maintenance of chol-orgs from various pediatric liver diseases under a single continuous culture condition.}, } @article {pmid36494694, year = {2022}, author = {Sun, H and Fang, T and Wang, T and Yu, Z and Gong, L and Wei, X and Wang, H and He, Y and Liu, L and Yan, Y and Sui, W and Xu, Y and Yi, S and Qiu, L and Hao, M}, title = {Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {576}, pmid = {36494694}, issn = {1479-5876}, mesh = {Humans ; *Ecosystem ; *Waldenstrom Macroglobulinemia/genetics/pathology ; Bone Marrow/pathology ; Tumor Microenvironment ; B-Lymphocytes/pathology ; }, abstract = {BACKGROUND: Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood.

METHODS: The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics.

RESULTS: Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19[+]CD3[+] and CD138[+]CD3[+], co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19[+]CD3[+] malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19[+]CD3[+] malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells.

CONCLUSIONS: Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.}, } @article {pmid36477143, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Author Correction: Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {1342}, doi = {10.1038/s42003-022-04312-w}, pmid = {36477143}, issn = {2399-3642}, } @article {pmid36476840, year = {2022}, author = {Nakabachi, A and Inoue, H and Hirose, Y}, title = {High-resolution Microbiome Analyses of Nine Psyllid Species of the Family Triozidae Identified Previously Unrecognized but Major Bacterial Populations, including Liberibacter and Wolbachia of Supergroup O.}, journal = {Microbes and environments}, volume = {37}, number = {4}, pages = {}, pmid = {36476840}, issn = {1347-4405}, mesh = {Humans ; Animals ; Liberibacter ; *Wolbachia/genetics ; *Hemiptera ; RNA, Ribosomal, 16S/genetics ; Europe ; }, abstract = {Psyllids (Hemiptera: Sternorrhyncha: Psylloidea) are plant sap-sucking insects that include important agricultural pests. To obtain insights into the ecological and evolutionary behaviors of microbes, including plant pathogens, in Psylloidea, high-resolution ana-lyses of the microbiomes of nine psyllid species belonging to the family Triozidae were performed using high-throughput amplicon sequencing of the 16S rRNA gene. Analyses identified various bacterial populations, showing that all nine psyllids have at least one secondary symbiont, along with the primary symbiont "Candidatus Carsonella ruddii" (Gammaproteobacteria: Oceanospirillales: Halomonadaceae). The majority of the secondary symbionts were gammaproteobacteria, particularly those of the order Enterobacterales, which included Arsenophonus and Serratia symbiotica, a bacterium formerly recognized only as a secondary symbiont of aphids (Hemiptera: Sternorrhyncha: Aphidoidea). The non-Enterobacterales gammaproteobacteria identified in the present study were Diplorickettsia (Diplorickettsiales: Diplorickettsiaceae), a potential human pathogen, and Carnimonas (Oceanospirillales: Halomonadaceae), a lineage detected for the first time in Psylloidea. Regarding alphaproteobacteria, the potential plant pathogen "Ca. Liberibacter europaeus" (Rhizobiales: Rhizobiaceae) was detected for the first time in Epitrioza yasumatsui, which feeds on the Japanese silverberry Elaeagnus umbellata (Elaeagnaceae), an aggressive invasive plant in the United States and Europe. Besides the detection of Wolbachia (Rickettsiales: Anaplasmataceae) of supergroup B in three psyllid species, a lineage belonging to supergroup O was identified for the first time in Psylloidea. These results suggest the rampant transfer of bacterial symbionts among animals and plants, thereby providing deeper insights into the evolution of interkingdom interactions among multicellular organisms and bacteria, which will facilitate the control of pest psyllids.}, } @article {pmid36469777, year = {2022}, author = {Zhang, DQ and Chen, PC and Li, ZY and Zhang, R and Li, B}, title = {Topological defect-mediated morphodynamics of active-active interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {50}, pages = {e2122494119}, pmid = {36469777}, issn = {1091-6490}, mesh = {*Liquid Crystals/chemistry ; Computer Simulation ; }, abstract = {Physical interfaces widely exist in nature and engineering. Although the formation of passive interfaces is well elucidated, the physical principles governing active interfaces remain largely unknown. Here, we combine simulation, theory, and cell-based experiment to investigate the evolution of an active-active interface. We adopt a biphasic framework of active nematic liquid crystals. We find that long-lived topological defects mechanically energized by activity display unanticipated dynamics nearby the interface, where defects perform "U-turns" to keep away from the interface, push the interface to develop local fingers, or penetrate the interface to enter the opposite phase, driving interfacial morphogenesis and cross-interface defect transport. We identify that the emergent interfacial morphodynamics stems from the instability of the interface and is further driven by the activity-dependent defect-interface interactions. Experiments of interacting multicellular monolayers with extensile and contractile differences in cell activity have confirmed our predictions. These findings reveal a crucial role of topological defects in active-active interfaces during, for example, boundary formation and tissue competition that underlie organogenesis and clinically relevant disorders.}, } @article {pmid36468669, year = {2022}, author = {Colizzi, ES and Hogeweg, P and Vroomans, RMA}, title = {Modelling the evolution of novelty: a review.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {727-735}, pmid = {36468669}, issn = {1744-1358}, abstract = {Evolution has been an inventive process since its inception, about 4 billion years ago. It has generated an astounding diversity of novel mechanisms and structures for adaptation to the environment, for competition and cooperation, and for organisation of the internal and external dynamics of the organism. How does this novelty come about? Evolution builds with the tools available, and on top of what it has already built - therefore, much novelty consists in repurposing old functions in a different context. In the process, the tools themselves evolve, allowing yet more novelty to arise. Despite evolutionary novelty being the most striking observable of evolution, it is not accounted for in classical evolutionary theory. Nevertheless, mathematical and computational models that illustrate mechanisms of evolutionary innovation have been developed. In the present review, we present and compare several examples of computational evo-devo models that capture two aspects of novelty: 'between-level novelty' and 'constructive novelty.' Novelty can evolve between predefined levels of organisation to dynamically transcode biological information across these levels - as occurs during development. Constructive novelty instead generates a level of biological organisation by exploiting the lower level as an informational scaffold to open a new space of possibilities - an example being the evolution of multicellularity. We propose that the field of computational evo-devo is well-poised to reveal many more exciting mechanisms for the evolution of novelty. A broader theory of evolutionary novelty may well be attainable in the near future.}, } @article {pmid36460873, year = {2022}, author = {Niculescu, VF}, title = {A comment on the article Jaques et al. "Origin and evolution of animal multicellularity in light of phylogenomics and cancer genetics ".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {1}, pages = {38}, pmid = {36460873}, issn = {1559-131X}, mesh = {Animals ; Humans ; Phylogeny ; *Health Personnel ; *Neoplasms/genetics ; }, abstract = {For developmental biologists, the work of Jaques et al. is quite surprising. It suggests that cancer genetics and cancer phylogenomics may contribute to the origin and evolution of multicellularity in animals. My commentary complements the work of Jaques et al. from the perspective of evolutionary life cycle biology and recalls the statement of Douglas H. Erwin, who said that understanding life cycle evolution is (equally) crucial to subsequent steps [1].}, } @article {pmid36449319, year = {2022}, author = {Baker, EA and Woollard, A}, title = {The road less travelled? Exploring the nuanced evolutionary consequences of duplicated genes.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {737-744}, pmid = {36449319}, issn = {1744-1358}, abstract = {Duplicated genes have long been appreciated as both substrates and catalysts of evolutionary processes. From even the simplest cell to complex multicellular animals and plants, duplicated genes have made immeasurable contributions to the phenotypic evolution of all life on Earth. Not merely drivers of morphological innovation and speciation events, however, gene duplications sculpt the evolution of genetic architecture in ways we are only just coming to understand now we have the experimental tools to do so. As such, the present article revisits our understanding of the ways in which duplicated genes evolve, examining closely the various fates they can adopt in light of recent work that yields insights from studies of paralogues from across the tree of life that challenge the classical framework.}, } @article {pmid36447160, year = {2022}, author = {Liu, Y and Ma, Y and Aray, H and Lan, H}, title = {Morphogenesis and cell wall composition of trichomes and their function in response to salt in halophyte Salsola ferganica.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {551}, pmid = {36447160}, issn = {1471-2229}, mesh = {*Salsola ; Salt-Tolerant Plants/genetics ; Trichomes ; *Arabidopsis/genetics ; Sodium Chloride ; Cell Wall ; Morphogenesis ; Gossypium ; }, abstract = {BACKGROUND: To survive harsh environmental conditions, desert plants show various adaptions, such as the evolution of trichomes, which are protective epidermal protrusions. Currently, the morphogenesis and function of trichomes in desert plants are not well understood. Salsola ferganica is an annual halophyte distributed in cold deserts; at the seedling stage, its rod-shaped true leaves are covered with long and thick trichomes and are affected by habitat conditions. Therefore, we evaluated the trichomes on morphogenesis and cell wall composition of S. ferganica compared to Arabidopsis thaliana and cotton, related gene expression, and preliminary function in salt accumulation of the leaves.

RESULTS: The trichomes of S. ferganica were initiated from the epidermal primordium, followed by two to three rounds of cell division to form a multicellular trichome, while some genes associated with them were positively involved. Cell wall composition analysis showed that different polysaccharides including heavily methyl-esterified and fully de-esterified pectins (before maturation, probably in the primary wall), xyloglucans (in the mid-early and middle stages, probably in the secondary wall), and extensin (during the whole developmental period) were detected, which were different from those found in trichomes of Arabidopsis and cotton. Moreover, trichome development was affected by abiotic stress, and might accumulate salt from the mesophyll cells and secrete outside.

CONCLUSIONS: S. ferganica has multicellular, non-branched trichomes that undergo two to three rounds of cell division and are affected by abiotic stress. They have a unique cell wall composition which is different from that of Arabidopsis and cotton. Furthermore, several genes positively or negatively regulate trichome development. Our findings should contribute to our further understanding of the biogenesis and adaptation of plant accessory structures in desert plant species.}, } @article {pmid36434792, year = {2022}, author = {Zhan, A and Luo, Y and Qin, H and Lin, W and Tian, L}, title = {Hypomagnetic Field Exposure Affecting Gut Microbiota, Reactive Oxygen Species Levels, and Colonic Cell Proliferation in Mice.}, journal = {Bioelectromagnetics}, volume = {43}, number = {8}, pages = {462-475}, doi = {10.1002/bem.22427}, pmid = {36434792}, issn = {1521-186X}, mesh = {Animals ; Mice ; Cell Proliferation ; *Colon ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Reactive Oxygen Species ; }, abstract = {The gut microbiota has been considered one of the key factors in host health, which is influenced by many environmental factors. The geomagnetic field (GMF) represents one of the important environmental conditions for living organisms. Previous studies have shown that the elimination of GMF, the so-called hypomagnetic field (HMF), could affect the physiological functions and resistance to antibiotics of some microorganisms. However, whether long-term HMF exposure could alter the gut microbiota to some extent in mammals remains unclear. Here, we investigated the effects of long-term (8- and 12-week) HMF exposure on the gut microbiota in C57BL/6J mice. Our results clearly showed that 8-week HMF significantly affected the diversity and function of the mouse gut microbiota. Compared with the GMF group, the concentrations of short-chain fatty acids tended to decrease in the HMF group. Immunofluorescence analysis showed that HMF promoted colonic cell proliferation, concomitant with an increased level of reactive oxygen species (ROS). To our knowledge, this is the first in vivo finding that long-term HMF exposure could affect the mouse gut microbiota, ROS levels, and colonic cell proliferation in the colon. Moreover, the changes in gut microbiota can be restored by returning mice to the GMF environment, thus the possible harm to the microbiota caused by HMF exposure can be alleviated. © 2022 Bioelectromagnetics Society.}, } @article {pmid36433975, year = {2022}, author = {Kreider, JJ and Janzen, T and Bernadou, A and Elsner, D and Kramer, BH and Weissing, FJ}, title = {Resource sharing is sufficient for the emergence of division of labour.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {7232}, pmid = {36433975}, issn = {2041-1723}, mesh = {Animals ; Female ; Pregnancy ; *Biological Evolution ; *Labor, Obstetric ; }, abstract = {Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.}, } @article {pmid36430514, year = {2022}, author = {Ojosnegros, S and Alvarez, JM and Grossmann, J and Gagliardini, V and Quintanilla, LG and Grossniklaus, U and Fernández, H}, title = {The Shared Proteome of the Apomictic Fern Dryopteris affinis ssp. affinis and Its Sexual Relative Dryopteris oreades.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430514}, issn = {1422-0067}, mesh = {*Dryopteris/genetics ; *Ferns/genetics ; Proteome ; Proteomics ; Plant Growth Regulators ; }, abstract = {Ferns are a diverse evolutionary lineage, sister to the seed plants, which is of great ecological importance and has a high biotechnological potential. Fern gametophytes represent one of the simplest autotrophic, multicellular plant forms and show several experimental advantages, including a simple and space-efficient in vitro culture system. However, the molecular basis of fern growth and development has hardly been studied. Here, we report on a proteomic study that identified 417 proteins shared by gametophytes of the apogamous fern Dryopteris affinis ssp. affinis and its sexual relative Dryopteris oreades. Most proteins are predicted to localize to the cytoplasm, the chloroplast, or the nucleus, and are linked to enzymatic, binding, and structural activities. A subset of 145 proteins are involved in growth, reproduction, phytohormone signaling and biosynthesis, and gene expression, including homologs of SHEPHERD (SHD), HEAT SHOCK PROTEIN 90-5 (CR88), TRP4, BOBBER 1 (BOB1), FLAVONE 3'-O-METHYLTRANSFERASE 1 (OMT1), ZEAXANTHIN EPOXIDASE (ABA1), GLUTAMATE DESCARBOXYLASE 1 (GAD), and dsRNA-BINDING DOMAIN-LIKE SUPERFAMILY PROTEIN (HLY1). Nearly 25% of the annotated proteins are associated with responses to biotic and abiotic stimuli. As for biotic stress, the proteins PROTEIN SGT1 HOMOLOG B (SGT1B), SUPPRESSOR OF SA INSENSITIVE2 (SSI2), PHOSPHOLIPASE D ALPHA 1 (PLDALPHA1), SERINE/THREONINE-PROTEIN KINASE SRK2E (OST1), ACYL CARRIER PROTEIN 4 (ACP4), and NONHOST RESISTANCE TO P. S. PHASEOLICOLA1 (GLPK) are worth mentioning. Regarding abiotic stimuli, we found proteins associated with oxidative stress: SUPEROXIDE DISMUTASE[CU-ZN] 1 (CSD1), and GLUTATHIONE S-TRANSFERASE U19 (GSTU19), light intensity SERINE HYDROXYMETHYLTRANSFERASE 1 (SHM1) and UBIQUITIN-CONJUGATING ENZYME E2 35 (UBC35), salt and heavy metal stress included MITOCHONDRIAL PHOSPHATE CARRIER PROTEIN 3 (PHT3;1), as well as drought and thermotolerance: LEA7, DEAD-BOX ATP-DEPENDENT RNA HELICASE 38 (LOS4), and abundant heat-shock proteins and other chaperones. In addition, we identified interactomes using the STRING platform, revealing protein-protein associations obtained from co-expression, co-occurrence, text mining, homology, databases, and experimental datasets. By focusing on ferns, this proteomic study increases our knowledge on plant development and evolution, and may inspire future applications in crop species.}, } @article {pmid36421702, year = {2022}, author = {Sowa, ST and Bosetti, C and Galera-Prat, A and Johnson, MS and Lehtiö, L}, title = {An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36421702}, issn = {2218-273X}, mesh = {Humans ; Animals ; *Tankyrases/genetics/chemistry/metabolism ; Telomere Homeostasis ; Wnt Signaling Pathway ; }, abstract = {Tankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species may exist. In this work, we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identify the single-celled choanoflagellates as earliest origin of tankyrases. We further show that the sequences and structural aspects of TNKSs are well-conserved even between distantly related species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners varies greatly between species, indicating that tankyrases may have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, and that their regulatory functions in cells have likely changed considerably throughout evolution.}, } @article {pmid36407558, year = {2022}, author = {Pandey, R and Mani, D and Shanker, K and Bawankule, DU and Chanda, D and Lal, RK and Pal, A and Khare, P and Kumar, N and Tandon, S and Saikia, D and Gupta, AK and Srivastava, RK and Kumar, S and Suresh, R and Singh, S and Kalra, A and Maurya, A and Singh, DP and Pandey, T and Trivedi, S and Smita, SS and Pant, A and Rathor, L and Asthana, J and Trivedi, M and Trivedi, PK}, title = {Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model.}, journal = {The Nucleus : an international journal of cytology and allied topics}, volume = {65}, number = {3}, pages = {303-320}, pmid = {36407558}, issn = {0029-568X}, abstract = {UNLABELLED: The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13237-022-00407-1.}, } @article {pmid36404107, year = {2023}, author = {Sepp, T and Giraudeau, M}, title = {Wild animals as an underused treasure trove for studying the genetics of cancer.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200188}, doi = {10.1002/bies.202200188}, pmid = {36404107}, issn = {1521-1878}, mesh = {Animals ; Humans ; *Animals, Wild/genetics ; Ecology ; Biodiversity ; *Neoplasms/genetics ; Genomics ; }, abstract = {Recent years have seen an emergence of the field of comparative cancer genomics. However, the advancements in this field are held back by the hesitation to use knowledge obtained from human studies to study cancer in other animals, and vice versa. Since cancer is an ancient disease that arose with multicellularity, oncogenes and tumour-suppressor genes are amongst the oldest gene classes, shared by most animal species. Acknowledging that other animals are, in terms of cancer genetics, ecology, and evolution, rather similar to humans, creates huge potential for advancing the fields of human and animal oncology, but also biodiversity conservation. Also see the video abstract here: https://youtu.be/UFqyMx5HETY.}, } @article {pmid36386690, year = {2022}, author = {Rodríguez-Rojas, A and Rolff, J}, title = {Antimicrobial activity of cationic antimicrobial peptides against stationary phase bacteria.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1029084}, pmid = {36386690}, issn = {1664-302X}, abstract = {Antimicrobial peptides (AMPs) are ancient antimicrobial weapons used by multicellular organisms as components of their innate immune defenses. Because of the antibiotic crisis, AMPs have also become candidates for developing new drugs. Here, we show that five different AMPs of different classes are effective against non-dividing Escherichia coli and Staphylococcus aureus. By comparison, three conventional antibiotics from the main three classes of antibiotics poorly kill non-dividing bacteria at clinically relevant doses. The killing of fast-growing bacteria by AMPs is faster than that of slow-dividing bacteria and, in some cases, without any difference. Still, non-dividing bacteria are effectively killed over time. Our results point to a general property of AMPs, which might explain why selection has favored AMPs in the evolution of metazoan immune systems. The ability to kill non-dividing cells is another reason that makes AMPs exciting candidates for drug development.}, } @article {pmid36384644, year = {2022}, author = {Pinskey, JM and Lagisetty, A and Gui, L and Phan, N and Reetz, E and Tavakoli, A and Fu, G and Nicastro, D}, title = {Three-dimensional flagella structures from animals' closest unicellular relatives, the Choanoflagellates.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36384644}, issn = {2050-084X}, support = {F32 GM137470/GM/NIGMS NIH HHS/United States ; R01 GM083122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cryoelectron Microscopy ; Flagella ; Axoneme ; Cilia ; }, abstract = {In most eukaryotic organisms, cilia and flagella perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of flagellar structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the Opisthokonta clade, leaving a sizeable gap in our understanding of flagella evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans' closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on flagella from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta flagella, including microtubule holes, microtubule inner proteins, and the flagellar vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the flagellar membrane. Together, our findings provide new insights into choanoflagellate biology and flagella evolution between unicellular and multicellular opisthokonts.}, } @article {pmid36379956, year = {2022}, author = {Huang, J and Zhao, L and Malik, S and Gentile, BR and Xiong, V and Arazi, T and Owen, HA and Friml, J and Zhao, D}, title = {Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6960}, pmid = {36379956}, issn = {2041-1723}, mesh = {*Arabidopsis/metabolism ; *Arabidopsis Proteins/metabolism ; *MicroRNAs/genetics/metabolism ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Germ Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.}, } @article {pmid36372985, year = {2022}, author = {Durbagula, S and Korlimarla, A and Ravikumar, G and Valiya Parambath, S and Kaku, SM and Visweswariah, AM}, title = {Prenatal epigenetic factors are predisposing for neurodevelopmental disorders-Considering placenta as a model.}, journal = {Birth defects research}, volume = {114}, number = {20}, pages = {1324-1342}, doi = {10.1002/bdr2.2119}, pmid = {36372985}, issn = {2472-1727}, mesh = {Animals ; Pregnancy ; Female ; *Placenta/metabolism ; *Neurodevelopmental Disorders/genetics ; Epigenomics ; Epigenesis, Genetic ; Fetal Development/physiology ; }, abstract = {The heterogeneous characteristics of neurodevelopmental disorders (NDDs) have resulted in varied perspectives on their causation. The biology behind the phenotypic heterogeneity in NDDs is not yet well-defined, but a strong genetic basis has become well accepted as causal for NDDs. Alongside this, there is growing focus on epigenetic mechanisms. The evidence mounting for in-utero origins of NDDs has promoted research focused on epigenetic mechanisms that impact genes that program early brain development. Considering that placenta is a vital organ, this review emphasizes the prenatal factors and their effects on epigenetic changes influencing the normal functioning of the placenta, and factors mediating pathology in the developing fetus. Overall, it is an attempt to bring focus on the hypothesis that "Prenatal epigenetic factors in the placenta could be predisposing to NDDs (with special interest on autism spectrum disorders)." This review finds growing evidence for epigenetic modifications in the placenta that affect glucocorticoid, nutrient, and immune signaling pathways, eventually impacting fetal brain development. This evidence largely comes from animal models. Given the multicellular nature of placenta, we conclude that, there is a need for placental research focused on employing single-cell approaches and genome-wide methylation profiles to bring insights into specific molecular pathways in the placenta that regulate early brain development.}, } @article {pmid36366977, year = {2023}, author = {Yu, L and Stachowicz, JJ and DuBois, K and Reusch, TBH}, title = {Detecting clonemate pairs in multicellular diploid clonal species based on a shared heterozygosity index.}, journal = {Molecular ecology resources}, volume = {23}, number = {3}, pages = {592-600}, doi = {10.1111/1755-0998.13736}, pmid = {36366977}, issn = {1755-0998}, mesh = {Animals ; *Diploidy ; Heterozygote ; *Genome ; Reproduction ; Genetic Loci ; }, abstract = {Clonal reproduction, the formation of nearly identical individuals via mitosis in the absence of genetic recombination, is a very common reproductive mode across plants, fungi and animals. To detect clonal genetic structure, genetic similarity indices based on shared alleles are widely used, such as the Jaccard index, or identity by state. Here we propose a new pairwise genetic similarity index, the SH index, based on segregating genetic marker loci (typically single nucleotide polymorphisms) that are identically heterozygous for pairs of samples (NSH). To test our method, we analyse two old seagrass clones (Posidonia australis, estimated to be around 8500 years old; Zostera marina, >750 years old) along with two young Z. marina clones of known age (17 years old). We show that focusing on shared heterozygosity amplifies the power to distinguish sample pairs belonging to different clones compared to methods focusing on all shared alleles. Our proposed workflow can successfully detect clonemates at a location dominated by a single clone. When the collected samples involve two or more clones, the SH index shows a clear gap between clonemate pairs and interclone sample pairs. Ideally NSH should be on the order of approximately ≥3000, a number easily achievable via restriction-site associated DNA (RAD) sequencing or whole-genome resequencing. Another potential application of the SH index is to detect possible parent-descendant pairs under selfing. Our proposed workflow takes advantage of the availability of the larger number of genetic markers in the genomic era, and improves the ability to distinguish clonemates from nonclonemates in multicellular diploid clonal species.}, } @article {pmid36356576, year = {2022}, author = {Peterson, AF and Ingram, K and Huang, EJ and Parksong, J and McKenney, C and Bever, GS and Regot, S}, title = {Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {885-894.e4}, pmid = {36356576}, issn = {2405-4720}, support = {R35 GM133499/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *JNK Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System ; Phosphorylation ; Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; }, abstract = {The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.}, } @article {pmid36342925, year = {2022}, author = {Oda, AH and Tamura, M and Kaneko, K and Ohta, K and Hatakeyama, TS}, title = {Autotoxin-mediated latecomer killing in yeast communities.}, journal = {PLoS biology}, volume = {20}, number = {11}, pages = {e3001844}, pmid = {36342925}, issn = {1545-7885}, mesh = {Humans ; *Saccharomyces cerevisiae/genetics ; *Yeast, Dried ; Cell Death ; Germ Cells ; Glucose ; }, abstract = {Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.}, } @article {pmid36331628, year = {2022}, author = {Alvarez, FE and Carrillo, JA and Clairambault, J}, title = {Evolution of a structured cell population endowed with plasticity of traits under constraints on and between the traits.}, journal = {Journal of mathematical biology}, volume = {85}, number = {6-7}, pages = {64}, pmid = {36331628}, issn = {1432-1416}, mesh = {Animals ; Phenotype ; Population Dynamics ; *Biological Evolution ; }, abstract = {Confronted with the biological problem of managing plasticity in cell populations, which is in particular responsible for transient and reversible drug resistance in cancer, we propose a rationale consisting of an integro-differential and a reaction-advection-diffusion equation, the properties of which are studied theoretically and numerically. By using a constructive finite volume method, we show the existence and uniqueness of a weak solution and illustrate by numerical approximations and their simulations the capacity of the model to exhibit divergence of traits. This feature may be theoretically interpreted as describing a physiological step towards multicellularity in animal evolution and, closer to present-day clinical challenges in oncology, as a possible representation of bet hedging in cancer cell populations.}, } @article {pmid36329610, year = {2022}, author = {Banijamali, M and Höjer, P and Nagy, A and Hååg, P and Gomero, EP and Stiller, C and Kaminskyy, VO and Ekman, S and Lewensohn, R and Karlström, AE and Viktorsson, K and Ahmadian, A}, title = {Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis.}, journal = {Journal of extracellular vesicles}, volume = {11}, number = {11}, pages = {e12277}, pmid = {36329610}, issn = {2001-3078}, mesh = {Humans ; *Extracellular Vesicles/genetics ; Biomarkers/metabolism ; Cell Line ; Membrane Proteins/metabolism ; }, abstract = {Small extracellular vesicles (sEVs) have in recent years evolved as a source of biomarkers for disease diagnosis and therapeutic follow up. sEV samples derived from multicellular organisms exhibit a high heterogeneous repertoire of vesicles which current methods based on ensemble measurements cannot capture. In this work we present droplet barcode sequencing for protein analysis (DBS-Pro) to profile surface proteins on individual sEVs, facilitating identification of sEV-subtypes within and between samples. The method allows for analysis of multiple proteins through use of DNA barcoded affinity reagents and sequencing as readout. High throughput single vesicle profiling is enabled through compartmentalization of individual sEVs in emulsion droplets followed by droplet barcoding through PCR. In this proof-of-concept study we demonstrate that DBS-Pro allows for analysis of single sEVs, with a mixing rate below 2%. A total of over 120,000 individual sEVs obtained from a NSCLC cell line and from malignant pleural effusion (MPE) fluid of NSCLC patients have been analyzed based on their surface proteins. We also show that the method enables single vesicle surface protein profiling and by extension characterization of sEV-subtypes, which is essential to identify the cellular origin of vesicles in heterogenous samples.}, } @article {pmid36325178, year = {2022}, author = {Sakai, D and Nishikawa, J and Kakiuchida, H and Hirose, E}, title = {Stack of cellular lamellae forms a silvered cortex to conceal the opaque organ in a transparent gastropod in epipelagic habitat.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14284}, pmid = {36325178}, issn = {2167-8359}, mesh = {Animals ; Cell Nucleus ; *Gastropoda ; Light ; Vision, Ocular ; }, abstract = {BACKGROUND: Gelatinous zooplankton in epipelagic environments often have highly transparent bodies to avoid detection by their visual predators and prey; however, the digestive systems are often exceptionally opaque even in these organisms. In a holoplanktonic gastropod, Pterotrachea coronata, the visceral nucleus is an opaque organ located at the posterior end of its alimentary system, but this organ has a mirrored surface to conceal its internal opaque tissue.

RESULTS: Our ultrastructural observation proved that the cortex of the visceral nucleus comprised a stack of thin cellular lamellae forming a Bragg reflector, and the thickness of lamellae (0.16 µm in average) and the spaces between the lamellae (0.1 µm in average) tended to become thinner toward inner lamellae. Based on the measured values, we built virtual models of the multilamellar layer comprising 50 lamellae and spaces, and the light reflection on the models was calculated using rigorous coupled wave analysis to evaluate their properties as reflectors. Our simulation supported the idea that the layer is a reflective tissue, and the thickness of the lamella/space must be chirped to reflect sunlight as white/silver light, mostly independent of the angle of incidence.

CONCLUSIONS: In P. coronata, the cortex of the visceral nucleus comprised multicellular lamellae that form a chirped Bragg reflector. It is distinct in structure from the intracellular Bragg structures of common iridophores. This novel Bragg reflector demonstrates the diversity and convergent evolution of reflective tissue using reflectin-like proteins in Mollusca.}, } @article {pmid36316013, year = {2022}, author = {Niklas, KJ and Tiffney, BH}, title = {Viridiplantae Body Plans Viewed Through the Lens of the Fossil Record and Molecular Biology.}, journal = {Integrative and comparative biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/icb/icac150}, pmid = {36316013}, issn = {1557-7023}, abstract = {A review of the fossil record coupled with insights gained from molecular and developmental biology reveal a series of body plan transformations that gave rise to the first land plants. Across diverse algal clades, including the green algae and their descendants, the plant body plan underwent a unicellul ar $\to$ colonial $\to$ simple multicellular $\to \,\,$complex multicellular transformation series. The colonization of land involved increasing body size and associated cell specialization, including cells capable of hydraulic transport. The evolution of the life-cycle that characterizes all known land plant species involved a divergence in body plan phenotypes between the haploid and diploid generations, one adapted to facilitate sexual reproduction (a free-water dependent gametophyte), and another adapted to the dissemination of spores (a more water-independent sporophyte). The amplification of this phenotypic divergence, combined with indeterminate growth in body size, resulted in a desiccation-adapted branched sporophyte with a cuticularized epidermis, stomates, and vascular tissues. Throughout the evolution of the land plants, the body plans of the sporophyte generation involved "axiation," i.e., the acquisition of a cylindrical geometry and subsequent organographic specializations.}, } @article {pmid36313615, year = {2022}, author = {Nicolicht-Amorim, P and Delgado-Garcia, LM and Nakamura, TKE and Courbassier, NR and Mosini, AC and Porcionatto, MA}, title = {Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {949412}, pmid = {36313615}, issn = {1662-5102}, abstract = {The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood-brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen-glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.}, } @article {pmid36305297, year = {2022}, author = {León-Ruiz, JA and Cruz Ramírez, A}, title = {Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.}, journal = {The Plant journal : for cell and molecular biology}, volume = {112}, number = {6}, pages = {1507-1524}, doi = {10.1111/tpj.16012}, pmid = {36305297}, issn = {1365-313X}, mesh = {Animals ; *Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; *Retinal Neoplasms ; }, abstract = {The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.}, } @article {pmid36283350, year = {2022}, author = {Keller, J and Delaux, PM}, title = {Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {R1028-R1029}, doi = {10.1016/j.cub.2022.09.006}, pmid = {36283350}, issn = {1879-0445}, mesh = {*Embryophyta ; Phylogeny ; Plants/genetics ; Evolution, Molecular ; Biological Evolution ; }, abstract = {The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.}, } @article {pmid36264199, year = {2022}, author = {Whye, D and Wood, D and Kim, KH and Chen, C and Makhortova, N and Sahin, M and Buttermore, ED}, title = {Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.}, journal = {Current protocols}, volume = {2}, number = {10}, pages = {e568}, pmid = {36264199}, issn = {2691-1299}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Pregnancy ; Female ; *Organoids ; Hedgehog Proteins ; Poloxamer ; *Pluripotent Stem Cells ; Fibroblast Growth Factors ; Retinoids ; }, abstract = {Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.}, } @article {pmid36255595, year = {2022}, author = {Bano, N and Aalam, S and Bag, SK}, title = {Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.}, journal = {Plant molecular biology}, volume = {110}, number = {6}, pages = {455-468}, pmid = {36255595}, issn = {1573-5028}, mesh = {Animals ; *Transcription Factors/genetics/metabolism ; Amino Acid Sequence ; *Plants/genetics/metabolism ; Stress, Physiological ; Plant Growth Regulators/metabolism ; }, abstract = {Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.}, } @article {pmid36252029, year = {2022}, author = {Günther, M and Reimer, C and Herbst, R and Kufs, JE and Rautschek, J and Ueberschaar, N and Zhang, S and Peschel, G and Reimer, L and Regestein, L and Valiante, V and Hillmann, F and Stallforth, P}, title = {Yellow polyketide pigment suppresses premature hatching in social amoeba.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {43}, pages = {e2116122119}, pmid = {36252029}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Products/metabolism ; *Dictyostelium/physiology ; Polyketide Synthases/genetics/metabolism ; *Polyketides/metabolism ; }, abstract = {Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.}, } @article {pmid36250956, year = {2022}, author = {Nedelcu, AM}, title = {Evo-devo perspectives on cancer.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {797-815}, doi = {10.1042/EBC20220041}, pmid = {36250956}, issn = {1744-1358}, abstract = {The integration of evolutionary and developmental approaches into the field of evolutionary developmental biology has opened new areas of inquiry- from understanding the evolution of development and its underlying genetic and molecular mechanisms to addressing the role of development in evolution. For the last several decades, the terms 'evolution' and 'development' have been increasingly linked to cancer, in many different frameworks and contexts. This mini-review, as part of a special issue on Evolutionary Developmental Biology, discusses the main areas in cancer research that have been addressed through the lenses of both evolutionary and developmental biology, though not always fully or explicitly integrated in an evo-devo framework. First, it briefly introduces the current views on carcinogenesis that invoke evolutionary and/or developmental perspectives. Then, it discusses the main mechanisms proposed to have specifically evolved to suppress cancer during the evolution of multicellularity. Lastly, it considers whether the evolution of multicellularity and development was shaped by the threat of cancer (a cancer-evo-devo perspective), and/or whether the evolution of developmental programs and life history traits can shape cancer resistance/risk in various lineages (an evo-devo-cancer perspective). A proper evolutionary developmental framework for cancer, both as a disease and in terms of its natural history (in the context of the evolution of multicellularity and development as well as life history traits), could bridge the currently disparate evolutionary and developmental perspectives and uncover aspects that will provide new insights for cancer prevention and treatment.}, } @article {pmid36237424, year = {2022}, author = {Kumar, P and Kumar, P and Mandal, D and Velayutham, R}, title = {The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {985178}, pmid = {36237424}, issn = {2235-2988}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/metabolism ; Animals ; Antiparasitic Agents ; Caspases/metabolism ; *Cryptosporidiosis ; *Cryptosporidium ; Deubiquitinating Enzymes/genetics/metabolism ; Humans ; *Parasites/metabolism ; Phylogeny ; Polyubiquitin/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Ubiquitination ; }, abstract = {Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.}, } @article {pmid36232785, year = {2022}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232785}, issn = {1422-0067}, mesh = {Animals ; Biology ; Cell Differentiation/genetics ; Embryonic Stem Cells ; Humans ; *Induced Pluripotent Stem Cells ; *Neoplasms/genetics/metabolism ; Regenerative Medicine ; }, abstract = {The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.}, } @article {pmid36229744, year = {2022}, author = {Akçelik, N and Akçelik, M}, title = {What makes another life possible in bacteria? Global regulators as architects of bacterial biofilms.}, journal = {World journal of microbiology & biotechnology}, volume = {38}, number = {12}, pages = {236}, pmid = {36229744}, issn = {1573-0972}, mesh = {Adenosine Monophosphate/metabolism ; Bacteria/genetics/metabolism ; Bacterial Proteins/metabolism ; Biofilms ; Cyclic GMP/metabolism ; *Ecosystem ; *Gene Expression Regulation, Bacterial ; Guanosine Monophosphate/metabolism ; Plankton/metabolism ; Quorum Sensing/genetics ; }, abstract = {Biofilm structures are the main mode of evolutionary reproductive adaptation of bacteria, and even these features alone, are sufficient to make them the focus of genetic and physiological studies. As this life form is a multicellular-like life form coordinated by genetic and physiological programming, it is quite different from the planktonic form. In bacterial biofilms, which are often composed of more than one species in nature, there is a clear division of labor, nutrient channels, and a language (signaling) established between the cells forming the biofilm. On the other hand, biofilms, especially formed by pathogens, cause important industrial and clinical problems due to their high resistance to environmental stress conditions. Obtaining new data on the molecular basis of bacterial evolution and understanding the intra- and inter-species ecosystem relations in this context, as well as finding permanent solutions to the serious problems they create, are directly related to a detailed understanding of the genetic regulation of bacterial biofilm structures. Today, it is becoming increasingly certain that environmental signals effective in the transition from planktonic form to biofilm form and their receptor/response molecules are generally managed by similar systems and global regulator molecules in bacteria. In this sense; Besides the quorum sensing (QS) systems, cyclic adenosine monophosphate-catabolite suppressor protein (cAMP-CRP) and bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP) signaling molecules are of critical importance. In this review article, current information on bacterial biofilms is summarized and interpreted based on this framework.}, } @article {pmid36218381, year = {2022}, author = {Silva, VSD and Machado, CR}, title = {Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3}, pages = {e20220065}, pmid = {36218381}, issn = {1415-4757}, abstract = {The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.}, } @article {pmid36217823, year = {2022}, author = {Datta, S and Ratcliff, WC}, title = {Illuminating a new path to multicellularity.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36217823}, issn = {2050-084X}, mesh = {*Biological Evolution ; }, abstract = {A new species of multicellular bacteria broadens our understanding of prokaryotic multicellularity and provides insight into how multicellular organisms arise.}, } @article {pmid36217817, year = {2022}, author = {Mizuno, K and Maree, M and Nagamura, T and Koga, A and Hirayama, S and Furukawa, S and Tanaka, K and Morikawa, K}, title = {Novel multicellular prokaryote discovered next to an underground stream.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36217817}, issn = {2050-084X}, mesh = {*Biological Evolution ; *Groundwater ; Pralidoxime Compounds ; Water ; }, abstract = {A diversity of prokaryotes currently exhibit multicellularity with different generation mechanisms in a variety of contexts of ecology on Earth. In the present study, we report a new type of multicellular bacterium, HS-3, isolated from an underground stream. HS-3 self-organizes its filamentous cells into a layer-structured colony with the properties of a nematic liquid crystal. After maturation, the colony starts to form a semi-closed sphere accommodating clusters of coccobacillus daughter cells and selectively releases them upon contact with water. This is the first report that shows that a liquid-crystal status of cells can support the prokaryotic multicellular behavior. Importantly, the observed behavior of HS-3 suggests that the recurrent intermittent exposure of colonies to water flow in the cave might have been the ecological context that cultivated the evolutionary transition from unicellular to multicellular life. This is the new extant model that underpins theories regarding a role of ecological context in the emergence of multicellularity.}, } @article {pmid36213345, year = {2022}, author = {Ren, P and Dong, X and Vijg, J}, title = {Age-related somatic mutation burden in human tissues.}, journal = {Frontiers in aging}, volume = {3}, number = {}, pages = {1018119}, pmid = {36213345}, issn = {2673-6217}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; }, abstract = {The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. De novo mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.}, } @article {pmid36202151, year = {2022}, author = {Wang, P and Chen, C and Wang, Q and Chen, H and Chen, C and Xu, J and Wang, X and Song, T}, title = {Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {351}, number = {}, pages = {941-953}, doi = {10.1016/j.jconrel.2022.09.059}, pmid = {36202151}, issn = {1873-4995}, mesh = {Animals ; *Magnetosomes/metabolism ; Gram-Negative Bacteria ; Bacteria/metabolism ; Magnetics ; Mammals ; }, abstract = {Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.}, } @article {pmid36199687, year = {2022}, author = {Fuloria, NK and Raheja, RK and Shah, KH and Oza, MJ and Kulkarni, YA and Subramaniyan, V and Sekar, M and Fuloria, S}, title = {Biological activities of meroterpenoids isolated from different sources.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {830103}, pmid = {36199687}, issn = {1663-9812}, abstract = {Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.}, } @article {pmid36198374, year = {2022}, author = {Grunt, TW and Valent, P}, title = {Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.}, journal = {Progress in biophysics and molecular biology}, volume = {175}, number = {}, pages = {131-139}, doi = {10.1016/j.pbiomolbio.2022.09.009}, pmid = {36198374}, issn = {1873-1732}, mesh = {Humans ; *Biological Evolution ; Thermodynamics ; Entropy ; *Neoplasms ; Mutation ; }, abstract = {Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.}, } @article {pmid36196535, year = {2022}, author = {Gauthier, AE and Rotjan, RD and Kagan, JC}, title = {Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.}, journal = {Open biology}, volume = {12}, number = {10}, pages = {220146}, pmid = {36196535}, issn = {2046-2441}, mesh = {Animals ; Immune System/metabolism ; Immunity, Innate ; *Lipopolysaccharides ; Mammals ; *Pathogen-Associated Molecular Pattern Molecules ; }, abstract = {Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.}, } @article {pmid36180988, year = {2022}, author = {Turishcheva, E and Vildanova, M and Onishchenko, G and Smirnova, E}, title = {The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {9}, pages = {916-931}, pmid = {36180988}, issn = {1608-3040}, mesh = {*COVID-19 ; Cell Differentiation ; *Endoplasmic Reticulum Stress ; Fibrosis ; Humans ; Unfolded Protein Response ; }, abstract = {Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.}, } @article {pmid36179980, year = {2022}, author = {Hiraki, HL and Matera, DL and Wang, WY and Prabhu, ES and Zhang, Z and Midekssa, F and Argento, AE and Buschhaus, JM and Humphries, BA and Luker, GD and Pena-Francesch, A and Baker, BM}, title = {Fiber density and matrix stiffness modulate distinct cell migration modes in a 3D stroma mimetic composite hydrogel.}, journal = {Acta biomaterialia}, volume = {}, number = {}, pages = {}, pmid = {36179980}, issn = {1878-7568}, support = {R01 EB030474/EB/NIBIB NIH HHS/United States ; T32 DE007057/DE/NIDCR NIH HHS/United States ; }, abstract = {The peritumoral stroma is a complex 3D tissue that provides cells with myriad biophysical and biochemical cues. Histologic observations suggest that during metastatic spread of carcinomas, these cues influence transformed epithelial cells, prompting a diversity of migration modes spanning single cell and multicellular phenotypes. Purported consequences of these variations in tumor escape strategies include differential metastatic capability and therapy resistance. Therefore, understanding how cues from the peritumoral stromal microenvironment regulate migration mode has both prognostic and therapeutic value. Here, we utilize a synthetic stromal mimetic in which matrix fiber density and bulk hydrogel mechanics can be orthogonally tuned to investigate the contribution of these two key matrix attributes on MCF10A migration mode phenotypes, epithelial-mesenchymal transition (EMT), and invasive potential. We develop an automated computational image analysis framework to extract migratory phenotypes from fluorescent images and determine 3D migration metrics relevant to metastatic spread. Using this analysis, we find that matrix fiber density and bulk hydrogel mechanics distinctly contribute to a variety of MCF10A migration modes including amoeboid, single mesenchymal, clusters, and strands. We identify combinations of physical and soluble cues that induce a variety of migration modes originating from the same MCF10A spheroid and use these settings to examine a functional consequence of migration mode -resistance to apoptosis. We find that cells migrating as strands are more resistant to staurosporine-induced apoptosis than either disconnected clusters or individual invading cells. Improved models of the peritumoral stromal microenvironment and understanding of the relationships between matrix attributes and cell migration mode can aid ongoing efforts to identify effective cancer therapeutics that address cell plasticity-based therapy resistances. STATEMENT OF SIGNIFICANCE: Stromal extracellular matrix structure dictates both cell homeostasis and activation towards migratory phenotypes. However decoupling the effects of myriad biophysical cues has been difficult to achieve. Here, we encapsulate electrospun fiber segments within an amorphous hydrogel to create a fiber-reinforced hydrogel composite in which fiber density and hydrogel stiffness can be orthogonally tuned. Quantification of 3D cell migration reveal these two parameters uniquely contribute to a diversity of migration phenotypes spanning amoeboid, single mesenchymal, multicellular cluster, and collective strand. By tuning biophysical and biochemical cues to elicit heterogeneous migration phenotypes, we find that collective strands best resist apoptosis. This work establishes a composite approach to modulate fibrous topography and bulk hydrogel mechanics and identified biomaterial parameters to direct distinct 3D cell migration phenotypes.}, } @article {pmid36178156, year = {2022}, author = {Liau, P and Kim, C and Saxton, MA and Malkin, SY}, title = {Microbial succession in a marine sediment: Inferring interspecific microbial interactions with marine cable bacteria.}, journal = {Environmental microbiology}, volume = {24}, number = {12}, pages = {6348-6364}, doi = {10.1111/1462-2920.16230}, pmid = {36178156}, issn = {1462-2920}, mesh = {RNA, Ribosomal, 16S/genetics ; Oxidation-Reduction ; Geologic Sediments/microbiology ; *Deltaproteobacteria/genetics ; Bacteria/genetics ; Sulfur ; *Gammaproteobacteria/genetics ; *Microbiota ; Microbial Interactions ; Phylogeny ; }, abstract = {Cable bacteria are long, filamentous, multicellular bacteria that grow in marine sediments and couple sulfide oxidation to oxygen reduction over centimetre-scale distances via long-distance electron transport. Cable bacteria can strongly modify biogeochemical cycling and may affect microbial community networks. Here we examine interspecific interactions with marine cable bacteria (Ca. Electrothrix) by monitoring the succession of 16S rRNA amplicons (DNA and RNA) and cell abundance across depth and time, contrasting sediments with and without cable bacteria growth. In the oxic zone, cable bacteria activity was positively associated with abundant predatory bacteria (Bdellovibrionota, Myxococcota, Bradymonadales), indicating putative predation on cathodic cells. At suboxic depths, cable bacteria activity was positively associated with sulfate-reducing and magnetotactic bacteria, consistent with cable bacteria functioning as ecosystem engineers that modify their local biogeochemical environment, benefitting certain microbes. Cable bacteria activity was negatively associated with chemoautotrophic sulfur-oxidizing Gammaproteobacteria (Thiogranum, Sedimenticola) at oxic depths, suggesting competition, and positively correlated with these taxa at suboxic depths, suggesting syntrophy and/or facilitation. These observations are consistent with chemoautotrophic sulfur oxidizers benefitting from an oxidizing potential imparted by cable bacteria at suboxic depths, possibly by using cable bacteria as acceptors for electrons or electron equivalents, but by an as yet enigmatic mechanism.}, } @article {pmid36147948, year = {2022}, author = {Boutry, J and Tissot, S and Mekaoui, N and Dujon, A and Meliani, J and Hamede, R and Ujvari, B and Roche, B and Nedelcu, AM and Tokolyi, J and Thomas, F}, title = {Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis.}, journal = {iScience}, volume = {25}, number = {10}, pages = {105034}, pmid = {36147948}, issn = {2589-0042}, abstract = {Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors. We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort. This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.}, } @article {pmid36138796, year = {2022}, author = {Gecow, A and Iantovics, LB and Tez, M}, title = {Cancer and Chaos and the Complex Network Model of a Multicellular Organism.}, journal = {Biology}, volume = {11}, number = {9}, pages = {}, pmid = {36138796}, issn = {2079-7737}, abstract = {In the search of theoretical models describing cancer, one of promising directions is chaos. It is connected to ideas of "genome chaos" and "life on the edge of chaos", but they profoundly differ in the meaning of the term "chaos". To build any coherent models, notions used by both ideas should be firstly brought closer. The hypothesis "life on the edge of chaos" using deterministic chaos has been radically deepened developed in recent years by the discovery of half-chaos. This new view requires a deeper interpretation within the range of the cell and the organism. It has impacts on understanding "chaos" in the term "genome chaos". This study intends to present such an interpretation on the basis of which such searches will be easier and closer to intuition. We interpret genome chaos as deterministic chaos in a large module of half-chaotic network modeling the cell. We observed such chaotic modules in simulations of evolution controlled by weaker variant of natural selection. We also discuss differences between free and somatic cells in modeling their disturbance using half-chaotic networks.}, } @article {pmid36135738, year = {2022}, author = {Guryanova, SV and Ovchinnikova, TV}, title = {Innate Immunity Mechanisms in Marine Multicellular Organisms.}, journal = {Marine drugs}, volume = {20}, number = {9}, pages = {}, pmid = {36135738}, issn = {1660-3397}, mesh = {*Immunity, Innate ; Receptors, Pattern Recognition/metabolism ; *Signal Transduction ; }, abstract = {The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body's homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology.}, } @article {pmid36134999, year = {2022}, author = {Ma, C and Liu, K and Li, Q and Xiong, Y and Xu, C and Zhang, W and Ruan, C and Li, X and Lei, X}, title = {Synthetic Extracellular Matrices for 3D Culture of Schwann Cells, Hepatocytes, and HUVECs.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {9}, number = {9}, pages = {}, pmid = {36134999}, issn = {2306-5354}, abstract = {Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.}, } @article {pmid36127898, year = {2022}, author = {Bargel, H and Trossmann, VT and Sommer, C and Scheibel, T}, title = {Bioselectivity of silk protein-based materials and their bio-inspired applications.}, journal = {Beilstein journal of nanotechnology}, volume = {13}, number = {}, pages = {902-921}, pmid = {36127898}, issn = {2190-4286}, abstract = {Adhesion to material surfaces is crucial for almost all organisms regarding subsequent biological responses. Mammalian cell attachment to a surrounding biological matrix is essential for maintaining their survival and function concerning tissue formation. Conversely, the adhesion and presence of microbes interferes with important multicellular processes of tissue development. Therefore, tailoring bioselective, biologically active, and multifunctional materials for biomedical applications is a modern focus of biomaterial research. Engineering biomaterials that stimulate and interact with cell receptors to support binding and subsequent physiological responses of multicellular systems attracted much interest in the last years. Further to this, the increasing threat of multidrug resistance of pathogens against antibiotics to human health urgently requires new material concepts for preventing microbial infestation and biofilm formation. Thus, materials exhibiting microbial repellence or antimicrobial behaviour to reduce inflammation, while selectively enhancing regeneration in host tissues are of utmost interest. In this context, protein-based materials are interesting candidates due to their natural origin, biological activity, and structural properties. Silk materials, in particular those made of spider silk proteins and their recombinant counterparts, are characterized by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses on biological processes and surface interactions involved in the bioselective adhesion of mammalian cells and repellence of microbes on protein-based material surfaces. In addition, it highlights the importance of materials made of recombinant spider silk proteins, focussing on the progress regarding bioselectivity.}, } @article {pmid36127662, year = {2022}, author = {Chai, S and Aria, C and Hua, H}, title = {A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {199}, pmid = {36127662}, issn = {1741-7007}, mesh = {Animals ; China ; *Chlorophyta/genetics ; *Ecosystem ; Eukaryotic Cells ; Fossils ; }, abstract = {BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.

RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.

CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.}, } @article {pmid36114258, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {977}, pmid = {36114258}, issn = {2399-3642}, mesh = {Agar ; Animals ; *Myxococcus xanthus/genetics ; Phenotype ; *Predatory Behavior ; }, abstract = {Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.}, } @article {pmid36105707, year = {2022}, author = {Huang, X and Yi, P and Liu, Y and Li, Q and Jiang, Y and Yi, Y and Yan, H}, title = {RrTTG1 promotes fruit prickle development through an MBW complex in Rosa roxburghii.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {939270}, pmid = {36105707}, issn = {1664-462X}, abstract = {Fruit prickles are widely distributed on the pericarp and exhibit polymorphic traits at different developmental stages. Although they are multicellular appendages that are well-known for helping plants defend against biotic and abiotic stresses, their origination and molecular mechanism are still less known. Here, we studied the origination and molecular mechanism of fruit prickles in Rosa roxburghii. Using morphological and histological observations, we found that the fruit prickle primordium of R. roxburghii originated from the ground meristem that underwent cell division to form flagelliform prickles, continued to enlarge, and finally lignified to form mature fruit prickles. We amplified a homolog of candidate gene TRANSPARENT TESTA GLABRA1 (TTG1) from R. roxburghii, named RrTTG1. RrTTG1 harbored four conserved WD-repeat domains and was exclusively nuclear-localized. Using qRT-PCR and in situ hybridization, we found that RrTTG1 was constitutively expressed and highly expressed during the initiation and cell expansion phases of fruit prickles. Ectopic expression analysis in Arabidopsis proved that RrTTG1 substantially enhanced the number of trichome and pigmentation production and inhibited root hair formation. Besides, RrTTG1 complemented the phenotypes of the ttg1 mutant in Arabidopsis, thus indicating that RrTTG1 played pleiotropic roles akin to AtTTG1. We demonstrated that the RrTTG1 only interacted with RrEGL3, a homolog of ENHANCER OF GLABRA3 (EGL3), via yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Briefly, RrTTG1 might positively regulate the initiation of fruit prickle primordium and cell enlargement by forming the RrTTG1-RrEGL3-RrGL1 complex in R. roxburghii. Therefore, our results help characterize the RrTTG1 in R. roxburghii and also elucidate the establishment of the prickles regulatory system in the Rosaceae plants.}, } @article {pmid36105585, year = {2022}, author = {Adiba, S and Forget, M and De Monte, S}, title = {Evolving social behavior through selection of single-cell adhesion in Dictyostelium discoideum.}, journal = {iScience}, volume = {25}, number = {9}, pages = {105006}, pmid = {36105585}, issn = {2589-0042}, abstract = {The social amoeba Dictyostelium discoideum commonly forms chimeric fruiting bodies. Genetic variants that produce a higher proportion of spores are predicted to undercut multicellular organization unless cooperators assort positively. Cell adhesion is considered a primary factor driving such assortment, but evolution of adhesion has not been experimentally connected to changes in social performance. We modified by experimental evolution the efficiency of individual cells in attaching to a surface. Surprisingly, evolution appears to have produced social cooperators irrespective of whether stronger or weaker adhesion was selected. Quantification of reproductive success, cell-cell adhesion, and developmental patterns, however, revealed two distinct social behaviors, as captured when the classical metric for social success is generalized by considering clonal spore production. Our work shows that cell mechanical interactions can constrain the evolution of development and sociality in chimeras and that elucidation of proximate mechanisms is necessary to understand the ultimate emergence of multicellular organization.}, } @article {pmid36103852, year = {2022}, author = {Zaman, R and Epelman, S}, title = {Resident cardiac macrophages: Heterogeneity and function in health and disease.}, journal = {Immunity}, volume = {55}, number = {9}, pages = {1549-1563}, doi = {10.1016/j.immuni.2022.08.009}, pmid = {36103852}, issn = {1097-4180}, mesh = {*Heart/physiology ; *Macrophages ; Myocardium ; }, abstract = {Understanding tissue macrophage biology has become challenging in recent years due the ever-increasing complexity in macrophage-subset identification and functional characterization. This is particularly important within the myocardium, as we have come to understand that macrophages play multifaceted roles in cardiac health and disease, and heart disease remains the leading cause of death worldwide. Here, we review recent progress in the field, focusing on resident cardiac macrophage heterogeneity, origins, and functions at steady state and after injury. We stratify resident cardiac macrophage functions by the ability of macrophages to either directly influence cardiac physiology or indirectly influence cardiac physiology through orchestrating multi-cellular communication with cardiomyocytes and stromal and immune populations.}, } @article {pmid36102042, year = {2022}, author = {Xie, Q and Xiong, C and Yang, Q and Zheng, F and Larkin, RM and Zhang, J and Wang, T and Zhang, Y and Ouyang, B and Lu, Y and Ye, J and Ye, Z and Yang, C}, title = {A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.}, journal = {The New phytologist}, volume = {236}, number = {6}, pages = {2294-2310}, doi = {10.1111/nph.18492}, pmid = {36102042}, issn = {1469-8137}, mesh = {*Trichomes/metabolism ; *Solanum lycopersicum/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Plant Epidermis/metabolism ; }, abstract = {Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.}, } @article {pmid36099169, year = {2022}, author = {Ress, V and Traulsen, A and Pichugin, Y}, title = {Eco-evolutionary dynamics of clonal multicellular life cycles.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36099169}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Life Cycle Stages ; Models, Theoretical ; }, abstract = {The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.}, } @article {pmid36098425, year = {2022}, author = {Noh, S and Capodanno, BJ and Xu, S and Hamilton, MC and Strassmann, JE and Queller, DC}, title = {Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0056222}, pmid = {36098425}, issn = {2379-5077}, support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Amoeba/microbiology ; *Dictyostelium/genetics ; Eukaryota ; *Burkholderiaceae/genetics ; Bacteria/genetics ; Soil ; }, abstract = {The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.}, } @article {pmid36077628, year = {2022}, author = {Nam, C and Ziman, B and Sheth, M and Zhao, H and Lin, DC}, title = {Genomic and Epigenomic Characterization of Tumor Organoid Models.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077628}, issn = {2072-6694}, support = {R37 CA237022/CA/NCI NIH HHS/United States ; P30CA014089/CA/NCI NIH HHS/United States ; R37CA237022/NH/NIH HHS/United States ; }, abstract = {Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene-drug interactions and genotype-phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research.}, } @article {pmid36077092, year = {2022}, author = {Anatskaya, OV and Vinogradov, AE}, title = {Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077092}, issn = {1422-0067}, mesh = {Chromatin ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; *Polyploidy ; Proto-Oncogenes ; }, abstract = {Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.}, } @article {pmid36076976, year = {2022}, author = {Burzacka-Hinz, A and Narajczyk, M and Dudek, M and Szlachetko, DL}, title = {Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36076976}, issn = {1422-0067}, mesh = {*Dendrobium ; Flowers/anatomy & histology ; Microscopy, Electron, Scanning ; *Orchidaceae/anatomy & histology ; Phylogeny ; Trichomes ; }, abstract = {Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.}, } @article {pmid36064151, year = {2022}, author = {Smiley, P and Levin, M}, title = {Competition for finite resources as coordination mechanism for morphogenesis: An evolutionary algorithm study of digital embryogeny.}, journal = {Bio Systems}, volume = {221}, number = {}, pages = {104762}, doi = {10.1016/j.biosystems.2022.104762}, pmid = {36064151}, issn = {1872-8324}, mesh = {Algorithms ; *Biological Evolution ; Computer Simulation ; *Embryonic Development/genetics ; Morphogenesis/genetics ; }, abstract = {The standard view of embryogenesis is one of cooperation driven by the cells' shared genetics and evolutionary interests. However, numerous examples from developmental biology and agriculture reveal a surprising amount of competition among body cells, tissues, and organs for both metabolic and informational resources. To explain the existence of such competition we had hypothesized that evolution uses limiting "reservoirs" of resource molecules as a communication medium - a global scratchpad, to enable tissues across the body to coordinate growth. Here, we test this hypothesis via an evolutionary simulation of embryogeny in silico. Genomes encode state transition rules for cells, such as proliferation, differentiation, and resource use, enabling virtual embryos to develop a specific large-scale morphology. An evolutionary algorithm operates over the genomes, with fitness defined as a function of specific morphological requirements for the final embryo shape. We found that not only does such an algorithm rapidly discover rules for cellular behavior that reliably make embryos with specific anatomical properties, but that it discovers the strategy of using finite resources to coordinate development. Given the option of using finite or infinite reservoirs (which determine cells' ability to carry out specific actions), evolution preferentially uses finite reservoirs, which results in higher fitness and increased consistency (without needing direct selection for morphological invariance). We report aspects of anatomical, physiological/transcriptional, and genomic analysis of evolved virtual embryos that help understand how evolution can use competition among genetically identical subunits within a multicellular body to coordinate reliable, complex morphogenesis. Our results suggest that under some conditions, composite multi-scale systems will promote conflict and artificial scarcity for their components.}, } @article {pmid36055238, year = {2022}, author = {Hess, S and Williams, SK and Busch, A and Irisarri, I and Delwiche, CF and de Vries, S and Darienko, T and Roger, AJ and Archibald, JM and Buschmann, H and von Schwartzenberg, K and de Vries, J}, title = {A phylogenomically informed five-order system for the closest relatives of land plants.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {4473-4482.e7}, pmid = {36055238}, issn = {1879-0445}, mesh = {Phylogeny ; Biological Evolution ; *Embryophyta/genetics ; *Charophyceae/genetics ; *Streptophyta ; Plants ; Soil ; }, abstract = {The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.}, } @article {pmid36045216, year = {2022}, author = {Michla, M and Wilhelm, C}, title = {Food for thought - ILC metabolism in the context of helminth infections.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1234-1242}, pmid = {36045216}, issn = {1935-3456}, mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; *Helminthiasis ; *Helminths ; Inflammation ; }, abstract = {Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.}, } @article {pmid36043790, year = {2022}, author = {Kuroda, K and Yamamoto, K and Nakai, R and Hirakata, Y and Kubota, K and Nobu, MK and Narihiro, T}, title = {Symbiosis between Candidatus Patescibacteria and Archaea Discovered in Wastewater-Treating Bioreactors.}, journal = {mBio}, volume = {13}, number = {5}, pages = {e0171122}, pmid = {36043790}, issn = {2150-7511}, mesh = {*Archaea/metabolism ; Symbiosis/genetics ; Wastewater ; Phylogeny ; In Situ Hybridization, Fluorescence ; Sewage ; Bacteria/genetics ; *Euryarchaeota ; Bioreactors ; Protein Sorting Signals/genetics ; }, abstract = {Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized by their ultrasmall cell size and symbiotic lifestyles (potentially commensal, mutualistic, and parasitic relationships), namely, Candidatus Patescibacteria (also known as the Candidate Phyla Radiation/CPR superphylum) and DPANN archaea, respectively. Cultivation-based approaches have revealed that Ca. Patescibacteria and DPANN symbiotically interact with bacterial and archaeal partners and hosts, respectively, but that cross-domain symbiosis and parasitism have never been observed. By amending wastewater treatment sludge samples with methanogenic archaea, we observed increased abundances of Ca. Patescibacteria (Ca. Yanofskybacteria/UBA5738) and, using fluorescence in situ hybridization (FISH), discovered that nearly all of the Ca. Yanofskybacteria/UBA5738 cells were attached to Methanothrix (95.7 ± 2.1%) and that none of the cells were attached to other lineages, implying high host dependency and specificity. Methanothrix filaments (multicellular) with Ca. Yanofskybacteria/UBA5738 attached had significantly more cells with no or low detectable ribosomal activity (based on FISH fluorescence) and often showed deformations at the sites of attachment (based on transmission electron microscopy), suggesting that the interaction is parasitic. Metagenome-assisted metabolic reconstruction showed that Ca. Yanofskybacteria/UBA5738 lacks most of the biosynthetic pathways necessary for cell growth and universally conserves three unique gene arrays that contain multiple genes with signal peptides in the metagenome-assembled genomes of the Ca. Yanofskybacteria/UBA5738 lineage. The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR and DPANN. IMPORTANCE One highly diverse phylogenetic group of Bacteria, Ca. Patescibacteria, remains poorly understood, but, from the few cultured representatives and metagenomic investigations, they are thought to live symbiotically or parasitically with other bacteria or even with eukarya. We explored the possibility of symbiotic interactions with Archaea by amending wastewater treatment sludge samples that were rich in Ca. Patescibacteria and Archaea with an isolate archaeon that is closely related to a methanogen population abundant in situ (Methanothrix). This strategic cultivation successfully established enrichment cultures that were mainly comprised of Ca. Patescibacteria (family level lineage Ca. Yanofskybacteria/UBA5738) and Methanothrix, in which we found highly specific physical interactions between the two organisms. Microscopic observations based on transmission electron microscopy, target-specific fluorescence in situ hybridization, and metagenomic analyses showed evidence that the interaction is likely parasitic. The results show a novel cross-domain parasitism between Bacteria and Archaea and suggest that the amendment of host Archaea may be an effective approach in culturing novel Ca. Patescibacteria.}, } @article {pmid36036016, year = {2022}, author = {Fujiwara, M and Akiyama-Oda, Y and Oda, H}, title = {Virtual spherical-shaped multicellular platform for simulating the morphogenetic processes of spider-like body axis formation.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {932814}, pmid = {36036016}, issn = {2296-634X}, abstract = {Remodeling of multicellular architecture is a critical developmental process for shaping the axis of a bilaterally symmetric animal body and involves coordinated cell-cell interactions and cell rearrangement. In arthropods, the early embryonic process that leads to the segmented body axis varies at the cellular and molecular levels depending on the species. Developmental studies using insect and spider model species have provided specific examples of these diversified mechanisms that regulate axis formation and segmentation in arthropod embryos. However, there are few theoretical models for how diversity in the early embryonic process occurred during evolution, in part because of a limited computational infrastructure. We developed a virtual spherical-shaped multicellular platform to reproduce body axis-forming processes. Each virtual cell behaves according to the cell vertex model, with the computational program organized in a hierarchical order from cells and tissues to whole embryos. Using an initial set of two different mechanical states for cell differentiation and global directional signals that are linked to the planar polarity of each cell, the virtual cell assembly exhibited morphogenetic processes similar to those observed in spider embryos. We found that the development of an elongating body axis is achieved through implementation of an interactive cell polarity parameter associated with edge tension at the cell-cell adhesion interface, with no local control of the cell division rate and direction. We also showed that modifying the settings can cause variation in morphogenetic processes. This platform also can embed a gene network that generates waves of gene expression in a virtual dynamic multicellular field. This study provides a computational platform for testing the development and evolution of animal body patterns.}, } @article {pmid36028058, year = {2022}, author = {Senthilkumar, I and Howley, E and McEvoy, E}, title = {Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.}, journal = {Experimental cell research}, volume = {419}, number = {2}, pages = {113317}, doi = {10.1016/j.yexcr.2022.113317}, pmid = {36028058}, issn = {1090-2422}, mesh = {Computer Simulation ; Humans ; *Models, Biological ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.}, } @article {pmid36013944, year = {2022}, author = {Guryanova, SV}, title = {Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36013944}, issn = {2076-2607}, abstract = {Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.}, } @article {pmid36011312, year = {2022}, author = {Le, NG and van Ulsen, P and van Spanning, R and Brouwer, A and van Straalen, NM and Roelofs, D}, title = {A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {36011312}, issn = {2073-4425}, mesh = {Animals ; *Arthropods/genetics ; Bacteria/genetics ; Carbohydrates ; Escherichia coli/genetics ; Eukaryota ; *Gene Transfer, Horizontal ; Insecta ; Protein Sorting Signals/genetics ; Soil ; }, abstract = {Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.}, } @article {pmid36002568, year = {2022}, author = {Ocaña-Pallarès, E and Williams, TA and López-Escardó, D and Arroyo, AS and Pathmanathan, JS and Bapteste, E and Tikhonenkov, DV and Keeling, PJ and Szöllősi, GJ and Ruiz-Trillo, I}, title = {Divergent genomic trajectories predate the origin of animals and fungi.}, journal = {Nature}, volume = {609}, number = {7928}, pages = {747-753}, pmid = {36002568}, issn = {1476-4687}, support = {616960/ERC_/European Research Council/International ; 714774/ERC_/European Research Council/International ; 615274/ERC_/European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Genes ; *Genome/genetics ; Genome, Fungal/genetics ; *Genomics ; Metabolism/genetics ; *Phylogeny ; }, abstract = {Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.}, } @article {pmid36002411, year = {2022}, author = {Shi, B and Huang, X and Fu, X and Wang, B}, title = {[Advances in the plant multicellular network analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {8}, pages = {2798-2810}, doi = {10.13345/j.cjb.220127}, pmid = {36002411}, issn = {1872-2075}, mesh = {*Plants ; }, abstract = {Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.}, } @article {pmid35999597, year = {2022}, author = {Gahan, JM and Leclère, L and Hernandez-Valladares, M and Rentzsch, F}, title = {A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {184}, pmid = {35999597}, issn = {1741-7007}, mesh = {Animals ; Cell Differentiation ; *Chromatin ; Histone Demethylases/genetics ; Mammals/genetics ; Phylogeny ; *Sea Anemones/metabolism ; }, abstract = {BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.

RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.

CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.}, } @article {pmid35995772, year = {2022}, author = {Nyongesa, S and Weber, PM and Bernet, È and Pulido, F and Nieves, C and Nieckarz, M and Delaby, M and Viehboeck, T and Krause, N and Rivera-Millot, A and Nakamura, A and Vischer, NOE and vanNieuwenhze, M and Brun, YV and Cava, F and Bulgheresi, S and Veyrier, FJ}, title = {Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {4853}, pmid = {35995772}, issn = {2041-1723}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Cell Division ; Cell Wall/metabolism ; Mammals/microbiology ; *Neisseriaceae/cytology ; Peptidoglycan/metabolism ; }, abstract = {Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.}, } @article {pmid35988806, year = {2022}, author = {Salminen, A}, title = {Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1α (AhR/HIF-1α) signaling: Impact on the aging process.}, journal = {Cellular signalling}, volume = {99}, number = {}, pages = {110445}, doi = {10.1016/j.cellsig.2022.110445}, pmid = {35988806}, issn = {1873-3913}, mesh = {DNA ; *Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Oxygen ; Prolyl Hydroxylases ; Pyridinolcarbamate ; *Receptors, Aryl Hydrocarbon/genetics/metabolism ; Tryptophan ; }, abstract = {The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for environmental toxins and UV radiation but also for many endogenous ligands, e.g., L-tryptophan metabolites. The AhR signaling system is evolutionarily conserved and AhR homologs existed as many as 600 million years ago. The ancient atmosphere demanded the evolution of an oxygen-sensing system, i.e., hypoxia-inducible transcription factors (HIF) and their prolyl hydroxylase regulators (PHD). Given that both signaling systems have important roles in embryogenesis, it seems that they have been involved in the evolution of multicellular organisms. The evolutionary origin of the aging process is unknown although it is most likely associated with the evolution of multicellularity. Intriguingly, there is compelling evidence that while HIF-1α signaling extends the lifespan, that of AhR promotes many age-related degenerative processes, e.g., it increases oxidative stress, inhibits autophagy, promotes cellular senescence, and aggravates extracellular matrix degeneration. In contrast, HIF-1α signaling stimulates autophagy, inhibits cellular senescence, and enhances cell proliferation. Interestingly, there is a clear antagonism between the AhR and HIF-1α signaling pathways. For instance, (i) AhR and HIF-1α factors heterodimerize with the same factor, ARNT/HIF-1β, leading to their competition for DNA-binding, (ii) AhR and HIF-1α signaling exert antagonistic effects on autophagy, and (iii) co-chaperone p23 exhibits specific functions in the signaling of AhR and HIF-1α factors. One might speculate that it is the competition between the AhR and HIF-1α signaling pathways that is a driving force in the aging process.}, } @article {pmid35975712, year = {2022}, author = {Bourrat, P and Doulcier, G and Rose, CJ and Rainey, PB and Hammerschmidt, K}, title = {Tradeoff breaking as a model of evolutionary transitions in individuality and limits of the fitness-decoupling metaphor.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35975712}, issn = {2050-084X}, mesh = {*Biological Evolution ; *Metaphor ; Phenotype ; Selection, Genetic ; }, abstract = {Evolutionary transitions in individuality (ETIs) involve the formation of Darwinian collectives from Darwinian particles. The transition from cells to multicellular life is a prime example. During an ETI, collectives become units of selection in their own right. However, the underlying processes are poorly understood. One observation used to identify the completion of an ETI is an increase in collective-level performance accompanied by a decrease in particle-level performance, for example measured by growth rate. This seemingly counterintuitive dynamic has been referred to as fitness decoupling and has been used to interpret both models and experimental data. Extending and unifying results from the literature, we show that fitness of particles and collectives can never decouple because calculations of fitness performed over appropriate and equivalent time intervals are necessarily the same provided the population reaches a stable collective size distribution. By way of solution, we draw attention to the value of mechanistic approaches that emphasise traits, and tradeoffs among traits, as opposed to fitness. This trait-based approach is sufficient to capture dynamics that underpin evolutionary transitions. In addition, drawing upon both experimental and theoretical studies, we show that while early stages of transitions might often involve tradeoffs among particle traits, later-and critical-stages are likely to involve the rupture of such tradeoffs. Thus, when observed in the context of ETIs, tradeoff-breaking events stand as a useful marker of these transitions.}, } @article {pmid35972622, year = {2022}, author = {Jacques, F and Baratchart, E and Pienta, KJ and Hammarlund, EU}, title = {Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {11}, pages = {160}, pmid = {35972622}, issn = {1559-131X}, support = {CA163124/CA/NCI NIH HHS/United States ; 949538/ERC_/European Research Council/International ; CA143055/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Differentiation/genetics ; Eukaryota/genetics ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.}, } @article {pmid35970862, year = {2022}, author = {Smith, TJ and Donoghue, PCJ}, title = {Evolution of fungal phenotypic disparity.}, journal = {Nature ecology & evolution}, volume = {6}, number = {10}, pages = {1489-1500}, pmid = {35970862}, issn = {2397-334X}, support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Fungi/genetics ; Phenotype ; Plants ; }, abstract = {Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.}, } @article {pmid35948712, year = {2022}, author = {Kim, H and Skinner, DJ and Glass, DS and Hamby, AE and Stuart, BAR and Dunkel, J and Riedel-Kruse, IH}, title = {4-bit adhesion logic enables universal multicellular interface patterning.}, journal = {Nature}, volume = {608}, number = {7922}, pages = {324-329}, pmid = {35948712}, issn = {1476-4687}, mesh = {*Algorithms ; *Artificial Cells/cytology ; Biofilms ; *Cell Adhesion ; Humans ; *Logic ; *Synthetic Biology/methods ; }, abstract = {Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].}, } @article {pmid35946347, year = {2022}, author = {Chen, MY and Teng, WK and Zhao, L and Han, BP and Song, LR and Shu, WS}, title = {Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria.}, journal = {Molecular biology and evolution}, volume = {39}, number = {9}, pages = {}, pmid = {35946347}, issn = {1537-1719}, mesh = {*Cyanobacteria/genetics ; Gene Transfer, Horizontal ; Nitrogen/metabolism ; *Nitrogen Fixation/genetics ; Photosynthesis/genetics ; Phylogeny ; }, abstract = {Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth's biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.}, } @article {pmid35938723, year = {2022}, author = {Sartor, F and Kovács, ÁT}, title = {Rhythmic Spatial Self-Organization of Bacterial Colonies.}, journal = {mBio}, volume = {13}, number = {4}, pages = {e0170322}, pmid = {35938723}, issn = {2150-7511}, mesh = {Bacteria ; *Circadian Clocks ; Circadian Rhythm/genetics ; Photoperiod ; }, abstract = {Bacteria display a remarkable capacity to organize themselves in space and time within biofilms. Traditionally, the spatial organization of biofilms has been dissected vertically; however, biofilms can exhibit complex, temporally structured, two-dimensional radial patterns while spreading on a surface. Kahl and colleagues report a ring pattern that indicates the alternating redox metabolism of P. aeruginosa biofilms under light/dark cycles. Does the presence of a rhythmic, daily phenotype imply a circadian rhythm? Here, we highlight several examples of rhythmic patterns reported in the literature for surface-colonizing multicellular assemblies and discuss the conceptual requirements for proving the presence of a prokaryotic circadian clock behind pattern formation.}, } @article {pmid35901418, year = {2022}, author = {Raguž, L and Peng, CC and Rutaganira, FUN and Krüger, T and Stanišić, A and Jautzus, T and Kries, H and Kniemeyer, O and Brakhage, AA and King, N and Beemelmanns, C}, title = {Total Synthesis and Functional Evaluation of IORs, Sulfonolipid-based Inhibitors of Cell Differentiation in Salpingoeca rosetta.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {41}, pages = {e202209105}, pmid = {35901418}, issn = {1521-3773}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Differentiation ; *Choanoflagellata ; Lipids ; Proteomics ; Sulfonic Acids ; Zinc ; }, abstract = {The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR-1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells, and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta.}, } @article {pmid35894230, year = {2022}, author = {Le Gloanec, C and Collet, L and Silveira, SR and Wang, B and Routier-Kierzkowska, AL and Kierzkowski, D}, title = {Cell type-specific dynamics underlie cellular growth variability in plants.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {14}, pages = {}, doi = {10.1242/dev.200783}, pmid = {35894230}, issn = {1477-9129}, mesh = {*Arabidopsis ; *Arabidopsis Proteins/genetics ; Cell Differentiation/genetics ; Cell Proliferation ; Plant Leaves ; Plant Stomata ; }, abstract = {Coordination of growth, patterning and differentiation is required for shaping organs in multicellular organisms. In plants, cell growth is controlled by positional information, yet the behavior of individual cells is often highly heterogeneous. The origin of this variability is still unclear. Using time-lapse imaging, we determined the source and relevance of cellular growth variability in developing organs of Arabidopsis thaliana. We show that growth is more heterogeneous in the leaf blade than in the midrib and petiole, correlating with higher local differences in growth rates between neighboring cells in the blade. This local growth variability coincides with developing stomata. Stomatal lineages follow a specific, time-dependent growth program that is different from that of their surroundings. Quantification of cellular dynamics in the leaves of a mutant lacking stomata, as well as analysis of floral organs, supports the idea that growth variability is mainly driven by stomata differentiation. Thus, the cell-autonomous behavior of specialized cells is the main source of local growth variability in otherwise homogeneously growing tissue. Those growth differences are buffered by the immediate neighbors of stomata and trichomes to achieve robust organ shapes.}, } @article {pmid35893123, year = {2022}, author = {Dijkwel, Y and Tremethick, DJ}, title = {The Role of the Histone Variant H2A.Z in Metazoan Development.}, journal = {Journal of developmental biology}, volume = {10}, number = {3}, pages = {}, pmid = {35893123}, issn = {2221-3759}, abstract = {During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.}, } @article {pmid35882195, year = {2022}, author = {Lyng, M and Kovács, ÁT}, title = {Microbial ecology: Metabolic heterogeneity and the division of labor in multicellular structures.}, journal = {Current biology : CB}, volume = {32}, number = {14}, pages = {R771-R774}, doi = {10.1016/j.cub.2022.06.008}, pmid = {35882195}, issn = {1879-0445}, abstract = {Many bacterial species are capable of differentiating to create phenotypic heterogeneity. Using the aggregate-forming marine bacterium Vibrio splendidus, a new study reveals how this organism differentiates to form spherical structures with a motile, carbon-storing core and a non-motile shell.}, } @article {pmid35879542, year = {2022}, author = {Ní Leathlobhair, M and Lenski, RE}, title = {Population genetics of clonally transmissible cancers.}, journal = {Nature ecology & evolution}, volume = {6}, number = {8}, pages = {1077-1089}, pmid = {35879542}, issn = {2397-334X}, mesh = {Animals ; Biological Evolution ; *Genetics, Population ; Genome ; *Neoplasms/genetics ; Population Dynamics ; }, abstract = {Populations of cancer cells are subject to the same core evolutionary processes as asexually reproducing, unicellular organisms. Transmissible cancers are particularly striking examples of these processes. These unusual cancers are clonal lineages that can spread through populations via physical transfer of living cancer cells from one host individual to another, and they have achieved long-term success in the colonization of at least eight different host species. Population genetic theory provides a useful framework for understanding the shift from a multicellular sexual animal into a unicellular asexual clone and its long-term effects on the genomes of these cancers. In this Review, we consider recent findings from transmissible cancer research with the goals of developing an evolutionarily informed perspective on transmissible cancers, examining possible implications for their long-term fate and identifying areas for future research on these exceptional lineages.}, } @article {pmid35862819, year = {2022}, author = {Nies, F and Springstein, BL and Hanke, DM and Dagan, T}, title = {Natural Competence in the Filamentous, Heterocystous Cyanobacterium Chlorogloeopsis fritschii PCC 6912.}, journal = {mSphere}, volume = {7}, number = {4}, pages = {e0099721}, pmid = {35862819}, issn = {2379-5042}, mesh = {*Cyanobacteria/genetics/metabolism ; Gene Transfer, Horizontal ; Photosynthesis ; }, abstract = {Lateral gene transfer plays an important role in the evolution of genetic diversity in prokaryotes. DNA transfer via natural transformation depends on the ability of recipient cells to actively transport DNA from the environment into the cytoplasm, termed natural competence, which relies on the presence of type IV pili and other competence proteins. Natural competence has been described in cyanobacteria for several organisms, including unicellular and filamentous species. However, natural competence in cyanobacteria that differentiate specialized cells for N2-fixation (heterocysts) and form branching or multiseriate cell filaments (termed subsection V) remains unknown. Here, we show that genes essential for natural competence are conserved in subsection V cyanobacteria. Furthermore, using the replicating plasmid pRL25C, we experimentally demonstrate natural competence in a subsection V organism: Chlorogloeopsis fritschii PCC 6912. Our results suggest that natural competence is a common trait in cyanobacteria forming complex cell filament morphologies. IMPORTANCE Cyanobacteria are crucial players in the global biogeochemical cycles, where they contribute to CO2- and N2-fixation. Their main ecological significance is the primary biomass production owing to oxygenic photosynthesis. Cyanobacteria are a diverse phylum, in which the most complex species differentiate specialized cell types and form true-branching or multiseriate cell filament structures (termed subsection V cyanobacteria). These bacteria are considered a peak in the evolution of prokaryotic multicellularity. Among others, species in that group inhabit fresh and marine water habitats, soil, and extreme habitats such as thermal springs. Here, we show that the core genes required for natural competence are frequent in subsection V cyanobacteria and demonstrate for the first time natural transformation in a member of subsection V. The prevalence of natural competence has implications for the role of DNA acquisition in the genome evolution of cyanobacteria. Furthermore, the presence of mechanisms for natural transformation opens up new possibilities for the genetic modification of subsection V cyanobacteria.}, } @article {pmid35862435, year = {2022}, author = {Howe, J and Rink, JC and Wang, B and Griffin, AS}, title = {Multicellularity in animals: The potential for within-organism conflict.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {32}, pages = {e2120457119}, pmid = {35862435}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Cell Lineage ; Clone Cells ; Developmental Biology ; *Insecta/growth & development ; Reproduction ; }, abstract = {Metazoans function as individual organisms but also as "colonies" of cells whose single-celled ancestors lived and reproduced independently. Insights from evolutionary biology about multicellular group formation help us understand the behavior of cells: why they cooperate, and why cooperation sometimes breaks down. Current explanations for multicellularity focus on two aspects of development which promote cooperation and limit conflict among cells: a single-cell bottleneck, which creates organisms composed of clones, and a separation of somatic and germ cell lineages, which reduces the selective advantage of cheating. However, many obligately multicellular organisms thrive with neither, creating the potential for within-organism conflict. Here, we argue that the prevalence of such organisms throughout the Metazoa requires us to refine our preconceptions of conflict-free multicellularity. Evolutionary theory must incorporate developmental mechanisms across a broad range of organisms-such as unusual reproductive strategies, totipotency, and cell competition-while developmental biology must incorporate evolutionary principles. To facilitate this cross-disciplinary approach, we provide a conceptual overview from evolutionary biology for developmental biologists, using analogous examples in the well-studied social insects.}, } @article {pmid35858311, year = {2022}, author = {Belcher, LJ and Madgwick, PG and Kuwana, S and Stewart, B and Thompson, CRL and Wolf, JB}, title = {Developmental constraints enforce altruism and avert the tragedy of the commons in a social microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {29}, pages = {e2111233119}, pmid = {35858311}, issn = {1091-6490}, mesh = {*Altruism ; Biological Evolution ; Cooperative Behavior ; *Dictyostelium ; Humans ; Motivation ; }, abstract = {Organisms often cooperate through the production of freely available public goods. This can greatly benefit the group but is vulnerable to the "tragedy of the commons" if individuals lack the motivation to make the necessary investment into public goods production. Relatedness to groupmates can motivate individual investment because group success ultimately benefits their genes' own self-interests. However, systems often lack mechanisms that can reliably ensure that relatedness is high enough to promote cooperation. Consequently, groups face a persistent threat from the tragedy unless they have a mechanism to enforce investment when relatedness fails to provide adequate motivation. To understand the real threat posed by the tragedy and whether groups can avert its impact, we determine how the social amoeba Dictyostelium discoideum responds as relatedness decreases to levels that should induce the tragedy. We find that, while investment in public goods declines as overall within-group relatedness declines, groups avert the expected catastrophic collapse of the commons by continuing to invest, even when relatedness should be too low to incentivize any contribution. We show that this is due to a developmental buffering system that generates enforcement because insufficient cooperation perturbs the balance of a negative feedback system controlling multicellular development. This developmental constraint enforces investment under the conditions expected to be most tragic, allowing groups to avert a collapse in cooperation. These results help explain how mechanisms that suppress selfishness and enforce cooperation can arise inadvertently as a by-product of constraints imposed by selection on different traits.}, } @article {pmid35853599, year = {2022}, author = {Arjoca, S and Robu, A and Neagu, M and Neagu, A}, title = {Mathematical and computational models in spheroid-based biofabrication.}, journal = {Acta biomaterialia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.actbio.2022.07.024}, pmid = {35853599}, issn = {1878-7568}, abstract = {Ubiquitous in embryonic development, tissue fusion is of interest to tissue engineers who use tissue spheroids or organoids as building blocks of three-dimensional (3D) multicellular constructs. This review presents mathematical models and computer simulations of the fusion of tissue spheroids. The motivation of this study stems from the need to predict the post-printing evolution of 3D bioprinted constructs. First, we provide a brief overview of differential adhesion, the main morphogenetic mechanism involved in post-printing structure formation. It will be shown that clusters of cohesive cells behave as an incompressible viscous fluid on the time scale of hours. The discussion turns then to mathematical models based on the continuum hydrodynamics of highly viscous liquids and on statistical mechanics. Next, we analyze the validity and practical use of computational models of multicellular self-assembly in live constructs created by tissue spheroid bioprinting. Finally, we discuss the perspectives of the field as machine learning starts to reshape experimental design, and modular robotic workstations tend to alleviate the burden of repetitive tasks in biofabrication. STATEMENT OF SIGNIFICANCE: Bioprinted constructs are living systems, which evolve via morphogenetic mechanisms known from developmental biology. This review presents mathematical and computational tools devised for modeling post-printing structure formation. They help achieving a desirable outcome without expensive optimization experiments. While previous reviews mainly focused on assumptions, technical details, strengths, and limitations of computational models of multicellular self-assembly, this article discusses their validity and practical use in biofabrication. It also presents an overview of mathematical models that proved to be useful in the evaluation of experimental data on tissue spheroid fusion, and in the calibration of computational models. Finally, the perspectives of the field are discussed in the advent of robotic biofabrication platforms and bioprinting process optimization by machine learning.}, } @article {pmid35852417, year = {2022}, author = {Chakravarty, AK and McGrail, DJ and Lozanoski, TM and Dunn, BS and Shih, DJH and Cirillo, KM and Cetinkaya, SH and Zheng, WJ and Mills, GB and Yi, SS and Jarosz, DF and Sahni, N}, title = {Biomolecular Condensation: A New Phase in Cancer Research.}, journal = {Cancer discovery}, volume = {12}, number = {9}, pages = {2031-2043}, pmid = {35852417}, issn = {2159-8290}, support = {K99 GM128180/GM/NIGMS NIH HHS/United States ; R35 GM137836/GM/NIGMS NIH HHS/United States ; K99 CA240689/CA/NCI NIH HHS/United States ; DRG2221-15/HHMI/Howard Hughes Medical Institute/United States ; U01 CA217842/CA/NCI NIH HHS/United States ; R35 GM133658/GM/NIGMS NIH HHS/United States ; DP2 GM119140/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/metabolism ; *Organelles/metabolism ; Research ; }, abstract = {UNLABELLED: Multicellularity was a watershed development in evolution. However, it also meant that individual cells could escape regulatory mechanisms that restrict proliferation at a severe cost to the organism: cancer. From the standpoint of cellular organization, evolutionary complexity scales to organize different molecules within the intracellular milieu. The recent realization that many biomolecules can "phase-separate" into membraneless organelles, reorganizing cellular biochemistry in space and time, has led to an explosion of research activity in this area. In this review, we explore mechanistic connections between phase separation and cancer-associated processes and emerging examples of how these become deranged in malignancy.

SIGNIFICANCE: One of the fundamental functions of phase separation is to rapidly and dynamically respond to environmental perturbations. Importantly, these changes often lead to alterations in cancer-relevant pathways and processes. This review covers recent advances in the field, including emerging principles and mechanisms of phase separation in cancer.}, } @article {pmid35849348, year = {2022}, author = {Wu, TY and Hoh, KL and Boonyaves, K and Krishnamoorthi, S and Urano, D}, title = {Diversification of heat shock transcription factors expanded thermal stress responses during early plant evolution.}, journal = {The Plant cell}, volume = {34}, number = {10}, pages = {3557-3576}, pmid = {35849348}, issn = {1532-298X}, mesh = {*Arabidopsis/metabolism ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks ; Heat Shock Transcription Factors/metabolism ; Heat-Shock Response/genetics ; *Marchantia/genetics/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {The copy numbers of many plant transcription factor (TF) genes substantially increased during terrestrialization. This allowed TFs to acquire new specificities and thus create gene regulatory networks (GRNs) with new biological functions to help plants adapt to terrestrial environments. Through characterizing heat shock factor (HSF) genes MpHSFA1 and MpHSFB1 in the liverwort Marchantia polymorpha, we explored how heat-responsive GRNs widened their functions in M. polymorpha and Arabidopsis thaliana. An interspecies comparison of heat-induced transcriptomes and the evolutionary rates of HSFs demonstrated the emergence and subsequent rapid evolution of HSFB prior to terrestrialization. Transcriptome and metabolome analyses of M. polymorpha HSF-null mutants revealed that MpHSFA1 controls canonical heat responses such as thermotolerance and metabolic changes. MpHSFB1 also plays essential roles in heat responses, as well as regulating developmental processes including meristem branching and antheridiophore formation. Analysis of cis-regulatory elements revealed development- and stress-related TFs that function directly or indirectly downstream of HSFB. Male gametophytes of M. polymorpha showed higher levels of thermotolerance than female gametophytes, which could be explained by different expression levels of MpHSFA1U and MpHSFA1V on sex chromosome. We propose that the diversification of HSFs is linked to the expansion of HS responses, which enabled coordinated multicellular reactions in land plants.}, } @article {pmid35841659, year = {2022}, author = {Gabaldón, T and Völcker, E and Torruella, G}, title = {On the Biology, Diversity and Evolution of Nucleariid Amoebae (Amorphea, Obazoa, Opisthokonta[1].}, journal = {Protist}, volume = {173}, number = {4}, pages = {125895}, doi = {10.1016/j.protis.2022.125895}, pmid = {35841659}, issn = {1618-0941}, mesh = {*Amoeba ; Animals ; Biology ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Nucleariids are a small group of free-living heterotrophic amoebae. Although these organisms present a variety of cell sizes and cell coverings, they are mostly spherical cells with radiating filopodia, sometimes with several nuclei. Nuclearia, the genus that gives the name to the group, contains species that are opportunistic consumers of detritus, bacteria, and algae. The beautiful Pompholyxophrys is covered with endogenous siliceous pearls. Lithocolla covers itself with sand particles, or otherwise diatom frustules. The tiny Parvularia exclusively feeds on bacteria, and Fonticula is adapted to solid substrates and presents aggregative multicellular stages. Nucleariids belong to the Opisthokonta, which comprise animals, fungi, and their protist relatives, and form the earliest branch in the holomycotan clade (fungi and closest relatives). Hence, they are key for understanding the origin and diversification of Opisthokonta, an eukaryotic supergroup that contains organisms with different feeding modes, life-styles, and cell organizations. In this review, the reader will find an introduction to nucleariids, from their discovery in the 19th century until the most recent studies. It summarizes available information on their morphology, life history, cell organisation, ecology, diversity, systematics and evolution.}, } @article {pmid35838349, year = {2022}, author = {Meléndez García, R and Haccard, O and Chesneau, A and Narassimprakash, H and Roger, J and Perron, M and Marheineke, K and Bronchain, O}, title = {A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35838349}, issn = {2050-084X}, mesh = {Animals ; DNA Replication ; DNA Replication Timing ; *Replication Origin ; S Phase/genetics ; *Telomere-Binding Proteins/genetics ; Xenopus laevis/genetics/metabolism ; }, abstract = {In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signalling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. Furthermore, we show that either Yap or Rif1 depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that either Yap or Rif1 depletion triggers an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as brakes to control the DNA replication program in early embryos and post-embryonic stem cells.}, } @article {pmid35835876, year = {2022}, author = {Marcon, L}, title = {Multicellular self-organization.}, journal = {Nature reviews. Molecular cell biology}, volume = {23}, number = {12}, pages = {777}, pmid = {35835876}, issn = {1471-0080}, mesh = {*Biological Evolution ; }, } @article {pmid35821097, year = {2022}, author = {Wright, CJ and Smith, CWJ and Jiggins, CD}, title = {Alternative splicing as a source of phenotypic diversity.}, journal = {Nature reviews. Genetics}, volume = {23}, number = {11}, pages = {697-710}, pmid = {35821097}, issn = {1471-0064}, support = {206194/WT_/Wellcome Trust/United Kingdom ; 218328/WT_/Wellcome Trust/United Kingdom ; BB/R007500/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 209368/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Alternative Splicing ; Biological Evolution ; Phenotype ; Proteins/genetics ; *RNA Splicing ; }, abstract = {A major goal of evolutionary genetics is to understand the genetic processes that give rise to phenotypic diversity in multicellular organisms. Alternative splicing generates multiple transcripts from a single gene, enriching the diversity of proteins and phenotypic traits. It is well established that alternative splicing contributes to key innovations over long evolutionary timescales, such as brain development in bilaterians. However, recent developments in long-read sequencing and the generation of high-quality genome assemblies for diverse organisms has facilitated comparisons of splicing profiles between closely related species, providing insights into how alternative splicing evolves over shorter timescales. Although most splicing variants are probably non-functional, alternative splicing is nonetheless emerging as a dynamic, evolutionarily labile process that can facilitate adaptation and contribute to species divergence.}, } @article {pmid35804300, year = {2022}, author = {Angaroni, F and Guidi, A and Ascolani, G and d'Onofrio, A and Antoniotti, M and Graudenzi, A}, title = {J-SPACE: a Julia package for the simulation of spatial models of cancer evolution and of sequencing experiments.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {269}, pmid = {35804300}, issn = {1471-2105}, support = {22790/CRUK_/Cancer Research UK/United Kingdom ; 22790/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Computer Simulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Neoplasms/genetics/pathology ; Phylogeny ; *Software ; }, abstract = {BACKGROUND: The combined effects of biological variability and measurement-related errors on cancer sequencing data remain largely unexplored. However, the spatio-temporal simulation of multi-cellular systems provides a powerful instrument to address this issue. In particular, efficient algorithmic frameworks are needed to overcome the harsh trade-off between scalability and expressivity, so to allow one to simulate both realistic cancer evolution scenarios and the related sequencing experiments, which can then be used to benchmark downstream bioinformatics methods.

RESULT: We introduce a Julia package for SPAtial Cancer Evolution (J-SPACE), which allows one to model and simulate a broad set of experimental scenarios, phenomenological rules and sequencing settings.Specifically, J-SPACE simulates the spatial dynamics of cells as a continuous-time multi-type birth-death stochastic process on a arbitrary graph, employing different rules of interaction and an optimised Gillespie algorithm. The evolutionary dynamics of genomic alterations (single-nucleotide variants and indels) is simulated either under the Infinite Sites Assumption or several different substitution models, including one based on mutational signatures. After mimicking the spatial sampling of tumour cells, J-SPACE returns the related phylogenetic model, and allows one to generate synthetic reads from several Next-Generation Sequencing (NGS) platforms, via the ART read simulator. The results are finally returned in standard FASTA, FASTQ, SAM, ALN and Newick file formats.

CONCLUSION: J-SPACE is designed to efficiently simulate the heterogeneous behaviour of a large number of cancer cells and produces a rich set of outputs. Our framework is useful to investigate the emergent spatial dynamics of cancer subpopulations, as well as to assess the impact of incomplete sampling and of experiment-specific errors. Importantly, the output of J-SPACE is designed to allow the performance assessment of downstream bioinformatics pipelines processing NGS data. J-SPACE is freely available at: https://github.com/BIMIB-DISCo/J-Space.jl .}, } @article {pmid35792830, year = {2022}, author = {Fukai, E and Yoshikawa, M and Shah, N and Sandal, N and Miyao, A and Ono, S and Hirakawa, H and Akyol, TY and Umehara, Y and Nonomura, KI and Stougaard, J and Hirochika, H and Hayashi, M and Sato, S and Andersen, SU and Okazaki, K}, title = {Widespread and transgenerational retrotransposon activation in inter- and intraspecies recombinant inbred populations of Lotus japonicus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {5}, pages = {1397-1410}, doi = {10.1111/tpj.15896}, pmid = {35792830}, issn = {1365-313X}, mesh = {Evolution, Molecular ; Genome, Plant/genetics ; Hybridization, Genetic ; *Lotus/genetics ; Plants/genetics ; *Retroelements/genetics ; Terminal Repeat Sequences/genetics ; }, abstract = {Transposable elements (TEs) constitute a large proportion of genomes of multicellular eukaryotes, including flowering plants. TEs are normally maintained in a silenced state and their transpositions rarely occur. Hybridization between distant species has been regarded as a 'shock' that stimulates genome reorganization, including TE mobilization. However, whether crosses between genetically close parents that result in viable and fertile offspring can induce TE transpositions has remained unclear. Here, we investigated the activation of long terminal repeat (LTR) retrotransposons in three Lotus japonicus recombinant inbred line (RIL) populations. We found that at least six LTR retrotransposon families were activated and transposed in 78% of the RILs investigated. LORE1a, one of the transposed LTR retrotransposons, showed transgenerational epigenetic activation, indicating the long-term effects of epigenetic instability induced by hybridization. Our study highlights TE activation as an unexpectedly common event in plant reproduction.}, } @article {pmid35790840, year = {2022}, author = {Beljan, S and Dominko, K and Talajić, A and Hloušek-Kasun, A and Škrobot Vidaček, N and Herak Bosnar, M and Vlahoviček, K and Ćetković, H}, title = {Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11379}, pmid = {35790840}, issn = {2045-2322}, mesh = {Animals ; GTP-Binding Proteins ; Genomics ; Humans ; *Neoplasms/genetics ; *Oncogenes ; RNA ; Transcription Factors ; }, abstract = {Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.}, } @article {pmid35778439, year = {2022}, author = {Belpaire, TER and Pešek, J and Lories, B and Verstrepen, KJ and Steenackers, HP and Ramon, H and Smeets, B}, title = {Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast.}, journal = {The ISME journal}, volume = {16}, number = {10}, pages = {2305-2312}, pmid = {35778439}, issn = {1751-7370}, mesh = {Biological Evolution ; Flocculation ; Mannose-Binding Lectins/chemistry/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and kin recognition, FLO1 has been termed a "green beard gene". Because of the heterophilic nature of the Flo1p bond however, we hypothesize that kin recognition is permissive and depends on the relative stability of the FLO1[+]/flo1[-] versus FLO1[+]/FLO1[+] detachment force F. We combine single-cell measurements of adhesion, individual cell-based simulations of cluster formation, and in vitro flocculation to study the impact of relative bond stability on the evolutionary stability of cooperation. We identify a trade-off between both aspects of the green beard mechanism, with reduced relative bond stability leading to increased kin recognition at the expense of cooperative benefits. We show that the fitness of FLO1 cooperators decreases as their frequency in the population increases, arising from the observed permissive character (F+- = 0.5 F++) of the Flo1p bond. Considering the costs associated with FLO1 expression, this asymmetric selection often results in a stable coexistence between cooperators and defectors.}, } @article {pmid35774229, year = {2022}, author = {Kaluthantrige Don, F and Kalebic, N}, title = {Forebrain Organoids to Model the Cell Biology of Basal Radial Glia in Neurodevelopmental Disorders and Brain Evolution.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {917166}, pmid = {35774229}, issn = {2296-634X}, abstract = {The acquisition of higher intellectual abilities that distinguish humans from their closest relatives correlates greatly with the expansion of the cerebral cortex. This expansion is a consequence of an increase in neuronal cell production driven by the higher proliferative capacity of neural progenitor cells, in particular basal radial glia (bRG). Furthermore, when the proliferation of neural progenitor cells is impaired and the final neuronal output is altered, severe neurodevelopmental disorders can arise. To effectively study the cell biology of human bRG, genetically accessible human experimental models are needed. With the pioneering success to isolate and culture pluripotent stem cells in vitro, we can now routinely investigate the developing human cerebral cortex in a dish using three-dimensional multicellular structures called organoids. Here, we will review the molecular and cell biological features of bRG that have recently been elucidated using brain organoids. We will further focus on the application of this simple model system to study in a mechanistically actionable way the molecular and cellular events in bRG that can lead to the onset of various neurodevelopmental diseases.}, } @article {pmid35756025, year = {2022}, author = {Chen, S and Yu, M and Zhang, W and He, K and Pan, H and Cui, K and Zhao, Y and Zhang, XH and Xiao, T and Zhang, W and Wu, LF}, title = {Metagenomic and Microscopic Analysis of Magnetotactic Bacteria in Tangyin Hydrothermal Field of Okinawa Trough.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {887136}, pmid = {35756025}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) have been found in a wide variety of marine habitats, ranging from intertidal sediments to deep-sea seamounts. Deep-sea hydrothermal fields are rich in metal sulfides, which are suitable areas for the growth of MTB. However, MTB in hydrothermal fields have never been reported. Here, the presence of MTB in sediments from the Tangyin hydrothermal field was analyzed by 16S rRNA gene amplicon analysis, metagenomics, and transmission electron microscopy. Sequencing 16S rRNA gene yielded a total of 709 MTB sequences belonging to 20 OTUs, affiliated with Desulfobacterota, Alphaproteobacteria, and Nitrospirae. Three shapes of magnetofossil were identified by transmission electron microscopy: elongated-prismatic, bullet-shaped, and cuboctahedron. All of these structures were composed of Fe3O4. A total of 121 sequences were found to be homologous to the published MTB magnetosome-function-related genes, and relevant domains were identified. Further analysis revealed that diverse MTB are present in the Tangyin hydrothermal field, and that multicellular magnetotactic prokaryote (MMPs) might be the dominant MTB.}, } @article {pmid35754813, year = {2022}, author = {Wang, H and Umer, MJ and Liu, F and Cai, X and Zheng, J and Xu, Y and Hou, Y and Zhou, Z}, title = {Genome-Wide Identification and Characterization of CPR5 Genes in Gossypium Reveals Their Potential Role in Trichome Development.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {921096}, pmid = {35754813}, issn = {1664-8021}, abstract = {Trichomes protect plants against insects, microbes, herbivores, and abiotic damages and assist seed dispersal. The function of CPR5 genes have been found to be involved in the trichome development but the research on the underlying genetic and molecular mechanisms are extremely limited. Herein, genome wide identification and characterization of CPR5 genes was performed. In total, 26 CPR5 family members were identified in Gossypium species. Phylogenetic analysis, structural characteristics, and synteny analysis of CPR5s showed the conserved evolution relationships of CPR5. The promoter analysis of CPR5 genes revealed hormone, stress, and development-related cis-elements. Gene ontology (GO) enrichment analysis showed that the CPR5 genes were largely related to biological regulation, developmental process, multicellular organismal process. Protein-protein interaction analysis predicted several trichome development related proteins (SIM, LGO, and GRL) directly interacting with CPR5 genes. Further, nine putative Gossypium-miRNAs were also identified, targeting Gossypium CPR5 genes. RNA-Seq data of G. arboreum (with trichomes) and G. herbaceum (with no trichomes) was used to perform the co-expression network analysis. GheCPR5.1 was identified as a hub gene in a co-expression network analysis. RT-qPCR of GheCPR5.1 gene in different tissues suggests that this gene has higher expressions in the petiole and might be a key candidate involved in the trichome development. Virus induced gene silencing of GheCPR5.1 (Ghe02G17590) confirms its role in trichome development and elongation. Current results provide proofs of the possible role of CPR5 genes and provide preliminary information for further studies of GheCPR5.1 functions in trichome development.}, } @article {pmid35728616, year = {2022}, author = {Cameron-Pack, ME and König, SG and Reyes-Guevara, A and Reyes-Prieto, A and Nedelcu, AM}, title = {A personal cost of cheating can stabilize reproductive altruism during the early evolution of clonal multicellularity.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220059}, pmid = {35728616}, issn = {1744-957X}, mesh = {*Altruism ; Biological Evolution ; Reproduction ; *Volvox/genetics ; }, abstract = {Understanding how cooperation evolved and is maintained remains an important and often controversial topic because cheaters that reap the benefits of cooperation without paying the costs can threaten the evolutionary stability of cooperative traits. Cooperation-and especially reproductive altruism-is particularly relevant to the evolution of multicellularity, as somatic cells give up their reproductive potential in order to contribute to the fitness of the newly emerged multicellular individual. Here, we investigated cheating in a simple multicellular species-the green alga Volvox carteri, in the context of the mechanisms that can stabilize reproductive altruism during the early evolution of clonal multicellularity. We found that the benefits cheater mutants can gain in terms of their own reproduction are pre-empted by a cost in survival due to increased sensitivity to stress. This personal cost of cheating reflects the antagonistic pleiotropic effects that the gene coding for reproductive altruism-regA-has at the cell level. Specifically, the expression of regA in somatic cells results in the suppression of their reproduction potential but also confers them with increased resistance to stress. Since regA evolved from a life-history trade-off gene, we suggest that co-opting trade-off genes into cooperative traits can provide a built-in safety system against cheaters in other clonal multicellular lineages.}, } @article {pmid35726057, year = {2022}, author = {Kaufmann, M and Schaupp, AL and Sun, R and Coscia, F and Dendrou, CA and Cortes, A and Kaur, G and Evans, HG and Mollbrink, A and Navarro, JF and Sonner, JK and Mayer, C and DeLuca, GC and Lundeberg, J and Matthews, PM and Attfield, KE and Friese, MA and Mann, M and Fugger, L}, title = {Identification of early neurodegenerative pathways in progressive multiple sclerosis.}, journal = {Nature neuroscience}, volume = {25}, number = {7}, pages = {944-955}, pmid = {35726057}, issn = {1546-1726}, support = {MC_UU_00008/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/3/MRC_/Medical Research Council/United Kingdom ; 100308/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*Central Nervous System Diseases/complications ; Disease Progression ; Humans ; *Multiple Sclerosis/pathology ; Neurons/metabolism ; Proteomics ; }, abstract = {Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand-receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.}, } @article {pmid35725583, year = {2022}, author = {Mori, G and Delfino, D and Pibiri, P and Rivetti, C and Percudani, R}, title = {Origin and significance of the human DNase repertoire.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10364}, pmid = {35725583}, issn = {2045-2322}, mesh = {Animals ; DNA/genetics ; Deoxyribonuclease I/genetics ; *Deoxyribonucleases/genetics ; *Evolution, Molecular ; Fishes/genetics ; Gene Duplication ; Humans ; Phylogeny ; Synteny ; Vertebrates/genetics ; }, abstract = {The human genome contains four DNase1 and two DNase2 genes. The origin and functional specialization of this repertoire are not fully understood. Here we use genomics and transcriptomics data to infer the evolutionary history of DNases and investigate their biological significance. Both DNase1 and DNase2 families have expanded in vertebrates since ~ 650 million years ago before the divergence of jawless and jawed vertebrates. DNase1, DNase1L1, and DNase1L3 co-existed in jawless fish, whereas DNase1L2 originated in amniotes by tandem duplication of DNase1. Among the non-human DNases, DNase1L4 and newly identified DNase1L5 derived from early duplications that were lost in terrestrial vertebrates. The ancestral gene of the DNase2 family, DNase2b, has been conserved in synteny with the Uox gene across 700 million years of animal evolution,while DNase2 originated in jawless fish. DNase1L1 acquired a GPI-anchor for plasma membrane attachment in bony fishes, and DNase1L3 acquired a C-terminal basic peptide for the degradation of microparticle DNA in jawed vertebrates. The appearance of DNase1L2, with a distinct low pH optimum and skin localization, is among the amniote adaptations to life on land. The expansion of the DNase repertoire in vertebrates meets the diversified demand for DNA debris removal in complex multicellular organisms.}, } @article {pmid35713948, year = {2022}, author = {Passer, AR and Clancey, SA and Shea, T and David-Palma, M and Averette, AF and Boekhout, T and Porcel, BM and Nowrousian, M and Cuomo, CA and Sun, S and Heitman, J and Coelho, MA}, title = {Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35713948}, issn = {2050-084X}, support = {R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cryptococcus neoformans/genetics ; *Genes, Mating Type, Fungal/genetics ; Humans ; Reproduction ; Saccharomyces cerevisiae/genetics ; }, abstract = {eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different 'mating types' contributing to produce a new individual. However, individuals of some species exhibit 'homothallism' or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population. Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease. With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism in Cryptococcus depauperatus, a close relative of C. neoformans, a species that causes fungal infections in humans. A combination of genetic sequencing techniques and experiments were applied to analyse, compare, and manipulate C. depauperatus' genome to see how this species evolved self-fertility. Passer, Clancey et al. showed that C. depauperatus evolved the ability to reproduce sexually by itself via a unique evolutionary pathway. The result is a form of homothallism never reported in fungi before. C. depauperatus lost some of the genes that control mating in other species of fungi, and acquired genes from the opposing mating types of a heterothallic ancestor to become self-fertile. Passer, Clancey et al. also found that, unlike other Cryptococcus species that switch between asexual and sexual reproduction, C. depauperatus grows only as long, branching filaments called hyphae, a sexual form. The species reproduces sexually with itself throughout its life cycle and is unable to produce a yeast (asexual) form, in contrast to other closely related species. This work offers new insights into how different modes of sexual reproduction have evolved in fungi. It also provides another interesting case of how genome plasticity and evolutionary pressures can produce similar outcomes, homothallism, via different evolutionary paths. Lastly, assembling the complete genome of C. depauperatus will foster comparative studies between pathogenic and non-pathogenic Cryptococcus species.}, } @article {pmid35685010, year = {2022}, author = {Barthlott, W and Büdel, B and Mail, M and Neumann, KM and Bartels, D and Fischer, E}, title = {Superhydrophobic Terrestrial Cyanobacteria and Land Plant Transition.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {880439}, pmid = {35685010}, issn = {1664-462X}, abstract = {Plants and other organisms have evolved structures and mechanisms for colonizing land since the Early Ordovician. In this context, their surfaces, the crucial physical interface with the environment, are mainly considered barriers against water loss. It is suggested that extreme water repellency (superhydrophobicity) was an additional key innovation for the transition of algae from water to land some 400 mya. Superhydrophobicity enhances gas exchange on land and excludes aquatic competitors in water films. In a different context, in material science and surface technology, superhydrophobicity has also become one of the most important bioinspired innovations enabling the avoidance of water films and contamination. Here, we present data for an extremely water-repellent cyanobacterial biofilm of the desiccation tolerant Hassallia byssoidea providing evidence for a much earlier prokaryotic Precambrian (ca. 1-2 bya) origin of superhydrophobicity and chemical heterogeneities associated with land transition. The multicellular cyanobacterium is functionally differentiated in a submerged basal hydrophilic absorbing portion like a "rhizoid" and an upright emersed superhydrophobic "phyllocauloid" filament for assimilation, nitrogen fixation, and splash dispersed diaspores. Additional data are provided for superhydrophobic surfaces in terrestrial green algae and in virtually all ancestral land plants (Bryophytes, ferns and allies, Amborella, Nelumbo), slime molds, and fungi. Rethinking of superhydrophobicity as an essential first step for life in terrestrial environments is suggested.}, } @article {pmid35681485, year = {2022}, author = {Minelli, A and Valero-Gracia, A}, title = {Spatially and Temporally Distributed Complexity-A Refreshed Framework for the Study of GRN Evolution.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, pmid = {35681485}, issn = {2073-4409}, mesh = {Animals ; *Gene Regulatory Networks ; Genotype ; Phenotype ; }, abstract = {Irrespective of the heuristic value of interpretations of developmental processes in terms of gene regulatory networks (GRNs), larger-angle views often suffer from: (i) an inadequate understanding of the relationship between genotype and phenotype; (ii) a predominantly zoocentric vision; and (iii) overconfidence in a putatively hierarchical organization of animal body plans. Here, we constructively criticize these assumptions. First, developmental biology is pervaded by adultocentrism, but development is not necessarily egg to adult. Second, during development, many unicells undergo transcriptomic profile transitions that are comparable to those recorded in pluricellular organisms; thus, their study should not be neglected from the GRN perspective. Third, the putatively hierarchical nature of the animal body is mirrored in the GRN logic, but in relating genotype to phenotype, independent assessments of the dynamics of the regulatory machinery and the animal's architecture are required, better served by a combinatorial than by a hierarchical approach. The trade-offs between spatial and temporal aspects of regulation, as well as their evolutionary consequences, are also discussed. Multicellularity may derive from a unicell's sequential phenotypes turned into different but coexisting, spatially arranged cell types. In turn, polyphenism may have been a crucial mechanism involved in the origin of complex life cycles.}, } @article {pmid35678467, year = {2022}, author = {Northey, JJ and Weaver, VM}, title = {Mechanosensitive Steroid Hormone Signaling and Cell Fate.}, journal = {Endocrinology}, volume = {163}, number = {8}, pages = {}, pmid = {35678467}, issn = {1945-7170}, support = {R35 CA242447/CA/NCI NIH HHS/United States ; R01 CA192914/CA/NCI NIH HHS/United States ; R01 CA222508/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation ; Hormones/physiology ; Humans ; *Neoplasms/pathology ; *Receptors, Steroid ; Signal Transduction ; Steroids ; }, abstract = {Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.}, } @article {pmid35673523, year = {2022}, author = {Day, TC and Márquez-Zacarías, P and Bravo, P and Pokhrel, AR and MacGillivray, KA and Ratcliff, WC and Yunker, PJ}, title = {Varied solutions to multicellularity: The biophysical and evolutionary consequences of diverse intercellular bonds.}, journal = {Biophysics reviews}, volume = {3}, number = {2}, pages = {021305}, pmid = {35673523}, issn = {2688-4089}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, abstract = {The diversity of multicellular organisms is, in large part, due to the fact that multicellularity has independently evolved many times. Nonetheless, multicellular organisms all share a universal biophysical trait: cells are attached to each other. All mechanisms of cellular attachment belong to one of two broad classes; intercellular bonds are either reformable or they are not. Both classes of multicellular assembly are common in nature, having independently evolved dozens of times. In this review, we detail these varied mechanisms as they exist in multicellular organisms. We also discuss the evolutionary implications of different intercellular attachment mechanisms on nascent multicellular organisms. The type of intercellular bond present during early steps in the transition to multicellularity constrains future evolutionary and biophysical dynamics for the lineage, affecting the origin of multicellular life cycles, cell-cell communication, cellular differentiation, and multicellular morphogenesis. The types of intercellular bonds used by multicellular organisms may thus result in some of the most impactful historical constraints on the evolution of multicellularity.}, } @article {pmid35663204, year = {2022}, author = {Nawabi, AK and Jinfang, S and Abbasi, R and Iqbal, MS and Heyat, MBB and Akhtar, F and Wu, K and Twumasi, BA}, title = {Segmentation of Drug-Treated Cell Image and Mitochondrial-Oxidative Stress Using Deep Convolutional Neural Network.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {5641727}, pmid = {35663204}, issn = {1942-0994}, mesh = {Algorithms ; *Image Processing, Computer-Assisted/methods ; *Neural Networks, Computer ; Oxidative Stress ; }, abstract = {Most multicellular organisms require apoptosis, or programmed cell death, to function properly and survive. On the other hand, morphological and biochemical characteristics of apoptosis have remained remarkably consistent throughout evolution. Apoptosis is thought to have at least three functionally distinct phases: induction, effector, and execution. Recent studies have revealed that reactive oxygen species (ROS) and the oxidative stress could play an essential role in apoptosis. Advanced microscopic imaging techniques allow biologists to acquire an extensive amount of cell images within a matter of minutes which rule out the manual analysis of image data acquisition. The segmentation of cell images is often considered the cornerstone and central problem for image analysis. Currently, the issue of segmentation of mitochondrial cell images via deep learning receives increasing attention. The manual labeling of cell images is time-consuming and challenging to train a pro. As a courtesy method, mitochondrial cell imaging (MCI) is proposed to identify the normal, drug-treated, and diseased cells. Furthermore, cell movement (fission and fusion) is measured to evaluate disease risk. The newly proposed drug-treated, normal, and diseased image segmentation (DNDIS) algorithm can quickly segment mitochondrial cell images without supervision and further segment the highly drug-treated cells in the picture, i.e., normal, diseased, and drug-treated cells. The proposed method is based on the ResNet-50 deep learning algorithm. The dataset consists of 414 images mainly categorised into different sets (drug, diseased, and normal) used microscopically. The proposed automated segmentation method has outperformed and secured high precision (90%, 92%, and 94%); moreover, it also achieves proper training. This study will benefit medicines and diseased cell measurements in medical tests and clinical practices.}, } @article {pmid35662747, year = {2022}, author = {Abumsimir, B and Al-Qaisi, TS and Kasmi, Y}, title = {Rereading the genetic origin of cancer: the puzzle of all eras.}, journal = {Future science OA}, volume = {8}, number = {5}, pages = {FSO799}, pmid = {35662747}, issn = {2056-5623}, } @article {pmid35660859, year = {2022}, author = {Bao, L and Ren, J and Nguyen, M and Slusarczyk, AS and Thole, JM and Martinez, SP and Huang, J and Fujita, T and Running, MP}, title = {The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {12}, pages = {}, doi = {10.1242/dev.200279}, pmid = {35660859}, issn = {1477-9129}, mesh = {*Bryopsida/metabolism ; Cell Wall/metabolism ; *GTP Phosphohydrolases/metabolism ; Prenylation ; Signal Transduction ; }, abstract = {A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.}, } @article {pmid35659869, year = {2022}, author = {Phillips, JE and Santos, M and Konchwala, M and Xing, C and Pan, D}, title = {Genome editing in the unicellular holozoan Capsaspora owczarzaki suggests a premetazoan role for the Hippo pathway in multicellular morphogenesis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35659869}, issn = {2050-084X}, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Editing ; Hippo Signaling Pathway ; Morphogenesis ; }, abstract = {Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch, and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components of these pathways in the closest unicellular relatives of animals. These findings raise questions about the ancestral functions of these developmental pathways and their potential role in the emergence of animal multicellularity. Here, we provide the first functional characterization of any of these developmental pathways in unicellular organisms by developing techniques for genetic manipulation in Capsaspora owczarzaki, a close unicellular relative of animals that displays aggregative multicellularity. We then use these tools to characterize the Capsaspora ortholog of the Hippo signaling nuclear effector YAP/TAZ/Yorkie (coYki), a key regulator of tissue size in animals. In contrast to what might be expected based on studies in animals, we show that coYki is dispensable for cell proliferation but regulates cytoskeletal dynamics and the three-dimensional (3D) shape of multicellular structures. We further demonstrate that the cytoskeletal abnormalities of individual coYki mutant cells underlie the abnormal 3D shape of coYki mutant aggregates. Taken together, these findings implicate an ancestral role for the Hippo pathway in cytoskeletal dynamics and multicellular morphogenesis predating the origin of animal multicellularity, which was co-opted during evolution to regulate cell proliferation.}, } @article {pmid35658016, year = {2022}, author = {Bentley, MA and Yates, CA and Hein, J and Preston, GM and Foster, KR}, title = {Pleiotropic constraints promote the evolution of cooperation in cellular groups.}, journal = {PLoS biology}, volume = {20}, number = {6}, pages = {e3001626}, pmid = {35658016}, issn = {1545-7885}, mesh = {*Biological Evolution ; Genotype ; *Microbiota ; Mutation ; Phenotype ; }, abstract = {The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.}, } @article {pmid35651757, year = {2022}, author = {Díaz, E and Febres, A and Giammarresi, M and Silva, A and Vanegas, O and Gomes, C and Ponte-Sucre, A}, title = {G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812848}, pmid = {35651757}, issn = {2235-2988}, mesh = {*Calcitonin Gene-Related Peptide/pharmacology ; Cell Communication ; Humans ; *Leishmania/metabolism ; Receptor Activity-Modifying Proteins/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Substance P/pharmacology ; }, abstract = {Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism's survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10[-6] M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.}, } @article {pmid35650214, year = {2022}, author = {Goswami, P and He, K and Li, J and Pan, Y and Roberts, AP and Lin, W}, title = {Magnetotactic bacteria and magnetofossils: ecology, evolution and environmental implications.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {43}, pmid = {35650214}, issn = {2055-5008}, mesh = {Bacteria/genetics ; *Ecosystem ; *Fresh Water ; Prospective Studies ; }, abstract = {Magnetotactic bacteria (MTB) are a group of phylogenetically diverse and morphologically varied microorganisms with a magnetoresponsive capability called magnetotaxis or microbial magnetoreception. MTB are a distinctive constituent of the microbiome of aquatic ecosystems because they use Earth's magnetic field to align themselves in a north or south facing direction and efficiently navigate to their favored microenvironments. They have been identified worldwide from diverse aquatic and waterlogged microbiomes, including freshwater, saline, brackish and marine ecosystems, and some extreme environments. MTB play important roles in the biogeochemical cycling of iron, sulphur, phosphorus, carbon and nitrogen in nature and have been recognized from in vitro cultures to sequester heavy metals like selenium, cadmium, and tellurium, which makes them prospective candidate organisms for aquatic pollution bioremediation. The role of MTB in environmental systems is not limited to their lifespan; after death, fossil magnetosomal magnetic nanoparticles (known as magnetofossils) are a promising proxy for recording paleoenvironmental change and geomagnetic field history. Here, we summarize the ecology, evolution, and environmental function of MTB and the paleoenvironmental implications of magnetofossils in light of recent discoveries.}, } @article {pmid35642429, year = {2022}, author = {Bonforti, A and Solé, R}, title = {Unicellular-multicellular evolutionary branching driven by resource limitations.}, journal = {Journal of the Royal Society, Interface}, volume = {19}, number = {191}, pages = {20220018}, pmid = {35642429}, issn = {1742-5662}, mesh = {*Biological Evolution ; Cell Adhesion ; }, abstract = {Multicellular life forms have evolved many times on our planet, suggesting that this is a common evolutionary innovation. Multiple advantages have been proposed for the emergence of multicellularity (MC). In this paper, we address the problem of how the first precondition for MC, namely 'stay together', might have occurred under spatially limited resources exploited by a population of unicellular agents. Using a minimal model of evolved cell-cell adhesion among growing and dividing cells that exploit a localized resource with a given size, we show that a transition occurs at a critical resource size separating a phase of evolved multicellular aggregates from a phase where unicellularity (UC) is favoured. The two phases are separated by an intermediate domain where both UC and MC can be selected by evolution. This model provides a minimal approach to the early stages that were required to transition from individuality to cohesive groups of cells associated with a physical cooperative effect: when resources are present only in a localized portion of the habitat, MC is a desirable property as it helps cells to keep close to the available local nutrients.}, } @article {pmid35630369, year = {2022}, author = {Cui, K and Pan, H and Chen, J and Liu, J and Zhao, Y and Chen, S and Zhang, W and Xiao, T and Wu, LF}, title = {A Novel Isolate of Spherical Multicellular Magnetotactic Prokaryotes Has Two Magnetosome Gene Clusters and Synthesizes Both Magnetite and Greigite Crystals.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, pmid = {35630369}, issn = {2076-2607}, abstract = {Multicellular magnetotactic prokaryotes (MMPs) are a unique group of magnetotactic bacteria that are composed of 10-100 individual cells and show coordinated swimming along magnetic field lines. MMPs produce nanometer-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals-termed magnetosomes. Two types of magnetosome gene cluster (MGC) that regulate biomineralization of magnetite and greigite have been found. Here, we describe a dominant spherical MMP (sMMP) species collected from the intertidal sediments of Jinsha Bay, in the South China Sea. The sMMPs were 4.78 ± 0.67 μm in diameter, comprised 14-40 cells helical symmetrically, and contained bullet-shaped magnetite and irregularly shaped greigite magnetosomes. Two sets of MGCs, one putatively related to magnetite biomineralization and the other to greigite biomineralization, were identified in the genome of the sMMP, and two sets of paralogous proteins (Mam and Mad) that may function separately and independently in magnetosome biomineralization were found. Phylogenetic analysis indicated that the sMMPs were affiliated with Deltaproteobacteria. This is the first direct report of two types of magnetosomes and two sets of MGCs being detected in the same sMMP. The study provides new insights into the mechanism of biomineralization of magnetosomes in MMPs, and the evolutionary origin of MGCs.}, } @article {pmid35628404, year = {2022}, author = {Paradžik, T and Podgorski, II and Vojvoda Zeljko, T and Paradžik, M}, title = {Ancient Origins of Cytoskeletal Crosstalk: Spectraplakin-like Proteins Precede the Emergence of Cortical Microtubule Stabilization Complexes as Crosslinkers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628404}, issn = {1422-0067}, mesh = {Actin Cytoskeleton/metabolism ; *Actins/metabolism ; Animals ; *Cytoskeleton/metabolism ; Microtubules/metabolism ; Phylogeny ; }, abstract = {Adhesion between cells and the extracellular matrix (ECM) is one of the prerequisites for multicellularity, motility, and tissue specialization. Focal adhesions (FAs) are defined as protein complexes that mediate signals from the ECM to major components of the cytoskeleton (microtubules, actin, and intermediate filaments), and their mutual communication determines a variety of cellular processes. In this study, human cytoskeletal crosstalk proteins were identified by comparing datasets with experimentally determined cytoskeletal proteins. The spectraplakin dystonin was the only protein found in all datasets. Other proteins (FAK, RAC1, septin 9, MISP, and ezrin) were detected at the intersections of FAs, microtubules, and actin cytoskeleton. Homology searches for human crosstalk proteins as queries were performed against a predefined dataset of proteomes. This analysis highlighted the importance of FA communication with the actin and microtubule cytoskeleton, as these crosstalk proteins exhibit the highest degree of evolutionary conservation. Finally, phylogenetic analyses elucidated the early evolutionary history of spectraplakins and cortical microtubule stabilization complexes (CMSCs) as model representatives of the human cytoskeletal crosstalk. While spectraplakins probably arose at the onset of opisthokont evolution, the crosstalk between FAs and microtubules is associated with the emergence of metazoans. The multiprotein complexes contributing to cytoskeletal crosstalk in animals gradually gained in complexity from the onset of metazoan evolution.}, } @article {pmid35626631, year = {2022}, author = {Paul, B and Sterner, ZR and Buchholz, DR and Shi, YB and Sachs, LM}, title = {Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626631}, issn = {2073-4409}, mesh = {Adrenal Cortex Hormones ; Amphibians ; Animals ; *Metamorphosis, Biological/physiology ; *Thyroid Gland/metabolism ; Thyroid Hormones/metabolism ; Vertebrates/metabolism ; }, abstract = {In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic-pituitary-thyroid axis controls thyroid hormone production and release, whereas the hypothalamic-pituitary-adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution.}, } @article {pmid35621103, year = {2022}, author = {Puzakov, MV and Puzakova, LV}, title = {[Prevalence, Diversity, and Evolution of L18 (DD37E) Transposons in the Genomes of Cnidarians].}, journal = {Molekuliarnaia biologiia}, volume = {56}, number = {3}, pages = {476-490}, doi = {10.31857/S0026898422030120}, pmid = {35621103}, issn = {0026-8984}, mesh = {Animals ; *Cnidaria/genetics ; *DNA Transposable Elements/genetics ; Prevalence ; }, abstract = {Transposable elements have a significant impact on the structure and functioning of multicellular genomes, and also serve as a source of new genes. Studying the diversity and evolution of transposable elements in different taxa is necessary for the fundamental understanding of their role in genomes. The Tc1/mariner elements are one of the most widespread and diverse groups of DNA transposons. In this work, the structure, distribution, diversity, and evolution of the L18 (DD37E) elements in the genomes of cnidarians (Cnidaria) were studied for the first time. As a result, it was found that the L18 group is an independent family (and not a subfamily of the TLE family, as previously thought) in the Tc1/mariner superfamily. Of the 51 detected elements, only four had potentially functional copies. It is assumed that the L18 transposons are of ancient origin, and, in addition, the elements found in the genomes of organisms of the Anthozoa and Hydrozoa classes do not come from a common ancestral transposon within the Cnidaria phylum. In organisms of the Hydrozoa class, L18 transposons appeared as a result of horizontal transfer at a later time period. An intraspecies comparison of the diversity of the L18 elements demonstrates high homogeneity with respect to "old" transposons, which have already lost their activity. At the same time, distant populations, as in the case of Hydra viridissima, have differences in the representation of DNA transposons and the number of copies. These data supplement the knowledge on the diversity and evolution of Tc1/mariner transposons and contribute to the study of the influence of mobile genetic elements on the evolution of multicellular organisms.}, } @article {pmid35606056, year = {2022}, author = {Bush, JO}, title = {Cellular and molecular mechanisms of EPH/EPHRIN signaling in evolution and development.}, journal = {Current topics in developmental biology}, volume = {149}, number = {}, pages = {153-201}, doi = {10.1016/bs.ctdb.2022.02.005}, pmid = {35606056}, issn = {1557-8933}, support = {R01 DE023337/DE/NIDCR NIH HHS/United States ; R01 DE025877/DE/NIDCR NIH HHS/United States ; R01 DE028753/DE/NIDCR NIH HHS/United States ; R01 HL144785/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Adhesion ; *Ephrins/metabolism ; Protein Binding ; *Receptors, Eph Family/metabolism ; Signal Transduction/physiology ; }, abstract = {The EPH receptor tyrosine kinases and their signaling partners, the EPHRINS, comprise a large class of cell signaling molecules that plays diverse roles in development. As cell membrane-anchored signaling molecules, they regulate cellular organization by modulating the strength of cellular contacts, usually by impacting the actin cytoskeleton or cell adhesion programs. Through these cellular functions, EPH/EPHRIN signaling often regulates tissue shape. Indeed, recent evidence indicates that this signaling family is ancient and associated with the origin of multicellularity. Though extensively studied, our understanding of the signaling mechanisms employed by this large family of signaling proteins remains patchwork, and a truly "canonical" EPH/EPHRIN signal transduction pathway is not known and may not exist. Instead, several foundational evolutionarily conserved mechanisms are overlaid by a myriad of tissue -specific functions, though common themes emerge from these as well. Here, I review recent advances and the related contexts that have provided new understanding of the conserved and varied molecular and cellular mechanisms employed by EPH/EPHRIN signaling during development.}, } @article {pmid35588907, year = {2022}, author = {Udayantha, HMV and Samaraweera, AV and Liyanage, DS and Sandamalika, WMG and Lim, C and Yang, H and Lee, JH and Lee, S and Lee, J}, title = {Molecular characterization, antiviral activity, and UV-B damage responses of Caspase-9 from Amphiprion clarkii.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {247-257}, doi = {10.1016/j.fsi.2022.05.023}, pmid = {35588907}, issn = {1095-9947}, mesh = {Animals ; Antiviral Agents ; Caspase 3 ; Caspase 9 ; *Cyprinidae ; *Perciformes ; Phylogeny ; Poly I-C/pharmacology ; }, abstract = {Apoptosis plays a vital role in maintaining cellular homeostasis in multicellular organisms. Caspase-9 (casp-9) is one of the major initiator caspases that induces apoptosis by activating downstream intrinsic apoptosis pathway genes. Here, we isolated the cDNA sequence (1992 bp) of caspase-9 from Amphiprion clarkii (Accasp-9) that consists of a 1305 bp coding region and encodes a 434 aa protein. In silico analysis showed that Accasp-9 has a theoretical isoelectric point of 5.81 and a molecular weight of 48.45 kDa. Multiple sequence alignment revealed that the CARD domain is located at the N-terminus, whereas the large P-20 and small P-10 domains are located at the C-terminus. Moreover, a highly conserved pentapeptide active site ([296]QACGG[301]), as well as histidine and cysteine active sites, are also retained at the C-terminus. In phylogenetic analysis, Accasp-9 formed a clade with casp-9 from different species, distinct from other caspases. Accasp-9 was highly expressed in the gill and intestine compared with other tissues analyzed in healthy A. clarkii. Accasp-9 expression was significantly elevated in the blood after stimulation with Vibrio harveyi and polyinosinic:polycytidylic acid (poly I:C; 12-48 h), but not with lipopolysaccharide. The nucleoprotein expression of the viral hemorrhagic septicemia virus was significantly reduced in Accasp-9 overexpressed fathead minnow (FHM) cells compared with that in the control. In addition, other in vitro assays revealed that cell apoptosis was significantly elevated in poly I:C and UV-B-treated Accasp-9 transfected FHM cells. However, H[248P] or C[298S] mutated Accasp-9 significantly reduced apoptosis in UV-B irradiated cells. Collectively, our results show that Accasp-9 might play a defensive role against invading pathogens and UV-B radiation and H[248] and C[298] active residues are significantly involved in apoptosis in teleosts.}, } @article {pmid35587048, year = {2022}, author = {Gardner, DS and Gray, C}, title = {Development and the art of nutritional maintenance.}, journal = {The British journal of nutrition}, volume = {128}, number = {5}, pages = {828-834}, pmid = {35587048}, issn = {1475-2662}, mesh = {Animals ; Nutritive Value ; *Nutrients ; *Energy Intake ; }, abstract = {Development from early conceptus to a complex, multi-cellular organism is a highly ordered process that is dependent on an adequate supply of nutrients. During this process, the pattern of organ growth is robust, driven by a genetic blueprint and matched to anticipated body mass with high precision and with built-in physiological reserve capacity. This apparent canalisation of the developmental process is particularly sensitive to variation in environmental stimuli, such as inappropriate drug or hormone exposure, or pattern of nutrient delivery. Significant variation in any of these factors can profoundly affect fetal and neonatal growth patterns, with later detriment for physiological function and/or reserve capacity of the resultant adult, with potential health impact. This paradigm shift in science has become known as the Developmental Origins of Health and Disease (DOHaD). Over the last 30 years, many animal and clinical studies have vastly expanded our fundamental knowledge of developmental biology, particularly in the context of later effects on health. In this horizons article, we discuss DOHaD through the lens of nutritional quality (e.g. micronutrient, amino acid, NSP intake). The concept of ‘Quality’ was considered undefinable by Robert Persig in his book, ‘Zen and the Art of Motorcycle Maintenance’. Here, development and the art of nutritional maintenance will define quality in terms of the pattern of nutrient intake, the quality of development and how each interact to influence later health outcomes.}, } @article {pmid35574025, year = {2022}, author = {Ritch, SJ and Telleria, CM}, title = {The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {886533}, pmid = {35574025}, issn = {1664-2392}, mesh = {Carcinoma, Ovarian Epithelial ; *Ecosystem ; Epithelial Cells/metabolism ; Female ; Humans ; Neoplasm Recurrence, Local ; *Ovarian Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.}, } @article {pmid35572413, year = {2022}, author = {Zhang, J and Shen, N and Li, C and Xiang, X and Liu, G and Gui, Y and Patev, S and Hibbett, DS and Barry, K and Andreopoulos, W and Lipzen, A and Riley, R and He, G and Yan, M and Grigoriev, IV and Shan Kwan, H and Kit Cheung, M and Bian, Y and Xiao, Y}, title = {Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes.}, journal = {Journal of advanced research}, volume = {38}, number = {}, pages = {91-106}, pmid = {35572413}, issn = {2090-1224}, mesh = {*Agaricales/genetics ; Genome ; Genome-Wide Association Study ; Metagenomics ; *Shiitake Mushrooms/genetics ; }, abstract = {INTRODUCTION: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.

OBJECTIVES: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.

METHODS: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.

RESULTS: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.

CONCLUSION: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.}, } @article {pmid35570706, year = {2022}, author = {Heinz, MC and Peters, NA and Oost, KC and Lindeboom, RGH and van Voorthuijsen, L and Fumagalli, A and van der Net, MC and de Medeiros, G and Hageman, JH and Verlaan-Klink, I and Borel Rinkes, IHM and Liberali, P and Gloerich, M and van Rheenen, J and Vermeulen, M and Kranenburg, O and Snippert, HJG}, title = {Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.}, journal = {Cancer research}, volume = {82}, number = {10}, pages = {1953-1968}, pmid = {35570706}, issn = {1538-7445}, mesh = {Animals ; *Colorectal Neoplasms/pathology ; Humans ; *Liver Neoplasms/metabolism ; Mice ; Neoplasm Micrometastasis/pathology ; Neoplastic Stem Cells/pathology ; }, abstract = {UNLABELLED: Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization). A better understanding of this step in the metastatic cascade could help improve metastasis prevention and treatment. Here we analyzed liver specimens of patients with colorectal cancer and monitored real-time metastasis formation in mouse livers using intravital microscopy to reveal that micrometastatic lesions are devoid of cancer stem cells (CSC). However, lesions that grow into overt metastases demonstrated appearance of de novo CSCs through cellular plasticity at a multicellular stage. Clonal outgrowth of patient-derived colorectal cancer organoids phenocopied the cellular and transcriptomic changes observed during in vivo metastasis formation. First, formation of mature CSCs occurred at a multicellular stage and promoted growth. Conversely, failure of immature CSCs to generate more differentiated cells arrested growth, implying that cellular heterogeneity is required for continuous growth. Second, early-stage YAP activity was required for the survival of organoid-forming cells. However, subsequent attenuation of early-stage YAP activity was essential to allow for the formation of cell type heterogeneity, while persistent YAP signaling locked micro-organoids in a cellularly homogenous and growth-stalled state. Analysis of metastasis formation in mouse livers using single-cell RNA sequencing confirmed the transient presence of early-stage YAP activity, followed by emergence of CSC and non-CSC phenotypes, irrespective of the initial phenotype of the metastatic cell of origin. Thus, establishment of cellular heterogeneity after an initial YAP-controlled outgrowth phase marks the transition to continuously growing macrometastases.

SIGNIFICANCE: Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases. See related commentary by LeBleu, p. 1870.}, } @article {pmid35563757, year = {2022}, author = {Stange, K and Keric, A and Friese, A and Röntgen, M}, title = {Preparation of Spheroids from Primary Pig Cells in a Mid-Scale Bioreactor Retaining Their Myogenic Potential.}, journal = {Cells}, volume = {11}, number = {9}, pages = {}, pmid = {35563757}, issn = {2073-4409}, mesh = {Animals ; Bioreactors ; Cell Differentiation ; *Muscle Development ; *Muscle Fibers, Skeletal ; Swine ; }, abstract = {Three-dimensional cell culture techniques mimic the in vivo cell environment more adequately than flat surfaces. Spheroids are multicellular aggregates and we aimed to produce scaffold-free spheroids of myogenic origin, called myospheres, using a mid-scale incubator and bioreactor hybrid. For the first time, we obtained spheroids from primary porcine muscle cells (PMCs) with this technology and compared their morphology and growth parameters, marker expression, and myogenic potential to C2C12-derived spheroids. Both cell types were able to form round-shaped spheroids in the bioreactor already after 24 h. The mean diameter of the C2C12 spheroids (44.6 µm) was larger than that of the PMCs (32.7 µm), and the maximum diameter exceeded 1 mm. C2C12 cells formed less aggregates than PMCs with a higher packing density (cell nuclei/mm[2]). After dissociation from the spheroids, C2C12 cells and PMCs started to proliferate again and were able to differentiate into the myogenic lineage, as shown by myotube formation and the expression of F-Actin, Desmin, MyoG, and Myosin. For C2C12, multinucleated syncytia and Myosin expression were observed in spheroids, pointing to accelerated myogenic differentiation. In conclusion, the mid-scale incubator and bioreactor system is suitable for spheroid formation and cultivation from primary muscle cells while preserving their myogenic potential.}, } @article {pmid35551578, year = {2022}, author = {Eskandari, E and Eaves, CJ}, title = {Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.}, journal = {The Journal of cell biology}, volume = {221}, number = {6}, pages = {}, pmid = {35551578}, issn = {1540-8140}, mesh = {Apoptosis/genetics ; *Carcinogenesis/genetics ; *Caspase 3/physiology ; *Cell Proliferation ; *Cell Survival/genetics ; Humans ; Saccharomyces cerevisiae ; }, abstract = {Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode of cell death. However, accumulating evidence indicates that caspase-3 also plays key roles in regulating the growth and homeostatic maintenance of both normal and malignant cells and tissues in multicellular organisms. Given that yeast possess an ancestral caspase-like gene suggests that the caspase-3 protein may have acquired different functions later during evolution to better meet the needs of more complex multicellular organisms, but without necessarily losing all of the functions of its ancestral yeast precursor. This review provides an update on what has been learned about these interesting dichotomous roles of caspase-3, their evolution, and their potential relevance to malignant as well as normal cell biology.}, } @article {pmid35530508, year = {2022}, author = {de la Fuente, M and Novo, M}, title = {Understanding Diversity, Evolution, and Structure of Small Heat Shock Proteins in Annelida Through in Silico Analyses.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {817272}, pmid = {35530508}, issn = {1664-042X}, abstract = {Small heat shock proteins (sHsps) are oligomeric stress proteins characterized by an α-crystallin domain (ACD). These proteins are localized in different subcellular compartments and play critical roles in the stress physiology of tissues, organs, and whole multicellular eukaryotes. They are ubiquitous proteins found in all living organisms, from bacteria to mammals, but they have never been studied in annelids. Here, a data set of 23 species spanning the annelid tree of life, including mostly transcriptomes but also two genomes, was interrogated and 228 novel putative sHsps were identified and manually curated. The analysis revealed very high protein diversity and showed that a significant number of sHsps have a particular dimeric architecture consisting of two tandemly repeated ACDs. The phylogenetic analysis distinguished three main clusters, two of them containing both monomeric sHsps, and ACDs located downstream in the dimeric sHsps, and the other one comprising the upstream ACDs from those dimeric forms. Our results support an evolutionary history of these proteins based on duplication events prior to the Spiralia split. Monomeric sHsps 76) were further divided into five subclusters. Physicochemical properties, subcellular location predictions, and sequence conservation analyses provided insights into the differentiating elements of these putative functional groups. Strikingly, three of those subclusters included sHsps with features typical of metazoans, while the other two presented characteristics resembling non-metazoan proteins. This study provides a solid background for further research on the diversity, evolution, and function in the family of the sHsps. The characterized annelid sHsps are disclosed as essential for improving our understanding of this important family of proteins and their pleotropic functions. The features and the great diversity of annelid sHsps position them as potential powerful molecular biomarkers of environmental stress for acting as prognostic tool in a diverse range of environments.}, } @article {pmid35526729, year = {2022}, author = {Nakajima, T}, title = {Computation by inverse causality: A universal principle to produce symbols for the external reality in living systems.}, journal = {Bio Systems}, volume = {218}, number = {}, pages = {104692}, doi = {10.1016/j.biosystems.2022.104692}, pmid = {35526729}, issn = {1872-8324}, mesh = {*Adaptation, Physiological ; Causality ; *Philosophy ; Probability ; }, abstract = {How can a living system escape the solipsistic self-making process? This problem has been ignored in mainstream biology. This study seeks a reasonable mechanism by which a living system produces symbols that signify external states. To this end, the inverse causality model proposed in previous studies was theoretically improved by refining the core concepts. Inverse causality is an epistemic principle operating in a subject system to produce symbols internally, signifying the past states of the external reality hidden to the subject. Inverse causality yields an important theorem for a system to produce symbols for external states. It asserts that if a system changes from state x to y1 in some instances, and from x to y2 in others (y1 ≠ y2), then x ⟼ y1 produces a symbol that signifies one external state, and x ⟼ y2 produces a different symbol for another state. These symbols are embodied as the states of the system components. The model postulates the equivalence principle in the subject-reality relationship, asserting that inverse causality is equivalent to causality in the external view. Living systems operate with inverse causality using biological devices called measurers, which include membrane receptors, second messengers, and molecular switches in cells, and neurons in multicellular organisms. A measurer is a medium of symbols signifying external states. Biological subsystems functioning as measurers are ubiquitous and essential in contemporary living systems for adaptation to their environments in particular ways by manipulating the symbols they produce. By the inverse causality operation, living systems can reduce the uncertainty of events and manage the probability distribution of future events favorable to survival and reproduction. Due to this function, their measurer systems were sophisticated and diversified in evolution. In philosophy and science, there has been endless debate between determinism and indeterminism. However, surprisingly, contemporary living systems use the inverse causality operation (ICW) to adapt to their environments, which is logically equivalent to the causal principle of determinism.}, } @article {pmid35514085, year = {2022}, author = {Yuan, F and Wang, X and Zhao, B and Xu, X and Shi, M and Leng, B and Dong, X and Lu, C and Feng, Z and Guo, J and Han, G and Zhang, H and Huang, J and Chen, M and Wang, BS}, title = {The genome of the recretohalophyte Limonium bicolor provides insights into salt gland development and salinity adaptation during terrestrial evolution.}, journal = {Molecular plant}, volume = {15}, number = {6}, pages = {1024-1044}, doi = {10.1016/j.molp.2022.04.011}, pmid = {35514085}, issn = {1752-9867}, mesh = {Animals ; *Arabidopsis ; Plant Leaves/genetics ; *Plumbaginaceae/genetics ; Salinity ; Salt Gland ; Salt Tolerance/genetics ; Salt-Tolerant Plants/genetics ; }, abstract = {Halophytes have evolved specialized strategies to cope with high salinity. The extreme halophyte sea lavender (Limonium bicolor) lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions, such as sodium, to avoid salt damage. Here, we report a high-quality, 2.92-Gb, chromosome-scale L. bicolor genome assembly based on a combination of Illumina short reads, single-molecule, real-time long reads, chromosome conformation capture (Hi-C) data, and Bionano genome maps, greatly enriching the genomic information on recretohalophytes with multicellular salt glands. Although the L. bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana, it lacks homologs of the decision fate genes GLABRA3, ENHANCER OF GLABRA3, GLABRA2, TRANSPARENT TESTA GLABRA2, and SIAMESE, providing a molecular explanation for the absence of trichomes in this species. We identified key genes (LbHLH and LbTTG1) controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation, salt secretion, and salt tolerance, thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin. In addition, a whole-genome duplication event occurred in the L. bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity. The L. bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.}, } @article {pmid35504284, year = {2022}, author = {Reyes-Rivera, J and Wu, Y and Guthrie, BGH and Marletta, MA and King, N and Brunet, T}, title = {Nitric oxide signaling controls collective contractions in a colonial choanoflagellate.}, journal = {Current biology : CB}, volume = {32}, number = {11}, pages = {2539-2547.e5}, doi = {10.1016/j.cub.2022.04.017}, pmid = {35504284}, issn = {1879-0445}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM127854/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cyclic GMP/metabolism ; Guanylate Cyclase/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {Although signaling by the gaseous molecule nitric oxide (NO) regulates key physiological processes in animals, including contractility,[1-3] immunity,[4][,][5] development,[6-9] and locomotion,[10][,][11] the early evolution of animal NO signaling remains unclear. To reconstruct the role of NO in the animal stem lineage, we set out to study NO signaling in choanoflagellates, the closest living relatives of animals.[12] In animals, NO produced by the nitric oxide synthase (NOS) canonically signals through cGMP by activating soluble guanylate cyclases (sGCs).[13][,][14] We surveyed the distribution of the NO signaling pathway components across the diversity of choanoflagellates and found three species that express NOS (of either bacterial or eukaryotic origin), sGCs, and downstream genes previously shown to be involved in the NO/cGMP pathway. One of the species coexpressing sGCs and a bacterial-type NOS, Choanoeca flexa, forms multicellular sheets that undergo collective contractions controlled by cGMP.[15] We found that treatment with NO induces cGMP synthesis and contraction in C. flexa. Biochemical assays show that NO directly binds C. flexa sGC1 and stimulates its cyclase activity. The NO/cGMP pathway acts independently from other inducers of C. flexa contraction, including mechanical stimuli and heat, but sGC activity is required for contractions induced by light-to-dark transitions. The output of NO signaling in C. flexa-contractions resulting in a switch from feeding to swimming-resembles the effect of NO in sponges[1-3] and cnidarians,[11][,][16][,][17] where it interrupts feeding and activates contractility. These data provide insights into the biology of the first animals and the evolution of NO signaling.}, } @article {pmid35486699, year = {2022}, author = {Staps, M and Tarnita, CE}, title = {When being flexible matters: Ecological underpinnings for the evolution of collective flexibility and task allocation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {18}, pages = {e2116066119}, pmid = {35486699}, issn = {1091-6490}, mesh = {Animals ; Ants ; *Behavior, Animal ; *Biological Evolution ; Ecology ; Humans ; *Social Behavior ; }, abstract = {Task allocation is a central feature of collective organization. Living collective systems, such as multicellular organisms or social insect colonies, have evolved diverse ways to allocate individuals to different tasks, ranging from rigid, inflexible task allocation that is not adjusted to changing circumstances to more fluid, flexible task allocation that is rapidly adjusted to the external environment. While the mechanisms underlying task allocation have been intensely studied, it remains poorly understood whether differences in the flexibility of task allocation can be viewed as adaptive responses to different ecological contexts—for example, different degrees of temporal variability. Motivated by this question, we develop an analytically tractable mathematical framework to explore the evolution of task allocation in dynamic environments. We find that collective flexibility is not necessarily always adaptive, and fails to evolve in environments that change too slowly (relative to how long tasks can be left unattended) or too quickly (relative to how rapidly task allocation can be adjusted). We further employ the framework to investigate how environmental variability impacts the internal organization of task allocation, which allows us to propose adaptive explanations for some puzzling empirical observations, such as seemingly unnecessary task switching under constant environmental conditions, apparent task specialization without efficiency benefits, and high levels of individual inactivity. Altogether, this work provides a general framework for probing the evolved diversity of task allocation strategies in nature and reinforces the idea that considering a system’s ecology is crucial to explaining its collective organization.}, } @article {pmid35484223, year = {2022}, author = {Goymer, P}, title = {Multicellularity gets real.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {666}, doi = {10.1038/s41559-022-01765-4}, pmid = {35484223}, issn = {2397-334X}, mesh = {*Biological Evolution ; Phylogeny ; }, } @article {pmid35484218, year = {2022}, author = {Farkas, Z and Kovács, K and Sarkadi, Z and Kalapis, D and Fekete, G and Birtyik, F and Ayaydin, F and Molnár, C and Horváth, P and Pál, C and Papp, B}, title = {Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {763-773}, pmid = {35484218}, issn = {2397-334X}, support = {098016/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics ; *Saccharomycetales/genetics ; }, abstract = {Deleterious mutations are generally considered to be irrelevant for morphological evolution. However, they could be compensated by conditionally beneficial mutations, thereby providing access to new adaptive paths. Here we use high-dimensional phenotyping of laboratory-evolved budding yeast lineages to demonstrate that new cellular morphologies emerge exceptionally rapidly as a by-product of gene loss and subsequent compensatory evolution. Unexpectedly, the capacities for invasive growth, multicellular aggregation and biofilm formation also spontaneously evolve in response to gene loss. These multicellular phenotypes can be achieved by diverse mutational routes and without reactivating the canonical regulatory pathways. These ecologically and clinically relevant traits originate as pleiotropic side effects of compensatory evolution and have no obvious utility in the laboratory environment. The extent of morphological diversity in the evolved lineages is comparable to that of natural yeast isolates with diverse genetic backgrounds and lifestyles. Finally, we show that both the initial gene loss and subsequent compensatory mutations contribute to new morphologies, with their synergistic effects underlying specific morphological changes. We conclude that compensatory evolution is a previously unrecognized source of morphological diversity and phenotypic novelties.}, } @article {pmid35483597, year = {2022}, author = {Wang, B and Zhu, F and Shi, Z and Huang, Z and Sun, R and Wang, Q and Ouyang, G and Ji, W}, title = {Molecular characteristics, polymorphism and expression analysis of mhc Ⅱ in yellow catfish(pelteobagrus fulvidraco)responding to Flavobacterium columnare infection.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {90-100}, doi = {10.1016/j.fsi.2022.04.036}, pmid = {35483597}, issn = {1095-9947}, mesh = {Animals ; *Catfishes ; Fish Proteins/chemistry ; Flavobacterium/genetics ; Phylogeny ; RNA, Messenger/metabolism ; }, abstract = {The major histocompatibility complex (MHC) is an important component of the immune system of vertebrates, which plays a vital role in presenting extrinsic antigens. In this study, we cloned and characterized the mhc ⅡA and mhc ⅡB genes of yellow catfish Pelteobagrus fulvidraco. The open reading frames (ORFs) of mhc ⅡA and mhc ⅡB genes were 708 bp and 747bp in length, encoding 235 and 248 amino acids, respectively. The structure of mhc ⅡA and mhc ⅡB includes a signal peptide, an α1/β1 domain, an α2/β2 domain, a transmembrane region and a cytoplasmic region. Homologous identity analysis revealed that both mhc ⅡA and mhc ⅡB shared high protein sequence similarity with that of Chinese longsnout catfish Leiocassis longirostris. mhc ⅡA and mhc ⅡB showed similar expression patterns in different tissues, with the higher expression level in spleen, head kidney and gill and lower expression in liver, stomach, gall bladder and heart. The mRNA expression level of mhc ⅡA and mhc ⅡB in different embryonic development stages also showed the similar trends. The higher expression was detected from fertilized egg to 32 cell stage, low expression from multicellular period to 3 days post hatching (dph), and then the expression increased to a higher level from 4 dph to 14 dph. The mRNA expression levels of mhc ⅡA and mhc ⅡB were significantly up-regulated not only in the body kidney and spleen, but also in the midgut, hindgut, liver and gill after challenge of Flavobacterium columnare. The results suggest that Mhc Ⅱ plays an important role in the anti-infection process of yellow catfish P. fulvidraco.}, } @article {pmid35477578, year = {2022}, author = {Zhang, Z and Shitut, S and Claushuis, B and Claessen, D and Rozen, DE}, title = {Mutational meltdown of putative microbial altruists in Streptomyces coelicolor colonies.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {2266}, pmid = {35477578}, issn = {2041-1723}, mesh = {Diploidy ; Mutation ; Point Mutation ; Spores, Bacterial/genetics ; *Streptomyces coelicolor/genetics ; }, abstract = {In colonies of the filamentous multicellular bacterium Streptomyces coelicolor, a subpopulation of cells arises that hyperproduces metabolically costly antibiotics, resulting in a division of labor that increases colony fitness. Because these cells contain large genomic deletions that cause massive reductions to individual fitness, their behavior is similar to altruistic worker castes in social insects or somatic cells in multicellular organisms. To understand these mutant cells' reproductive and genomic fate after their emergence, we use experimental evolution by serially transferring populations via spore-to-spore transfer for 25 cycles, reflective of the natural mode of bottlenecked transmission for these spore-forming bacteria. We show that in contrast to wild-type cells, putatively altruistic mutant cells continue to decline in fitness during transfer while they lose more fragments from their chromosome ends. In addition, the base-substitution rate in mutants increases roughly 10-fold, possibly due to mutations in genes for DNA replication and repair. Ecological damage, caused by reduced sporulation, coupled with DNA damage due to point mutations and deletions, leads to an inevitable and irreversible type of mutational meltdown in these cells. Taken together, these results suggest the cells arising in the S. coelicolor division of labor are analogous to altruistic reproductively sterile castes of social insects.}, } @article {pmid35472432, year = {2022}, author = {Chaigne, A and Brunet, T}, title = {Incomplete abscission and cytoplasmic bridges in the evolution of eukaryotic multicellularity.}, journal = {Current biology : CB}, volume = {32}, number = {8}, pages = {R385-R397}, doi = {10.1016/j.cub.2022.03.021}, pmid = {35472432}, issn = {1879-0445}, support = {201334/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Evolution ; Cytoplasm ; Cytosol ; *Eukaryota ; Eukaryotic Cells ; }, abstract = {The textbook view of cell division terminates with the final separation of the two daughter cells in the process called abscission. However, in contrast to this classical view, a variety of cell types in multicellular organisms are connected through cytoplasmic bridges, which most often form by incomplete abscission or - more rarely - by local fusion of plasma membranes. In this review, we survey the distribution, function, and formation of cytoplasmic bridges across the eukaryotic tree of life. We find that cytoplasmic bridges are widespread, and were likely ancestrally present, in almost all lineages of eukaryotes with clonal multicellularity - including the five 'complex multicellular' lineages: animals, fungi, land plants, red algae, and brown algae. In animals, cytoplasmic bridges resulting from incomplete abscission are ubiquitous in the germline and common in pluripotent cell types. Although cytoplasmic bridges have been less studied than other structural mediators of multicellularity (such as adhesion proteins and extracellular matrix), we propose that they have played a pivotal role in the repeated evolution of eukaryotic clonal multicellularity - possibly by first performing a structural role and later by allowing exchange of nutrients and/or intercellular communication, which notably buffered cell-cell competition by averaging gene expression. Bridges were eventually lost from many animal tissues in concert with the evolution of spatial cell differentiation, cell motility within the organism, and other mechanisms for intercellular distribution of signals and metabolites. Finally, we discuss the molecular basis for the evolution of incomplete abscission and examine the alternative hypotheses of single or multiple origins.}, } @article {pmid35470227, year = {2022}, author = {Mulcahey, PJ and Chen, Y and Driscoll, N and Murphy, BB and Dickens, OO and Johnson, ATC and Vitale, F and Takano, H}, title = {Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays.}, journal = {eNeuro}, volume = {9}, number = {3}, pages = {}, pmid = {35470227}, issn = {2373-2822}, support = {R21 NS106434/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Epilepsy, Temporal Lobe ; *Graphite ; Hippocampus ; Mice ; Microelectrodes ; Seizures ; }, abstract = {Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.}, } @article {pmid35468249, year = {2022}, author = {Melnikov, NP and Bolshakov, FV and Frolova, VS and Skorentseva, KV and Ereskovsky, AV and Saidova, AA and Lavrov, AI}, title = {Tissue homeostasis in sponges: Quantitative analysis of cell proliferation and apoptosis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {338}, number = {6}, pages = {360-381}, doi = {10.1002/jez.b.23138}, pmid = {35468249}, issn = {1552-5015}, mesh = {Animals ; *Apoptosis ; Cell Proliferation ; Homeostasis ; *Signal Transduction ; }, abstract = {Tissues of multicellular animals are maintained due to a tight balance between cell proliferation and programmed cell death. Sponges are early branching metazoans essential to understanding the key mechanisms of tissue homeostasis. This article is dedicated to the comparative analysis of proliferation and apoptosis in intact tissues of two sponges, Halisarca dujardinii (class Demospongiae) and Leucosolenia variabilis (class Calcarea). Labeled nucleotides EdU and anti-phosphorylated histone 3 antibodies reveal a considerable number of cycling cells in intact tissues of both species. Quantitative DNA staining reveals the classic cell cycle distribution curve. The main type of cycling cells are choanocytes - flagellated cells of the aquiferous system. The rate of proliferation remains constant throughout various areas of sponge bodies that contain choanocytes. The EdU tracking experiments conducted in H. dujardinii indicate that choanocytes may give rise to mesohyl cells through migration. The number of apoptotic cells in tissues of both species is insignificant, although being comparable to the renewing tissues of other animals. In vivo studies with tetramethylrhodamine ethyl ester and CellEvent Caspase-3/7 indicate that apoptosis might be independent of mitochondrial outer membrane permeabilization. Altogether, a combination of confocal laser scanning microscopy and flow cytometry provides a quantitative description of cell proliferation and apoptosis in sponges displaying either rapid growth or cell turnover.}, } @article {pmid35446582, year = {2022}, author = {Gates, C and Ananyev, G and Roy-Chowdhury, S and Cullinane, B and Miller, M and Fromme, P and Dismukes, GC}, title = {Why Did Nature Choose Manganese over Cobalt to Make Oxygen Photosynthetically on the Earth?.}, journal = {The journal of physical chemistry. B}, volume = {126}, number = {17}, pages = {3257-3268}, doi = {10.1021/acs.jpcb.2c00749}, pmid = {35446582}, issn = {1520-5207}, mesh = {Cobalt ; *Cyanobacteria/metabolism ; Manganese/chemistry ; Oxidation-Reduction ; Oxygen/chemistry ; *Photosystem II Protein Complex/chemistry ; Water/chemistry ; }, abstract = {All contemporary oxygenic phototrophs─from primitive cyanobacteria to complex multicellular plants─split water using a single invariant cluster comprising Mn4CaO5 (the water oxidation catalyst) as the catalyst within photosystem II, the universal oxygenic reaction center of natural photosynthesis. This cluster is unstable outside of PSII and can be reconstituted, both in vivo and in vitro, using elemental aqueous ions and light, via photoassembly. Here, we demonstrate the first functional substitution of manganese in any oxygenic reaction center by in vitro photoassembly. Following complete removal of inorganic cofactors from cyanobacterial photosystem II microcrystal (PSIIX), photoassembly with free cobalt (Co[2+]), calcium (Ca[2+]), and water (OH[-]) restores O2 evolution activity. Photoassembly occurs at least threefold faster using Co[2+] versus Mn[2+] due to a higher quantum yield for PSIIX-mediated charge separation (P*): Co[2+] → P* → Co[3+]QA[-]. However, this kinetic preference for Co[2+] over native Mn[2+] during photoassembly is offset by significantly poorer catalytic activity (∼25% of the activity with Mn[2+]) and ∼3- to 30-fold faster photoinactivation rate. The resulting reconstituted Co-PSIIX oxidizes water by the standard four-flash photocycle, although they produce 4-fold less O2 per PSII, suggested to arise from faster charge recombination (Co[3+]QA ← Co[4+]QA[-]) in the catalytic cycle. The faster photoinactivation of reconstituted Co-PSIIX occurs under anaerobic conditions during the catalytic cycle, suggesting direct photodamage without the involvement of O2. Manganese offers two advantages for oxygenic phototrophs, which may explain its exclusive retention throughout Darwinian evolution: significantly slower charge recombination (Mn[3+]QA ← Mn[4+]QA[-]) permits more water oxidation at low and fluctuating solar irradiation (greater net energy conversion) and much greater tolerance to photodamage at high light intensities (Mn[4+] is less oxidizing than Co[4+]). Future work to identify the chemical nature of the intermediates will be needed for further interpretation.}, } @article {pmid35444563, year = {2022}, author = {Mendez-Romero, O and Ricardez-García, C and Castañeda-Tamez, P and Chiquete-Félix, N and Uribe-Carvajal, S}, title = {Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {874321}, pmid = {35444563}, issn = {1664-042X}, abstract = {From 2.5 to 2.0 billion years ago, atmospheric oxygen concentration [O2] rose thousands of times, leading to the first mass extinction. Reactive Oxygen Species (ROS) produced by the non-catalyzed partial reduction of O2 were highly toxic eliminating many species. Survivors developed different strategies to cope with ROS toxicity. At the same time, using O2 as the final acceptor in respiratory chains increased ATP production manifold. Thus, both O2 and ROS were strong drivers of evolution, as species optimized aerobic metabolism while developing ROS-neutralizing mechanisms. The first line of defense is preventing ROS overproduction and two mechanisms were developed in parallel: 1) Physiological uncoupling systems (PUS), which increase the rate of electron fluxes in respiratory systems. 2) Avoidance of excess [O2]. However, it seems that as avoidance efficiency improved, PUSs became less efficient. PUS includes branched respiratory chains and proton sinks, which may be proton specific, the mitochondrial uncoupling proteins (UCPs) or unspecific, the mitochondrial permeability transition pore (PTP). High [O2] avoidance also involved different strategies: 1) Cell association, as in biofilms or in multi-cellularity allowed gas-permeable organisms (oxyconformers) from bacterial to arthropods to exclude O2. 2) Motility, to migrate from hypoxic niches. 3) Oxyregulator organisms: as early as in fish, and O2-impermeable epithelium excluded all gases and only exact amounts entered through specialized respiratory systems. Here we follow the parallel evolution of PUS and O2-avoidance, PUS became less critical and lost efficiency. In regard, to proton sinks, there is fewer evidence on their evolution, although UCPs have indeed drifted in function while in some species it is not clear whether PTPs exist.}, } @article {pmid35421922, year = {2022}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of vegetative cells and zygotes of the multicellular volvocine green alga Gonium pectorale.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {103}, pmid = {35421922}, issn = {1471-2180}, mesh = {*Chlorophyta ; Cryopreservation ; Nitrogen ; Phylogeny ; *Zygote ; }, abstract = {BACKGROUND: Colonial and multicellular volvocine green algae have been extensively studied recently in various fields of the biological sciences. However, only one species (Pandorina morum) has been cryopreserved in public culture collections.

RESULTS: Here, we investigated conditions for cryopreservation of the multicellular volvocine alga Gonium pectorale using vegetative colonies or cells and zygotes. Rates of vegetative cell survival in a G. pectorale strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3% and 6%) of the cryoprotectant N,N-dimethylformamide (DMF) and two types of tubes (0.2-mL polymerase chain reaction tubes and 2-mL cryotubes) used for cryopreservation. Among the four conditions investigated, the highest rate of survival [2.7 ± 3.6% (0.54-10%) by the most probable number (MPN) method] was obtained when 2.0-mL cryotubes containing 1.0 mL of culture samples with 6% DMF were subjected to cryogenic treatment. Using these optimized cryopreservation conditions, survival rates after freezing in liquid nitrogen were examined for twelve other strains of G. pectorale and twelve strains of five other Gonium species. We obtained ≥ 0.1% MPN survival in nine of the twelve G. pectorale strains tested. However, < 0.1% MPN survival was detected in eleven of twelve strains of five other Gonium species. In total, ten cryopreserved strains of G. pectorale were newly established in the Microbial Culture Collection at the National Institute for Environmental Studies. Although the cryopreservation of zygotes of volvocine algae has not been previously reported, high rates (approximately 60%) of G. pectorale zygote germination were observed after thawing zygotes that had been cryopreserved with 5% or 10% methanol as the cryoprotectant during two-step cooling and freezing in liquid nitrogen.

CONCLUSIONS: The present study demonstrated that cryopreservation of G. pectorale is possible with 6% DMF as a cryoprotectant and 1.0-mL culture samples in 2.0-mL cryotubes subjected to two-step cooling in a programmable freezer.}, } @article {pmid35420439, year = {2022}, author = {Rohkin Shalom, S and Weiss, B and Lalzar, M and Kaltenpoth, M and Chiel, E}, title = {Abundance and Localization of Symbiotic Bacterial Communities in the Fly Parasitoid Spalangia cameroni.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {9}, pages = {e0254921}, pmid = {35420439}, issn = {1098-5336}, mesh = {Animals ; Enterobacteriaceae/genetics ; Female ; *Gammaproteobacteria ; In Situ Hybridization, Fluorescence ; Male ; *Rickettsia/genetics ; Symbiosis/physiology ; *Wasps/microbiology ; *Wolbachia/physiology ; }, abstract = {Multicellular eukaryotes often host multiple microbial symbionts that may cooperate or compete for host resources, such as space and nutrients. Here, we studied the abundances and localization of four bacterial symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, in the parasitic wasp Spalangia cameroni. Using quantitative PCR (qPCR), we measured the symbionts' titers in wasps that harbor different combinations of these symbionts. We found that the titer of each symbiont decreased as the number of symbiont species in the community increased. Symbionts' titers were higher in females than in males. Rickettsia was the most abundant symbiont in all the communities, followed by Sodalis and Wolbachia. The titers of these three symbionts were positively correlated in some of the colonies. Fluorescence in situ hybridization was in line with the qPCR results: Rickettsia, Wolbachia, and Sodalis were observed in high densities in multiple organs, including brain, muscles, gut, Malpighian tubules, fat body, ovaries, and testes, while Arsenophonus was localized to fewer organs and in lower densities. Sodalis and Arsenophonus were observed in ovarian follicle cells but not within oocytes or laid eggs. This study highlights the connection between symbionts' abundance and localization. We discuss the possible connections between our findings to symbiont transmission success. IMPORTANCE Many insects carry intracellular bacterial symbionts (bacteria that reside within the cells of the insect). When multiple symbiont species cohabit in a host, they may compete or cooperate for space, nutrients, and transmission, and the nature of such interactions would be reflected in the abundance of each symbiont species. Given the widespread occurrence of coinfections with maternally transmitted symbionts in insects, it is important to learn more about how they interact, where they are localized, and how these two aspects affect their co-occurrence within individual insects. Here, we studied the abundance and the localization of four symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, that cohabit the parasitic wasp Spalangia cameroni. We found that symbionts' titers differed between symbiotic communities. These results were corroborated by microscopy, which shows differential localization patterns. We discuss the findings in the contexts of community ecology, possible symbiont-symbiont interactions, and host control mechanisms that may shape the symbiotic community structure.}, } @article {pmid35418164, year = {2022}, author = {Lin, Y and Xu, X and Maróti, G and Strube, ML and Kovács, ÁT}, title = {Adaptation and phenotypic diversification of Bacillus thuringiensis biofilm are accompanied by fuzzy spreader morphotypes.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {27}, pmid = {35418164}, issn = {2055-5008}, mesh = {Bacillus cereus ; *Bacillus thuringiensis/genetics ; Biofilms ; DNA Transposable Elements ; }, abstract = {Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that produce biofilms on abiotic and biotic surfaces. While genetic and morphological diversification enables the adaptation of multicellular communities, this area remains largely unknown in the Bacillus cereus group. In this work, we dissected the experimental evolution of Bacillus thuringiensis 407 Cry- during continuous recolonization of plastic beads. We observed the evolution of a distinct colony morphotype that we named fuzzy spreader (FS) variant. Most multicellular traits of the FS variant displayed higher competitive ability versus the ancestral strain, suggesting an important role for diversification in the adaptation of B. thuringiensis to the biofilm lifestyle. Further genetic characterization of FS variant revealed the disruption of a guanylyltransferase gene by an insertion sequence (IS) element, which could be similarly observed in the genome of a natural isolate. The evolved FS and the deletion mutant in the guanylyltransferase gene (Bt407ΔrfbM) displayed similarly altered aggregation and hydrophobicity compared to the ancestor strain, suggesting that the adaptation process highly depends on the physical adhesive forces.}, } @article {pmid35417559, year = {2022}, author = {Kambayashi, C and Kakehashi, R and Sato, Y and Mizuno, H and Tanabe, H and Rakotoarison, A and Künzel, S and Furuno, N and Ohshima, K and Kumazawa, Y and Nagy, ZT and Mori, A and Allison, A and Donnellan, SC and Ota, H and Hoso, M and Yanagida, T and Sato, H and Vences, M and Kurabayashi, A}, title = {Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35417559}, issn = {1537-1719}, mesh = {Animals ; Cattle ; *Gene Transfer, Horizontal ; Geography ; *Parasites/genetics ; Phylogeny ; Predatory Behavior ; Retroelements ; Vertebrates/genetics ; }, abstract = {Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35406795, year = {2022}, author = {Zschüntzsch, J and Meyer, S and Shahriyari, M and Kummer, K and Schmidt, M and Kummer, S and Tiburcy, M}, title = {The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.}, journal = {Cells}, volume = {11}, number = {7}, pages = {}, pmid = {35406795}, issn = {2073-4409}, mesh = {Coculture Techniques ; Drug Development ; Humans ; Muscle Cells ; *Neuromuscular Diseases/drug therapy ; *Organoids ; }, abstract = {Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.}, } @article {pmid35396623, year = {2022}, author = {Koide, RT}, title = {On Holobionts, Holospecies, and Holoniches: the Role of Microbial Symbioses in Ecology and Evolution.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, pmid = {35396623}, issn = {1432-184X}, abstract = {My goal in writing this is to increase awareness of the roles played by microbial symbionts in eukaryote ecology and evolution. Most eukaryotes host one or more species of symbiotic microorganisms, including prokaryotes and fungi. Many of these have profound impacts on the biology of their hosts. For example, microbial symbionts may expand the niches of their hosts, cause rapid adaptation of the host to the environment and re-adaptation to novel conditions via symbiont swapping, facilitate speciation, and fundamentally alter our concept of the species. In some cases, microbial symbionts and multicellular eukaryote hosts have a mutual dependency, which has obvious conservation implications. Hopefully, this contribution will stimulate a reevaluation of important ecological and evolutionary concepts including niche, adaptation, the species, speciation, and conservation of multicellular eukaryotes.}, } @article {pmid35395246, year = {2022}, author = {Yang, Y and Jiang, H}, title = {Intercellular water exchanges trigger soliton-like waves in multicellular systems.}, journal = {Biophysical journal}, volume = {121}, number = {9}, pages = {1610-1618}, pmid = {35395246}, issn = {1542-0086}, mesh = {*Water ; }, abstract = {Oscillations and waves are ubiquitous in living cellular systems. Generations of these spatiotemporal patterns are generally attributed to some mechanochemical feedbacks. Here, we treat cells as open systems, i.e., water and ions can pass through the cell membrane passively or actively, and reveal a new origin of wave generation. We show that osmotic shocks above a shock threshold will trigger self-sustained cell oscillations and result in long-range waves propagating without decrement, a phenomenon that is analogous to the excitable medium. The traveling wave propagates along the intercellular osmotic pressure gradient, and its wave speed scales with the magnitude of intercellular water flows. Furthermore, we also find that the traveling wave exhibits several hallmarks of solitary waves. Together, our findings predict a new mechanism of wave generation in living multicellular systems. The ubiquity of intercellular water exchanges implies that this mechanism may be relevant to a broad class of systems.}, } @article {pmid35394842, year = {2022}, author = {Dupin, A and Aufinger, L and Styazhkin, I and Rothfischer, F and Kaufmann, BK and Schwarz, S and Galensowske, N and Clausen-Schaumann, H and Simmel, FC}, title = {Synthetic cell-based materials extract positional information from morphogen gradients.}, journal = {Science advances}, volume = {8}, number = {14}, pages = {eabl9228}, pmid = {35394842}, issn = {2375-2548}, abstract = {Biomaterials composed of synthetic cells have the potential to adapt and differentiate guided by physicochemical environmental cues. Inspired by biological systems in development, which extract positional information (PI) from morphogen gradients in the presence of uncertainties, we here investigate how well synthetic cells can determine their position within a multicellular structure. To calculate PI, we created and analyzed a large number of synthetic cellular assemblies composed of emulsion droplets connected via lipid bilayer membranes. These droplets contained cell-free feedback gene circuits that responded to gradients of a genetic inducer acting as a morphogen. PI is found to be limited by gene expression noise and affected by the temporal evolution of the morphogen gradient and the cell-free expression system itself. The generation of PI can be rationalized by computational modeling of the system. We scale our approach using three-dimensional printing and demonstrate morphogen-based differentiation in larger tissue-like assemblies.}, } @article {pmid35391738, year = {2022}, author = {Nagy, K and Dukic, B and Hodula, O and Ábrahám, Á and Csákvári, E and Dér, L and Wetherington, MT and Noorlag, J and Keymer, JE and Galajda, P}, title = {Emergence of Resistant Escherichia coli Mutants in Microfluidic On-Chip Antibiotic Gradients.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {820738}, pmid = {35391738}, issn = {1664-302X}, abstract = {Spatiotemporal structures and heterogeneities are common in natural habitats, yet their role in the evolution of antibiotic resistance is still to be uncovered. We applied a microfluidic gradient generator device to study the emergence of resistant bacteria in spatial ciprofloxacin gradients. We observed biofilm formation in regions with sub-inhibitory concentrations of antibiotics, which quickly expanded into the high antibiotic regions. In the absence of an explicit structure of the habitat, this multicellular formation led to a spatial structure of the population with local competition and limited migration. Therefore, such structures can function as amplifiers of selection and aid the spread of beneficial mutations. We found that the physical environment itself induces stress-related mutations that later prove beneficial when cells are exposed to antibiotics. This shift in function suggests that exaptation occurs in such experimental scenarios. The above two processes pave the way for the subsequent emergence of highly resistant specific mutations.}, } @article {pmid35386829, year = {2022}, author = {van der Zee, MJ and Whiting, JR and Paris, JR and Bassar, RD and Travis, J and Weigel, D and Reznick, DN and Fraser, BA}, title = {Rapid genomic convergent evolution in experimental populations of Trinidadian guppies (Poecilia reticulata).}, journal = {Evolution letters}, volume = {6}, number = {2}, pages = {149-161}, pmid = {35386829}, issn = {2056-3744}, abstract = {Although rapid phenotypic evolution has been documented often, the genomic basis of rapid adaptation to natural environments is largely unknown in multicellular organisms. Population genomic studies of experimental populations of Trinidadian guppies (Poecilia reticulata) provide a unique opportunity to study this phenomenon. Guppy populations that were transplanted from high-predation (HP) to low-predation (LP) environments have been shown to evolve toward the phenotypes of naturally colonized LP populations in as few as eight generations. These changes persist in common garden experiments, indicating that they have a genetic basis. Here, we report results of whole genome variation in four experimental populations colonizing LP sites along with the corresponding HP source population. We examined genome-wide patterns of genetic variation to estimate past demography and used a combination of genome scans, forward simulations, and a novel analysis of allele frequency change vectors to uncover the signature of selection. We detected clear signals of population growth and bottlenecks at the genome-wide level that matched the known history of population numbers. We found a region on chromosome 15 under strong selection in three of the four populations and with our multivariate approach revealing subtle parallel changes in allele frequency in all four populations across this region. Investigating patterns of genome-wide selection in this uniquely replicated experiment offers remarkable insight into the mechanisms underlying rapid adaptation, providing a basis for comparison with other species and populations experiencing rapidly changing environments.}, } @article {pmid35369456, year = {2022}, author = {Chen, K and Gao, Y and Li, L and Zhang, W and Li, J and Zhou, Z and He, H and Chen, Z and Liao, M and Zhang, J}, title = {Increased Drug Resistance and Biofilm Formation Ability in ST34-Type Salmonella Typhimurium Exhibiting Multicellular Behavior in China.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {876500}, pmid = {35369456}, issn = {1664-302X}, abstract = {Salmonella Typhimurium is an important food-borne pathogen. In this paper, multicellular behavior and associated characteristics of S. Typhimurium isolated from human and animal source food were studied. All the S. Typhimurium strains exhibiting multicellular behavior (100%) belonged to the ST34 type. In addition, most of the ST34-type multicellular behavior S. Typhimurium strains had a human origin (69.11%) and 98% of the ST34-type multicellular behavior strains exhibited strong biofilm formation capacity, which was much higher than that of non-multicellular behavior strains (7%, P < 0.01). Antibiotic resistance in ST34-type multicellular behavior strains was significantly higher than in strains with non-multicellular behavior for most conventional drugs (P < 0.05); notably, Polymyxin B (8%) and Imipenem (1%) resistances were also observed in the ST34-type strains. Furthermore, all the ST34-type multicellular behavior strains (100%) exhibited Multiple Drug Resistance (resistance to ≥3antibiotics), which was much higher than that of the non-multicellular behavior strains (P < 0.05). Consistent with the drug-resistant phenotype, the carrying rates of most drug-resistant genes in ST34-type multicellular behavior strains were higher than that those in non-multicellular behavior strains (P < 0.05). Therefore, this study revealed the emergence of a prevalent ST34-type multicellular behavior S. Typhimurium strains with increased biofilm formation ability and drug resistance rate, which poses a threat to public health safety, and highlights the need for comprehensive monitoring of the strains.}, } @article {pmid35359304, year = {2022}, author = {Ramon-Mateu, J and Edgar, A and Mitchell, D and Martindale, MQ}, title = {Studying Ctenophora WBR Using Mnemiopsis leidyi.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2450}, number = {}, pages = {95-119}, pmid = {35359304}, issn = {1940-6029}, mesh = {Animals ; Cell Lineage ; *Ctenophora/genetics ; Genome ; Phylogeny ; }, abstract = {Ctenophores, also known as comb jellies, are a clade of fragile holopelagic, carnivorous marine invertebrates, that represent one of the most ancient extant groups of multicellular animals. Ctenophores show a remarkable ability to regenerate in the adult form, being capable of replacing all body parts (i.e., whole-body regeneration) after loss/amputation. With many favorable experimental features (optical clarity, stereotyped cell lineage, multiple cell types), a full genome sequence available and their early branching phylogenetic position, ctenophores are well placed to provide information about the evolution of regenerative ability throughout the Metazoa. Here, we provide a collection of detailed protocols for use of the lobate ctenophore Mnemiopsis leidyi to study whole-body regeneration, including specimen collection, husbandry, surgical manipulation, and imaging techniques.}, } @article {pmid35358607, year = {2022}, author = {Shapiro, JA}, title = {What we have learned about evolutionary genome change in the past 7 decades.}, journal = {Bio Systems}, volume = {215-216}, number = {}, pages = {104669}, doi = {10.1016/j.biosystems.2022.104669}, pmid = {35358607}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; *DNA Transposable Elements/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics ; Hybridization, Genetic ; }, abstract = {Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations. Genomic analysis confirms the role of TEs in wiring novel networks at major evolutionary transitions. TEs and other forms of repetitive DNA are also important contributors to genome regions that serve as transcriptional templates for regulatory and other biologically functional noncoding ncRNAs. The many functions documented for ncRNAs shows the concept of abundant "selfish" or "junk" DNA in complex genomes is mistaken. Natural and artificial speciation by interspecific hybridization demonstrates that TEs and other biochemical systems of genome restructuring are subject to rapid activation and can generate changes throughout the genomes of the novel species that emerge. In addition to TEs and hybrid species, cancer cells have taught us important lessons about chromothripsis, chromoplexy and other forms of non-random multisite genome restructuring. In many of these restructured genomes, alternative end-joining processes display the capacities of eukaryotes to generate novel combinations of templated and untemplated DNA sequences at the sites of break repair. Sequence innovation by alternative end-joining is widespread among eukaryotes from single cells to advanced plants and animals. In sum, the cellular and genomic capacities of eukaryotic cells have proven to be capable of executing rapid macroevolutionary change under a variety of conditions.}, } @article {pmid35353805, year = {2022}, author = {Burnetti, A and Ratcliff, WC}, title = {Experimental evolution is not just for model organisms.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001587}, pmid = {35353805}, issn = {1545-7885}, mesh = {Animals ; *Biological Evolution ; }, abstract = {In a new paper published in PLOS Biology, Dudin and colleagues evolve simple multicellularity in Sphaeroforma arctica, a unicellular relative of animals. This work establishes a new and open-ended avenue for examining the evolution of multicellularity in an important but understudied group of organisms.}, } @article {pmid35349792, year = {2022}, author = {Toret, C and Picco, A and Boiero-Sanders, M and Michelot, A and Kaksonen, M}, title = {The cellular slime mold Fonticula alba forms a dynamic, multicellular collective while feeding on bacteria.}, journal = {Current biology : CB}, volume = {32}, number = {9}, pages = {1961-1973.e4}, pmid = {35349792}, issn = {1879-0445}, mesh = {Animals ; Bacteria ; *Dictyosteliida ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Multicellularity evolved in fungi and animals, or the opisthokonts, from their common amoeboflagellate ancestor but resulted in strikingly distinct cellular organizations. The origins of this multicellularity divergence are not known. The stark mechanistic differences that underlie the two groups and the lack of information about ancestral cellular organizations limits progress in this field. We discovered a new type of invasive multicellular behavior in Fonticula alba, a unique species in the opisthokont tree, which has a simple, bacteria-feeding sorocarpic amoeba lifestyle. This invasive multicellularity follows germination dependent on the bacterial culture state, after which amoebae coalesce to form dynamic collectives that invade virgin bacterial resources. This bacteria-dependent social behavior emerges from amoeba density and allows for rapid and directed invasion. The motile collectives have animal-like properties but also hyphal-like search and invasive behavior. These surprising findings enrich the diverse multicellularities present within the opisthokont lineage and offer a new perspective on fungal origins.}, } @article {pmid35349578, year = {2022}, author = {Dudin, O and Wielgoss, S and New, AM and Ruiz-Trillo, I}, title = {Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001551}, pmid = {35349578}, issn = {1545-7885}, mesh = {Animals ; Cell Size ; *Cytokinesis ; Phenotype ; }, abstract = {Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. However, how genetic and cellular traits control this process, their likelihood of emergence over evolutionary timescales, and the variation in these traits as multicellularity evolves are still poorly understood. Here, using isolates of the ichthyosporean genus Sphaeroforma-close unicellular relatives of animals with brief transient multicellular life stages-we demonstrate that sedimentation rate is a highly variable and evolvable trait affected by at least 2 distinct physical mechanisms. First, we find extensive (>300×) variation in sedimentation rates for different Sphaeroforma species, mainly driven by size and density during the unicellular-to-multicellular life cycle transition. Second, using experimental evolution with sedimentation rate as a focal trait, we readily obtained, for the first time, fast settling and multicellular Sphaeroforma arctica isolates. Quantitative microscopy showed that increased sedimentation rates most often arose by incomplete cellular separation after cell division, leading to clonal "clumping" multicellular variants with increased size and density. Strikingly, density increases also arose by an acceleration of the nuclear doubling time relative to cell size. Similar size- and density-affecting phenotypes were observed in 4 additional species from the Sphaeroforma genus, suggesting that variation in these traits might be widespread in the marine habitat. By resequencing evolved isolates to high genomic coverage, we identified mutations in regulators of cytokinesis, plasma membrane remodeling, and chromatin condensation that may contribute to both clump formation and the increase in the nuclear number-to-volume ratio. Taken together, this study illustrates how extensive cellular control of density and size drive sedimentation rate variation, likely shaping the onset and further evolution of multicellularity.}, } @article {pmid35337467, year = {2022}, author = {Booth, DS and King, N}, title = {The history of Salpingoeca rosetta as a model for reconstructing animal origins.}, journal = {Current topics in developmental biology}, volume = {147}, number = {}, pages = {73-91}, doi = {10.1016/bs.ctdb.2022.01.001}, pmid = {35337467}, issn = {1557-8933}, mesh = {Animals ; *Choanoflagellata/genetics ; Developmental Biology ; }, abstract = {Choanoflagellates, the closest living relatives of animals, have the potential to reveal the genetic and cell biological foundations of complex multicellular development in animals. Here we describe the history of research on the choanoflagellate Salpingoeca rosetta. From its original isolation in 2000 to the establishment of CRISPR-mediated genome editing in 2020, S. rosetta provides an instructive case study in the establishment of a new model organism.}, } @article {pmid35320517, year = {2022}, author = {Verkerke, H and Dias-Baruffi, M and Cummings, RD and Arthur, CM and Stowell, SR}, title = {Galectins: An Ancient Family of Carbohydrate Binding Proteins with Modern Functions.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2442}, number = {}, pages = {1-40}, pmid = {35320517}, issn = {1940-6029}, mesh = {Cell Cycle ; *Galectins/metabolism ; Glycosylation ; *Immune System/metabolism ; Signal Transduction ; }, abstract = {Galectins are a large family of carbohydrate binding proteins with members in nearly every lineage of multicellular life. Through tandem and en-mass genome duplications, over 15 known vertebrate galectins likely evolved from a single common ancestor extant in pre-chordate lineages. While galectins have divergently evolved numerous functions, some of which do not involve carbohydrate recognition, the vast majority of the galectins have retained the conserved ability to bind variably modified polylactosamine (polyLacNAc) residues on glycans that modify proteins and lipids on the surface of host cells and pathogens. In addition to their direct role in microbial killing, many proposed galectin functions in the immune system and cancer involve crosslinking glycosylated receptors and modifying signaling pathways or sensitivity to antigen from the outside in. However, a large body of work has uncovered intracellular galectin functions mediated by carbohydrate- and non-carbohydrate-dependent interactions. In the cytoplasm, galectins can tune intracellular kinase and G-protein-coupled signaling cascades important for nutrient sensing, cell cycle progression, and transformation. Particularly, but interconnected pathways, cytoplasmic galectins serve the innate immune system as sensors of endolysosomal damage, recruiting and assembling the components of autophagosomes during intracellular infection through carbohydrate-dependent and -independent activities. In the nucleus, galectins participate in pre-mRNA splicing perhaps through interactions with non-coding RNAs required for assembly of spliceosomes. Together, studies of galectin function paint a picture of a functionally dynamic protein family recruited during eons of evolution to regulate numerous essential cellular processes in the context of multicellular life.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35317961, year = {2023}, author = {Bogaert, KA and Zakka, EE and Coelho, SM and De Clerck, O}, title = {Polarization of brown algal zygotes.}, journal = {Seminars in cell & developmental biology}, volume = {134}, number = {}, pages = {90-102}, doi = {10.1016/j.semcdb.2022.03.008}, pmid = {35317961}, issn = {1096-3634}, mesh = {Animals ; Zygote ; *Arabidopsis ; *Phaeophyta/genetics/metabolism ; Cell Polarity ; Cell Division ; Plants ; }, abstract = {Brown algae are a group of multicellular, heterokont algae that have convergently evolved developmental complexity that rivals that of embryophytes, animals or fungi. Early in development, brown algal zygotes establish a basal and an apical pole, which will become respectively the basal system (holdfast) and the apical system (thallus) of the adult alga. Brown algae are interesting models for understanding the establishment of cell polarity in a broad evolutionary context, because they exhibit a large diversity of life cycles, reproductive strategies and, importantly, their zygotes are produced in large quantities free of parental tissue, with symmetry breaking and asymmetric division taking place in a highly synchronous manner. This review describes the current knowledge about the establishment of the apical-basal axis in the model brown seaweeds Ectocarpus, Dictyota, Fucus and Saccharina, highlighting the advantages and specific interests of each system. Ectocarpus is a genetic model system that allows access to the molecular basis of early development and life-cycle control over apical-basal polarity. The oogamous brown alga Fucus, together with emerging comparative models Dictyota and Saccharina, emphasize the diversity of strategies of symmetry breaking in determining a cell polarity vector in brown algae. A comparison with symmetry-breaking mechanisms in land plants, animals and fungi, reveals that the one-step zygote polarisation of Fucus compares well to Saccharomyces budding and Arabidopsis stomata development, while the two-phased symmetry breaking in the Dictyota zygote compares to Schizosaccharomyces fission, the Caenorhabditis anterior-posterior zygote polarisation and Arabidopsis prolate pollen polarisation. The apical-basal patterning in Saccharina zygotes on the other hand, may be seen as analogous to that of land plants. Overall, brown algae have the potential to bring exciting new information on how a single cell gives rise to an entire complex body plan.}, } @article {pmid35311270, year = {2022}, author = {Chen, C and Wang, P and Chen, H and Wang, X and Halgamuge, MN and Chen, C and Song, T}, title = {Smart Magnetotactic Bacteria Enable the Inhibition of Neuroblastoma under an Alternating Magnetic Field.}, journal = {ACS applied materials & interfaces}, volume = {14}, number = {12}, pages = {14049-14058}, doi = {10.1021/acsami.1c24154}, pmid = {35311270}, issn = {1944-8252}, mesh = {Animals ; *Hyperthermia, Induced ; Magnetic Fields ; *Magnetosomes/metabolism ; Mice ; Mice, Nude ; *Neuroblastoma/metabolism/therapy ; }, abstract = {Magnetotactic bacteria are ubiquitous microorganisms in nature that synthesize intracellular magnetic nanoparticles called magnetosomes in a gene-controlled way and arrange them in chains. From in vitro to in vivo, we demonstrate that the intact body of Magnetospirillum magneticum AMB-1 has potential as a natural magnetic hyperthermia material for cancer therapy. Compared to chains of magnetosomes and individual magnetosomes, the entire AMB-1 cell exhibits superior heating capability under an alternating magnetic field. When incubating with tumor cells, the intact AMB-1 cells disperse better than the other two types of magnetosomes, decreasing cellular viability under the control of an alternating magnetic field. Furthermore, in vivo experiments in nude mice with neuroblastoma found that intact AMB-1 cells had the best antitumor activity with magnetic hyperthermia therapy compared to other treatment groups. These findings suggest that the intact body of magnetotactic bacteria has enormous promise as a natural material for tumor magnetic hyperthermia. In biomedical applications, intact and living magnetotactic bacteria play an increasingly essential function as a targeting robot due to their magnetotaxis.}, } @article {pmid35295942, year = {2022}, author = {Jiménez-Marín, B and Olson, BJSC}, title = {The Curious Case of Multicellularity in the Volvocine Algae.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {787665}, pmid = {35295942}, issn = {1664-8021}, abstract = {The evolution of multicellularity is a major evolutionary transition that underlies the radiation of many species in all domains of life, especially in eukaryotes. The volvocine green algae are an unconventional model system that holds great promise in the field given its genetic tractability, late transition to multicellularity, and phenotypic diversity. Multiple efforts at linking multicellularity-related developmental landmarks to key molecular changes, especially at the genome level, have provided key insights into the molecular innovations or lack thereof that underlie multicellularity. Twelve developmental changes have been proposed to explain the evolution of complex differentiated multicellularity in the volvocine algae. Co-option of key genes, such as cell cycle and developmental regulators has been observed, but with few exceptions, known co-option events do not seem to coincide with most developmental features observed in multicellular volvocines. The apparent lack of "master multicellularity genes" combined with no apparent correlation between gene gains for developmental processes suggest the possibility that many multicellular traits might be the product gene-regulatory and functional innovations; in other words, multicellularity can arise from shared genomic repertoires that undergo regulatory and functional overhauls.}, } @article {pmid35294281, year = {2022}, author = {Pichugin, Y and Traulsen, A}, title = {The possible modes of microbial reproduction are fundamentally restricted by distribution of mass between parent and offspring.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {12}, pages = {e2122197119}, pmid = {35294281}, issn = {1091-6490}, mesh = {*Bacteria ; *Reproduction ; }, abstract = {Multiple modes of asexual reproduction are observed among microbial organisms in natural populations. These modes are not only subject to evolution, but may drive evolutionary competition directly through their impact on population growth rates. The most prominent transition between two such modes is the one from unicellularity to multicellularity. We present a model of the evolution of reproduction modes, where a parent organism fragments into smaller parts. While the size of an organism at fragmentation, the number of offspring, and their sizes may vary a lot, the combined mass of fragments is limited by the mass of the parent organism. We found that mass conservation can fundamentally limit the number of possible reproduction modes. This has important direct implications for microbial life: For unicellular species, the interplay between cell shape and kinetics of the cell growth implies that the largest and the smallest possible cells should be rod shaped rather than spherical. For primitive multicellular species, these considerations can explain why rosette cell colonies evolved a mechanistically complex binary split reproduction. Finally, we show that the loss of organism mass during sporulation can explain the macroscopic sizes of the formally unicellular microorganism Myxomycetes plasmodium. Our findings demonstrate that a number of seemingly unconnected phenomena observed in unrelated species may be different manifestations of the same underlying process.}, } @article {pmid35287173, year = {2022}, author = {Benureau, FCY and Tani, J}, title = {Morphological Development at the Evolutionary Timescale: Robotic Developmental Evolution.}, journal = {Artificial life}, volume = {28}, number = {1}, pages = {3-21}, doi = {10.1162/artl_a_00357}, pmid = {35287173}, issn = {1530-9185}, mesh = {Algorithms ; Gait ; Learning ; Phylogeny ; *Robotics/methods ; }, abstract = {Evolution and development operate at different timescales; generations for the one, a lifetime for the other. These two processes, the basis of much of life on earth, interact in many non-trivial ways, but their temporal hierarchy-evolution overarching development-is observed for most multicellular life forms. When designing robots, however, this tenet lifts: It becomes-however natural-a design choice. We propose to inverse this temporal hierarchy and design a developmental process happening at the phylogenetic timescale. Over a classic evolutionary search aimed at finding good gaits for tentacle 2D robots, we add a developmental process over the robots' morphologies. Within a generation, the morphology of the robots does not change. But from one generation to the next, the morphology develops. Much like we become bigger, stronger, and heavier as we age, our robots are bigger, stronger, and heavier with each passing generation. Our robots start with baby morphologies, and a few thousand generations later, end-up with adult ones. We show that this produces better and qualitatively different gaits than an evolutionary search with only adult robots, and that it prevents premature convergence by fostering exploration. In addition, we validate our method on voxel lattice 3D robots from the literature and compare it to a recent evolutionary developmental approach. Our method is conceptually simple, and it can be effective on small or large populations of robots, and intrinsic to the robot and its morphology, not the task or environment. Furthermore, by recasting the evolutionary search as a learning process, these results can be viewed in the context of developmental learning robotics.}, } @article {pmid35251134, year = {2022}, author = {Palazzo, AF and Kejiou, NS}, title = {Non-Darwinian Molecular Biology.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {831068}, pmid = {35251134}, issn = {1664-8021}, abstract = {With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper "Non-Darwinian Evolution", where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura's new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.}, } @article {pmid35247708, year = {2022}, author = {Tong, K and Bozdag, GO and Ratcliff, WC}, title = {Selective drivers of simple multicellularity.}, journal = {Current opinion in microbiology}, volume = {67}, number = {}, pages = {102141}, doi = {10.1016/j.mib.2022.102141}, pmid = {35247708}, issn = {1879-0364}, mesh = {*Biological Evolution ; }, abstract = {In order to understand the evolution of multicellularity, we must understand how and why selection favors the first steps in this process: the evolution of simple multicellular groups. Multicellularity has evolved many times in independent lineages with fundamentally different ecologies, yet no work has yet systematically examined these diverse selective drivers. Here we review recent developments in systematics, comparative biology, paleontology, synthetic biology, theory, and experimental evolution, highlighting ten selective drivers of simple multicellularity. Our survey highlights the many ecological opportunities available for simple multicellularity, and stresses the need for additional work examining how these first steps impact the subsequent evolution of complex multicellularity.}, } @article {pmid35246710, year = {2022}, author = {Frenkel-Pinter, M and Petrov, AS and Matange, K and Travisano, M and Glass, JB and Williams, LD}, title = {Adaptation and Exaptation: From Small Molecules to Feathers.}, journal = {Journal of molecular evolution}, volume = {90}, number = {2}, pages = {166-175}, pmid = {35246710}, issn = {1432-1432}, support = {80NSSC18K1139/ImNASA/Intramural NASA/United States ; }, mesh = {Acclimatization ; *Adaptation, Physiological/genetics ; Animals ; Biological Evolution ; *Feathers ; }, abstract = {Evolution works by adaptation and exaptation. At an organismal level, exaptation and adaptation are seen in the formation of organelles and the advent of multicellularity. At the sub-organismal level, molecular systems such as proteins and RNAs readily undergo adaptation and exaptation. Here we suggest that the concepts of adaptation and exaptation are universal, synergistic, and recursive and apply to small molecules such as metabolites, cofactors, and the building blocks of extant polymers. For example, adenosine has been extensively adapted and exapted throughout biological evolution. Chemical variants of adenosine that are products of adaptation include 2' deoxyadenosine in DNA and a wide array of modified forms in mRNAs, tRNAs, rRNAs, and viral RNAs. Adenosine and its variants have been extensively exapted for various functions, including informational polymers (RNA, DNA), energy storage (ATP), metabolism (e.g., coenzyme A), and signaling (cyclic AMP). According to Gould, Vrba, and Darwin, exaptation imposes a general constraint on interpretation of history and origins; because of exaptation, extant function should not be used to explain evolutionary history. While this notion is accepted in evolutionary biology, it can also guide the study of the chemical origins of life. We propose that (i) evolutionary theory is broadly applicable from the dawn of life to the present time from molecules to organisms, (ii) exaptation and adaptation were important and simultaneous processes, and (iii) robust origin of life models can be constructed without conflating extant utility with historical basis of origins.}, } @article {pmid35246304, year = {2022}, author = {Li, XG and Jiao, ZX and Zhang, HH and Xu, J and Zhang, WJ and Qi, XQ and Wu, LF}, title = {Complete genome sequence of Crassaminicella sp. 143-21,isolated from a deep-sea hydrothermal vent.}, journal = {Marine genomics}, volume = {62}, number = {}, pages = {100899}, doi = {10.1016/j.margen.2021.100899}, pmid = {35246304}, issn = {1876-7478}, mesh = {Base Composition ; Clostridiaceae/genetics ; Genome, Bacterial ; *Hydrothermal Vents/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; }, abstract = {Crassaminicella sp. 143-21, a putative new species isolated from deep-sea hydrothermal vent chimney on the Central Indian Ridge (CIR), is an anaerobic, thermophilic and rod-shaped bacterium belonging to the family Clostridiaceae. In this study, we present the complete genome sequence of strain 143-21, comprising 2,756,133 bp with a G + C content of 31.1%. In total, 2427 protein coding genes, 121 tRNA genes and 33 rRNA genes were obtained. Genomic analysis of strain 143-21 revealed that numerous genes related to organic matter transport and catabolism, including peptide transport, amino acid transport, saccharide transport, ethanolamine transport and corresponding metabolic pathways. Further, the genome contains a large proportion of genes involved in translation, ribosomal structure, and signal transduction. These genes might facilitate microbial survival in deep-sea hydrothermal vent environment. The genome of strain 143-21 will be helpful for further understanding its adaptive strategies in the deep-sea hydrothermal vent environment.}, } @article {pmid35235070, year = {2022}, author = {Kwantes, M and Wichard, T}, title = {The APAF1_C/WD40 repeat domain-encoding gene from the sea lettuce Ulva mutabilis sheds light on the evolution of NB-ARC domain-containing proteins in green plants.}, journal = {Planta}, volume = {255}, number = {4}, pages = {76}, pmid = {35235070}, issn = {1432-2048}, mesh = {Ecosystem ; Phylogeny ; Plant Proteins/metabolism ; Proteins/genetics ; *Ulva/genetics ; WD40 Repeats ; }, abstract = {We advance Ulva's genetic tractability and highlight its value as a model organism by characterizing its APAF1_C/WD40 domain-encoding gene, which belongs to a family that bears homology to R genes. The multicellular chlorophyte alga Ulva mutabilis (Ulvophyceae, Ulvales) is native to coastal ecosystems worldwide and attracts both high socio-economic and scientific interest. To further understand the genetic mechanisms that guide its biology, we present a protocol, based on adapter ligation-mediated PCR, for retrieving flanking sequences in U. mutabilis vector-insertion mutants. In the created insertional library, we identified a null mutant with an insertion in an apoptotic protease activating factor 1 helical domain (APAF1_C)/WD40 repeat domain-encoding gene. Protein domain architecture analysis combined with phylogenetic analysis revealed that this gene is a member of a subfamily that arose early in the evolution of green plants (Viridiplantae) through the acquisition of a gene that also encoded N-terminal nucleotide-binding adaptor shared by APAF-1, certain R-gene products and CED-4 (NB-ARC) and winged helix-like (WH-like) DNA-binding domains. Although phenotypic analysis revealed no mutant phenotype, gene expression levels in control plants correlated to the presence of bacterial symbionts, which U. mutabilis requires for proper morphogenesis. In addition, our analysis led to the discovery of a putative Ulva nucleotide-binding site and leucine-rich repeat (NBS-LRR) Resistance protein (R-protein), and we discuss how the emergence of these R proteins in green plants may be linked to the evolution of the APAF1_C/WD40 protein subfamily.}, } @article {pmid35232276, year = {2022}, author = {Gao, Y and Pichugin, Y and Gokhale, CS and Traulsen, A}, title = {Evolution of reproductive strategies in incipient multicellularity.}, journal = {Journal of the Royal Society, Interface}, volume = {19}, number = {188}, pages = {20210716}, pmid = {35232276}, issn = {1742-5662}, mesh = {*Biological Evolution ; Cell Communication ; *Reproduction ; }, abstract = {Multicellular organisms potentially show a large degree of diversity in reproductive strategies, producing offspring with varying sizes and compositions compared to their unicellular ancestors. In reality, only a few of these reproductive strategies are prevalent. To understand why this could be the case, we develop a stage-structured population model to probe the evolutionary growth advantages of reproductive strategies in incipient multicellular organisms. The performance of reproductive strategies is evaluated by the growth rates of the corresponding populations. We identify the optimal reproductive strategy, leading to the largest growth rate for a population. Considering the effects of organism size and cellular interaction, we found that distinct reproductive strategies could perform uniquely or equally well under different conditions. If a single reproductive strategy is optimal, it is binary splitting, dividing into two parts. Our results show that organism size and cellular interaction can play crucial roles in shaping reproductive strategies in nascent multicellularity. Our model sheds light on understanding the mechanism driving the evolution of reproductive strategies in incipient multicellularity. Beyond multicellularity, our results imply that a crucial factor in the evolution of unicellular species' reproductive strategies is organism size.}, } @article {pmid35218347, year = {2022}, author = {Spang, A and Mahendrarajah, TA and Offre, P and Stairs, CW}, title = {Evolving Perspective on the Origin and Diversification of Cellular Life and the Virosphere.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35218347}, issn = {1759-6653}, mesh = {*Archaea ; Biological Evolution ; Eukaryota ; Phylogeny ; *Viruses/genetics ; }, abstract = {The tree of life (TOL) is a powerful framework to depict the evolutionary history of cellular organisms through time, from our microbial origins to the diversification of multicellular eukaryotes that shape the visible biosphere today. During the past decades, our perception of the TOL has fundamentally changed, in part, due to profound methodological advances, which allowed a more objective approach to studying organismal and viral diversity and led to the discovery of major new branches in the TOL as well as viral lineages. Phylogenetic and comparative genomics analyses of these data have, among others, revolutionized our understanding of the deep roots and diversity of microbial life, the origin of the eukaryotic cell, eukaryotic diversity, as well as the origin, and diversification of viruses. In this review, we provide an overview of some of the recent discoveries on the evolutionary history of cellular organisms and their viruses and discuss a variety of complementary techniques that we consider crucial for making further progress in our understanding of the TOL and its interconnection with the virosphere.}, } @article {pmid35215297, year = {2022}, author = {Ashoorzadeh, A and Mowday, AM and Guise, CP and Silva, S and Bull, MR and Abbattista, MR and Copp, JN and Williams, EM and Ackerley, DF and Patterson, AV and Smaill, JB}, title = {Interrogation of the Structure-Activity Relationship of a Lipophilic Nitroaromatic Prodrug Series Designed for Cancer Gene Therapy Applications.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, pmid = {35215297}, issn = {1424-8247}, abstract = {PR-104A is a dual hypoxia/nitroreductase gene therapy prodrug by virtue of its ability to undergo either one- or two-electron reduction to its cytotoxic species. It has been evaluated extensively in pre-clinical GDEPT studies, yet off-target human aldo-keto reductase AKR1C3-mediated activation has limited its use. Re-evaluation of this chemical scaffold has previously identified SN29176 as an improved hypoxia-activated prodrug analogue of PR-104A that is free from AKR1C3 activation. However, optimization of the bystander effect of SN29176 is required for use in a GDEPT setting to compensate for the non-uniform distribution of therapeutic gene transfer that is often observed with current gene therapy vectors. A lipophilic series of eight analogues were synthesized from commercially available 3,4-difluorobenzaldehyde. Calculated octanol-water partition coefficients (LogD7.4) spanned > 2 orders of magnitude. 2D anti-proliferative and 3D multicellular layer assays were performed using isogenic HCT116 cells expressing E. coli NfsA nitroreductase (NfsA_Ec) or AKR1C3 to determine enzyme activity and measure bystander effect. A variation in potency for NfsA_Ec was observed, while all prodrugs appeared AKR1C3-resistant by 2D assay. However, 3D assays indicated that increasing prodrug lipophilicity correlated with increased AKR1C3 activation and NfsA_Ec activity, suggesting that metabolite loss from the cell of origin into media during 2D monolayer assays could mask cytotoxicity. Three prodrugs were identified as bono fide AKR1C3-negative candidates whilst maintaining activity with NfsA_Ec. These were converted to their phosphate ester pre-prodrugs before being taken forward into in vivo therapeutic efficacy studies. Ultimately, 2-(5-(bis(2-bromoethyl)amino)-4-(ethylsulfonyl)-N-methyl-2-nitrobenzamido)ethyl dihydrogen phosphate possessed a significant 156% improvement in median survival in mixed NfsA_Ec/WT tumors compared to untreated controls (p = 0.005), whilst still maintaining hypoxia selectivity comparable to PR-104A.}, } @article {pmid35211015, year = {2022}, author = {Jackson-Patel, V and Liu, E and Bull, MR and Ashoorzadeh, A and Bogle, G and Wolfram, A and Hicks, KO and Smaill, JB and Patterson, AV}, title = {Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {803602}, pmid = {35211015}, issn = {1663-9812}, abstract = {Hypoxia-activated prodrugs are bioactivated in oxygen-deficient tumour regions and represent a novel strategy to exploit this pharmacological sanctuary for therapeutic gain. The approach relies on the selective metabolism of the prodrug under pathological hypoxia to generate active metabolites with the potential to diffuse throughout the tumour microenvironment and potentiate cell killing by means of a "bystander effect". In the present study, we investigate the pharmacological properties of the nitrogen mustard prodrug CP-506 in tumour tissues using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling. The approach employs a number of experimental model systems to define parameters for the cellular uptake, metabolism and diffusion of both the prodrug and its metabolites. The model predicts rapid uptake of CP-506 to high intracellular concentrations with its long plasma half-life driving tissue diffusion to a penetration depth of 190 µm, deep within hypoxic activating regions. While bioreductive metabolism is restricted to regions of severe pathological hypoxia (<1 µM O2), its active metabolites show substantial bystander potential with release from the cell of origin into the extracellular space. Model predictions of bystander efficiency were validated using spheroid co-cultures, where the clonogenic killing of metabolically defective "target" cells increased with the proportion of metabolically competent "activator" cells. Our simulations predict a striking bystander efficiency at tissue-like densities with the bis-chloro-mustard amine metabolite (CP-506M-Cl2) identified as a major diffusible metabolite. Overall, this study shows that CP-506 has favourable pharmacological properties in tumour tissue and supports its ongoing development for use in the treatment of patients with advanced solid malignancies.}, } @article {pmid35207574, year = {2022}, author = {Smith, D and Palacios-Pérez, M and Jheeta, S}, title = {The Enclosed Intestinal Microbiome: Semiochemical Signals from the Precambrian and Their Disruption by Heavy Metal Pollution.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207574}, issn = {2075-1729}, abstract = {It is increasingly likely that many non-communicable diseases of humans and associated animals are due to the degradation of their intestinal microbiomes, a situation often referred to as dysbiosis. An analysis of the resultant diseases offers an opportunity to probe the function of these microbial partners of multicellular animals. In our view, it now seems likely that vertebrate animals and their microbiomes have coevolved throughout the Ediacaran-Cambrian transition and beyond, operating by semiochemical messaging between the multicellular host and its microbial community guest. A consideration of the overall role of the mutualistic intestinal microbiome as an enclosed bioreactor throws up a variety of challenging concepts. In particular: the significance of the microbiome with respect to the immune system suggests that microeukaryotes could act as microbial sentinel cells; the ubiquity of bacteriophage viruses implies the rapid turnover of microbial composition by a viral-shunt mechanism; and high microbial diversity is needed to ensure that horizontal gene transfer allows valuable genetic functions to be expressed. We have previously postulated that microbes of sufficient diversity must be transferred from mother to infant by seemingly accidental contamination during the process of natural birth. We termed this maternal microbial inheritance and suggested that it operates alongside parental genetic inheritance to modify gene expression. In this way, the adjustment of the neonate immune system by the microbiome may represent one of the ways in which the genome of a vertebrate animal interacts with its microbial environment. The absence of such critical functions in the neonate may help to explain the observation of persistent immune-system problems in affected adults. Equally, granted that the survival of the guest microbiome depends on the viability of its host, one function of microbiome-generated semiochemicals could be to facilitate the movement of food through the digestive tract, effectively partitioning nutrition between host and guest. In the event of famine, downregulation of microbial growth and therefore of semiochemical production would allow all available food to be consumed by the host. Although it is often thought that non-communicable diseases, such as type 2 diabetes, are caused by consumption of food containing insufficient dietary fibre, our hypothesis suggests that poor-quality food is not the prime cause but that the tendency for disease follows the degradation of the intestinal microbiome, when fat build-up occurs because the relevant semiochemicals can no longer be produced. It is the purpose of this paper to highlight the possibility that the origins of the microbiome lie in the Precambrian and that the disconnection of body and microbiome gives rise to non-communicable disease through the loss of semiochemical signalling. We further surmise that this disconnect has been largely brought about by heavy metal poisoning, potentially illuminating a facet of the exposome, the sum total of environmental insults that influence the expression of the genetic inheritance of an animal.}, } @article {pmid35205423, year = {2022}, author = {Alfieri, JM and Wang, G and Jonika, MM and Gill, CA and Blackmon, H and Athrey, GN}, title = {A Primer for Single-Cell Sequencing in Non-Model Organisms.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205423}, issn = {2073-4425}, support = {R35 GM138098/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genotype ; *Phenotype ; }, abstract = {Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation.}, } @article {pmid35194081, year = {2022}, author = {Lin, HK and Cheng, JH and Wu, CC and Hsieh, FS and Dunlap, C and Chen, SH}, title = {Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2974}, pmid = {35194081}, issn = {2045-2322}, mesh = {*Databases, Nucleic Acid ; *Gene Expression Regulation, Neoplastic ; *Homeostasis ; Humans ; *Neoplasms/genetics/metabolism ; Organ Specificity ; }, abstract = {Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.}, } @article {pmid35189700, year = {2022}, author = {Simon-Soro, A and Ren, Z and Krom, BP and Hoogenkamp, MA and Cabello-Yeves, PJ and Daniel, SG and Bittinger, K and Tomas, I and Koo, H and Mira, A}, title = {Polymicrobial Aggregates in Human Saliva Build the Oral Biofilm.}, journal = {mBio}, volume = {13}, number = {1}, pages = {e0013122}, pmid = {35189700}, issn = {2150-7511}, support = {R01 DE025220/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria ; Biofilms ; *Ecosystem ; Humans ; Phylogeny ; *Saliva/microbiology ; }, abstract = {Biofilm community development has been established as a sequential process starting from the attachment of single cells on a surface. However, microorganisms are often found as aggregates in the environment and in biological fluids. Here, we conduct a comprehensive analysis of the native structure and composition of aggregated microbial assemblages in human saliva and investigate their spatiotemporal attachment and biofilm community development. Using multiscale imaging, cell sorting, and computational approaches combined with sequencing analysis, a diverse mixture of aggregates varying in size, structure, and microbial composition, including bacteria associated with host epithelial cells, can be found in saliva in addition to a few single-cell forms. Phylogenetic analysis reveals a mixture of complex consortia of aerobes and anaerobes in which bacteria traditionally considered early and late colonizers are found mixed together. When individually tracked during colonization and biofilm initiation, aggregates rapidly proliferate and expand tridimensionally, modulating population growth, spatial organization, and community scaffolding. In contrast, most single cells remain static or are incorporated by actively growing aggregates. These results suggest an alternative biofilm development process whereby aggregates containing different species or associated with human cells collectively adhere to the surface as "growth nuclei" to build the biofilm and shape polymicrobial communities at various spatial and taxonomic scales. IMPORTANCE Microbes in biological fluids can be found as aggregates. How these multicellular structures bind to surfaces and initiate the biofilm life cycle remains understudied. Here, we investigate the structural organization of microbial aggregates in human saliva and their role in biofilm formation. We found diverse mixtures of aggregates with different sizes, structures, and compositions in addition to free-living cells. When individually tracked during binding and growth on tooth-like surfaces, most aggregates developed into structured biofilm communities, whereas most single cells remained static or were engulfed by the growing aggregates. Our results reveal that preformed microbial consortia adhere as "buds of growth," governing biofilm initiation without specific taxonomic order or cell-by-cell succession, which provide new insights into spatial and population heterogeneity development in complex ecosystems.}, } @article {pmid35188101, year = {2022}, author = {Day, TC and Höhn, SS and Zamani-Dahaj, SA and Yanni, D and Burnetti, A and Pentz, J and Honerkamp-Smith, AR and Wioland, H and Sleath, HR and Ratcliff, WC and Goldstein, RE and Yunker, PJ}, title = {Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188101}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Size ; *Directed Molecular Evolution ; Phylogeny ; Volvox/cytology/*genetics/physiology ; Yeasts/cytology/*genetics/physiology ; }, abstract = {The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved 'snowflake' yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.}, } @article {pmid35186015, year = {2021}, author = {Zeng, Q and Liu, H and Chu, X and Niu, Y and Wang, C and Markov, GV and Teng, L}, title = {Independent Evolution of the MYB Family in Brown Algae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {811993}, pmid = {35186015}, issn = {1664-8021}, abstract = {Myeloblastosis (MYB) proteins represent one of the largest families of eukaryotic transcription factors and regulate important processes in growth and development. Studies on MYBs have mainly focused on animals and plants; however, comprehensive analysis across other supergroups such as SAR (stramenopiles, alveolates, and rhizarians) is lacking. This study characterized the structure, evolution, and expression of MYBs in four brown algae, which comprise the biggest multicellular lineage of SAR. Subfamily 1R-MYB comprised heterogeneous proteins, with fewer conserved motifs found outside the MYB domain. Unlike the SHAQKY subgroup of plant 1R-MYB, THAQKY comprised the largest subgroup of brown algal 1R-MYBs. Unlike the expansion of 2R-MYBs in plants, brown algae harbored more 3R-MYBs than 2R-MYBs. At least ten 2R-MYBs, fifteen 3R-MYBs, and one 6R-MYB orthologs existed in the common ancestor of brown algae. Phylogenetic analysis showed that brown algal MYBs had ancient origins and a diverged evolution. They showed strong affinity with stramenopile species, while not with red algae, green algae, or animals, suggesting that brown algal MYBs did not come from the secondary endosymbiosis of red and green plastids. Sequence comparison among all repeats of the three types of MYB subfamilies revealed that the repeat of 1R-MYBs showed higher sequence identity with the R3 of 2R-MYBs and 3R-MYBs, which supports the idea that 1R-MYB was derived from loss of the first and second repeats of the ancestor MYB. Compared with other species of SAR, brown algal MYB proteins exhibited a higher proportion of intrinsic disordered regions, which might contribute to multicellular evolution. Expression analysis showed that many MYB genes are responsive to different stress conditions and developmental stages. The evolution and expression analyses provided a comprehensive analysis of the phylogeny and functions of MYBs in brown algae.}, } @article {pmid35175900, year = {2022}, author = {Milocco, L and Salazar-Ciudad, I}, title = {Evolution of the G Matrix under Nonlinear Genotype-Phenotype Maps.}, journal = {The American naturalist}, volume = {199}, number = {3}, pages = {420-435}, doi = {10.1086/717814}, pmid = {35175900}, issn = {1537-5323}, mesh = {*Biological Evolution ; Evolution, Molecular ; Genetic Variation ; *Genetics, Population ; Genotype ; Models, Genetic ; Phenotype ; Selection, Genetic ; }, abstract = {AbstractThe G matrix is a statistical summary of the genetic basis of a set of traits and a central pillar of quantitative genetics. A persistent controversy is whether G changes slowly or quickly over time. The evolution of G is important because it affects the ability to predict, or reconstruct, evolution by selection. Empirical studies have found mixed results on how fast G evolves. Theoretical work has largely been developed under the assumption that the relationship between genetic variation and phenotypic variation-the genotype-phenotype map (GPM)-is linear. Under this assumption, G is expected to remain constant over long periods of time. However, according to developmental biology, the GPM is typically complex and nonlinear. Here, we use a GPM model based on the development of a multicellular organ to study how G evolves. We find that G can change relatively fast and in qualitative different ways, which we describe in detail. Changes can be particularly large when the population crosses between regions of the GPM that have different properties. This can result in the additive genetic variance in the direction of selection fluctuating over time and even increasing despite the eroding effect of selection.}, } @article {pmid35170314, year = {2022}, author = {Kulkarni, P and Bhattacharya, S and Achuthan, S and Behal, A and Jolly, MK and Kotnala, S and Mohanty, A and Rangarajan, G and Salgia, R and Uversky, V}, title = {Intrinsically Disordered Proteins: Critical Components of the Wetware.}, journal = {Chemical reviews}, volume = {122}, number = {6}, pages = {6614-6633}, pmid = {35170314}, issn = {1520-6890}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; }, mesh = {*Intrinsically Disordered Proteins/chemistry ; Organelles/chemistry ; Protein Conformation ; Protein Interaction Maps ; }, abstract = {Despite the wealth of knowledge gained about intrinsically disordered proteins (IDPs) since their discovery, there are several aspects that remain unexplored and, hence, poorly understood. A living cell is a complex adaptive system that can be described as a wetware─a metaphor used to describe the cell as a computer comprising both hardware and software and attuned to logic gates─capable of "making" decisions. In this focused Review, we discuss how IDPs, as critical components of the wetware, influence cell-fate decisions by wiring protein interaction networks to keep them minimally frustrated. Because IDPs lie between order and chaos, we explore the possibility that they can be modeled as attractors. Further, we discuss how the conformational dynamics of IDPs manifests itself as conformational noise, which can potentially amplify transcriptional noise to stochastically switch cellular phenotypes. Finally, we explore the potential role of IDPs in prebiotic evolution, in forming proteinaceous membrane-less organelles, in the origin of multicellularity, and in protein conformation-based transgenerational inheritance of acquired characteristics. Together, these ideas provide a new conceptual framework to discern how IDPs may perform critical biological functions despite their lack of structure.}, } @article {pmid35167804, year = {2022}, author = {Davis, JR and Ainslie, AP and Williamson, JJ and Ferreira, A and Torres-Sánchez, A and Hoppe, A and Mangione, F and Smith, MB and Martin-Blanco, E and Salbreux, G and Tapon, N}, title = {ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit.}, journal = {Current biology : CB}, volume = {32}, number = {6}, pages = {1285-1300.e4}, pmid = {35167804}, issn = {1879-0445}, support = {FC001175/MRC_/Medical Research Council/United Kingdom ; FC001317/WT_/Wellcome Trust/United Kingdom ; 107885/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; FC001175/WT_/Wellcome Trust/United Kingdom ; FC001175/ARC_/Arthritis Research UK/United Kingdom ; FC001317/ARC_/Arthritis Research UK/United Kingdom ; FC001317/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001317/MRC_/Medical Research Council/United Kingdom ; FC001175/CRUK_/Cancer Research UK/United Kingdom ; 201358/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle ; Cell Division ; *Drosophila ; *Epidermal Cells ; Epidermis ; Mice ; }, abstract = {During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.}, } @article {pmid35159213, year = {2022}, author = {Ribba, AS and Fraboulet, S and Sadoul, K and Lafanechère, L}, title = {The Role of LIM Kinases during Development: A Lens to Get a Glimpse of Their Implication in Pathologies.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159213}, issn = {2073-4409}, mesh = {Actin Depolymerizing Factors/metabolism ; Animals ; *Lim Kinases/metabolism ; Phosphorylation ; Phylogeny ; *Protein Kinases/metabolism ; }, abstract = {The organization of cell populations within animal tissues is essential for the morphogenesis of organs during development. Cells recognize three-dimensional positions with respect to the whole organism and regulate their cell shape, motility, migration, polarization, growth, differentiation, gene expression and cell death according to extracellular signals. Remodeling of the actin filaments is essential to achieve these cell morphological changes. Cofilin is an important binding protein for these filaments; it increases their elasticity in terms of flexion and torsion and also severs them. The activity of cofilin is spatiotemporally inhibited via phosphorylation by the LIM domain kinases 1 and 2 (LIMK1 and LIMK2). Phylogenetic analysis indicates that the phospho-regulation of cofilin has evolved as a mechanism controlling the reorganization of the actin cytoskeleton during complex multicellular processes, such as those that occur during embryogenesis. In this context, the main objective of this review is to provide an update of the respective role of each of the LIM kinases during embryonic development.}, } @article {pmid35154170, year = {2021}, author = {Žárský, J and Žárský, V and Hanáček, M and Žárský, V}, title = {Cryogenian Glacial Habitats as a Plant Terrestrialisation Cradle - The Origin of the Anydrophytes and Zygnematophyceae Split.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {735020}, pmid = {35154170}, issn = {1664-462X}, abstract = {For tens of millions of years (Ma), the terrestrial habitats of Snowball Earth during the Cryogenian period (between 720 and 635 Ma before present-Neoproterozoic Era) were possibly dominated by global snow and ice cover up to the equatorial sublimative desert. The most recent time-calibrated phylogenies calibrated not only on plants but on a comprehensive set of eukaryotes indicate that within the Streptophyta, multicellular charophytes (Phragmoplastophyta) evolved in the Mesoproterozoic to the early Neoproterozoic. At the same time, Cryogenian is the time of the likely origin of the common ancestor of Zygnematophyceae and Embryophyta and later, also of the Zygnematophyceae-Embryophyta split. This common ancestor is proposed to be called Anydrophyta; here, we use anydrophytes. Based on the combination of published phylogenomic studies and estimated diversification time comparisons, we deem it highly likely that anydrophytes evolved in response to Cryogenian cooling. Also, later in the Cryogenian, secondary simplification of multicellular anydrophytes and loss of flagella resulted in Zygnematophyceae diversification as an adaptation to the extended cold glacial environment. We propose that the Marinoan geochemically documented expansion of first terrestrial flora has been represented not only by Chlorophyta but also by Streptophyta, including the anydrophytes, and later by Zygnematophyceae, thriving on glacial surfaces until today. It is possible that multicellular early Embryophyta survived in less abundant (possibly relatively warmer) refugia, relying more on mineral substrates, allowing the retention of flagella-based sexuality. The loss of flagella and sexual reproduction by conjugation evolved in Zygnematophyceae and zygomycetous fungi during the Cryogenian in a remarkably convergent way. Thus, we support the concept that the important basal cellular adaptations to terrestrial environments were exapted in streptophyte algae for terrestrialization and propose that this was stimulated by the adaptation to glacial habitats dominating the Cryogenian Snowball Earth. Including the glacial lifestyle when considering the rise of land plants increases the parsimony of connecting different ecological, phylogenetic, and physiological puzzles of the journey from aquatic algae to terrestrial floras.}, } @article {pmid35143662, year = {2022}, author = {Benzerara, K and Duprat, E and Bitard-Feildel, T and Caumes, G and Cassier-Chauvat, C and Chauvat, F and Dezi, M and Diop, SI and Gaschignard, G and Görgen, S and Gugger, M and López-García, P and Millet, M and Skouri-Panet, F and Moreira, D and Callebaut, I}, title = {A New Gene Family Diagnostic for Intracellular Biomineralization of Amorphous Ca Carbonates by Cyanobacteria.}, journal = {Genome biology and evolution}, volume = {14}, number = {3}, pages = {}, pmid = {35143662}, issn = {1759-6653}, mesh = {*Biomineralization/genetics ; Calcium Carbonate/metabolism ; Carbonates/metabolism ; *Cyanobacteria/metabolism ; Phylogeny ; }, abstract = {Cyanobacteria have massively contributed to carbonate deposition over the geological history. They are traditionally thought to biomineralize CaCO3 extracellularly as an indirect byproduct of photosynthesis. However, the recent discovery of freshwater cyanobacteria-forming intracellular amorphous calcium carbonates (iACC) challenges this view. Despite the geochemical interest of such a biomineralization process, its molecular mechanisms and evolutionary history remain elusive. Here, using comparative genomics, we identify a new gene (ccyA) and protein family (calcyanin) possibly associated with cyanobacterial iACC biomineralization. Proteins of the calcyanin family are composed of a conserved C-terminal domain, which likely adopts an original fold, and a variable N-terminal domain whose structure allows differentiating four major types among the 35 known calcyanin homologs. Calcyanin lacks detectable full-length homologs with known function. The overexpression of ccyA in iACC-lacking cyanobacteria resulted in an increased intracellular Ca content. Moreover, ccyA presence was correlated and/or colocalized with genes involved in Ca or HCO3- transport and homeostasis, supporting the hypothesis of a functional role of calcyanin in iACC biomineralization. Whatever its function, ccyA appears as diagnostic of intracellular calcification in cyanobacteria. By searching for ccyA in publicly available genomes, we identified 13 additional cyanobacterial strains forming iACC, as confirmed by microscopy. This extends our knowledge about the phylogenetic and environmental distribution of cyanobacterial iACC biomineralization, especially with the detection of multicellular genera as well as a marine species. Moreover, ccyA was probably present in ancient cyanobacteria, with independent losses in various lineages that resulted in a broad but patchy distribution across modern cyanobacteria.}, } @article {pmid35143488, year = {2022}, author = {Yaguchi, S and Taniguchi, Y and Suzuki, H and Kamata, M and Yaguchi, J}, title = {Planktonic sea urchin larvae change their swimming direction in response to strong photoirradiation.}, journal = {PLoS genetics}, volume = {18}, number = {2}, pages = {e1010033}, pmid = {35143488}, issn = {1553-7404}, mesh = {Animals ; Cilia/metabolism ; Larva/metabolism ; Light ; Locomotion/physiology ; Movement/*physiology ; Muscles/physiology ; Opsins/genetics/metabolism ; Photoreceptor Cells/*metabolism ; Plankton ; Sea Urchins/*metabolism ; }, abstract = {To survive, organisms need to precisely respond to various environmental factors, such as light and gravity. Among these, light is so important for most life on Earth that light-response systems have become extraordinarily developed during evolution, especially in multicellular animals. A combination of photoreceptors, nervous system components, and effectors allows these animals to respond to light stimuli. In most macroscopic animals, muscles function as effectors responding to light, and in some microscopic aquatic animals, cilia play a role. It is likely that the cilia-based response was the first to develop and that it has been substituted by the muscle-based response along with increases in body size. However, although the function of muscle appears prominent, it is poorly understood whether ciliary responses to light are present and/or functional, especially in deuterostomes, because it is possible that these responses are too subtle to be observed, unlike muscle responses. Here, we show that planktonic sea urchin larvae reverse their swimming direction due to the inhibitory effect of light on the cholinergic neuron signaling>forward swimming pathway. We found that strong photoirradiation of larvae that stay on the surface of seawater immediately drives the larvae away from the surface due to backward swimming. When Opsin2, which is expressed in mesenchymal cells in larval arms, is knocked down, the larvae do not show backward swimming under photoirradiation. Although Opsin2-expressing cells are not neuronal cells, immunohistochemical analysis revealed that they directly attach to cholinergic neurons, which are thought to regulate forward swimming. These data indicate that light, through Opsin2, inhibits the activity of cholinergic signaling, which normally promotes larval forward swimming, and that the light-dependent ciliary response is present in deuterostomes. These findings shed light on how light-responsive tissues/organelles have been conserved and diversified during evolution.}, } @article {pmid35135345, year = {2022}, author = {La Richelière, F and Muñoz, G and Guénard, B and Dunn, RR and Economo, EP and Powell, S and Sanders, NJ and Weiser, MD and Abouheif, E and Lessard, JP}, title = {Warm and arid regions of the world are hotspots of superorganism complexity.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20211899}, pmid = {35135345}, issn = {1471-2954}, mesh = {Animals ; *Ants/genetics ; Desert Climate ; Neurons ; Phenotype ; }, abstract = {Biologists have long been fascinated by the processes that give rise to phenotypic complexity of organisms, yet whether there exist geographical hotspots of phenotypic complexity remains poorly explored. Phenotypic complexity can be readily observed in ant colonies, which are superorganisms with morphologically differentiated queen and worker castes analogous to the germline and soma of multicellular organisms. Several ant species have evolved 'worker polymorphism', where workers in a single colony show quantifiable differences in size and head-to-body scaling. Here, we use 256 754 occurrence points from 8990 ant species to investigate the geography of worker polymorphism. We show that arid regions of the world are the hotspots of superorganism complexity. Tropical savannahs and deserts, which are typically species-poor relative to tropical or even temperate forests, harbour the highest densities of polymorphic ants. We discuss the possible adaptive advantages that worker polymorphism provides in arid environments. Our work may provide a window into the environmental conditions that promote the emergence of highly complex phenotypes.}, } @article {pmid35107212, year = {2023}, author = {Nishizawa, H and Yamanaka, M and Igarashi, K}, title = {Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal.}, journal = {The FEBS journal}, volume = {290}, number = {7}, pages = {1688-1704}, doi = {10.1111/febs.16382}, pmid = {35107212}, issn = {1742-4658}, mesh = {Humans ; Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; *Ferroptosis/genetics ; Iron/metabolism ; *Neoplasms ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; }, abstract = {Ferroptosis is triggered by a chain of intracellular labile iron-dependent peroxidation of cell membrane phospholipids. Ferroptosis is important not only as a cause of ischaemic and neurodegenerative diseases but also as a mechanism of cancer suppression, and a better understanding of its regulatory mechanism is required. It has become clear that ferroptosis is finely controlled by two oxidative stress-responsive transcription factors, NRF2 (NF-E2-related factor 2) and BACH1 (BTB and CNC homology 1). NRF2 and BACH1 inhibit and promote ferroptosis, respectively, by activating or suppressing the expression of genes in the major regulatory pathways of ferroptosis: intracellular labile iron metabolism, the GSH (glutathione) -GPX4 (glutathione peroxidase 4) pathway and the FSP1 (ferroptosis suppressor protein 1)-CoQ (coenzyme Q) pathway. In addition to this, NRF2 and BACH1 control ferroptosis through the regulation of lipid metabolism and cell differentiation. This multifaceted regulation of ferroptosis by NRF2 and BACH1 is considered to have been acquired during the evolution of multicellular organisms, allowing the utilization of ferroptosis for maintaining homeostasis, including cancer suppression. In terms of cell-cell interaction, it has been revealed that ferroptosis has the property of propagating to surrounding cells along with lipid peroxidation. The regulation of ferroptosis by NRF2 and BACH1 and the propagation phenomenon could be used to realize anticancer cell therapy in the future. In this review, these points will be summarized and discussed.}, } @article {pmid35078543, year = {2022}, author = {Purschke, G and Vodopyanov, S and Baller, A and von Palubitzki, T and Bartolomaeus, T and Beckers, P}, title = {Ultrastructure of cerebral eyes in Oweniidae and Chaetopteridae (Annelida) - implications for the evolution of eyes in Annelida.}, journal = {Zoological letters}, volume = {8}, number = {1}, pages = {3}, pmid = {35078543}, issn = {2056-306X}, abstract = {BACKGROUND: Recent phylogenomic studies have revealed a robust, new hypothesis of annelid phylogeny. Most surprisingly, a few early branching lineages formed a basal grade, whereas the majority of taxa were categorized as monophyletic Pleistoannelida. Members of these basal groups show a comparatively simple organization lacking certain characters regarded to be annelid specific. Thus, the evolution of organ systems and the characteristics probably present in the last common annelid ancestor require reevaluation. With respect to light-sensitive organs, a pair of simple larval eyes is regarded as being present in their last common ancestor. However, the evolutionary origin and structure of adult eyes remain obscure. Typically, adult eyes are multicellular pigment cups or pinhole eyes with or without a lens comprising rhabdomeric photoreceptor cells (PRCs) and pigmented supportive cells (PSCs) in converse design. However, in the most basal lineages, eyes are only present in a few taxa, and thus far, their ultrastructure is unknown.

RESULTS: Ultrastructural investigations of members of Oweniidae and Chaetopteridae reveal a corresponding design of adult cerebral eyes and PRCs. The eyes in species of these groups are simple pigment spot eyes, either forming a flat patch or embedded in a tube-like invagination. They are part of the epidermis and comprise two cell types, PSCs and rhabdomeric PRCs. Both cell types bear microvilli and one more or less reduced cilium. However, the PRCs showed only a moderate increase in the apical membrane surface in the form of irregularly arranged microvilli intermingling with those of the PSCs; a densely arranged brush border of rhabdomeric microvilli was absent. Additionally, both cell types show certain characteristics elsewhere observable in typical epidermal supportive cells.

CONCLUSIONS: These findings shed new light on the evolutionary history of adult eyes in Annelida. Most likely, the adult eye of the annelid stem species was a pair of simple pigment spot eyes with only slightly specialized PSCs and PRCs being an integrative part of the epidermis. As is the case for the nuchal organs, typical pigment cup adult eyes presumably evolved later in the annelid phylogeny, namely, in the stem lineages of Amphinomida and Pleistoannelida.}, } @article {pmid35056939, year = {2021}, author = {Shipunova, VO and Kovalenko, VL and Kotelnikova, PA and Sogomonyan, AS and Shilova, ON and Komedchikova, EN and Zvyagin, AV and Nikitin, MP and Deyev, SM}, title = {Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers' Performance In Vitro and In Vivo.}, journal = {Pharmaceutics}, volume = {14}, number = {1}, pages = {}, pmid = {35056939}, issn = {1999-4923}, abstract = {The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial-mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.}, } @article {pmid35054440, year = {2021}, author = {Alekseev, VR and Hwang, JS and Levinskikh, MA}, title = {Effect of Space Flight Factor on Dormant Stages in Aquatic Organisms: A Review of International Space Station and Terrestrial Experiments.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054440}, issn = {2075-1729}, abstract = {This work is a review of the experiments carried out in the Russian segment of the ISS (inside and outside) from 2005 to 2016 on the effect of the space flight factor on the resting stages of organisms. In outer space, ultraviolet, a wide range of high and low temperatures, cosmic radiation, altered gravity, modified electromagnetic field, vacuum, factors of technical origin, ultrasound, microwave radiation, etc. and their combination determine the damaging effect on living organisms. At the same time, biological dormancy, known in a wide range of bacteria, fungi, animals and plants, allows them to maintain the viability of their dormant stages in extreme conditions for a long time, which possibly allows them to survive during space flight. From 2005 to 2016, the resting stages (propagules) of micro- and multicellular organisms were tested on the ISS to assess their ability to survive after prolonged exposure to the conditions of open space and space flight. Among the more than 40 species studied, about a third were dormant stages of aquatic organisms (eggs of cyprinodont fish, daphnia embryos, resting eggs of fairy shrimps, tadpole shrimps, copepods and ostracods, diapausing larvae of dipterans, as well as resting cysts of algae). The experiments were carried out within the framework of four research programs: (1) inside the ISS with a limited set of investigated species (Akvarium program); (2) outside the station in outer space without exposure to ultraviolet radiation (Biorisk program); (3) under modified space conditions simulating the surface of Mars (Expose program); and (4) in an Earth-based laboratory where single-factor experiments were carried out with neutron radiation, modified magnetic field, microwave radiation and ultrasound. Fundamentally new data were obtained on the stability of the resting stages of aquatic organisms exposed to the factors of the space environment, which modified the idea of the possibility of bringing Earth life forms to other planets with spacecraft and astronauts. It also can be used for creating an extraterrestrial artificial ecosystem and searching for extraterrestrial life.}, } @article {pmid35053310, year = {2022}, author = {Shevyrev, D and Tereshchenko, V and Kozlov, V and Sennikov, S}, title = {Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets.}, journal = {Cells}, volume = {11}, number = {2}, pages = {}, pmid = {35053310}, issn = {2073-4409}, mesh = {Evolution, Molecular ; Humans ; Peptides/metabolism ; *Phylogeny ; T-Lymphocyte Subsets/*metabolism ; Transcription Factors/*chemistry/classification/*metabolism ; Transcriptome/genetics ; }, abstract = {It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the "calibration" of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.}, } @article {pmid35051729, year = {2022}, author = {Masqué-Soler, N and Gehrung, M and Kosmidou, C and Li, X and Diwan, I and Rafferty, C and Atabakhsh, E and Markowetz, F and Fitzgerald, RC}, title = {Computational pathology aids derivation of microRNA biomarker signals from Cytosponge samples.}, journal = {EBioMedicine}, volume = {76}, number = {}, pages = {103814}, pmid = {35051729}, issn = {2352-3964}, support = {MR/W014122/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Artificial Intelligence ; *Barrett Esophagus/genetics ; Biomarkers/metabolism ; Cross-Sectional Studies ; *Esophageal Neoplasms/diagnosis/genetics/pathology ; Humans ; *MicroRNAs/genetics ; }, abstract = {BACKGROUND: Non-endoscopic cell collection devices combined with biomarkers can detect Barrett's intestinal metaplasia and early oesophageal cancer. However, assays performed on multi-cellular samples lose information about the cell source of the biomarker signal. This cross-sectional study examines whether a bespoke artificial intelligence-based computational pathology tool could ascertain the cellular origin of microRNA biomarkers, to inform interpretation of the disease pathology, and confirm biomarker validity.

METHODS: The microRNA expression profiles of 110 targets were assessed with a custom multiplexed panel in a cohort of 117 individuals with reflux that took a Cytosponge test. A computational pathology tool quantified the amount of columnar epithelium present in pathology slides, and results were correlated with microRNA signals. An independent cohort of 139 Cytosponges, each from an individual patient, was used to validate the findings via qPCR.

FINDINGS: Seventeen microRNAs are upregulated in BE compared to healthy squamous epithelia, of which 13 remain upregulated in dysplasia. A pathway enrichment analysis confirmed association to neoplastic and cell cycle regulation processes. Ten microRNAs positively correlated with columnar epithelium content, with miRNA-192-5p and -194-5p accurately detecting the presence of gastric cells (AUC 0.97 and 0.95). In contrast, miR-196a-5p is confirmed as a specific BE marker.

INTERPRETATION: Computational pathology tools aid accurate cellular attribution of molecular signals. This innovative design with multiplex microRNA coupled with artificial intelligence has led to discovery of a quality control metric suitable for large scale application of the Cytosponge. Similar approaches could aid optimal interpretation of biomarkers for clinical use.

FUNDING: Funded by the NIHR Cambridge Biomedical Research Centre, the Medical Research Council, the Rosetrees and Stoneygate Trusts, and CRUK core grants.}, } @article {pmid35032334, year = {2022}, author = {Nemec-Venza, Z and Madden, C and Stewart, A and Liu, W and Novák, O and Pěnčík, A and Cuming, AC and Kamisugi, Y and Harrison, CJ}, title = {CLAVATA modulates auxin homeostasis and transport to regulate stem cell identity and plant shape in a moss.}, journal = {The New phytologist}, volume = {234}, number = {1}, pages = {149-163}, pmid = {35032334}, issn = {1469-8137}, mesh = {*Arabidopsis Proteins/genetics/metabolism ; *Bryophyta/metabolism ; *Bryopsida/genetics/metabolism ; Gene Expression Regulation, Plant ; Homeostasis ; Indoleacetic Acids/metabolism ; Stem Cells/metabolism ; }, abstract = {The CLAVATA pathway is a key regulator of stem cell function in the multicellular shoot tips of Arabidopsis, where it acts via the WUSCHEL transcription factor to modulate hormone homeostasis. Broad-scale evolutionary comparisons have shown that CLAVATA is a conserved regulator of land plant stem cell function, but CLAVATA acts independently of WUSCHEL-like (WOX) proteins in bryophytes. The relationship between CLAVATA, hormone homeostasis and the evolution of land plant stem cell functions is unknown. Here we show that in the moss, Physcomitrella (Physcomitrium patens), CLAVATA affects stem cell activity by modulating hormone homeostasis. CLAVATA pathway genes are expressed in the tip cells of filamentous tissues, regulating cell identity, filament branching, plant spread and auxin synthesis. The receptor-like kinase PpRPK2 plays the major role, and Pprpk2 mutants have abnormal responses to cytokinin, auxin and auxin transport inhibition, and show reduced expression of PIN auxin transporters. We propose a model whereby PpRPK2 modulates auxin gradients in filaments to determine stem cell identity and overall plant form. Our data indicate that CLAVATA-mediated auxin homeostasis is a fundamental property of plant stem cell function, probably exhibited by the last shared common ancestor of land plants.}, } @article {pmid35023778, year = {2022}, author = {Ji, R and Zhang, W and Pan, Y and Lin, W}, title = {MagCluster: a Tool for Identification, Annotation, and Visualization of Magnetosome Gene Clusters.}, journal = {Microbiology resource announcements}, volume = {11}, number = {1}, pages = {e0103121}, pmid = {35023778}, issn = {2576-098X}, abstract = {Magnetosome gene clusters (MGCs), which are responsible for magnetosome biosynthesis and organization in magnetotactic bacteria (MTB), are the key to deciphering the mechanisms and evolutionary origin of magnetoreception, organelle biogenesis, and intracellular biomineralization in bacteria. Here, we report the development of MagCluster, a Python stand-alone tool for efficient exploration of MGCs from large-scale (meta)genomic data.}, } @article {pmid35018470, year = {2022}, author = {von der Heyde, EL and Hallmann, A}, title = {Molecular and cellular dynamics of early embryonic cell divisions in Volvox carteri.}, journal = {The Plant cell}, volume = {34}, number = {4}, pages = {1326-1353}, pmid = {35018470}, issn = {1532-298X}, mesh = {Animals ; Cell Division/genetics ; *Volvox/genetics ; }, abstract = {Cell division is fundamental to all organisms and the green alga used here exhibits both key animal and plant functions. Specifically, we analyzed the molecular and cellular dynamics of early embryonic divisions of the multicellular green alga Volvox carteri (Chlamydomonadales). Relevant proteins related to mitosis and cytokinesis were identified in silico, the corresponding genes were cloned, fused to yfp, and stably expressed in Volvox, and the tagged proteins were studied by live-cell imaging. We reveal rearrangements of the microtubule cytoskeleton during centrosome separation, spindle formation, establishment of the phycoplast, and generation of previously unknown structures. The centrosomes participate in initiation of spindle formation and determination of spindle orientation. Although the nuclear envelope does not break down during early mitosis, intermixing of cytoplasm and nucleoplasm results in loss of nuclear identity. Finally, we present a model for mitosis in Volvox. Our study reveals enormous dynamics, clarifies spatio-temporal relationships of subcellular structures, and provides insight into the evolution of cell division.}, } @article {pmid35014399, year = {2021}, author = {Klein, S and Distel, LVR and Neuhuber, W}, title = {X-ray Dose-Enhancing Impact of Functionalized Au-Fe3O4 Nanoheterodimers on MCF-7 and A549 Multicellular Tumor Spheroids.}, journal = {ACS applied bio materials}, volume = {4}, number = {4}, pages = {3113-3123}, doi = {10.1021/acsabm.0c01494}, pmid = {35014399}, issn = {2576-6422}, mesh = {Biocompatible Materials/chemistry/*pharmacology ; Cell Survival/drug effects ; Ferric Compounds/chemistry/*pharmacology ; Gold/chemistry/*pharmacology ; Humans ; MCF-7 Cells ; Materials Testing ; Nanoparticles/*chemistry ; Particle Size ; Spheroids, Cellular/*drug effects ; *X-Rays ; }, abstract = {The efficiency of nanoparticle-enhanced radiotherapy was studied by loading MCF-7 and A549 multicellular tumor spheroids (MCTSs) with caffeic acid- and nitrosonium-functionalized Au-Fe3O4 nanoheterodimers (Au-Fe3O4 NHDs). Transmission electron microscope images of MCTS cross-sectional sections visualized the invasion and distribution of the nitrosonium- and caffeic acid-functionalized Au-Fe3O4 NHDs (NO- and CA-NHDs) in the A549 and MCF-7 MCTSs, whereas the iron content of the MCTSs were quantified using the ferrozine assay. The synergistic impact of intracellular NO- and CA-NHDs and X-ray irradiation on the growth dynamics of the A549 and MCF-7 MCTSs was surveyed by monitoring their temporal evolution under a light microscope over a period of 14 days. The emergence of hypoxia during the spheroid growth was followed by detecting the lactate efflux of MCTSs without and with NO- and CA-NHDs. The performance of the NO- and CA-NHDs as X-ray dose-enhancing agents in the A549 and MCF-7 MCTSs was clarified by performing clonogenic cell survival assays and determining the respective dose-modifying factors for X-ray doses of 0, 2, 4, and 6 Gy. The NO- and CA-NHDs were shown to perform as potent X-ray dose-enhancing agents in A549 and MCF-7 MCTSs. Moreover, the CA-NHDs boosted their radio-sensitizing efficacy by inhibiting the lactate efflux as impairing metabolic reprogramming. A synergistic effect on the MCTS destruction was observed for the combination of both NHDs since the surfactants differ in their antitumor effect.}, } @article {pmid35013306, year = {2022}, author = {Sforna, MC and Loron, CC and Demoulin, CF and François, C and Cornet, Y and Lara, YJ and Grolimund, D and Ferreira Sanchez, D and Medjoubi, K and Somogyi, A and Addad, A and Fadel, A and Compère, P and Baudet, D and Brocks, JJ and Javaux, EJ}, title = {Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {146}, pmid = {35013306}, issn = {2041-1723}, mesh = {Biological Evolution ; Chlorophyll/*chemistry/history ; Chlorophyta/anatomy & histology/classification/physiology/*ultrastructure ; Coordination Complexes/*chemistry ; Democratic Republic of the Congo ; Ecosystem ; Eukaryotic Cells ; *Fossils ; Geologic Sediments/analysis ; History, Ancient ; Microscopy, Electron, Transmission ; Nickel/chemistry ; Photosynthesis/*physiology ; Phylogeny ; Plant Cells/physiology/ultrastructure ; Tetrapyrroles/chemistry ; X-Ray Absorption Spectroscopy ; }, abstract = {The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.}, } @article {pmid35012580, year = {2022}, author = {Kozlov, AP}, title = {Mammalian tumor-like organs. 1. The role of tumor-like normal organs and atypical tumor organs in the evolution of development (carcino-evo-devo).}, journal = {Infectious agents and cancer}, volume = {17}, number = {1}, pages = {2}, pmid = {35012580}, issn = {1750-9378}, abstract = {BACKGROUND: Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory-the carcino-evo-devo theory-has been developed based on this hypothesis.

MAIN TEXT: My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs.

CONCLUSION: Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.}, } @article {pmid34999783, year = {2022}, author = {Leger, MM and Ros-Rocher, N and Najle, SR and Ruiz-Trillo, I}, title = {Rel/NF-κB Transcription Factors Emerged at the Onset of Opisthokonts.}, journal = {Genome biology and evolution}, volume = {14}, number = {1}, pages = {}, pmid = {34999783}, issn = {1759-6653}, mesh = {Animals ; *Eukaryota/metabolism ; *Evolution, Molecular ; *NF-kappa B/genetics/metabolism ; Transcription Factor RelA/genetics/metabolism ; Transcription Factor RelB/genetics/metabolism ; }, abstract = {The Rel/NF-κB transcription factor family has myriad roles in immunity, development, and differentiation in animals, and was considered a key innovation for animal multicellularity. Rel homology domain-containing proteins were previously hypothesized to have originated in a last common ancestor of animals and some of their closest unicellular relatives. However, key taxa were missing from previous analyses, necessitating a systematic investigation into the distribution and evolution of these proteins. Here, we address this knowledge gap by surveying taxonomically broad data from eukaryotes, with a special emphasis on lineages closely related to animals. We report an earlier origin for Rel/NF-κB proteins than previously described, in the last common ancestor of animals and fungi, and show that even in the sister group to fungi, these proteins contain elements that in animals are necessary for the subcellular regulation of Rel/NF-κB.}, } @article {pmid34998872, year = {2022}, author = {Kulkarni, P and Behal, A and Mohanty, A and Salgia, R and Nedelcu, AM and Uversky, VN}, title = {Co-opting disorder into order: Intrinsically disordered proteins and the early evolution of complex multicellularity.}, journal = {International journal of biological macromolecules}, volume = {201}, number = {}, pages = {29-36}, doi = {10.1016/j.ijbiomac.2021.12.182}, pmid = {34998872}, issn = {1879-0003}, mesh = {*Intrinsically Disordered Proteins ; *Volvox ; }, abstract = {Intrinsically disordered proteins (IDPs) are proteins that lack rigid structures yet play important roles in myriad biological phenomena. A distinguishing feature of IDPs is that they often mediate specific biological outcomes via multivalent weak cooperative interactions with multiple partners. Here, we show that several proteins specifically associated with processes that were key in the evolution of complex multicellularity in the lineage leading to the multicellular green alga Volvox carteri are IDPs. We suggest that, by rewiring cellular protein interaction networks, IDPs facilitated the co-option of ancestral pathways for specialized multicellular functions, underscoring the importance of IDPs in the early evolution of complex multicellularity.}, } @article {pmid34992624, year = {2021}, author = {Hemleben, V and Grierson, D and Borisjuk, N and Volkov, RA and Kovarik, A}, title = {Personal Perspectives on Plant Ribosomal RNA Genes Research: From Precursor-rRNA to Molecular Evolution.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {797348}, pmid = {34992624}, issn = {1664-462X}, abstract = {The history of rDNA research started almost 90 years ago when the geneticist, Barbara McClintock observed that in interphase nuclei of maize the nucleolus was formed in association with a specific region normally located near the end of a chromosome, which she called the nucleolar organizer region (NOR). Cytologists in the twentieth century recognized the nucleolus as a common structure in all eukaryotic cells, using both light and electron microscopy and biochemical and genetic studies identified ribosomes as the subcellular sites of protein synthesis. In the mid- to late 1960s, the synthesis of nuclear-encoded rRNA was the only system in multicellular organisms where transcripts of known function could be isolated, and their synthesis and processing could be studied. Cytogenetic observations of NOR regions with altered structure in plant interspecific hybrids and detailed knowledge of structure and function of rDNA were prerequisites for studies of nucleolar dominance, epistatic interactions of rDNA loci, and epigenetic silencing. In this article, we focus on the early rDNA research in plants, performed mainly at the dawn of molecular biology in the 60 to 80-ties of the last century which presented a prequel to the modern genomic era. We discuss - from a personal view - the topics such as synthesis of rRNA precursor (35S pre-rRNA in plants), processing, and the organization of 35S and 5S rDNA. Cloning and sequencing led to the observation that the transcribed and processed regions of the rRNA genes vary enormously, even between populations and species, in comparison with the more conserved regions coding for the mature rRNAs. Epigenetic phenomena and the impact of hybridization and allopolyploidy on rDNA expression and homogenization are discussed. This historical view of scientific progress and achievements sets the scene for the other articles highlighting the immense progress in rDNA research published in this special issue of Frontiers in Plant Science on "Molecular organization, evolution, and function of ribosomal DNA."}, } @article {pmid34949534, year = {2022}, author = {Graham, AL and Schrom, EC and Metcalf, CJE}, title = {The evolution of powerful yet perilous immune systems.}, journal = {Trends in immunology}, volume = {43}, number = {2}, pages = {117-131}, pmid = {34949534}, issn = {1471-4981}, mesh = {Adaptation, Physiological ; Animals ; Biological Evolution ; *COVID-19 ; Cytokines/genetics ; Humans ; Immune System ; SARS-CoV-2 ; }, abstract = {The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.}, } @article {pmid34944066, year = {2021}, author = {Yeh, CY and Huang, WH and Chen, HC and Meir, YJ}, title = {Capturing Pluripotency and Beyond.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944066}, issn = {2073-4409}, mesh = {Animals ; Blastocyst/metabolism ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/*growth & development ; Humans ; Mice ; Pluripotent Stem Cells/*cytology ; }, abstract = {During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast's identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.}, } @article {pmid34940504, year = {2021}, author = {Folkendt, L and Lohmann, I and Domsch, K}, title = {An Evolutionary Perspective on Hox Binding Site Preferences in Two Different Tissues.}, journal = {Journal of developmental biology}, volume = {9}, number = {4}, pages = {}, pmid = {34940504}, issn = {2221-3759}, abstract = {Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions in the different cellular contexts. To uncover differences that could explain tissue-specific functions of such TFs, we analyzed here genomic chromatin interactions of the broadly expressed Drosophila Hox TF Ultrabithorax (Ubx) in the mesodermal and neuronal tissues using bioinformatics. Our investigations showed that Ubx preferentially interacts with multiple yet tissue-specific chromatin sites in putative regulatory regions of genes in both tissues. Importantly, we found the classical Hox/Ubx DNA binding motif to be enriched only among the neuronal Ubx chromatin interactions, whereas a novel Ubx-like motif with rather low predicted Hox affinities was identified among the regions bound by Ubx in the mesoderm. Finally, our analysis revealed that tissues-specific Ubx chromatin sites are also different with regards to the distribution of active and repressive histone marks. Based on our data, we propose that the tissue-related differences in Ubx binding behavior could be a result of the emergence of the mesoderm as a new germ layer in triploblastic animals, which might have required the Hox TFs to relax their binding specificity.}, } @article {pmid34937533, year = {2021}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Altruism and Phenoptosis as Programs Supported by Evolution.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {12}, pages = {1540-1552}, pmid = {34937533}, issn = {1608-3040}, mesh = {*Altruism ; Animals ; *Apoptosis ; *Biological Evolution ; *COVID-19 ; Humans ; Insecta/physiology ; *SARS-CoV-2 ; }, abstract = {Phenoptosis is a programmed death that has emerged in the process of evolution, sometimes taking the form of an altruistic program. In particular, it is believed to be a weapon against the spread of pandemics in the past and an obstacle in fighting pandemics in the present (COVID). However, on the evolutionary scale, deterministic death is not associated with random relationships (for example, bacteria with a particular mutation), but is a product of higher nervous activity or a consequence of established hierarchy that reaches its maximal expression in eusocial communities of Hymenoptera and highly social communities of mammals. Unlike a simple association of individuals, eusociality is characterized by the appearance of non-reproductive individuals as the highest form of altruism. In contrast to primitive programs for unicellular organisms, higher multicellular organisms are characterized by the development of behavior-based phenoptotic programs, especially in the case of reproduction-associated limitation of lifespan. Therefore, we can say that the development of altruism in the course of evolution of sociality leads in its extreme manifestation to phenoptosis. Development of mathematical models for the emergence of altruism and programmed death contributes to our understanding of mechanisms underlying these paradoxical counterproductive (harmful) programs. In theory, this model can be applied not only to insects, but also to other social animals and even to the human society. Adaptive death is an extreme form of altruism. We consider altruism and programmed death as programmed processes in the mechanistic and adaptive sense, respectively. Mechanistically, this is a program existing as a predetermined chain of certain responses, regardless of its adaptive value. As to its adaptive value (regardless of the degree of "phenoptoticity"), this is a characteristic of organisms that demonstrate high levels of kinship, social organization, and physical association typical for higher-order individuals, e.g., unicellular organisms forming colonies with some characteristics of multicellular animals or colonies of multicellular animals displaying features of supraorganisms.}, } @article {pmid34934939, year = {2021}, author = {Sherlock, BE and Chen, J and Mansfield, JC and Green, E and Winlove, CP}, title = {Biophotonic tools for probing extracellular matrix mechanics.}, journal = {Matrix biology plus}, volume = {12}, number = {}, pages = {100093}, pmid = {34934939}, issn = {2590-0285}, abstract = {The complex, hierarchical and heterogeneous biomechanics of the extracellular matrix (ECM) are central to the health of multicellular organisms. Characterising the distribution, dynamics and above all else origins of ECM biomechanics are challenges that have captivated researchers for decades. Recently, a suite of biophotonics techniques have emerged as powerful new tools to investigate ECM biomechanics. In this mini-review, we discuss how the non-destructive, sub-micron resolution imaging capabilities of Raman spectroscopy and nonlinear microscopy are being used to interrogate the biomechanics of thick, living tissues. These high speed, label-free techniques are implemented during mechanical testing, providing unprecedented insight into the compositional and structural response of the ECM to changes in the mechanical environment.}, } @article {pmid34932575, year = {2021}, author = {Maltseva, AL and Varfolomeeva, MA and Gafarova, ER and Panova, MAZ and Mikhailova, NA and Granovitch, AI}, title = {Divergence together with microbes: A comparative study of the associated microbiomes in the closely related Littorina species.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260792}, pmid = {34932575}, issn = {1932-6203}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; Environmental Microbiology ; *Genetic Variation ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Snails/classification/*microbiology ; Species Specificity ; }, abstract = {Any multicellular organism during its life is involved in relatively stable interactions with microorganisms. The organism and its microbiome make up a holobiont, possessing a unique set of characteristics and evolving as a whole system. This study aimed to evaluate the degree of the conservativeness of microbiomes associated with intertidal gastropods. We studied the composition and the geographic and phylogenetic variability of the gut and body surface microbiomes of five closely related sympatric Littorina (Neritrema) spp. and a more distant species, L. littorea, from the sister subgenus Littorina (Littorina). Although snail-associated microbiomes included many lineages (207-603), they were dominated by a small number of OTUs of the genera Psychromonas, Vibrio, and Psychrilyobacter. The geographic variability was greater than the interspecific differences at the same collection site. While the microbiomes of the six Littorina spp. did not differ at the high taxonomic level, the OTU composition differed between groups of cryptic species and subgenera. A few species-specific OTUs were detected within the collection sites; notably, such OTUs never dominated microbiomes. We conclude that the composition of the high-rank taxa of the associated microbiome ("scaffolding enterotype") is more evolutionarily conserved than the composition of the low-rank individual OTUs, which may be site- and / or species-specific.}, } @article {pmid34913456, year = {2022}, author = {Gurney, J and Simonet, C and Wollein Waldetoft, K and Brown, SP}, title = {Challenges and opportunities for cheat therapy in the control of bacterial infections.}, journal = {Natural product reports}, volume = {39}, number = {2}, pages = {325-334}, doi = {10.1039/d1np00053e}, pmid = {34913456}, issn = {1460-4752}, mesh = {*Bacterial Infections/drug therapy ; *Biological Evolution ; Humans ; }, abstract = {Covering: 1999 to 2021Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. The requirement for collective action in pathogens presents novel therapeutic avenues that seek to undermine cooperative behavior, what we call here 'cheat therapies'. We review two broad avenues of cheat therapy: first, the introduction of genetically engineered 'cheat' strains (bio-control cheats), and second the chemical induction of 'cheat' behavior in the infecting pathogens (chemical-control cheats). Both genetically engineered and chemically induced cheats can socially exploit the cooperative wildtype infection, reducing pathogen burden and the severity of disease. We review the costs and benefits of cheat therapies, highlighting advantages of evolutionary robustness and also the challenges of low to moderate efficacy, compared to conventional antibiotic treatments. We end with a summary of what we see as the most valuable next steps, focusing on adjuvant treatments and use as alternate therapies for mild, self-resolving infections - allowing the reservation of current and highly effective antibiotics for more critical patient needs.}, } @article {pmid34890552, year = {2021}, author = {Brückner, A and Badroos, JM and Learsch, RW and Yousefelahiyeh, M and Kitchen, SA and Parker, J}, title = {Evolutionary assembly of cooperating cell types in an animal chemical defense system.}, journal = {Cell}, volume = {184}, number = {25}, pages = {6138-6156.e28}, doi = {10.1016/j.cell.2021.11.014}, pmid = {34890552}, issn = {1097-4172}, mesh = {Animals ; Benzoquinones/*metabolism ; Biological Evolution ; Biosynthetic Pathways ; Coleoptera/*metabolism ; Drosophila melanogaster/*metabolism ; Pheromones/*metabolism ; }, abstract = {How the functions of multicellular organs emerge from the underlying evolution of cell types is poorly understood. We deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. We show how gland function arose via assembly of two cell types that manufacture distinct compounds. One cell type, comprising a chemical reservoir within the abdomen, produces alkane and ester compounds. We demonstrate that this cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, executing its function via a mosaic of enzymes from each parental cell type. The second cell type synthesizes benzoquinones using a chimera of conserved cellular energy and cuticle formation pathways. We show that evolution of each cell type was shaped by coevolution between the two cell types, yielding a potent secretion that confers adaptive value. Our findings illustrate how cooperation between cell types arises, generating new, organ-level behaviors.}, } @article {pmid34884742, year = {2021}, author = {Troitskaya, O and Novak, D and Nushtaeva, A and Savinkova, M and Varlamov, M and Ermakov, M and Richter, V and Koval, O}, title = {EGFR Transgene Stimulates Spontaneous Formation of MCF7 Breast Cancer Cells Spheroids with Partly Loss of HER3 Receptor.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884742}, issn = {1422-0067}, mesh = {CD24 Antigen/metabolism ; Cell Culture Techniques, Three Dimensional ; *Genes, erbB-1 ; Humans ; Hyaluronan Receptors/metabolism ; *MCF-7 Cells ; Receptor, ErbB-3/*metabolism ; Rhodamine 123 ; *Spheroids, Cellular ; Transgenes ; Tumor Cells, Cultured ; }, abstract = {Multicellular spheroids with 3D cell-cell interactions are a useful model to simulate the growth conditions of cancer. There is evidence that in tumor spheroids, the expression of various essential molecules is changed compared to the adherent form of cell cultures. These changes include growth factor receptors and ABC transporters and result in the enhanced invasiveness of the cells and drug resistance. It is known that breast adenocarcinoma MCF7 cells can spontaneously form 3D spheroids and such spheroids are characterized by high expression of EGFR/HER2, while the natural phenotype of MCF7 cells is EGFR[low]/HER2[low]. Therefore, it was interesting to reveal if high epidermal growth factor receptor (EGFR) expression is sufficient for the conversion of adherent MCF7 to spheroids. In this study, an MCF7 cell line with high expression of EGFR was engineered using the retroviral transduction method. These MCF7-EGFR cells assembled in spheroids very quickly and grew predominantly as a 3D suspension culture with no special plates, scaffolds, growth supplements, or exogenous matrixes. These spheroids were characterized by a rounded shape with a well-defined external border and 100 µM median diameter. The sphere-forming ability of MCF7-EGFR cells was up to 5 times stronger than in MCF7[wt] cells. Thus, high EGFR expression was the initiation factor of conversion of adherent MCF7[wt] cells to spheroids. MCF7-EGFR spheroids were enriched by the cells with a cancer stem cell (CSC) phenotype CD24[-/low]/CD44[-] in comparison with parental MCF7[wt] cells and MCF7-EGFR adhesive cells. We suppose that these properties of MCF7-EGFR spheroids originate from the typical features of parental MCF7 cells. We showed the decreasing of HER3 receptors in MCF7-EGFR spheroids compared to that in MCF[wt] and in adherent MCF7-EGFR cells, and the same decrease was observed in the MCF7[wt] spheroids growing under the growth factors stimulation. To summarize, the expression of EGFR transgene in MCF7 cells stimulates rapid spheroids formation; these spheroids are enriched by CSC-like CD24[-]/CD44[-] cells, they partly lose HER3 receptors, and are characterized by a lower potency in drug resistance pomp activation compared to MCF7[wt]. These MCF7-EGFR spheroids are a useful cancer model for the development of anticancer drugs, including EGFR-targeted therapeutics.}, } @article {pmid34878516, year = {2022}, author = {Suissa, JS}, title = {Fern fronds that move like pine cones: humidity-driven motion of fertile leaflets governs the timing of spore dispersal in a widespread fern species.}, journal = {Annals of botany}, volume = {129}, number = {5}, pages = {519-528}, pmid = {34878516}, issn = {1095-8290}, mesh = {*Ferns/physiology ; Germ Cells, Plant ; Humidity ; Plant Cone ; Spores/physiology ; Spores, Fungal ; }, abstract = {BACKGROUND AND AIMS: The sensitive fern, Onoclea sensibilis, is a widespread species in eastern North America and has an atypical timing of spore dispersal among temperate ferns. During early summer, this dimorphic species produces heavily modified spore-bearing fronds with leaflets tightly enveloping their sporangia and spores. These fronds senesce and persist above ground as dead mature structures until the following early spring when the leaflets finally open and spores are dispersed. While this timing of spore dispersal has been observed for over 120 years, the structural mechanisms underpinning this phenology have remained elusive.

METHODS: Based on field observations, growth chamber manipulations and scanning electron microscopy, the mechanisms underlying this distinctive timing of spore dispersal in the sensitive fern were investigated.

KEY RESULTS: I show that fertile leaflets of the sensitive fern move in direct response to changes in humidity, exhibiting structural and functional parallels with multicellular hygromorphic structures in seed plants, such as pine cones. These parallels include differences in cellulose microfibril orientation in cells on the abaxial and adaxial sides of the leaflet. The dynamics of this hygroscopic movement concomitant with regular abscission zones along the pinnules and coordinated senescence lead to the specific timing of early spring spore dispersal in the sensitive fern.

CONCLUSIONS: While hygroscopic movement is common in seed-free plants, it mostly occurs in small structures that are either one or a few cells in size, such as the leptosporangium. Given its multicellular structure and integration across many cells and tissues, the movement and construction of the sensitive fern pinnules are more similar to structures in seed plants. The evolution of this complex trait in the sensitive fern efficiently regulates the timing of spore release, leading to early spring dispersal. This phenology likely gives gametophytes and subsequent sporophytes an advantage with early germination and growth.}, } @article {pmid34873026, year = {2021}, author = {Wade, J and Byrne, DJ and Ballentine, CJ and Drakesmith, H}, title = {Temporal variation of planetary iron as a driver of evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {51}, pages = {}, pmid = {34873026}, issn = {1091-6490}, support = {MC_UU_00008/10/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/10/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Availability ; *Biological Evolution ; Earth, Planet ; Ecosystem ; *Evolution, Planetary ; Genetic Variation ; Geology ; Host-Pathogen Interactions ; Iron/chemistry/*metabolism ; Oxidation-Reduction ; Siderophores/metabolism ; Water/chemistry/metabolism ; }, abstract = {Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO2.}, } @article {pmid34870903, year = {2021}, author = {Prostak, SM and Fritz-Laylin, LK}, title = {Laboratory Maintenance of the Chytrid Fungus Batrachochytrium dendrobatidis.}, journal = {Current protocols}, volume = {1}, number = {12}, pages = {e309}, doi = {10.1002/cpz1.309}, pmid = {34870903}, issn = {2691-1299}, mesh = {Amphibians ; Animals ; Batrachochytrium ; *Chytridiomycota ; Ecosystem ; Laboratories ; }, abstract = {The chytrid fungus Batrachochytrium dendrobatidis (Bd) is a causative agent of chytridiomycosis, a skin disease associated with amphibian population declines around the world. Despite the major impact Bd is having on global ecosystems, much of Bd's basic biology remains unstudied. In addition to revealing mechanisms driving the spread of chytridiomycosis, studying Bd can shed light on the evolution of key fungal traits because chytrid fungi, including Bd, diverged before the radiation of the Dikaryotic fungi (multicellular fungi and yeast). Studying Bd in the laboratory is, therefore, of growing interest to a wide range of scientists, ranging from herpetologists and disease ecologists to molecular, cell, and evolutionary biologists. This protocol describes how to maintain developmentally synchronized liquid cultures of Bd for use in the laboratory, how to grow Bd on solid media, as well as cryopreservation and revival of frozen stocks. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Reviving cryopreserved Bd cultures Basic Protocol 2: Establishing synchronized liquid cultures of Bd Basic Protocol 3: Regular maintenance of synchronous Bd in liquid culture Alternate Protocol 1: Regular maintenance of asynchronous Bd in liquid culture Basic Protocol 4: Regular maintenance of synchronous Bd on solid medium Alternate Protocol 2: Starting a culture on solid medium from a liquid culture Basic Protocol 5: Cryopreservation of Bd.}, } @article {pmid34857936, year = {2021}, author = {Liu, K and Deng, S and Ye, C and Yao, Z and Wang, J and Gong, H and Liu, L and He, X}, title = {Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.}, journal = {Nature methods}, volume = {18}, number = {12}, pages = {1506-1514}, pmid = {34857936}, issn = {1548-7105}, mesh = {Alleles ; Animals ; Animals, Genetically Modified ; Cell Division ; Cell Lineage ; Computational Biology/*methods ; DNA Replication ; Drosophila melanogaster/embryology/*metabolism ; Endonucleases/metabolism ; Likelihood Functions ; Male ; Microscopy/*methods ; Mutagenesis ; *Mutation ; Phenotype ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Single-Cell Analysis ; }, abstract = {Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84-93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.}, } @article {pmid34853303, year = {2021}, author = {Pennemann, FL and Mussabekova, A and Urban, C and Stukalov, A and Andersen, LL and Grass, V and Lavacca, TM and Holze, C and Oubraham, L and Benamrouche, Y and Girardi, E and Boulos, RE and Hartmann, R and Superti-Furga, G and Habjan, M and Imler, JL and Meignin, C and Pichlmair, A}, title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7009}, pmid = {34853303}, issn = {2041-1723}, mesh = {Animals ; Antiviral Agents ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; *Immunity, Innate ; Mice ; Nucleic Acids/*chemistry/*immunology ; Protein Serine-Threonine Kinases ; Proteomics ; RNA Interference ; RNA, Double-Stranded ; Species Specificity ; THP-1 Cells ; Viral Proteins/*chemistry/*immunology ; }, abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.}, } @article {pmid34849893, year = {2022}, author = {Takeuchi, N and Mitarai, N and Kaneko, K}, title = {A scaling law of multilevel evolution: how the balance between within- and among-collective evolution is determined.}, journal = {Genetics}, volume = {220}, number = {2}, pages = {}, pmid = {34849893}, issn = {1943-2631}, mesh = {*Altruism ; *Biological Evolution ; Computer Simulation ; Genetics, Population ; Phenotype ; Selection, Genetic ; }, abstract = {Numerous living systems are hierarchically organized, whereby replicating components are grouped into reproducing collectives-e.g., organelles are grouped into cells, and cells are grouped into multicellular organisms. In such systems, evolution can operate at two levels: evolution among collectives, which tends to promote selfless cooperation among components within collectives (called altruism), and evolution within collectives, which tends to promote cheating among components within collectives. The balance between within- and among-collective evolution thus exerts profound impacts on the fitness of these systems. Here, we investigate how this balance depends on the size of a collective (denoted by N) and the mutation rate of components (m) through mathematical analyses and computer simulations of multiple population genetics models. We first confirm a previous result that increasing N or m accelerates within-collective evolution relative to among-collective evolution, thus promoting the evolution of cheating. Moreover, we show that when within- and among-collective evolution exactly balance each other out, the following scaling relation generally holds: Nmα is a constant, where scaling exponent α depends on multiple parameters, such as the strength of selection and whether altruism is a binary or quantitative trait. This relation indicates that although N and m have quantitatively distinct impacts on the balance between within- and among-collective evolution, their impacts become identical if m is scaled with a proper exponent. Our results thus provide a novel insight into conditions under which cheating or altruism evolves in hierarchically organized replicating systems.}, } @article {pmid34849891, year = {2021}, author = {Varahan, S and Laxman, S}, title = {Bend or break: how biochemically versatile molecules enable metabolic division of labor in clonal microbial communities.}, journal = {Genetics}, volume = {219}, number = {2}, pages = {}, pmid = {34849891}, issn = {1943-2631}, mesh = {Evolution, Molecular ; *Microbial Consortia ; *Microbial Interactions ; Yeasts/genetics/metabolism/physiology ; }, abstract = {In fluctuating nutrient environments, isogenic microbial cells transition into "multicellular" communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.}, } @article {pmid34848727, year = {2021}, author = {Benaissa, H and Ounoughi, K and Aujard, I and Fischer, E and Goïame, R and Nguyen, J and Tebo, AG and Li, C and Le Saux, T and Bertolin, G and Tramier, M and Danglot, L and Pietrancosta, N and Morin, X and Jullien, L and Gautier, A}, title = {Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6989}, pmid = {34848727}, issn = {2041-1723}, mesh = {Animals ; Biocompatible Materials ; Biosensing Techniques ; Color ; Coloring Agents ; Diagnostic Imaging/*methods ; Electronics ; Female ; *Fluorescence ; Fluorescence Resonance Energy Transfer ; Fluorescent Dyes ; Green Fluorescent Proteins ; Male ; Neurons ; Protein Engineering/*methods ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Biocompatible fluorescent reporters with spectral properties spanning the entire visible spectrum are indispensable tools for imaging the biochemistry of living cells and organisms in real time. Here, we report the engineering of a fluorescent chemogenetic reporter with tunable optical and spectral properties. A collection of fluorogenic chromophores with various electronic properties enables to generate bimolecular fluorescent assemblies that cover the visible spectrum from blue to red using a single protein tag engineered and optimized by directed evolution and rational design. The ability to tune the fluorescence color and properties through simple molecular modulation provides a broad experimental versatility for imaging proteins in live cells, including neurons, and in multicellular organisms, and opens avenues for optimizing Förster resonance energy transfer (FRET) biosensors in live cells. The ability to tune the spectral properties and fluorescence performance enables furthermore to match the specifications and requirements of advanced super-resolution imaging techniques.}, } @article {pmid34841798, year = {2021}, author = {Yu, D and Cao, H and Wang, X}, title = {[Advances and applications of organoids: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3961-3974}, doi = {10.13345/j.cjb.200764}, pmid = {34841798}, issn = {1872-2075}, mesh = {*Gene Editing ; Humans ; Models, Biological ; *Organoids ; Regenerative Medicine ; Stem Cells ; }, abstract = {Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.}, } @article {pmid34838795, year = {2022}, author = {Tverskoi, D and Gavrilets, S}, title = {The evolution of germ-soma specialization under different genetic and environmental effects.}, journal = {Journal of theoretical biology}, volume = {534}, number = {}, pages = {110964}, doi = {10.1016/j.jtbi.2021.110964}, pmid = {34838795}, issn = {1095-8541}, mesh = {*Biological Evolution ; Cell Differentiation ; Climate ; Fertility ; Humans ; *Models, Biological ; }, abstract = {Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene effects on fecundity and activity are influenced by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.}, } @article {pmid34834691, year = {2021}, author = {Medina, MC and Sousa-Baena, MS and Capelli, NDV and Koch, R and Demarco, D}, title = {Stinging Trichomes in Apocynaceae and Their Evolution in Angiosperms.}, journal = {Plants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34834691}, issn = {2223-7747}, abstract = {Stinging trichomes are rare in plants, occurring only in angiosperms, where they are reported for a few genera belonging to six families. Although there is no report of stinging trichomes in Apocynaceae, previous fieldwork collections of Fischeria and Matelea caused us a mild allergic reaction on the skin when we contacted the dense indumentum of the plants. This fact associated with the well-known presence of glandular trichomes with acute apex in both genera raised suspicions that stinging trichomes could be present in the family. Hence, this study aimed to investigate the likely occurrence of stinging trichomes in Fischeria and Matelea. We analyzed vegetative shoots and leaves of Fischeria stellata and Matelea denticulata through the usual procedures of light and scanning electron microscopy. We also performed several histochemical tests to investigate the chemical composition of trichome secretion. We detected that glandular trichomes occur throughout the surface of the leaf and stem. They are multicellular, uniseriate with an apical secretory cell, which has a dilated base and a needle-shaped apex. The secretion is compressed into the acuminate portion of the apical cell by a large vacuole, and crystals are deposited in the cell wall in a subapical position, providing a preferential site of rupture. The secretion, composed of amino acids and/or proteins, is released under mechanical action, causing skin irritation. Based on our detailed morphological and anatomical analyses, and in the functional aspects observed, we concluded that the glandular trichomes in Fischeria and Matelea can indeed be classified as stinging. Thus, Apocynaceae is the seventh family for which this type of trichome has been reported. We also compiled information on stinging trichomes in all families of angiosperms. Their phylogenetic distribution indicates that they have evolved at least 12 times during angiosperm evolution and may represent an evolutionary convergence of plant defense against herbivory.}, } @article {pmid34830470, year = {2021}, author = {Kertmen, A and Petrenko, I and Schimpf, C and Rafaja, D and Petrova, O and Sivkov, V and Nekipelov, S and Fursov, A and Stelling, AL and Heimler, K and Rogoll, A and Vogt, C and Ehrlich, H}, title = {Calcite Nanotuned Chitinous Skeletons of Giant Ianthella basta Marine Demosponge.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830470}, issn = {1422-0067}, mesh = {Animals ; Aquatic Organisms/*chemistry ; Biomineralization ; Calcium Carbonate/*chemistry ; Chitin/chemistry ; Porifera/*chemistry ; Skeleton/*chemistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; X-Ray Diffraction ; }, abstract = {Marine sponges were among the first multicellular organisms on our planet and have survived to this day thanks to their unique mechanisms of chemical defense and the specific design of their skeletons, which have been optimized over millions of years of evolution to effectively inhabit the aquatic environment. In this work, we carried out studies to elucidate the nature and nanostructural organization of three-dimensional skeletal microfibers of the giant marine demosponge Ianthella basta, the body of which is a micro-reticular, durable structure that determines the ideal filtration function of this organism. For the first time, using the battery of analytical tools including three-dimensional micro-X-ray Fluorescence (3D-µXRF), X-ray diffraction (XRD), infra-red (FTIR), Raman and Near Edge X-ray Fine Structure (NEXAFS) spectroscopy, we have shown that biomineral calcite is responsible for nano-tuning the skeletal fibers of this sponge species. This is the first report on the presence of a calcitic mineral phase in representatives of verongiid sponges which belong to the class Demospongiae. Our experimental data suggest a possible role for structural amino polysaccharide chitin as a template for calcification. Our study suggests further experiments to elucidate both the origin of calcium carbonate inside the skeleton of this sponge and the mechanisms of biomineralization in the surface layers of chitin microfibers saturated with bromotyrosines, which have effective antimicrobial properties and are responsible for the chemical defense of this organism. The discovery of the calcified phase in the chitinous template of I. basta skeleton is expected to broaden the knowledge in biomineralization science where the calcium carbonate is regarded as a valuable material for applications in biomedicine, environmental science, and even in civil engineering.}, } @article {pmid34830263, year = {2021}, author = {Pereira, PHS and Garcia, CRS}, title = {Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum-Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830263}, issn = {1422-0067}, mesh = {Animals ; Antimalarials/pharmacology/therapeutic use ; Calcium/metabolism ; Calcium Signaling/drug effects/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/drug therapy/*metabolism/parasitology ; Molecular Targeted Therapy/methods ; Perception/drug effects/*physiology ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protozoan Proteins/*metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors/*metabolism ; }, abstract = {Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells' external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K[+] shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.}, } @article {pmid34825884, year = {2021}, author = {Li, XG and Lin, J and Bai, SJ and Dai, J and Jiao, ZX and Tang, HZ and Qi, XQ and Zhang, WJ and Liu, M and Xu, JS and Wu, LF}, title = {Crassaminicella thermophila sp. nov., a moderately thermophilic bacterium isolated from a deep-sea hydrothermal vent chimney and emended description of the genus Crassaminicella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {71}, number = {11}, pages = {}, doi = {10.1099/ijsem.0.005112}, pmid = {34825884}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridiaceae/*classification/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Hydrothermal Vents/microbiology ; Indian Ocean ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; }, abstract = {A novel moderately thermophilic, anaerobic, heterotrophic bacterium (strain SY095[T]) was isolated from a hydrothermal vent chimney located on the Southwest Indian Ridge at a depth of 2730 m. Cells were Gram-stain-positive, motile, straight to slightly curved rods forming terminal endospores. SY095[T] was grown at 45-60 °C (optimum 50-55 °C), pH 6.0-7.5 (optimum 7.0), and in a salinity of 1-4.5 % (w/v) NaCl (optimum 2.5 %). Substrates utilized by SY095[T] included fructose, glucose, maltose, N-acetyl glucosamine and tryptone. Casamino acid and amino acids (glutamate, glutamine, lysine, methionine, serine and histidine) were also utilized. The main end products from glucose fermentation were acetate, H2 and CO2. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe(III) were not used as terminal electron acceptors. The predominant cellular fatty acids were C14 : 0 (60.5%) and C16 : 0 (7.6 %). The main polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified phospholipids and two unidentified aminophospholipids. No respiratory quinones were detected. The chromosomal DNA G+C content was 30.8 mol%. The results of phylogenetic analysis of the 16S rRNA gene sequences indicated that SY095[T] was closely related to Crassaminicella profunda Ra1766H[T] (95.8 % 16S rRNA gene sequence identity). SY095[T] exhibited 78.1 % average nucleotide identity (ANI) to C. profunda Ra1766H[T]. The in silico DNA-DNA hybridization (DDH) value indicated that SY095[T] shared 22.7 % DNA relatedness with C. profunda Ra1766H[T]. On the basis of its phenotypic, genotypic and phylogenetic characteristics, SY095[T] is suggested to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella thermophila sp. nov. is proposed. The type strain is SY095[T] (=JCM 34213=MCCC 1K04191). An emended description of the genus Crassaminicella is also proposed.}, } @article {pmid34814752, year = {2021}, author = {Irisarri, I and Darienko, T and Pröschold, T and Fürst-Jansen, JMR and Jamy, M and de Vries, J}, title = {Unexpected cryptic species among streptophyte algae most distant to land plants.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20212168}, pmid = {34814752}, issn = {1471-2954}, mesh = {*Chlorophyta/genetics ; *Embryophyta/genetics ; Evolution, Molecular ; Genome ; Phylogeny ; Plants/genetics ; }, abstract = {Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae, Spirotaenia spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species, Chlorokybus atmophyticus. In this study, we used phylogenomic analyses to shed light into the diversity within Chlorokybus using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the Chlorokybus isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among Chlorokybus species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.}, } @article {pmid34814750, year = {2021}, author = {La Fortezza, M and Velicer, GJ}, title = {Social selection within aggregative multicellular development drives morphological evolution.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20211522}, pmid = {34814750}, issn = {1471-2954}, mesh = {*Biological Evolution ; Genotype ; *Myxococcus xanthus/genetics ; }, abstract = {Aggregative multicellular development is a social process involving complex forms of cooperation among unicellular organisms. In some aggregative systems, development culminates in the construction of spore-packed fruiting bodies and often unfolds within genetically and behaviourally diverse conspecific cellular environments. Here, we use the bacterium Myxococcus xanthus to test whether the character of the cellular environment during aggregative development shapes its morphological evolution. We manipulated the cellular composition of Myxococcus development in an experiment in which evolving populations initiated from a single ancestor repeatedly co-developed with one of several non-evolving partners-a cooperator, three cheaters and three antagonists. Fruiting body morphology was found to diversify not only as a function of partner genotype but more broadly as a function of partner social character, with antagonistic partners selecting for greater fruiting body formation than cheaters or the cooperator. Yet even small degrees of genetic divergence between distinct cheater partners sufficed to drive treatment-level morphological divergence. Co-developmental partners also determined the magnitude and dynamics of stochastic morphological diversification and subsequent convergence. In summary, we find that even just a few genetic differences affecting developmental and social features can greatly impact morphological evolution of multicellular bodies and experimentally demonstrate that microbial warfare can promote cooperation.}, } @article {pmid34811380, year = {2021}, author = {Yamashita, S and Yamamoto, K and Matsuzaki, R and Suzuki, S and Yamaguchi, H and Hirooka, S and Minakuchi, Y and Miyagishima, SY and Kawachi, M and Toyoda, A and Nozaki, H}, title = {Genome sequencing of the multicellular alga Astrephomene provides insights into convergent evolution of germ-soma differentiation.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22231}, pmid = {34811380}, issn = {2045-2322}, mesh = {Algal Proteins/genetics/metabolism ; *Biological Evolution ; Cell Differentiation/*genetics ; Chlorophyceae/*genetics ; Chlorophyta/*genetics ; Germ Cells ; Volvox/genetics ; Whole Genome Sequencing ; }, abstract = {Germ-soma differentiation evolved independently in many eukaryotic lineages and contributed to complex multicellular organizations. However, the molecular genetic bases of such convergent evolution remain unresolved. Two multicellular volvocine green algae, Volvox and Astrephomene, exhibit convergent evolution of germ-soma differentiation. The complete genome sequence is now available for Volvox, while genome information is scarce for Astrephomene. Here, we generated the de novo whole genome sequence of Astrephomene gubernaculifera and conducted RNA-seq analysis of isolated somatic and reproductive cells. In Volvox, tandem duplication and neofunctionalization of the ancestral transcription factor gene (RLS1/rlsD) might have led to the evolution of regA, the master regulator for Volvox germ-soma differentiation. However, our genome data demonstrated that Astrephomene has not undergone tandem duplication of the RLS1/rlsD homolog or acquisition of a regA-like gene. Our RNA-seq analysis revealed the downregulation of photosynthetic and anabolic gene expression in Astrephomene somatic cells, as in Volvox. Among genes with high expression in somatic cells of Astrephomene, we identified three genes encoding putative transcription factors, which may regulate somatic cell differentiation. Thus, the convergent evolution of germ-soma differentiation in the volvocine algae may have occurred by the acquisition of different regulatory circuits that generate a similar division of labor.}, } @article {pmid34789585, year = {2021}, author = {Miller, EA and Leidholt, S and Galvin, T and Norton, A and Van Houtan, KS and Vega Thurber, R and Boustany, A}, title = {Electron microscopy reveals viral-like particles and mitochondrial degradation in scombrid puffy snout syndrome.}, journal = {Diseases of aquatic organisms}, volume = {147}, number = {}, pages = {25-31}, doi = {10.3354/dao03634}, pmid = {34789585}, issn = {0177-5103}, mesh = {Animals ; Eukaryota ; Fishes ; Microscopy, Electron/veterinary ; *Mitophagy ; *Perciformes ; }, abstract = {Aquaculture is an increasingly important food resource, but its sustainability is often limited by disease. In Scombridae fishes, puffy snout syndrome (PSS) is a debilitating condition where tumor-like collagenous growths form around the eyes, nares, and mandibles which impair vision and feeding and frequently lead to mortality. While PSS is considered an infectious or metabolic disease, no disease agents or promoters have been identified. Here, we used electron microscopy (EM) to describe the cellular pathology and search for etiological agents of PSS in Pacific mackerel Scomber japonicus, the first use of this approach for PSS. We examined aquaculture specimens across a range of apparent PSS severity, comparing the results to both wild and aquaculture asymptomatic mackerel. EM imagery consistently revealed viral-like particles in PSS samples, as well as the uniform absence of bacteria, protists, fungi, and other multicellular parasites. In addition to viral-like particles, symptomatic fish had a higher mean percentage of swollen and disintegrating mitochondria than both asymptomatic aquaculture and wild mackerel. This suggests that degraded mitochondria may be related to PSS and could be important to further understanding the origin, promoters, and prevention of PSS. This study serves as a first step in identifying the etiological agents of PSS.}, } @article {pmid34788294, year = {2021}, author = {Fortunato, A and Fleming, A and Aktipis, A and Maley, CC}, title = {Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens.}, journal = {PLoS biology}, volume = {19}, number = {11}, pages = {e3001471}, pmid = {34788294}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Damage/genetics/radiation effects ; DNA Repair/*genetics/radiation effects ; Gene Expression Regulation/radiation effects ; Placozoa/anatomy & histology/*genetics/radiation effects ; Radiation Exposure ; Radiation Tolerance/*genetics ; Sequence Analysis, DNA ; Up-Regulation/*genetics/radiation effects ; Whole Genome Sequencing ; X-Rays ; }, abstract = {Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.}, } @article {pmid34785682, year = {2021}, author = {He, H and Wu, X and Xian, H and Zhu, J and Yang, Y and Lv, Y and Li, Y and Konhauser, KO}, title = {An abiotic source of Archean hydrogen peroxide and oxygen that pre-dates oxygenic photosynthesis.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6611}, pmid = {34785682}, issn = {2041-1723}, mesh = {Atmosphere ; Biological Evolution ; Cyanobacteria/metabolism ; Earth, Planet ; Environment ; Hydrogen Peroxide/*chemistry/*metabolism ; Oxidation-Reduction ; Oxygen/*chemistry/*metabolism ; Particle Size ; Photosynthesis/*physiology ; }, abstract = {The evolution of oxygenic photosynthesis is a pivotal event in Earth's history because the O2 released fundamentally changed the planet's redox state and facilitated the emergence of multicellular life. An intriguing hypothesis proposes that hydrogen peroxide (H2O2) once acted as the electron donor prior to the evolution of oxygenic photosynthesis, but its abundance during the Archean would have been limited. Here, we report a previously unrecognized abiotic pathway for Archean H2O2 production that involves the abrasion of quartz surfaces and the subsequent generation of surface-bound radicals that can efficiently oxidize H2O to H2O2 and O2. We propose that in turbulent subaqueous environments, such as rivers, estuaries and deltas, this process could have provided a sufficient H2O2 source that led to the generation of biogenic O2, creating an evolutionary impetus for the origin of oxygenic photosynthesis.}, } @article {pmid34778256, year = {2021}, author = {Daignan-Fornier, B and Laporte, D and Sagot, I}, title = {Quiescence Through the Prism of Evolution.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {745069}, pmid = {34778256}, issn = {2296-634X}, abstract = {Being able to reproduce and survive is fundamental to all forms of life. In primitive unicellular organisms, the emergence of quiescence as a reversible proliferation arrest has most likely improved cell survival under unfavorable environmental conditions. During evolution, with the repeated appearances of multicellularity, several aspects of unicellular quiescence were conserved while new quiescent cell intrinsic abilities arose. We propose that the formation of a microenvironment by neighboring cells has allowed disconnecting quiescence from nutritional cues. In this new context, non-proliferative cells can stay metabolically active, potentially authorizing the emergence of new quiescent cell properties, and thereby favoring cell specialization. Through its co-evolution with cell specialization, quiescence may have been a key motor of the fascinating diversity of multicellular complexity.}, } @article {pmid34771463, year = {2021}, author = {Riol, A and Cervera, J and Levin, M and Mafe, S}, title = {Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771463}, issn = {2072-6694}, abstract = {Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity.}, } @article {pmid34769394, year = {2021}, author = {Marijuán, PC and Navarro, J}, title = {From Molecular Recognition to the "Vehicles" of Evolutionary Complexity: An Informational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769394}, issn = {1422-0067}, mesh = {Animals ; *Biological Evolution ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; *Mutation ; Signal Transduction ; }, abstract = {Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this "omic" era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational 'vehicles' evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.}, } @article {pmid34769071, year = {2021}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769071}, issn = {1422-0067}, mesh = {Animals ; Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; *Genome, Human ; Hominidae/genetics ; Humans ; Multigene Family ; Oncogenes ; Prokaryotic Cells/metabolism ; Transcription Factors/genetics ; }, abstract = {The growth of complexity in evolution is a most intriguing phenomenon. Using gene phylostratigraphy, we showed this growth (as reflected in regulatory mechanisms) in the human genome, tracing the path from prokaryotes to hominids. Generally, the different regulatory gene families expanded at different times, yet only up to the Euteleostomi (bony vertebrates). The only exception was the expansion of transcription factors (TF) in placentals; however, we argue that this was not related to increase in general complexity. Surprisingly, although TF originated in the Prokaryota while chromatin appeared only in the Eukaryota, the expansion of epigenetic factors predated the expansion of TF. Signaling receptors, tumor suppressors, oncogenes, and aging- and disease-associated genes (indicating vulnerabilities in terms of complex organization and strongly enrichment in regulatory genes) also expanded only up to the Euteleostomi. The complexity-related gene properties (protein size, number of alternative splicing mRNA, length of untranslated mRNA, number of biological processes per gene, number of disordered regions in a protein, and density of TF-TF interactions) rose in multicellular organisms and declined after the Euteleostomi, and possibly earlier. At the same time, the speed of protein sequence evolution sharply increased in the genes that originated after the Euteleostomi. Thus, several lines of evidence indicate that molecular mechanisms of complexity growth were changing with time, and in the phyletic lineage leading to humans, the most salient shift occurred after the basic vertebrate body plan was fixed with bony skeleton. The obtained results can be useful for evolutionary medicine.}, } @article {pmid34752334, year = {2021}, author = {Pereira, PHS and Garcia, CRS and Bouvier, M}, title = {Identifying Plasmodium falciparum receptor activation using bioluminescence resonance energy transfer (BRET)-based biosensors in HEK293 cells.}, journal = {Methods in cell biology}, volume = {166}, number = {}, pages = {223-233}, doi = {10.1016/bs.mcb.2021.06.018}, pmid = {34752334}, issn = {0091-679X}, mesh = {*Biosensing Techniques ; Energy Transfer ; HEK293 Cells ; Humans ; *Plasmodium falciparum/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Throughout evolution the need for unicellular organisms to associate and form a single cluster of cells had several evolutionary advantages. G protein coupled receptors (GPCRs) are responsible for a large part of the senses that allow this clustering to succeed, playing a fundamental role in the perception of cell's external environment, enabling the interaction and coordinated development between each cell of a multicellular organism. GPCRs are not exclusive to complex multicellular organisms. In single-celled organisms, GPCRs are also present and have a similar function of detecting changes in the external environment and transforming them into a biological response. There are no reports of GPCRs in parasitic protozoa, such as the Plasmodium genus, and the identification of a protein of this family in P. falciparum would have a significant impact both on the understanding of the basic biology of the parasite and on the history of the evolution of GPCRs. The protocol described here was successfully applied to study a GPCR candidate in P. falciparum for the first time, and we hope that it helps other groups to use the same approach to study this deadly parasite.}, } @article {pmid34740967, year = {2021}, author = {Krespach, MKC and Stroe, MC and Flak, M and Komor, AJ and Nietzsche, S and Sasso, S and Hertweck, C and Brakhage, AA}, title = {Bacterial marginolactones trigger formation of algal gloeocapsoids, protective aggregates on the verge of multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {45}, pages = {}, pmid = {34740967}, issn = {1091-6490}, mesh = {*Cell Aggregation ; Chlamydomonas reinhardtii/*physiology/ultrastructure ; Macrolides/metabolism ; Microbial Interactions ; Streptomyces/metabolism ; }, abstract = {Photosynthetic microorganisms including the green alga Chlamydomonas reinhardtii are essential to terrestrial habitats as they start the carbon cycle by conversion of CO2 to energy-rich organic carbohydrates. Terrestrial habitats are densely populated, and hence, microbial interactions mediated by natural products are inevitable. We previously discovered such an interaction between Streptomyces iranensis releasing the marginolactone azalomycin F in the presence of C. reinhardtii Whether the alga senses and reacts to azalomycin F remained unknown. Here, we report that sublethal concentrations of azalomycin F trigger the formation of a protective multicellular structure by C. reinhardtii, which we named gloeocapsoid. Gloeocapsoids contain several cells which share multiple cell membranes and cell walls and are surrounded by a spacious matrix consisting of acidic polysaccharides. After azalomycin F removal, gloeocapsoid aggregates readily disassemble, and single cells are released. The presence of marginolactone biosynthesis gene clusters in numerous streptomycetes, their ubiquity in soil, and our observation that other marginolactones such as desertomycin A and monazomycin also trigger the formation of gloeocapsoids suggests a cross-kingdom competition with ecological relevance. Furthermore, gloeocapsoids allow for the survival of C. reinhardtii at alkaline pH and otherwise lethal concentrations of azalomycin F. Their structure and polysaccharide matrix may be ancestral to the complex mucilage formed by multicellular members of the Chlamydomonadales such as Eudorina and Volvox Our finding suggests that multicellularity may have evolved to endure the presence of harmful competing bacteria. Additionally, it underlines the importance of natural products as microbial cues, which initiate interesting ecological scenarios of attack and counter defense.}, } @article {pmid34740727, year = {2022}, author = {Quan, X and Kato, D and Daria, V and Matoba, O and Wake, H}, title = {Holographic microscope and its biological application.}, journal = {Neuroscience research}, volume = {179}, number = {}, pages = {57-64}, doi = {10.1016/j.neures.2021.10.012}, pmid = {34740727}, issn = {1872-8111}, mesh = {Animals ; *Holography/methods ; Mice ; Neurons/physiology ; Optogenetics/methods ; Photic Stimulation/methods ; Photons ; }, abstract = {Holographic structured illumination combined with optogenetics enables patterned stimulation of neurons and glial cells in an intact living brain. Moreover, in vivo functional imaging of cellular activity with recent advanced microscope technologies allows for visualization of the cellular responses during learning, emotion and cognition. Integrating these techniques can be used to verify the link between cell function and behavior output. However, there are technical limitations to stimulate multiple cells with high spatial and temporal resolution with available techniques of optogenetic stimulation. Here, we summarized a two-photon microscope combined with holographic system to stimulate multiple cells with high spatial and temporal resolution for living mice and their biological application.}, } @article {pmid34738176, year = {2022}, author = {Verdan, M and Resende, E and Cypriano, J and Werneck, C and Lins, U and Abreu, F}, title = {Occurrence of south- and north-seeking multicellular magnetotactic prokaryotes in a coastal lagoon in the South Hemisphere.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {25}, number = {2}, pages = {309-323}, pmid = {34738176}, issn = {1618-1905}, mesh = {Brazil ; *Deltaproteobacteria/genetics ; Matrix Metalloproteinases/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Magnetotactic bacteria (MTB) response to the magnetic field can be classified into north-seeking (NS) and south-seeking (SS), which usually depends on their inhabiting site in the North and South Hemisphere, respectively. However, uncommon inverted polarity was observed on both hemispheres. Here, we studied magnetotactic multicellular prokaryotes (MMPs) from a coastal lagoon in Brazil collected in April and August 2014. MMPs from the first sampling period presented both magnetotactic behaviors, while MMPs collected in August/2014 were only SS. Phylogenetic analysis based on the 16S rRNA coding gene showed that these organisms belong to the Deltaproteobacteria class. The 16S rRNA gene sequences varied among MMPs regardless of the sampling period, and similarity values were not related to the type of magnetotactic response presented by the microorganisms. Therefore, differences in the magnetotactic behavior might result from the physiological state of MMPs, the availability of resources, or the instability of the chemical gradient in the environment. This is the first report of NS magnetotactic behavior on MMPs from the South Hemisphere.}, } @article {pmid34725037, year = {2021}, author = {Hakala, SM and Meurville, MP and Stumpe, M and LeBoeuf, AC}, title = {Biomarkers in a socially exchanged /fluid reflect colony maturity, behavior, and distributed metabolism.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34725037}, issn = {2050-084X}, mesh = {Animals ; Ants/metabolism/*physiology ; Biomarkers/*metabolism ; Social Behavior ; }, abstract = {In cooperative systems exhibiting division of labor, such as microbial communities, multicellular organisms, and social insect colonies, individual units share costs and benefits through both task specialization and exchanged materials. Socially exchanged fluids, like seminal fluid and milk, allow individuals to molecularly influence conspecifics. Many social insects have a social circulatory system, where food and endogenously produced molecules are transferred mouth-to-mouth (stomodeal trophallaxis), connecting all the individuals in the society. To understand how these endogenous molecules relate to colony life, we used quantitative proteomics to investigate the trophallactic fluid within colonies of the carpenter ant Camponotus floridanus. We show that different stages of the colony life cycle circulate different types of proteins: young colonies prioritize direct carbohydrate processing; mature colonies prioritize accumulation and transmission of stored resources. Further, colonies circulate proteins implicated in oxidative stress, ageing, and social insect caste determination, potentially acting as superorganismal hormones. Brood-caring individuals that are also closer to the queen in the social network (nurses) showed higher abundance of oxidative stress-related proteins. Thus, trophallaxis behavior could provide a mechanism for distributed metabolism in social insect societies. The ability to thoroughly analyze the materials exchanged between cooperative units makes social insect colonies useful models to understand the evolution and consequences of metabolic division of labor at other scales.}, } @article {pmid34721057, year = {2021}, author = {Larie, D and An, G and Cockrell, RC}, title = {The Use of Artificial Neural Networks to Forecast the Behavior of Agent-Based Models of Pathophysiology: An Example Utilizing an Agent-Based Model of Sepsis.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {716434}, pmid = {34721057}, issn = {1664-042X}, abstract = {Introduction: Disease states are being characterized at finer and finer levels of resolution via biomarker or gene expression profiles, while at the same time. Machine learning (ML) is increasingly used to analyze and potentially classify or predict the behavior of biological systems based on such characterization. As ML applications are extremely data-intensive, given the relative sparsity of biomedical data sets ML training of artificial neural networks (ANNs) often require the use of synthetic training data. Agent-based models (ABMs) that incorporate known biological mechanisms and their associated stochastic properties are a potential means of generating synthetic data. Herein we present an example of ML used to train an artificial neural network (ANN) as a surrogate system used to predict the time evolution of an ABM focusing on the clinical condition of sepsis. Methods: The disease trajectories for clinical sepsis, in terms of temporal cytokine and phenotypic dynamics, can be interpreted as a random dynamical system. The Innate Immune Response Agent-based Model (IIRABM) is a well-established model that utilizes known cellular and molecular rules to simulate disease trajectories corresponding to clinical sepsis. We have utilized two distinct neural network architectures, Long Short-Term Memory and Multi-Layer Perceptron, to take a time sequence of five measurements of eleven IIRABM simulated serum cytokine concentrations as input and to return both the future cytokine trajectories as well as an aggregate metric representing the patient's state of health. Results: The ANNs predicted model trajectories with the expected amount of error, due to stochasticity in the simulation, and recognizing that the mapping from a specific cytokine profile to a state-of-health is not unique. The Multi-Layer Perceptron neural network, generated predictions with a more accurate forecasted trajectory cone. Discussion: This work serves as a proof-of-concept for the use of ANNs to predict disease progression in sepsis as represented by an ABM. The findings demonstrate that multicellular systems with intrinsic stochasticity can be approximated with an ANN, but that forecasting a specific trajectory of the system requires sequential updating of the system state to provide a rolling forecast horizon.}, } @article {pmid34716269, year = {2021}, author = {Yang, H and Pegoraro, AF and Han, Y and Tang, W and Abeyaratne, R and Bi, D and Guo, M}, title = {Configurational fingerprints of multicellular living systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {44}, pages = {}, pmid = {34716269}, issn = {1091-6490}, support = {R01 GM140108/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biophysical Phenomena/*physiology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Epithelial Cells/cytology ; Humans ; Image Processing, Computer-Assisted/*methods ; Morphogenesis ; Neoplasms ; Organ Specificity/*physiology ; *Phase Transition ; Spheroids, Cellular/cytology ; Wound Healing ; }, abstract = {Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.}, } @article {pmid34716098, year = {2022}, author = {Bogaert, KA and Blomme, J and Beeckman, T and De Clerck, O}, title = {Auxin's origin: do PILS hold the key?.}, journal = {Trends in plant science}, volume = {27}, number = {3}, pages = {227-236}, doi = {10.1016/j.tplants.2021.09.008}, pmid = {34716098}, issn = {1878-4372}, mesh = {Biological Transport ; *Indoleacetic Acids/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Plants/genetics/metabolism ; }, abstract = {Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging evidence shows that the PIN and PIN-like (PILS) auxin transporter families have preceded the evolution of the canonical auxin response pathway. A wide conservation of PILS-mediated auxin transport, together with reports of auxin function in unicellular algae, would suggest that auxin function preceded the advent of multicellularity. We find that PIN and PILS transporters form two eukaryotic subfamilies within a larger bacterial family. We argue that future functional characterisation of algal PIN and PILS transporters can shed light on a common origin of an auxin function followed by independent co-option in a multicellular context.}, } @article {pmid34714532, year = {2022}, author = {Cao, Y}, title = {Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential.}, journal = {Stem cell reviews and reports}, volume = {18}, number = {1}, pages = {37-55}, pmid = {34714532}, issn = {2629-3277}, mesh = {Carcinogenesis/genetics ; Cell Differentiation/genetics ; *Germ Layers ; Humans ; *Neural Stem Cells ; }, abstract = {Tumorigenic cells are similar to neural stem cells or embryonic neural cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. By integrating the evidence from developmental biology, tumor biology and evolution, I will make a detailed discussion on the observations and propose that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Neural stemness property of tumorigenic cells can hopefully integrate different observations/concepts underlying tumorigenesis. Neural stem cells and tumorigenic cells share regulatory networks; both exhibit neural stemness, tumorigenicity and pluripotent differentiation potential; both depend on expression or activation of ancestral genes; both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells/tissues that are derived from three germ layers, leading to tumor formation resembling severely disorganized or more degenerated process of embryonic tissue differentiation; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. Neural regulatory networks, which include higher levels of basic machineries of cell physiological functions and developmental programs, work concertedly to define a basic state with fast cell cycle and proliferation. This is predestined by the evolutionary advantage of neural state, the ground or initial state for multicellularity with adaptation to an ancient environment. Tumorigenesis might represent a process of restoration of neural ground state, thereby restoring a state with fast proliferation and pluripotent differentiation potential in somatic cells. Tumorigenesis and pluripotent differentiation potential might be better understood from understanding neural stemness, and cancer therapy should benefit more from targeting neural stemness.}, } @article {pmid34711923, year = {2021}, author = {Wan, X and Saito, JA and Hou, S and Geib, SM and Yuryev, A and Higa, LM and Womersley, CZ and Alam, M}, title = {The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1232}, pmid = {34711923}, issn = {2399-3642}, mesh = {Adaptation, Biological/*physiology ; Animals ; Biological Evolution ; *Desiccation ; Gene Duplication/physiology ; Gene Expression Profiling ; Helminth Proteins/*genetics/metabolism ; Humidity ; Phosphotransferases/*genetics/metabolism ; Tylenchida/enzymology/*genetics ; Water/*metabolism ; }, abstract = {Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.}, } @article {pmid34699573, year = {2021}, author = {Tanno, A and Tokutsu, R and Arakaki, Y and Ueki, N and Minagawa, J and Yoshimura, K and Hisabori, T and Nozaki, H and Wakabayashi, KI}, title = {The four-celled Volvocales green alga Tetrabaena socialis exhibits weak photobehavior and high-photoprotection ability.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259138}, pmid = {34699573}, issn = {1932-6203}, mesh = {Chlorophyta/*physiology ; Photic Stimulation ; Phototropism/*physiology ; Volvox/*physiology ; }, abstract = {Photo-induced behavioral responses (photobehaviors) are crucial to the survival of motile phototrophic organisms in changing light conditions. Volvocine green algae are excellent model organisms for studying the regulatory mechanisms of photobehavior. We recently reported that unicellular Chlamydomonas reinhardtii and multicellular Volvox rousseletii exhibit similar photobehaviors, such as phototactic and photoshock responses, via different ciliary regulations. To clarify how the regulatory systems have changed during the evolution of multicellularity, we investigated the photobehaviors of four-celled Tetrabaena socialis. Surprisingly, unlike C. reinhardtii and V. rousseletii, T. socialis did not exhibit immediate photobehaviors after light illumination. Electrophysiological analysis revealed that the T. socialis eyespot does not function as a photoreceptor. Instead, T. socialis exhibited slow accumulation toward the light source in a photosynthesis-dependent manner. Our assessment of photosynthetic activities showed that T. socialis chloroplasts possess higher photoprotection abilities against strong light than C. reinhardtii. These data suggest that C. reinhardtii and T. socialis employ different strategies to avoid high-light stress (moving away rapidly and gaining photoprotection, respectively) despite their close phylogenetic relationship.}, } @article {pmid34695730, year = {2021}, author = {Grochau-Wright, ZI and Ferris, PJ and Tumberger, J and Jiménez-Marin, B and Olson, BJSC and Michod, RE}, title = {Characterization and Transformation of reg Cluster Genes in Volvox powersii Enable Investigation of Convergent Evolution of Cellular Differentiation in Volvox.}, journal = {Protist}, volume = {172}, number = {5-6}, pages = {125834}, doi = {10.1016/j.protis.2021.125834}, pmid = {34695730}, issn = {1618-0941}, support = {GT11065/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Base Sequence ; Cell Differentiation ; *Chlorophyta ; *Volvox/genetics ; }, abstract = {The evolution of germ-soma cellular differentiation represents a key step in the evolution of multicellular individuality. Volvox carteri and its relatives, the volvocine green algae, provide a model system for studying the evolution of cellular differentiation. In V. carteri, the regA gene controls somatic cell differentiation and is found in a group of paralogs called the reg cluster, along with rlsA, rlsB, and rlsC. However, the developmental program of V. carteri is derived compared to other volvocine algae. Here we examine Volvox powersii which possesses an ancestral developmental program and independent evolution of the Volvox body plan. We sequenced the reg cluster from V. powersii wild-type and a mutant with fewer cells and altered germ-soma ratio. We found that the mutant strain's rlsB gene has a deletion predicted to cause a truncated protein product. We developed a genetic transformation procedure to insert wild-type rlsB into the mutant strain. Transformation did not result in phenotypic rescue, suggesting the rlsB mutation is insufficient for generating the mutant phenotype. The transformation techniques and sequences described here provide essential tools to study V. powersii, a species well suited for studying the evolution of cellular differentiation and convergent evolution of Volvox morphology.}, } @article {pmid34685730, year = {2021}, author = {Ni, Z and Cheng, X}, title = {Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685730}, issn = {2073-4409}, support = {R35 GM122536/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Evolution, Molecular ; Guanine Nucleotide Exchange Factors/chemistry/*metabolism ; Humans ; *Phylogeny ; Protein Domains ; Protein Isoforms/chemistry/metabolism ; }, abstract = {Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the EPAC family, EPAC1 is only associated with chordates, while EPAC2 spans the entire animal kingdom. Despite a much more contemporary origin, EPAC1 proteins show much more sequence diversity among species, suggesting that EPAC1 has undergone more selection and evolved faster than EPAC2. Phylogenetic analyses of the individual cAMP binding domain (CBD) and guanine nucleotide exchange (GEF) domain of EPACs, two most conserved regions between the two isoforms, further reveal that EPAC1 and EPAC2 are closely clustered together within both the larger cyclic nucleotide receptor and RAPGEF families. These results support the notion that EPAC1 and EPAC2 share a common ancestor resulting from a fusion between the CBD of PKA and the GEF from RAPGEF1. On the other hand, the two terminal extremities and the RAS-association (RA) domains show the most sequence diversity between the two isoforms. Sequence diversities within these regions contribute significantly to the isoform-specific functions of EPACs. Importantly, unique isoform-specific sequence motifs within the RA domain have been identified.}, } @article {pmid34683464, year = {2021}, author = {Whitworth, DE and Sydney, N and Radford, EJ}, title = {Myxobacterial Genomics and Post-Genomics: A Review of Genome Biology, Genome Sequences and Related 'Omics Studies.}, journal = {Microorganisms}, volume = {9}, number = {10}, pages = {}, pmid = {34683464}, issn = {2076-2607}, abstract = {Myxobacteria are fascinating and complex microbes. They prey upon other members of the soil microbiome by secreting antimicrobial proteins and metabolites, and will undergo multicellular development if starved. The genome sequence of the model myxobacterium Myxococcus xanthus DK1622 was published in 2006 and 15 years later, 163 myxobacterial genome sequences have now been made public. This explosion in genomic data has enabled comparative genomics analyses to be performed across the taxon, providing important insights into myxobacterial gene conservation and evolution. The availability of myxobacterial genome sequences has allowed system-wide functional genomic investigations into entire classes of genes. It has also enabled post-genomic technologies to be applied to myxobacteria, including transcriptome analyses (microarrays and RNA-seq), proteome studies (gel-based and gel-free), investigations into protein-DNA interactions (ChIP-seq) and metabolism. Here, we review myxobacterial genome sequencing, and summarise the insights into myxobacterial biology that have emerged as a result. We also outline the application of functional genomics and post-genomic approaches in myxobacterial research, highlighting important findings to emerge from seminal studies. The review also provides a comprehensive guide to the genomic datasets available in mid-2021 for myxobacteria (including 24 genomes that we have sequenced and which are described here for the first time).}, } @article {pmid34681022, year = {2021}, author = {Luna, SK and Chain, FJJ}, title = {Lineage-Specific Genes and Family Expansions in Dictyostelid Genomes Display Expression Bias and Evolutionary Diversification during Development.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34681022}, issn = {2073-4425}, support = {R15 GM134498/GM/NIGMS NIH HHS/United States ; }, mesh = {Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; Gene Duplication/genetics ; Gene Expression Regulation, Developmental/genetics ; Genome/genetics ; *Phylogeny ; Species Specificity ; }, abstract = {Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes and gene family expansions were studied across five dictyostelid species to determine when and how they are expressed during multicellular development. Lineage-specific genes were found to be enriched among genes with biased expression (predominant expression in one developmental stage) in each species and at most developmental time points, suggesting independent functional innovations of new genes throughout the phylogeny. Biased duplicate genes had greater expression divergence than their orthologs and paralogs, consistent with subfunctionalization or neofunctionalization. Lineage-specific expansions in particular had biased genes with both molecular signals of positive selection and high expression, suggesting adaptive genetic and transcriptional diversification following duplication. Our results present insights into the potential contributions of lineage-specific genes and families in generating species-specific phenotypes during multicellular development in dictyostelids.}, } @article {pmid34680926, year = {2021}, author = {Cock, JM}, title = {Evolution of Multicellularity.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34680926}, issn = {2073-4425}, mesh = {Eukaryota/classification/cytology/genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {The emergence of multicellular organisms was, perhaps, the most spectacular of the major transitions during the evolutionary history of life on this planet [...].}, } @article {pmid34671319, year = {2021}, author = {Quinting, T and Heymann, AK and Bicker, A and Nauth, T and Bernardini, A and Hankeln, T and Fandrey, J and Schreiber, T}, title = {Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {732190}, pmid = {34671319}, issn = {1664-2392}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Cell Survival/drug effects/genetics ; Female ; Free Radical Scavengers/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Myoglobin/genetics/metabolism/*physiology ; Nitric Oxide/*metabolism ; Protective Agents/metabolism ; RNA, Small Interfering/pharmacology ; Reactive Oxygen Species/*metabolism ; Signal Transduction/drug effects/genetics ; Tumor Cells, Cultured ; }, abstract = {Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.}, } @article {pmid34665225, year = {2021}, author = {Zagoskin, MV and Wang, J}, title = {Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells.}, journal = {Biochemical Society transactions}, volume = {49}, number = {5}, pages = {1891-1903}, pmid = {34665225}, issn = {1470-8752}, support = {R01 AI155588/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chromosomes/genetics ; DNA Transposable Elements/*genetics ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression ; Gene Expression Regulation ; *Gene Silencing ; Germ Cells ; Humans ; }, abstract = {In a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected genes and repeats in somatic cells. Recent studies in nematodes suggest that DNA elimination removes all chromosome ends, resolves sex chromosome fusions, and may also promote the birth of novel genes. Programmed DNA elimination processes are diverse among species, suggesting DNA elimination likely has evolved multiple times in different taxa. The growing list of organisms that undergo DNA elimination indicates that DNA elimination may be more widespread than previously appreciated. These various organisms will serve as complementary and comparative models to study the function, mechanism, and evolution of programmed DNA elimination in metazoans.}, } @article {pmid34661335, year = {2022}, author = {Stüeken, EE and Viehmann, S and Hohl, SV}, title = {Contrasting nutrient availability between marine and brackish waters in the late Mesoproterozoic: Evidence from the Paranoá Group, Brazil.}, journal = {Geobiology}, volume = {20}, number = {2}, pages = {159-174}, doi = {10.1111/gbi.12478}, pmid = {34661335}, issn = {1472-4669}, mesh = {Brazil ; *Ecosystem ; Eukaryota ; Nutrients ; *Seawater ; }, abstract = {Understanding the delayed rise of eukaryotic life on Earth is one of the most fundamental questions about biological evolution. Numerous studies have presented evidence for oxygen and nutrient limitations in seawater during the Mesoproterozoic era, indicating that open marine settings may not have been able to sustain a eukaryotic biosphere with complex, multicellular organisms. However, many of these data sets represent restricted marine basins, which may bias our view of habitability. Furthermore, it remains untested whether rivers could have supplied significant nutrient fluxes to coastal habitats. To better characterize the sources of the major nutrients nitrogen and phosphorus, we turned to the late Mesoproterozoic Paranoá Group in Brazil (~1.1 Ga), which was deposited on a passive margin of the São Francisco craton. We present carbon, nitrogen and sulphur isotope data from an open shelf setting (Fazenda Funil) and from a brackish-water environment with significant riverine input (São Gabriel). Our results show that waters were well-oxygenated and nitrate was bioavailable in the open ocean setting at Fazenda Funil; the redoxcline appears to have been deeper and further offshore compared to restricted marine basins elsewhere in the Mesoproterozoic. In contrast, the brackish site at São Gabriel received only limited input of marine nitrate and sulphate. Nevertheless, previous reports of acritarchs reveal that this brackish-water setting was habitable to eukaryotic life. Paired with previously published cadmium isotope data, which can be used as a proxy for phosphorus cycling, our results suggest that complex organisms were perhaps not strictly dependent on marine nutrient supplies. Riverine influxes of P and possibly other nutrients likely rendered coastal waters perhaps equally habitable to the Mesoproterozoic open ocean. This conclusion supports the notion that eukaryotic organisms may have thrived in brackish or perhaps even freshwater environments.}, } @article {pmid34661162, year = {2021}, author = {Koya, J and Saito, Y and Kameda, T and Kogure, Y and Yuasa, M and Nagasaki, J and McClure, MB and Shingaki, S and Tabata, M and Tahira, Y and Akizuki, K and Kamiunten, A and Sekine, M and Shide, K and Kubuki, Y and Hidaka, T and Kitanaka, A and Nakano, N and Utsunomiya, A and Togashi, Y and Ogawa, S and Shimoda, K and Kataoka, K}, title = {Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1.}, journal = {Blood cancer discovery}, volume = {2}, number = {5}, pages = {450-467}, pmid = {34661162}, issn = {2643-3249}, mesh = {Animals ; Carcinogenesis/genetics ; Ecosystem ; *Human T-lymphotropic virus 1/genetics ; *Leukemia-Lymphoma, Adult T-Cell/genetics ; Mice ; Single-Cell Analysis ; }, abstract = {UNLABELLED: Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)-infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1-infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell-restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.

SIGNIFICANCE: Our multimodal single-cell analyses comprehensively dissect the cellular and molecular alterations of the peripheral blood in HTLV-1 infection, with and without progression to leukemia. This study not only sheds light on premalignant clonal expansion in viral carcinogenesis, but also helps to devise novel diagnostic and therapeutic strategies for HTLV-1-related disorders.}, } @article {pmid34648394, year = {2021}, author = {Simpson, C}, title = {Adaptation to a Viscous Snowball Earth Ocean as a Path to Complex Multicellularity.}, journal = {The American naturalist}, volume = {198}, number = {5}, pages = {590-609}, doi = {10.1086/716634}, pmid = {34648394}, issn = {1537-5323}, mesh = {Acclimatization ; Fungi ; *Ice Cover ; *Seawater ; Viscosity ; }, abstract = {AbstractAnimals, fungi, and algae with complex multicellular bodies all evolved independently from unicellular ancestors. The early history of these major eukaryotic multicellular clades, if not their origins, co-occur with an extreme phase of global glaciations known as the Snowball Earth. Here, I propose that the long-term loss of low-viscosity environments due to several rounds global glaciation drove the multiple origins of complex multicellularity in eukaryotes and the subsequent radiation of complex multicellular groups into previously unoccupied niches. In this scenario, life adapts to Snowball Earth oceans by evolving large size and faster speeds through multicellularity, which acts to compensate for high-viscosity seawater and achieve fluid flow at sufficient levels to satisfy metabolic needs. Warm, low-viscosity seawater returned with the melting of the Snowball glaciers, and with it, by virtue of large and fast multicellular bodies, new ways of life were unveiled.}, } @article {pmid34643506, year = {2021}, author = {Gao, Y and Park, HJ and Traulsen, A and Pichugin, Y}, title = {Evolution of irreversible somatic differentiation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34643506}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; *Cell Lineage ; Gene Expression Regulation ; Germ Cells/*physiology ; *Models, Biological ; Phenotype ; }, abstract = {A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism's performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.}, } @article {pmid34641578, year = {2021}, author = {Wofford, HA and Myers-Dean, J and Vogel, BA and Alamo, KAE and Longshore-Neate, FA and Jagodzinski, F and Amacher, JF}, title = {Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ Domains Using Human PDZ Data.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641578}, issn = {1420-3049}, mesh = {Amino Acid Sequence ; Choanoflagellata/*chemistry/*metabolism ; Computational Biology/*methods ; Evolution, Molecular ; Humans ; *PDZ Domains ; Phylogeny ; *Protein Binding ; Protein Conformation ; Signal Transduction ; Software ; Substrate Specificity ; }, abstract = {Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational software suite, Domain Analysis and Motif Matcher (DAMM), that analyzes peptide-binding cleft sequence identity as compared with human PDZ domains and that can be used in combination with literature searches of known human PDZ-interacting sequences to predict target specificity in choanoflagellate PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 μM affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contribute to investigations into choanoflagellate signaling and how it informs metazoan evolution.}, } @article {pmid34639193, year = {2021}, author = {Siletsky, SA and Borisov, VB}, title = {Proton Pumping and Non-Pumping Terminal Respiratory Oxidases: Active Sites Intermediates of These Molecular Machines and Their Derivatives.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639193}, issn = {1422-0067}, mesh = {Catalysis ; Catalytic Domain ; Electron Transport ; Oxidoreductases/chemistry/*metabolism ; Proton Pumps/chemistry/*metabolism ; *Protons ; }, abstract = {Terminal respiratory oxidases are highly efficient molecular machines. These most important bioenergetic membrane enzymes transform the energy of chemical bonds released during the transfer of electrons along the respiratory chains of eukaryotes and prokaryotes from cytochromes or quinols to molecular oxygen into a transmembrane proton gradient. They participate in regulatory cascades and physiological anti-stress reactions in multicellular organisms. They also allow microorganisms to adapt to low-oxygen conditions, survive in chemically aggressive environments and acquire antibiotic resistance. To date, three-dimensional structures with atomic resolution of members of all major groups of terminal respiratory oxidases, heme-copper oxidases, and bd-type cytochromes, have been obtained. These groups of enzymes have different origins and a wide range of functional significance in cells. At the same time, all of them are united by a catalytic reaction of four-electron reduction in oxygen into water which proceeds without the formation and release of potentially dangerous ROS from active sites. The review analyzes recent structural and functional studies of oxygen reduction intermediates in the active sites of terminal respiratory oxidases, the features of catalytic cycles, and the properties of the active sites of these enzymes.}, } @article {pmid34636664, year = {2021}, author = {Lin, Y and Alstrup, M and Pang, JKY and Maróti, G and Er-Rafik, M and Tourasse, N and Økstad, OA and Kovács, ÁT}, title = {Adaptation of Bacillus thuringiensis to Plant Colonization Affects Differentiation and Toxicity.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0086421}, pmid = {34636664}, issn = {2379-5077}, abstract = {The Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that are vertebrate or invertebrate pathogens. Few isolates from the B. cereus group have however been demonstrated to benefit plant growth. Therefore, it is crucial to explore how bacterial development and pathogenesis evolve during plant colonization. Herein, we investigated Bacillus thuringiensis (Cry[-]) adaptation to the colonization of Arabidopsis thaliana roots and monitored changes in cellular differentiation in experimentally evolved isolates. Isolates from two populations displayed improved iterative ecesis on roots and increased virulence against insect larvae. Molecular dissection and recreation of a causative mutation revealed the importance of a nonsense mutation in the rho transcription terminator gene. Transcriptome analysis revealed how Rho impacts various B. thuringiensis genes involved in carbohydrate metabolism and virulence. Our work suggests that evolved multicellular aggregates have a fitness advantage over single cells when colonizing plants, creating a trade-off between swimming and multicellularity in evolved lineages, in addition to unrelated alterations in pathogenicity. IMPORTANCE Biologicals-based plant protection relies on the use of safe microbial strains. During application of biologicals to the rhizosphere, microbes adapt to the niche, including genetic mutations shaping the physiology of the cells. Here, the experimental evolution of Bacillus thuringiensis lacking the insecticide crystal toxins was examined on the plant root to reveal how adaptation shapes the differentiation of this bacterium. Interestingly, evolution of certain lineages led to increased hemolysis and insect larva pathogenesis in B. thuringiensis driven by transcriptional rewiring. Further, our detailed study reveals how inactivation of the transcription termination protein Rho promotes aggregation on the plant root in addition to altered differentiation and pathogenesis in B. thuringiensis.}, } @article {pmid34635955, year = {2021}, author = {Schneider, C}, title = {Tuft cell integration of luminal states and interaction modules in tissues.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {473}, number = {11}, pages = {1713-1722}, pmid = {34635955}, issn = {1432-2013}, mesh = {Animals ; Chemoreceptor Cells/*physiology ; Epithelial Cells/*physiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {Chemosensory processes are integral to the physiology of most organisms. This function is typically performed by specialized cells that are able to detect input signals and to convert them to an output dedicated to a particular group of target cells. Tuft cells are cholinergic chemosensory epithelial cells capable of producing immunologically relevant effector molecules. They are scattered throughout endoderm-derived hollow organs and function as sensors of luminal stimuli, which has been best studied in mucosal barrier epithelia. Given their epithelial origin and broad distribution, and based on their interplay with immune pathways, tuft cells can be considered a prototypical example of how complex multicellular organisms engage innate immune mechanisms to modulate and optimize organ physiology. In this review, I provide a concise overview of tuft cells and discuss how these cells influence organ adaptation to dynamic luminal conditions.}, } @article {pmid34628994, year = {2021}, author = {Caetano-Anollés, G and Aziz, MF and Mughal, F and Caetano-Anollés, D}, title = {Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution.}, journal = {Expert review of proteomics}, volume = {18}, number = {10}, pages = {863-880}, doi = {10.1080/14789450.2021.1992277}, pmid = {34628994}, issn = {1744-8387}, mesh = {*Evolution, Molecular ; Genomics ; Humans ; Phylogeny ; Protein Folding ; *Proteome/genetics ; }, abstract = {INTRODUCTION: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past.

AREAS COVERED: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations.

EXPERT OPINION: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.}, } @article {pmid34596678, year = {2021}, author = {Schiller, EA and Bergstralh, DT}, title = {Interaction between Discs large and Pins/LGN/GPSM2: a comparison across species.}, journal = {Biology open}, volume = {10}, number = {11}, pages = {}, pmid = {34596678}, issn = {2046-6390}, support = {R01 GM125839/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Batrachoidiformes/genetics ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/*metabolism ; Cell Cycle Proteins/*metabolism ; Cell Division/*genetics ; Cnidaria/genetics ; Drosophila Proteins/metabolism ; Guanylate Kinases/metabolism ; Phylogeny ; Spindle Apparatus/*metabolism ; }, abstract = {The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge Opsacas minuta and propose that this divergence may correspond with differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.}, } @article {pmid34592312, year = {2021}, author = {Shrestha, S and Clark, AC}, title = {Evolution of the folding landscape of effector caspases.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101249}, pmid = {34592312}, issn = {1083-351X}, support = {R01 GM127654/GM/NIGMS NIH HHS/United States ; }, mesh = {Caspases, Effector/*chemistry/genetics/metabolism ; *Evolution, Molecular ; Humans ; *Models, Molecular ; *Protein Folding ; *Protein Multimerization ; }, abstract = {Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases [PCPs]) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor, whereas others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor (CA) into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their CA. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (PCP-7, CA) or dimeric (PCP-6) intermediate. In comparison, the unfolding pathway of PCP-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the CA and was retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.}, } @article {pmid34592264, year = {2022}, author = {Sego, TJ and Mochan, ED and Ermentrout, GB and Glazier, JA}, title = {A multiscale multicellular spatiotemporal model of local influenza infection and immune response.}, journal = {Journal of theoretical biology}, volume = {532}, number = {}, pages = {110918}, pmid = {34592264}, issn = {1095-8541}, support = {U24 EB028887/EB/NIBIB NIH HHS/United States ; R01 GM122424/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19 ; Humans ; Immunity, Innate ; *Influenza, Human ; SARS-CoV-2 ; *Virus Diseases ; }, abstract = {Respiratory viral infections pose a serious public health concern, from mild seasonal influenza to pandemics like those of SARS-CoV-2. Spatiotemporal dynamics of viral infection impact nearly all aspects of the progression of a viral infection, like the dependence of viral replication rates on the type of cell and pathogen, the strength of the immune response and localization of infection. Mathematical modeling is often used to describe respiratory viral infections and the immune response to them using ordinary differential equation (ODE) models. However, ODE models neglect spatially-resolved biophysical mechanisms like lesion shape and the details of viral transport, and so cannot model spatial effects of a viral infection and immune response. In this work, we develop a multiscale, multicellular spatiotemporal model of influenza infection and immune response by combining non-spatial ODE modeling and spatial, cell-based modeling. We employ cellularization, a recently developed method for generating spatial, cell-based, stochastic models from non-spatial ODE models, to generate much of our model from a calibrated ODE model that describes infection, death and recovery of susceptible cells and innate and adaptive responses during influenza infection, and develop models of cell migration and other mechanisms not explicitly described by the ODE model. We determine new model parameters to generate agreement between the spatial and original ODE models under certain conditions, where simulation replicas using our model serve as microconfigurations of the ODE model, and compare results between the models to investigate the nature of viral exposure and impact of heterogeneous infection on the time-evolution of the viral infection. We found that using spatially homogeneous initial exposure conditions consistently with those employed during calibration of the ODE model generates far less severe infection, and that local exposure to virus must be multiple orders of magnitude greater than a uniformly applied exposure to all available susceptible cells. This strongly suggests a prominent role of localization of exposure in influenza A infection. We propose that the particularities of the microenvironment to which a virus is introduced plays a dominant role in disease onset and progression, and that spatially resolved models like ours may be important to better understand and more reliably predict future health states based on susceptibility of potential lesion sites using spatially resolved patient data of the state of an infection. We can readily integrate the immune response components of our model into other modeling and simulation frameworks of viral infection dynamics that do detailed modeling of other mechanisms like viral internalization and intracellular viral replication dynamics, which are not explicitly represented in the ODE model. We can also combine our model with available experimental data and modeling of exposure scenarios and spatiotemporal aspects of mechanisms like mucociliary clearance that are only implicitly described by the ODE model, which would significantly improve the ability of our model to present spatially resolved predictions about the progression of influenza infection and immune response.}, } @article {pmid34575761, year = {2021}, author = {Gostinčar, C and Stajich, JE and Kejžar, A and Sinha, S and Nislow, C and Lenassi, M and Gunde-Cimerman, N}, title = {Seven Years at High Salinity-Experimental Evolution of the Extremely Halotolerant Black Yeast Hortaea werneckii.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {7}, number = {9}, pages = {}, pmid = {34575761}, issn = {2309-608X}, abstract = {The experimental evolution of microorganisms exposed to extreme conditions can provide insight into cellular adaptation to stress. Typically, stress-sensitive species are exposed to stress over many generations and then examined for improvements in their stress tolerance. In contrast, when starting with an already stress-tolerant progenitor there may be less room for further improvement, it may still be able to tweak its cellular machinery to increase extremotolerance, perhaps at the cost of poorer performance under non-extreme conditions. To investigate these possibilities, a strain of extremely halotolerant black yeast Hortaea werneckii was grown for over seven years through at least 800 generations in a medium containing 4.3 M NaCl. Although this salinity is well above the optimum (0.8-1.7 M) for the species, the growth rate of the evolved H. werneckii did not change in the absence of salt or at high concentrations of NaCl, KCl, sorbitol, or glycerol. Other phenotypic traits did change during the course of the experimental evolution, including fewer multicellular chains in the evolved strains, significantly narrower cells, increased resistance to caspofungin, and altered melanisation. Whole-genome sequencing revealed the occurrence of multiple aneuploidies during the experimental evolution of the otherwise diploid H. werneckii. A significant overrepresentation of several gene groups was observed in aneuploid regions. Taken together, these changes suggest that long-term growth at extreme salinity led to alterations in cell wall and morphology, signalling pathways, and the pentose phosphate cycle. Although there is currently limited evidence for the adaptive value of these changes, they offer promising starting points for future studies of fungal halotolerance.}, } @article {pmid34571874, year = {2021}, author = {Buravkova, L and Larina, I and Andreeva, E and Grigoriev, A}, title = {Microgravity Effects on the Matrisome.}, journal = {Cells}, volume = {10}, number = {9}, pages = {}, pmid = {34571874}, issn = {2073-4409}, mesh = {Animals ; Extracellular Matrix/*physiology ; Gravity, Altered ; Humans ; Space Flight/methods ; Weightlessness ; }, abstract = {Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the "gravisensors" in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth.}, } @article {pmid34571814, year = {2021}, author = {Reuveni, M}, title = {Sex and Regeneration.}, journal = {Biology}, volume = {10}, number = {9}, pages = {}, pmid = {34571814}, issn = {2079-7737}, abstract = {Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms (from simple animals such as hydra and planaria to plants and complex animals). The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to organs or tissues in nonreproductive conditions or by exposure to sex hormones.}, } @article {pmid34567752, year = {2021}, author = {Qu, F and Zhao, S and Cheng, G and Rahman, H and Xiao, Q and Chan, RWY and Ho, YP}, title = {Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis.}, journal = {Microsystems & nanoengineering}, volume = {7}, number = {}, pages = {38}, pmid = {34567752}, issn = {2055-7434}, abstract = {Multicellular spheroids have served as a promising preclinical model for drug efficacy testing and disease modeling. Many microfluidic technologies, including those based on water-oil-water double emulsions, have been introduced for the production of spheroids. However, sustained culture and the in situ characterization of the generated spheroids are currently unavailable for the double emulsion-based spheroid model. This study presents a streamlined workflow, termed the double emulsion-pretreated microwell culture (DEPMiC), incorporating the features of (1) effective initiation of uniform-sized multicellular spheroids by the pretreatment of double emulsions produced by microfluidics without the requirement of biomaterial scaffolds; (2) sustained maintenance and culture of the produced spheroids with facile removal of the oil confinement; and (3) in situ characterization of individual spheroids localized in microwells by a built-in analytical station. Characterized by microscopic observations and Raman spectroscopy, the DEPMiC cultivated spheroids accumulated elevated lipid ordering on the apical membrane, similar to that observed in their Matrigel counterparts. Made possible by the proposed technological advancement, this study subsequently examined the drug responses of these in vitro-generated multicellular spheroids. The developed DEPMiC platform is expected to generate health benefits in personalized cancer treatment by offering a pre-animal tool to dissect heterogeneity from individual tumor spheroids.}, } @article {pmid34564856, year = {2021}, author = {Charles Campbell, F}, title = {Untangling the complexities of micropapillary cancer[†].}, journal = {The Journal of pathology}, volume = {255}, number = {4}, pages = {343-345}, doi = {10.1002/path.5809}, pmid = {34564856}, issn = {1096-9896}, support = {C9136/A15342/CRUK_/Cancer Research UK/United Kingdom ; MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Adenocarcinoma of Lung ; *Carcinoma, Papillary ; Cell Polarity ; *Colorectal Neoplasms ; Humans ; *Lung Neoplasms ; }, abstract = {Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology, Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three-dimensional (3D) patient-derived CRC tissue-originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho-ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho-ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid34556094, year = {2021}, author = {Krishna, A and Gardiner, J and Donner, TJ and Scarpella, E}, title = {Control of vein-forming, striped gene expression by auxin signaling.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {213}, pmid = {34556094}, issn = {1741-7007}, mesh = {*Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Plant ; Indoleacetic Acids ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Activation of gene expression in striped domains is a key building block of biological patterning, from the recursive formation of veins in plant leaves to that of ribs and vertebrae in our bodies. In animals, gene expression is activated in striped domains by the differential affinity of broadly expressed transcription factors for their target genes and the combinatorial interaction between such target genes. In plants, how gene expression is activated in striped domains is instead unknown. We address this question for the broadly expressed MONOPTEROS (MP) transcription factor and its target gene ARABIDOPSIS THALIANA HOMEOBOX FACTOR8 (ATHB8).

RESULTS: We find that ATHB8 promotes vein formation and that such vein-forming function depends on both levels of ATHB8 expression and width of ATHB8 expression domains. We further find that ATHB8 expression is activated in striped domains by a combination of (1) activation of ATHB8 expression through binding of peak levels of MP to a low-affinity MP-binding site in the ATHB8 promoter and (2) repression of ATHB8 expression by MP target genes of the AUXIN/INDOLE-3-ACETIC-ACID-INDUCIBLE family.

CONCLUSIONS: Our findings suggest that a common regulatory logic controls activation of gene expression in striped domains in both plants and animals despite the independent evolution of their multicellularity.}, } @article {pmid34547424, year = {2021}, author = {Kun, Á}, title = {The major evolutionary transitions and codes of life.}, journal = {Bio Systems}, volume = {210}, number = {}, pages = {104548}, doi = {10.1016/j.biosystems.2021.104548}, pmid = {34547424}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Genetic Code/*genetics ; Humans ; Organelles/*physiology ; *Origin of Life ; Spheroids, Cellular/physiology ; }, abstract = {Major evolutionary transitions as well as the evolution of codes of life are key elements in macroevolution which are characterized by increase in complexity Major evolutionary transitions ensues by a transition in individuality and by the evolution of a novel mode of using, transmitting or storing information. Here is where codes of life enter the picture: they are arbitrary mappings between different (mostly) molecular species. This flexibility allows information to be employed in a variety of ways, which can fuel evolutionary innovation. The collation of the list of major evolutionary transitions and the list of codes of life show a clear pattern: codes evolved prior to a major evolutionary transition and then played roles in the transition and/or in the transformation of the new individual. The evolution of a new code of life is in itself not a major evolutionary transition but allow major evolutionary transitions to happen. This could help us to identify new organic codes.}, } @article {pmid34546795, year = {2021}, author = {Umen, J and Herron, MD}, title = {Green Algal Models for Multicellularity.}, journal = {Annual review of genetics}, volume = {55}, number = {}, pages = {603-632}, doi = {10.1146/annurev-genet-032321-091533}, pmid = {34546795}, issn = {1545-2948}, support = {R01 GM126557/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Chlorophyta/genetics ; Genome ; Phylogeny ; *Volvox/genetics ; }, abstract = {The repeated evolution of multicellularity across the tree of life has profoundly affected the ecology and evolution of nearly all life on Earth. Many of these origins were in different groups of photosynthetic eukaryotes, or algae. Here, we review the evolution and genetics of multicellularity in several groups of green algae, which include the closest relatives of land plants. These include millimeter-scale, motile spheroids of up to 50,000 cells in the volvocine algae; decimeter-scale seaweeds in the genus Ulva (sea lettuce); and very plantlike, meter-scale freshwater algae in the genus Chara (stoneworts). We also describe algae in the genus Caulerpa, which are giant, multinucleate, morphologically complex single cells. In each case, we review the life cycle, phylogeny, and genetics of traits relevant to the evolution of multicellularity, and genetic and genomic resources available for the group in question. Finally, we suggest routes toward developing these groups as model organisms for the evolution of multicellularity.}, } @article {pmid34545570, year = {2021}, author = {Maryenti, T and Ishii, T and Okamoto, T}, title = {Development and regeneration of wheat-rice hybrid zygotes produced by in vitro fertilization system.}, journal = {The New phytologist}, volume = {232}, number = {6}, pages = {2369-2383}, pmid = {34545570}, issn = {1469-8137}, mesh = {Fertilization in Vitro ; *Oryza/genetics ; Seeds/genetics ; Triticum/genetics ; *Zygote ; }, abstract = {Hybridization plays a decisive role in the evolution and diversification of angiosperms. However, the mechanisms of wide hybridization remain open because pre- and post-fertilization barriers limit the production and development of inter-subfamily/intergeneric zygotes, respectively. We examined hybridization between wheat and rice using an in vitro fertilization (IVF) system to bypass these barriers. Several gamete combinations of allopolyploid wheat-rice hybrid zygotes were successfully produced, and the developmental profiles of hybrid zygotes were analyzed. Hybrid zygotes derived from one rice egg cell and one wheat sperm cell ceased at the multicellular embryo-like structure stage. This developmental barrier was overcome by adding one wheat egg cell to the wheat-rice hybrid zygote. In the reciprocal combination, one wheat egg and one rice sperm cell, the resulting hybrid zygotes failed to divide. However, doubling the dosage of rice sperm cell allowed the hybrid zygotes to develop into plantlets. Rice chromosomes appeared to be progressively eliminated during the early developmental stage of these hybrid embryos, and c. 20% of regenerated plants showed abnormal morphology. These results suggest that hybrid breakdown can be overcome through optimization of gamete combinations, and the present hybrid will provide a new horizon for utilization of inter-subfamily genetic resources.}, } @article {pmid34529755, year = {2021}, author = {Turney, PD}, title = {Evolution of Autopoiesis and Multicellularity in the Game of Life.}, journal = {Artificial life}, volume = {27}, number = {1}, pages = {26-43}, doi = {10.1162/artl_a_00334}, pmid = {34529755}, issn = {1530-9185}, mesh = {Biological Evolution ; Models, Biological ; *Reproduction ; *Selection, Genetic ; Symbiosis ; }, abstract = {Recently we introduced a model of symbiosis, Model-S, based on the evolution of seed patterns in Conway's Game of Life. In the model, the fitness of a seed pattern is measured by one-on-one competitions in the Immigration Game, a two-player variation of the Game of Life. Our previous article showed that Model-S can serve as a highly abstract, simplified model of biological life: (1) The initial seed pattern is analogous to a genome. (2) The changes as the game runs are analogous to the development of the phenome. (3) Tournament selection in Model-S is analogous to natural selection in biology. (4) The Immigration Game in Model-S is analogous to competition in biology. (5) The first three layers in Model-S are analogous to biological reproduction. (6) The fusion of seed patterns in Model-S is analogous to symbiosis. The current article takes this analogy two steps further: (7) Autopoietic structures in the Game of Life (still lifes, oscillators, and spaceships-collectively known as ashes) are analogous to cells in biology. (8) The seed patterns in the Game of Life give rise to multiple, diverse, cooperating autopoietic structures, analogous to multicellular biological life. We use the apgsearch software (Ash Pattern Generator Search), developed by Adam Goucher for the study of ashes, to analyze autopoiesis and multicellularity in Model-S. We find that the fitness of evolved seed patterns in Model-S is highly correlated with the diversity and quantity of multicellular autopoietic structures.}, } @article {pmid34529461, year = {2021}, author = {Leslie, AB and Simpson, C and Mander, L}, title = {Reproductive innovations and pulsed rise in plant complexity.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6561}, pages = {1368-1372}, doi = {10.1126/science.abi6984}, pmid = {34529461}, issn = {1095-9203}, mesh = {*Biological Evolution ; Cycadopsida/anatomy & histology/genetics/growth & development ; Embryophyta/*anatomy & histology/growth & development/physiology ; Flowers/*anatomy & histology ; Fossils ; Magnoliopsida/anatomy & histology/genetics/growth & development/physiology ; Plant Structures/*anatomy & histology/growth & development ; Pollination ; Reproduction ; *Seeds ; Sporangia/anatomy & histology ; }, abstract = {Morphological complexity is a notable feature of multicellular life, although whether it evolves gradually or in early bursts is unclear. Vascular plant reproductive structures, such as flowers, are familiar examples of complex morphology. In this study, we use a simple approach based on the number of part types to analyze changes in complexity over time. We find that reproductive complexity increased in two pulses separated by ~250 million years of stasis, including an initial rise in the Devonian with the radiation of vascular plants and a pronounced increase in the Late Cretaceous that reflects flowering plant diversification. These pulses are associated with innovations that increased functional diversity, suggesting that shifts in complexity are linked to changes in function regardless of whether they occur early or late in the history of vascular plants.}, } @article {pmid34525330, year = {2021}, author = {Martinez-Miguel, VE and Lujan, C and Espie-Caullet, T and Martinez-Martinez, D and Moore, S and Backes, C and Gonzalez, S and Galimov, ER and Brown, AEX and Halic, M and Tomita, K and Rallis, C and von der Haar, T and Cabreiro, F and Bjedov, I}, title = {Increased fidelity of protein synthesis extends lifespan.}, journal = {Cell metabolism}, volume = {33}, number = {11}, pages = {2288-2300.e12}, pmid = {34525330}, issn = {1932-7420}, support = {R01 GM135599/GM/NIGMS NIH HHS/United States ; C416/A25145/CRUK_/Cancer Research UK/United Kingdom ; C7893/A28990/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1102/6/MRC_/Medical Research Council/United Kingdom ; MC_UP_1605/6/MRC_/Medical Research Council/United Kingdom ; 201487/WT_/Wellcome Trust/United Kingdom ; 102532/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/V006916/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 102531/Z/13/A/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; MC-A654-5QC80/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Longevity/genetics ; Phylogeny ; Protein Biosynthesis ; *Proteostasis/genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.}, } @article {pmid34524972, year = {2021}, author = {Gajdács, M and Kárpáti, K and Nagy, ÁL and Gugolya, M and Stájer, A and Burián, K}, title = {Association between biofilm-production and antibiotic resistance in Escherichia coli isolates: A laboratory-based case study and a literature review.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2021.01487}, pmid = {34524972}, issn = {1588-2640}, abstract = {Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.}, } @article {pmid34521896, year = {2021}, author = {Elsner, D and Hartfelder, K and Korb, J}, title = {Molecular underpinnings of division of labour among workers in a socially complex termite.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {18269}, pmid = {34521896}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Female ; Gene Expression ; Gene Expression Profiling ; Genes, Insect/genetics ; Isoptera/*genetics/physiology ; Male ; *Social Behavior ; Transcriptome/genetics ; }, abstract = {Division of labour characterizes all major evolutionary transitions, such as the evolution of eukaryotic cells or multicellular organisms. Social insects are characterized by reproductive division of labour, with one or a few reproducing individuals (queens) and many non-reproducing nestmates (workers) forming a colony. Among the workers, further division of labour can occur with different individuals performing different tasks such as foraging, brood care or building. While mechanisms underlying task division are intensively studied in social Hymenoptera, less is known for termites, which independently evolved eusociality. We investigated molecular mechanisms underlying task division in termite workers to test for communality with social Hymenoptera. We compared similar-aged foraging workers with builders of the fungus-growing termite Macrotermes bellicosus using transcriptomes, endocrine measures and estimators of physiological condition. Based on results for social Hymenoptera and theory, we tested the hypotheses that (i) foragers are in worse physiological conditions than builders, (ii) builders are more similar in their gene expression profile to queens than foragers are, and (iii) builders invest more in anti-ageing mechanism than foragers. Our results support all three hypotheses. We found storage proteins to underlie task division of these similar-aged termite workers and these genes also characterize reproductive division of labour between queens and workers. This implies a co-option of nutrient-based pathways to regulate division of labour across lineages of termites and social Hymenoptera, which are separated by more than 133 million years.}, } @article {pmid34520764, year = {2021}, author = {Steventon, B and Busby, L and Arias, AM}, title = {Establishment of the vertebrate body plan: Rethinking gastrulation through stem cell models of early embryogenesis.}, journal = {Developmental cell}, volume = {56}, number = {17}, pages = {2405-2418}, doi = {10.1016/j.devcel.2021.08.012}, pmid = {34520764}, issn = {1878-1551}, support = {109408/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Embryonic Development/genetics/*physiology ; Gastrulation/*physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Humans ; Morphogenesis/*physiology ; Stem Cells/*cytology ; Vertebrates/genetics ; }, abstract = {A striking property of vertebrate embryos is the emergence of a conserved body plan across a wide range of organisms through the process of gastrulation. As the body plan unfolds, gene regulatory networks (GRNs) and multicellular interactions (cell regulatory networks, CRNs) combine to generate a conserved set of morphogenetic events that lead to the phylotypic stage. Interrogation of these multilevel interactions requires manipulation of the mechanical environment, which is difficult in vivo. We review recent studies of stem cell models of early embryogenesis from different species showing that, independent of species origin, cells in culture form similar structures. The main difference between embryos and in vitro models is the boundary conditions of the multicellular ensembles. We discuss these observations and suggest that the mechanical and geometric boundary conditions of different embryos before gastrulation hide a morphogenetic ground state that is revealed in the stem-cell-based models of embryo development.}, } @article {pmid34516543, year = {2021}, author = {Henriques, GJB and van Vliet, S and Doebeli, M}, title = {Multilevel selection favors fragmentation modes that maintain cooperative interactions in multispecies communities.}, journal = {PLoS computational biology}, volume = {17}, number = {9}, pages = {e1008896}, pmid = {34516543}, issn = {1553-7358}, mesh = {*Models, Biological ; Mutation ; Plants/classification/genetics ; Reproduction/genetics ; *Selection, Genetic ; Species Specificity ; }, abstract = {Reproduction is one of the requirements for evolution and a defining feature of life. Yet, across the tree of life, organisms reproduce in many different ways. Groups of cells (e.g., multicellular organisms, colonial microbes, or multispecies biofilms) divide by releasing propagules that can be single-celled or multicellular. What conditions determine the number and size of reproductive propagules? In multicellular organisms, existing theory suggests that single-cell propagules prevent the accumulation of deleterious mutations (e.g., cheaters). However, groups of cells, such as biofilms, sometimes contain multiple metabolically interdependent species. This creates a reproductive dilemma: small daughter groups, which prevent the accumulation of cheaters, are also unlikely to contain the species diversity that is required for ecological success. Here, we developed an individual-based, multilevel selection model to investigate how such multi-species groups can resolve this dilemma. By tracking the dynamics of groups of cells that reproduce by fragmenting into smaller groups, we identified fragmentation modes that can maintain cooperative interactions. We systematically varied the fragmentation mode and calculated the maximum mutation rate that communities can withstand before being driven to extinction by the accumulation of cheaters. We find that for groups consisting of a single species, the optimal fragmentation mode consists of releasing single-cell propagules. For multi-species groups we find various optimal strategies. With migration between groups, single-cell propagules are favored. Without migration, larger propagules sizes are optimal; in this case, group-size dependent fissioning rates can prevent the accumulation of cheaters. Our work shows that multi-species groups can evolve reproductive strategies that allow them to maintain cooperative interactions.}, } @article {pmid34515793, year = {2021}, author = {Yeung, W and Kwon, A and Taujale, R and Bunn, C and Venkat, A and Kannan, N}, title = {Evolution of Functional Diversity in the Holozoan Tyrosine Kinome.}, journal = {Molecular biology and evolution}, volume = {38}, number = {12}, pages = {5625-5639}, pmid = {34515793}, issn = {1537-1719}, support = {R01 GM114409/GM/NIGMS NIH HHS/United States ; R35 GM139656/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Phosphorylation ; Phylogeny ; *Protein-Tyrosine Kinases/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Signal Transduction ; *Tyrosine/metabolism ; }, abstract = {The emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E-helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities, such as post-translational modification sites and regulatory interactions. Eph and EGFR receptor tyrosine kinases are two exceptions which lack this insert, each forming an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src module (SrcM), insulin receptor kinase-like (IRKL), and fibroblast, platelet-derived, vascular, and growth factor receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and coevolving protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM, and Csk, originated from unicellular premetazoans and were coopted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.}, } @article {pmid34512720, year = {2021}, author = {Lemoine, M}, title = {The Evolution of the Hallmarks of Aging.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {693071}, pmid = {34512720}, issn = {1664-8021}, abstract = {The evolutionary theory of aging has set the foundations for a comprehensive understanding of aging. The biology of aging has listed and described the "hallmarks of aging," i.e., cellular and molecular mechanisms involved in human aging. The present paper is the first to infer the order of appearance of the hallmarks of bilaterian and thereby human aging throughout evolution from their presence in progressively narrower clades. Its first result is that all organisms, even non-senescent, have to deal with at least one mechanism of aging - the progressive accumulation of misfolded or unstable proteins. Due to their cumulation, these mechanisms are called "layers of aging." A difference should be made between the first four layers of unicellular aging, present in some unicellular organisms and in all multicellular opisthokonts, that stem and strike "from the inside" of individual cells and span from increasingly abnormal protein folding to deregulated nutrient sensing, and the last four layers of metacellular aging, progressively appearing in metazoans, that strike the cells of a multicellular organism "from the outside," i.e., because of other cells, and span from transcriptional alterations to the disruption of intercellular communication. The evolution of metazoans and eumetazoans probably solved the problem of aging along with the problem of unicellular aging. However, metacellular aging originates in the mechanisms by which the effects of unicellular aging are kept under control - e.g., the exhaustion of stem cells that contribute to replace damaged somatic cells. In bilaterians, additional functions have taken a toll on generally useless potentially limited lifespan to increase the fitness of organisms at the price of a progressively less efficient containment of the damage of unicellular aging. In the end, this picture suggests that geroscience should be more efficient in targeting conditions of metacellular aging rather than unicellular aging itself.}, } @article {pmid34486115, year = {2021}, author = {Roy, SW}, title = {Digest: Three sexes from two loci in one genome: A haploid alga expands the diversity of trioecious species.}, journal = {Evolution; international journal of organic evolution}, volume = {75}, number = {11}, pages = {3002-3003}, doi = {10.1111/evo.14345}, pmid = {34486115}, issn = {1558-5646}, mesh = {Female ; *Genome ; Haploidy ; Humans ; Male ; }, abstract = {Multicellular eukaryotes exhibit a remarkable diversity of sexual systems; however, trioecy, the coexistence of male, female, and cosexual or hermaphrodite individuals in a single species, is remarkably rare. Takahashi et al. (2021) report the first known instance of trioecy in a haploid organism. In contrast to other known cases of trioecy, the authors report evidence for genetic control of all three sexes by two loci. These results complicate models for sexual system turnover and expand the known diversity of trioecy species in several ways.}, } @article {pmid34485312, year = {2021}, author = {Gómez, DP and Boudreau, F}, title = {Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {732137}, pmid = {34485312}, issn = {2296-634X}, abstract = {Maintenance of intestinal epithelium homeostasis is a complex process because of the multicellular and molecular composition of the gastrointestinal wall and the involvement of surrounding interactive signals. The complex nature of this intestinal barrier system poses challenges in the detailed mechanistic understanding of intestinal morphogenesis and the onset of several gut pathologies, including intestinal inflammatory disorders, food allergies, and cancer. For several years, the gut scientific community has explored different alternatives in research involving animals and in vitro models consisting of cultured monolayers derived from the immortalized or cancerous origin cell lines. The recent ability to recapitulate intestinal epithelial dynamics from mini-gut cultures has proven to be a promising step in the field of scientific research and biomedicine. The organoids can be grown as two- or three-dimensional structures, and are derived from adult or pluripotent stem cells that ultimately establish an intestinal epithelium that is composed of all differentiated cell types present in the normal epithelium. In this review, we summarize the different origins and recent use of organoids in modeling intestinal epithelial differentiation and barrier properties.}, } @article {pmid34483853, year = {2021}, author = {Marshall, PJ and Houser, TM and Weiss, SM}, title = {The Shared Origins of Embodiment and Development.}, journal = {Frontiers in systems neuroscience}, volume = {15}, number = {}, pages = {726403}, pmid = {34483853}, issn = {1662-5137}, abstract = {As a domain of study centering on the nature of the body in the functioning of the individual organism, embodiment encompasses a diverse array of topics and questions. One useful organizing framework places embodiment as a bridge construct connecting three standpoints on the body: the form of the body, the body as actively engaged in and with the world, and the body as lived experience. Through connecting these standpoints, the construct of embodiment shows that they are not mutually exclusive: inherent in form is the capacity for engagement, and inherent in engagement is a lived perspective that confers agency and meaning. Here, we employ this framework to underscore the deep connections between embodiment and development. We begin with a discussion of the origins of multicellularity, highlighting how the evolution of bodies was the evolution of development itself. The evolution of the metazoan (animal) body is of particular interest, because most animals possess complex bodies with sensorimotor capacities for perceiving and acting that bring forth a particular sort of embodiment. However, we also emphasize that the thread of embodiment runs through all living things, which share an organizational property of self-determination that endows them with a specific kind of autonomy. This realization moves us away from a Cartesian machine metaphor and instead puts an emphasis on the lived perspective that arises from being embodied. This broad view of embodiment presents opportunities to transcend the boundaries of individual disciplines to create a novel integrative vision for the scientific study of development.}, } @article {pmid34480926, year = {2021}, author = {Mani, S and Tlusty, T}, title = {A topological look into the evolution of developmental programs.}, journal = {Biophysical journal}, volume = {120}, number = {19}, pages = {4193-4201}, pmid = {34480926}, issn = {1542-0086}, mesh = {*Biological Evolution ; *Selection, Genetic ; }, abstract = {Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describing the intertwined network of spatiotemporal processes underlying the development of complex multicellular organisms. Nonetheless, an overview of developmental trajectories can be obtained from cell type lineage maps. Here, we propose that these lineage maps can also reveal how developmental programs evolve: the modes of evolving new cell types in an organism should be visible in its developmental trajectories and therefore in the geometry of its cell type lineage map. This idea is demonstrated using a parsimonious generative model of developmental programs, which allows us to reliably survey the universe of all possible programs and examine their topological features. We find that, contrary to belief, tree-like lineage maps are rare, and lineage maps of complex multicellular organisms are likely to be directed acyclic graphs in which multiple developmental routes can converge on the same cell type. Although cell type evolution prescribes what developmental programs come into existence, natural selection prunes those programs that produce low-functioning organisms. Our model indicates that additionally, lineage map topologies are correlated with such a functional property: the ability of organisms to regenerate.}, } @article {pmid34477897, year = {2021}, author = {Swiatczak, B}, title = {Struggle within: evolution and ecology of somatic cell populations.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {21-22}, pages = {6797-6806}, pmid = {34477897}, issn = {1420-9071}, mesh = {Adaptive Immunity/genetics ; Animals ; Biological Evolution ; DNA/genetics ; Ecology ; Humans ; Mutation/*genetics ; Selection, Genetic/genetics ; }, abstract = {The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives.}, } @article {pmid34476388, year = {2021}, author = {Boedicker, JQ and Gangan, M and Naughton, K and Zhao, F and Gralnick, JA and El-Naggar, MY}, title = {Engineering Biological Electron Transfer and Redox Pathways for Nanoparticle Synthesis.}, journal = {Bioelectricity}, volume = {3}, number = {2}, pages = {126-135}, pmid = {34476388}, issn = {2576-3113}, abstract = {Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.}, } @article {pmid34467433, year = {2021}, author = {Wang, X and Dong, F and Liu, J and Tan, Y and Hu, S and Zhao, H}, title = {The self-healing of Bacillus subtilis biofilms.}, journal = {Archives of microbiology}, volume = {203}, number = {9}, pages = {5635-5645}, pmid = {34467433}, issn = {1432-072X}, mesh = {*Bacillus subtilis ; *Biofilms ; Humans ; }, abstract = {Self-healing is an intrinsic ability that exists widely in every multicellular biological organism. Our recent experiments have shown that bacterial biofilms also have the ability to self-heal after man-make cuts, but the mechanism of biofilm self-healing have not been studied. We find that the healing process of cuts on the biofilm depends on cut geometries like its location or direction, the biofilm itself like the biofilm age, the growing substrate properties like its hardness, and also the environments such as the competitive growth of multiple biofilms. What is more, the healing rate along the cut is heterogeneous, and the maximum healing rate can reach 260 μm/h, which is three times the undestroyed biofilm expansion rate. The cut does not change the rounded shape growth of biofilms. Further study of phenotypic evolution shows that the cut delays bacterial differentiation; motile cells perceive the cut and move to the cut area, while the cut only heals when there are enough matrix-producing cells in the cut area. Our work suggests new ideas for developing self-healing materials.}, } @article {pmid34465312, year = {2021}, author = {Lindsey, CR and Rosenzweig, F and Herron, MD}, title = {Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {182}, pmid = {34465312}, issn = {1741-7007}, mesh = {Bayes Theorem ; Biological Evolution ; Cell Differentiation ; Chlamydomonas reinhardtii ; *Phylogeny ; Transcriptome ; Volvox/genetics ; }, abstract = {BACKGROUND: The volvocine algae, which include the single-celled species Chlamydomonas reinhardtii and the colonial species Volvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the history of this group have by and large relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. As a result, volvocine phylogenies lack concordance depending on the number and/or type of genes (i.e., chloroplast vs nuclear) chosen for phylogenetic inference. While multiple studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group, other studies call into question one or more of these conclusions. An accurate assessment of the evolutionary history of the volvocine algae requires inference of a more robust phylogeny.

RESULTS: We performed RNA sequencing (RNA-seq) on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We then compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes and subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation arose independently at least four, and possibly as many as six times, within the volvocine algae.

CONCLUSIONS: Altogether, our results demonstrate that multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming the importance of this group as a model system for the study of major transitions in the history of life.}, } @article {pmid34463760, year = {2021}, author = {Diegmiller, R and Doherty, CA and Stern, T and Imran Alsous, J and Shvartsman, SY}, title = {Size scaling in collective cell growth.}, journal = {Development (Cambridge, England)}, volume = {148}, number = {18}, pages = {}, pmid = {34463760}, issn = {1477-9129}, support = {R01 GM134204/GM/NIGMS NIH HHS/United States ; F31 HD098835/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Proliferation/*physiology ; Developmental Biology/methods ; Diptera/physiology ; Germ Cells/physiology ; Oogenesis/physiology ; Organelles/physiology ; }, abstract = {Size is a fundamental feature of living entities and is intimately tied to their function. Scaling laws, which can be traced to D'Arcy Thompson and Julian Huxley, have emerged as a powerful tool for studying regulation of the growth dynamics of organisms and their constituent parts. Yet, throughout the 20th century, as scaling laws were established for single cells, quantitative studies of the coordinated growth of multicellular structures have lagged, largely owing to technical challenges associated with imaging and image processing. Here, we present a supervised learning approach for quantifying the growth dynamics of germline cysts during oogenesis. Our analysis uncovers growth patterns induced by the groupwise developmental dynamics among connected cells, and differential growth rates of their organelles. We also identify inter-organelle volumetric scaling laws, finding that nurse cell growth is linear over several orders of magnitude. Our approach leverages the ever-increasing quantity and quality of imaging data, and is readily amenable for studies of collective cell growth in other developmental contexts, including early mammalian embryogenesis and germline development.}, } @article {pmid34462837, year = {2021}, author = {Mikhalevich, VI}, title = {Aromorphoses in the Evolution of Unicellular Eukaryotes (as Exemplified by Foraminifera D'orbigny, 1826).}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {499}, number = {1}, pages = {105-108}, pmid = {34462837}, issn = {1608-3105}, mesh = {Eukaryota ; *Foraminifera/genetics ; }, abstract = {Aromorphoses of unicellular organisms are almost unexplored. Foraminifera provide a unique opportunity of such studies, having the most complex structure and being most fully represented in the geological record. In their development, more than 10 aromorphoses (key advances) have first been discovered, which arose in different classes of Foraminifera independently and in parallel. Of these, the key ones are the emergence of an agglutinated and then secreted calcareous shell, a bifontinal (bilamellar) wall, multichamberedness, differentiation of chambers, an integrating system of channels and nuclear dualism. They represent peculiar ways of evolution at the unicellular level. Multicameredness can be compared with multicellularity; differentiation of chambers, with differentiation of tissues; a system of channels, striking in its complexity and carrying O2, with the Metazoa circulatory system.}, } @article {pmid34458231, year = {2021}, author = {Pellissier, L and Koval, A and Marcourt, L and Ferreira Queiroz, E and Lecoultre, N and Leoni, S and Quiros-Guerrero, LM and Barthélémy, M and Duivelshof, BL and Guillarme, D and Tardy, S and Eparvier, V and Perron, K and Chave, J and Stien, D and Gindro, K and Katanaev, V and Wolfender, JL}, title = {Isolation and Identification of Isocoumarin Derivatives With Specific Inhibitory Activity Against Wnt Pathway and Metabolome Characterization of Lasiodiplodia venezuelensis.}, journal = {Frontiers in chemistry}, volume = {9}, number = {}, pages = {664489}, pmid = {34458231}, issn = {2296-2646}, abstract = {The Wnt signaling pathway controls multiple events during embryonic development of multicellular animals and is carcinogenic when aberrantly activated in adults. Breast cancers are dependent on Wnt pathway overactivation mostly through dysregulation of pathway component protein expression, which necessitates the search for therapeutically relevant compounds targeting them. Highly diverse microorganisms as endophytes represent an underexplored field in the therapeutic natural products research. In the present work, the objective was to explore the chemical diversity and presence of selective Wnt inhibitors within a unique collection of fungi isolated as foliar endophytes from the long-lived tropical palm Astrocaryum sciophilum. The fungi were cultured, extracted with ethyl acetate, and screened for their effects on the Wnt pathway and cell proliferation. The endophytic strain Lasiodiplodia venezuelensis was prioritized for scaled-up fractionation based on its selective activity. Application of geometric transfer from analytical HPLC conditions to semi-preparative scale and use of dry load sample introduction enabled the isolation of 15 pure compounds in a single step. Among the molecules identified, five are original natural products described for the first time, and six are new to this species. An active fraction obtained by semi-preparative HPLC was re-purified by UHPLC-PDA using a 1.7 µm phenyl column. 75 injections of 8 µg were necessary to obtain sufficient amounts of each compound for structure elucidation and bioassays. Using this original approach, in addition to the two major compounds, a third minor compound identified as (R)-(-)-5-hydroxymellein (18) was obtained, which was found to be responsible for the significant Wnt inhibition activity recorded. Further studies of this compound and its structural analogs showed that only 18 acts in a highly specific manner, with no acute cytotoxicity. This compound is notably selective for upstream components of the Wnt pathway and is able to inhibit the proliferation of three triple negative breast cancer cell lines. In addition to the discovery of Wnt inhibitors of interest, this study contributes to better characterize the biosynthetic potential of L. venezuelensis.}, } @article {pmid34455760, year = {2021}, author = {Louka, A and Takan, I and Pavlopoulou, A and Georgakilas, AG}, title = {Bioinformatic approaches to the investigation of the atavistic genes implicated in cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {26}, number = {8}, pages = {279-311}, doi = {10.52586/4944}, pmid = {34455760}, issn = {2768-6698}, mesh = {Biological Evolution ; *Computational Biology ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {Introduction: Cancer is a widespread phenomenon occurring across multicellular organisms and represents a condition of atavism, wherein cells follow a path of reverse evolution that unlocks a toolkit of ancient pre-existing adaptations by disturbing hub genes of the human gene network. This results to a primitive cellular phenotype which resembles a unicellular life form. Methods: In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (ACTG1, CTNNA1, CTNND1, CTTN, DSP, ILK, PKN2, PKP3, PLEC, RCC2, TLN1 and VASP), which exhibit highly disrupted interactions in diverse types of cancer and are associated with the formation of metastasis. To this end, phylogenetic analyses were conducted towards unravelling the evolutionary history of those hubs and tracing the origin of cancer in the Tree of Life. Results: Based on our results, most of those genes are of unicellular origin, and some of them can be traced back to the emergence of cellular life itself (atavistic theory). Our findings indicate how deep the evolutionary roots of cancer actually are, and may be exploited in the clinical setting for the design of novel therapeutic approaches and, particularly, in overcoming resistance to antineoplastic treatment.}, } @article {pmid34440622, year = {2021}, author = {Mandujano-Tinoco, EA and Sultan, E and Ottolenghi, A and Gershoni-Yahalom, O and Rosental, B}, title = {Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440622}, issn = {2073-4409}, mesh = {Animals ; Bacteria/immunology/pathogenicity ; *Cell Lineage ; Communicable Diseases/*immunology/metabolism ; *Cytotoxicity, Immunologic ; Host-Pathogen Interactions ; Humans ; *Immunity, Cellular ; *Immunity, Innate ; Parasites/immunology/pathogenicity ; Phagocytes/*immunology/metabolism ; *Phagocytosis ; Signal Transduction ; Viruses/immunology/pathogenicity ; }, abstract = {The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.}, } @article {pmid34430989, year = {2021}, author = {Suthar, J and Al-Jufaili, S and Bray, RA and Frank, M and Theisen, S and Palm, HW}, title = {Redescription of Aspidogaster limacoides Diesing, 1834 (Aspidogastrea: Aspidogastridae) from freshwater fishes of northern Germany.}, journal = {Parasitology research}, volume = {120}, number = {10}, pages = {3405-3416}, pmid = {34430989}, issn = {1432-1955}, mesh = {Animals ; *Cyprinidae ; Fishes ; Fresh Water ; Germany ; Phylogeny ; *Trematoda ; }, abstract = {Aspidogaster limacoides Diesing, 1834 (Aspidogastridae) is redescribed based on light and scanning electron microscopy of specimens from the stomach and intestine of Abramis brama, Rutilus rutilus and Scardinius erythrophthalmus (Actinopterygii: Cyprinidae). The fishes were sampled during 2018 and 2019 at Lake Tollense in Mecklenburg-Western Pomerania, Germany. The prevalence of A. limacoides was highest in R. rutilus (61.7%) followed by Scardinius erythrophthalmus (7.7%) and A. brama (2.9%), while it was absent in Perca fluviatilis from the same lake. The following structures of A. limacoides are described for the first time: a depression on the ventral side of the neck, variations in the number and the arrangement of alveoli, numerous pits scattered all over the body surface, the presence of a few papillae-like structures posterior lateral to the mouth, the number of marginal organs represented by openings of exocrine multicellular glands as shown in histology and the subterminal position of the excretory pore. These characters can be used to distinguish three species of Aspidogaster, namely, A. ijimai, A. conchicola and A. limacoides, suggesting that SEM is a useful and promising tool in differentiating Aspidogaster species. Comparison of molecular data of the ITS1-5.8S-ITS2 regions showed a 94% similarity to A. limacoides from the European part of Russia. Phylogenetic analysis showed that the present specimens clustered in the same clade with A. limacoides sensu stricto, forming a distinct group to the exclusion of congeners.}, } @article {pmid34411089, year = {2021}, author = {Leray, M and Wilkins, LGE and Apprill, A and Bik, HM and Clever, F and Connolly, SR and De León, ME and Duffy, JE and Ezzat, L and Gignoux-Wolfsohn, S and Herre, EA and Kaye, JZ and Kline, DI and Kueneman, JG and McCormick, MK and McMillan, WO and O'Dea, A and Pereira, TJ and Petersen, JM and Petticord, DF and Torchin, ME and Vega Thurber, R and Videvall, E and Wcislo, WT and Yuen, B and Eisen, JA}, title = {Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution.}, journal = {PLoS biology}, volume = {19}, number = {8}, pages = {e3001322}, pmid = {34411089}, issn = {1545-7885}, mesh = {*Acclimatization ; Animals ; Aquatic Organisms/*microbiology ; *Biological Evolution ; *Ecology ; Ecosystem ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host's physiological capacities; however, the identity and functional role(s) of key members of the microbiome ("core microbiome") in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems' capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts' plastic and adaptive responses to environmental change requires (i) recognizing that individual host-microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.}, } @article {pmid34408733, year = {2021}, author = {Schapheer, C and Pellens, R and Scherson, R}, title = {Arthropod-Microbiota Integration: Its Importance for Ecosystem Conservation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {702763}, pmid = {34408733}, issn = {1664-302X}, abstract = {Recent reports indicate that the health of our planet is getting worse and that genuine transformative changes are pressing. So far, efforts to ameliorate Earth's ecosystem crises have been insufficient, as these often depart from current knowledge of the underlying ecological processes. Nowadays, biodiversity loss and the alterations in biogeochemical cycles are reaching thresholds that put the survival of our species at risk. Biological interactions are fundamental for achieving biological conservation and restoration of ecological processes, especially those that contribute to nutrient cycles. Microorganism are recognized as key players in ecological interactions and nutrient cycling, both free-living and in symbiotic associations with multicellular organisms. This latter assemblage work as a functional ecological unit called "holobiont." Here, we review the emergent ecosystem properties derived from holobionts, with special emphasis on detritivorous terrestrial arthropods and their symbiotic microorganisms. We revisit their relevance in the cycling of recalcitrant organic compounds (e.g., lignin and cellulose). Finally, based on the interconnection between biodiversity and nutrient cycling, we propose that a multicellular organism and its associates constitute an Ecosystem Holobiont (EH). This EH is the functional unit characterized by carrying out key ecosystem processes. We emphasize that in order to meet the challenge to restore the health of our planet it is critical to reduce anthropic pressures that may threaten not only individual entities (known as "bionts") but also the stability of the associations that give rise to EH and their ecological functions.}, } @article {pmid34404788, year = {2021}, author = {Galindo, LJ and López-García, P and Torruella, G and Karpov, S and Moreira, D}, title = {Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4973}, pmid = {34404788}, issn = {2041-1723}, mesh = {Basal Bodies ; Blastocladiomycota ; Chytridiomycota/classification ; Flagella ; Fungi/*classification/cytology/genetics/metabolism ; Genomics ; Hepatophyta/*classification ; Hyphae ; Phenotype ; *Phylogeny ; Specimen Handling ; Transcriptome ; }, abstract = {Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytrids Amoeboradix gromovi and Sanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids' phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.}, } @article {pmid34395440, year = {2021}, author = {Richter, M and Piwocka, O and Musielak, M and Piotrowski, I and Suchorska, WM and Trzeciak, T}, title = {From Donor to the Lab: A Fascinating Journey of Primary Cell Lines.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {711381}, pmid = {34395440}, issn = {2296-634X}, abstract = {Primary cancer cell lines are ex vivo cell cultures originating from resected tissues during biopsies and surgeries. Primary cell cultures are objects of intense research due to their high impact on molecular biology and oncology advancement. Initially, the patient-derived specimen must be subjected to dissociation and isolation. Techniques for tumour dissociation are usually reliant on the organisation of connecting tissue. The most common methods include enzymatic digestion (with collagenase, dispase, and DNase), chemical treatment (with ethylene diamine tetraacetic acid and ethylene glycol tetraacetic acid), or mechanical disaggregation to obtain a uniform cell population. Cells isolated from the tissue specimen are cultured as a monolayer or three-dimensional culture, in the form of multicellular spheroids, scaffold-based cultures (i.e., organoids), or matrix-embedded cultures. Every primary cell line must be characterised to identify its origin, purity, and significant features. The process of characterisation should include different assays utilising specific (extra- and intracellular) markers. The most frequently used approaches comprise immunohistochemistry, immunocytochemistry, western blot, flow cytometry, real-time polymerase chain reaction, karyotyping, confocal microscopy, and next-generation sequencing. The growing body of evidence indicates the validity of the usage of primary cancer cell lines in the formulation of novel anti-cancer treatments and their contribution to drug development.}, } @article {pmid34394122, year = {2021}, author = {Sun, V and Sharpley, M and Kaczor-Urbanowicz, KE and Chang, P and Montel-Hagen, A and Lopez, S and Zampieri, A and Zhu, Y and de Barros, SC and Parekh, C and Casero, D and Banerjee, U and Crooks, GM}, title = {The Metabolic Landscape of Thymic T Cell Development In Vivo and In Vitro.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {716661}, pmid = {34394122}, issn = {1664-3224}, support = {P30 AG028748/AG/NIA NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Biomarkers ; *Cell Differentiation ; Cell Line ; Computational Biology/methods ; *Energy Metabolism ; Gene Expression Profiling ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Lymphopoiesis ; Metabolome ; Metabolomics/methods ; Mice ; Organoids ; T-Lymphocytes/*cytology/*metabolism ; Thymocytes/*cytology/immunology/*metabolism ; Tissue Culture Techniques ; }, abstract = {Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and in vitro-derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus. Remarkably, despite the absence of the complex multicellular thymic microenvironment, in vitro murine and human T cell development recapitulated the coordinated decrease in glycolytic and oxidative phosphorylation activity between the DN and DP stages seen in primary thymus. Moreover, by inducing in vitro T cell differentiation from Rag1[-/-] mouse bone marrow, we show that reduced metabolic activity at the DP stage is independent of TCR rearrangement. Thus, our findings suggest that highly conserved metabolic transitions are critical for thymic T cell development.}, } @article {pmid34385986, year = {2021}, author = {Zhang, W and Wang, Y and Liu, L and Pan, Y and Lin, W}, title = {Identification and Genomic Characterization of Two Previously Unknown Magnetotactic Nitrospirae.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {690052}, pmid = {34385986}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) are a group of microbes that biomineralize membrane-bound, nanosized magnetite (Fe3O4), and/or greigite (Fe3S4) crystals in intracellular magnetic organelle magnetosomes. MTB belonging to the Nitrospirae phylum can form up to several hundreds of Fe3O4 magnetosome crystals and dozens of sulfur globules in a single cell. These MTB are widespread in aquatic environments and sometimes account for a significant proportion of microbial biomass near the oxycline, linking these lineages to the key steps of global iron and sulfur cycling. Despite their ecological and biogeochemical importance, our understanding of the diversity and ecophysiology of magnetotactic Nitrospirae is still very limited because this group of MTB remains unculturable. Here, we identify and characterize two previously unknown MTB populations within the Nitrospirae phylum through a combination of 16S rRNA gene-based and genome-resolved metagenomic analyses. These two MTB populations represent distinct morphotypes (rod-shaped and coccoid, designated as XYR, and XYC, respectively), and both form more than 100 bullet-shaped magnetosomal crystals per cell. High-quality draft genomes of XYR and XYC have been reconstructed, and they represent a novel species and a novel genus, respectively, according to their average amino-acid identity values with respect to available genomes. Accordingly, the names Candidatus Magnetobacterium cryptolimnobacter and Candidatus Magnetomicrobium cryptolimnococcus for XYR and XYC, respectively, were proposed. Further comparative genomic analyses of XYR, XYC, and previously reported magnetotactic Nitrospirae reveal the general metabolic potential of this MTB group in distinct microenvironments, including CO2 fixation, dissimilatory sulfate reduction, sulfide oxidation, nitrogen fixation, or denitrification processes. A remarkably conserved magnetosome gene cluster has been identified across Nitrospirae MTB genomes, indicating its putative important adaptive roles in these bacteria. Taken together, the present study provides novel insights into the phylogenomic diversity and ecophysiology of this intriguing, yet poorly understood MTB group.}, } @article {pmid34384851, year = {2021}, author = {Cisbani, G and Metherel, AH and Smith, ME and Bazinet, RP}, title = {Murine and human microglial cells are relatively enriched with eicosapentaenoic acid compared to the whole brain.}, journal = {Neurochemistry international}, volume = {150}, number = {}, pages = {105154}, doi = {10.1016/j.neuint.2021.105154}, pmid = {34384851}, issn = {1872-9754}, support = {//CIHR/Canada ; }, mesh = {Animals ; Brain/cytology/*metabolism ; Brain Chemistry/*physiology ; Eicosapentaenoic Acid/analysis/*metabolism ; Female ; Fetus ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Microglia/chemistry/*metabolism ; }, abstract = {The brain is a multicellular organ enriched with lipids. While the fatty acid composition of gross cerebral tissue is well characterized, the fatty acid composition of specific brain cells, particularly microglia cells, is less well characterized. Microglia cells are the innate immune cells of the brain, and a paucity of studies measuring their fatty acid composition using either immortalized or primary microglia cells report a higher ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) than widely observed in whole brain tissue. Here we further characterize the fatty acid composition of murine microglia cells from young male and female mice as well as of human origin and compared it with a myelin-enriched fraction from the same mice. Our results show that saturated and monounsaturated fatty acids are the most abundant followed by polyunsaturated fatty acids (PUFA), with no statistical differences between sexes. Regarding PUFA, although DHA levels did not differ between human and murine cells, EPA was statistically higher in murine microglia. Notably, the DHA to EPA ratio was about 400 times lower in microglial cells compared to the myelin-enriched fraction. Thus, our results suggest that as compared to whole brain tissue EPA is relatively abundant in microglia cells, particularly in comparison to other n-3 PUFA such as DHA. Since the fatty acid composition of microglia can influence their functionality, a better understanding of EPA and DHA metabolism in microglia and the brain could identify new targets to modify microglial activity.}, } @article {pmid34382225, year = {2021}, author = {Baluška, F and Reber, AS}, title = {CBC-Clock Theory of Life - Integration of cellular circadian clocks and cellular sentience is essential for cognitive basis of life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {10}, pages = {e2100121}, doi = {10.1002/bies.202100121}, pmid = {34382225}, issn = {1521-1878}, mesh = {*Circadian Clocks ; Circadian Rhythm ; Cognition ; Oxidation-Reduction ; Photosynthesis ; }, abstract = {Cellular circadian clocks represent ancient anticipatory systems which co-evolved with the first cells to safeguard their survival. Cyanobacteria represent one of the most ancient cells, having essentially invented photosynthesis together with redox-based cellular circadian clocks some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted in excitable membranes, play important roles, not only in the cellular circadian clocks and in anesthetics-sensitive cellular sentience (awareness of environment), but also in the coupling of single cells into tissues and organs of unitary multicellular organisms. This integration of cellular circadian clocks with cellular basis of sentience is an essential feature of the cognitive CBC-Clock basis of cellular life.}, } @article {pmid34374500, year = {2021}, author = {Dzik, J}, title = {Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase.}, journal = {Acta biochimica Polonica}, volume = {68}, number = {3}, pages = {457-476}, doi = {10.18388/abp.2020_5683}, pmid = {34374500}, issn = {1734-154X}, mesh = {Adenylate Kinase/*metabolism ; Amoeba/immunology/*metabolism ; Animals ; Bacteria/immunology/*metabolism ; Cytokines/metabolism ; Glycolysis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1/*metabolism ; Immunity/immunology ; Legionella/immunology/metabolism ; Macrophages/*immunology ; NF-kappa B/metabolism ; Phagocytosis ; Toll-Like Receptors/metabolism ; }, abstract = {The bacteria Legionella, being able to infect both macrophages and protozoans, reduce oxidative phosphorylation and induce glycolysis, which allows pathogens to grow and replicate in these cells. In amoeba-like inflammatory macrophages (M1), the phagocytizing cells of the primary immune defense, an increase in the rate of glycolysis is followed by a decrease of oxidative phosphorylation. The opposite takes place in anti-inflammatory macrophages (M2). They change from glycolysis to oxidative metabolism when AMP-dependent kinase (AMPK) is activated by a high ratio of AMP/ATP. Stimulation of macrophages with anti-inflammatory cytokines causes activation of AMPK. Infection of macrophages with the parasitic flagellate Leishmania infantum induces a switch from an initial glycolytic phase to oxidative phase with the essential role of AMPK in this change. Activated AMPK induces catabolic pathways effectively producing ATP as well as processes requiring the energy supply. AMPK regulates the migration of cells and enhances the phagocytic activity of macrophages. In macrophages, bacterial products activate TLRs and NF-κB signaling, causing an increase of transcription of hypoxia-induced factor HIF-1α (a subunit of HIF-1). This brings about induction of the enzyme and transporter expression essential for glycolysis and the pentose phosphate pathway to proceed and makes biosynthetic processes and ROS production in macrophages possible. Hypoxia augments macrophage phagocytosis in a HIF-1α-dependent manner. Multicellular parasites experience changes in the availability of oxygen in their life cycle. In the nematode Ascaris suum, HIF participates in the pre-adaptation to hypoxic conditions after infection of their hosts. Also, the freshwater and marine invertebrates meet changes of oxygen concentrations. In the anaerobic branch of the respiratory chain of these invertebrates, fumarate serves as the terminal electron acceptor that is reduced to succinate in complex II of the ETC. In mammalian cells, accumulation of succinate under hypoxic conditions suggests that the mammalian complex II may reduce fumarate to succinate, too. The data reviewed here show that the ability to shift the cell metabolism towards glycolysis observed in activated macrophages can be traced back in evolution to metabolic changes characterizing protozoans infected with bacteria. Anabolic needs of multiplying bacteria direct host metabolism to glycolysis that produces, aside from ATP, precursors of the amino acids used by the pathogen for its protein synthesis. M1-activated mammalian macrophages behave in the same way. Regulation of metabolism in M1 and M2 macrophages is further enhanced by HIF-1 and AMPK, respectively. These archaic functions of AMPK and HIF, important also to control phagocytosis and cell migration were extended to embryonic development in multicellular organisms.}, } @article {pmid34373443, year = {2021}, author = {Cao, Q and Wu, S and Xiao, C and Chen, S and Chi, X and Cui, X and Tang, H and Su, W and Zheng, Y and Zhong, J and Li, Z and Li, F and Chen, H and Hou, L and Wang, H and Wen, W}, title = {Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization.}, journal = {Cell discovery}, volume = {7}, number = {1}, pages = {64}, pmid = {34373443}, issn = {2056-5968}, abstract = {Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.}, } @article {pmid34371024, year = {2021}, author = {Bussey, KJ and Davies, PCW}, title = {Reverting to single-cell biology: The predictions of the atavism theory of cancer.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {49-55}, pmid = {34371024}, issn = {1873-1732}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Biological Evolution ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate - a well-known hallmark of cancer - is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.}, } @article {pmid34359962, year = {2021}, author = {Van Goor, J and Shakes, DC and Haag, ES}, title = {Fisher vs. the Worms: Extraordinary Sex Ratios in Nematodes and the Mechanisms that Produce Them.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359962}, issn = {2073-4409}, mesh = {Animals ; Fertility/*physiology ; Humans ; Male ; Nematoda/*metabolism ; Reproduction/*physiology ; Selection, Genetic ; *Sex Ratio ; Spermatozoa/cytology ; }, abstract = {Parker, Baker, and Smith provided the first robust theory explaining why anisogamy evolves in parallel in multicellular organisms. Anisogamy sets the stage for the emergence of separate sexes, and for another phenomenon with which Parker is associated: sperm competition. In outcrossing taxa with separate sexes, Fisher proposed that the sex ratio will tend towards unity in large, randomly mating populations due to a fitness advantage that accrues in individuals of the rarer sex. This creates a vast excess of sperm over that required to fertilize all available eggs, and intense competition as a result. However, small, inbred populations can experience selection for skewed sex ratios. This is widely appreciated in haplodiploid organisms, in which females can control the sex ratio behaviorally. In this review, we discuss recent research in nematodes that has characterized the mechanisms underlying highly skewed sex ratios in fully diploid systems. These include self-fertile hermaphroditism and the adaptive elimination of sperm competition factors, facultative parthenogenesis, non-Mendelian meiotic oddities involving the sex chromosomes, and environmental sex determination. By connecting sex ratio evolution and sperm biology in surprising ways, these phenomena link two "seminal" contributions of G. A. Parker.}, } @article {pmid34356075, year = {2021}, author = {Kloareg, B and Badis, Y and Cock, JM and Michel, G}, title = {Role and Evolution of the Extracellular Matrix in the Acquisition of Complex Multicellularity in Eukaryotes: A Macroalgal Perspective.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356075}, issn = {2073-4425}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/*physiology ; Extracellular Matrix/*physiology ; Seaweed/classification/*physiology ; }, abstract = {Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular eukaryotes. This review addresses the origin and evolution of the ECM, with a focus on multicellular marine algae. We show that in these lineages the expansion of extracellular matrix played a major role in the acquisition of complex multicellularity through its capacity to connect, position, shield, and defend the cells. Multiple innovations were necessary during these evolutionary processes, leading to striking convergences in the structures and functions of the ECMs of algae, animals, and plants.}, } @article {pmid34356071, year = {2021}, author = {Petroll, R and Schreiber, M and Finke, H and Cock, JM and Gould, SB and Rensing, SA}, title = {Signatures of Transcription Factor Evolution and the Secondary Gain of Red Algae Complexity.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356071}, issn = {2073-4425}, mesh = {*Evolution, Molecular ; *Genetic Variation ; *Genome ; *Phylogeny ; Rhodophyta/chemistry/*classification/*genetics/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Red algae (Rhodophyta) belong to the superphylum Archaeplastida, and are a species-rich group exhibiting diverse morphologies. Theory has it that the unicellular red algal ancestor went through a phase of genome contraction caused by adaptation to extreme environments. More recently, the classes Porphyridiophyceae, Bangiophyceae, and Florideophyceae experienced genome expansions, coinciding with an increase in morphological complexity. Transcription-associated proteins (TAPs) regulate transcription, show lineage-specific patterns, and are related to organismal complexity. To better understand red algal TAP complexity and evolution, we investigated the TAP family complement of uni- and multi-cellular red algae. We found that the TAP family complement correlates with gain of morphological complexity in the multicellular Bangiophyceae and Florideophyceae, and that abundance of the C2H2 zinc finger transcription factor family may be associated with the acquisition of morphological complexity. An expansion of heat shock transcription factors (HSF) occurred within the unicellular Cyanidiales, potentially as an adaption to extreme environmental conditions.}, } @article {pmid34354328, year = {2021}, author = {Zion, E and Chen, X}, title = {Breaking Symmetry: The Asymmetries in Epigenetic Inheritance.}, journal = {The biochemist}, volume = {43}, number = {1}, pages = {14-19}, pmid = {34354328}, issn = {0954-982X}, support = {F31 DK122702/DK/NIDDK NIH HHS/United States ; R35 GM127075/GM/NIGMS NIH HHS/United States ; T32 GM007231/GM/NIGMS NIH HHS/United States ; }, abstract = {Symmetry and asymmetry are fundamental aspects of life. Most cells within a multicellular organism contain the same genetic information, passed on from one originating cell - the zygote; however, these cells can take on a variety of different identities, with diverse appearances and functions. A fundamental question in biology ponders how cells containing identical DNA content can take on different cell identities. Epigenetic mechanisms could be the symmetry breaking factor, as they are able to change gene expression in cells without changing the DNA sequence. While the process of duplication and segregation of DNA during cell division has been well studied, it is less understood how the epigenetic information is established and inherited in the cells within a multicellular organism. Studies of asymmetric stem cell division, where a stem cell division gives rise to a self-renewed stem cell and a differentiating daughter cell, provides a model to study how epigenetic information is maintained or changed to produce daughter cells with identical genetic information but distinct cell fates. Here, we discuss findings and ideas of how epigenetic information is maintained or changed during asymmetric cell division and the importance of this asymmetry in influencing cell fate.}, } @article {pmid34343611, year = {2021}, author = {Moroz, LL and Nikitin, MA and Poličar, PG and Kohn, AB and Romanova, DY}, title = {Evolution of glutamatergic signaling and synapses.}, journal = {Neuropharmacology}, volume = {199}, number = {}, pages = {108740}, pmid = {34343611}, issn = {1873-7064}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Glutamic Acid/*physiology ; Receptors, Glutamate/*physiology ; Signal Transduction/*physiology ; Synapses/*physiology ; }, abstract = {Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.}, } @article {pmid34343465, year = {2021}, author = {Anda, S and Boye, E and Schink, KO and Grallert, B}, title = {Cosegregation of asymmetric features during cell division.}, journal = {Open biology}, volume = {11}, number = {8}, pages = {210116}, pmid = {34343465}, issn = {2046-2441}, mesh = {*Cell Division ; Centrosome/*physiology ; *Chromosome Segregation ; Chromosomes, Fungal/*genetics ; *Mitosis ; Schizosaccharomyces/*physiology ; Spindle Apparatus/*physiology ; }, abstract = {Cellular asymmetry plays a major role in the ageing and evolution of multicellular organisms. However, it remains unknown how the cell distinguishes 'old' from 'new' and whether asymmetry is an attribute of highly specialized cells or a feature inherent in all cells. Here, we investigate the segregation of three asymmetric features: old and new DNA, the spindle pole body (SPB, the centrosome analogue) and the old and new cell ends, using a simple unicellular eukaryote, Schizosaccharomyces pombe. To our knowledge, this is the first study exploring three asymmetric features in the same cells. We show that of the three chromosomes of S. pombe, chromosome I containing the new parental strand, preferentially segregated to the cells inheriting the old cell end. Furthermore, the new SPB also preferentially segregated to the cells inheriting the old end. Our results suggest that the ability to distinguish 'old' from 'new' and to segregate DNA asymmetrically are inherent features even in simple unicellular eukaryotes.}, } @article {pmid34343062, year = {2021}, author = {Li, XG and Tang, HZ and Zhang, WJ and Qi, XQ and Qu, ZG and Xu, J and Wu, LF}, title = {Thermococcus aciditolerans sp. nov., a piezotolerant, hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent chimney in the Southwest Indian Ridge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {71}, number = {8}, pages = {}, doi = {10.1099/ijsem.0.004934}, pmid = {34343062}, issn = {1466-5034}, mesh = {Base Composition ; DNA, Archaeal/genetics ; *Hydrothermal Vents/microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; *Thermococcus/classification/isolation & purification ; }, abstract = {A hyperthermophilic, strictly anaerobic archaeon, designated strain SY113[T], was isolated from a deep-sea hydrothermal vent chimney on the Southwest Indian Ridge at a water depth of 2770 m. Enrichment and isolation of strain SY113[T] were performed at 85 °C at 0.1 MPa. Cells of strain SY113[T] were irregular motile cocci with peritrichous flagella and generally 0.8-2.4 µm in diameter. Growth was observed at temperatures between 50 and 90 °C (optimum at 85 °C) and under hydrostatic pressures of 0.1-60 MPa (optimum, 27 MPa). Cells of SY113[T] grew at pH 4.0-9.0 (optimum, pH 5.5) and a NaCl concentration of 0.5-5.5 % (w/v; optimum concentration, 3.0 % NaCl). Strain SY113[T] was an anaerobic chemoorganoheterotroph and grew on complex proteinaceous substrates such as yeast extract and tryptone, as well as on maltose and starch. Elemental sulphur stimulated growth, but not obligatory for its growth. The G+C content of the genomic DNA was 55.0 mol%. Phylogenetic analysis of the 16S rRNA sequence of strain SY113[T] showed that the novel isolate belonged to the genus Thermococcus. On the basis of physiological characteristics, average nucleotide identity values and in silico DNA-DNA hybridization results, we propose a novel species, named Thermococcus aciditolerans sp. nov. The type strain is SY113[T] (=MCCC 1K04190[T]=JCM 39083[T]).}, } @article {pmid34338785, year = {2022}, author = {Ramalho, JJ and Jones, VAS and Mutte, S and Weijers, D}, title = {Pole position: How plant cells polarize along the axes.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {174-192}, pmid = {34338785}, issn = {1532-298X}, mesh = {Biological Evolution ; *Cell Polarity ; *Phylogeny ; Plant Cells/*physiology ; *Plant Physiological Phenomena ; Plant Proteins/*classification ; }, abstract = {Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.}, } @article {pmid34332367, year = {2021}, author = {Thorup, C and Petro, C and Bøggild, A and Ebsen, TS and Brokjær, S and Nielsen, LP and Schramm, A and Bjerg, JJ}, title = {How to grow your cable bacteria: Establishment of a stable single-strain culture in sediment and proposal of Candidatus Electronema aureum GS.}, journal = {Systematic and applied microbiology}, volume = {44}, number = {5}, pages = {126236}, doi = {10.1016/j.syapm.2021.126236}, pmid = {34332367}, issn = {1618-0984}, support = {291650/ERC_/European Research Council/International ; }, mesh = {*Bacteriological Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Deltaproteobacteria/classification/growth & development ; *Geologic Sediments/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Cable bacteria are multicellular filamentous bacteria within the Desulfobulbaceae that couple the oxidation of sulfide to the reduction of oxygen over centimeter distances via long distance electron transport (LDET). So far, none of the freshwater or marine cable bacteria species have been isolated into pure culture. Here we describe a method for establishing a stable single-strain cable bacterium culture in partially sterilized sediment. By repeated transfers of a single cable bacterium filament from freshwater pond sediment into autoclaved sediment, we obtained strain GS, identified by its 16S rRNA gene as a member of Ca. Electronema. This strain was further propagated by transferring sediment clumps, and has now been stable within its semi-natural microbial community for several years. Its metagenome-assembled genome was 93% complete, had a size of 2.76 Mbp, and a DNA G + C content of 52%. Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) suggest the affiliation of strain GS to Ca. Electronema as a novel species. Cell size, number of outer ridges, and detection of LDET in the GS culture are likewise consistent with Ca. Electronema. Based on these combined features, we therefore describe strain GS as a new cable bacterium species of the candidate genus Electronema, for which we propose the name Candidatus Electronema aureum sp.nov. Although not a pure culture, this stable single-strain culture will be useful for physiological and omics-based studies; similar approaches with single-cell or single-filament transfers into natural medium may also aid the characterization of other difficult-to-culture microbes.}, } @article {pmid34319226, year = {2021}, author = {Zhang, WJ and Zhang, C and Zhou, S and Li, XG and Mangenot, S and Fouteau, S and Guerin, T and Qi, XQ and Yang, J and Bartlett, DH and Wu, LF}, title = {Comparative genomic analysis of obligately piezophilic Moritella yayanosii DB21MT-5 reveals bacterial adaptation to the Challenger Deep, Mariana Trench.}, journal = {Microbial genomics}, volume = {7}, number = {7}, pages = {}, pmid = {34319226}, issn = {2057-5858}, mesh = {Acclimatization/*genetics ; Choline/metabolism ; Ecosystem ; Energy Metabolism/*genetics ; Fermentation/genetics/physiology ; Genome, Bacterial/*genetics ; Hydrostatic Pressure ; Moritella/*genetics/physiology ; Oceans and Seas ; Water Microbiology ; Whole Genome Sequencing ; }, abstract = {Hadal trenches are the deepest but underexplored ecosystems on the Earth. Inhabiting the trench bottom is a group of micro-organisms termed obligate piezophiles that grow exclusively under high hydrostatic pressures (HHP). To reveal the genetic and physiological characteristics of their peculiar lifestyles and microbial adaptation to extreme high pressures, we sequenced the complete genome of the obligately piezophilic bacterium Moritella yayanosii DB21MT-5 isolated from the deepest oceanic sediment at the Challenger Deep, Mariana Trench. Through comparative analysis against pressure sensitive and deep-sea piezophilic Moritella strains, we identified over a hundred genes that present exclusively in hadal strain DB21MT-5. The hadal strain encodes fewer signal transduction proteins and secreted polysaccharases, but has more abundant metal ion transporters and the potential to utilize plant-derived saccharides. Instead of producing osmolyte betaine from choline as other Moritella strains, strain DB21MT-5 ferments on choline within a dedicated bacterial microcompartment organelle. Furthermore, the defence systems possessed by DB21MT-5 are distinct from other Moritella strains but resemble those in obligate piezophiles obtained from the same geographical setting. Collectively, the intensive comparative genomic analysis of an obligately piezophilic strain Moritella yayanosii DB21MT-5 demonstrates a depth-dependent distribution of energy metabolic pathways, compartmentalization of important metabolism and use of distinct defence systems, which likely contribute to microbial adaptation to the bottom of hadal trench.}, } @article {pmid34315265, year = {2021}, author = {Chen, L and Wiens, JJ}, title = {Multicellularity and sex helped shape the Tree of Life.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1955}, pages = {20211265}, pmid = {34315265}, issn = {1471-2954}, mesh = {*Biodiversity ; Genetic Speciation ; Phenotype ; Phylogeny ; *Reproduction ; }, abstract = {Across the Tree of Life, there are dramatic differences in species numbers among groups. However, the factors that explain the differences among the deepest branches have remained unknown. We tested whether multicellularity and sexual reproduction might explain these patterns, since the most species-rich groups share these traits. We found that groups with multicellularity and sexual reproduction have accelerated rates of species proliferation (diversification), and that multicellularity has a stronger effect than sexual reproduction. Patterns of species richness among clades are then strongly related to these differences in diversification rates. Taken together, these results help explain patterns of biodiversity among groups of organisms at the very broadest scales. They may also help explain the mysterious preponderance of sexual reproduction among species (the 'paradox of sex') by showing that organisms with sexual reproduction proliferate more rapidly.}, } @article {pmid34302147, year = {2021}, author = {Zhao, YG and Codogno, P and Zhang, H}, title = {Machinery, regulation and pathophysiological implications of autophagosome maturation.}, journal = {Nature reviews. Molecular cell biology}, volume = {22}, number = {11}, pages = {733-750}, pmid = {34302147}, issn = {1471-0080}, mesh = {Autophagosomes/*genetics ; Autophagy/*genetics ; Endosomes/genetics ; Humans ; Lysosomes/genetics ; Neurodegenerative Diseases/*genetics/pathology ; Phagosomes/genetics ; Protein Processing, Post-Translational/genetics ; SNARE Proteins/genetics ; Transport Vesicles/*genetics ; rab GTP-Binding Proteins/genetics ; }, abstract = {Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.}, } @article {pmid34301628, year = {2021}, author = {Waldvogel, AM and Pfenninger, M}, title = {Temperature dependence of spontaneous mutation rates.}, journal = {Genome research}, volume = {31}, number = {9}, pages = {1582-1589}, pmid = {34301628}, issn = {1549-5469}, mesh = {Evolution, Molecular ; Mutation ; *Mutation Accumulation ; *Mutation Rate ; Temperature ; }, abstract = {Mutation is the source of genetic variation and the fundament of evolution. Temperature has long been suggested to have a direct impact on realized spontaneous mutation rates. If mutation rates vary in response to environmental conditions, such as the variation of the ambient temperature through space and time, they should no longer be described as species-specific constants. By combining mutation accumulation with whole-genome sequencing in a multicellular organism, we provide empirical support to reject the null hypothesis of a constant, temperature-independent mutation rate. Instead, mutation rates depended on temperature in a U-shaped manner with increasing rates toward both temperature extremes. This relation has important implications for mutation-dependent processes in molecular evolution, processes shaping the evolution of mutation rates, and even the evolution of biodiversity as such.}, } @article {pmid34293333, year = {2021}, author = {Kożyczkowska, A and Najle, SR and Ocaña-Pallarès, E and Aresté, C and Shabardina, V and Ara, PS and Ruiz-Trillo, I and Casacuberta, E}, title = {Stable transfection in protist Corallochytrium limacisporum identifies novel cellular features among unicellular animals relatives.}, journal = {Current biology : CB}, volume = {31}, number = {18}, pages = {4104-4110.e5}, doi = {10.1016/j.cub.2021.06.061}, pmid = {34293333}, issn = {1879-0445}, mesh = {Animals ; Cell Nucleus Division ; *Eukaryota/genetics ; *Fungi/genetics ; Phylogeny ; Transfection ; }, abstract = {The evolutionary path from protists to multicellular animals remains a mystery. Recent work on the genomes of several unicellular relatives of animals has shaped our understanding of the genetic changes that may have occurred in this transition.[1-3] However, the specific cellular modifications that took place to accommodate these changes remain unclear. To address this, we need to compare metazoan cells with those of their extant relatives, which are choanoflagellates, filastereans, ichthyosporeans, and corallochytreans/pluriformeans. Interestingly, these lineages display a range of developmental patterns potentially homologous to animal ones. Genetic tools have already been established in three of those lineages.[4-7] However, there are no genetic tools available for Corallochytrea. We here report the development of stable transfection in the corallochytrean Corallochytrium limacisporum. Using these tools, we discern previously unknown biological features of C. limacisporum. In particular, we identify two different paths for cell division-binary fission and coenocytic growth-that reveal a non-linear life cycle. Additionally, we found that C. limacisporum is binucleate for most of its life cycle, and that, contrary to what happens in most eukaryotes, nuclear division is decoupled from cellular division. Moreover, its actin cytoskeleton shares characteristics with both fungal and animal cells. The establishment of these tools in C. limacisporum fills an important gap in the unicellular relatives of animals, opening up new avenues of research to elucidate the specific cellular changes that occurred in the evolution of animals.}, } @article {pmid34279742, year = {2021}, author = {de Souza, ID and Reis, CF and Morais, DAA and Fernandes, VGS and Cavalcante, JVF and Dalmolin, RJS}, title = {Ancestry analysis indicates two different sets of essential genes in eukaryotic model species.}, journal = {Functional & integrative genomics}, volume = {21}, number = {3-4}, pages = {523-531}, pmid = {34279742}, issn = {1438-7948}, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Drosophila melanogaster/genetics ; *Evolution, Molecular ; *Genes, Essential ; Mice ; *Saccharomyces cerevisiae/genetics ; *Schizosaccharomyces/genetics ; }, abstract = {Essential genes are so-called because they are crucial for organism perpetuation. Those genes are usually related to essential functions to cellular metabolism or multicellular homeostasis. Deleterious alterations on essential genes produce a spectrum of phenotypes in multicellular organisms. The effects range from the impairment of the fertilization process, disruption of fetal development, to loss of reproductive capacity. Essential genes are described as more evolutionarily conserved than non-essential genes. However, there is no consensus about the relationship between gene essentiality and gene age. Here, we identified essential genes in five model eukaryotic species (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus) and estimate their evolutionary ancestry and their network properties. We observed that essential genes, on average, are older than other genes in all species investigated. The relationship of network properties and gene essentiality convey with previous findings, showing essential genes as important nodes in biological networks. As expected, we also observed that essential orthologs shared by the five species evaluated here are old. However, all the species evaluated here have a specific set of young essential genes not shared among them. Additionally, these two groups of essential genes are involved with distinct biological functions, suggesting two sets of essential genes: (i) a set of old essential genes common to all the evaluated species, regulating basic cellular functions, and (ii) a set of young essential genes exclusive to each species, which perform specific essential functions in each species.}, } @article {pmid34275698, year = {2022}, author = {Verdonck, R and Legrand, D and Jacob, S and Philippe, H}, title = {Phenotypic plasticity through disposable genetic adaptation in ciliates.}, journal = {Trends in microbiology}, volume = {30}, number = {2}, pages = {120-130}, doi = {10.1016/j.tim.2021.06.007}, pmid = {34275698}, issn = {1878-4380}, mesh = {Adaptation, Physiological/genetics ; Biological Evolution ; *Ciliophora/genetics ; *Paramecium/genetics ; }, abstract = {Ciliates have an extraordinary genetic system in which each cell harbors two distinct kinds of nucleus, a transcriptionally active somatic nucleus and a quiescent germline nucleus. The latter undergoes classical, heritable genetic adaptation, while adaptation of the somatic nucleus is only short-term and thus disposable. The ecological and evolutionary relevance of this nuclear dimorphism have never been well formalized, which is surprising given the long history of using ciliates such as Tetrahymena and Paramecium as model organisms. We present a novel, alternative explanation for ciliate nuclear dimorphism which, we argue, should be considered an instrument of phenotypic plasticity by somatic selection on the level of the ciliate clone, as if it were a diffuse multicellular organism. This viewpoint helps to put some enigmatic aspects of ciliate biology into perspective and presents the diversity of ciliates as a large natural experiment that we can exploit to study phenotypic plasticity and organismality.}, } @article {pmid34268901, year = {2021}, author = {Bik, HM}, title = {Just keep it simple? Benchmarking the accuracy of taxonomy assignment software in metabarcoding studies.}, journal = {Molecular ecology resources}, volume = {21}, number = {7}, pages = {2187-2189}, doi = {10.1111/1755-0998.13473}, pmid = {34268901}, issn = {1755-0998}, mesh = {Animals ; *Benchmarking ; Biodiversity ; *DNA Barcoding, Taxonomic ; Humans ; Phylogeny ; RNA, Ribosomal, 16S ; Software ; }, abstract = {How do you put a name on an unknown piece of DNA? From microbes to mammals, high-throughput metabarcoding studies provide a more objective view of natural communities, overcoming many of the inherent limitations of traditional field surveys and microscopy-based observations (Deiner et al., 2017). Taxonomy assignment is one of the most critical aspects of any metabarcoding study, yet this important bioinformatics task is routinely overlooked. Biodiversity surveys and conservation efforts often depend on formal species inventories: the presence (or absence) of species, and the number of individuals reported across space and time. However, computational workflows applied in eukaryotic metabarcoding studies were originally developed for use with bacterial/archaeal data sets, where microbial researchers rely on one conserved locus (nuclear 16S rRNA) and have access to vast databases with good coverage across most prokaryotic lineages - a situation not mirrored in most multicellular taxa. In this issue of Molecular Ecology Resources, Hleap et al. (2021) carry out an extensive benchmarking exercise focused on taxonomy assignment strategies for eukaryotic metabarcoding studies utilizing the mitochondrial Cytochrome C oxidase I marker gene (COI). They assess the performance and accuracy of software tools representing diverse methodological approaches: from "simple" strategies based on sequence similarity and composition, to model-based phylogenetic and probabilistic classification tools. Contrary to popular assumptions, less complex approaches (BLAST and the QIIME2 feature classifier) consistently outperformed more sophisticated mathematical algorithms and were highly accurate for assigning taxonomy at higher levels (e.g. family). Lower-level assignments at the genus and species level still pose significant challenge for most existing algorithms, and sparse eukaryotic reference databases further limit software performance. This study illuminates current best practices for metabarcoding taxonomy assignments, and underscores the need for community-driven efforts to expand taxonomic and geographic representation in reference DNA barcode databases.}, } @article {pmid34264933, year = {2021}, author = {Loidl, J}, title = {Tetrahymena meiosis: Simple yet ingenious.}, journal = {PLoS genetics}, volume = {17}, number = {7}, pages = {e1009627}, pmid = {34264933}, issn = {1553-7404}, support = {P 31606/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Chromosome Painting ; *Epigenesis, Genetic ; *Meiosis ; Reproduction/*physiology ; Tetrahymena thermophila/*genetics ; }, abstract = {The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial feature of eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. The ciliated protist Tetrahymena thermophila, which diverged from animals, plants, and fungi early in evolution, provides one example of a rather unconventional meiosis. Tetrahymena has a simpler meiosis compared with most other organisms: It lacks both a synaptonemal complex (SC) and specialized meiotic machinery for chromosome cohesion and has a reduced capacity to regulate meiotic recombination. Despite this, it also features several unique mechanisms, including elongation of the nucleus to twice the cell length to promote homologous pairing and prevent recombination between sister chromatids. Comparison of the meiotic programs of Tetrahymena and higher multicellular organisms may reveal how extant meiosis evolved from proto-meiosis.}, } @article {pmid34259548, year = {2021}, author = {Wang, J and Wang, J and Wu, S and Zhang, Z and Li, Y}, title = {Global Geographic Diversity and Distribution of the Myxobacteria.}, journal = {Microbiology spectrum}, volume = {9}, number = {1}, pages = {e0001221}, pmid = {34259548}, issn = {2165-0497}, mesh = {*Biodiversity ; Environmental Microbiology ; Myxococcales/*classification/genetics/*isolation & purification ; Phylogeny ; Soil/chemistry ; Soil Microbiology ; }, abstract = {Bacteria are globally distributed in various environments on earth, but a global view of the geographic diversity and distribution of a single taxon is lacking. The Earth Microbiome Project (EMP) has established a global collection of microbial communities, providing the possibility for such a survey. Myxococcales is a bacterial order with a potent ability to produce diverse natural products and have wide application potential in agriculture, biomedicine, and environmental protection. In this study, through a comparative analysis of the EMP data and public information, we determined that myxobacteria account for 2.34% of the total bacterial operational taxonomic units (OTUs), and are one of the most diverse bacterial groups on Earth. Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. Myxobacteria are among the least-investigated bacterial groups. The presently cultured and genome-sequenced myxobacteria are most likely environmentally widespread and abundant taxa, and account for approximately 10% and 7% of the myxobacterial community (>97% similarity), respectively. This global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently. The diversity and distribution of myxobacteria beyond the EMP data are further discussed. IMPORTANCE The diversity and distribution of bacteria are crucial for our understanding of their ecological importance and application potential. Myxobacteria are fascinating prokaryotes with multicellular behaviors and a potent capacity for producing secondary metabolites, and have a wide range of potential applications. The ecological importance of myxobacteria in major ecosystems is becoming established, but the global geographic diversity and distribution remain unclear. From a global survey we revealed that Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. The global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently.}, } @article {pmid34257365, year = {2021}, author = {Bestová, H and Segrestin, J and von Schwartzenberg, K and Škaloud, P and Lenormand, T and Violle, C}, title = {Biological scaling in green algae: the role of cell size and geometry.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14425}, pmid = {34257365}, issn = {2045-2322}, mesh = {*Cell Size ; *Chlorophyta ; Models, Biological ; }, abstract = {The Metabolic Scaling Theory (MST), hypothesizes limitations of resource-transport networks in organisms and predicts their optimization into fractal-like structures. As a result, the relationship between population growth rate and body size should follow a cross-species universal quarter-power scaling. However, the universality of metabolic scaling has been challenged, particularly across transitions from bacteria to protists to multicellulars. The population growth rate of unicellulars should be constrained by external diffusion, ruling nutrient uptake, and internal diffusion, operating nutrient distribution. Both constraints intensify with increasing size possibly leading to shifting in the scaling exponent. We focused on unicellular algae Micrasterias. Large size and fractal-like morphology make this species a transitional group between unicellular and multicellular organisms in the evolution of allometry. We tested MST predictions using measurements of growth rate, size, and morphology-related traits. We showed that growth scaling of Micrasterias follows MST predictions, reflecting constraints by internal diffusion transport. Cell fractality and density decrease led to a proportional increase in surface area with body mass relaxing external constraints. Complex allometric optimization enables to maintain quarter-power scaling of population growth rate even with a large unicellular plan. Overall, our findings support fractality as a key factor in the evolution of biological scaling.}, } @article {pmid34244514, year = {2021}, author = {Bernardes, JP and John, U and Woltermann, N and Valiadi, M and Hermann, RJ and Becks, L}, title = {The evolution of convex trade-offs enables the transition towards multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4222}, pmid = {34244514}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Cell Survival/physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; Predatory Behavior ; Rotifera/physiology ; }, abstract = {The evolutionary transition towards multicellular life often involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. Theory predicts that germ soma differentiation is facilitated by a convex trade-off between survival and reproduction. However, this has never been tested and these transitions remain poorly understood at the ecological and genetic level. Here, we study the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirm that growth in cell groups is heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolve in all cell group isolates; these are linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection were sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.}, } @article {pmid34236522, year = {2021}, author = {Vigneau, J and Borg, M}, title = {The epigenetic origin of life history transitions in plants and algae.}, journal = {Plant reproduction}, volume = {34}, number = {4}, pages = {267-285}, pmid = {34236522}, issn = {2194-7961}, mesh = {Animals ; Biological Evolution ; *Chlorophyta ; Epigenesis, Genetic ; Germ Cells, Plant ; *Magnoliopsida/genetics ; Phylogeny ; Plants/genetics ; }, abstract = {Plants and algae have a complex life history that transitions between distinct life forms called the sporophyte and the gametophyte. This phenomenon-called the alternation of generations-has fascinated botanists and phycologists for over 170 years. Despite the mesmerizing array of life histories described in plants and algae, we are only now beginning to learn about the molecular mechanisms controlling them and how they evolved. Epigenetic silencing plays an essential role in regulating gene expression during multicellular development in eukaryotes, raising questions about its impact on the life history strategy of plants and algae. Here, we trace the origin and function of epigenetic mechanisms across the plant kingdom, from unicellular green algae through to angiosperms, and attempt to reconstruct the evolutionary steps that influenced life history transitions during plant evolution. Central to this evolutionary scenario is the adaption of epigenetic silencing from a mechanism of genome defense to the repression and control of alternating generations. We extend our discussion beyond the green lineage and highlight the peculiar case of the brown algae. Unlike their unicellular diatom relatives, brown algae lack epigenetic silencing pathways common to animals and plants yet display complex life histories, hinting at the emergence of novel life history controls during stramenopile evolution.}, } @article {pmid34234152, year = {2021}, author = {Mitchell, RN and Gernon, TM and Cox, GM and Nordsvan, AR and Kirscher, U and Xuan, C and Liu, Y and Liu, X and He, X}, title = {Orbital forcing of ice sheets during snowball Earth.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4187}, pmid = {34234152}, issn = {2041-1723}, abstract = {The snowball Earth hypothesis-that a runaway ice-albedo feedback can cause global glaciation-seeks to explain low-latitude glacial deposits, as well as geological anomalies including the re-emergence of banded iron formation and "cap" carbonates. One of the most significant challenges to snowball Earth has been sedimentological cyclicity that has been taken to imply more climate dynamics than expected when the ocean is completely covered in ice. However, recent climate models suggest that as atmospheric CO2 accumulates, the snowball climate system becomes sensitive to orbital forcing. Here we show the presence of nearly all Milankovitch (orbital) cycles preserved in stratified banded iron formation deposited during the Sturtian snowball Earth. These results provide evidence for orbitally forced cyclicity of global ice sheets that resulted in periodic oxidation of ferrous iron. Orbital glacial advance and retreat cycles provide a simple mechanism to reconcile both the sedimentary dynamics and the enigmatic survival of multicellular life during snowball Earth.}, } @article {pmid34221665, year = {2021}, author = {Yan, F and Gunay, G and Valerio, TI and Wang, C and Wilson, JA and Haddad, MS and Watson, M and Connell, MO and Davidson, N and Fung, KM and Acar, H and Tang, Q}, title = {Characterization and quantification of necrotic tissues and morphology in multicellular ovarian cancer tumor spheroids using optical coherence tomography.}, journal = {Biomedical optics express}, volume = {12}, number = {6}, pages = {3352-3371}, pmid = {34221665}, issn = {2156-7085}, support = {P30 CA225520/CA/NCI NIH HHS/United States ; }, abstract = {The three-dimensional (3D) tumor spheroid model is a critical tool for high-throughput ovarian cancer research and anticancer drug development in vitro. However, the 3D structure prevents high-resolution imaging of the inner side of the spheroids. We aim to visualize and characterize 3D morphological and physiological information of the contact multicellular ovarian tumor spheroids growing over time. We intend to further evaluate the distinctive evolutions of the tumor spheroid and necrotic tissue volumes in different cell numbers and determine the most appropriate mathematical model for fitting the growth of tumor spheroids and necrotic tissues. A label-free and noninvasive swept-source optical coherence tomography (SS-OCT) imaging platform was applied to obtain two-dimensional (2D) and 3D morphologies of ovarian tumor spheroids over 18 days. Ovarian tumor spheroids of two different initial cell numbers (5,000- and 50,000- cells) were cultured and imaged (each day) over the time of growth in 18 days. Four mathematical models (Exponential-Linear, Gompertz, logistic, and Boltzmann) were employed to describe the growth kinetics of the tumor spheroids volume and necrotic tissues. Ovarian tumor spheroids have different growth curves with different initial cell numbers and their growths contain different stages with various growth rates over 18 days. The volumes of 50,000-cells spheroids and the corresponding necrotic tissues are larger than that of the 5,000-cells spheroids. The formation of necrotic tissue in 5,000-cells numbers is slower than that in the 50,000-cells ones. Moreover, the Boltzmann model exhibits the best fitting performance for the growth of tumor spheroids and necrotic tissues. Optical coherence tomography (OCT) can serve as a promising imaging modality to visualize and characterize morphological and physiological features of multicellular ovarian tumor spheroids. The Boltzmann model integrating with 3D OCT data of ovarian tumor spheroids provides great potential for high-throughput cancer research in vitro and aiding in drug development.}, } @article {pmid34215938, year = {2021}, author = {Machado, SR and Rodrigues, TM}, title = {Apoplasmic barrier in the extrafloral nectary of Citharexylum myrianthum (Verbenaceae).}, journal = {Planta}, volume = {254}, number = {2}, pages = {19}, pmid = {34215938}, issn = {1432-2048}, mesh = {Biological Transport ; Cell Wall ; Plant Nectar ; Trichomes ; *Verbenaceae ; }, abstract = {The cytological changes underlying the formation of an apoplasmic barrier in the multi-layered extrafloral nectaries of Citharexylum myrianthum are compatible with the synthesis, transport and deposition of suberin. In terms of ontogenesis and function, the intermediate layers of these nectaries are homologous with the stalks of nectar-secreting trichomes. Anticlinal cell wall impregnations are common in trichomatic nectaries and their functions as endodermis-like barriers have been discussed because of possible direct effects on the nectary physiology, mainly in the nectar secretion and resorption. However, the cytological events linked to nectary wall impregnations remain little explored. This study documents the ontogenesis and the fine structure of the EFN cells, and cytological events linked to the wall impregnations of multi-layered extrafloral nectaries (EFNs) in Citharexylum myrianthum Cham. (Verbenaceae). EFNs are patelliform, and differentiated into (a) a multicellular foot, which is compound in structure and vascularised with phloem strands, (b) a bi-layered intermediate region with thickened cell walls and (c) a single-layered secretory region with palisade-like cells. EFNs are protodermal in origin, starting with a single protodermal cell and ending with the complex, multi-layered structure. The cell wall impregnations first appear in the very young EFN and increase towards maturity. Lipid patches (assumed to be suberin) are deposited on the inner faces of the primary walls, first along the anticlinal walls and then extend to the periclinal walls. On both walls, plasmodesmata remain apparently intact during the maturation of the EFNs. In the peripheral cytoplasm there are abundant polymorphic plastids, well-developed Golgi bodies often close to rough endoplasmic reticulum profiles, mitochondria and polyribosomes. Cytological events linked to the wall impregnations are consistent with suberin synthesis, transport and deposition. Our findings offer new insights into the structure-properties of specialised nectary cell walls and so should contribute to our knowledge of the physiological and protective roles of this structure in nectar glands.}, } @article {pmid34205034, year = {2021}, author = {Francés-Herrero, E and Juárez-Barber, E and Campo, H and López-Martínez, S and de Miguel-Gómez, L and Faus, A and Pellicer, A and Ferrero, H and Cervelló, I}, title = {Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium.}, journal = {Journal of personalized medicine}, volume = {11}, number = {6}, pages = {}, pmid = {34205034}, issn = {2075-4426}, abstract = {Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids.}, } @article {pmid34204452, year = {2021}, author = {Cricrì, G and Bellucci, L and Montini, G and Collino, F}, title = {Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204452}, issn = {1422-0067}, mesh = {Animals ; Biomarkers/*urine ; Cell Communication ; Cell-Derived Microparticles/metabolism ; Chemical Fractionation ; Disease Management ; Disease Susceptibility ; Exosomes/metabolism ; Extracellular Vesicles/*metabolism ; Humans ; Kidney Diseases/diagnosis/etiology/*metabolism/urine ; Liquid Biopsy/methods ; Precision Medicine/methods ; Urinalysis/methods ; }, abstract = {Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier-or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.}, } @article {pmid34199921, year = {2021}, author = {Mikuła, A and Tomaszewicz, W and Dziurka, M and Kaźmierczak, A and Grzyb, M and Sobczak, M and Zdańkowski, P and Rybczyński, J}, title = {The Origin of the Cyathea delgadii Sternb. Somatic Embryos Is Determined by the Developmental State of Donor Tissue and Mutual Balance of Selected Metabolites.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34199921}, issn = {2073-4409}, mesh = {Cytokinins/*pharmacology ; Ferns/cytology/*metabolism ; *Plant Somatic Embryogenesis Techniques ; }, abstract = {Somatic embryogenesis is the formation of a plant embryo from a cell other than the product of gametic fusion. The need to recognize the determinants of somatic cell fate has prompted investigations on how endogenous factors of donor tissues can determine the pattern of somatic embryo origin. The undertaking of this study was enabled by the newly developed experimental system of somatic embryogenesis of the tree fern Cyathea delgadii Sternb., in which the embryos are produced in hormone-free medium. The contents of 89 endogenous compounds (such as sugars, auxins, cytokinins, gibberellins, stress-related hormones, phenolic acids, polyamines, and amino acids) and cytomorphological features were compared between two types of explants giving rise to somatic embryos of unicellular or multicellular origin. We found that a large content of maltose, 1-kestose, abscisic acid, biologically active gibberellins, and phenolic acids was characteristic for single-cell somatic embryo formation pattern. In contrast, high levels of starch, callose, kinetin riboside, arginine, and ethylene promoted their multicellular origin. Networks for visualization of the relations between studied compounds were constructed based on the data obtained from analyses of a Pearson correlation coefficient heatmap. Our findings present for the first time detailed features of donor tissue that can play an important role in the somatic-to-embryogenic transition and the somatic embryo origin.}, } @article {pmid34181730, year = {2021}, author = {Wu, X and Yan, A and McAdam, SAM and Banks, JA and Zhang, S and Zhou, Y}, title = {Timing of meristem initiation and maintenance determines the morphology of fern gametophytes.}, journal = {Journal of experimental botany}, volume = {72}, number = {20}, pages = {6990-7001}, doi = {10.1093/jxb/erab307}, pmid = {34181730}, issn = {1460-2431}, mesh = {Biological Evolution ; *Ferns ; Germ Cells, Plant ; Meristem ; *Pteridaceae ; }, abstract = {The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared with meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in gametophytes of two closely related Pteridaceae ferns, Pteris vittata and Ceratopteris richardii. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of the two ferns. They further provide evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants.}, } @article {pmid34178962, year = {2021}, author = {Ellis, MA and Dalwadi, MP and Ellis, MJ and Byrne, HM and Waters, SL}, title = {A Systematically Reduced Mathematical Model for Organoid Expansion.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {9}, number = {}, pages = {670186}, pmid = {34178962}, issn = {2296-4185}, abstract = {Organoids are three-dimensional multicellular tissue constructs. When cultured in vitro, they recapitulate the structure, heterogeneity, and function of their in vivo counterparts. As awareness of the multiple uses of organoids has grown, e.g. in drug discovery and personalised medicine, demand has increased for low-cost and efficient methods of producing them in a reproducible manner and at scale. Here we focus on a bioreactor technology for organoid production, which exploits fluid flow to enhance mass transport to and from the organoids. To ensure large numbers of organoids can be grown within the bioreactor in a reproducible manner, nutrient delivery to, and waste product removal from, the organoids must be carefully controlled. We develop a continuum mathematical model to investigate how mass transport within the bioreactor depends on the inlet flow rate and cell seeding density, focusing on the transport of two key metabolites: glucose and lactate. We exploit the thin geometry of the bioreactor to systematically simplify our model. This significantly reduces the computational cost of generating model solutions, and provides insight into the dominant mass transport mechanisms. We test the validity of the reduced models by comparison with simulations of the full model. We then exploit our reduced mathematical model to determine, for a given inlet flow rate and cell seeding density, the evolution of the spatial metabolite distributions throughout the bioreactor. To assess the bioreactor transport characteristics, we introduce metrics quantifying glucose conversion (the ratio between the total amounts of consumed and supplied glucose), the maximum lactate concentration, the proportion of the bioreactor with intolerable lactate concentrations, and the time when intolerable lactate concentrations are first experienced within the bioreactor. We determine the dependence of these metrics on organoid-line characteristics such as proliferation rate and rate of glucose consumption per cell. Finally, for a given organoid line, we determine how the distribution of metabolites and the associated metrics depend on the inlet flow rate. Insights from this study can be used to inform bioreactor operating conditions, ultimately improving the quality and number of bioreactor-expanded organoids.}, } @article {pmid34161405, year = {2021}, author = {Tan, A and Liu, Q and Septiadi, D and Chu, S and Liu, T and Richards, SJ and Rothen-Rutishauser, B and Petri-Fink, A and Gibson, MI and Boyd, BJ}, title = {Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.}, journal = {Journal of materials chemistry. B}, volume = {9}, number = {26}, pages = {5365-5373}, doi = {10.1039/d1tb00721a}, pmid = {34161405}, issn = {2050-7518}, support = {BB/M02878X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Line ; Click Chemistry ; Cyclooctanes/chemistry/*metabolism ; *Drug Delivery Systems ; Epithelial Cells/chemistry/metabolism ; Fibroblasts/chemistry/metabolism ; Gold/chemistry/*metabolism ; Hexosamines/chemistry/*metabolism ; Humans ; Metal Nanoparticles/*chemistry ; Molecular Structure ; Particle Size ; Polysaccharides/chemistry/*metabolism ; Surface Properties ; }, abstract = {Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.}, } @article {pmid34150724, year = {2021}, author = {Martínez-Reina, J and Calvo-Gallego, JL and Pivonka, P}, title = {Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis-Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {9}, number = {}, pages = {635056}, pmid = {34150724}, issn = {2296-4185}, abstract = {Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk. A novel mechanobiological model of bone remodelling was developed to investigate how these counter-acting mechanisms are affected both by exercise and long-term denosumab treatment. This model incorporates Frost's mechanostat feedback, a bone mineralisation algorithm and an evolution law for microdamage accumulation. Mechanical disuse and microdamage were assumed to stimulate RANKL production, which modulates activation frequency of basic multicellular units in bone remodelling. This mechanical feedback mechanism controls removal of excess bone mass and microdamage. Furthermore, a novel measure of bone local failure due to instantaneous overloading was developed. Numerical simulations indicate that trabecular bone volume fraction and bone matrix damage are determined by the respective bone turnover and homeostatic loading conditions. PMO patients treated with the currently WHO-approved dose of denosumab (60 mg administrated every 6 months) exhibit increased BMD, increased bone ash fraction and damage. In untreated patients, BMD will significantly decrease, as will ash fraction; while damage will increase. The model predicted that, depending on the time elapsed between the onset of PMO and the beginning of treatment, BMD slowly converges to the same steady-state value, while damage is low in patients treated soon after the onset of the disease and high in patients having PMO for a longer period. The simulations show that late treatment PMO patients have a significantly higher risk of local failure compared to patients that are treated soon after the onset of the disease. Furthermore, overloading resulted in an increase of BMD, but also in a faster increase of damage, which may consequently promote the risk of fracture, specially in late treatment scenarios. In case of mechanical disuse, the model predicted reduced BMD gains due to denosumab, while no significant change in damage occurred, thus leading to an increased risk of local failure compared to habitual loading.}, } @article {pmid34149674, year = {2021}, author = {Sánchez-Romero, MA and Casadesús, J}, title = {Waddington's Landscapes in the Bacterial World.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {685080}, pmid = {34149674}, issn = {1664-302X}, abstract = {Conrad Waddington's epigenetic landscape, a visual metaphor for the development of multicellular organisms, is appropriate to depict the formation of phenotypic variants of bacterial cells. Examples of bacterial differentiation that result in morphological change have been known for decades. In addition, bacterial populations contain phenotypic cell variants that lack morphological change, and the advent of fluorescent protein technology and single-cell analysis has unveiled scores of examples. Cell-specific gene expression patterns can have a random origin or arise as a programmed event. When phenotypic cell-to-cell differences are heritable, bacterial lineages are formed. The mechanisms that transmit epigenetic states to daughter cells can have strikingly different levels of complexity, from the propagation of simple feedback loops to the formation of complex DNA methylation patterns. Game theory predicts that phenotypic heterogeneity can facilitate bacterial adaptation to hostile or unpredictable environments, serving either as a division of labor or as a bet hedging that anticipates future challenges. Experimental observation confirms the existence of both types of strategies in the bacterial world.}, } @article {pmid34149428, year = {2021}, author = {Földes, A and Sang-Ngoen, T and Kádár, K and Rácz, R and Zsembery, Á and DenBesten, P and Steward, MC and Varga, G}, title = {Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {682654}, pmid = {34149428}, issn = {1663-9812}, support = {R01 DE027971/DE/NIDCR NIH HHS/United States ; }, abstract = {Background: Amelogenesis, the formation of dental enamel, is well understood at the histomorphological level but the underlying molecular mechanisms are poorly characterized. Ameloblasts secrete enamel matrix proteins and Ca[2+], and also regulate extracellular pH as the formation of hydroxyapatite crystals generates large quantities of protons. Genetic or environmental impairment of transport and regulatory processes (e.g. dental fluorosis) leads to the development of enamel defects such as hypomineralization. Aims: Our aims were to optimize the culture conditions for the three-dimensional growth of ameloblast-derived HAT-7 cells and to test the effects of fluoride exposure on HAT-7 spheroid formation. Methods: To generate 3D HAT-7 structures, cells were dispersed and plated within a Matrigel extracellular matrix scaffold and incubated in three different culture media. Spheroid formation was then monitored over a two-week period. Ion transporter and tight-junction protein expression was investigated by RT-qPCR. Intracellular Ca[2+] and pH changes were measured by microfluorometry using the fluorescent dyes fura-2 and BCECF. Results: A combination of Hepato-STIM epithelial cell differentiation medium and Matrigel induced the expansion and formation of 3D HAT-7 spheroids. The cells retained their epithelial cell morphology and continued to express both ameloblast-specific and ion transport-specific marker genes. Furthermore, like two-dimensional HAT-7 monolayers, the HAT-7 spheroids were able to regulate their intracellular pH and to show intracellular calcium responses to extracellular stimulation. Finally, we demonstrated that HAT-7 spheroids may serve as a disease model for studying the effects of fluoride exposure during amelogenesis. Conclusion: In conclusion, HAT-7 cells cultivated within a Matrigel extracellular matrix form three-dimensional, multi-cellular, spheroidal structures that retain their functional capacity for pH regulation and intracellular Ca[2+] signaling. This new 3D model will allow us to gain a better understanding of the molecular mechanisms involved in amelogenesis, not only in health but also in disorders of enamel formation, such as those resulting from fluoride exposure.}, } @article {pmid34147614, year = {2021}, author = {Shang-Guan, XY and Cai, YJ and Xu, HZ and Cheng, X and Zhang, RF and Liu, HX}, title = {A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.}, journal = {Fish & shellfish immunology}, volume = {115}, number = {}, pages = {160-170}, doi = {10.1016/j.fsi.2021.06.007}, pmid = {34147614}, issn = {1095-9947}, mesh = {Aeromonas hydrophila/physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cyprinidae/*genetics/*immunology ; Fish Diseases/*immunology ; Fish Proteins/chemistry/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; Gram-Negative Bacterial Infections/immunology/veterinary ; Immunity, Innate/*genetics ; Lectins, C-Type/chemistry/*genetics/*immunology ; Phylogeny ; Sequence Alignment/veterinary ; }, abstract = {C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca[2+], showing a typical Ca[2+]-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca[2+]-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.}, } @article {pmid34147034, year = {2022}, author = {Caipa Garcia, AL and Arlt, VM and Phillips, DH}, title = {Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis.}, journal = {Mutagenesis}, volume = {37}, number = {2}, pages = {143-154}, pmid = {34147034}, issn = {1464-3804}, support = {MR/N013700/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; C98/A24032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Carcinogenesis ; Cell Culture Techniques ; Humans ; Mammals ; Models, Biological ; *Organoids ; *Pluripotent Stem Cells ; }, abstract = {Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.}, } @article {pmid34136267, year = {2021}, author = {Kreider, JJ and Pen, I and Kramer, BH}, title = {Antagonistic pleiotropy and the evolution of extraordinary lifespans in eusocial organisms.}, journal = {Evolution letters}, volume = {5}, number = {3}, pages = {178-186}, pmid = {34136267}, issn = {2056-3744}, abstract = {Queens of eusocial species live extraordinarily long compared to their workers. So far, it has been argued that these lifespan divergences are readily explained by the classical evolutionary theory of ageing. As workers predominantly perform risky tasks, such as foraging and nest defense, and queens stay in the well-protected nests, selection against harmful genetic mutations expressed in old age should be weaker in workers than in queens due to caste differences in extrinsic mortality risk, and thus, lead to the evolution of longer queen and shorter worker lifespans. However, these arguments have not been supported by formal models. Here, we present a model for the evolution of caste-specific ageing in social insects, based on Williams' antagonistic pleiotropy theory of ageing. In individual-based simulations, we assume that mutations with antagonistic fitness effects can act within castes, that is, mutations in early life are accompanied by an antagonistic effect acting in later life, or between castes, where antagonistic effects emerge due to caste antagonism or indirect genetic effects between castes. In monogynous social insect species with sterile workers, large lifespan divergences between castes evolved under all different scenarios of antagonistic effects, but regardless of the degree of caste-specific extrinsic mortality. Mutations with antagonistic fitness effects within castes reduced lifespans of both castes, while mutations with between-caste antagonistic effects decreased worker lifespans more than queen lifespans, and consequently increased lifespan divergences. Our results challenge the central explanatory role of extrinsic mortality for caste-specific ageing in eusocial organisms and suggest that antagonistic pleiotropy affects castes differently due to reproductive monopolization by queens, hence, reproductive division of labor. Finally, these findings provide new insights into the evolution of tissue-specific ageing in multicellular organisms in general.}, } @article {pmid34133948, year = {2021}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV and Sang, Y}, title = {The IS630/Tc1/mariner transposons in three ctenophore genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.ympev.2021.107231}, pmid = {34133948}, issn = {1095-9513}, mesh = {Animals ; *Ctenophora/genetics ; *Culicidae ; DNA Transposable Elements/genetics ; Phylogeny ; Transposases/genetics ; }, abstract = {Transposable elements (TEs) exert a significant effect on the structure and functioning of the genomes and also serve as a source of the new genes. The study of the TE diversity and evolution in different taxa is indispensable for the fundamental understanding of their roles in the genomes. IS630/Tc1/mariner (ITm) transposable elements represent the most prevalent and diverse group of DNA transposons. In this work, we studied the diversity, evolutionary dynamics and the phylogenetic relationships of the ITm transposons found in three ctenophore species: Mnemiopsis leidyi, Pleurobrachia bachei, Beroe ovata. We identified 29 ITm transposons, seven of which possess the terminal inverted repeats (TIRs) and an intact transposase, and, thus, are, presumably, active. Four other ITm transposons have the features of domesticated TEs. According to the results of the phylogenetic analysis, the ITm transposons of the ctenophores represent five groups - MLE/DD34D, TLE/DD34-38E, mosquito/DD37E, Visiror/DD41D and pogo/DDxD. Pogo/DDxD superfamily turnes out to be the most diverse and prevalent, since it accounts for more than 40% of the TEs identified. The data obtained in this research will fill the gap of knowledge of the diversity and evolution of the ITm transposons in the multicellular genomes and will lay the ground for the study of the TE effects on the evolution of the ctenophores.}, } @article {pmid34127736, year = {2021}, author = {Opazo, JC and Vandewege, MW and Gutierrez, J and Zavala, K and Vargas-Chacoff, L and Morera, FJ and Mardones, GA}, title = {Independent duplications of the Golgi phosphoprotein 3 oncogene in birds.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12483}, pmid = {34127736}, issn = {2045-2322}, mesh = {Amino Acid Sequence/genetics ; Animals ; Birds/*genetics ; Carcinogenesis/genetics ; *Evolution, Molecular ; Gene Duplication ; Golgi Apparatus/*genetics ; Humans ; Membrane Proteins/*genetics ; Neoplasms/genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; Sequence Alignment ; }, abstract = {Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.}, } @article {pmid34120565, year = {2021}, author = {Miguel-Tomé, S and Llinás, RR}, title = {Broadening the definition of a nervous system to better understand the evolution of plants and animals.}, journal = {Plant signaling & behavior}, volume = {16}, number = {10}, pages = {1927562}, pmid = {34120565}, issn = {1559-2324}, mesh = {Animals ; *Biological Evolution ; Electrophysiological Phenomena ; *Nervous System Physiological Phenomena ; *Plant Physiological Phenomena ; Signal Transduction ; Terminology as Topic ; }, abstract = {Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.}, } @article {pmid34114607, year = {2021}, author = {Aevarsson, A and Kaczorowska, AK and Adalsteinsson, BT and Ahlqvist, J and Al-Karadaghi, S and Altenbuchner, J and Arsin, H and Átlasson, ÚÁ and Brandt, D and Cichowicz-Cieślak, M and Cornish, KAS and Courtin, J and Dabrowski, S and Dahle, H and Djeffane, S and Dorawa, S and Dusaucy, J and Enault, F and Fedøy, AE and Freitag-Pohl, S and Fridjonsson, OH and Galiez, C and Glomsaker, E and Guérin, M and Gundesø, SE and Gudmundsdóttir, EE and Gudmundsson, H and Håkansson, M and Henke, C and Helleux, A and Henriksen, JR and Hjörleifdóttir, S and Hreggvidsson, GO and Jasilionis, A and Jochheim, A and Jónsdóttir, I and Jónsdóttir, LB and Jurczak-Kurek, A and Kaczorowski, T and Kalinowski, J and Kozlowski, LP and Krupovic, M and Kwiatkowska-Semrau, K and Lanes, O and Lange, J and Lebrat, J and Linares-Pastén, J and Liu, Y and Lorentsen, SA and Lutterman, T and Mas, T and Merré, W and Mirdita, M and Morzywołek, A and Ndela, EO and Karlsson, EN and Olgudóttir, E and Pedersen, C and Perler, F and Pétursdóttir, SK and Plotka, M and Pohl, E and Prangishvili, D and Ray, JL and Reynisson, B and Róbertsdóttir, T and Sandaa, RA and Sczyrba, A and Skírnisdóttir, S and Söding, J and Solstad, T and Steen, IH and Stefánsson, SK and Steinegger, M and Overå, KS and Striberny, B and Svensson, A and Szadkowska, M and Tarrant, EJ and Terzian, P and Tourigny, M and Bergh, TVD and Vanhalst, J and Vincent, J and Vroling, B and Walse, B and Wang, L and Watzlawick, H and Welin, M and Werbowy, O and Wons, E and Zhang, R}, title = {Going to extremes - a metagenomic journey into the dark matter of life.}, journal = {FEMS microbiology letters}, volume = {368}, number = {12}, pages = {}, doi = {10.1093/femsle/fnab067}, pmid = {34114607}, issn = {1574-6968}, mesh = {Bioprospecting/organization & administration ; Computational Biology ; Databases, Genetic ; Europe ; Genome, Viral/*genetics ; Hydrothermal Vents/virology ; *Metagenomics ; Viral Proteins/chemistry/genetics/metabolism ; Virome/genetics ; Viruses/classification/genetics ; }, abstract = {The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.}, } @article {pmid34114051, year = {2021}, author = {Márquez-Zacarías, P and Conlin, PL and Tong, K and Pentz, JT and Ratcliff, WC}, title = {Why have aggregative multicellular organisms stayed simple?.}, journal = {Current genetics}, volume = {67}, number = {6}, pages = {871-876}, pmid = {34114051}, issn = {1432-0983}, mesh = {*Biological Evolution ; Clonal Evolution ; Eukaryota/cytology/*physiology ; }, abstract = {Multicellularity has evolved numerous times across the tree of life. One of the most fundamental distinctions among multicellular organisms is their developmental mode: whether they stay together during growth and develop clonally, or form a group through the aggregation of free-living cells. The five eukaryotic lineages to independently evolve complex multicellularity (animals, plants, red algae, brown algae, and fungi) all develop clonally. This fact has largely been explained through social evolutionary theory's lens of cooperation and conflict, where cheating within non-clonal groups has the potential to undermine multicellular adaptation. Multicellular organisms that form groups via aggregation could mitigate the costs of cheating by evolving kin recognition systems that prevent the formation of chimeric groups. However, recent work suggests that selection for the ability to aggregate quickly may constrain the evolution of highly specific kin recognition, sowing the seeds for persistent evolutionary conflict. Importantly, other features of aggregative multicellular life cycles may independently act to constrain the evolution of complex multicellularity. All known aggregative multicellular organisms are facultatively multicellular (as opposed to obligately multicellular), allowing unicellular-level adaptation to environmental selection. Because they primarily exist in a unicellular state, it may be difficult for aggregative multicellular organisms to evolve multicellular traits that carry pleiotropic cell-level fitness costs. Thus, even in the absence of social conflict, aggregative multicellular organisms may have limited potential for the evolution of complex multicellularity.}, } @article {pmid34102596, year = {2021}, author = {Amaral-Zettler, LA and Zettler, ER and Mincer, TJ and Klaassen, MA and Gallager, SM}, title = {Biofouling impacts on polyethylene density and sinking in coastal waters: A macro/micro tipping point?.}, journal = {Water research}, volume = {201}, number = {}, pages = {117289}, doi = {10.1016/j.watres.2021.117289}, pmid = {34102596}, issn = {1879-2448}, mesh = {Animals ; *Biofouling ; Environmental Monitoring ; North Sea ; Plastics ; Polyethylene ; *Water Pollutants, Chemical/analysis ; }, abstract = {Biofouling causing an increase in plastic density and sinking is one of the hypotheses to account for the unexpectedly low amount of buoyant plastic debris encountered at the ocean surface. Field surveys show that polyethylene and polypropylene, the two most abundant buoyant plastics, both occur below the surface and in sediments, and experimental studies confirm that biofouling can cause both of these plastics to sink. However, studies quantifying the actual density of fouled plastics are rare, despite the fact that density will determine the transport and eventual fate of plastic in the ocean. Here we investigated the role of microbial biofilms in sinking of polyethylene microplastic and quantified the density changes natural biofouling communities cause in the coastal waters of the North Sea. Molecular data confirmed the variety of bacteria and eukaryotes (including animals and other multicellular organisms) colonizing the plastic over time. Fouling communities increased the density of plastic and caused sinking, and the plastic remained negatively buoyant even during the winter with lower growth rates. Relative surface area alone, however, did not predict whether a plastic piece sank. Due to patchy colonization, fragmentation of sinking pieces may result in smaller pieces regaining buoyancy and returning to the surface. Our results suggest that primarily multicellular organisms cause sinking of plastic pieces with surface area to volume ratios (SA:V) below 100 (generally pieces above a couple hundred micrometers in size), and that this is a "tipping point" at which microbial biofilms become the key players causing sinking of smaller pieces with higher SA:V ratios, including most fibers that are too small for larger (multicellular) organisms to colonize.}, } @article {pmid34102232, year = {2021}, author = {Torday, JS}, title = {Cellular evolution of language.}, journal = {Progress in biophysics and molecular biology}, volume = {167}, number = {}, pages = {140-146}, doi = {10.1016/j.pbiomolbio.2021.05.009}, pmid = {34102232}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Humans ; *Language ; Phenotype ; }, abstract = {The evolutionary origin of language remains unknown despite many efforts to determine the origin of this signature human trait. Based on epigenetic inheritance, the current article hypothesizes that language evolved from cell-cell communication as the basis for generating structure and function embryologically and phylogenetically, as did all physiologic traits. Beginning with lipids forming the first micelle, a vertical integration of the evolved properties of the cell, from multicellular organisms to the introduction of cholesterol into the cell membrane, to the evolution of the peroxisome, the water-land transition and duplication of the βAdrenergic Receptor, the evolution of endothermy, leading to bipedalism, freeing the forelimbs for toolmaking and language, selection pressure for myelinization of the central nervous system to facilitate calcium flux, bespeaks human expression, culminating in the evolution of civilization. This process is epitomized by the Area of Broca as the structural-functional site for both motor control and language formation. The mechanistic interrelationship between motor control and language formation is underscored by the role of FoxP2 gene expression in both bipedalism and language. The effect of endothermy on bipedalism, freeing the forelimbs for toolmaking and language as the vertical integration from Cosmology to Physiology as the basis for language bespeaks human expression.}, } @article {pmid34097041, year = {2021}, author = {Li, Y and Shen, XX and Evans, B and Dunn, CW and Rokas, A}, title = {Rooting the Animal Tree of Life.}, journal = {Molecular biology and evolution}, volume = {38}, number = {10}, pages = {4322-4333}, pmid = {34097041}, issn = {1537-1719}, support = {R56 AI146096/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Ctenophora ; Phylogeny ; }, abstract = {Identifying our most distant animal relatives has emerged as one of the most challenging problems in phylogenetics. This debate has major implications for our understanding of the origin of multicellular animals and of the earliest events in animal evolution, including the origin of the nervous system. Some analyses identify sponges as our most distant animal relatives (Porifera-sister hypothesis), and others identify comb jellies (Ctenophora-sister hypothesis). These analyses vary in many respects, making it difficult to interpret previous tests of these hypotheses. To gain insight into why different studies yield different results, an important next step in the ongoing debate, we systematically test these hypotheses by synthesizing 15 previous phylogenomic studies and performing new standardized analyses under consistent conditions with additional models. We find that Ctenophora-sister is recovered across the full range of examined conditions, and Porifera-sister is recovered in some analyses under narrow conditions when most outgroups are excluded and site-heterogeneous CAT models are used. We additionally find that the number of categories in site-heterogeneous models is sufficient to explain the Porifera-sister results. Furthermore, our cross-validation analyses show CAT models that recover Porifera-sister have hundreds of additional categories and fail to fit significantly better than site-heterogenuous models with far fewer categories. Systematic and standardized testing of diverse phylogenetic models suggests that we should be skeptical of Porifera-sister results both because they are recovered under such narrow conditions and because the models in these conditions fit the data no better than other models that recover Ctenophora-sister.}, } @article {pmid34077702, year = {2021}, author = {Kang, S and Tice, AK and Stairs, CW and Jones, RE and Lahr, DJG and Brown, MW}, title = {The integrin-mediated adhesive complex in the ancestor of animals, fungi, and amoebae.}, journal = {Current biology : CB}, volume = {31}, number = {14}, pages = {3073-3085.e3}, doi = {10.1016/j.cub.2021.04.076}, pmid = {34077702}, issn = {1879-0445}, support = {MOP-142349//CIHR/Canada ; }, mesh = {Amoeba ; Animals ; *Cell Adhesion ; *Eukaryota ; Evolution, Molecular ; Fungi ; *Integrins ; Phylogeny ; }, abstract = {Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.}, } @article {pmid34076889, year = {2021}, author = {Badis, Y and Scornet, D and Harada, M and Caillard, C and Godfroy, O and Raphalen, M and Gachon, CMM and Coelho, SM and Motomura, T and Nagasato, C and Cock, JM}, title = {Targeted CRISPR-Cas9-based gene knockouts in the model brown alga Ectocarpus.}, journal = {The New phytologist}, volume = {231}, number = {5}, pages = {2077-2091}, doi = {10.1111/nph.17525}, pmid = {34076889}, issn = {1469-8137}, mesh = {Animals ; *CRISPR-Cas Systems/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Eukaryota ; Gene Knockout Techniques ; *Phaeophyta/genetics ; }, abstract = {Brown algae are an important group of multicellular eukaryotes, phylogenetically distinct from both the animal and land plant lineages. Ectocarpus has emerged as a model organism to study diverse aspects of brown algal biology, but this system currently lacks an effective reverse genetics methodology to analyse the functions of selected target genes. Here, we report that mutations at specific target sites are generated following the introduction of CRISPR-Cas9 ribonucleoproteins into Ectocarpus cells, using either biolistics or microinjection as the delivery method. Individuals with mutations affecting the ADENINE PHOSPHORIBOSYL TRANSFERASE (APT) gene were isolated following treatment with 2-fluoroadenine, and this selection system was used to isolate individuals in which mutations had been introduced simultaneously at APT and at a second gene. This double mutation approach could potentially be used to isolate mutants affecting any Ectocarpus gene, providing an effective reverse genetics tool for this model organism. The availability of this tool will significantly enhance the utility of Ectocarpus as a model organism for this ecologically and economically important group of marine organisms. Moreover, the methodology described here should be readily transferable to other brown algal species.}, } @article {pmid34069435, year = {2021}, author = {Elders, H and Hennicke, F}, title = {The Pacific Tree-Parasitic Fungus Cyclocybe parasitica Exhibits Monokaryotic Fruiting, Showing Phenotypes Known from Bracket Fungi and from Cyclocybe aegerita.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {7}, number = {5}, pages = {}, pmid = {34069435}, issn = {2309-608X}, abstract = {Cyclocybe parasitica is a wood-destroying parasitic edible mushroom growing on diverse broad-leafed trees in New Zealand and other Pacific areas. Recent molecular systematics of European Cyclocybe aegerita, a newly delimited Asian phylum and of related species, corroborated the distinction of the chiefly saprobic cultivated edible mushroom C. aegerita from C. parasitica. Here, we show that C. parasitica exhibits a morpho-physiological trait characteristic to its European cousin, i.e., monokaryotic fruiting sensu stricto (basidiome formation without mating). Monokaryotic fruiting structures formed by C. parasitica ICMP 11668-derived monokaryons were categorized into four phenotypes. One of them displays ulcer-like structures previously reported from bracket fungi. Histology of dikaryotic and monokaryotic C. parasitica fruiting structures revealed anatomical commonalities and differences between them, and towards monokaryotic fruiting structures of C. aegerita. Mating experiments with C. parasitica strains representative of each fruiting phenotype identified compatible sibling monokaryons. Given reports on hypothetically monokaryotic basidiome field populations of 'C. aegerita sensu lato', it seems worthwhile to prospectively investigate whether monokaryotic fruiting s.str. occurs in nature. Sampling from such populations including karyotyping, comparative -omics, and competition assays may help to answer this question and provide evidence whether this trait may confer competitive advantages to a species capable of it.}, } @article {pmid34066959, year = {2021}, author = {Miller, WB and Enguita, FJ and Leitão, AL}, title = {Non-Random Genome Editing and Natural Cellular Engineering in Cognition-Based Evolution.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34066959}, issn = {2073-4409}, mesh = {Animals ; *Biological Evolution ; *Cell Engineering ; Cognition/*physiology ; *Gene Editing ; *Homeostasis ; Humans ; *Selection, Genetic ; }, abstract = {Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.}, } @article {pmid34063320, year = {2021}, author = {Mahajan, D and Kancharla, S and Kolli, P and Sharma, AK and Singh, S and Kumar, S and Mohanty, AK and Jena, MK}, title = {Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.}, journal = {Biomolecules}, volume = {11}, number = {5}, pages = {}, pmid = {34063320}, issn = {2218-273X}, mesh = {Animals ; Calcium-Binding Proteins/genetics/*metabolism ; *Embryonic Development ; Extracellular Matrix/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Neoplasms/*genetics/metabolism ; Protein Isoforms/metabolism ; }, abstract = {The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.}, } @article {pmid34061031, year = {2021}, author = {Kaur, G and Iyer, LM and Burroughs, AM and Aravind, L}, title = {Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34061031}, issn = {2050-084X}, support = {F38 LM000084/LM/NLM NIH HHS/United States ; Z01 LM000084/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Bacteria/genetics/immunology/*metabolism ; Bacterial Proteins/genetics/immunology/*metabolism ; *Death Domain Superfamily ; Evolution, Molecular ; Genomics ; Host-Pathogen Interactions ; Microbial Viability ; Phylogeny ; Prokaryotic Cells/immunology/*metabolism ; Signal Transduction ; Symbiosis ; TNF Receptor-Associated Death Domain Protein/genetics/immunology/*metabolism ; }, abstract = {Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retroviruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring underappreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic acid receptors), and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.}, } @article {pmid34052880, year = {2022}, author = {Fernández, LD and Seppey, CVW and Singer, D and Fournier, B and Tatti, D and Mitchell, EAD and Lara, E}, title = {Niche Conservatism Drives the Elevational Diversity Gradient in Major Groups of Free-Living Soil Unicellular Eukaryotes.}, journal = {Microbial ecology}, volume = {83}, number = {2}, pages = {459-469}, pmid = {34052880}, issn = {1432-184X}, mesh = {Biodiversity ; *Ciliophora/genetics ; Ecosystem ; Phylogeny ; *Soil ; }, abstract = {Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.}, } @article {pmid34050941, year = {2021}, author = {Grandhi, TSP and To, J and Romero, A and Luna, F and Barnes, W and Walker, J and Moran, R and Newlin, R and Miraglia, L and Orth, AP and Horman, SR}, title = {High-throughput CRISPR-mediated 3D enrichment platform for functional interrogation of chemotherapeutic resistance.}, journal = {Biotechnology and bioengineering}, volume = {118}, number = {8}, pages = {3187-3199}, doi = {10.1002/bit.27844}, pmid = {34050941}, issn = {1097-0290}, mesh = {Antineoplastic Agents/*pharmacology ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *CRISPR-Cas Systems ; *Cell Culture Techniques ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Female ; Humans ; Spheroids, Cellular/*metabolism ; *Tumor Microenvironment ; }, abstract = {Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target-specific oncogenic driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is a need for rapid, high-throughput, unbiased in vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identify mutations that confer chemotherapeutic drug resistance. Taking the example of the CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a three-dimensional (3D) setting. Gene-edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug-resistant phenotypes, detectable by next-gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug-resistant cell within a large, drug-responsive complex 3D tumor spheroid. The genome-wide 3D CRISPR-mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Furthermore, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring noncell autonomous interactions, selection pressures, and clonal competition.}, } @article {pmid34047647, year = {2021}, author = {Sheng, Y and Pan, B and Wei, F and Wang, Y and Gao, S}, title = {Case Study of the Response of N[6]-Methyladenine DNA Modification to Environmental Stressors in the Unicellular Eukaryote Tetrahymena thermophila.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {e0120820}, pmid = {34047647}, issn = {2379-5042}, mesh = {Adenine/*analogs & derivatives/pharmacology ; Epigenesis, Genetic ; Genome, Protozoan ; Methylation ; Protein Processing, Post-Translational ; Stress, Physiological/*drug effects/genetics ; Tetrahymena thermophila/*drug effects/*genetics/metabolism ; }, abstract = {Rediscovered as a potential epigenetic mark, N[6]-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation. The reduction of symmetric 6mA and the increase of asymmetric 6mA coincide with the downregulation of AMT1 and upregulation of AMT2 and AMT5, which are supposedly the MT-A70 methyltransferases required for symmetric and asymmetric 6mA, respectively. These results demonstrated that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes. IMPORTANCE Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. In the present work, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Our results provide insights into how Tetrahymena fine-tunes its 6mA level and composition upon starvation, suggesting that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes.}, } @article {pmid34031540, year = {2021}, author = {Kumari, P and Dahiya, P and Livanos, P and Zergiebel, L and Kölling, M and Poeschl, Y and Stamm, G and Hermann, A and Abel, S and Müller, S and Bürstenbinder, K}, title = {IQ67 DOMAIN proteins facilitate preprophase band formation and division-plane orientation.}, journal = {Nature plants}, volume = {7}, number = {6}, pages = {739-747}, pmid = {34031540}, issn = {2055-0278}, mesh = {Arabidopsis/*cytology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Dinitrobenzenes ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics/metabolism ; Microtubules/drug effects/metabolism ; Mutation ; Phylogeny ; Plant Cells/drug effects/metabolism ; Plants, Genetically Modified ; Prophase ; Protein Domains ; Sulfanilamides ; Tobacco/genetics ; Vesicular Transport Proteins/metabolism ; }, abstract = {Spatiotemporal control of cell division is essential for the growth and development of multicellular organisms. In plant cells, proper cell plate insertion during cytokinesis relies on the premitotic establishment of the division plane at the cell cortex. Two plant-specific cytoskeleton arrays, the preprophase band (PPB) and the phragmoplast, play important roles in division-plane orientation and cell plate formation, respectively[1]. Microtubule organization and dynamics and their communication with membranes at the cortex and cell plate are coordinated by multiple, mostly distinct microtubule-associated proteins[2]. How division-plane selection and establishment are linked, however, is still unknown. Here, we report members of the Arabidopsis IQ67 DOMAIN (IQD) family[3] as microtubule-targeted proteins that localize to the PPB and phragmoplast and additionally reside at the cell plate and a polarized cortical region including the cortical division zone (CDZ). IQDs physically interact with PHRAGMOPLAST ORIENTING KINESIN (POK) proteins[4,5] and PLECKSTRIN HOMOLOGY GTPase ACTIVATING (PHGAP) proteins[6], which are core components of the CDZ[1]. The loss of IQD function impairs PPB formation and affects CDZ recruitment of POKs and PHGAPs, resulting in division-plane positioning defects. We propose that IQDs act as cellular scaffolds that facilitate PPB formation and CDZ set-up during symmetric cell division.}, } @article {pmid34026448, year = {2021}, author = {Jiang, S and Li, H and Zeng, Q and Xiao, Z and Zhang, X and Xu, M and He, Y and Wei, Y and Deng, X}, title = {The Dynamic Counterbalance of RAC1-YAP/OB-Cadherin Coordinates Tissue Spreading with Stem Cell Fate Patterning.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {10}, pages = {2004000}, pmid = {34026448}, issn = {2198-3844}, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/physiology ; Cell Differentiation/physiology ; Cell Lineage ; Cell Movement/physiology ; Cells, Cultured ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Models, Animal ; Morphogenesis ; Signal Transduction ; YAP-Signaling Proteins/*metabolism ; rac1 GTP-Binding Protein/*metabolism ; }, abstract = {Tissue spreading represents a key morphogenetic feature of embryonic development and regenerative medicine. However, how molecular signaling orchestrates the spreading dynamics and cell fate commitment of multicellular tissue remains poorly understood. Here, it is demonstrated that the dynamic counterbalance between RAC1-YAP and OB-cadherin plays a key role in coordinating heterogeneous spreading dynamics with distinct cell fate patterning during collective spreading. The spatiotemporal evolution of individual stem cells in spheroids during collective spreading is mapped. Time-lapse cell migratory trajectory analysis combined with in situ cellular biomechanics detection reveal heterogeneous patterns of collective spreading characteristics, where the cells at the periphery are faster, stiffer, and directional compared to those in the center of the spheroid. Single-cell sequencing shows that the divergent spreading result in distinct cell fate patterning, where differentiation, proliferation, and metabolism are enhanced in peripheral cells. Molecular analysis demonstrates that the increased expression of RAC1-YAP rather than OB-cadherin facilitated cell spreading and induced differentiation, and vice versa. The in vivo wound healing experiment confirms the functional role of RAC1-YAP signaling in tissue spreading. These findings shed light on the mechanism of tissue morphogenesis in the progression of development and provide a practical strategy for desirable regenerative therapies.}, } @article {pmid34023299, year = {2021}, author = {Schneider, P and Reece, SE}, title = {The private life of malaria parasites: Strategies for sexual reproduction.}, journal = {Molecular and biochemical parasitology}, volume = {244}, number = {}, pages = {111375}, pmid = {34023299}, issn = {1872-9428}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Coevolution ; Culicidae/parasitology ; Erythrocytes/parasitology ; Female ; *Gametogenesis ; Host-Parasite Interactions/genetics ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/*genetics ; Liver/parasitology ; Malaria/*parasitology/transmission ; Male ; Plasmodium berghei/genetics/*growth & development/metabolism ; Plasmodium chabaudi/genetics/*growth & development/metabolism ; Plasmodium falciparum/genetics/*growth & development/metabolism ; Plasmodium knowlesi/genetics/*growth & development/metabolism ; Reproduction, Asexual ; Sex Ratio ; }, abstract = {Malaria parasites exhibit a complex lifecycle, requiring extensive asexual replication in the liver and blood of the vertebrate host, and in the haemocoel of the insect vector. Yet, they must also undergo a single round of sexual reproduction, which occurs in the vector's midgut upon uptake of a blood meal. Sexual reproduction is obligate for infection of the vector and thus, is essential for onwards transmission to new hosts. Sex in malaria parasites involves several bottlenecks in parasite number, making the stages involved attractive targets for blocking disease transmission. Malaria parasites have evolved a suite of adaptations ("strategies") to maximise the success of sexual reproduction and transmission, which could undermine transmission-blocking interventions. Yet, understanding parasite strategies may also reveal novel opportunities for such interventions. Here, we outline how evolutionary and ecological theories, developed to explain reproductive strategies in multicellular taxa, can be applied to explain two reproductive strategies (conversion rate and sex ratio) expressed by malaria parasites within the vertebrate host.}, } @article {pmid34020820, year = {2021}, author = {Tanay, A and Sebé-Pedrós, A}, title = {Evolutionary cell type mapping with single-cell genomics.}, journal = {Trends in genetics : TIG}, volume = {37}, number = {10}, pages = {919-932}, doi = {10.1016/j.tig.2021.04.008}, pmid = {34020820}, issn = {0168-9525}, mesh = {Animals ; Cells/*classification/*metabolism ; *Evolution, Molecular ; Genome/*genetics ; *Genomics ; Humans ; Organ Specificity ; *Single-Cell Analysis ; }, abstract = {A fundamental characteristic of animal multicellularity is the spatial coexistence of functionally specialized cell types that are all encoded by a single genome sequence. Cell type transcriptional programs are deployed and maintained by regulatory mechanisms that control the asymmetric, differential access to genomic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the emergence, diversity, and evolutionary dynamics of animal cell types remain almost completely unexplored beyond a few species. Single-cell genomics is emerging as a powerful tool to build comprehensive catalogs of cell types and their associated gene regulatory programs in non-traditional model species. We review the current state of sampling efforts across the animal tree of life and challenges ahead for the comparative study of cell type programs. We also discuss how the phylogenetic integration of cell atlases can lead to the development of models of cell type evolution and a phylogenetic taxonomy of cells.}, } @article {pmid34007033, year = {2021}, author = {Maier, BA and Kiefer, P and Field, CM and Hemmerle, L and Bortfeld-Miller, M and Emmenegger, B and Schäfer, M and Pfeilmeier, S and Sunagawa, S and Vogel, CM and Vorholt, JA}, title = {A general non-self response as part of plant immunity.}, journal = {Nature plants}, volume = {7}, number = {5}, pages = {696-705}, pmid = {34007033}, issn = {2055-0278}, support = {668991/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/*immunology/microbiology/physiology ; Bacteria/genetics/immunology ; Gene Expression Regulation, Plant ; Genes, Plant/immunology/physiology ; Metabolome ; Phylogeny ; Plant Diseases/immunology/microbiology ; Plant Immunity/genetics/physiology ; Secondary Metabolism ; Tryptophan/metabolism ; }, abstract = {Plants, like other multicellular lifeforms, are colonized by microorganisms. How plants respond to their microbiota is currently not well understood. We used a phylogenetically diverse set of 39 endogenous bacterial strains from Arabidopsis thaliana leaves to assess host transcriptional and metabolic adaptations to bacterial encounters. We identified a molecular response, which we termed the general non-self response (GNSR) that involves the expression of a core set of 24 genes. The GNSR genes are not only consistently induced by the presence of most strains, they also comprise the most differentially regulated genes across treatments and are predictive of a hierarchical transcriptional reprogramming beyond the GNSR. Using a complementary untargeted metabolomics approach we link the GNSR to the tryptophan-derived secondary metabolism, highlighting the importance of small molecules in plant-microbe interactions. We demonstrate that several of the GNSR genes are required for resistance against the bacterial pathogen Pseudomonas syringae. Our results suggest that the GNSR constitutes a defence adaptation strategy that is consistently elicited by diverse strains from various phyla, contributes to host protection and involves secondary metabolism.}, } @article {pmid33990594, year = {2021}, author = {Bozdag, GO and Libby, E and Pineau, R and Reinhard, CT and Ratcliff, WC}, title = {Oxygen suppression of macroscopic multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2838}, pmid = {33990594}, issn = {2041-1723}, mesh = {Aerobiosis ; Anaerobiosis ; *Biological Evolution ; Biophysical Phenomena ; DNA-Binding Proteins/genetics ; Directed Molecular Evolution ; Eukaryotic Cells/*cytology/*metabolism ; Gene Deletion ; Genetic Engineering ; *Models, Biological ; Oxygen/*metabolism ; Saccharomyces cerevisiae/*cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Selection, Genetic ; Synthetic Biology ; Transcription Factors/genetics ; }, abstract = {Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular 'snowflake' yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.}, } @article {pmid33988501, year = {2021}, author = {Lu, YX and Regan, JC and Eßer, J and Drews, LF and Weinseis, T and Stinn, J and Hahn, O and Miller, RA and Grönke, S and Partridge, L}, title = {A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33988501}, issn = {2050-084X}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; U01 AG022303/AG/NIA NIH HHS/United States ; U19 AG023122/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*drug effects/metabolism ; Animals ; *Autophagy ; Chromatin/metabolism ; Drosophila melanogaster ; Eukaryotic Initiation Factor-3/metabolism ; Female ; Gene Expression Regulation ; Histones/genetics/*metabolism ; Intestines ; Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism ; Mice ; Sirolimus/pharmacology ; }, abstract = {Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organisation, induces intestinal autophagy through transcriptional regulation, and prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting that the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.}, } @article {pmid33984158, year = {2021}, author = {Lineweaver, CH and Bussey, KJ and Blackburn, AC and Davies, PCW}, title = {Cancer progression as a sequence of atavistic reversions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {7}, pages = {e2000305}, pmid = {33984158}, issn = {1521-1878}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; U54-CA143682/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota ; Eukaryotic Cells ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi-unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular-to-unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one-off multicellular-to-unicellular reversion, and are better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular-eukaryote-to-multicellular-eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ.}, } @article {pmid33983920, year = {2021}, author = {van Gestel, J and Wagner, A}, title = {Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation.}, journal = {PLoS biology}, volume = {19}, number = {5}, pages = {e3001250}, pmid = {33983920}, issn = {1545-7885}, mesh = {Animals ; Bacteria/metabolism ; Bacterial Adhesion/*physiology ; Biological Evolution ; Cell Adhesion/*physiology ; Cell Communication/physiology ; Cell Polarity/physiology ; Evolution, Molecular ; Fungi/metabolism ; Humans ; }, abstract = {The repeated evolution of multicellularity led to a wide diversity of organisms, many of which are sessile, including land plants, many fungi, and colonial animals. Sessile organisms adhere to a surface for most of their lives, where they grow and compete for space. Despite the prevalence of surface-associated multicellularity, little is known about its evolutionary origin. Here, we introduce a novel theoretical approach, based on spatial lineage tracking of cells, to study this origin. We show that multicellularity can rapidly evolve from two widespread cellular properties: cell adhesion and the regulatory control of adhesion. By evolving adhesion, cells attach to a surface, where they spontaneously give rise to primitive cell collectives that differ in size, life span, and mode of propagation. Selection in favor of large collectives increases the fraction of adhesive cells until a surface becomes fully occupied. Through kin recognition, collectives then evolve a central-peripheral polarity in cell adhesion that supports a division of labor between cells and profoundly impacts growth. Despite this spatial organization, nascent collectives remain cryptic, lack well-defined boundaries, and would require experimental lineage tracking technologies for their identification. Our results suggest that cryptic multicellularity could readily evolve and originate well before multicellular individuals become morphologically evident.}, } @article {pmid33979602, year = {2021}, author = {Joy, DA and Libby, ARG and McDevitt, TC}, title = {Deep neural net tracking of human pluripotent stem cells reveals intrinsic behaviors directing morphogenesis.}, journal = {Stem cell reports}, volume = {16}, number = {5}, pages = {1317-1330}, pmid = {33979602}, issn = {2213-6711}, support = {T32 HD007470/HD/NICHD NIH HHS/United States ; }, mesh = {Bone Morphogenetic Protein 4/pharmacology ; Cell Count ; Cell Differentiation/drug effects ; Cell Lineage/drug effects ; Cell Movement/drug effects ; Cell Tracking ; Cells, Cultured ; Humans ; Image Processing, Computer-Assisted ; Induced Pluripotent Stem Cells/*cytology/drug effects ; *Morphogenesis/drug effects ; *Neural Networks, Computer ; Smad Proteins/metabolism ; }, abstract = {Lineage tracing is a powerful tool in developmental biology to interrogate the evolution of tissue formation, but the dense, three-dimensional nature of tissue limits the assembly of individual cell trajectories into complete reconstructions of development. Human induced pluripotent stem cells (hiPSCs) can recapitulate aspects of developmental processes, providing an in vitro platform to assess the dynamic collective behaviors directing tissue morphogenesis. Here, we trained an ensemble of neural networks to track individual hiPSCs in time-lapse microscopy, generating longitudinal measures of cell and cellular neighborhood properties on timescales from minutes to days. Our analysis reveals that, while individual cell parameters are not strongly affected by pluripotency maintenance conditions or morphogenic cues, regional changes in cell behavior predict cell fate and colony organization. By generating complete multicellular reconstructions of hiPSC behavior, our tracking pipeline enables fine-grained understanding of morphogenesis by elucidating the role of regional behavior in early tissue formation.}, } @article {pmid33972551, year = {2021}, author = {Tsutsui, K and Machida, H and Nakagawa, A and Ahn, K and Morita, R and Sekiguchi, K and Miner, JH and Fujiwara, H}, title = {Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2577}, pmid = {33972551}, issn = {2041-1723}, support = {R01 DK078314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*cytology/metabolism/ultrastructure ; Epithelial Cells/metabolism ; Extracellular Matrix/genetics/*metabolism ; Female ; Fibroblasts/metabolism ; Hair Follicle/*metabolism ; Immunohistochemistry ; Laminin/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission ; Multigene Family ; Muscle Cells/metabolism ; Neurons/metabolism ; Single-Cell Analysis ; Transcriptome/*genetics ; }, abstract = {Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.}, } @article {pmid33961843, year = {2021}, author = {Levin, M}, title = {Bioelectrical approaches to cancer as a problem of the scaling of the cellular self.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {102-113}, doi = {10.1016/j.pbiomolbio.2021.04.007}, pmid = {33961843}, issn = {1873-1732}, mesh = {Electrophysiological Phenomena ; Humans ; Membrane Potentials ; Morphogenesis ; *Neoplasms ; *Signal Transduction ; }, abstract = {One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging approaches to cancer.}, } @article {pmid33952585, year = {2021}, author = {Russo, M and Sogari, A and Bardelli, A}, title = {Adaptive Evolution: How Bacteria and Cancer Cells Survive Stressful Conditions and Drug Treatment.}, journal = {Cancer discovery}, volume = {11}, number = {8}, pages = {1886-1895}, doi = {10.1158/2159-8290.CD-20-1588}, pmid = {33952585}, issn = {2159-8290}, mesh = {*Bacteria ; *Biological Evolution ; *Homeostas