Systems Biology
Significance of birth in the maintenance of quiescent neural stem cells
Sci Adv. 2025 Jan 24;11(4):eadn6377. doi: 10.1126/sciadv.adn6377. Epub 2025 Jan 22.
ABSTRACT
Birth is one of the most important life events for animals. However, its significance in the developmental process is not fully understood. Here, we found that birth-induced alteration of glutamine metabolism in radial glia (RG), the embryonic neural stem cells (NSCs), is required for the acquisition of quiescence and long-term maintenance of postnatal NSCs. Preterm birth impairs this cellular process, leading to transient hyperactivation of RG. Consequently, in the postnatal brain, the NSC pool is depleted and neurogenesis is decreased. We also found that the maintenance of quiescent RG after preterm birth improves postnatal neurogenesis. This study demonstrates the significance of birth in the maintenance of quiescent NSCs.
PMID:39841848 | DOI:10.1126/sciadv.adn6377
A change language for ontologies and knowledge graphs
Database (Oxford). 2025 Jan 22;2025:baae133. doi: 10.1093/database/baae133.
ABSTRACT
Ontologies and knowledge graphs (KGs) are general-purpose computable representations of some domain, such as human anatomy, and are frequently a crucial part of modern information systems. Most of these structures change over time, incorporating new knowledge or information that was previously missing. Managing these changes is a challenge, both in terms of communicating changes to users and providing mechanisms to make it easier for multiple stakeholders to contribute. To fill that need, we have created KGCL, the Knowledge Graph Change Language (https://github.com/INCATools/kgcl), a standard data model for describing changes to KGs and ontologies at a high level, and an accompanying human-readable Controlled Natural Language (CNL). This language serves two purposes: a curator can use it to request desired changes, and it can also be used to describe changes that have already happened, corresponding to the concepts of "apply patch" and "diff" commonly used for managing changes in text documents and computer programs. Another key feature of KGCL is that descriptions are at a high enough level to be useful and understood by a variety of stakeholders-e.g. ontology edits can be specified by commands like "add synonym 'arm' to 'forelimb'" or "move 'Parkinson disease' under 'neurodegenerative disease'." We have also built a suite of tools for managing ontology changes. These include an automated agent that integrates with and monitors GitHub ontology repositories and applies any requested changes and a new component in the BioPortal ontology resource that allows users to make change requests directly from within the BioPortal user interface. Overall, the KGCL data model, its CNL, and associated tooling allow for easier management and processing of changes associated with the development of ontologies and KGs. Database URL: https://github.com/INCATools/kgcl.
PMID:39841813 | DOI:10.1093/database/baae133
Hypoxia as a medicine
Sci Transl Med. 2025 Jan 22;17(782):eadr4049. doi: 10.1126/scitranslmed.adr4049. Epub 2025 Jan 22.
ABSTRACT
Oxygen is essential for human life, yet a growing body of preclinical research is demonstrating that chronic continuous hypoxia can be beneficial in models of mitochondrial disease, autoimmunity, ischemia, and aging. This research is revealing exciting new and unexpected facets of oxygen biology, but translating these findings to patients poses major challenges, because hypoxia can be dangerous. Overcoming these barriers will require integrating insights from basic science, high-altitude physiology, clinical medicine, and sports technology. Here, we explore the foundations of this nascent field and outline a path to determine how chronic continuous hypoxia can be safely, effectively, and practically delivered to patients.
PMID:39841808 | DOI:10.1126/scitranslmed.adr4049
Transgene-free genome editing in poplar
New Phytol. 2025 Jan 22. doi: 10.1111/nph.20415. Online ahead of print.
ABSTRACT
Precise gene-editing methods are valuable tools to enhance genetic traits. Gene editing is commonly achieved via stable integration of a gene-editing cassette in the plant's genome. However, this technique is unfavorable for field applications, especially in vegetatively propagated plants, such as many commercial tree species, where the gene-editing cassette cannot be segregated away without breaking the genetic constitution of the elite variety. Here, we describe an efficient method for generating gene-edited Populus tremula × P. alba (poplar) trees without incorporating foreign DNA into its genome. Using Agrobacterium tumefaciens, we expressed a base-editing construct targeting CCoAOMT1 along with the ALS genes for positive selection on a chlorsulfuron-containing medium. About 50% of the regenerated shoots were derived from transient transformation and were free of T-DNA. Overall, 7% of the chlorsulfuron-resistant shoots were T-DNA free, edited in the CCoAOMT1 gene and nonchimeric. Long-read whole-genome sequencing confirmed the absence of any foreign DNA in the tested gene-edited lines. Additionally, we evaluated the CodA gene as a negative selection marker to eliminate lines that stably incorporated the T-DNA into their genome. Although the latter negative selection is not essential for selecting transgene-free, gene-edited Populus tremula × P. alba shoots, it may prove valuable for other genotypes or varieties.
PMID:39841625 | DOI:10.1111/nph.20415
Deep learning-based image classification reveals heterogeneous execution of cell death fates during viral infection
Mol Biol Cell. 2025 Jan 22:mbcE24100438. doi: 10.1091/mbc.E24-10-0438. Online ahead of print.
ABSTRACT
Cell fate decisions, such as proliferation, differentiation, and death, are driven by complex molecular interactions and signaling cascades. While significant progress has been made in understanding the molecular determinants of these processes, historically, cell fate transitions were identified through light microscopy that focused on changes in cell morphology and function. Modern techniques have shifted towards probing molecular effectors to quantify these transitions, offering more precise quantification and mechanistic understanding. However, challenges remain in cases where the molecular signals are ambiguous, complicating the assignment of cell fate. During viral infection, programmed cell death (PCD) pathways, including apoptosis, necroptosis, and pyroptosis, exhibit complex signaling and molecular crosstalk. This can lead to simultaneous activation of multiple PCD pathways, which confounds assignment of cell fate based on molecular information alone. To address this challenge, we employed deep learning-based image classification of dying cells to analyze PCD in single Herpes Simplex Virus-1 (HSV-1)-infected cells. Our approach reveals that despite heterogeneous activation of signaling, individual cells adopt predominantly prototypical death morphologies. Nevertheless, PCD is executed heterogeneously within a uniform population of virus-infected cells and varies over time. These findings demonstrate that image-based phenotyping can provide valuable insights into cell fate decisions, complementing molecular assays. [Media: see text] [Media: see text] [Media: see text] [Media: see text].
PMID:39841552 | DOI:10.1091/mbc.E24-10-0438
Multisensory integration operates on correlated input from unimodal transient channels
Elife. 2025 Jan 22;12:RP90841. doi: 10.7554/eLife.90841.
ABSTRACT
Audiovisual information reaches the brain via both sustained and transient input channels, representing signals' intensity over time or changes thereof, respectively. To date, it is unclear to what extent transient and sustained input channels contribute to the combined percept obtained through multisensory integration. Based on the results of two novel psychophysical experiments, here we demonstrate the importance of the transient (instead of the sustained) channel for the integration of audiovisual signals. To account for the present results, we developed a biologically inspired, general-purpose model for multisensory integration, the multisensory correlation detectors, which combines correlated input from unimodal transient channels. Besides accounting for the results of our psychophysical experiments, this model could quantitatively replicate several recent findings in multisensory research, as tested against a large collection of published datasets. In particular, the model could simultaneously account for the perceived timing of audiovisual events, multisensory facilitation in detection tasks, causality judgments, and optimal integration. This study demonstrates that several phenomena in multisensory research that were previously considered unrelated, all stem from the integration of correlated input from unimodal transient channels.
PMID:39841060 | DOI:10.7554/eLife.90841
Murine Models and Human Cell Line Models to Study Altered Dynamics of Ovarian Follicles in Polycystic Ovary Syndrome
Adv Biol (Weinh). 2025 Jan 22:e2400713. doi: 10.1002/adbi.202400713. Online ahead of print.
ABSTRACT
Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models are used to analyze various aspects of the pathology by replicating the conditions of the syndrome. Even though the complexity of polycystic ovary syndrome and the challenge of reproducing all its features leave several questions unanswered, studies conducted to date have elucidated some of the alterations in ovarian follicle molecular and cellular mechanisms involved in the syndrome, and do not require the employment of complex and invasive techniques on human patients. This review examines ovarian functions and their alterations in polycystic ovary syndrome, explores preclinical in vivo and in vitro models, and highlights emerging research and medical perspectives. It targets researchers, healthcare professionals, and academics, including endocrinologists, cell biologists, and reproductive medicine specialists, studying the molecular and cellular mechanisms of the syndrome.
PMID:39840999 | DOI:10.1002/adbi.202400713
LEA_4 motifs function alone and in conjunction with synergistic cosolutes to protect a labile enzyme during desiccation
Protein Sci. 2025 Feb;34(2):e70028. doi: 10.1002/pro.70028.
ABSTRACT
Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by 11-residue motifs, plays a crucial role in the desiccation tolerance of numerous species. However, the role of these motifs in the function of LEA_4 proteins is unclear, with some studies finding that they recapitulate the function of full-length LEA_4 proteins in vivo, and other studies finding the opposite result. In this study, we characterize the ability of LEA_4 motifs to protect a desiccation-sensitive enzyme, citrate synthase (CS), from loss of function during desiccation. We show here that LEA_4 motifs not only prevent the loss of function of CS during desiccation but also that they can do so more robustly via synergistically interactions with cosolutes. Our analysis further suggests that cosolutes induce synergy with LEA_4 motifs in a manner that correlates with transfer free energy. This research advances our understanding of LEA_4 proteins by demonstrating that during desiccation their motifs can protect specific clients to varying degrees and that their protective capacity is modulated by their chemical environment. Our findings extend beyond the realm of desiccation tolerance, offering insights into the interplay between IDPs and cosolutes. By investigating the function of LEA_4 motifs, we highlight broader strategies for understanding protein stability and function.
PMID:39840786 | DOI:10.1002/pro.70028
WDR74-Mediated Ribosome Biogenesis and Proteome Dynamics During Mouse Preimplantation Development
Genes Cells. 2025 Jan;30(1):e70001. doi: 10.1111/gtc.70001.
ABSTRACT
Preimplantation embryonic development is orchestrated by dynamic changes in the proteome and transcriptome, regulated by mechanisms such as maternal-to-zygotic transition. Here, we employed label-free quantitative proteomics to comprehensively analyze proteome dynamics from germinal vesicle oocytes to blastocysts in mouse embryos. We identified 3490 proteins, including 715 consistently detected across all stages, revealing stage-specific changes in proteins associated with translation, protein modification, and mitochondrial metabolism. Comparison with transcriptomic data highlighted a low correlation between mRNA and protein levels, underscoring the significance of non-transcriptional regulatory mechanisms during early development. Additionally, we analyzed WD repeat-containing protein 74 (WDR74)-deficient embryos generated using CRISPR-Cas9 genome editing. WDR74, a pre-60S ribosome maturation factor, was found to be critical for ribosome biogenesis and cell division. Furthermore, WDR74 deficiency led to a significant reduction in ribosomal protein large subunit and impaired progression beyond the morula stage. Key ribosomal proteins such as ribosomal protein L24 (RPL24) and ribosomal protein L26 (RPL26), which influence cell division timing, were notably affected, while small subunit proteins remained largely unchanged. Taken together, our study demonstrates the utility of integrating genome editing with proteomic analysis to elucidate molecular mechanisms underlying early embryogenesis, and provides new insights into protein-level regulation of preimplantation development.
PMID:39840464 | DOI:10.1111/gtc.70001
Review of cancer cell volatile organic compounds: their metabolism and evolution
Front Mol Biosci. 2025 Jan 7;11:1499104. doi: 10.3389/fmolb.2024.1499104. eCollection 2024.
ABSTRACT
Cancer is ranked as the top cause of premature mortality. Volatile organic compounds (VOCs) are produced from catalytic peroxidation by reactive oxygen species (ROS) and have become a highly attractive non-invasive cancer screening approach. For future clinical applications, however, the correlation between cancer hallmarks and cancer-specific VOCs requires further study. This review discusses and compares cellular metabolism, signal transduction as well as mitochondrial metabolite translocation in view of cancer evolution and the basic biology of VOCs production. Certain cancerous characteristics as well as the origin of the ROS removal system date back to procaryotes and early eukaryotes and share commonalities with non-cancerous proliferative cells. This calls for future studies on metabolic cross talks and regulation of the VOCs production pathway.
PMID:39840075 | PMC:PMC11747368 | DOI:10.3389/fmolb.2024.1499104
Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
Front Immunol. 2025 Jan 7;15:1488860. doi: 10.3389/fimmu.2024.1488860. eCollection 2024.
ABSTRACT
INTRODUCTION: T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
METHODS: Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.
RESULTS: Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]).
DISCUSSION: The approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.
PMID:39840037 | PMC:PMC11747429 | DOI:10.3389/fimmu.2024.1488860
Comparison of sampling and culture methods for the recovery of yeast from hospital surfaces
Antimicrob Steward Healthc Epidemiol. 2025 Jan 17;5(1):e10. doi: 10.1017/ash.2024.481. eCollection 2025.
ABSTRACT
OBJECTIVE: To compare the recovery of yeast from hospital surfaces from two different collection methods: Eswab moistened with molecular water, and premoistened stick-mounted sponge.
DESIGN: Comparison of collection methods for the recovery of yeast in the hospital environment.
SETTING: This study took place at intensive care units of a large academic medical center.
PMID:39839357 | PMC:PMC11748012 | DOI:10.1017/ash.2024.481
MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays
Genome Biol. 2025 Jan 21;26(1):13. doi: 10.1186/s13059-025-03476-y.
ABSTRACT
Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.org/ ) with four key improvements to the MAVE community's database of record: more available data including over 7 million variant effect measurements, an improved data model supporting assays such as saturation genome editing, new built-in exploration and visualization tools, and powerful APIs for data federation and streamlined submission and access. Together these changes support MaveDB's role as a hub for the analysis and dissemination of MAVEs now and into the future.
PMID:39838450 | DOI:10.1186/s13059-025-03476-y
Data-driven model discovery and model selection for noisy biological systems
PLoS Comput Biol. 2025 Jan 21;21(1):e1012762. doi: 10.1371/journal.pcbi.1012762. eCollection 2025 Jan.
ABSTRACT
Biological systems exhibit complex dynamics that differential equations can often adeptly represent. Ordinary differential equation models are widespread; until recently their construction has required extensive prior knowledge of the system. Machine learning methods offer alternative means of model construction: differential equation models can be learnt from data via model discovery using sparse identification of nonlinear dynamics (SINDy). However, SINDy struggles with realistic levels of biological noise and is limited in its ability to incorporate prior knowledge of the system. We propose a data-driven framework for model discovery and model selection using hybrid dynamical systems: partial models containing missing terms. Neural networks are used to approximate the unknown dynamics of a system, enabling the denoising of the data while simultaneously learning the latent dynamics. Simulations from the fitted neural network are then used to infer models using sparse regression. We show, via model selection, that model discovery using hybrid dynamical systems outperforms alternative approaches. We find it possible to infer models correctly up to high levels of biological noise of different types. We demonstrate the potential to learn models from sparse, noisy data in application to a canonical cell state transition using data derived from single-cell transcriptomics. Overall, this approach provides a practical framework for model discovery in biology in cases where data are noisy and sparse, of particular utility when the underlying biological mechanisms are partially but incompletely known.
PMID:39836686 | DOI:10.1371/journal.pcbi.1012762
Small extracellular vesicles derived from sequential stimulation of canine adipose-derived mesenchymal stem cells enhance anti-inflammatory activity
BMC Vet Res. 2025 Jan 21;21(1):31. doi: 10.1186/s12917-024-04465-2.
ABSTRACT
BACKGROUND: Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are recognized for their therapeutic potential in immune modulation and tissue repair, especially in veterinary medicine. This study introduces an innovative sequential stimulation (IVES) technique, involving low-oxygen gas mixture preconditioning using in vitro fertilization gas (IVFG) and direct current electrical stimulation (ES20), to enhance the anti-inflammatory properties of sEVs from canine adipose-derived MSCs (cAD-MSCs). Initial steps involved isolation and comprehensive characterization of cAD-MSCs, including morphology, gene expression, and differentiation potentials, alongside validation of the electrical stimulation protocol. IVFG, ES20, and IVES were applied simultaneously with a control condition. Stimulated cAD-MSCs were evaluated for morphological changes, cell viability, and gene expressions. Conditioned media were collected and purified for sEV isolation on Day1, Day2, and Day3. To validate the efficacy of IVES for sEV production, various analyses were conducted, including microscopic examination, surface marker assessment, zeta-potential measurement, protein quantification, nanoparticle tracking analysis, and determination of anti-inflammatory activity.
RESULTS: We found that IVES demonstrated non-cytotoxicity and induced crucial genotypic changes associated with sEV production in cAD-MSCs. Interestingly, IVFG influenced cellular adaptation, while ES20 induced hypoxia activation. By merging these stimulations, IVES enhanced sEV stability and quality profiles. The cAD-MSC-derived sEVs exhibited anti-inflammatory activity in lipopolysaccharide-induced RAW264.7 macrophages, emphasizing their improved effectiveness without cytotoxicity or immunogenicity. These effects were consistent across day 3 collection, indicating the establishment of an effective protocol for sEV production.
CONCLUSIONS: This research established an innovative sequential stimulation method with positive impact on sEV characteristics including stability, quality, and anti-inflammatory activity. This study not only contributes to the enhancement of sEV production but also sheds light on their functional aspects for therapeutic interventions.
PMID:39838398 | DOI:10.1186/s12917-024-04465-2
Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction
Commun Biol. 2025 Jan 21;8(1):105. doi: 10.1038/s42003-025-07457-6.
ABSTRACT
Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction. Mechanistically, we show that excess BCAA-induced mitochondrial reactive oxygen species (ROS) triggered the binding of protein phosphatase 2 A catalytic subunit (PP2Ac) to AMPK, suppressing AMPK activity. This initiated a dysregulated feedback loop of AMPK-mitochondrial interactions, exacerbating mitochondrial dysfunction and oxidative neuronal damage. Our study identifies BCAA imbalance as a critical driver of neuronal damage through AMPK suppression and autophagy dysfunction, offering insights into metabolic-neuronal interactions in neurological diseases and potential therapeutic targets for BCAA-related neurological conditions.
PMID:39838082 | DOI:10.1038/s42003-025-07457-6
Transport and inhibition mechanism for human TauT-mediated taurine uptake
Cell Res. 2025 Jan 21. doi: 10.1038/s41422-025-01076-w. Online ahead of print.
NO ABSTRACT
PMID:39837997 | DOI:10.1038/s41422-025-01076-w
Comprehensive evaluation of pure and hybrid collaborative filtering in drug repurposing
Sci Rep. 2025 Jan 21;15(1):2711. doi: 10.1038/s41598-025-85927-x.
ABSTRACT
Drug development is known to be a costly and time-consuming process, which is prone to high failure rates. Drug repurposing allows drug discovery by reusing already approved compounds. The outcomes of past clinical trials can be used to predict novel drug-disease associations by leveraging drug- and disease-related similarities. To tackle this classification problem, collaborative filtering with implicit feedback (and potentially additional data on drugs and diseases) has become popular. It can handle large imbalances between negative and positive known associations and known and unknown associations. However, properly evaluating the improvement over the state of the art is challenging, as there is no consensus approach to compare models. We propose a reproducible methodology for comparing collaborative filtering-based drug repurposing. We illustrate this method by comparing 11 models from the literature on eight diverse drug repurposing datasets. Based on this benchmark, we derive guidelines to ensure a fair and comprehensive evaluation of the performance of those models. In particular, an uncontrolled bias on unknown associations might lead to severe data leakage and a misestimation of the model's true performance. Moreover, in drug repurposing, the ability of a model to extrapolate beyond its training distribution is crucial and should also be assessed. Finally, we identified a subcategory of collaborative filtering that seems efficient and robust to distribution shifts. Benchmarks constitute an essential step towards increased reproducibility and more accessible development of competitive drug repurposing methods.
PMID:39837888 | DOI:10.1038/s41598-025-85927-x
Coronin1A regulates the trafficking of alpha synuclein in microglia
J Neurosci. 2025 Jan 21:e1337242025. doi: 10.1523/JNEUROSCI.1337-24.2025. Online ahead of print.
ABSTRACT
Microglia respond to cytotoxic protein aggregates associated with the progression of neurodegenerative disease. Pathological protein aggregates activate the microglial NLRP3 inflammasome resulting in proinflammatory signaling, secretion, and potentially pyroptotic cell death. We characterized mixed sex primary mouse microglia exposed to microbial stressors and alpha synuclein preformed fibrils (αsyn PFFs) to identify cellular mechanisms related to Parkinson's disease. Microglia package and release the endosome fate regulator Coronin1A (Coro1A) in EVs in an Nlrp3-dependent manner in widely used experimental activation conditions. We were surprised to find that Coro1A packaging and release was not Nlrp3-dependent in αsyn PFF exposure conditions. Coro1A-/- microglia exposed to αsyn PFFs trafficked more αsyn to lysosomal compartment increasing lysosomal membrane permeabilization. This corresponds to a decrease in αsyn released in EVs suggesting that Coro1A functions to shunt pathological proteins to a secretory pathway to attenuate lysosomal stress. αsyn PFF driven lysosomal stress resulting from Coro1a loss was associated with enhanced cytotoxicity. Intrinsic apoptosis signaling was unaffected, but we observed elevated cytosolic cathepsin B and the presence of a cathepsin associated 55kD PARP cleavage product. Post-mortem analysis of the PD mesencephalon supported a role for Coro1a in microglia, revealing elevated levels of Coro1A protein in human PD brains compared to those of healthy donors. Findings are relevant to the distribution of pathological αsyn and indicate that Coro1a protects microglia from lysosomal overload, inflammasome activation, and pyroptotic demise.Significance Statement Microglia are responsible for clearing toxic protein aggregates such as alpha synuclein (αsyn) in Parkinson's Disease (PD). PD is slowly progressive, implying that microglia are under proteinaceous stress for an extended time, maintaining some level of homeostasis while attempting to clear pathologically aggregated proteins. Pathological proteins can overload the lysosomes resulting in rupture, decreasing the ability of microglia to clear protein aggregates, and contributing to a hyperreactive inflammatory state. We determined that the protein Coronin1A functions in microglia to attenuate αsyn-induced lysosomal stress, preventing Nlrp3-inflammasome activation, and cell death. These findings identify a protective cellular mechanism operating in microglia that may contribute to the distribution of pathological proteins into the microenvironment.
PMID:39837661 | DOI:10.1523/JNEUROSCI.1337-24.2025
Continuous colonization of the Atlantic coastal rain forests of South America from Amazônia
Proc Biol Sci. 2025 Jan;292(2039):20241559. doi: 10.1098/rspb.2024.1559. Epub 2025 Jan 22.
ABSTRACT
The two main extensions of rain forest in South America are the Amazon (Amazônia) and the Atlantic rain forest (Mata Atlântica), which are separated by a wide 'dry diagonal' of seasonal vegetation. We used the species-rich tree genus Inga to test if Amazônia-Mata Atlântica dispersals have been clustered during specific time periods corresponding to past, humid climates. We performed hybrid capture DNA sequencing of 810 nuclear loci for 453 accessions representing 164 species that included 62% of Mata Atlântica species and estimated a dated phylogeny for all accessions using maximum likelihood, and a species-level tree using coalescent methods. There have been 16-20 dispersal events to the Mata Atlântica from Amazônia with only one or two dispersals in the reverse direction. These events have occurred over the evolutionary history of Inga, with no evidence for temporal clustering, and model comparisons of alternative biogeographic histories and null simulations showing the timing of dispersal events matches a random expectation. Time-specific biogeographic corridors are not required to explain dispersal between Amazônia and the Mata Atlântica for rain forest trees such as Inga, which are likely to have used a dendritic net of gallery forests to cross the dry diagonal.
PMID:39837505 | DOI:10.1098/rspb.2024.1559