@article {pmid40276264,
year = {2025},
author = {Compton, ZT and Ågren, JA and Marusyk, A and Nedelcu, AM},
title = {The Elephant and the Spandrel.},
journal = {Evolution, medicine, and public health},
volume = {13},
number = {1},
pages = {92-100},
pmid = {40276264},
issn = {2050-6201},
abstract = {Comparative oncology has made great strides in identifying patterns of cancer prevalence and risk across the tree of life. Such studies have often centered on elucidating the evolution of mechanisms that prevent the development and progression of cancer, especially in large animals such as elephants. Conclusions from this approach, however, may have been exaggerated, given that the deep evolutionary origins of multicellularity suggest that the preeminent functions of the identified mechanisms may be unrelated to cancer. Instead, cancer suppression may have emerged as an evolutionary byproduct, or "spandrel". We propose a novel evolutionary perspective that highlights the importance of somatic maintenance as the underlying axis of natural selection. We argue that by shifting the focus of study from cancer suppression to somatic maintenance, we can gain a deeper understanding of the evolutionary pressures that shaped the mechanisms responsible for the observed variation in cancer prevalence across species.},
}

@article {pmid40263560,
year = {2025},
author = {Mukhopadhyay, J and Ngobeli, R and Ghosh, G and Elburg, MA},
title = {Age of the Western Iron Ore Group, India, and implications for pre-GOE oxygenation of oceans at the twilight of Archean-Proterozoic transition.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13951},
pmid = {40263560},
issn = {2045-2322},
abstract = {Increasing concentrations of oxygen in the early atmosphere contributed to the development of the Earth's ozone shield and thus ushered in the growth of photoautotrophs. The proliferation of multicellular life is linked with the rise of atmospheric oxygen, known as the Great Oxidation Event (GOE). However, it has become evident that the permanent trend of rising oxygen in the atmosphere was preceded by multiple fluctuations. It is imperative to gather information from immediate pre- and post-GOE successions for constraining this transformation. The greenstone successions from > 3.8 Ga to the Archean-Proterozoic transition are important candidates for deciphering the evolution of the atmosphere and hydrosphere. The Archean Singhbhum craton, eastern India, hosts a well-preserved low-grade greenstone succession, the Western Iron Ore Group (W-IOG), containing banded iron formations (BIF) from pre-GOE stratigraphy. We report here zircon U-Pb LA-ICPMS age of ~ 2500 Ma from felsic tuff below the BIF and detrital zircon age of ~ 2730 Ma from underlying sandstones that constrain the age of the younger cycle of BIF deposition in the W-IOG as Neoarchean grading into the Paleoproterozoic. The newly reported Neoarchean to Paleoproterozoic age of the W-IOG provides potential opportunity for future research on the tempos and events immediately ahead of the GOE in the oceanic realm at the Archean-Proterozoic boundary.},
}

@article {pmid40263484,
year = {2025},
author = {Pai, VP and Pio-Lopez, L and Sperry, MM and Erickson, P and Tayyebi, P and Levin, M},
title = {Basal Xenobot transcriptomics reveals changes and novel control modality in cells freed from organismal influence.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {646},
pmid = {40263484},
issn = {2399-3642},
support = {62212//John Templeton Foundation (JTF)/ ; },
abstract = {Would transcriptomes change if cell collectives acquired a novel morphogenetic and behavioral phenotype in the absence of genomic editing, transgenes, heterologous materials, or drugs? We investigate the effects of morphology and nascent emergent life history on gene expression in the basal (no engineering, no sculpting) form of Xenobots -autonomously motile constructs derived from Xenopus embryo ectodermal cell explants. To investigate gene expression differences between cells in the context of an embryo with those that have been freed from instructive signals and acquired novel lived experiences, we compare transcriptomes of these basal Xenobots with age-matched Xenopus embryos. Basal Xenobots show significantly larger inter-individual gene variability than age-matched embryos, suggesting increased exploration of the transcriptional space. We identify at least 537 (non-epidermal) transcripts uniquely upregulated in these Xenobots. Phylostratigraphy shows a majority of transcriptomic shifts in the basal Xenobots towards evolutionarily ancient transcripts. Pathway analyses indicate transcriptomic shifts in the categories of motility machinery, multicellularity, stress and immune response, metabolism, thanatotranscriptome, and sensory perception of sound and mechanical stimuli. We experimentally confirm that basal Xenobots respond to acoustic stimuli via changes in behavior. Together, these data may have implications for evolution, biomedicine, and synthetic morphoengineering.},
}

@article {pmid40262731,
year = {2025},
author = {Kong, Z and Zhu, L and Liu, Y and Liu, Y and Chen, G and Wang, H},
title = {Effects of different stages, dosages and courses of prenatal dexamethasone exposure on testicular development in mice.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {115468},
doi = {10.1016/j.fct.2025.115468},
pmid = {40262731},
issn = {1873-6351},
abstract = {PURPOSE: Observe the effects of prenatal dexamethasone exposure (PDE) at different stages, dosages, and courses on testicular morphology and multicellular function in offspring mice.

METHODS: Pregnant Kunming mice were subjected to subcutaneous injections of dexamethasone at different stages [GD (gestational day) 14-15 and 16-17], dosages (0.2, 0.4, and 0.8 mg/kg·d), and courses (GD 14-15 and 14-17). Pregnant mice were euthanized on GD 18, and fetal serum and testicular samples were collected to assess serum testosterone level, testicular morphology, cellular proliferation/apoptosis function, expression of multicellular marker/functional gene, and the expression of developmental regulatory signalling pathways such as Notch and Wnt.

RESULTS: PDE could lead to widening of the interstitial area and reduction of seminiferous tubules in fetal testicular tissue, accompanied by significant impairment of Sertoli cell function, particularly evident during late gestation, at high doses, and with multiple courses. However, changes in Leydig cells and spermatogonia function of PDE are not significant. Furthermore, we discovered that PDE could activate the Notch signalling pathway in Sertoli cells while inhibiting the Wnt signalling pathway.

CONCLUSION: PDE could affect fetal testicular development, especially for Sertoli cells during late gestation, at high doses and multiple courses. This study confirms the effects of PDE on testicular tissue morphology and multicellular function, providing a comprehensive understanding of the testicular developmental toxicity of dexamethasone and evidence for guiding rational medication during pregnancy.},
}

@article {pmid40254399,
year = {2025},
author = {Durymanov, M},
title = {Tumor Spheroids, Tumor Organoids, Tumor Explants, and Tumoroids: What Are the Differences between Them?.},
journal = {Biochemistry. Biokhimiia},
volume = {90},
number = {2},
pages = {200-213},
doi = {10.1134/S0006297924604234},
pmid = {40254399},
issn = {1608-3040},
mesh = {Humans ; *Organoids/pathology/metabolism ; *Spheroids, Cellular/pathology/metabolism ; *Neoplasms/pathology/metabolism ; Tumor Microenvironment ; Animals ; Cell Culture Techniques, Three Dimensional ; },
abstract = {Three-dimensional (3D) cell cultures that mimic tumor microenvironment have become an essential tool in cancer research and drug response analysis, significantly enhancing our understanding of tumor biology and advancing personalized medicine. Currently, the most widely mentioned 3D multicellular culture models include spheroids, organoids, tumor explants, and tumoroids. These 3D structures, exploited for various applications, are generated from cancer and non-cancer cells of different origin using multiple techniques. However, despite extensive research and numerous studies, consistent definitions of these 3D culture models are not clearly established. The manuscript provides a comprehensive overview of these models, detailing brief history of their research, unique biological characteristics, advantages, limitations, and specific applications.},
}

Humans
*Organoids/pathology/metabolism
*Spheroids, Cellular/pathology/metabolism
*Neoplasms/pathology/metabolism
Tumor Microenvironment
Animals
Cell Culture Techniques, Three Dimensional

@article {pmid40245677,
year = {2025},
author = {Tsubota, KI and Horikoshi, S and Hiraiwa, T and Okuda, S},
title = {Strain softening and hysteresis arising from 3D multicellular dynamics during long-term large deformation.},
journal = {Journal of the mechanical behavior of biomedical materials},
volume = {168},
number = {},
pages = {107001},
doi = {10.1016/j.jmbbm.2025.107001},
pmid = {40245677},
issn = {1878-0180},
abstract = {Living tissues exhibit complex mechanical properties, including viscoelastic and elastoplastic responses, that are crucial for regulating cell behaviors and tissue deformations. Despite their significance, the intricate properties of three-dimensional (3D) cell constructs are not well understood and are inadequately implemented in biomaterial engineering. To address this gap, we developed a numerical method to analyze the dynamic properties of cell constructs using a 3D vertex model framework. By focusing on 3D tissues composed of confluent homogeneous cells, we characterized their properties in response to various deformation magnitudes and time scales. Stress relaxation tests revealed that large deformations initially induced relaxation in the shapes of individual cells. This process is amplified by subsequent transient cell rearrangements, homogenizing cell shapes and leading to tissue fluidization. Additionally, dynamic viscoelastic analyses showed that tissues exhibited strain softening and hysteresis during large deformations. Interestingly, this strain softening originates from multicellular structures independent of cell rearrangement, while hysteresis arises from cell rearrangement. Moreover, tissues exhibit elastoplastic responses over the long term, which are well represented by the Ramberg-Osgood model. These findings highlight the characteristic properties of cell constructs emerging from their structures and rearrangements, especially during long-term large deformations. The developed method offers a new approach to uncover the dynamic nature of 3D tissue mechanics and could serve as a technical foundation for exploring tissue mechanics and advancing biomaterial engineering.},
}

@article {pmid40231984,
year = {2025},
author = {Chen, C and Zhao, H and Yuan, W and Chen, H and Wang, P and Wang, Q and Chen, C and Song, T},
title = {Tumoral Nanovesicles-Loaded Magnetotactic Bacteria for Tumor-Targeted Therapy under a Swing Magnetic Field.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c02422},
pmid = {40231984},
issn = {1944-8252},
abstract = {Tumor heterogeneity poses numerous challenges for targeted drug therapy. Although tumor cell-derived nanovesicles (NVs) have emerged as an intriguing method for tumor targeting, how to exert the antitumor effect after targeting remains a key concern. Magnetotactic bacteria (MTB) synthesize chain-like magnetite (Fe3O4) crystals with inherent magnetic moments, which could generate significant torque under a desired magnetic field and move along the magnetic field using their own flagella. Herein, a composite of MTB AMB-1 and NVs was fabricated via electrostatic adsorption where AMB-1 could transport NVs to the tumor site by a guiding magnetic field, while NVs also assist AMB-1 in binding to tumor cells. Subsequently, under the influence of a swing magnetic field (sMF), MTB exert physical stimuli on the cells, inducing the changes of mitochondrial membrane potential and cellular reactive oxygen species (ROS). Finally, it is revealed that the NVs-loaded AMB-1 induced a decrease in cellular viability and significantly inhibited the growth of tumors in vivo under the sMF. Therefore, by remote control of the guidance and stimuli production, the NVs-loaded AMB-1 was highly promising to advance the development of targeted therapeutic strategies for tumors under the context of tumor heterogeneity.},
}

@article {pmid40230370,
year = {2025},
author = {Jahan, I and Scott, TJ and Strassmann, JE and Queller, DC},
title = {Testing the coordination hypothesis: incompatibilities in aggregative development of an experimentally evolved social amoeba.},
journal = {Evolution letters},
volume = {9},
number = {2},
pages = {236-248},
pmid = {40230370},
issn = {2056-3744},
abstract = {Multicellular organisms that form by aggregation of cells arguably do not achieve high levels of complexity. Conflict among the cells is a widely accepted explanation for this, but an alternative hypothesis is that mixing cells of different genotypes leads to failures of coordination, which we call the "coordination hypothesis." We empirically tested the coordination hypothesis in the social amoeba Dictyostelium discoideum. We mixed D. discoideum clones that had evolved in isolation for generations and acquired mutations that have not been tested against each other by selection. To quantify the effect of incompatibilities, we measured performance in terms of the developmental traits of slug migration and spore production. Importantly, we mixed lines evolved from the same ancestor under conditions that would not select for the evolution of de novo kin recognition. Our results show no evidence of incompatibilities in four traits related to the coordinated movement of slugs toward light in the social amoeba. Spore production was higher than expected in mixtures, in apparent contradiction to the coordination hypothesis. However, we found support for coordination incompatibilities in an interaction between migration and spore production: in mixtures, fewer cells succeeded at both migrating and becoming spores.},
}

@article {pmid40228789,
year = {2025},
author = {McFarland, A and Fenton, M and Madsen, JJ and Ye, L},
title = {Unraveling a Receptor-Mediated Bioluminescence Signaling Pathway in Red Tide Algae.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169153},
doi = {10.1016/j.jmb.2025.169153},
pmid = {40228789},
issn = {1089-8638},
abstract = {G protein-coupled receptors (GPCRs) are ubiquitous transmembrane proteins in multicellular life. Human vision, taste, and neuron activity are all mediated by GPCRs, and a large percentage of currently approved drugs target GPCRs. However, our understanding of GPCRs in single-celled eukaryotes is incomplete, and many of the components of GPCR signal transduction have not been identified in unicellular eukaryotes. Previous works studying bioluminescent dinoflagellates-single-celled algae involved in coral reef endosymbiosis and toxic red tide blooms-implicate GPCRs in a signaling pathway for bioluminescence but have not elucidated the individual components comprising the pathway. Herein, we identified a novel GPCR in dinoflagellates-Bioluminescence-Inducing Receptor 1 (BIR1)-which plays a significant role in the signaling pathway for bioluminescence in red tide blooms in response to wave turbulence. Additionally, we identified a full endogenous G-protein complex and downstream effectors that are integral to known calcium signaling networks. Based on these identifications, we used knockdown and knockout techniques to demonstrate the integral role of BIR1 in bioluminescence and highlight its role in predator response and shear force-elicited GPCR signaling in red tide blooms. This advance opens avenues for red tide control and supports the existence of similar GPCR pathways involved in bloom toxicity dynamics.},
}

@article {pmid40226989,
year = {2025},
author = {Lv, CL and Li, B},
title = {Interface morphodynamics in living tissues.},
journal = {Soft matter},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5sm00145e},
pmid = {40226989},
issn = {1744-6848},
abstract = {Interfaces between distinct tissues or between tissues and environments are common in multicellular organisms. The evolution and stability of these interfaces are essential for tissue development, and their dysfunction can lead to diseases such as cancer. Mounting efforts, either theoretical or experimental, have been devoted to uncovering the morphodynamics of tissue interfaces. Here, we review the recent progress of studies on interface morphodynamics. The regulatory mechanisms governing interface evolution are dissected, with a focus on adhesion, cortical tension, cell activity, extracellular matrix, and microenvironment. We examine the methodologies used to study morphodynamics, emphasizing the characteristics of experimental techniques and theoretical models. Finally, we explore the broader implications of interface morphodynamics in tissue morphogenesis and diseases, offering a comprehensive perspective on this rapidly developing field.},
}

@article {pmid40220996,
year = {2025},
author = {Page-McCaw, PS and Pokidysheva, EN and Darris, CE and Chetyrkin, S and Fidler, AL and Gallup, J and , and Murawala, P and Hudson, JK and Boudko, SP and Hudson, BG},
title = {Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling metazoan multicellularity, evolution and adaptation.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {108496},
doi = {10.1016/j.jbc.2025.108496},
pmid = {40220996},
issn = {1083-351X},
abstract = {Collagen IV is a major component of basement membranes, a specialized form of extracellular matrix that enabled the assembly of multicellular epithelial tissues. In mammals, collagen IV assembles from a family of six α-chains (α1 to α6), forming three supramolecular scaffolds: Col-IV[α121], Col-IV[α345] and Col-IV[α121-α556]. The α-chains are encoded by six genes (COL4A1-6) that occur in pairs in a head-to-head arrangement. In Alport syndrome, variants in COL4A3, 4 or 5 genes, encoding Col-IV[α345] scaffold in glomerular basement membrane (GBM), the kidney ultrafilter, cause progressive renal failure in millions of people worldwide. The molecular mechanisms of how variants cause dysfunction remain obscure. Here, we gained insights into Col-IV[α345] function by determining its evolutionary lineage, as revealed from phylogenetic analyses and tissue expression of COL4 gene-pairs. We found that the COL4A⟨1|2⟩ gene-pair emerged in basal Ctenophores and Cnidaria phyla and is highly conserved across metazoans. The COL4A⟨1|2⟩ duplicated and arose as the progenitor to the COL4A⟨3|4⟩ gene-pair in cyclostomes, coinciding with emergence of kidney GBM, and expressed and conserved in jawed-vertebrates, except for amphibians, and a second duplication as the progenitor to the COL4A⟨5|6⟩ gene-pair and conserved in jawed-vertebrates. These findings revealed that Col-IV[α121] is the progenitor scaffold, expressed ubiquitously in metazoan basement membranes, and which evolved into vertebrate Col-IV[α345] and expressed in GBM. The Col-IV[α345] scaffold, in comparison, has an increased number of cysteine residues, varying in number with osmolarity of the environment. Cysteines mediate disulfide crosslinks between protomers, an adaptation enabling a compact GBM that withstands the high hydrostatic pressure associated with glomerular ultrafiltration.},
}

@article {pmid40214419,
year = {2025},
author = {Wei, Y and Chen, H and Li, X and Wang, Z and Song, T},
title = {A magneto-optical microscopic control system for analysis of magnetotaxis and phototaxis sensing in magnetotactic bacteria.},
journal = {The Review of scientific instruments},
volume = {96},
number = {4},
pages = {},
doi = {10.1063/5.0254144},
pmid = {40214419},
issn = {1089-7623},
mesh = {*Magnetospirillum/physiology ; Magnetic Fields ; *Phototaxis ; *Microscopy/instrumentation/methods ; Bacterial Proteins/metabolism ; Light ; },
abstract = {A magneto-optical microscopic control system (MO-MCS) was developed for analyzing the magnetotaxis and phototaxis sensing in magnetotactic bacteria (MTB). The system includes a microscopic image acquisition device, a planar magnetic field generator, a multi-wavelength illumination device, and a host computer control system. The MO-MCS can accurately adjust parameters such as the magnetic field intensity, direction, and the duration and intensity of illumination. Using the system, we analyzed the motion characteristics of Magnetospirillum magneticum AMB-1 wild-type and corresponding mutant strains under various illumination conditions when the magnetic field was reversed. The experiments indicated that the photoreceptor protein Amb2291 and the magnetosensitive protein Amb0994 play complementary roles in the motion behavior of bacteria in response to magnetic field changes under blue light. The MO-MCS provides a valuable tool for investigating the response mechanisms of micro-organisms to environmental physical factors.},
}

*Magnetospirillum/physiology
Magnetic Fields
*Phototaxis
*Microscopy/instrumentation/methods
Bacterial Proteins/metabolism
Light

@article {pmid40198726,
year = {2025},
author = {Liu, X and Pitchford, JW and Constable, GWA},
title = {Cell size and selection for stress-induced cell fusion in unicellular eukaryotes.},
journal = {PLoS computational biology},
volume = {21},
number = {4},
pages = {e1012418},
doi = {10.1371/journal.pcbi.1012418},
pmid = {40198726},
issn = {1553-7358},
mesh = {*Cell Fusion ; *Models, Biological ; *Cell Size ; Biological Evolution ; *Stress, Physiological/physiology ; *Eukaryota/physiology/cytology ; *Eukaryotic Cells/physiology/cytology ; Selection, Genetic ; },
abstract = {In unicellular organisms, sexual reproduction typically begins with the fusion of two cells (plasmogamy) followed by the fusion of their two haploid nuclei (karyogamy) and finally meiosis. Most work on the evolution of sexual reproduction focuses on the benefits of the genetic recombination that takes place during meiosis. However, the selection pressures that may have driven the early evolution of binary cell fusion, which sets the stage for the evolution of karyogamy by bringing nuclei together in the same cell, have seen less attention. In this paper we develop a model for the coevolution of cell size and binary cell fusion rate. The model assumes that larger cells experience a survival advantage from their larger cytoplasmic volume. We find that under favourable environmental conditions, populations can evolve to produce larger cells that undergo obligate binary cell fission. However, under challenging environmental conditions, populations can evolve to subsequently produce smaller cells under binary cell fission that nevertheless retain a survival advantage by fusing with other cells. The model thus parsimoniously recaptures the empirical observation that sexual reproduction is typically triggered by adverse environmental conditions in many unicellular eukaryotes and draws conceptual links to the literature on the evolution of multicellularity.},
}

*Cell Fusion
*Models, Biological
*Cell Size
Biological Evolution
*Stress, Physiological/physiology
*Eukaryota/physiology/cytology
*Eukaryotic Cells/physiology/cytology
Selection, Genetic

@article {pmid40188154,
year = {2025},
author = {Nguyen, AQ and Huang, J and Bi, D},
title = {Origin of yield stress and mechanical plasticity in model biological tissues.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3260},
pmid = {40188154},
issn = {2041-1723},
support = {DMR-2046683//National Science Foundation (NSF)/ ; PHY-2019745//National Science Foundation (NSF)/ ; RGP0007/2022//Human Frontier Science Program (HFSP)/ ; },
mesh = {*Stress, Mechanical ; *Models, Biological ; Biomechanical Phenomena ; Animals ; Humans ; },
abstract = {During development and under normal physiological conditions, biological tissues are continuously subjected to substantial mechanical stresses. In response to large deformations, cells in a tissue must undergo multicellular rearrangements to maintain integrity and robustness. However, how these events are connected in time and space remains unknown. Here, using theoretical modeling, we study the mechanical plasticity of cell monolayers under large deformations. Our results suggest that the jamming-unjamming (solid-fluid) transition can vary significantly depending on the degree of deformation, implying that tissues are highly unconventional materials. We elucidate the origins of this behavior. We also demonstrate how large deformations are accommodated through a series of cellular rearrangements, similar to avalanches in non-living materials. We find that these 'tissue avalanches' are governed by stress redistribution and the spatial distribution of "soft" or vulnerable spots, which are more prone to undergo rearrangements. Finally, we propose a simple and experimentally accessible framework to infer tissue-level stress and predict avalanches based on static images.},
}

*Stress, Mechanical
*Models, Biological
Biomechanical Phenomena
Animals
Humans

@article {pmid40183649,
year = {2025},
author = {Zielenkiewicz, U and Kaushal, V and Kaczanowski, S},
title = {On the origins and evolution of apoptosis: the predator‒mitochondrial prey hypothesis.},
journal = {Journal of evolutionary biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jeb/voaf039},
pmid = {40183649},
issn = {1420-9101},
abstract = {Different types of programmed cell death have been described both in unicellular and multicellular organisms. The fundamental mode of eukaryotic cell death is programmed cell death initiated by mitochondria, which is frequently referred to as apoptosis (or mitochondrial apoptosis). It is initiated by mitochondria through mitochondrial permeability transition and the release of apoptotic factors. It is widely thought that mitochondrial apoptosis evolved concurrently with mitochondrial domestication. Programmed cell death initiated by mitochondria is observed in various multicellular and unicellular eukaryotes. We discuss key hypotheses-namely, the "pleiotropy", "addiction", "immunological", and our "predator-mitochondrial prey" hypotheses-to explain the mechanisms of mitochondrial domestication that lead to apoptosis. In this perspective paper, we present evidence from various phylogenetic and experimental studies that strongly indicates our hypothesis is the most plausible. For the first time, we also present evidence that challenges the assumptions underlying all other hypotheses.},
}

@article {pmid40181506,
year = {2025},
author = {Lewis, EM and Becker, O and Symons, AN and LaCoss, C and Baclig, AJ and Guzman, A and Sanders, C and Gonzalez, L and Warner, LR and Lewis, K},
title = {The LARP6 La module from Tetrabaena socialis reveals structural and functional differences from plant and animal LARP6 homologues.},
journal = {RNA biology},
volume = {},
number = {},
pages = {},
doi = {10.1080/15476286.2025.2489303},
pmid = {40181506},
issn = {1555-8584},
abstract = {This study identified the LARP6 La Module from Tetrabaena socialis (T. socialis), a four-celled green algae, in an effort to better understand the evolution of LARP6 structure and RNA binding activity in multicellular eukaryotes. Using a combination of sequence alignments, domain boundary screens, and structural modelling, we recombinantly expressed and isolated the TsLARP6 La Module to > 98% purity for in vitro biochemical characterization. The La Module is stably folded and exerts minimal RNA binding activity against single-stranded homopolymeric RNAs. Surprisingly, it exhibits low micromolar binding affinity for the vertebrate LARP6 cognate ligand, a bulged-stem loop found in the 5'UTR of collagen type I mRNA, but does not bind double-stranded RNAs of similar size. These result suggests that the TsLARP6 La Module may prefer structured RNA ligands. In contrast, however, the TsLARP6 La Module does not exhibit the RNA chaperone activity that is observed in vertebrate homologs. Therefore, we conclude that protist LARP6 May have both distinct RNA ligands and binding mechanisms from the previously characterized LARP6 proteins of animals and vascular plants, thus establishing a distinct third class of the LARP6 protein family.},
}

@article {pmid40179202,
year = {2025},
author = {Pillai, EK and Brunet, T},
title = {Archaea go multicellular under pressure.},
journal = {Science (New York, N.Y.)},
volume = {388},
number = {6742},
pages = {28-29},
doi = {10.1126/science.adw6689},
pmid = {40179202},
issn = {1095-9203},
mesh = {*Archaea/physiology/cytology ; },
abstract = {A microbe from the Dead Sea switches to a tissue-like form when compressed.},
}

*Archaea/physiology/cytology

@article {pmid40179183,
year = {2025},
author = {Rados, T and Leland, OS and Escudeiro, P and Mallon, J and Andre, K and Caspy, I and von Kügelgen, A and Stolovicki, E and Nguyen, S and Patop, IL and Rangel, LT and Kadener, S and Renner, LD and Thiel, V and Soen, Y and Bharat, TAM and Alva, V and Bisson, A},
title = {Tissue-like multicellular development triggered by mechanical compression in archaea.},
journal = {Science (New York, N.Y.)},
volume = {388},
number = {6742},
pages = {109-115},
doi = {10.1126/science.adu0047},
pmid = {40179183},
issn = {1095-9203},
mesh = {Actins/metabolism ; Archaeal Proteins/metabolism ; Glycosylation ; Elasticity ; Biological Evolution ; Biomechanical Phenomena ; Stress, Mechanical ; },
abstract = {The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once in archaea. We show that uniaxial compression induces clonal multicellularity in haloarchaea, forming tissue-like structures. These archaeal tissues are mechanically and molecularly distinct from their unicellular lifestyle, mimicking several eukaryotic features. Archaeal tissues undergo a multinucleate stage followed by tubulin-independent cellularization, orchestrated by active membrane tension at a critical cell size. After cellularization, tissue junction elasticity becomes akin to that of animal tissues, giving rise to two cell types-peripheral (Per) and central scutoid (Scu) cells-with distinct actin and protein glycosylation polarity patterns. Our findings highlight the potential convergent evolution of a biophysical mechanism in the emergence of multicellular systems across domains of life.},
}

Actins/metabolism
Archaeal Proteins/metabolism
Glycosylation
Elasticity
Biological Evolution
Biomechanical Phenomena
Stress, Mechanical

@article {pmid39508584,
year = {2024},
author = {Thomas, F and Asselin, K and MacDonald, N and Brazier, L and Meliani, J and Ujvari, B and Dujon, AM},
title = {Oncogenic processes: a neglected parameter in the evolutionary ecology of animals.},
journal = {Comptes rendus biologies},
volume = {347},
number = {},
pages = {137-157},
doi = {10.5802/crbiol.159},
pmid = {39508584},
issn = {1768-3238},
abstract = {Cancer is a biological process that emerged at the end of the Precambrian era with the rise of multicellular organisms. Traditionally, cancer has been viewed primarily as a disease relevant to human and domesticated animal health, attracting attention mainly from oncologists. In recent years, however, the community of ecologists and evolutionary biologists has recognized the pivotal role of cancer-related issues in the evolutionary paths of various species, influencing multiple facets of their biology. It has become evident that overlooking these issues is untenable for a comprehensive understanding of species evolution and ecosystem functioning. In this article, we highlight some significant advancements in this field, also underscoring the pressing need to consider reciprocal interactions not only between cancer cells and their hosts but also with all entities comprising the holobiont. This reflection gains particular relevance as ecosystems face increasing pollution from mutagenic substances, resulting in a resurgence of cancer cases in wildlife.},
}

@article {pmid39345214,
year = {2024},
author = {Mathieu, J and Huynh, JR},
title = {Incomplete divisions between sister germline cells require Usp8 function.},
journal = {Comptes rendus biologies},
volume = {347},
number = {},
pages = {109-117},
doi = {10.5802/crbiol.161},
pmid = {39345214},
issn = {1768-3238},
mesh = {*Germ Cells ; Animals ; Cell Division ; Endosomal Sorting Complexes Required for Transport/genetics ; Humans ; Ubiquitin Thiolesterase/genetics/metabolism ; },
abstract = {Cytokinetic abscission is the final step of cell division, resulting in two separate daughter cells. While abscission is typically complete across most cell types, germline cells, which produce sexual gametes, do not finish cytokinesis, maintaining connections between sister cells. These connections are essential for sharing cytoplasm as they differentiate into oocyte and sperm. First, we outline the molecular events of cytokinesis during both complete and delayed abscission, highlighting the role of the ESCRT-III proteins. We then focus on recent discoveries that reveal the molecular mechanisms blocking abscission in Drosophila germline cells. The enzyme Usp8 was identified as vital for ensuring incomplete cytokinesis through the regulation of ESCRT-III ubiquitination and localization. Finally, we explore how the processes of incomplete cytokinesis could hold evolutionary importance, suggesting additional studies into choanoflagellates to comprehend the origins of multicellularity.},
}

*Germ Cells
Animals
Cell Division
Endosomal Sorting Complexes Required for Transport/genetics
Humans
Ubiquitin Thiolesterase/genetics/metabolism

@article {pmid40174588,
year = {2025},
author = {Wang, K and Lu, Z and Yao, Z and He, X and Hu, Z and Zhou, D},
title = {Single-cell phylodynamic inference of stem cell differentiation and tumor evolution.},
journal = {Cell systems},
volume = {},
number = {},
pages = {101244},
doi = {10.1016/j.cels.2025.101244},
pmid = {40174588},
issn = {2405-4720},
abstract = {Phylodynamic inference (PI) quantifies population dynamics and evolutionary trajectories using phylogenetic trees. Single-cell lineage tracing enables phylogenetic tree reconstruction for thousands of cells in multicellular organisms, facilitating PI at the cellular level. However, cell differentiation and somatic evolution challenge the direct application of existing PI frameworks to somatic tissues. We introduce scPhyloX, a computational framework modeling structured cell populations by leveraging single-cell phylogenetic trees to infer tissue development and tumor evolution dynamics. A key advancement is its ability to infer time-varying parameters, capturing dynamic biological processes. Simulations demonstrate scPhyloX's accuracy in scenarios including tissue development, disease treatment, and tumor growth. Application to three real datasets reveals insights into somatic dynamics: cycling stem cell overshoot in fly organ development, clonal expansion of multipotent hematopoietic progenitors during human aging, and pronounced subclonal selection in early colorectal tumorigenesis. scPhyloX thus provides a computational approach for investigating somatic tissue development and evolution.},
}

@article {pmid40168695,
year = {2025},
author = {Wang, Q and Chen, C and Zhao, H and Jiao, Y and Chen, H and Wang, P and Song, T},
title = {Magnetotactic bacteria-mediated integrated magnetic targeted hyperthermia for in-situ deep-seated tumor.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {252},
number = {},
pages = {114658},
doi = {10.1016/j.colsurfb.2025.114658},
pmid = {40168695},
issn = {1873-4367},
abstract = {Unlike hyperthermia after intratumoral injection, the method of integrated magnetic targeted hyperthermia (iMTH) guides magnetic medium to the target site and then directly performs in-situ heating, showing great potential for effective treatment of deep-seated tumors in the body. Magnetotactic bacteria (MTB), having chain-like arranged magnetic nanoparticles within its body and active movement along an external magnetic field, are considered as a very fitted material for iMTH. However, the amount of MTB concentrated on the deep-seated tumor posed a significant challenge for the successful implementation of iMTH. Herein, we aim to validate the strategy of integrating magnetic targeting and hyperthermia. An in-situ liver tumor model in mouse was developed as deep-seated tumors. After administering the polar MTB MO-1 intravenously via the tail vein, a focusing magnetic field navigated these bacteria to effectively accumulate at the deep-seated tumor site. Immediately afterwards, this targeted aggregation of MO-1 cells triggered a localized magnetic hyperthermia directly at the cancer site under an applied alternating magnetic field. Our findings demonstrated that this hyperthermia induced by the bacteria led to the death of liver cancer cells, thereby effectively curbing the progression and growth of the cancer. These promising results suggested that an iMTH approach was developed, harnessing the power of MTB. This method stands as an exciting and potential therapeutic strategy for the treatment of deep-seated tumors, offering new hope in the fight against cancer.},
}

@article {pmid38562769,
year = {2025},
author = {Zhu, Q and Balasubramanian, A and Asirvatham, JR and Chatterjee, M and Piyarathna, B and Kaur, J and Mohamed, N and Wu, L and Wang, S and Pourfarrokh, N and Binsol, PD and Bhargava, M and Rasaily, U and Xu, Y and Zheng, J and Jebakumar, D and Rao, A and Gutierrez, C and Omilian, A and Morrison, C and Das, GM and Ambrosone, C and Seeley, EH and Chen, SH and Li, Y and Chang, E and Li, X and Baker, E and Aneja, R and Zhang, XH and Sreekumar, A},
title = {Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in Black American and White American patients with TNBC.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.03.17.585428},
pmid = {38562769},
issn = {2692-8205},
abstract = {UNLABELLED: Racial disparities in the clinical outcomes of triple-negative breast cancer (TNBC) have been well-documented, but the underlying biological mechanisms remain poorly understood. To investigate these disparities, we employed a multi-omic approach integrating imaging mass cytometry and spatial transcriptomics to characterize the tumor microenvironment (TME) in self-identified Black American (BA) and White American (WA) TNBC patients. Our analysis revealed that the TME in BA patients is marked by a network of endothelial cells, macrophages, and mesenchymal-like cells, which correlates with reduced patient survival. In contrast, the WA TNBC microenvironment is enriched in T-cells and neutrophils, indicative of T-cell exhaustion and suppressed immune responses. Ligand-receptor and pathway analyses further demonstrated that BA TNBC tumors exhibit a relatively "immune-cold" profile, while WA TNBC tumors display features of an "inflamed" TME, suggesting the evolution of a unique immunosuppressive mechanism. These findings provide insight into racially distinct tumor-promoting and immunosuppressive microenvironments, which may contribute to the observed differences in clinical outcomes among BA and WA TNBC patients.

STATEMENT OF SIGNIFICANCE: This study identifies distinct tumor microenvironment (TME) profiles in Black and White American TNBC patients, providing new insights into the biological mechanisms driving outcome disparities. Our findings highlight the role of the tumor-endothelial-macrophage niche in these disparities, offering a potential therapeutic target for race-inclusive strategies aimed at improving clinical outcomes. By revealing racial differences in treatment response profiles, this work underscores the necessity for tailored therapies in TNBC. These insights lay the groundwork for the development of inclusive, precision-driven treatment approaches that may help mitigate racial disparities and enhance patient outcomes.},
}

@article {pmid40156877,
year = {2025},
author = {Momoi, Y and Kumagai, S and Nishikawa, H},
title = {Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution.},
journal = {International immunology},
volume = {},
number = {},
pages = {},
doi = {10.1093/intimm/dxaf020},
pmid = {40156877},
issn = {1460-2377},
abstract = {Cancer progression can be understood as a process of diversification and selection (the evolutionary theory of cancer). The immune system also plays a critical role in this process of diversification and selection. The cancer immunoediting hypothesis provides a partial explanation of this evolutionary process; immune-evading cancer clones with genomic and/or epigenomic alterations are selected under the pressure of immune surveillance and can become equipped with multiple immunosuppressive mechanisms, leading to the development of clinically apparent cancers. Indeed, inflammatory cancers equip immunosuppressive mechanisms in response to the pressure of the immune system. However, recent studies focusing on human cancers have revealed that certain non-inflammatory cancers, which often harbor a single driver oncogenic mutation, are equipped with immunosuppressive machinery sufficient to evade immune surveillance at the time of malignant transformation. The sequential model of the cancer immunoediting hypothesis is inadequate to explain the development of these non-inflammatory cancers, highlighting the need for a novel concept that can explain their co-evolutionary processes. Moreover, inhibition of oncogenic signaling by specific driver oncogenes has been shown not only to kill cancer cells but also to augment antitumor immunity, suggesting the potential for the advent of molecularly targeted reagents with a variety of immunomodulatory functions from the perspective of personalized therapies. Here, we discuss the processes by which cancer cells and the immune system co-evolve to establish clinically apparent cancers, thereby introducing a new concept of 'immunogenomic cancer evolution', that provides a rationale for the potential of personalized 'immunogenomic cancer precision medicine'.},
}

@article {pmid40153489,
year = {2025},
author = {Kumagai, S and Momoi, Y and Nishikawa, H},
title = {Immunogenomic cancer evolution: A framework to understand cancer immunosuppression.},
journal = {Science immunology},
volume = {10},
number = {105},
pages = {eabo5570},
doi = {10.1126/sciimmunol.abo5570},
pmid = {40153489},
issn = {2470-9468},
mesh = {Humans ; *Neoplasms/immunology/genetics/therapy ; *Tumor Microenvironment/immunology/genetics ; Animals ; Immunotherapy/methods ; Immune Tolerance/immunology/genetics ; Precision Medicine ; Tumor Escape/immunology/genetics ; Genomics ; },
abstract = {The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic aberrant signaling is involved in both carcinogenesis and immune evasion. In noninflamed cancers such as epidermal growth factor receptor (EGFR)-mutated lung cancers, genetic abnormalities in cancer cells contribute to the formation of an immunosuppressive TME by recruiting immunosuppressive cells, which cannot be fully explained by the cancer immunoediting hypothesis. This review summarizes the latest findings regarding the links between cancer genetic abnormalities and immunosuppression causing clinical resistance to immunotherapy. We propose the concepts of immunogenomic cancer evolution, in which cancer cell genomic evolution shapes the immunosuppressive TME, and immunogenomic precision medicine, in which cancer immunotherapy can be combined with molecularly targeted reagents that modulate the immunosuppressive TME.},
}

Humans
*Neoplasms/immunology/genetics/therapy
*Tumor Microenvironment/immunology/genetics
Animals
Immunotherapy/methods
Immune Tolerance/immunology/genetics
Precision Medicine
Tumor Escape/immunology/genetics
Genomics

@article {pmid40147421,
year = {2025},
author = {Goswami, P and Ji, R and Shen, J and Roberts, AP and Lin, W},
title = {Genomic and metabolic characterisation of a novel species Magnetominusculus dajiuhuensis DJH-1[Ts] sp. nov. from an acidic peatland.},
journal = {Systematic and applied microbiology},
volume = {48},
number = {3},
pages = {126605},
doi = {10.1016/j.syapm.2025.126605},
pmid = {40147421},
issn = {1618-0984},
abstract = {Magnetotactic bacteria (MTB) are recognised widely for their ability to synthesise intracellular magnetite (Fe3O4) and/or greigite (Fe3S4) nanocrystals and align with Earth's magnetic field. They are crucial for understanding prokaryotic organelle biogenesis. MTB members of the Nitrospirota phylum (previously known as the Nitrospirae phylum) are of interest due to their important ecological roles in the biogeochemical cycling of iron and sulphur. Here, we introduce Magnetominusculus dajiuhuensis DJH-1[Ts], a newly discovered Nitrospirota MTB species that thrives in the acidic Dajiuhu Peatland of central China. By combining electron microscopy, 16S rRNA gene-based analysis and genome-resolved metagenomics, we elucidate its distinctive morphology, genomic features, and metabolic functions. The metagenome-assembled genome, assigned to the genus Magnetominusculus, family Magnetobacteriaceae, order Thermodesulfovibrionales, class Thermodesulfovibrionia according to the GTDB taxonomy, reveals an obligate anaerobe that lives in central China's largest wetland. We propose the formal name Magnetominusculus dajiuhuensis DJH-1[Ts] sp. nov., following the SeqCode system. Genomic and metabolic characterisation of this novel species suggests its potential role in nitrogen, sulphur, and carbon metabolism in aquatic biogeochemistry, particularly in peatlands. The genome of this novel strain indicates that it harnesses the Wood-Ljungdahl pathway for carbon fixation and acetate metabolism in anaerobic conditions, while its potential role in nitrogen cycling is characterised by denitrification and nitrogen fixation. It also participates in reduction of sulphate to sulphide, indicating a role in sulphur cycling in its ecological niche. Taken together, the discovery and characterisation of Magnetominusculus dajiuhuensis DJH-1[Ts] provide new insights into MTB diversity and ecological functions, particularly in peatland biogeochemistry.},
}

@article {pmid40146859,
year = {2025},
author = {Muro, EM and Ballesteros, FJ and Luque, B and Bascompte, J},
title = {The emergence of eukaryotes as an evolutionary algorithmic phase transition.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {13},
pages = {e2422968122},
doi = {10.1073/pnas.2422968122},
pmid = {40146859},
issn = {1091-6490},
support = {310030_197201/SNSF_/Swiss National Science Foundation/Switzerland ; PID2019-109592GBI00//Ministerio de Ciencia, Innovación y Universidades (MICIU)/ ; Excellence Prometeo/2020/085//Conselleria d'Educacio, Universitats i Ocupacio de la Generalitat Valenciana/ ; ASFAE/2022/025//European Union NextGenerationEU 922 and Generalitat Valenciana/ ; PID2020-113737GB-I00//Ministerio de Ciencia, Innovación y Universidades (MICIU)/ ; },
mesh = {*Algorithms ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Biological Evolution ; Eukaryotic Cells/metabolism ; Proteins/genetics/metabolism ; Phylogeny ; Models, Genetic ; },
abstract = {The origin of eukaryotes represents one of the most significant events in evolution since it allowed the posterior emergence of multicellular organisms. Yet, it remains unclear how existing regulatory mechanisms of gene activity were transformed to allow this increase in complexity. Here, we address this question by analyzing the length distribution of proteins and their corresponding genes for 6,519 species across the tree of life. We find a scale-invariant relationship between gene mean length and variance maintained across the entire evolutionary history. Using a simple model, we show that this scale-invariant relationship naturally originates through a simple multiplicative process of gene growth. During the first phase of this process, corresponding to prokaryotes, protein length follows gene growth. At the onset of the eukaryotic cell, however, mean protein length stabilizes around 500 amino acids. While genes continued growing at the same rate as before, this growth primarily involved noncoding sequences that complemented proteins in regulating gene activity. Our analysis indicates that this shift at the origin of the eukaryotic cell was due to an algorithmic phase transition equivalent to that of certain search algorithms triggered by the constraints in finding increasingly larger proteins.},
}

*Algorithms
*Eukaryota/genetics/metabolism
Evolution, Molecular
Biological Evolution
Eukaryotic Cells/metabolism
Proteins/genetics/metabolism
Phylogeny
Models, Genetic

@article {pmid40127687,
year = {2025},
author = {Petroll, R and Papareddy, RK and Krela, R and Laigle, A and Riviere, Q and Bišová, K and Mozgová, I and Borg, M},
title = {The expansion and diversification of epigenetic regulatory networks underpins major transitions in the evolution of land plants.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msaf064},
pmid = {40127687},
issn = {1537-1719},
abstract = {Epigenetic silencing is essential for regulating gene expression and cellular diversity in eukaryotes. While DNA and H3K9 methylation silence transposable elements (TEs), H3K27me3 marks deposited by the Polycomb repressive complex 2 (PRC2) silence varying proportions of TEs and genes across different lineages. Despite the major development role epigenetic silencing plays in multicellular eukaryotes, little is known about how epigenetic regulatory networks were shaped over evolutionary time. Here, we analyse epigenomes from diverse species across the green lineage to infer the chronological epigenetic recruitment of genes during land plant evolution. We first reveal the nature of plant heterochromatin in the unicellular chlorophyte microalga Chlorella sorokiniana and identify several genes marked with H3K27me3, highlighting the deep origin of PRC2-regulated genes in the green lineage. By incorporating genomic phylostratigraphy, we show how genes of differing evolutionary age occupy distinct epigenetic states in plants. While young genes tend to be silenced by H3K9 methylation, genes that emerged in land plants are preferentially marked with H3K27me3, some of which form part of a common network of PRC2-repressed genes across distantly-related species. Finally, we analyse the potential recruitment of PRC2 to plant H3K27me3 domains and identify conserved DNA-binding sites of ancient transcription factor (TF) families known to interact with PRC2. Our findings shed light on the conservation and potential origin of epigenetic regulatory networks in the green lineage, while also providing insight into the evolutionary dynamics and molecular triggers that underlie the adaptation and elaboration of epigenetic regulation, laying the groundwork for its future consideration in other eukaryotic lineages.},
}

@article {pmid40121259,
year = {2025},
author = {Chow, PCK and Bentley, PJ},
title = {Development necessitates evolutionarily conserved factors.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {9910},
pmid = {40121259},
issn = {2045-2322},
mesh = {*Biological Evolution ; Animals ; Transcription Factors/metabolism/genetics ; Morphogenesis/genetics ; Models, Biological ; Evolution, Molecular ; },
abstract = {Early-stage generalised transcription factors in biological development are often evolutionarily conserved across species. Here, we find for the first time that similar factors functionally emerge in an alternative medium of development. Through comprehensively analysing a Neural Cellular Automata (NCA) model of morphogenesis, we find multiple properties of the hidden units that are functionally analogous to early factors in biological development. We test the generalisation abilities of our model through transfer learning of other morphologies and find that developmental strategies learnt by the model are reused to grow new body forms by conserving its early generalised factors. Our paper therefore provides evidence that nature did not become locked into one arbitrary method of developing multicellular organisms: the use of early generalised factors as fundamental control mechanisms and the resulting necessity for evolutionary conservation of those factors may be fundamental to development, regardless of the details of how development is implemented.},
}

*Biological Evolution
Animals
Transcription Factors/metabolism/genetics
Morphogenesis/genetics
Models, Biological
Evolution, Molecular

@article {pmid40112176,
year = {2025},
author = {Matthews, S and Nikoonejad Fard, V and Tollis, M and Seoighe, C},
title = {Variable gene copy number in cancer-related pathways is associated with cancer prevalence across mammals.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msaf056},
pmid = {40112176},
issn = {1537-1719},
abstract = {Cancer is a disease of multicellularity, observed across the tree of life. In principle, animals with larger body sizes and longer lifespans should be at increased risk of developing cancer. However, there is no strong relationship between these traits and cancer across mammals. Previous studies have proposed that increased copy number of cancer-related genes may enhance the robustness of cancer suppression pathways in long-lived mammals, but these studies have not extended beyond known cancer-related genes. In this study, we conducted a phylogenetic generalised least squares (PGLS) analysis to test for associations between copy number of all protein-coding genes and longevity, body size, and cancer prevalence across 94 species of mammals. In addition to investigating the copy number of individual genes, we tested sets of related genes for a relationship between the aggregated gene copy number of the set and these traits. We did not find strong evidence to support the hypothesis that adaptive changes in gene copy number contribute to the lack of correlation between cancer prevalence and body size or lifespan. However, we found several biological processes where aggregate copy number was associated with malignancy rate. The strongest association was for the gene set relating to transforming growth factor-beta (TGF-β), a cytokine that plays a role in cancer progression. Overall, this study provides a comprehensive evaluation of the role of gene copy number in adaptation to body size and lifespan and sheds light on the contribution of gene copy number to variation in cancer prevalence across mammals.},
}

@article {pmid40109106,
year = {2025},
author = {Korb, J},
title = {Changes of division of labour along the eusociality spectrum in termites, with comparisons to multicellularity.},
journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences},
volume = {380},
number = {1922},
pages = {20230268},
pmid = {40109106},
issn = {1471-2970},
mesh = {*Isoptera/physiology ; Animals ; *Social Behavior ; Reproduction/physiology ; },
abstract = {Eusocial insects are characterized by reproductive division of labour, with one (or a few) individuals specialized in reproduction (queen and in termites, also a king) and the other individuals performing all other tasks (workers). Among workers, further division of labour can occur. Termites have three main castes: reproductives, comprising a queen and king; morphologically differentiated sterile soldiers; and workers. Task division among workers varies greatly depending on lifestyle and degree of workers' reproductive potential, which varies from totipotency to reproduce up to sterility. In wood-dwelling species, which do not forage outside the nest, all tasks are performed by totipotent workers, comprising multiple-instars with less further division of labour. Foraging species with pluripotent workers also have a multi-instar worker caste, but some division of labour between brood care versus foraging and defence exists. The first task seems mainly to be done by smaller-and potentially younger-instars, while the latter two tasks are performed by larger-and potentially older-workers. The highest degree of division of labour occurs in foraging species with sterile workers. Here, morphological worker castes with defined tasks and age polyethism occur. Comparisons with Metazoa reveal striking similarities with termites concerning gradients in germline/soma differentiation and cell totipotency.This article is part of the theme issue 'Division of labour as key driver of social evolution'.},
}

*Isoptera/physiology
Animals
*Social Behavior
Reproduction/physiology

@article {pmid40106424,
year = {2025},
author = {Wright, BA and Osigus, HJ and Schmidt, MJ and Ratcliffe, J and Kamm, K and Martinez-Ortiz, GC and Rehn, M and Kvansakul, M and Schierwater, B and Humbert, PO},
title = {Tolerance of Placozoa for temperate climates: Evidence for known and new placozoan clades in the southern waters of Australia.},
journal = {PloS one},
volume = {20},
number = {3},
pages = {e0317878},
pmid = {40106424},
issn = {1932-6203},
mesh = {Animals ; *Placozoa/genetics/classification ; Haplotypes ; Phylogeny ; Australia ; Climate ; Genetic Variation ; },
abstract = {Placozoans are small multicellular sea-dwelling animals that are typically found in shallow, warm ocean waters and have been reported in various marine environments worldwide. Their unique morphology makes them a powerful new model organism to study the evolutionary cell biology in early metazoans. Yet, knowledge on their biodiversity and ecological distribution is severely limited. Here, we report the isolation of placozoans in the temperate waters of Victoria, Australia, their most southern location known to date. Using light, electron, and confocal microscopy, we describe their morphology and behaviour. In addition to the known haplotypes H2 and H17, we have identified a new haplotype, here designated as H20, which defines a new placozoan clade. This study provides novel insights into the distribution, ecological niche separation and genetic diversity of placozoans, and reports the first morphological and ultrastructural characterisation of placozoan clades isolated from the southern waters of Victoria, Australia.},
}

Animals
*Placozoa/genetics/classification
Haplotypes
Phylogeny
Australia
Climate
Genetic Variation

@article {pmid40103550,
year = {2025},
author = {Davison, DR and Nedelcu, AM and Eneji, OA and Michod, RE},
title = {Plasticity and the evolution of group-level regulation of cellular differentiation in the volvocine algae.},
journal = {Proceedings. Biological sciences},
volume = {292},
number = {2043},
pages = {20242477},
pmid = {40103550},
issn = {1471-2954},
support = {/NASA/NASA/United States ; //Division of Molecular and Cellular Biosciences/ ; NSF Postdoctoral Research Fellowships in Biology Program under Grant No. 2209373//Division of Biological Infrastructure/ ; 2029999//Division of Environmental Biology/ ; },
mesh = {*Cell Differentiation ; *Biological Evolution ; },
abstract = {During the evolution of multicellularity, the unit of selection transitions from single cells to integrated multicellular cell groups, necessitating the evolution of group-level traits such as somatic differentiation. However, the processes involved in this change in units of selection are poorly understood. We propose that the evolution of soma in the volvocine algae included an intermediate step involving the plastic development of somatic-like cells. We show that Eudorina elegans, a multicellular volvocine algae species previously thought to be undifferentiated, can develop somatic-like cells following environmental stress (i.e. cold shock). These cells resemble obligate soma in closely related species. We find that somatic-like cells can differentiate directly from cold-shocked cells. This differentiation is a cell-level trait, and the differentiated colony phenotype is a cross-level by-product of cell-level processes. The offspring of cold-shocked colonies also develop somatic-like cells. Since these cells were not directly exposed to the stressor, their differentiation was regulated during group development. Consequently, they are a true group-level trait and not a by-product of cell-level traits. We argue that group-level traits, such as obligate somatic differentiation, can originate through plasticity and that cross-level by-products may be an intermediate step in the evolution of group-level traits.},
}

*Cell Differentiation
*Biological Evolution

@article {pmid40103259,
year = {2025},
author = {Fonseca, A and Ishoey, T and Espinoza, C and Marshall, IPG and Nielsen, LP and Gallardo, VA},
title = {Large Filamentous Bacteria Isolated From Sulphidic Sediments Reveal Novel Species and Distinct Energy and Defence Mechanisms for Survival.},
journal = {Environmental microbiology},
volume = {27},
number = {3},
pages = {e70083},
pmid = {40103259},
issn = {1462-2920},
support = {//the Program "Doctorado en el extranjero Becas Chile" from ANID (former CONICYT)/ ; 1070552//Agencia Nacional de Investigación y Desarrollo/ ; //J. Craig Venter Institute/ ; },
mesh = {*Geologic Sediments/microbiology ; Chile ; *Phylogeny ; Bacteria/genetics/classification/metabolism/isolation & purification ; Genome, Bacterial ; RNA, Ribosomal, 16S/genetics ; Deltaproteobacteria/genetics/classification/isolation & purification/metabolism ; Sulfides/metabolism ; },
abstract = {Various morphotypes of large filamentous bacteria were isolated through micromanipulation from sulphidic sediment mats in the Bay of Concepción, central Chile. This study employed DNA amplification, whole-genome sequencing and bioinformatics analyses to unveil the taxonomic and genomic features of previously unidentified bacteria. The results revealed several novel genera, families and species, including three specimens belonging to Beggiatoales (Beggiatoaceae family), five to Desulfobacterales (Desulfobacteraceae family), two to the Chloroflexi phylum and one to the phylum Firmicutes. Metabolically, Beggiatoaceae bacteria exhibit a flexible and versatile genomic repertoire, enabling them to adapt to variable conditions at the sediment-water interface. All the bacteria demonstrated a mixotrophic mode, gaining energy from both inorganic and organic carbon sources. Except for the Firmicutes bacterium, all others displayed the ability to grow chemolithoautotrophically using H2 and CO2. Remarkably, the reverse tricarboxylic acid (rTCA) and Calvin-Benson-Bassham (CBB) pathways coexisted in one Beggiatoaceae bacterium. Additionally, various defence systems, such as CRISPR-Cas, along with evidence of viral interactions, have been identified. These defence mechanisms suggest that large filamentous bacteria inhabiting sulphidic sediments frequently encounter bacteriophages. Thus, robust defence mechanisms coupled with multicellularity may determine the survival or death of these large bacteria.},
}

*Geologic Sediments/microbiology
Chile
*Phylogeny
Bacteria/genetics/classification/metabolism/isolation & purification
Genome, Bacterial
RNA, Ribosomal, 16S/genetics
Deltaproteobacteria/genetics/classification/isolation & purification/metabolism
Sulfides/metabolism

@article {pmid40086443,
year = {2025},
author = {Weiss, B and Rohkin Shalom, S and Dolgova, A and Teh, LS and Kaltenpoth, M and Dale, C and Chiel, E},
title = {Maternal symbiont transmission via envenomation in the parasitoid wasp Spalangia cameroni.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2025.02.035},
pmid = {40086443},
issn = {1879-0445},
abstract = {Microbial symbionts of multicellular hosts originate from free-living ancestors and often persist through vertical transmission, but their mechanisms of establishment are not well understood. Here, we studied acquisition and transmission routes in a nascent symbiosis involving the bacterium Sodalis praecaptivus subsp. spalangiae (Sodalis SC) and the parasitoid wasp Spalangia cameroni. Using fluorescence in situ hybridization, transmission electron microscopy, and experimental infections, we found that oocytes are devoid of Sodalis SC, but the female venom gland is densely colonized. Sodalis SC is injected with the venom into the fly host, subsequently acquired by larval progeny during feeding, invades through the larval gut epithelium into multiple host organs, and eventually localizes in the venom gland. Adult wasps can also acquire Sodalis SC by artificial feeding, but, in this case, the bacterium is not transmitted vertically. Additionally, Sodalis SC is localized in the testes of some males, transmitted paternally at low frequency, and females that inherit Sodalis SC paternally can subsequently transmit it via the venom. To assess the specificity of the symbiosis, we performed experiments with the closely related free-living species Sodalis praecaptivus subsp. praecaptivus (Sodalis PP), known to initiate symbiosis with other insects. Sodalis PP is readily acquired when supplied artificially to wasp larvae but not transmitted to wasp progeny, because it fails to proliferate in the parasitized host. Our results indicate that non-ovarian transmission routes of intracellular symbionts may be more common than currently appreciated and provide a scenario for the early steps in establishing persistent symbiotic associations in insects.},
}

@article {pmid40070872,
year = {2025},
author = {Dong, Y and Qian, S and Wang, X and Zhang, W and Lu, W and Qu, J and Cui, M and Chen, L and Zhao, Y and Gao, Y and Giomo, M and Urciuolo, A and Feng, J and Zheng, Y and Jiang, B and Shen, R and Zhu, X and Elvassore, N},
title = {In situ tailored confining microenvironment for lung cancer spheroids.},
journal = {Materials today. Bio},
volume = {31},
number = {},
pages = {101602},
pmid = {40070872},
issn = {2590-0064},
abstract = {The mechanical properties and physical confinement of the extracellular matrix (ECM) are crucial roles in regulating tumor growth and progression. Extensive efforts have been dedicated to replicating the physical characteristics of tumor tissue by developing two-dimensional (2D) and three-dimensional (3D) in vitro models. However, it remains a significant challenge to modulate the local microenvironment around the specific cells according to the culture progress. In this study, we develop a 3D culture platform for multicellular lung cancer spheroids using a gelatin-based hydrogel with adjustable density and stiffness. Then, by utilizing a two-photon mediated bioprinting technique, we construct 3D confining microstructures with micrometer accuracy to enclose the selected spheroids within the hydrogel matrix. Diverse transcriptional profilings of cells are observed in response to the increased ECM density and stiffness compared to the additional confining stress. In addition, changed confining stress can regulate the tumor cells with contrary impacts on the cell cycle-related pathways. Our model not only allows for modifications to the mechanical microenvironment of the overall matrix but also facilitates localized adjustments throughout the culture evolution. This approach serves as a valuable tool for investigating tumor progression and understanding cell-ECM interactions.},
}

@article {pmid40067883,
year = {2025},
author = {Gray, C and Chitnavis, S and Buja, T and Duffy, CDP},
title = {Predicting the diversity of photosynthetic light-harvesting using thermodynamics and machine learning.},
journal = {PLoS computational biology},
volume = {21},
number = {3},
pages = {e1012845},
pmid = {40067883},
issn = {1553-7358},
mesh = {*Photosynthesis/physiology ; *Machine Learning ; *Thermodynamics ; *Light-Harvesting Protein Complexes/metabolism/chemistry ; Computational Biology ; Algorithms ; Models, Biological ; Biological Evolution ; Light ; },
abstract = {Oxygenic photosynthesis is responsible for nearly all biomass production on Earth, and may have been a prerequisite for establishing a complex biosphere rich in multicellular life. Life on Earth has evolved to perform photosynthesis in a wide range of light environments, but with a common basic architecture of a light-harvesting antenna system coupled to a photochemical reaction centre. Using a generalized thermodynamic model of light-harvesting, coupled with an evolutionary algorithm, we predict the type of light-harvesting structures that might evolve in light of different intensities and spectral profiles. We reproduce qualitatively the pigment composition, linear absorption profile and structural topology of the antenna systems of multiple types of oxygenic photoautotrophs, suggesting that the same physical principles underlie the development of distinct antenna structures in various light environments. Finally we apply our model to representative light environments that would exist on Earth-like exoplanets, predicting that both oxygenic and anoxygenic photosynthesis could evolve around low mass stars, though the latter would seem to work better around the coolest M-dwarfs. We see this as an interesting first step toward a general evolutionary model of basic biological processes and proof that it is meaningful to hypothesize on the nature of biology beyond Earth.},
}

*Photosynthesis/physiology
*Machine Learning
*Thermodynamics
*Light-Harvesting Protein Complexes/metabolism/chemistry
Computational Biology
Algorithms
Models, Biological
Biological Evolution
Light

@article {pmid40060608,
year = {2025},
author = {Theriault, HS and Kimmel, HRC and Nunes, AC and Paxhia, A and Hashim, S and Clancy, KBH and Underhill, GH and Harley, BAC},
title = {Matrix tropism influences endometriotic cell attachment patterns.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.22.639314},
pmid = {40060608},
issn = {2692-8205},
abstract = {Due to the extended period for clinical diagnosis, the etiology of endometriotic lesion initiation is not well understood or characterized. Endometriotic lesions are most often found on pelvic tissues and organs, especially the ovaries. To investigate the role of tissue tropism on ovarian endometrioma initiation, we adapted a well-characterized polyacrylamide microarray system to investigate the role of tissue-specific extracellular matrix and adhesion motifs on endometriotic cell attachment, morphology, and size. We report the influence of cell origin (endometriotic vs. non-endometriotic), substrate stiffness mimicking aging and fibrosis, and the role of multicellular (epithelial-stromal) cohorts on cell attachment patterns. We identify multiple ovarian-specific attachment motifs that significantly increase endometriotic (vs. non-endometriotic) cell cohort attachment that could be implicated in early disease etiology.},
}

@article {pmid40059518,
year = {2025},
author = {Tice, AK and Regis, K and Shutt, TE and Spiegel, FW and Brown, MW and Silberman, JD},
title = {Validating the Genus Pocheina (Acrasidae, Heterolobosea, Discoba) Leads to the Recognition of Three Major Lineages Within Acrasidae.},
journal = {The Journal of eukaryotic microbiology},
volume = {72},
number = {2},
pages = {e70004},
doi = {10.1111/jeu.70004},
pmid = {40059518},
issn = {1550-7408},
support = {DEB2100888//National Science Foundation/ ; DEB0329102//National Science Foundation/ ; DEB0316284//National Science Foundation/ ; //Arkansas Biosciences Institute/ ; },
mesh = {*Phylogeny ; *DNA, Protozoan/genetics ; Amoebozoa/classification/genetics ; DNA, Ribosomal Spacer/genetics ; Sequence Analysis, DNA ; DNA, Ribosomal/genetics ; RNA, Ribosomal, 18S/genetics ; },
abstract = {Pocheina and Acrasis are two genera of heterolobosean sorocarpic amoebae within Acrasidae that have historically been considered close relatives. The two genera were differentiated based on their differing fruiting body morphologies. The validity of this taxonomic distinction was challenged when a SSU rRNA phylogenetic study placed an isolate morphologically identified as "Pocheina" rosea within a clade of Acrasis rosea isolates. The authors speculated that pocheinoid fruiting body morphology might be the result of aberrant Ac. rosea fruiting body development, which, if true, would nullify this taxonomic distinction between genera. To clarify Acrasidae systematics, we analyzed SSU rRNA and ITS region sequences from multiple isolates of Pocheina, Acrasis, and Allovahlkampfia generated by Polymerase Chain Reaction (PCR) and transcriptomics. We demonstrate that the initial SSU sequence attributed to "P. rosea" originated from an Ac. rosea DNA contamination in its amplification reaction. Our analyses, based on morphology, SSU and 5.8S rRNA gene phylogenies, as well as comparative analyses of ITS1 and ITS2 sequences, resolve Acrasidae into three major lineages: Allovahlkampfia and the strongly supported clades comprising Pocheina and Acrasis. We confirm that the latter two genera can be identified by their fruiting body morphologies.},
}

*Phylogeny
*DNA, Protozoan/genetics
Amoebozoa/classification/genetics
DNA, Ribosomal Spacer/genetics
Sequence Analysis, DNA
DNA, Ribosomal/genetics
RNA, Ribosomal, 18S/genetics

@article {pmid40056574,
year = {2025},
author = {Klompstra, TM and Yoon, KJ and Koo, BK},
title = {Evolution of organoid genetics.},
journal = {European journal of cell biology},
volume = {104},
number = {2},
pages = {151481},
doi = {10.1016/j.ejcb.2025.151481},
pmid = {40056574},
issn = {1618-1298},
abstract = {Organoids have revolutionized in vitro research by offering three-dimensional, multicellular systems that recapitulate the structure, function, and genetics of human tissues. Initially developed from both pluripotent stem cells (PSCs) and adult stem cells (AdSCs), organoids have expanded to model nearly every major human organ, significantly advancing developmental biology, disease modeling, and therapeutic screening. This review highlights the progression of organoid technologies, emphasizing the integration of genetic tools, including CRISPR-Cas9, prime editing, and lineage tracing. These advancements have facilitated precise modeling of human-specific pathologies and drug responses, often surpassing traditional 2D cultures and animal models in accuracy. Emerging technologies, such as organoid fusion, xenografting, and optogenetics, are expected to further enhance our understanding of cellular interactions and microenvironmental dynamics. As organoid complexity and genetic engineering methods continue to evolve, they will become increasingly indispensable for personalized medicine and translational research, bridging gaps between in vitro and in vivo systems.},
}

@article {pmid40052705,
year = {2025},
author = {Kataki, AD and Gupta, PG and Cheema, U and Nisbet, A and Wang, Y and Kocher, HM and Pérez-Mancera, PA and Velliou, EG},
title = {Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.},
journal = {ACS applied materials & interfaces},
volume = {17},
number = {11},
pages = {16708-16724},
pmid = {40052705},
issn = {1944-8252},
mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism ; *Extracellular Matrix/metabolism ; *Tumor Microenvironment ; *Stromal Cells/pathology/metabolism ; *Tissue Scaffolds/chemistry ; Cell Line, Tumor ; Carcinoma, Pancreatic Ductal/pathology/metabolism ; Polyurethanes/chemistry ; Extracellular Matrix Proteins/metabolism ; },
abstract = {Bioengineering-based in vitro tumor models are increasingly important as tools for studying disease progression and therapy response for many cancers, including the deadly pancreatic ductal adenocarcinoma (PDAC) that exhibits a tumor/tissue microenvironment of high cellular/biochemical complexity. Therefore, it is crucial for in vitro models to capture that complexity and to enable investigation of the interplay between cancer cells and factors such as extracellular matrix (ECM) proteins or stroma cells. Using polyurethane (PU) scaffolds, we performed a systematic study on how different ECM protein scaffold coatings impact the long-term cell evolution in scaffolds containing only cancer or only stroma cells (activated stellate and endothelial cells). To investigate potential further changes in those biomarkers due to cancer-stroma interactions, we mapped their expression in dual/zonal scaffolds consisting of a cancer core and a stroma periphery, spatially mimicking the fibrotic/desmoplastic reaction in PDAC. In our single scaffolds, we observed that the protein coating affected the cancer cell spatial aggregation, matrix deposition, and biomarker upregulation in a cell-line-dependent manner. In single stroma scaffolds, different levels of fibrosis/desmoplasia in terms of ECM composition/quantity were generated depending on the ECM coating. When studying the evolution of cancer and stroma cells in our dual/zonal model, biomarkers linked to cell aggressiveness/invasiveness were further upregulated by both cancer and stroma cells as compared to single scaffold models. Collectively, our study advances the understanding of how different ECM proteins impact the long-term cell evolution in PU scaffolds. Our findings show that within our bioengineered models, we can stimulate the cells of the PDAC microenvironment to develop different levels of aggressiveness/invasiveness, as well as different levels of fibrosis. Furthermore, we highlight the importance of considering spatial complexity to map cell invasion. Our work contributes to the design of in vitro models with variable, yet biomimetic, tissue-like properties for studying the tumor microenvironment's role in cancer progression.},
}

Humans
*Pancreatic Neoplasms/pathology/metabolism
*Extracellular Matrix/metabolism
*Tumor Microenvironment
*Stromal Cells/pathology/metabolism
*Tissue Scaffolds/chemistry
Cell Line, Tumor
Carcinoma, Pancreatic Ductal/pathology/metabolism
Polyurethanes/chemistry
Extracellular Matrix Proteins/metabolism

@article {pmid40044858,
year = {2025},
author = {Tong, K and Datta, S and Cheng, V and Haas, DJ and Gourisetti, S and Yopp, HL and Day, TC and Lac, DT and Khalil, AS and Conlin, PL and Bozdag, GO and Ratcliff, WC},
title = {Genome duplication in a long-term multicellularity evolution experiment.},
journal = {Nature},
volume = {639},
number = {8055},
pages = {691-699},
pmid = {40044858},
issn = {1476-4687},
mesh = {*Saccharomyces cerevisiae/genetics/cytology ; *Diploidy ; *Gene Duplication ; *Evolution, Molecular ; *Genome, Fungal/genetics ; *Aneuploidy ; Tetraploidy ; Genetic Fitness ; Selection, Genetic ; Time Factors ; Models, Genetic ; Cell Size ; Biological Evolution ; Genomic Instability/genetics ; },
abstract = {Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution[1-4]. However, given the instability of newly formed polyploid genomes[5-7], understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Here, using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)[8], we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly evolve to be tetraploid. From their origin within the first 50 days of the experiment, tetraploids persisted for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in 10 replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modelling and counter-selection, we found that tetraploidy evolved because it confers immediate fitness benefits under this selection, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, having a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection and fuel long-term innovations by creating additional dimensions of heritable genetic variation.},
}

*Saccharomyces cerevisiae/genetics/cytology
*Diploidy
*Gene Duplication
*Evolution, Molecular
*Genome, Fungal/genetics
*Aneuploidy
Tetraploidy
Genetic Fitness
Selection, Genetic
Time Factors
Models, Genetic
Cell Size
Biological Evolution
Genomic Instability/genetics

@article {pmid40044726,
year = {2025},
author = {Gao, Y and Pichugin, Y and Traulsen, A and Zapién-Campos, R},
title = {Evolution of irreversible differentiation under stage-dependent cell differentiation.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {7786},
pmid = {40044726},
issn = {2045-2322},
support = {12401644//National Natural Science Foundation of China/ ; 2024JC-YBQN-0005//Natural Science Basic Research Program of Shaanxi Province/ ; },
mesh = {*Cell Differentiation ; *Biological Evolution ; Germ Cells/cytology ; Models, Biological ; Animals ; Cell Division ; Selection, Genetic ; },
abstract = {The specialization of cells is a hallmark of complex multicellularity. Cell differentiation enables the emergence of specialized cell types that carry out separate functions previously executed by a multifunctional ancestor cell. One view about the origin of cell differentiation is that it first occurred randomly in genetically identical cells exposed to the same life history environment. Under these conditions, differentiation trajectories producing more offspring could be favored by natural selection; yet, how dynamic variation in differentiation probabilities can affect the evolution of differentiation patterns is unclear. We develop a theoretical model to investigate the effect of dynamic-stage-dependent-cell differentiation on the evolution of optimal differentiation patterns. Concretely, we model trajectories in which cells can randomly differentiate into germ or soma cell types at each cell division. After comparing many of these trajectories, we found that irreversible differentiation, where cells gradually lose their ability to produce the other cell type, is more favored in small organisms under dynamic than under constant (stage-independent) cell differentiation. Furthermore, we found that the irreversible differentiation of germ cells, where germ cells gradually lose their ability to produce soma cells, is prominent among irreversible patterns. Only large variations in the differentiation probabilities prohibit irreversible trajectories from being the optimal pattern.},
}

*Cell Differentiation
*Biological Evolution
Germ Cells/cytology
Models, Biological
Animals
Cell Division
Selection, Genetic

@article {pmid40042639,
year = {2025},
author = {Zhu, T and Ning, P and Liu, Y and Liu, M and Yang, J and Wang, Z and Li, M},
title = {Knowledge of microalgal Rubiscos helps to improve photosynthetic efficiency of crops.},
journal = {Planta},
volume = {261},
number = {4},
pages = {78},
pmid = {40042639},
issn = {1432-2048},
support = {6651121004//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 6651120032//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 22278233//National Natural Science Foundation of China/ ; ZR2022QB143//Natural Science Foundation of Shandong Province/ ; ZR2020QC069//Natural Science Foundation of Shandong Province/ ; M2023-05//State Key Laboratory of Microbial Resources, Chinese Academy of Sciences/ ; M2022-07//State Key Laboratory of Microbial Technology Open Projects Fund/ ; },
mesh = {*Microalgae/physiology/metabolism ; *Crops, Agricultural/metabolism/physiology ; *Photosynthesis/physiology ; *Ribulose-Bisphosphate Carboxylase/metabolism ; },
abstract = {A comprehensive understanding of microalgal Rubiscos offers opportunities to enhance photosynthetic efficiency of crops. As food production fails to meet the needs of the expanding population, there is increasing concern about Ribulose-1, 5-diphosphate (RuBP) carboxylase/oxygenase (Rubisco), the enzyme that catalyzes CO2 fixation in photosynthesis. There have been many attempts to optimize Rubisco in crops, but the complex multicellular structure of higher plants makes optimization more difficult. Microalgae have the characteristics of rapid growth, simple structure and easy molecular modification, and the function and properties of their Rubiscos are basically the same as those of higher plants. Research on microalgal Rubiscos helps to broaden the understanding of Rubiscos of higher plants. Also, transferring all or part of better microalgal Rubiscos into crop cells or giving crop Rubiscos the advantages of microalgal Rubiscos can help improve the photosynthesis of crops. In this review, the distribution, origin, evolution, molecular structure, folding, assembly, activation and kinetic properties of microalgal Rubiscos are summarized. Moreover, the development of some effective methods to improve the properties and application of Rubiscos in microalgae are also described.},
}

*Microalgae/physiology/metabolism
*Crops, Agricultural/metabolism/physiology
*Photosynthesis/physiology
*Ribulose-Bisphosphate Carboxylase/metabolism

@article {pmid40027827,
year = {2025},
author = {Price, KL and Tharakan, DM and Salvenmoser, W and Ayers, K and Mah, J and Dunn, C and Hobmayer, B and Cooley, L},
title = {Examination of germline and somatic intercellular bridges in Hydra vulgaris reveals insights into the evolutionarily conserved mechanism of intercellular bridge formation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027827},
issn = {2692-8205},
support = {F32 GM136029/GM/NIGMS NIH HHS/United States ; R35 GM141961/GM/NIGMS NIH HHS/United States ; },
abstract = {Incomplete cytokinesis results in the formation of stable intercellular bridges that have been extensively studied in bilaterians, where they play essential roles in cell-cell communication and coordination of differentiation. However, little is known about their structure and molecular composition in non-bilaterian animals. This study characterizes germline and somatic intercellular bridges in the cnidarian Hydra vulgaris, providing insights into their evolutionary origins and functional significance. We identified key conserved components, including KIF23, F-actin, and phosphotyrosine. Notably, we observed microtubule localization within Hydra ring canals, suggesting previously unrecognized functions for this cytoskeletal component in intercellular bridge formation. Bioinformatic analyses confirmed the conserved expression of Kif23 and suggested its role as a molecular marker for identifying ring canal-associated components. EdU incorporation during DNA replication demonstrated that cells connected by ring canals exhibit synchronized cell cycles, which may be critical for the coordination of division and differentiation. Our findings reveal that the molecular and structural features of intercellular bridges in Hydra are conserved across evolutionary lineages, highlighting their ancient origins and functional significance in cellular connectivity. The presence of synchronized cell cycles in ring canal-connected cells underscores their role in promoting coordinated cellular behaviors, processes fundamental to multicellular organization. This study provides new perspectives on the evolution of incomplete cytokinesis and establishes a framework for comparative investigations into the diversity and conservation of intercellular bridge mechanisms across metazoans.},
}

@article {pmid40027720,
year = {2025},
author = {Zheng, H and Sarkar, H and Raphael, BJ},
title = {Joint imputation and deconvolution of gene expression across spatial transcriptomics platforms.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027720},
issn = {2692-8205},
support = {U24 CA248453/CA/NCI NIH HHS/United States ; U24 CA264027/CA/NCI NIH HHS/United States ; },
abstract = {Spatially resolved transcriptomics (SRT) technologies measure gene expression across thousands of spatial locations within a tissue slice. Multiple SRT technologies are currently available and others are in active development with each technology having varying spatial resolution (subcellular, single-cell, or multicellular regions), gene coverage (targeted vs. whole-transcriptome), and sequencing depth per location. For example, the widely used 10x Genomics Visium platform measures whole transcriptomes from multiple-cell-sized spots, while the 10x Genomics Xenium platform measures a few hundred genes at subcellular resolution. A number of studies apply multiple SRT technologies to slices that originate from the same biological tissue. Integration of data from different SRT technologies can overcome limitations of the individual technologies enabling the imputation of expression from unmeasured genes in targeted technologies and/or the deconvolution of ad-mixed expression from technologies with lower spatial resolution. We introduce Spatial Integration for Imputation and Deconvolution (SIID), an algorithm to reconstruct a latent spatial gene expression matrix from a pair of observations from different SRT technologies. SIID leverages a spatial alignment and uses a joint non-negative factorization model to accurately impute missing gene expression and infer gene expression signatures of cell types from ad-mixed SRT data. In simulations involving paired SRT datasets from different technologies (e.g., Xenium and Visium), SIID shows superior performance in reconstructing spot-to-cell-type assignments, recovering cell-type-specific gene expression, and imputing missing data compared to contemporary tools. When applied to real-world 10x Xenium-Visium pairs from human breast and colon cancer tissues, SIID achieves highest performance in imputing holdout gene expression. A PyTorch implementation of SIID is available at https://github.com/raphael-group/siid.},
}

@article {pmid40027677,
year = {2025},
author = {Stoy, KS and MacGillivray, KA and Burnetti, AJ and Barrett, C and Ratcliff, WC},
title = {Multiple pathways to the evolution of positive assortment in aggregative multicellularity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027677},
issn = {2692-8205},
support = {T32 GM142616/GM/NIGMS NIH HHS/United States ; },
abstract = {The evolutionary transition to multicellularity requires shifting the primary unit of selection from cells to multicellular collectives. How this occurs in aggregative organisms remains poorly understood. Clonal development provides a direct path to multicellular adaptation through genetic identity between cells, but aggregative organisms face a constraint: selection on collective-level traits cannot drive adaptation without positive genetic assortment. We leveraged experimental evolution of flocculating Saccharomyces cerevisiae to examine the evolution and role of genetic assortment in multicellular adaptation. After 840 generations of selection for rapid settling, 13 of 19 lineages evolved increased positive assortment relative to their ancestor. However, assortment provided no competitive advantage during settling selection, suggesting it arose as an indirect effect of selection on cell-level traits rather than through direct selection on collective-level properties. Genetic reconstruction experiments and protein structure modeling revealed two distinct pathways to assortment: kin recognition mediated by mutations in the FLO1 adhesion gene and generally enhanced cellular adhesion that improved flocculation efficiency independent of partner genotype. The evolution of assortment without immediate adaptive benefit suggests that key innovations enabling multicellular adaptation may arise indirectly through cell-level selection. Our results demonstrate fundamental constraints on aggregative multicellularity and help explain why aggregative lineages have remained simple.},
}

@article {pmid40027608,
year = {2025},
author = {Rossine, F and Sanchez, C and Eaton, D and Paulsson, J and Baym, M},
title = {Intracellular competition shapes plasmid population dynamics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027608},
issn = {2692-8205},
support = {R35 GM133700/GM/NIGMS NIH HHS/United States ; },
abstract = {Conflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements in microbes. Plasmids are extrachromosomal, self-replicating genetic elements that underlie much of the evolutionary flexibility of bacteria. Evolving plasmids face selective pressures on their hosts, but also compete within the cell for replication, making them an ideal system for studying the joint dynamics of multilevel selection. While theory indicates that within-cell selection should matter for plasmid evolution, experimental measurement of within-cell plasmid fitness and its consequences has remained elusive. Here we measure the within-cell fitness of competing plasmids and characterize drift and selective dynamics. We achieve this by the controlled splitting of synthetic plasmid dimers to create balanced competition experiments. We find that incompatible plasmids co-occur for longer than expected due to methylation-based plasmid eclipsing. During this period of co-occurrence, less transcriptionally active plasmids display a within-cell selective advantage over their competing plasmids, leading to preferential fixation of silent plasmids. When the transcribed gene is beneficial to the cell, for example an antibiotic resistance gene, there is a cell-plasmid fitness tradeoff mediated by the dominance of the beneficial trait. Surprisingly, more dominant plasmid-encoded traits are less likely to fix but more likely to initially invade than less dominant traits. Taken together, our results show that plasmid evolution is driven by dynamics at two levels, with a transient, but critical, contribution of within-cell fitness.},
}

@article {pmid40008892,
year = {2025},
author = {Leon, F and Espinoza-Esparza, JM and Deng, V and Coyle, MC and Espinoza, S and Booth, DS},
title = {Cell differentiation controls iron assimilation in the choanoflagellate Salpingoeca rosetta.},
journal = {mSphere},
volume = {10},
number = {3},
pages = {e0091724},
doi = {10.1128/msphere.00917-24},
pmid = {40008892},
issn = {2379-5042},
support = {R35GM147404//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; //David and Lucile Packard Foundation (PF)/ ; //NSF | National Science Foundation Graduate Research Fellowship Program (GRFP)/ ; T32GM139786//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {*Choanoflagellata/genetics/metabolism ; *Iron/metabolism ; *Cell Differentiation ; FMN Reductase/metabolism/genetics ; Protozoan Proteins/metabolism/genetics ; },
abstract = {UNLABELLED: Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate Salpingoeca rosetta endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that S. rosetta can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (cytb561a). This gene and its mammalian ortholog, the duodenal cytochrome b561 (DCYTB) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.

IMPORTANCE: This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate, S. rosetta, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that S. rosetta has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.},
}

*Choanoflagellata/genetics/metabolism
*Iron/metabolism
*Cell Differentiation
FMN Reductase/metabolism/genetics
Protozoan Proteins/metabolism/genetics

@article {pmid40001581,
year = {2025},
author = {Liu, Z and Fan, X and Wu, Y and Zhang, W and Zhang, X and Xu, D and Wang, Y and Sun, K and Wang, W and Ye, N},
title = {Comparative Genomics of Bryopsis hypnoides: Structural Conservation and Gene Transfer Between Chloroplast and Mitochondrial Genomes.},
journal = {Biomolecules},
volume = {15},
number = {2},
pages = {},
pmid = {40001581},
issn = {2218-273X},
mesh = {*Genome, Mitochondrial/genetics ; *Genome, Chloroplast/genetics ; *Phylogeny ; *Genomics/methods ; Codon Usage ; Evolution, Molecular ; Gene Transfer, Horizontal ; RNA, Transfer/genetics ; },
abstract = {Bryopsis hypnoides, a unicellular multinucleate green alga in the genus Bryopsis, plays vital ecological roles and represents a key evolutionary link between unicellular and multicellular algae. However, its weak genetic baseline data have constrained the progress of evolutionary research. In this study, we successfully assembled and annotated the complete circular chloroplast and mitochondrial genomes of B. hypnoides. The chloroplast genome has a total length of 139,745 bp and contains 59 protein-coding genes, 2 rRNA genes, and 11 tRNA genes, with 31 genes associated with photosynthesis. The mitochondrial genome has a total length of 408,555 bp and contains 41 protein-coding genes, 3 rRNA genes, and 18 tRNA genes, with 18 genes involved in oxidative phosphorylation. Based on the data, we conducted a genetic comparison involving repeat sequences, phylogenetic relationships, codon usage preferences, and gene transfer between the two organellar genomes. The major results highlighted that (1) the chloroplast genome favors A/T repeats, whereas the mitochondrial genome prefers C/G repeats; (2) codon usage preference analysis indicated that both organellar genomes prefer codons ending in A/T, with a stronger bias observed in the chloroplast genome; and (3) sixteen fragments with high sequence identity were identified between the two organellar genomes, indicating potential gene transfer. These findings provide critical insights into the organellar genome characteristics and evolution of B. hypnoides.},
}

*Genome, Mitochondrial/genetics
*Genome, Chloroplast/genetics
*Phylogeny
*Genomics/methods
Codon Usage
Evolution, Molecular
Gene Transfer, Horizontal
RNA, Transfer/genetics

@article {pmid39999802,
year = {2025},
author = {Saier, MH},
title = {Cooperation and competition were primary driving forces for biological evolution.},
journal = {Microbial physiology},
volume = {},
number = {},
pages = {1-25},
doi = {10.1159/000544890},
pmid = {39999802},
issn = {2673-1673},
abstract = {BACKGROUND: For many years, scientists have accepted Darwin's conclusion that "Survival of the Fittest" involves successful competition with other organisms for life-endowing molecules and conditions.

SUMMARY: Newly discovered "partial" organisms with minimal genomes that require symbiotic or parasitic relationships for growth and reproduction suggest that cooperation in addition to competition was and still is a primary driving force for survival. These two phenomena are not mutually exclusive, and both can confer a competitive advantage for survival. In fact, cooperation may have been more important in the early evolution for life on Earth before autonomous organisms developed, becoming large genome organisms.

KEY MESSAGES: This suggestion has tremendous consequences with respect to our conception of the early evolution of life on Earth as well as the appearance of intercellular interactions, multicellularity and the nature of interactions between humans and their societies (e.g., Social Darwinism).},
}

@article {pmid39999174,
year = {2025},
author = {Matte, A and LeBoeuf, AC},
title = {Innovation in ant larval feeding facilitated queen-worker divergence and social complexity.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {9},
pages = {e2413742122},
pmid = {39999174},
issn = {1091-6490},
support = {PR00P3_179776//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)/ ; },
mesh = {Animals ; *Ants/physiology ; *Larva/physiology/growth & development ; *Feeding Behavior/physiology ; *Social Behavior ; Phylogeny ; Biological Evolution ; Female ; Reproduction/physiology ; Behavior, Animal/physiology ; },
abstract = {Building differences between genetically equivalent units is a fundamental challenge for all multicellular organisms and superorganisms. In ants, reproductive or worker fate is typically determined during the larval stage, through feeding regimes managed by adult caretakers. However, the feeding care provided to larvae varies significantly across ants, as does phenotypic divergence between queen and worker castes. Here, we employed comparative phylogenetic methods and causal inference to investigate the relationships between larval feeding care, caste size dimorphism, and social complexity across ant diversity. We digitized the life's work of George and Jeanette Wheeler, cataloging the larval morphology of over 700 species, and we compiled data on species diets and larval feeding behaviors from the literature and our own observations. We measured queen-worker size dimorphism in 392 species and gathered data for colony size, worker polymorphism, and worker reproduction. Our analyses revealed that ancestral active-feeding larvae evolved passive morphologies when adults began feeding them individually, typically with processed material and often following a shift to nonpredatory diets. Greater queen-worker size dimorphism coevolved with larval passiveness, alongside traits indicative of increased social complexity, including larger colony sizes, worker subcastes, and a reduction in workers' reproductive potential. Likelihood comparisons of causal phylogenetic models support that extended alloparental care facilitated stronger caste dimorphism, which, in turn and along with increased colony sizes, promoted higher social complexity. Our results suggest that enhanced adult control over larval development enabled greater phenotypic specialization within colonies, with profound implications for social evolution.},
}

Animals
*Ants/physiology
*Larva/physiology/growth & development
*Feeding Behavior/physiology
*Social Behavior
Phylogeny
Biological Evolution
Female
Reproduction/physiology
Behavior, Animal/physiology

@article {pmid39998200,
year = {2025},
author = {Hu, P},
title = {mSphere of Influence: Rapid evolution of pathogenesis and drug resistance in human pathogenic fungi.},
journal = {mSphere},
volume = {10},
number = {3},
pages = {e0057024},
doi = {10.1128/msphere.00570-24},
pmid = {39998200},
issn = {2379-5042},
mesh = {Humans ; *Drug Resistance, Fungal/genetics ; Virulence ; Antifungal Agents/pharmacology ; Cryptococcus/genetics/pathogenicity/drug effects ; Fungi/genetics/pathogenicity/drug effects ; Candida/genetics/drug effects/pathogenicity ; Evolution, Molecular ; DNA Transposable Elements/genetics ; Mycoses/microbiology ; },
abstract = {Pengjie Hu works in the field of fungal pathogenesis, drug resistance, and evolution. In this mSphere of Influence article, he reflects on how three works, "Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro" and "Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans" by Gusa et al. and "Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection" by Bing et al. have impacted his work on the evolution of virulence, resistance, and adaptation in human fungal pathogens.},
}

Humans
*Drug Resistance, Fungal/genetics
Virulence
Antifungal Agents/pharmacology
Cryptococcus/genetics/pathogenicity/drug effects
Fungi/genetics/pathogenicity/drug effects
Candida/genetics/drug effects/pathogenicity
Evolution, Molecular
DNA Transposable Elements/genetics
Mycoses/microbiology

@article {pmid39983731,
year = {2025},
author = {Saha, S and Kalathera, J and Sumi, TS and Mane, V and Zimmermann, S and Waschina, S and Pande, S},
title = {Mass lysis of predatory bacteria drives the enrichment of antibiotic resistance in soil microbial communities.},
journal = {Current biology : CB},
volume = {35},
number = {6},
pages = {1258-1268.e6},
doi = {10.1016/j.cub.2025.01.068},
pmid = {39983731},
issn = {1879-0445},
mesh = {*Soil Microbiology ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects ; Bacteria/drug effects/genetics ; Drug Resistance, Bacterial ; Microbial Interactions ; Drug Resistance, Microbial ; },
abstract = {Numerous studies have investigated the effects of antibiotics on the evolution and maintenance of antimicrobial resistance (AMR). However, the impact of microbial interactions in antibiotic-free environments on resistance within complex communities remains unclear. We investigated whether the predatory bacterium M. xanthus, which can produce antimicrobials and employ various contact-dependent and -independent prey-killing mechanisms, influences the abundance of antibiotic-resistant bacteria in its local environment simply through its presence, regardless of active predation. We observed an association between the presence of M. xanthus in soil and the frequency of antibiotic-resistant bacteria. Additionally, culture-based and metagenomic analysis showed that coculturing M. xanthus with soil-derived communities in liquid cultures enriched AMR among non-myxobacterial isolates. This is because the lysis of M. xanthus, triggered during the starvation phase of the coculture experiments, releases diffusible growth-inhibitory compounds that enrich pre-existing resistant bacteria. Furthermore, our results show that death during multicellular fruiting body formation-a starvation-induced stress response in M. xanthus that results in over 90% cell death-also releases growth-inhibitory molecules that enrich resistant bacteria. Hence, the higher abundance of resistant bacteria in soil communities, where M. xanthus can be detected, was because of the diffusible growth-inhibitory substances that were released due to the death of M. xanthus cells during fruiting body formation. Together, our findings demonstrate how the death of M. xanthus, an important aspect of its life cycle, can impact antibiotic resistomes in natural soil communities without the anthropogenic influx of antibiotics.},
}

*Soil Microbiology
*Anti-Bacterial Agents/pharmacology
*Microbiota/drug effects
Bacteria/drug effects/genetics
Drug Resistance, Bacterial
Microbial Interactions
Drug Resistance, Microbial

@article {pmid39981820,
year = {2025},
author = {Du, Y and Wang, C and Zhang, Y and Liu, H},
title = {Evolutionary Origins and Adaptive Significance of A-to-I RNA Editing in Animals and Fungi.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e202400220},
doi = {10.1002/bies.202400220},
pmid = {39981820},
issn = {1521-1878},
support = {32170200//National Natural Science Foundation of China/ ; 31872918//National Natural Science Foundation of China/ ; },
abstract = {Adenosine-to-inosine (A-to-I) RNA editing, capable of protein recoding, has evolved independently in animals and fungi. This study proposes adaptive hypotheses regarding its origins and phenotypic significance, suggesting that A-to-I editing enhances adaptability by alleviating genetic trade-offs. In metazoans, its emergence may have been driven by a development-defense trade-off associated with transposable element activation during the evolution of multicellularity. Late Devonian cooling and End-Permian warming are hypothesized to have driven the emergence of extensive A-to-I recoding in coleoid nervous systems and Sordariomycete sexual fruiting bodies, respectively. These adaptations may have influenced key evolutionary innovations, including the evolution of metazoan nervous systems, coleoid intelligence, and shell loss, and fungal sexual reproductive structures. Additionally, extensive A-to-I recoding is proposed to facilitate accelerated development and specific life-history strategies in both animals and fungi. This paper provides new perspectives on the evolutionary forces shaping A-to-I RNA editing and its role in phenotypic diversity across taxa.},
}

@article {pmid39981724,
year = {2025},
author = {Siemons, C and Jonkers, S and Vlieg, RC and Corral-Martínez, P and van Noort, J and Boutilier, K},
title = {Establishment and maintenance of embryogenic cell fate during microspore embryogenesis.},
journal = {The Plant journal : for cell and molecular biology},
volume = {121},
number = {4},
pages = {e17243},
pmid = {39981724},
issn = {1365-313X},
support = {656579//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; 435005024/ZONMW_/ZonMw/Netherlands ; 737.016.013//NWO Building Blocks of Life/ ; },
mesh = {*Pollen/genetics/cytology/embryology ; *Brassica napus/genetics/embryology/cytology ; Seeds/genetics/cytology/growth & development ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism/genetics ; Indoleacetic Acids/metabolism ; Cell Differentiation ; Time-Lapse Imaging ; Plants, Genetically Modified ; },
abstract = {Microspore embryogenesis is a type of in vitro totipotency in which the immature male gametophyte (pollen) develops into a haploid embryo after an abiotic stress treatment. In Brassica napus, heat-stress treatment of male gametophytes induces the development of different types of multicellular embryogenic structures, each with different cellular characteristics and the capacity to form a differentiated embryo. The origin and early development of these different embryogenic structures have not been determined. We used two-photon excitation fluorescence microscopy and time-lapse imaging of cells expressing either a LEAFY COTYLEDON1 (LEC1) embryo identity reporter or a DR5v2 auxin response reporter to follow the development of embryogenic structures starting at the single- to few-cell stage. We show for the first time that the developmental fate of embryogenic structures is defined by the symmetry of the first embryogenic division and that the division plane also predicts the timing of subsequent pollen wall (exine) rupture: suspensorless embryos develop after a symmetric division and undergo late exine rupture, while suspensor-bearing embryos and embryogenic callus develop after an asymmetric division and undergo early exine rupture. Live imaging also captured previously unknown dynamic LEC1 and DR5v2 expression patterns that are associated with changes in exine integrity. This study highlights the developmental plasticity of cultured pollen and uncovers new roles for the first embryogenic cell division plane and the exine in defining and maintaining cell fate during microspore embryogenesis.},
}

*Pollen/genetics/cytology/embryology
*Brassica napus/genetics/embryology/cytology
Seeds/genetics/cytology/growth & development
Gene Expression Regulation, Plant
Plant Proteins/metabolism/genetics
Indoleacetic Acids/metabolism
Cell Differentiation
Time-Lapse Imaging
Plants, Genetically Modified

@article {pmid39979449,
year = {2025},
author = {Thibault, B and Thole, A and D'Angelo, R and Basset, C and Guillermet-Guibert, J},
title = {PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6265},
pmid = {39979449},
issn = {2045-2322},
support = {ARCPGA2022120005630_6362//Foundation for Cancer Research (ARC)/ ; TOUCAN//ANR/ ; },
mesh = {Humans ; *Cisplatin/pharmacology ; Female ; *Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism ; *Ovarian Neoplasms/drug therapy/genetics/pathology/metabolism ; Cell Line, Tumor ; *Drug Synergism ; *Mutation ; *Thiazoles/pharmacology ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism/antagonists & inhibitors ; Signal Transduction/drug effects ; Antineoplastic Agents/pharmacology ; Drug Resistance, Neoplasm/drug effects/genetics ; },
abstract = {Peritoneal carcinomatosis in ovarian cancer is often associated with ascites where cancer cells grow as aggregates. Given the emerging evidence that multicellular growth enhances resistance to conventional therapies, and that patients frequently develop resistance to platinum salts, we investigated the efficiency of PI3K/Akt signalling pathway targeting in multicellular growth and its importance as a potential therapeutic target in cells resistant to platinum salts. Due to its importance in many cancers and to the frequent mutations of its encoding gene PIK3CA, we focused on targeting PI3Kα using BYL-719 (Alpelisib), an isoform-specific inhibitor already used in clinics. We used a panel of 3 ovarian cancer cell lines, SKOV-3, EFO-21 and OVCAR-3, which come from different histological origins and bear different mutations. PI3K targeting drugs inhibit the activity of the PI3K/Akt pathway in all tested ovarian cancer cell lines with a drastic reduction of the phosphorylation of Akt on the serine 473, regardless the histology or the mutational profile. We showed that when cultured in 3D aggregates, ovarian cancer cells are more resistant to the PI3Kα-specific inhibitor BYL-719 and cisplatin compared to 2D monolayers. BYL-719 synergizes with cisplatin in 3D cultures only in PIK3CA-mutated SKOV-3 cells. This drug combination leads to a major cytotoxicity in 3D aggregates of this cell line. Finally, BYL-719 in combination with cisplatin remains active in 3D aggregates of SKOV-3 cells co-cultured with mesenchymal stem cells. We have identified a signalling pathway of interest for the treatment of advanced ovarian cancer in vitro, which could limit the progression of this disease. These data pave the road to investigate whether PI3Kα-specific inhibitor BYL-719 should be proposed in combination with cisplatin, in priority in patients bearing a PIK3CA mutation.},
}

Humans
*Cisplatin/pharmacology
Female
*Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism
*Ovarian Neoplasms/drug therapy/genetics/pathology/metabolism
Cell Line, Tumor
*Drug Synergism
*Mutation
*Thiazoles/pharmacology
Phosphoinositide-3 Kinase Inhibitors/pharmacology
Proto-Oncogene Proteins c-akt/metabolism/antagonists & inhibitors
Signal Transduction/drug effects
Antineoplastic Agents/pharmacology
Drug Resistance, Neoplasm/drug effects/genetics

@article {pmid39972731,
year = {2025},
author = {Hoffmann, LA and Giomi, L},
title = {Homochirality in the Vicsek model: Fluctuations and potential implications for cellular flocks.},
journal = {Physical review. E},
volume = {111},
number = {1-2},
pages = {015427},
doi = {10.1103/PhysRevE.111.015427},
pmid = {39972731},
issn = {2470-0053},
mesh = {*Models, Biological ; Animals ; },
abstract = {Chirality is a feature of many biological systems, and much research has been focused on understanding the origin and implications of this property. Famously, sugars and amino acids found in nature are homochiral, i.e., chiral symmetry is broken and only one of the two possible chiral states is ever observed. Certain types of cells show chiral behavior, too. Understanding the origin of cellular chirality and its effect on tissues and cellular dynamics is still an open problem and subject to much (recent) research, e.g., in the context of drosophila morphogenesis. Here, we develop a simple model to describe the possible origin of homochirality in cells. Combining the Vicsek model for collective behavior with the model of Jafarpour et al. [Phys. Rev. Lett. 115, 158101 (2015)0031-900710.1103/PhysRevLett.115.158101], developed to describe the emergence of molecular homochirality, we investigate how a homochiral state might have evolved in cells from an initially symmetric state without any mechanisms that explicitly break chiral symmetry. We investigate the transition to homochirality and show how the "openness" of the system as well as noise determine if and when a globally homochiral state is reached. While hypothetical and explorative in nature, our analysis may serve as a starting point for more realistic models of chirality in flocking multicellular systems.},
}

*Models, Biological
Animals

@article {pmid39970120,
year = {2024},
author = {Finoshin, AD and Kravchuk, OI and Mikhailov, KV and Ziganshin, RH and Adameyko, KI and Mikhailov, VS and Lyupina, YV},
title = {[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)].},
journal = {Molekuliarnaia biologiia},
volume = {58},
number = {5},
pages = {797-810},
pmid = {39970120},
issn = {0026-8984},
mesh = {Animals ; *Transglutaminases/genetics/metabolism ; *Porifera/enzymology/genetics ; Multigene Family ; Reactive Oxygen Species/metabolism ; Cystamine ; Gene Expression Regulation, Enzymologic ; },
abstract = {Transglutaminases are enzymes that carry out post-translational modifications of proteins and participate in the regulation of their activities. Here, we show for the first time that the transglutaminase genes in the basal metazoan, the sea sponge Halisarca dujardinii, are organized in a cluster, similarly to mammalian transglutaminases. The regulatory regions of six transglutaminase genes and their differential expression in the course of the life cycle of H. dujardinii suggest independent regulation of these genes. The decrease in transglutaminase activities by cystamine facilitates restoration of the multicellular structures of this sponge after its mechanical dissociation. For the first time we observed that this decrease in transglutaminase activities was accompanied by generation of the reactive oxygen species in the cells of a basal metazoan. The study of transglutaminases in the basal metazoans and other sea-dwelling organisms might provide better understanding of the evolution and specific functions of these enzymes in higher animals.},
}

Animals
*Transglutaminases/genetics/metabolism
*Porifera/enzymology/genetics
Multigene Family
Reactive Oxygen Species/metabolism
Cystamine
Gene Expression Regulation, Enzymologic

@article {pmid39964480,
year = {2025},
author = {Raynal, F and Sengupta, K and Plewczynski, D and Aliaga, B and Pancaldi, V},
title = {Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
pmid = {39964480},
issn = {1362-4962},
support = {//Fondation Toulouse Cancer Santé/ ; //Pierre Fabre Foundation for Research/ ; ANR-23-CE12-0023//Agence Nationale de la Recherche/ ; //Warsaw University of Technology/ ; 2020/37/B/NZ2/03757//National Science Centre/ ; },
mesh = {Humans ; *Cell Differentiation/genetics ; *Chromatin/metabolism/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; Chromatin Assembly and Disassembly/genetics ; RNA Polymerase II/metabolism/genetics ; Embryonic Stem Cells/metabolism ; Polycomb-Group Proteins/genetics/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology ; Colorectal Neoplasms/genetics/pathology ; Epigenesis, Genetic ; Neoplasms/genetics/pathology ; },
abstract = {Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.},
}

Humans
*Cell Differentiation/genetics
*Chromatin/metabolism/genetics
*Evolution, Molecular
Gene Expression Regulation, Neoplastic
Chromatin Assembly and Disassembly/genetics
RNA Polymerase II/metabolism/genetics
Embryonic Stem Cells/metabolism
Polycomb-Group Proteins/genetics/metabolism
Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology
Colorectal Neoplasms/genetics/pathology
Epigenesis, Genetic
Neoplasms/genetics/pathology

@article {pmid39957902,
year = {2025},
author = {Liao, W and Wang, J and Li, Y},
title = {Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: Current status and future perspective.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {2},
pages = {101075},
pmid = {39957902},
issn = {2214-0883},
abstract = {Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phase I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In phase I, NPs modulate Helicobacter pylori urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting H. pylori-induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.},
}

@article {pmid39957727,
year = {2024},
author = {Pineau, RM and Kahn, PC and Lac, DT and Belpaire, TER and Denning, MG and Wong, W and Ratcliff, WC and Bozdag, GO},
title = {Experimental evolution of multicellularity via cuboidal cell packing in fission yeast.},
journal = {Evolution letters},
volume = {8},
number = {5},
pages = {695-704},
pmid = {39957727},
issn = {2056-3744},
abstract = {The evolution of multicellularity represents a major transition in life's history, enabling the rise of complex organisms. Multicellular groups can evolve through multiple developmental modes, but a common step is the formation of permanent cell-cell attachments after division. The characteristics of the multicellular morphology that emerges have profound consequences for the subsequent evolution of a nascent multicellular lineage, but little prior work has investigated these dynamics directly. Here, we examine a widespread yet understudied emergent multicellular morphology: cuboidal packing. Extinct and extant multicellular organisms across the tree of life have evolved to form groups in which spherical cells divide but remain attached, forming approximately cubic subunits. To experimentally investigate the evolution of cuboidal cell packing, we used settling selection to favor the evolution of simple multicellularity in unicellular, spherical Schizosaccharomyces pombe yeast. Multicellular clusters with cuboidal organization rapidly evolved, displacing the unicellular ancestor. These clusters displayed key hallmarks of an evolutionary transition in individuality: groups possess an emergent life cycle driven by physical fracture, group size is heritable, and they respond to group-level selection via multicellular adaptation. In 2 out of 5 lineages, group formation was driven by mutations in the ace2 gene, preventing daughter cell separation after division. Remarkably, ace2 mutations also underlie the transition to multicellularity in Saccharomyces cerevisiae and Candida glabrata, lineages that last shared a common ancestor > 300 million years ago. Our results provide insight into the evolution of cuboidal cell packing, an understudied multicellular morphology, and highlight the deeply convergent potential for a transition to multicellular individuality within fungi.},
}

@article {pmid39954315,
year = {2025},
author = {Chen, H and Chen, C and Zhao, H and Wei, Y and Wang, P and Wu, LF and Song, T},
title = {Synergistic mechanism of magneto-optical sensing mediated by magnetic response protein Amb0994 and LOV-like protein Amb2291 in Magnetospirillum magneticum AMB-1.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {265},
number = {},
pages = {113124},
doi = {10.1016/j.jphotobiol.2025.113124},
pmid = {39954315},
issn = {1873-2682},
mesh = {*Magnetospirillum/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics ; *Light ; *Magnetic Fields ; Gene Expression Regulation, Bacterial/radiation effects ; Mutation ; Phototaxis ; Flagella/metabolism ; },
abstract = {Magnetotactic bacteria (MTB), known for their precision in navigating along magnetic fields, also exhibit light-sensitive behaviors. In Magnetospirillum magneticum AMB-1, the photoreceptor Amb2291 is involved in phototaxis regulation and magnetosome synthesis, particularly under oxidative stress. The magnetoreceptor Amb0994 modulates flagellar activity in response to magnetic field changes. Our study used a magneto-optical system to analyze the U-turn motility of north-seeking AMB-1 wild type (WT), amb2291 and amb0994 mutants under reversed magnetic fields and controlled light conditions. The results showed that WT strains consistently executed U-turns in response to magnetic fields, regardless of light variations. The diameters of U-turn of amb0994 mutant were smaller than those of the WT control. When illuminated with blue light in a direction opposite to the magnetic field, Δamb0994 exhibited slower U-turns with diameters similar to WT. In contrast, the Δamb2291 strain exhibited exaggerated U-turn movements under blue light, characterized by larger movement diameters and times compared to the WT, particularly whatever the light propagation direction is the same or opposite to the magnetic field in the initial state of motility. Gene expression analysis revealed that long-term exposure to blue light and magnetic fields led to a significant upregulation of amb2291 in Δamb0994 mutant strains and amb0994 in Δamb2291 mutant strains. These indicate a potential cooperative role of amb2291 and amb0994 in modulating bacterial motility under blue light. This research enhances our understanding of photoreception in MTB and its impact on magnetotaxis, shedding light on how environmental factors interact with microorganisms.},
}

*Magnetospirillum/metabolism/genetics
*Bacterial Proteins/metabolism/genetics
*Light
*Magnetic Fields
Gene Expression Regulation, Bacterial/radiation effects
Mutation
Phototaxis
Flagella/metabolism

@article {pmid39947017,
year = {2025},
author = {Zunjarrao, S and Gambetta, MC},
title = {Principles of long-range gene regulation.},
journal = {Current opinion in genetics & development},
volume = {91},
number = {},
pages = {102323},
doi = {10.1016/j.gde.2025.102323},
pmid = {39947017},
issn = {1879-0380},
mesh = {Animals ; *Gene Expression Regulation/genetics ; *Promoter Regions, Genetic ; Drosophila/genetics ; Genome/genetics ; Humans ; Transcription, Genetic ; Mammals/genetics ; Evolution, Molecular ; },
abstract = {Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.},
}

Animals
*Gene Expression Regulation/genetics
*Promoter Regions, Genetic
Drosophila/genetics
Genome/genetics
Humans
Transcription, Genetic
Mammals/genetics
Evolution, Molecular

@article {pmid39944812,
year = {2024},
author = {Klimontov, VV and Shishin, KS and Ivanov, RA and Ponomarenko, MP and Zolotareva, KA and Lashin, SA},
title = {GlucoGenes®, a database of genes and proteins associated with glucose metabolism disorders, its description and applications in bioinformatics research.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {28},
number = {8},
pages = {1008-1017},
doi = {10.18699/vjgb-24-107},
pmid = {39944812},
issn = {2500-0462},
abstract = {Data on the genetics and molecular biology of diabetes are accumulating rapidly. This poses the challenge of creating research tools for a rapid search for, structuring and analysis of information in this field. We have developed a web resource, GlucoGenes®, which includes a database and an Internet portal of genes and proteins associated with high glucose (hyperglycemia), low glucose (hypoglycemia), and both metabolic disorders. The data were collected using text mining of the publications indexed in PubMed and PubMed Central and analysis of gene networks associated with hyperglycemia, hypoglycemia and glucose variability performed with ANDSystems, a bioinformatics tool. GlucoGenes® is freely available at: https://glucogenes.sysbio.ru/genes/main. GlucoGenes® enables users to access and download information about genes and proteins associated with the risk of hyperglycemia and hypoglycemia, molecular regulators with hyperglycemic and antihyperglycemic activity, genes up-regulated by high glucose and/or low glucose, genes down-regulated by high glucose and/or low glucose, and molecules otherwise associated with the glucose metabolism disorders. With GlucoGenes®, an evolutionary analysis of genes associated with glucose metabolism disorders was performed. The results of the analysis revealed a significant increase (up to 40 %) in the proportion of genes with phylostratigraphic age index (PAI) values corresponding to the time of origin of multicellular organisms. Analysis of sequence conservation using the divergence index (DI) showed that most of the corresponding genes are highly conserved (DI < 0.6) or conservative (DI < 1). When analyzing single nucleotide polymorphism (SNP) in the proximal regions of promoters affecting the affinity of the TATA-binding protein, 181 SNP markers were found in the GlucoGenes® database, which can reduce (45 SNP markers) or increase (136 SNP markers) the expression of 52 genes. We believe that this resource will be a useful tool for further research in the field of molecular biology of diabetes.},
}

@article {pmid39939306,
year = {2025},
author = {Bijonowski, BM and Park, J and Bergert, M and Teubert, C and Diz-Muñoz, A and Galic, M and Wegner, SV},
title = {Intercellular adhesion boots collective cell migration through elevated membrane tension.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1588},
pmid = {39939306},
issn = {2041-1723},
support = {757593//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; GA2268/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 386797833//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {*Cell Movement ; *Cell Adhesion/physiology ; *Cell Membrane/metabolism ; *Phospholipase D/metabolism ; Humans ; Animals ; Cytoskeleton/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidic Acids/metabolism ; Signal Transduction ; },
abstract = {In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.},
}

*Cell Movement
*Cell Adhesion/physiology
*Cell Membrane/metabolism
*Phospholipase D/metabolism
Humans
Animals
Cytoskeleton/metabolism
TOR Serine-Threonine Kinases/metabolism
Phosphatidic Acids/metabolism
Signal Transduction

@article {pmid39935786,
year = {2024},
author = {Paredes-Espinosa, MB and Paluh, JL},
title = {Synthetic embryology of the human heart.},
journal = {Frontiers in cell and developmental biology},
volume = {12},
number = {},
pages = {1478549},
pmid = {39935786},
issn = {2296-634X},
abstract = {The evolution of stem cell-based heart models from cells and tissues to organoids and assembloids and recently synthetic embryology gastruloids, is poised to revolutionize our understanding of cardiac development, congenital to adult diseases, and patient customized therapies. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have already been integrated into transplantable patches and are in preclinical efforts to reverse fibrotic scarring from myocardial infarctions. To inform on the complexity of heart diseases, multi-tissue morphogenic heart models are needed that replicate fundamental components of heart function to heart organogenesis in vitro and which require a deep understanding of heart development. Organoid and assembloid models capture selected multicellular cardiac processes, such as chamber formation and priming events for vascularization. Gastruloid heart models offer deeper insights as synthetic embryology to mimic multi-staged developmental events of in vivo heart organogenesis including established heart fields, crescent formation and heart tube development along with vascular systemic foundation and even further steps. The human Elongating Multi-Lineage Organized Cardiac (EMLOC) gastruloid model captures these stages and additional events including chamber genesis, patterned vascularization, and extrinsic central and intrinsic cardiac nervous system (CNS-ICNS) integration guided by spatiotemporal and morphogenic processes with neural crest cells. Gastruloid synthetic embryology heart models offer new insights into previously hidden processes of development and provide powerful platforms for addressing heart disease that extends beyond cardiomyocytes, such as arrhythmogenic diseases, congenital defects, and systemic injury interactions, as in spinal cord injuries. The holistic view that is emerging will reveal heart development and disease in unprecedented detail to drive transformative state-of-the-art innovative applications for heart health.},
}

@article {pmid39932998,
year = {2025},
author = {Loiodice, M and Drula, E and McIver, Z and Antonyuk, S and Baslé, A and Lima, M and Yates, EA and Byrne, DP and Coughlan, J and Leech, A and Mesdaghi, S and Rigden, DJ and Drouillard, S and Helbert, W and Henrissat, B and Terrapon, N and Wright, GSA and Couturier, M and Cartmell, A},
title = {Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {7},
pages = {e2421623122},
pmid = {39932998},
issn = {1091-6490},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {*Polysaccharide-Lyases/metabolism/genetics/chemistry ; Substrate Specificity ; Bacterial Proteins/metabolism/genetics/chemistry ; Bacteria/enzymology/genetics ; Evolution, Molecular ; Models, Molecular ; Amino Acid Sequence ; Binding Sites ; Protein Binding ; Polysaccharides/metabolism ; Glycosaminoglycans/metabolism ; },
abstract = {Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a β-elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosaminoglycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed 10 PL33 members derived from all major environments and further elucidated the detailed biochemical and biophysical properties of five, showing that their substrate specificity is conferred by variations in tunnel length and topography. The key amino acids involved in catalysis and substrate interactions were identified, and employing a combination of complementary biochemical, structural, and modeling approaches, we show that the tunnel topography is induced by substrate binding to the glycan. Structural and bioinformatic analyses revealed that these features are conserved across several lyase families as well as in mammalian GAG epimerases.},
}

*Polysaccharide-Lyases/metabolism/genetics/chemistry
Substrate Specificity
Bacterial Proteins/metabolism/genetics/chemistry
Bacteria/enzymology/genetics
Evolution, Molecular
Models, Molecular
Amino Acid Sequence
Binding Sites
Protein Binding
Polysaccharides/metabolism
Glycosaminoglycans/metabolism

@article {pmid39926383,
year = {2024},
author = {King, MR},
title = {Simulation of Somatic Evolution Through the Introduction of Random Mutation to the Rules of Conway's Game of Life.},
journal = {Cellular and molecular bioengineering},
volume = {17},
number = {6},
pages = {563-571},
pmid = {39926383},
issn = {1865-5025},
abstract = {INTRODUCTION: Conway's Game of Life (GOL), and related cellular automata (CA) models, have served as interesting simulations of complex behaviors resulting from simple rules of interactions between neighboring cells, that sometime resemble the growth and reproduction of living things. Thus, CA has been applied towards understanding the interaction and reproduction of single-cell organisms, and the growth of larger, disorganized tissues such as tumors. Surprisingly, however, there have been few attempts to adapt simple CA models to recreate the evolution of either new species, or subclones within a multicellular, tumor-like tissue.

METHODS: In this article, I present a modified form of the classic Conway's GOL simulation, in which the three integer thresholds that define GOL (number of neighboring cells, below which a cell will "die of loneliness"; number of neighboring cells, above which a cell will die of overcrowding; and number of neighboring cells that will result in spontaneous birth of a new cell within an empty lattice location) are occasionally altered with a randomized mutation of fractional magnitude during new "cell birth" events. Newly born cells "inherit" the current mutation state of a neighboring parent cell, and over the course of 10,000 generations these mutations tend to accumulate until they impact the behaviors of individual cells, causing them to transition from the sparse, small patterns of live cells characteristic of GOL into a more dense, unregulated growth resembling a connected tumor tissue.

RESULTS: The mutation rate and mutation magnitude were systematically varied in repeated randomized simulation runs, and it was determined that the most important mutated rule for the transition to unregulated, tumor-like growth was the overcrowding threshold, with the spontaneous birth and loneliness thresholds being of secondary importance. Spatial maps of the different "subclones" of cells that spontaneously develop during a typical simulation trial reveal that cells with greater fitness will overgrow the lattice and proliferate while the less fit, "wildtype" GOL cells die out and are replaced with mutant cells.

CONCLUSIONS: This simple modeling approach can be easily modified to add complexity and more realistic biological details, and may yield new understanding of cancer and somatic evolution.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-024-00828-9.},
}

@article {pmid39898884,
year = {2025},
author = {Vanhoeijen, R and Okkelman, IA and Rogier, N and Sedlačík, T and Stöbener, DD and Devriendt, B and Dmitriev, RI and Hoogenboom, R},
title = {Poly(2-alkyl-2-oxazoline) Hydrogels as Synthetic Matrices for Multicellular Spheroid and Intestinal Organoid Cultures.},
journal = {Biomacromolecules},
volume = {26},
number = {3},
pages = {1860-1872},
doi = {10.1021/acs.biomac.4c01627},
pmid = {39898884},
issn = {1526-4602},
mesh = {*Hydrogels/chemistry/pharmacology ; *Organoids/cytology ; *Spheroids, Cellular/cytology ; Humans ; Extracellular Matrix/chemistry ; Intestines/cytology ; Cell Proliferation/drug effects ; Animals ; Oxazoles/chemistry ; Cell Culture Techniques, Three Dimensional/methods ; Cell Culture Techniques/methods ; },
abstract = {The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.},
}

*Hydrogels/chemistry/pharmacology
*Organoids/cytology
*Spheroids, Cellular/cytology
Humans
Extracellular Matrix/chemistry
Intestines/cytology
Cell Proliferation/drug effects
Animals
Oxazoles/chemistry
Cell Culture Techniques, Three Dimensional/methods
Cell Culture Techniques/methods

@article {pmid39896451,
year = {2025},
author = {Scherer, J and Hinczewski, M and Nelms, B},
title = {Ultra-deep sequencing of somatic mutations induced by a maize transposon.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39896451},
issn = {2692-8205},
support = {R35 GM151237/GM/NIGMS NIH HHS/United States ; },
abstract = {Cells accumulate mutations throughout development, contributing to cancer, aging, and evolution. Quantitative data on the abundance of de novo mutations within plants or animals are limited, as new mutations are often rare within a tissue and fall below the limits of current sequencing depths and error rates. Here, we show that mutations induced by the maize Mutator (Mu) transposon can be reliably quantified down to a detection limit of 1 part in 12,000. We measured the abundance of millions of de novo Mu insertions across four tissue types. Within a tissue, the distribution of de novo Mu allele frequencies was highly reproducible between plants, showing that, despite the stochastic nature of mutation, repeated statistical patterns of mutation abundance emerge. In contrast, there were significant differences in the allele frequency distribution between tissues. At the extremes, root was dominated by a small number of highly abundant de novo insertions, while endosperm was characterized by thousands of insertions at low allele frequencies. Finally, we used the measured pollen allele frequencies to reinterpret a classic genetic experiment, showing that evidence for late Mu activity in pollen are better explained by cell division statistics. These results provide insight into the complexity of mutation accumulation in multicellular organisms and a system to interrogate the factors that shape mutation abundance.},
}

@article {pmid39894974,
year = {2025},
author = {Voronkina, A and Cárdenas, P and Adam, J and Meissner, H and Nowacki, K and Joseph, Y and Tabachnick, KR and Ehrlich, H},
title = {Biosilica 3D Micromorphology of Geodiidae Sponge Spicules Is Patterned by F-Actin.},
journal = {Microscopy research and technique},
volume = {},
number = {},
pages = {},
doi = {10.1002/jemt.24798},
pmid = {39894974},
issn = {1097-0029},
support = {2020/38/A/ST5/00151//National Science Centre/ ; },
abstract = {Demosponges (phylum Porifera) are among the first multicellular organisms on the planet and represent a unique archive of biosilica-based skeletal structures with species-specific microstructures called spicules. With more than 80 morphotypes, this class of sponges is recognized as a unique source of amorphous silica with superficial ornamentation patterned by organic phases. In this study, we investigated spicules of selected representatives of the family Geodiidae (order Tetractinellida), to identify F-actin-containing axial filaments within these 3D skeletal microconstructs defined as oxyspherasters and sterrasters. Their desilicification using 10% HF leads to isolation of multifilamentous, radially oriented organic matrices, which resemble the shape and size of the original spicules. Our data show that highly specific indicators of F-actin such as iFluorTM 594-Phalloidin, iFluorTM 488-Phalloidin, as well as iFluorTM 350-Phalloidin unambiguously confirm its localization within demineralized oxyspherasters and sterrasters of 11 diverse demosponges species belonging to the subfamily Geodiinae (genera Geodia, Rhabdastrella) and the subfamily Erylinae (genera Caminella, Caminus, Erylus, Pachymatisma). Well-defined periodicity in Geodia cydonium sterrasters actin filaments has been observed using atomic force microscopy (AFM) for the first time. The findings of F-actin as a possible pattern driver in spicules of geodiids brings additional light to our knowledge of spiculogenesis in this group. However, no specific actin structures were found between the geodiid subfamilies or genera thereby suggesting a common actin process, present already at the emergence of the family (~170 million years ago).},
}

@article {pmid39890889,
year = {2025},
author = {Paul, CD and Yankaskas, C and Shahi Thakuri, P and Balhouse, B and Salen, S and Bullock, A and Beam, S and Chatman, A and Djikeng, S and Yang, XJ and Wong, G and Dey, I and Holmes, S and Dockey, A and Bailey-Steinitz, L and Zheng, L and Li, W and Chandra, V and Nguyen, J and Sharp, J and Willems, E and Kennedy, M and Dallas, MR and Kuninger, D},
title = {Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {3933},
pmid = {39890889},
issn = {2045-2322},
mesh = {Humans ; *Neoplasms/pathology/genetics ; *Organoids/pathology/metabolism ; Cell Line, Tumor ; Female ; Cell Culture Techniques/methods ; Tumor Cells, Cultured ; },
abstract = {Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e.g., genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies. However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use. Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples. Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems. Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development. We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community.},
}

Humans
*Neoplasms/pathology/genetics
*Organoids/pathology/metabolism
Cell Line, Tumor
Female
Cell Culture Techniques/methods
Tumor Cells, Cultured

@article {pmid39884276,
year = {2025},
author = {Van Goor, J and Turdiev, A and Speir, SJ and Manning, J and Haag, ES},
title = {Male secreted short glycoproteins link sperm competition to the reproductive isolation of species.},
journal = {Current biology : CB},
volume = {35},
number = {4},
pages = {911-917.e5},
doi = {10.1016/j.cub.2024.12.040},
pmid = {39884276},
issn = {1879-0445},
mesh = {Animals ; Male ; *Spermatozoa/physiology/metabolism ; *Reproductive Isolation ; Glycoproteins/metabolism/genetics ; Female ; Caenorhabditis elegans/physiology/genetics/metabolism ; },
abstract = {Sperm competition is found across multicellular organisms[1][,][2][,][3][,][4] using both external and internal fertilization.[5][,][6] Sperm competition and post-copulatory cryptic female choice can promote incompatibility between species due to the antagonistic coevolution of the sexes within a species.[7][,][8][,][9][,][10][,][11] This between-species incompatibility is accelerated and markedly asymmetrical when sexual mode differs, producing the "weak inbreeder, strong outcrosser" (WISO) pattern.[12] Here, we show that male secreted short (MSS) sperm glycoproteins of nematodes constitute a gametic effector of WISO. In obligately outcrossing Caenorhabditis, MSS is dispensable for baseline fertility but required for intraspecific sperm competitiveness.[13] MSS is lost in self-fertile lineages, likely as a response to selection for a hermaphrodite-biased sex ratio.[14] Selfing hermaphrodites that mate with males of closely related outcrossing species are rapidly sterilized due to ovarian sperm invasion.[11] The simplification of the male proteome in selfing species suggests that many factors could contribute to invasivity.[13][,][15][,][16] However, restoration of just MSS to the self-fertile C. briggsae is sufficient to induce mild invasivity. Further, MSS+ sperm appear to derive their competitive advantage from this behavior, directly linking interspecies incompatibility with intraspecific competition. MSS-related proteins (MSRPs) remaining in the C. briggsae genome are similar in structure, expression, and localization to MSS but are not necessary for normal sperm competitiveness. Further, overexpression of the MSRP most similar to MSS, Cbr-MSRP-3, is insufficient to enhance competitiveness. We conclude that outcrossing species retain sperm competition factors that contribute to their reproductive isolation from selfing relatives that lost them.},
}

Animals
Male
*Spermatozoa/physiology/metabolism
*Reproductive Isolation
Glycoproteins/metabolism/genetics
Female
Caenorhabditis elegans/physiology/genetics/metabolism

@article {pmid39883703,
year = {2025},
author = {Wong, W and Bravo, P and Yunker, PJ and Ratcliff, WC and Burnetti, AJ},
title = {Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.},
journal = {PLoS biology},
volume = {23},
number = {1},
pages = {e3002975},
pmid = {39883703},
issn = {1545-7885},
support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; },
mesh = {*Oxygen/metabolism ; *Saccharomyces cerevisiae/metabolism/genetics ; Diffusion ; Myoglobin/metabolism/genetics ; Hemerythrin/metabolism/genetics ; Models, Biological ; Genetic Fitness ; Oxygen Consumption ; },
abstract = {Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.},
}

*Oxygen/metabolism
*Saccharomyces cerevisiae/metabolism/genetics
Diffusion
Myoglobin/metabolism/genetics
Hemerythrin/metabolism/genetics
Models, Biological
Genetic Fitness
Oxygen Consumption

@article {pmid39883596,
year = {2025},
author = {Pullen, RM and Decker, SR and Subramanian, V and Adler, MJ and Tobias, AV and Perisin, M and Sund, CJ and Servinsky, MD and Kozlowski, MT},
title = {Considerations for Domestication of Novel Strains of Filamentous Fungi.},
journal = {ACS synthetic biology},
volume = {14},
number = {2},
pages = {343-362},
pmid = {39883596},
issn = {2161-5063},
mesh = {*Fungi/genetics/metabolism ; *Synthetic Biology/methods ; Metabolic Engineering/methods ; Genome, Fungal ; Biotechnology/methods ; },
abstract = {Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.},
}

*Fungi/genetics/metabolism
*Synthetic Biology/methods
Metabolic Engineering/methods
Genome, Fungal
Biotechnology/methods

@article {pmid39877976,
year = {2025},
author = {Pereira Lobo, F and Benjamim, DM and da Silva, TTM and de Oliveira, MD},
title = {Molecular and Functional Convergences Associated with Complex Multicellularity in Eukarya.},
journal = {Molecular biology and evolution},
volume = {42},
number = {2},
pages = {},
pmid = {39877976},
issn = {1537-1719},
mesh = {*Phylogeny ; Eukaryota/genetics ; Biological Evolution ; Animals ; Genomics/methods ; Evolution, Molecular ; },
abstract = {A key trait of Eukarya is the independent evolution of complex multicellularity in animals, land plants, fungi, brown algae, and red algae. This phenotype is characterized by the initial exaptation of cell-cell adhesion genes followed by the emergence of mechanisms for cell-cell communication, together with the expansion of transcription factor gene families responsible for cell and tissue identity. The number of cell types is commonly used as a quantitative proxy for biological complexity in comparative genomics studies. While expansions of individual gene families have been associated with variations in the number of cell types within individual complex multicellular lineages, the molecular and functional roles responsible for the independent evolution of complex multicellular across Eukarya remain poorly understood. We employed a phylogeny-aware strategy to conduct a genomic-scale search for associations between the number of cell types and the abundance of genomic components across a phylogenetically diverse set of 81 eukaryotic species, including species from all complex multicellular lineages. Our annotation schemas represent 2 complimentary aspects of genomic information: homology, represented by conserved sequences, and function, represented by Gene Ontology terms. We found many gene families sharing common biological themes that define complex multicellular to be independently expanded in 2 or more complex multicellular lineages, such as components of the extracellular matrix, cell-cell communication mechanisms, and developmental pathways. Additionally, we describe many previously unknown associations of biological themes and biological complexity, such as expansions of genes playing roles in wound response, immunity, cell migration, regulatory processes, and response to natural rhythms. Together, our findings unveil a set of functional and molecular convergences independently expanded in complex multicellular lineages likely due to the common selective pressures in their lifestyles.},
}

*Phylogeny
Eukaryota/genetics
Biological Evolution
Animals
Genomics/methods
Evolution, Molecular

@article {pmid39872364,
year = {2025},
author = {Russo, A and Moy, J and Khin, M and Dorsey, TR and Lopez Carrero, A and Burdette, JE},
title = {Loss of phosphatase and tensin homolog (PTEN) increases Lysyl oxidase-like 2 (LOXL2) expression enhancing the growth of fallopian tube epithelial cells as three-dimensional spheroids.},
journal = {Cancer pathogenesis and therapy},
volume = {3},
number = {1},
pages = {68-75},
pmid = {39872364},
issn = {2949-7132},
abstract = {BACKGROUND: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of all ovarian cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as the cell of origin of HGSOC. Phosphatase and tensin homolog (PTEN) is a tumor suppressor and its loss is sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation of multicellular tumor spheroids (MTSs), and ovarian colonization. In murine oviductal epithelial (MOE) cells (the equivalent of human FTE) loss of PTEN results in the upregulation of transcripts associated with the extracellular matrix, with a specific focus on the elevation of lysyl oxidase-like 2 (LOXL2). Although LOXL2 is known to drive transformation and invasion in solid tumors and is associated with a poor prognosis in ovarian cancer, its specific role in the tumorigenesis of ovarian cancer originating from FTE remains unclear. Therefore, we aim to investigate whether LOXL2 mediates tumorigenesis from the fallopian tube epithelium.

METHODS: In this study, we utilized clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CAS9) technology to delete LOXL2 in PTEN-deficient MOE cells to understand its role in mediating the oncogenic effects of PTEN loss. In addition, CRISPR-CAS9 was used to delete LOXL2 in OVCAR8 ovarian cancer cells. We monitored the changes in tumorigenic properties, such as migration, invasion, and growth of three-dimensional (3D) spheroids, to assess whether the loss of LOXL2 resulted in any changes.

RESULTS: We found that a reduction in LOXL2 expression did not significantly change the migration or invasive capabilities of PTEN-depleted MOE or human ovarian cancer cells. However, we found that a reduction in LOXL2 expression resulted in a significant reduction in 3D MTS formation and survival in both lines.

CONCLUSIONS: These results reveal for the first time that PTEN loss in FTE cells increases LOXL2 expression through downregulation of Pax2, and LOXL2 deletion blocks 3D spheroid formation.},
}

@article {pmid39869795,
year = {2025},
author = {Pérez Gallego, R and von Meijenfeldt, FAB and Bale, NJ and Sinninghe Damsté, JS and Villanueva, L},
title = {Emergence and evolution of heterocyte glycolipid biosynthesis enabled specialized nitrogen fixation in cyanobacteria.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {5},
pages = {e2413972122},
pmid = {39869795},
issn = {1091-6490},
support = {694569-MICROLIPIDS//EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; Spinoza Award//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; 024.002.002//Ministerie van Onderwijs, Cultuur en Wetenschap (OCW)/ ; },
mesh = {*Nitrogen Fixation/genetics ; *Cyanobacteria/metabolism/genetics ; *Glycolipids/biosynthesis/metabolism ; Phylogeny ; Multigene Family ; Evolution, Molecular ; Biological Evolution ; },
abstract = {Heterocytes, specialized cells for nitrogen fixation in cyanobacteria, are surrounded by heterocyte glycolipids (HGs), which contribute to protection of the nitrogenase enzyme from oxygen. Diverse HGs preserve in the sediment and have been widely used as evidence of past nitrogen fixation, and structural variation has been suggested to preserve taxonomic information and reflect paleoenvironmental conditions. Here, by comprehensive HG identification and screening of HG biosynthetic gene clusters throughout cyanobacteria, we reconstruct the convergent evolutionary history of HG structure, in which different clades produce the same HGs. We find that rudimentary HG biosynthetic machinery was already present in cyanobacteria before the emergence of heterocytes for functions unrelated to nitrogen fixation and identify HG analogs produced by specific and distantly related nonheterocytous cyanobacteria. These structurally less complex molecules represent precursors of HGs, suggesting that HGs arose after a genomic reorganization and expansion of ancestral biosynthetic machinery, enabling the rise of cyanobacterial heterocytes in an increasingly oxygenated atmosphere. Our results open a chapter in the potential use of diagenetic products of HGs and HG analogs as fossils for reconstructing the evolution of multicellularity and division of labor in cyanobacteria.},
}

*Nitrogen Fixation/genetics
*Cyanobacteria/metabolism/genetics
*Glycolipids/biosynthesis/metabolism
Phylogeny
Multigene Family
Evolution, Molecular
Biological Evolution

@article {pmid39868713,
year = {2024},
author = {Montagné, N},
title = {[The role of volatile organic compounds in plant-insect communication].},
journal = {Biologie aujourd'hui},
volume = {218},
number = {3-4},
pages = {141-144},
doi = {10.1051/jbio/2024016},
pmid = {39868713},
issn = {2105-0686},
mesh = {Animals ; *Volatile Organic Compounds/metabolism ; *Insecta/physiology ; *Plants/chemistry/metabolism/parasitology ; Herbivory/physiology ; Animal Communication ; Pollination/physiology ; },
abstract = {Insects and flowering plants are the most abundant and diverse multicellular organisms on Earth, accounting for 75% of known species. Their evolution has been largely interdependent since the so-called Angiosperm Terrestrial Revolution (100-50 Mya), when the explosion of plant diversity stimulated the evolution of pollinating and herbivorous insects. Plant-insect interactions rely heavily on chemical communication via volatile organic compounds (VOCs). These molecules are synthesised by the secondary metabolism of plants through various pathways and include terpenes, benzenoids and aliphatic compounds. As of today, more than 1,700 of these VOCs have notably been identified in flowers. Plants use these molecules to attract pollinators or repel herbivorous insects. VOCs also act as chemical signals for insects, helping them to find food or egg-laying sites. Chemical communication has thus played an important role in the evolutionary history of insects and flowering plants. Tritrophic interactions are a fascinating example of VOC-driven communication. When plants are attacked by herbivores, they emit herbivore-induced volatiles, such as green leaf volatiles and specific terpenes. These signals attract predators or parasitoids of the herbivores, acting as a chemical distress call. For example, parasitoid wasps can identify plants that have been attacked by their host herbivores, even in the absence of the herbivores themselves, thanks to the plant's odour profile. But herbivore-induced volatiles also affect the herbivores themselves. Female moths, for example, use these olfactory cues to avoid laying eggs on plants that have already been attacked. Insects detect VOCs using highly sensitive odorant receptors on their antennae. Herbivorous insects, such as the model moth species S. littoralis, have receptors specific for floral VOCs and herbivore-induced volatiles. Current research aims to understand how the evolution of these receptors has contributed to the adaptation of insects to plant volatiles. In moths, receptors for benzenoids appear to be more ancient and conserved, whereas receptors for terpenes and aliphatic molecules show more recent diversification in response to plant evolution. Research into plant-insect communication also opens up avenues for sustainable agriculture, as VOCs can be used to attract natural pest predators or deter herbivores, reducing the need for chemical pesticides.},
}

Animals
*Volatile Organic Compounds/metabolism
*Insecta/physiology
*Plants/chemistry/metabolism/parasitology
Herbivory/physiology
Animal Communication
Pollination/physiology

@article {pmid39863161,
year = {2025},
author = {Dubey, A and Muthu, G and Seshasayee, ASN},
title = {Evolution of Transcription Factor-containing Superfamilies in Eukaryotes.},
journal = {Journal of molecular biology},
volume = {437},
number = {5},
pages = {168959},
doi = {10.1016/j.jmb.2025.168959},
pmid = {39863161},
issn = {1089-8638},
mesh = {*Evolution, Molecular ; *Transcription Factors/genetics/metabolism ; *Eukaryota/genetics ; Animals ; Phylogeny ; Multigene Family ; },
abstract = {Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs in some TF-SFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.},
}

*Evolution, Molecular
*Transcription Factors/genetics/metabolism
*Eukaryota/genetics
Animals
Phylogeny
Multigene Family

@article {pmid39853129,
year = {2025},
author = {Espinoza Miranda, SS and Abbaszade, G and Hess, WR and Drescher, K and Saliba, A-E and Zaburdaev, V and Chai, L and Dreisewerd, K and Grünberger, A and Westendorf, C and Müller, S and Mascher, T},
title = {Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.},
journal = {Microbiology and molecular biology reviews : MMBR},
volume = {},
number = {},
pages = {e0013824},
doi = {10.1128/mmbr.00138-24},
pmid = {39853129},
issn = {1098-5557},
abstract = {SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.},
}

@article {pmid39849824,
year = {2025},
author = {Ndinyanka Fabrice, T and Buczak, K and Schmidt, A and Pieters, J},
title = {T cell population size control by coronin 1 uncovered: from a spot identified by two-dimensional gel electrophoresis to quantitative proteomics.},
journal = {Expert review of proteomics},
volume = {22},
number = {1},
pages = {35-44},
doi = {10.1080/14789450.2025.2450812},
pmid = {39849824},
issn = {1744-8387},
mesh = {*Proteomics/methods ; Humans ; *Electrophoresis, Gel, Two-Dimensional/methods ; *Microfilament Proteins/metabolism ; Proteome/metabolism ; Mycobacterium tuberculosis/metabolism/pathogenicity/genetics ; Animals ; Mass Spectrometry/methods ; },
abstract = {INTRODUCTION: Recent work identified members of the evolutionarily conserved coronin protein family as key regulators of cell population size. This work originated ~25 years ago through the identification, by two-dimensional gel electrophoresis, of coronin 1 as a host protein involved in the virulence of Mycobacterium tuberculosis. We here describe the journey from a spot on a 2D gel to the recent realization that coronin proteins represent key controllers of eukaryotic cell population sizes, using ever more sophisticated proteomic techniques.

AREAS COVERED: We discuss the value of 'old school' proteomics using relatively simple and cost-effective technologies that allowed to gain insights into subcellular proteomes and describe how label-free quantitative (phospho)proteomics using mass spectrometry allowed to disentangle the role for coronin 1 in eukaryotic cell population size control. Finally, we mention potential implications of coronin-mediated cell population size control for health and disease.

EXPERT OPINION: Proteome analysis has been revolutionized by the advent of modern-day mass spectrometers and is indispensable for a better understanding of biology. Here, we discuss how careful dissection of physio-pathological processes by a combination of proteomics, genomics, biochemistry and cell biology may allow to zoom in on the unexplored, thereby possibly tackling hitherto unasked questions and defining novel mechanisms.},
}

*Proteomics/methods
Humans
*Electrophoresis, Gel, Two-Dimensional/methods
*Microfilament Proteins/metabolism
Proteome/metabolism
Mycobacterium tuberculosis/metabolism/pathogenicity/genetics
Animals
Mass Spectrometry/methods

@article {pmid39841150,
year = {2025},
author = {Isaksson, H and Lind, P and Libby, E},
title = {Adaptive evolutionary trajectories in complexity: Transitions between unicellularity and facultative differentiated multicellularity.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {4},
pages = {e2411692122},
pmid = {39841150},
issn = {1091-6490},
support = {2018-03630//Vetenskapsrådet (VR)/ ; },
mesh = {*Biological Evolution ; Mutation ; Cell Differentiation ; Adaptation, Physiological ; Models, Biological ; Genetic Fitness ; Stress, Physiological ; },
abstract = {Multicellularity spans a wide gamut in terms of complexity, from simple clonal clusters of cells to large-scale organisms composed of differentiated cells and tissues. While recent experiments have demonstrated that simple forms of multicellularity can readily evolve in response to different selective pressures, it is unknown if continued exposure to those same selective pressures will result in the evolution of increased multicellular complexity. We use mathematical models to consider the adaptive trajectories of unicellular organisms exposed to periodic bouts of abiotic stress, such as drought or antibiotics. Populations can improve survival in response to the stress by evolving multicellularity or cell differentiation-or both; however, these responses have associated costs when the stress is absent. We define a parameter space of fitness-relevant traits and identify where multicellularity, differentiation, or their combination is fittest. We then study the effects of adaptation by allowing populations to fix mutations that improve their fitness. We find that while the same mutation can be beneficial to populations of different complexity, e.g., strict unicellularity or life cycles with stages of differentiated multicellularity, the magnitudes of their effects can differ and alter which is fittest. As a result, we observe adaptive trajectories that gain and lose complexity. We also show that the order of mutations, historical contingency, can cause some transitions to be permanent in the absence of neutral evolution. Ultimately, we find that continued exposure to a selective driver for multicellularity can either lead to increasing complexity or a return to unicellularity.},
}

*Biological Evolution
Mutation
Cell Differentiation
Adaptation, Physiological
Models, Biological
Genetic Fitness
Stress, Physiological

@article {pmid39838007,
year = {2025},
author = {McCaig, CD},
title = {Epithelia Are Scaffolds for Electricity-Dependent Molecular Interactions.},
journal = {Reviews of physiology, biochemistry and pharmacology},
volume = {187},
number = {},
pages = {47-52},
pmid = {39838007},
issn = {0303-4240},
mesh = {Animals ; Epithelium/physiology/metabolism ; Humans ; *Basement Membrane/metabolism/physiology ; Electricity ; Epithelial Cells/metabolism ; Electrophysiological Phenomena ; },
abstract = {Once multicellularity was thriving, a key development involved the emergence of epithelial layers that separated "inside" from "outside". Most epithelia then generate their own transepithelial electrical signals. So electrical forces were instrumental in the development of epithelial tissues, which themselves generate further electrical signals. Epithelia also developed extracellular basement membranes which act as spatially diverse scaffolds to organize multiple molecular interactions, dependent on electrical forces.Epithelia and basement membranes were constructed using electrical forces and their evolution had electrophysiological consequences.},
}

Animals
Epithelium/physiology/metabolism
Humans
*Basement Membrane/metabolism/physiology
Electricity
Epithelial Cells/metabolism
Electrophysiological Phenomena

@article {pmid39838006,
year = {2025},
author = {McCaig, CD},
title = {Multicellularity and Electrical Forces.},
journal = {Reviews of physiology, biochemistry and pharmacology},
volume = {187},
number = {},
pages = {39-46},
pmid = {39838006},
issn = {0303-4240},
mesh = {*Electricity ; *Electrophysiological Phenomena ; *Biological Evolution ; },
abstract = {Multiple single-celled life forms existed for millennia before some individual cells found ways of gathering together to form multicellular organisms. Several of the key elements that drove this step-change in life on Earth involved electrical forces.},
}

*Electricity
*Electrophysiological Phenomena
*Biological Evolution

@article {pmid39833858,
year = {2025},
author = {Hure, V and Piron-Prunier, F and Yehouessi, T and Vitte, C and Kornienko, AE and Adam, G and Nordborg, M and Déléris, A},
title = {Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {11},
pmid = {39833858},
issn = {1474-760X},
mesh = {*Arabidopsis/genetics ; *DNA Transposable Elements ; *Histones/metabolism ; *Gene Silencing ; *DNA Methylation ; Gene Expression Regulation, Plant ; Arabidopsis Proteins/genetics/metabolism ; Epigenesis, Genetic ; Polycomb-Group Proteins/metabolism/genetics ; },
abstract = {BACKGROUND: The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.

RESULTS: In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs-which we refer to as "bifrons"-that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan.

CONCLUSIONS: Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.},
}

*Arabidopsis/genetics
*DNA Transposable Elements
*Histones/metabolism
*Gene Silencing
*DNA Methylation
Gene Expression Regulation, Plant
Arabidopsis Proteins/genetics/metabolism
Epigenesis, Genetic
Polycomb-Group Proteins/metabolism/genetics

@article {pmid39826309,
year = {2025},
author = {Mendes, M and Morais, AS and Carlos, A and Sousa, JJ and Pais, AC and Mihăilă, SM and Vitorino, C},
title = {Organ-on-a-chip: Quo vademus? Applications and regulatory status.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {249},
number = {},
pages = {114507},
doi = {10.1016/j.colsurfb.2025.114507},
pmid = {39826309},
issn = {1873-4367},
mesh = {Humans ; *Lab-On-A-Chip Devices ; Drug Discovery ; Animals ; Microphysiological Systems ; },
abstract = {Organ-on-a-chip systems, also referred to as microphysiological systems (MPS), represent an advance in bioengineering microsystems designed to mimic key aspects of human organ physiology and function. Drawing inspiration from the intricate and hierarchical architecture of the human body, these innovative platforms have emerged as invaluable in vitro tools with wide-ranging applications in drug discovery and development, as well as in enhancing our understanding of disease physiology. The facility to replicate human tissues within physiologically relevant three-dimensional multicellular environments empowers organ-on-a-chip systems with versatility throughout different stages of the drug development process. Moreover, these systems can be tailored to mimic specific disease states, facilitating the investigation of disease progression, drug responses, and potential therapeutic interventions. In particular, they can demonstrate, in early-phase pre-clinical studies, the safety and toxicity profiles of potential therapeutic compounds. Furthermore, they play a pivotal role in the in vitro evaluation of drug efficacy and the modeling of human diseases. One of the most promising prospects of organ-on-a-chip technology is to simulate the pathophysiology of specific subpopulations and even individual patients, thereby being used in personalized medicine. By mimicking the physiological responses of diverse patient groups, these systems hold the promise of revolutionizing therapeutic strategies, guiding them towards tailored intervention to the unique needs of each patient. This review presents the development status and evolution of microfluidic platforms that have facilitated the transition from cells to organs recreated on chips and some of the opportunities and applications offered by organ-on-a-chip technology. Additionally, the current potential and future perspectives of these microphysiological systems and the challenges this technology still faces are discussed.},
}

Humans
*Lab-On-A-Chip Devices
Drug Discovery
Animals
Microphysiological Systems

@article {pmid39817858,
year = {2025},
author = {Yang, X and Yan, A and Liu, X and Volkening, A and Zhou, Y},
title = {Single cell-derived multicellular meristem: insights into male-to-hermaphrodite conversion and de novo meristem formation in Ceratopteris.},
journal = {Development (Cambridge, England)},
volume = {152},
number = {3},
pages = {},
pmid = {39817858},
issn = {1477-9129},
support = {NSF DMS 1764421//Northwestern University/ ; R01 GM157611/GM/NIGMS NIH HHS/United States ; SFARI 597491-RWC//Simons Foundation/ ; R01GM157611/GM/NIGMS NIH HHS/United States ; IOS 1931114//National Science Foundation/ ; },
mesh = {*Meristem/cytology/metabolism/growth & development ; Pteridaceae/metabolism/genetics ; Cell Lineage ; Germ Cells, Plant/cytology/metabolism/growth & development ; Cell Division ; },
abstract = {Land plants alternate between asexual sporophytes and sexual gametophytes. Unlike seed plants, ferns develop free-living gametophytes. Gametophytes of the model fern Ceratopteris exhibit two sex types: hermaphrodites with pluripotent meristems and males lacking meristems. In the absence of the pheromone antheridiogen, males convert to hermaphrodites by forming de novo meristems, although the mechanisms remain unclear. Using long-term time-lapse imaging and computational analyses, we captured male-to-hermaphrodite conversion at single-cell resolution and reconstructed the lineage and division atlas of newly formed meristems. Lineage tracing revealed that the de novo-formed meristem originates from a single non-antheridium cell: the meristem progenitor cell (MPC). During conversion, the MPC lineage showed increased mitotic activity, with marginal cells proliferating faster than inner cells. A mathematical model suggested that stochastic variation in cell division, combined with strong inhibitory signals from dividing marginal cells, is sufficient to explain gametophyte dynamics. Experimental disruption of division timing agreed with the model, showing that precise cell cycle progression is essential for MPC establishment and sex-type conversion. These findings reveal cellular mechanisms governing sex conversion and de novo meristem formation in land plants.},
}

*Meristem/cytology/metabolism/growth & development
Pteridaceae/metabolism/genetics
Cell Lineage
Germ Cells, Plant/cytology/metabolism/growth & development
Cell Division

@article {pmid39803458,
year = {2025},
author = {Yoffe, L and Bhinder, B and Kang, SW and Zhang, H and Singh, A and Ravichandran, H and Markowitz, G and Martin, M and Kim, J and Zhang, C and Elemento, O and Tansey, W and Bates, S and McGraw, TE and Borczuk, A and Lee, HS and Altorki, NK and Mittal, V},
title = {Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39803458},
issn = {2692-8205},
support = {R21 AI159379/AI/NIAID NIH HHS/United States ; UH3 CA244697/CA/NCI NIH HHS/United States ; },
abstract = {Computerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules. We found that early disease initiation and subsequent progression are associated with the evolution of immune-suppressive cellular phenotypes characterized by decreased cytotoxic CD8 T and NK cells, increased T cell exhaustion and accumulation of immunosuppressive regulatory T cells (Tregs) and M2-like macrophages expressing TREM2. Within Tregs, we identified a unique population of 4-1BB+ Treg subset enriched for the IL2-STAT5 suppressive pathway with transcription profiles supporting discrete metabolic alterations. Spatial analysis showed increased density of suppressive immune cells around tumor cells, increased exhaustion phenotype of both CD4 and CD8 T cells expressing chemokine CXCL13, and spatial microcomplex of endothelial and lymphocyte interactions within tertiary lymphoid structures. The single-cell architecture identifies determinants of early disease emergence and progression, which may be developed not only as diagnostic/prognostic biomarkers but also as targets for disease interception. Additionally, our dataset constitutes a valuable resource for the preinvasive lung cancer research community.},
}

@article {pmid39801500,
year = {2025},
author = {Putra, VDL and Kilian, KA and Knothe Tate, ML},
title = {Stem cell mechanoadaptation. I. Effect of microtubule stabilization and volume changing stresses on cytoskeletal remodeling.},
journal = {APL bioengineering},
volume = {9},
number = {1},
pages = {016102},
pmid = {39801500},
issn = {2473-2877},
abstract = {Here, we report on the first part of a two-part experimental series to elucidate spatiotemporal cytoskeletal remodeling, which underpins the evolution of stem cell shape and fate, and the emergence of tissue structure and function. In Part I of these studies, we first develop protocols to stabilize microtubules exogenously using paclitaxel (PAX) in a standardized model murine embryonic stem cell line (C3H/10T1/2) to maximize comparability with previously published studies. We then probe native and microtubule-stabilized stem cells' capacity to adapt to volume changing stresses effected by seeding at increasing cell densities, which emulates local compression and tissue template formation during development. Within the concentration range of 1-100 nM, microtubule-stabilized stem cells maintain viability and reduce proliferation. PAX stabilization of microtubules is associated with increased cell volume as well as flattening of the cell and nucleus. Compared to control cells, microtubule-stabilized cells exhibit thick, bundled microtubules and highly aligned, thicker and longer F-actin fibers, corresponding to an increase in the Young's modulus of the cell. Both F-actin and microtubule concentration increase with increasing PAX concentration, whereby the increase in F-actin is more prominent in the basal region of the cell. The corresponding increase in microtubule is observed more globally across the apical and basal region of the cell. Seeding at increasing target densities induces local compression on cells. This increase in local compression modulates cell volume and concomitant increases in F-actin and microtubule concentration to a greater degree than microtubule stabilization via PAX. Cells seeded at high density exhibit higher bulk modulus than corresponding cells seeded at low density. These data demonstrate the capacity of stem cells to adapt to an interplay of mechanical and chemical cues, i.e., respective compression and exogenous microtubule stabilization; the resulting cytoskeletal remodeling manifests as evolution of mechanical properties relevant to development of multicellular tissue constructs.},
}

@article {pmid39793585,
year = {2025},
author = {Liesner, D and Cossard, GG and Zheng, M and Godfroy, O and Barrera-Redondo, J and Haas, FB and Coelho, SM},
title = {Developmental pathways underlying sexual differentiation in the U/V sex chromosome system of giant kelp.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2024.12.022},
pmid = {39793585},
issn = {1878-1551},
abstract = {In many multicellular organisms, sexual development is not determined by XX/XY or ZW/ZZ systems but by U/V sex chromosomes. In U/V systems, sex determination occurs in the haploid phase, with U chromosomes in females and V chromosomes in males. Here, we explore several male, female, and partially sex-reversed male lines of giant kelp to decipher how U/V sex chromosomes and autosomes initiate male versus female development. We identify a key set of genes on the sex chromosomes involved in triggering sexual development and characterize autosomal effector genes underlying sexual differentiation. We show that male, but not female, development involves large-scale transcriptome reorganization with pervasive enrichment in regulatory genes, faster evolutionary rates, and high species-specificity of male-biased genes. Our observations imply that a female-like phenotype is the "ground state", which is complemented by the presence of a U-chromosome but overridden by a dominant male developmental program triggered by the V-chromosome.},
}

@article {pmid39772683,
year = {2025},
author = {Colgren, J and Burkhardt, P},
title = {Electrical signaling and coordinated behavior in the closest relative of animals.},
journal = {Science advances},
volume = {11},
number = {2},
pages = {eadr7434},
pmid = {39772683},
issn = {2375-2548},
mesh = {*Choanoflagellata/physiology ; Animals ; Calcium/metabolism ; Cilia/physiology/metabolism ; Signal Transduction ; },
abstract = {The transition from simple to complex multicellularity involves division of labor and specialization of cell types. In animals, complex sensory-motor systems are primarily built around specialized cells of muscles and neurons, though the evolutionary origins of these and their integration remain unclear. Here, to investigate sensory-behavior coupling in the closest relatives of animals, we established a line of the choanoflagellate, Salpingoeca rosetta, which stably expresses the calcium indicator RGECO1. Using this, we identify a previously unknown cellular behavior associated with electrical signaling, in which ciliary arrest is coupled with apical-basal contraction of the cell. This behavior and the associated calcium transients are synchronized in the multicellular state and result in coordinated ciliary arrest and colony-wide contraction, suggesting that information is spread among the cells. Our work reveals fundamental insights into how choanoflagellates sense and respond to their environment and enhances our understanding of the integration of cellular and organism-wide behavior in the closest protistan relatives of animals.},
}

*Choanoflagellata/physiology
Animals
Calcium/metabolism
Cilia/physiology/metabolism
Signal Transduction

@article {pmid39768330,
year = {2024},
author = {Rehnke, RD},
title = {The "Culture" of Organs: A Holistic Theory on the Origins of the Cancer Tissue Environment.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {12},
pages = {},
pmid = {39768330},
issn = {2075-1729},
abstract = {For over a century, the somatic gene mutation theory of cancer has been a scientific orthodoxy. The recent failures of causal explanations using this theory and the lack of significant progress in addressing the cancer problem medically have led to a new competition of ideas about just what cancer is. This essay presents an alternative view of cancer as a developmental process gone wrong. More specifically, cancer is a breakdown in the autopoietic process of organ maintenance and the multicellular coordination of tissues. Breast cancer is viewed through a systems science perspective as an example of the importance of framing one's theoretical assumptions before making empirical judgments. Finally, a new understanding of the histoarchitecture of the interstitium is presented as a first principle of cancer: a process of cells coming from cells, invading the space between cells.},
}

@article {pmid39763889,
year = {2024},
author = {Park, J and Prokopchuk, G and Popchock, AR and Hao, J and Liao, TW and Yan, S and Hedman, DJ and Larson, JD and Walther, BK and Becker, NA and Basu, A and Maher, LJ and Wheeler, RJ and Asbury, CL and Biggins, S and Lukeš, J and Ha, T},
title = {Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763889},
issn = {2692-8205},
support = {R35 GM143949/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R35 GM122569/GM/NIGMS NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; },
abstract = {Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos, an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.},
}

@article {pmid39763787,
year = {2024},
author = {Week, B and Ralph, PL and Tavalire, HF and Cresko, WA and Bohannan, BJM},
title = {Quantitative Genetics of Microbiome Mediated Traits.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.12.16.628599},
pmid = {39763787},
issn = {2692-8205},
support = {R01 HG012473/HG/NHGRI NIH HHS/United States ; R56 HG011395/HG/NHGRI NIH HHS/United States ; },
abstract = {Multicellular organisms host a rich assemblage of associated microorganisms, collectively known as their "microbiomes". Microbiomes have the capacity to influence their hosts' fitnesses, but the conditions under which such influences contribute to evolution are not clear. This is due in part to a lack of a comprehensive theoretical framework for describing the combined effects of host and associated microbes on phenotypic variation. Here we begin to address this gap by extending the foundations of quantitative genetic theory to include host-associated microbes, as well as alleles of hosts, as factors that explain quantitative host trait variation. We introduce a way to partition host-associated microbiomes into componenents relevant for predicting a microbiome-mediated response to selection. We then apply our general framework to a simulation model of microbiome inheritance to illustrate principles for predicting host trait dynamics, and to generalize classical narrow and broad sense heritabilities to account for microbial effects. We demonstrate that microbiome-mediated responses to host selection can arise from various transmission modes, not solely vertical, with the contribution of non-vertical modes depending on host life history. Our work lays a foundation for integrating microbiome-mediated host variation and adaptation into our understanding of natural variation.},
}

@article {pmid39752622,
year = {2025},
author = {Bandyadka, S and Lebo, DPV and Mondragon, AA and Serizier, SB and Kwan, J and Peterson, JS and Chasse, AY and Jenkins, VK and Calikyan, A and Ortega, AJ and Campbell, JD and Emili, A and McCall, K},
title = {Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis.},
journal = {PLoS genetics},
volume = {21},
number = {1},
pages = {e1011220},
pmid = {39752622},
issn = {1553-7404},
support = {F31 GM115177/GM/NIGMS NIH HHS/United States ; R01 LM013154/LM/NLM NIH HHS/United States ; R35 GM127338/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; *Drosophila melanogaster/genetics ; *Oogenesis/genetics ; Female ; *Apoptosis/genetics ; *Drosophila Proteins/genetics/metabolism ; Oocytes/metabolism ; Ovarian Follicle/metabolism/cytology ; Cell Death/genetics ; Phagocytosis/genetics ; },
abstract = {The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally. Alternatively, stressors such as starvation can induce the death of nurse cells earlier in mid-oogenesis, manifesting apoptosis signatures, followed by their engulfment by epithelial follicle cells. To identify and contrast the molecular pathways underlying these morphologically and genetically distinct cell death paradigms, both mediated by follicle cells, we compared their genome-wide transcriptional, translational, and secretion profiles before and after differentiating to acquire a phagocytic capability, as well as during well-fed and nutrient-deprived conditions. By coupling the GAL4-UAS system to Translating Ribosome Affinity Purification (TRAP-seq) and proximity labeling (HRP-KDEL) followed by Liquid Chromatography tandem mass-spectrometry, we performed high-throughput screens to identify pathways selectively activated or repressed by follicle cells to employ nurse cell-clearance routines. We also integrated two publicly available single-cell RNAseq atlases of the Drosophila ovary to define the transcriptomic profiles of follicle cells. In this report, we describe the genes and major pathways identified in the screens and the striking consequences to Drosophila melanogaster oogenesis caused by RNAi perturbation of prioritized candidates. To our knowledge, our study is the first of its kind to comprehensively characterize two distinct apoptotic and non-apoptotic cell death paradigms in the same multi-cellular system. Beyond molecular differences in cell death, our investigation may also provide insights into how key systemic trade-offs are made between survival and reproduction when faced with physiological stress.},
}

Animals
*Drosophila melanogaster/genetics
*Oogenesis/genetics
Female
*Apoptosis/genetics
*Drosophila Proteins/genetics/metabolism
Oocytes/metabolism
Ovarian Follicle/metabolism/cytology
Cell Death/genetics
Phagocytosis/genetics

@article {pmid39741147,
year = {2024},
author = {Solé, R and Conde-Pueyo, N and Pla-Mauri, J and Garcia-Ojalvo, J and Montserrat, N and Levin, M},
title = {Open problems in synthetic multicellularity.},
journal = {NPJ systems biology and applications},
volume = {10},
number = {1},
pages = {151},
pmid = {39741147},
issn = {2056-7189},
support = {ERCCoG-2020 101002478 ENGINORG//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; Grant 62212//John Templeton Foundation (JTF)/ ; },
mesh = {Animals ; Humans ; Bioengineering/methods ; Biological Evolution ; Models, Biological ; *Synthetic Biology/methods ; Systems Biology/methods ; },
abstract = {Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.},
}

Animals
Humans
Bioengineering/methods
Biological Evolution
Models, Biological
*Synthetic Biology/methods
Systems Biology/methods

@article {pmid39737561,
year = {2025},
author = {Horiuchi, Y and Umakawa, N and Otani, R and Tamada, Y and Kosetsu, K and Hiwatashi, Y and Wakisaka, R and Yoshida, S and Murata, T and Hasebe, M and Ishikawa, M and Kofuji, R},
title = {Physcomitrium LATERAL SUPPRESSOR genes promote formative cell divisions to produce germ cell lineages in both male and female gametangia.},
journal = {The New phytologist},
volume = {245},
number = {5},
pages = {2004-2015},
pmid = {39737561},
issn = {1469-8137},
mesh = {*Cell Division/genetics ; *Cell Lineage/genetics ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Germ Cells, Plant/growth & development/cytology ; *Bryopsida/genetics/growth & development/cytology ; *Genes, Plant ; Transcription Factors/genetics/metabolism ; Ovule/genetics/growth & development/cytology ; Mutation/genetics ; Pollen/genetics/cytology/growth & development ; },
abstract = {The evolution of green plants from aquatic to terrestrial environments is thought to have been facilitated by the acquisition of gametangia, specialized multicellular organs housing gametes. Antheridia and archegonia, responsible for producing and protecting sperm and egg cells, undergo formative cell divisions to produce a cell to differentiate into germ cell lineages and the other cell to give rise to surrounding structures. However, the genes governing this process remain unidentified. We isolated genes expressed during gametangia development from previously established gene-trap lines of Physcomitrium patens and characterized their function during gametangia formation. We identified P. patens LATERAL SUPPRESSOR 1 (PpLAS1) from the gene-trap library, encoding a GRAS transcription factor. The double-deletion mutant with its paralog PpLAS2 failed to form inner cells in both gametangia. PpLASs are expressed in cells undergoing formative cell division, and introducing PpLAS1 into the double-deletion mutant successfully rescued the phenotype. These findings underscore the pivotal role of PpLASs in regulating formative cell divisions, ensuring the separation of reproductive cell lineages from surrounding cells in antheridia and archegonia. Furthermore, they suggest a link between PpLASs and the evolutionary origin of male and female gametangia in the common ancestor of land plants.},
}

*Cell Division/genetics
*Cell Lineage/genetics
*Gene Expression Regulation, Plant
*Plant Proteins/genetics/metabolism
*Germ Cells, Plant/growth & development/cytology
*Bryopsida/genetics/growth & development/cytology
*Genes, Plant
Transcription Factors/genetics/metabolism
Ovule/genetics/growth & development/cytology
Mutation/genetics
Pollen/genetics/cytology/growth & development

@article {pmid39732540,
year = {2025},
author = {Golomb, R and Dahan, O and Dahary, D and Pilpel, Y},
title = {Cell-autonomous adaptation: an overlooked avenue of adaptation in human evolution.},
journal = {Trends in genetics : TIG},
volume = {41},
number = {1},
pages = {12-22},
doi = {10.1016/j.tig.2024.10.009},
pmid = {39732540},
issn = {0168-9525},
mesh = {Animals ; Humans ; *Adaptation, Physiological/genetics ; *Biological Evolution ; Evolution, Molecular ; Mitochondria/genetics/metabolism ; Selection, Genetic/genetics ; },
abstract = {Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.},
}

Animals
Humans
*Adaptation, Physiological/genetics
*Biological Evolution
Evolution, Molecular
Mitochondria/genetics/metabolism
Selection, Genetic/genetics