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Local and Global Variability in Developing Human T-Cell Repertoires. 人类 T 细胞发育过程中的局部和整体变异性

PRX life Pub Date : 2024-01-01 Epub Date: 2024-03-08 DOI: 10.1103/prxlife.2.013011

Giulio Isacchini, Valentin Quiniou, Pierre Barennes, Vanessa Mhanna, Hélène Vantomme, Paul Stys, Encarnita Mariotti-Ferrandiz, David Klatzmann, Aleksandra M Walczak, Thierry Mora, Armita Nourmohammad

{"title":"Local and Global Variability in Developing Human T-Cell Repertoires.","authors":"Giulio Isacchini, Valentin Quiniou, Pierre Barennes, Vanessa Mhanna, Hélène Vantomme, Paul Stys, Encarnita Mariotti-Ferrandiz, David Klatzmann, Aleksandra M Walczak, Thierry Mora, Armita Nourmohammad","doi":"10.1103/prxlife.2.013011","DOIUrl":"10.1103/prxlife.2.013011","url":null,"abstract":"The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T-cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T-cell maturation in the thymus. Characterizing TCR repertoires across individuals and T-cell maturation stages is important for better understanding adaptive immune responses and for developing new diagnostics and therapies. Analyzing a dataset of human TCR repertoires from thymocyte subsets, we find that the variability between individuals generated during the TCR V(D)J recombination is maintained through all stages of T-cell maturation and differentiation. The interindividual variability of repertoires of the same cell type is of comparable magnitude to the variability across cell types within the same individual. To zoom in on smaller scales than whole repertoires, we defined a distance measuring the relative overlap of locally similar sequences in repertoires. We find that the whole repertoire models correctly predict local similarity networks, suggesting a lack of forbidden T-cell receptor sequences. The local measure correlates well with distances calculated using whole repertoire traits and carries information about cell types.","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Finding the last bits of positional information. 找到最后的位置信息。

PRX life Pub Date : 2024-01-01 Epub Date: 2024-03-26 DOI: 10.1103/prxlife.2.013016

Lauren McGough, Helena Casademunt, Miloš Nikolić, Zoe Aridor, Mariela D Petkova, Thomas Gregor, William Bialek

{"title":"Finding the last bits of positional information.","authors":"Lauren McGough, Helena Casademunt, Miloš Nikolić, Zoe Aridor, Mariela D Petkova, Thomas Gregor, William Bialek","doi":"10.1103/prxlife.2.013016","DOIUrl":"10.1103/prxlife.2.013016","url":null,"abstract":"In a developing embryo, information about the position of cells is encoded in the concentrations of morphogen molecules. In the fruit fly, the local concentrations of just a handful of proteins encoded by the gap genes are sufficient to specify position with a precision comparable to the spacing between cells along the anterior-posterior axis. This matches the precision of downstream events such as the striped patterns of expression in the pair-rule genes, but is not quite sufficient to define unique identities for individual cells. We demonstrate theoretically that this information gap can be bridged if positional errors are spatially correlated, with correlation lengths ~ 20% of the embryo length. We then show experimentally that these correlations are present, with the required strength, in the fluctuating positions of the pair-rule stripes, and this can be traced back to the gap genes. Taking account of these correlations, the available information matches the information needed for unique cellular specification, within error bars of ~ 2%. These observation support a precisionist view of information flow through the underlying genetic networks, in which accurate signals are available from the start and preserved as they are transformed into the final spatial patterns.","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene Expression Tradeoffs Determine Bacterial Survival and Adaptation to Antibiotic Stress. 基因表达权衡决定了细菌的生存和对抗生素压力的适应。

PRX life Pub Date : 2024-01-01 Epub Date: 2024-02-29 DOI: 10.1103/prxlife.2.013010

Josiah C Kratz, Shiladitya Banerjee

{"title":"Gene Expression Tradeoffs Determine Bacterial Survival and Adaptation to Antibiotic Stress.","authors":"Josiah C Kratz, Shiladitya Banerjee","doi":"10.1103/prxlife.2.013010","DOIUrl":"https://doi.org/10.1103/prxlife.2.013010","url":null,"abstract":"To optimize their fitness, cells face the crucial task of efficiently responding to various stresses. This necessitates striking a balance between conserving resources for survival and allocating resources for growth and division. The fundamental principles governing these tradeoffs is an outstanding challenge in the physics of living systems. In this study, we introduce a coarse-grained theoretical framework for bacterial physiology that establishes a connection between the physiological state of cells and their survival outcomes in dynamic environments, particularly in the context of antibiotic exposure. Predicting bacterial survival responses to varying antibiotic doses proves challenging due to the profound influence of the physiological state on critical parameters, such as the minimum inhibitory concentration (MIC) and killing rates, even within an isogenic cell population. Our proposed theoretical model bridges the gap by linking extracellular antibiotic concentration and nutrient quality to intracellular damage accumulation and gene expression. This framework allows us to predict and explain the control of cellular growth rate, death rate, MIC, and survival fraction in a wide range of time-varying environments. Surprisingly, our model reveals that cell death is rarely due to antibiotic levels being above the maximum physiological limit, but instead survival is limited by the inability to alter gene expression sufficiently quickly to transition to a less susceptible physiological state. Moreover, bacteria tend to overexpress stress response genes at the expense of reduced growth, conferring greater protection against further antibiotic exposure. This strategy is in contrast to those employed in different nutrient environments, in which bacteria allocate resources to maximize growth rate. This highlights an important tradeoff between the cellular capacity for growth and the ability to survive antibiotic exposure.","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0