PLoS Biology最新文献

{"title":"Harnessing plant biosynthesis for the development of next-generation therapeutics.","authors":"Philip Spence, James Reed, Anne Osbourn","doi":"10.1371/journal.pbio.3002886","DOIUrl":"10.1371/journal.pbio.3002886","url":null,"abstract":"<p><p>Genomics-based predictions indicate that plants harbor the ability to make a vast array of as yet undiscovered chemistry. Recent advances open up the potential to harness this capability at unprecedented scale for the discovery and development of new therapeutics.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002886"},"PeriodicalIF":9.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region.","authors":"Armando Romani, Alberto Antonietti, Davide Bella, Julian Budd, Elisabetta Giacalone, Kerem Kurban, Sára Sáray, Marwan Abdellah, Alexis Arnaudon, Elvis Boci, Cristina Colangelo, Jean-Denis Courcol, Thomas Delemontex, András Ecker, Joanne Falck, Cyrille Favreau, Michael Gevaert, Juan B Hernando, Joni Herttuainen, Genrich Ivaska, Lida Kanari, Anna-Kristin Kaufmann, James Gonzalo King, Pramod Kumbhar, Sigrun Lange, Huanxiang Lu, Carmen Alina Lupascu, Rosanna Migliore, Fabien Petitjean, Judit Planas, Pranav Rai, Srikanth Ramaswamy, Michael W Reimann, Juan Luis Riquelme, Nadir Román Guerrero, Ying Shi, Vishal Sood, Mohameth François Sy, Werner Van Geit, Liesbeth Vanherpe, Tamás F Freund, Audrey Mercer, Eilif Muller, Felix Schürmann, Alex M Thomson, Michele Migliore, Szabolcs Káli, Henry Markram","doi":"10.1371/journal.pbio.3002861","DOIUrl":"10.1371/journal.pbio.3002861","url":null,"abstract":"<p><p>The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002861"},"PeriodicalIF":9.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of the 12 major human breast cell types reveals mechanisms of cell and tissue function.","authors":"Katelyn Del Toro, Rosalyn Sayaman, Kate Thi, Yamhilette Licon-Munoz, William Curtis Hines","doi":"10.1371/journal.pbio.3002820","DOIUrl":"10.1371/journal.pbio.3002820","url":null,"abstract":"<p><p>A fundamental question in biology, central to our understanding of cancer and other pathologies, is determining how different cell types coordinate to form and maintain tissues. Recognizing the distinct features and capabilities of the cells that compose these tissues is critical. Unfortunately, the complexity of tissues often hinders our ability to distinguish between neighboring cell types and, in turn, scrutinize their transcriptomes and generate reliable and tractable cell models for studying their inherently different biologies. We have recently introduced a novel method that permits the identification and purification of the 12 cell types that compose the human breast-nearly all of which could be reliably propagated in the laboratory. Here, we explore the nature of these cell types. We sequence mRNAs from each purified population and investigate transcriptional patterns that reveal their distinguishing features. We describe the differentially expressed genes and enriched biological pathways that capture the essence of each cell type, and we highlight transcripts that display intriguing expression patterns. These data, analytic tools, and transcriptional analyses form a rich resource whose exploration provides remarkable insights into the inner workings of the cell types composing the breast, thus furthering our understanding of the rules governing normal cell and tissue function.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002820"},"PeriodicalIF":9.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomedical researchers' perspectives on the reproducibility of research.","authors":"Kelly D Cobey, Sanam Ebrahimzadeh, Matthew J Page, Robert T Thibault, Phi-Yen Nguyen, Farah Abu-Dalfa, David Moher","doi":"10.1371/journal.pbio.3002870","DOIUrl":"10.1371/journal.pbio.3002870","url":null,"abstract":"<p><p>We conducted an international cross-sectional survey of biomedical researchers' perspectives on the reproducibility of research. This study builds on a widely cited 2016 survey on reproducibility and provides a biomedical-specific and contemporary perspective on reproducibility. To sample the community, we randomly selected 400 journals indexed in MEDLINE, from which we extracted the author names and emails from all articles published between October 1, 2020 and October 1, 2021. We invited participants to complete an anonymous online survey which collected basic demographic information, perceptions about a reproducibility crisis, perceived causes of irreproducibility of research results, experience conducting reproducibility studies, and knowledge of funding and training for research on reproducibility. A total of 1,924 participants accessed our survey, of which 1,630 provided useable responses (response rate 7% of 23,234). Key findings include that 72% of participants agreed there was a reproducibility crisis in biomedicine, with 27% of participants indicating the crisis was \"significant.\" The leading perceived cause of irreproducibility was a \"pressure to publish\" with 62% of participants indicating it \"always\" or \"very often\" contributes. About half of the participants (54%) had run a replication of their own previously published study while slightly more (57%) had run a replication of another researcher's study. Just 16% of participants indicated their institution had established procedures to enhance the reproducibility of biomedical research and 67% felt their institution valued new research over replication studies. Participants also reported few opportunities to obtain funding to attempt to reproduce a study and 83% perceived it would be harder to do so than to get funding to do a novel study. Our results may be used to guide training and interventions to improve research reproducibility and to monitor rates of reproducibility over time. The findings are also relevant to policy makers and academic leadership looking to create incentives and research cultures that support reproducibility and value research quality.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002870"},"PeriodicalIF":9.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic extracellular vesicles carrying Mif regulate macrophage recruitment and compensatory proliferation in neighboring epithelial stem cells during tissue maintenance.","authors":"Safia A Essien, Ivanshi Ahuja, George T Eisenhoffer","doi":"10.1371/journal.pbio.3002194","DOIUrl":"10.1371/journal.pbio.3002194","url":null,"abstract":"<p><p>Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss to maintain tissue homeostasis. While apoptotic cell-derived extracellular vesicles (AEVs) can transmit instructional cues to mediate communication with neighboring cells, the molecular mechanisms that induce cell division are not well understood. Here, we show that macrophage migration inhibitory factor (Mif)-containing AEVs regulate compensatory proliferation via ERK signaling in epithelial stem cells of larval zebrafish. Time-lapse imaging showed efferocytosis of AEVs from dying epithelial stem cells by healthy neighboring stem cells. Proteomic and ultrastructure analysis of purified AEVs identified Mif localization on the AEV surface. Pharmacological inhibition or genetic mutation of Mif, or its cognate receptor CD74, decreased levels of phosphorylated ERK and compensatory proliferation in the neighboring epithelial stem cells. Disruption of Mif activity also caused decreased numbers of macrophages patrolling near AEVs, while depletion of the macrophage lineage resulted in a reduced proliferative response by the epithelial stem cells. We propose that AEVs carrying Mif directly stimulate epithelial stem cell repopulation and guide macrophages to cell non-autonomously induce localized proliferation to sustain overall cell numbers during tissue maintenance.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002194"},"PeriodicalIF":9.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climate and ecology predict latitudinal trends in sexual selection inferred from avian mating systems.","authors":"Robert A Barber, Jingyi Yang, Chenyue Yang, Oonagh Barker, Tim Janicke, Joseph A Tobias","doi":"10.1371/journal.pbio.3002856","DOIUrl":"10.1371/journal.pbio.3002856","url":null,"abstract":"<p><p>Sexual selection, one of the central pillars of evolutionary theory, has powerful effects on organismal morphology, behaviour, and population dynamics. However, current knowledge about geographical variation in this evolutionary mechanism and its underlying drivers remains highly incomplete, in part because standardised data on the strength of sexual selection is sparse even for well-studied organisms. Here, we use information on mating systems-including the incidence of polygamy and extra-pair paternity-to estimate the intensity of sexual selection in 10,671 (>99.9%) bird species distributed worldwide. We show that avian sexual selection varies latitudinally, peaking at higher latitudes, although the gradient is reversed in the world's most sexually selected birds-specialist frugivores-which are strongly associated with tropical forests. Phylogenetic models further reveal that the strength of sexual selection is explained by temperature seasonality coupled with a suite of climate-associated factors, including migration, diet, and territoriality. Overall, these analyses suggest that climatic conditions leading to short, intense breeding seasons, or highly abundant and patchy food resources, increase the potential for polygamy in birds, driving latitudinal gradients in sexual selection. Our findings help to resolve longstanding debates about spatial variation in evolutionary mechanisms linked to reproductive biology and also provide a comprehensive species-level data set for further studies of selection and phenotypic evolution in the context of global climatic change.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002856"},"PeriodicalIF":9.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid accelerator polyphosphate fits as the mystery density in α-synuclein fibrils.","authors":"Philipp Huettemann, Pavithra Mahadevan, Justine Lempart, Eric Tse, Budheswar Dehury, Brian F P Edwards, Daniel R Southworth, Bikash R Sahoo, Ursula Jakob","doi":"10.1371/journal.pbio.3002650","DOIUrl":"10.1371/journal.pbio.3002650","url":null,"abstract":"<p><p>Aberrant aggregation of α-Synuclein is the pathological hallmark of a set of neurodegenerative diseases termed synucleinopathies. Recent advances in cryo-electron microscopy have led to the structural determination of the first synucleinopathy-derived α-Synuclein fibrils, which contain a non-proteinaceous, \"mystery density\" at the core of the protofilaments, hypothesized to be highly negatively charged. Guided by previous studies that demonstrated that polyphosphate (polyP), a universally conserved polyanion, significantly accelerates α-Synuclein fibril formation, we conducted blind docking and molecular dynamics simulation experiments to model the polyP binding site in α-Synuclein fibrils. Here, we demonstrate that our models uniformly place polyP into the lysine-rich pocket, which coordinates the mystery density in patient-derived fibrils. Subsequent in vitro studies and experiments in cells revealed that substitution of the 2 critical lysine residues K43 and K45 with alanine residues leads to a loss of all previously reported effects of polyP binding on α-Synuclein, including stimulation of fibril formation, change in filament conformation and stability as well as alleviation of cytotoxicity. In summary, our study demonstrates that polyP fits the unknown electron density present in in vivo α-Synuclein fibrils and suggests that polyP exerts its functions by neutralizing charge repulsion between neighboring lysine residues.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 10","pages":"e3002650"},"PeriodicalIF":9.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multichannel electrophysiological approach to noninvasively and precisely record human spinal cord activity.","authors":"Birgit Nierula, Tilman Stephani, Emma Bailey, Merve Kaptan, Lisa-Marie Geertje Pohle, Ulrike Horn, André Mouraux, Burkhard Maess, Arno Villringer, Gabriel Curio, Vadim V Nikulin, Falk Eippert","doi":"10.1371/journal.pbio.3002828","DOIUrl":"10.1371/journal.pbio.3002828","url":null,"abstract":"<p><p>The spinal cord is of fundamental importance for integrative processing in brain-body communication, yet routine noninvasive recordings in humans are hindered by vast methodological challenges. Here, we overcome these challenges by developing an easy-to-use electrophysiological approach based on high-density multichannel spinal recordings combined with multivariate spatial-filtering analyses. These advances enable a spatiotemporal characterization of spinal cord responses and demonstrate a sensitivity that permits assessing even single-trial responses. To furthermore enable the study of integrative processing along the neural processing hierarchy in somatosensation, we expand this approach by simultaneous peripheral, spinal, and cortical recordings and provide direct evidence that bottom-up integrative processing occurs already within the spinal cord and thus after the first synaptic relay in the central nervous system. Finally, we demonstrate the versatility of this approach by providing noninvasive recordings of nociceptive spinal cord responses during heat-pain stimulation. Beyond establishing a new window on human spinal cord function at millisecond timescale, this work provides the foundation to study brain-body communication in its entirety in health and disease.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 10","pages":"e3002828"},"PeriodicalIF":9.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia cannibalism during neurodevelopment results in necroptotic cell death.","authors":"F Chris Bennett, Mariko L Bennett","doi":"10.1371/journal.pbio.3002869","DOIUrl":"10.1371/journal.pbio.3002869","url":null,"abstract":"<p><p>Clearance of dying neurons by microglia is critical to healthy neurodevelopment, but what else do microglia eat? A new study in PLOS Biology demonstrates that microglia not only eat neurons but each other, and that this \"microglia cannibalism\" causes necroptotic cell death.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 10","pages":"e3002869"},"PeriodicalIF":9.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ortholog of autism candidate gene RBM27 regulates mitoribosomal assembly factor MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment.","authors":"Tamjid A Chowdhury, David A Luy, Garrett Scapellato, Dorian Farache, Amy S Y Lee, Christopher C Quinn","doi":"10.1371/journal.pbio.3002876","DOIUrl":"10.1371/journal.pbio.3002876","url":null,"abstract":"<p><p>Mitochondrial dysfunction is thought to be a key component of neurodevelopmental disorders such as autism, intellectual disability, and attention-deficit hyperactivity disorder (ADHD). However, little is known about the molecular mechanisms that protect against mitochondrial dysfunction during neurodevelopment. Here, we address this question through the investigation of rbm-26, the Caenorhabditis elegans ortholog of the RBM27 autism candidate gene, which encodes an RNA-binding protein whose role in neurons is unknown. We report that RBM-26 (RBM26/27) protects against axonal defects by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Autism-associated missense variants in RBM-26 cause a sharp decrease in RBM-26 protein expression along with defects in axon overlap and axon degeneration that occurs during larval development. Using a biochemical screen, we identified the mRNA for the MALS-1 mitoribosomal assembly factor as a binding partner for RBM-26. Loss of RBM-26 function causes a dramatic overexpression of mals-1 mRNA and MALS-1 protein. Moreover, genetic analysis indicates that this overexpression of MALS-1 is responsible for the mitochondrial and axon degeneration defects in rbm-26 mutants. These observations reveal a mechanism that regulates expression of a mitoribosomal assembly factor to protect against axon degeneration during neurodevelopment.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 10","pages":"e3002876"},"PeriodicalIF":9.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}