PLoS Biology最新文献

{"title":"Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.","authors":"Lavisha Parab, Jordan Romeyer Dherbey, Norma Rivera, Michael Schwarz, Jenna Gallie, Frederic Bertels","doi":"10.1371/journal.pbio.3002952","DOIUrl":"10.1371/journal.pbio.3002952","url":null,"abstract":"<p><p>Bacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic synergism. The evolutionary mechanism(s) behind such synergistic interactions remain largely unclear. Here, we show that the presence of antibiotics can affect the evolution of resistance to phage infection, using phage ΦX174 and Escherichia coli C. We use a collection of 34 E. coli C LPS strains, each of which is resistant to ΦX174, and has either a \"rough\" or \"deep rough\" LPS phenotype. Growth of the bacterial strains with the deep rough phenotype is inhibited at low concentrations of chloramphenicol and, to a much lesser degree, gentamicin. Treating E. coli C wild type with ΦX174 and chloramphenicol eliminates the emergence of mutants with the deep rough phenotype, and thereby slows the evolution of resistance to phage infection. At slightly lower chloramphenicol concentrations, phage resistance rates are similar to those observed at high concentrations; yet, we show that the diversity of possible mutants is much larger than at higher chloramphenicol concentrations. These data suggest that specific antibiotic concentrations can lead to synergistic phage-antibiotic interactions that disappear at higher antibiotic concentrations. Overall, we show that the change in survival of various ΦX174-resistant E. coli C mutants in the presence of antibiotics can explain the observed phage-antibiotic synergism.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002952"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014628","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":"Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.","authors":"Nicolas Tessandier, Baptiste Elie, Vanina Boué, Christian Selinger, Massilva Rahmoun, Claire Bernat, Sophie Grasset, Soraya Groc, Anne-Sophie Bedin, Thomas Beneteau, Marine Bonneau, Christelle Graf, Nathalie Jacobs, Tsukushi Kamiya, Marion Kerioui, Julie Lajoie, Imène Melki, Jean-Luc Prétet, Bastien Reyné, Géraldine Schlecht-Louf, Mircea T Sofonea, Olivier Supplisson, Chris Wymant, Vincent Foulongne, Jérémie Guedj, Christophe Hirtz, Marie-Christine Picot, Jacques Reynes, Vincent Tribout, Édouard Tuaillon, Tim Waterboer, Michel Segondy, Ignacio G Bravo, Nathalie Boulle, Carmen Lía Murall, Samuel Alizon","doi":"10.1371/journal.pbio.3002949","DOIUrl":"10.1371/journal.pbio.3002949","url":null,"abstract":"<p><p>Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies. To understand viral and immune dynamics in non-persisting HPV infections, we set up an observational longitudinal cohort study with frequent on-site visits for biological sample collection. We enrolled 189 women aged from 18 to 25 and living in the area of Montpellier (France) between 2016 and 2020. We performed 974 on-site visits for a total of 1,619 months of follow-up. We collected data on virus load, local immune cell populations, local concentrations of cytokines, and circulating antibody titres. Using hierarchical Bayesian statistical modelling to simultaneously analyse the data from 164 HPV infections from 76 participants, we show that in two months after infection, HPV viral load in non-persisting infections reaches a plateau that lasts on average for 13 to 20 months (95% credibility interval) and is then followed by a rapid clearance phase. This first description of the dynamics of HPV infections comes with the identification of immune correlates associated with infection clearance, especially gamma-delta T cells and CXCL10 concentration. A limitation of this study on HPV kinetics is that many infection follow-ups are censored. Furthermore, some immune cell populations are difficult to label because cervical immunity is less well characterised than systemic immunity. These results open new perspectives for understanding the frontier between acute and chronic infections, and for controlling HPV-associated diseases, as well as for research on human cancers of infectious origin. Trial Registration: This trial was registered is registered at ClinicalTrials.gov under the ID NCT02946346. This study has been approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/ AR1612278, decision number DR-2016-488), by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007).</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002949"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014647","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":"Spontaneous slow cortical potentials and brain oscillations independently influence conscious visual perception.","authors":"Lua Koenig, Biyu J He","doi":"10.1371/journal.pbio.3002964","DOIUrl":"10.1371/journal.pbio.3002964","url":null,"abstract":"<p><p>Perceptual awareness results from an intricate interaction between external sensory input and the brain's spontaneous activity. Pre-stimulus ongoing activity influencing conscious perception includes both brain oscillations in the alpha (7 to 14 Hz) and beta (14 to 30 Hz) frequency ranges and aperiodic activity in the slow cortical potential (SCP, <5 Hz) range. However, whether brain oscillations and SCPs independently influence conscious perception or do so through shared mechanisms remains unknown. Here, we addressed this question in 2 independent magnetoencephalography (MEG) data sets involving near-threshold visual perception tasks in humans using low-level (Gabor patches) and high-level (objects, faces, houses, animals) stimuli, respectively. We found that oscillatory power and large-scale SCP activity influence conscious perception through independent mechanisms that do not have shared variance. In addition, through mediation analysis, we show that pre-stimulus oscillatory power and SCP activity have different relations to pupil size-an index of arousal-in their influences on conscious perception. Together, these findings suggest that oscillatory power and SCPs independently contribute to perceptual awareness, with distinct relations to pupil-linked arousal.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002964"},"PeriodicalIF":9.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014641","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":"How can modeling responsibly inform decision-making in malaria?","authors":"Jaline Gerardin, Melissa A Penny","doi":"10.1371/journal.pbio.3002991","DOIUrl":"10.1371/journal.pbio.3002991","url":null,"abstract":"<p><p>When models are used to inform decision-making, both their strengths and limitations must be considered. Using malaria as an example, we explain how and why models are limited and offer guidance for ensuring a model is well-suited for its intended purpose.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002991"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014632","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":"Towards ensuring reproducibility of outsourced data generation.","authors":"Daniel B Sloan, Mark D Stenglein","doi":"10.1371/journal.pbio.3002988","DOIUrl":"10.1371/journal.pbio.3002988","url":null,"abstract":"<p><p>\"Big data\" generated from outsourced or centralized facilities often lacks methodological information. Here, we outline how and why researchers, service providers, and other parties should report on methodology and sample metadata to improve scientific reproducibility.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002988"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014644","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":"Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression.","authors":"Ankita Chavan, Lena Skrutl, Federico Uliana, Melanie Pfister, Franziska Brändle, Laszlo Tirian, Delora Baptista, Dominik Handler, David Burke, Anna Sintsova, Pedro Beltrao, Julius Brennecke, Madhav Jagannathan","doi":"10.1371/journal.pbio.3002984","DOIUrl":"10.1371/journal.pbio.3002984","url":null,"abstract":"<p><p>Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized. Here, we use 2 satellite DNA-binding proteins, D1 and Prod, as baits to characterize the chromocenter-associated proteome in Drosophila embryos, ovaries, and testes through quantitative mass spectrometry. We identify D1- and Prod-associated proteins, including known heterochromatin proteins as well as proteins previously unlinked to satellite DNA or chromocenters, thereby laying the foundation for a comprehensive understanding of cellular functions enabled by satellite DNA repeats and their associated proteins. Interestingly, we find that multiple components of the transposon-silencing piRNA pathway are associated with D1 and Prod in embryos. Using genetics, transcriptomics, and small RNA profiling, we show that flies lacking D1 during embryogenesis exhibit transposon expression and gonadal atrophy as adults. We further demonstrate that this gonadal atrophy can be rescued by mutating the checkpoint kinase, Chk2, which mediates germ cell arrest in response to transposon mobilization. Thus, we reveal that a satellite DNA-binding protein functions during embryogenesis to silence transposons, in a manner that is heritable across later stages of development.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002984"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014636","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":"Dorsal hippocampus represents locations to avoid as well as locations to approach during approach-avoidance conflict.","authors":"Olivia L Calvin, Matthew T Erickson, Cody J Walters, A David Redish","doi":"10.1371/journal.pbio.3002954","DOIUrl":"10.1371/journal.pbio.3002954","url":null,"abstract":"<p><p>Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta cycles. Similarly, important information that is distant from the animal's position is represented during hippocampal high-synchrony events (HSEs), which coincide with sharp-wave ripples (SWRs). It is likely that potential future threats may be similarly represented. We examined how threats and rewards were represented within the hippocampus during approach-avoidance conflicts in rats faced with a predator-like robot guarding a food reward. We found decoding of the pseudo-predator's location during HSEs when hesitating in the nest and during theta prior to retreating as the rats approached the pseudo-predator. After the first attack, we observed new place fields appearing at the location of the robot (not the location the rat was when attacked). The anxiolytic diazepam reduced anxiety-like behavior and altered hippocampal local field potentials (LFPs), including reducing SWRs, suggesting that one potential mechanism of diazepam's actions may be through altered representations of imagined threat. These results suggest that hippocampal representation of potential threats could be an important mechanism that underlies worry and a potential target for anxiolytics.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002954"},"PeriodicalIF":9.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985140","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":"Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.","authors":"Joseph T Ortega, Jacklyn M Gallagher, Andrew G McKee, Yidan Tang, Miguel Carmena-Bargueňo, Maria Azam, Zaiddodine Pashandi, Marcin Golczak, Jens Meiler, Horacio Pérez-Sánchez, Jonathan P Schlebach, Beata Jastrzebska","doi":"10.1371/journal.pbio.3002932","DOIUrl":"10.1371/journal.pbio.3002932","url":null,"abstract":"<p><p>Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking. We identified and validated the biological effects of 2 non-retinoid compounds with favorable pharmacological properties that cross the blood-retina barrier. These compounds reversibly bind to unliganded rod opsin, each with a Kd comparable to 9-cis-retinal and improve opsin stability. By improving the internal protein structure network (PSN), these rod opsin ligands also enhanced the plasma membrane expression of total 36 of 123 tested clinical RP variants, including the most prevalent P23H variant. Importantly, these compounds protected retinas against light-induced degeneration in mice vulnerable to bright light injury and prolonged survival of photoreceptors in a retinitis pigmentosa mouse model for rod opsin misfolding.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002932"},"PeriodicalIF":9.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985136","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":"Subregions in the ventromedial prefrontal cortex integrate threat and protective information to meta-represent safety.","authors":"Sarah M Tashjian, Joseph Cussen, Wenning Deng, Bo Zhang, Dean Mobbs","doi":"10.1371/journal.pbio.3002986","DOIUrl":"10.1371/journal.pbio.3002986","url":null,"abstract":"<p><p>Pivotal to self-preservation is the ability to identify when we are safe and when we are in danger. Previous studies have focused on safety estimations based on the features of external threats and do not consider how the brain integrates other key factors, including estimates about our ability to protect ourselves. Here, we examine the neural systems underlying the online dynamic encoding of safety. The current preregistered study used 2 novel tasks to test 4 facets of safety estimation: Safety Prediction, Meta-representation, Recognition, and Value Updating. We experimentally manipulated safety estimation changing both levels of external threats and self-protection. Data were collected in 2 independent samples (behavioral N = 100; MRI N = 30). We found consistent evidence of subjective changes in the sensitivity to safety conferred through protection. Neural responses in the ventromedial prefrontal cortex (vmPFC) tracked increases in safety during all safety estimation facets, with specific tuning to protection. Further, informational connectivity analyses revealed distinct hubs of safety coding in the posterior and anterior vmPFC for external threats and protection, respectively. These findings reveal a central role of the vmPFC for coding safety.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002986"},"PeriodicalIF":9.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980354","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":"The ability of pentose pathways to form all essential metabolites provides clues to the origins of metabolism.","authors":"Steffen N Lindner, Markus Ralser","doi":"10.1371/journal.pbio.3002996","DOIUrl":"10.1371/journal.pbio.3002996","url":null,"abstract":"<p><p>The structure of the early metabolic network is unknown. Here, we report that when considered together, pentose utilization pathways form all life-essential precursors. We speculate that the chemistry preserved in pentose metabolism could therefore have been a central structural element in early metabolism.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002996"},"PeriodicalIF":9.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962526","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}