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Nature computational science 2023年第9期3卷 805页

作者： Xi Chen Yuan Wang Antonio Cappuccio Wan-Sze Cheng Frederique Ruf Zamojski Venugopalan D Nair Clare M Miller Aliza B Rubenstein German Nudelman Alicja Tadych Chandra L Theesfeld Alexandria Vornholt Mary-Catherine George Felicia Ruffin Michael Dagher Daniel G Chawla Alessandra Soares-Schanoski Rachel R Spurbeck Lishomwa C Ndhlovu Robert Sebra Steven H Kleinstein Andrew G Letizia Irene Ramos Vance G Fowler Christopher W Woods Elena Zaslavsky Olga G Troyanskaya Stuart C Sealfon Center for Computational Biology Flatiron Institute New York NY USA. Lewis-Sigler Institute of Integrative Genomics Princeton University Princeton NJ USA. Department of Computer Science Princeton University Princeton NJ USA. Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA. Division of Infectious Diseases Department of Medicine Duke University School of Medicine Durham NC USA. Program in Computational Biology and Bioinformatics Yale University New Haven CT USA. Battelle Memorial Institute Columbus OH USA. Division of Infectious Diseases Department of Medicine Weill Cornell Medicine New York NY USA. Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA. Department of Pathology and Department of Immunobiology Yale School of Medicine New Haven CT USA. Naval Medical Research Center Silver Spring MD USA. Precision Immunology Institute Icahn School of Medicine at Mount Sinai New York NY USA. Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA. elena.zaslavsky@mssm.edu. Center for Computational Biology Flatiron Institute New York NY USA. ogt@genomics.princeton.edu. Lewis-Sigler Institute of Integrative Genomics Princeton University Princeton NJ USA. ogt@genomics.princeton.edu. Department of Computer Science Princeton University Princeton NJ USA. ogt@genomics.princeton.edu. Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA. stuart.sealfon@mssm.edu.

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Structural basis and synergism of ATP and Na⁺ activation in bacterial K⁺ uptake system KtrAB

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Nature Communications 2024年第1期15卷 3850页

作者： Chiang, Wesley Tien Chang, Yao-Kai Hui, Wei-Han Chang, Shu-Wei Liao, Chen-Yi Chang, Yi-Chuan Chen, Chun-Jung Wang, Wei-Chen Lai, Chien-Chen Wang, Chun-Hsiung Luo, Siou-Ying Huang, Ya-Ping Chou, Shan-Ho Horng, Tzyy-Leng Hou, Ming-Hon Muench, Stephen P. Chen, Ren-Shiang Tsai, Ming-Daw Hu, Nien-Jen Graduate Institute of Biochemistry National Chung Hsing University Taichung 402202 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115201 Taiwan Department of Civil Engineering National Taiwan University Taipei 106319 Taiwan Department of Biomedical Engineering National Taiwan University Taipei 10663 Taiwan Life Science Group Scientific Research Division National Synchrotron Radiation Research Center Hsinchu 30092 Taiwan Institute of Molecular Biology National Chung Hsing University Taichung 402202 Taiwan Graduate Institute of Chinese Medical Science China Medical University Taichung 406040 Taiwan Department of Applied Mathematics Feng Chia University Taichung 407102 Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402202 Taiwan School of Biomedical Sciences Faculty of Biological Sciences and the Astbury Centre for Structural Molecular Biology University of Leeds Leeds LS2 9JT United Kingdom Department of Life Science Tunghai University Taichung 407224 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei 106319 Taiwan Ph.D Program in Translational Medicine National Chung Hsing University Taichung 402202 Taiwan

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated...

The K⁺ uptake system KtrAB is essential for bacterial survival in low K⁺ environments. The activity of KtrAB is regulated by nucleotides and Na⁺. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na⁺ activates KtrAB and the Na⁺ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na⁺, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na⁺ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K⁺ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na⁺ in activating BsKtrAB is likely applicable to Na⁺-activated K⁺ channels in central nervous system. © The Author(s) 2024.

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An open science study of ageing in companion dogs (vol 602, g 51, 2022)

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NATURE 2022年第7924期608卷 E33-E33页

作者： Creevy, Kate E. Akey, Joshua M. Kaeberlein, Matt Promislow, Daniel E. L. Department of Small Animal Clinical Sciences Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Lewis-Sigler Institute for Integrative Genomics Princeton University Princeton NJ USA Department of Laboratory Medicine and Pathology University of Washington School of Medicine Seattle WA USA Department of Biology University of Washington Seattle WA USA Institute for Stem Cell and Regenerative Medicine University of Washington Seattle WA USA Department of Clinical Microbiology and Immunology Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel Blavatnik School of Computer Science Tel Aviv University Tel Aviv Israel Santa Fe Institute Santa Fe NM USA Cornell Veterinary Biobank College of Veterinary Medicine Cornell University Ithaca NY USA Department of Sociology University of Washington Seattle WA USA Center for Studies in Demography and Ecology Seattle WA USA Department of Small Animal Medicine and Surgery University of Georgia College of Veterinary Medicine Athens GA USA Department of Veterinary Physiology and Pharmacology Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Department of Family Medicine University of Washington Seattle WA USA Department of Epidemiology University of Washington Seattle WA USA Department of Global Health University of Washington Seattle WA USA Epidemiology Program Fred Hutchinson Cancer Research Center Seattle WA USA Department of Veterinary Pathobiology Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Bioinformatics and Integrative Biology University of Massachusetts Chan Medical School Worcester MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Biostatistics University of Washington Seattle WA USA Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA USA Department of Population Health Sciences Vir

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Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice

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Cell Reports 2023年第5期42卷 112499页

作者： Moore, Timothy M. Lee, Sindre Olsen, Thomas Morselli, Marco Strumwasser, Alexander R. Lin, Amanda J. Zhou, Zhenqi Abrishami, Aaron Garcia, Steven M. Bribiesca, Jennifer Cory, Kevin Whitney, Kate Ho, Theodore Ho, Timothy Lee, Joseph L. Rucker, Daniel H. Nguyen, Christina Q.A. Anand, Akshay T.S. Yackly, Aidan Mendoza, Lorna Q. Leyva, Brayden K. Aliman, Claudia Artiga, Daniel J. Meng, Yonghong Charugundla, Sarada Pan, Calvin Jedian, Vida Seldin, Marcus M. Ahn, In Sook Diamante, Graciel Blencowe, Montgomery Yang, Xia Mouisel, Etienne Pellegrini, Matteo Turcotte, Lorraine P. Birkeland, Kåre I. Norheim, Frode Drevon, Christian A. Lusis, Aldons J. Hevener, Andrea L. Division of Cardiology Diabetes and Hypertension Department of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles CA United States Division of Endocrinology Diabetes and Hypertension Department of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles CA United States Department of Transplantation Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway Department of Nutrition Institute of Basic Medical Sciences Faculty of Medicine University of Oslo Oslo Norway Department of Molecular Cell and Developmental Biology University of California Los Angeles Los Angeles CA United States UCLA-DOE Institute for Genomics and Proteomics University of California Los Angeles Los Angeles CA United States Institute for Quantitative and Computational Biosciences – The Collaboratory University of California Los Angeles Los Angeles CA United States Department of Chemical and Systems Biology Stanford School of Medicine Stanford CA United States Department of Biological Chemistry and Center for Epigenetics and Metabolism University of California Irvine Irvine CA United States Molecular Cellular and Integrative Physiology Interdepartmental Program University of California Los Angeles Los Angeles CA United States Department of Integrative Biology and Physiology University of California Los Angeles Los Angeles CA United States Institute for Quantitative and Computational Biosciences University of California Los Angeles Los Angeles CA United States Institute of Metabolic and Cardiovascular Diseases UMR1297 Inserm Paul Sabatier University Toulouse France Department of Biological Sciences Dana & David Dornsife College of Letters Arts and Sciences University of Southern California Los Angeles CA United States Department of Human Genetics University of California Los Angeles Los Angeles CA United States Department of Microbiology Immunology and Molecular Geneti

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ∼33% of genes differentially expressed in skeletal muscle following the exercise intervention are similar in mice and humans independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears controlled by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. The human and mouse data are publicly available via a user-friendly Web-based application to enhance data mining and hypothesis development. © 2023 The Authors

关键词： CP: Metabolism CP: Molecular biology exercise genetics HMDP multi-omics physical activity physiology systems biology

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Democratising Knowledge Representation with BioCypher

arXiv

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arXiv 2022年

作者： Lobentanzer, Sebastian Aloy, Patrick Baumbach, Jan Bohar, Balazs Charoentong, Pornpimol Danhauser, Katharina Doğan, Tunca Dreo, Johann Dunham, Ian Fernandez-Torras, Adrià Gyori, Benjamin M. Hartung, Michael Hoyt, Charles Tapley Klein, Christoph Korcsmaros, Tamas Maier, Andreas Mann, Matthias Ochoa, David Pareja-Lorente, Elena Popp, Ferdinand Preusse, Martin Probul, Niklas Schwikowski, Benno Sen, Bünyamin Strauss, Maximilian T. Turei, Denes Ulusoy, Erva Heidrun Wodke, Judith Andrea Saez-Rodriguez, Julio Heidelberg University Faculty of Medicine Heidelberg University Hospital Institute for Computational Biomedicine Bioquant Heidelberg Germany The Barcelona Institute of Science and Technology Catalonia Barcelona Spain Catalonia Barcelona Spain Institute for Computational Systems Biology University of Hamburg Germany Earlham Institute Norwich United Kingdom Biological Research Centre Szeged Hungary Heidelberg University Im Neuenheimer Feld 267 Heidelberg69120 Germany Im Neuenheimer Feld 460 Heidelberg69120 Germany Department of Pediatrics Dr. von Hauner Children’s Hospital University Hospital LMU Munich Germany Biological Data Science Lab Department of Computer Engineering Hacettepe University Ankara Turkey Department of Bioinformatics Graduate School of Health Sciences Hacettepe University Ankara Turkey Computational Systems Biomedicine Lab Department of Computational Biology Institut Pasteur Université Paris Cité Paris France Bioinformatics and Biostatistics Hub Institut Pasteur Université Paris Cité Paris France Wellcome Genome Campus Cambridgeshire HinxtonCB10 1SD United Kingdom Open Targets Wellcome Genome Campus Cambridgeshire HinxtonCB10 1SD United Kingdom Laboratory of Systems Pharmacology Harvard Medical School Boston United States Imperial College London London United Kingdom Quadram Institute Bioscience Norwich United Kingdom Proteomics Program Novo Nordisk Foundation Centre for Protein Research University of Copenhagen Copenhagen Denmark Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried Germany Im Neuenheimer Feld 460 Heidelberg69120 Germany Neuherberg Germany Medical Informatics Laboratory University Medicine Greifswald Germany

Standardising the representation of biomedical knowledge among all researchers is an insurmountable task, hindering the effectiveness of many computational methods. To facilitate harmonisation and interoperability despite this fundamental challenge, we propose to standardise the framework of knowledge graph creation instead. We implement this standardisation in BioCypher, a FAIR (findable, accessible, interoperable, reusable) framework to transparently build biomedical knowledge graphs while preserving provenances of the source data. Mapping the knowledge onto biomedical ontologies helps to balance the needs for harmonisation, human and machine readability, and ease of use and accessibility to nonspecialist researchers. We demonstrate the usefulness of this framework on a variety of use cases, from maintenance of task-specific knowledge stores, to interoperability between biomedical domains, to on-demand building of task-specific knowledge graphs for federated learning. BioCypher (https://***) frees up valuable developer time;we encourage further development and usage by the community. © 2022, CC BY-NC-ND.

关键词： Ontology

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Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

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Nature genetics 2023年第10期55卷 1778-1779页

作者： Nick Shrine Abril G Izquierdo Jing Chen Richard Packer Robert J Hall Anna L Guyatt Chiara Batini Rebecca J Thompson Chandan Pavuluri Vidhi Malik Brian D Hobbs Matthew Moll Wonji Kim Ruth Tal-Singer Per Bakke Katherine A Fawcett Catherine John Kayesha Coley Noemi Nicole Piga Alfred Pozarickij Kuang Lin Iona Y Millwood Zhengming Chen Liming Li Sara R A Wijnant Lies Lahousse Guy Brusselle Andre G Uitterlinden Ani Manichaikul Elizabeth C Oelsner Stephen S Rich R Graham Barr Shona M Kerr Veronique Vitart Michael R Brown Matthias Wielscher Medea Imboden Ayoung Jeong Traci M Bartz Sina A Gharib Claudia Flexeder Stefan Karrasch Christian Gieger Annette Peters Beate Stubbe Xiaowei Hu Victor E Ortega Deborah A Meyers Eugene R Bleecker Stacey B Gabriel Namrata Gupta Albert Vernon Smith Jian'an Luan Jing-Hua Zhao Ailin F Hansen Arnulf Langhammer Cristen Willer Laxmi Bhatta David Porteous Blair H Smith Archie Campbell Tamar Sofer Jiwon Lee Martha L Daviglus Bing Yu Elise Lim Hanfei Xu George T O'Connor Gaurav Thareja Omar M E Albagha Karsten Suhre Raquel Granell Tariq O Faquih Pieter S Hiemstra Annelies M Slats Benjamin H Mullin Jennie Hui Alan James John Beilby Karina Patasova Pirro Hysi Jukka T Koskela Annah B Wyss Jianping Jin Sinjini Sikdar Mikyeong Lee Sebastian May-Wilson Nicola Pirastu Katherine A Kentistou Peter K Joshi Paul R H J Timmers Alexander T Williams Robert C Free Xueyang Wang John L Morrison Frank D Gilliland Zhanghua Chen Carol A Wang Rachel E Foong Sarah E Harris Adele Taylor Paul Redmond James P Cook Anubha Mahajan Lars Lind Teemu Palviainen Terho Lehtimäki Olli T Raitakari Jaakko Kaprio Taina Rantanen Kirsi H Pietiläinen Simon R Cox Craig E Pennell Graham L Hall W James Gauderman Chris Brightling James F Wilson Tuula Vasankari Tarja Laitinen Veikko Salomaa Dennis O Mook-Kanamori Nicholas J Timpson Eleftheria Zeggini Josée Dupuis Caroline Hayward Ben Brumpton Claudia Langenberg Stefan Weiss Georg Homuth Carsten Oliver Schmidt Nicole Probst-Hensch Marjo-Riitta Jarvelin Alanna C Morrison Ozren Polasek Igor Department of Population Health Sciences University of Leicester Leicester UK. nick.shrine@leicester.ac.uk. Department of Population Health Sciences University of Leicester Leicester UK. Division of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre University of Nottingham Nottingham UK. Leicester National Institute for Health and Care Research Biomedical Research Centre Glenfield Hospital Leicester UK. Channing Division of Network Medicine Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Boston MA USA. Harvard Medical School Boston MA USA. COPD Foundation Washington DC USA. Department of Clinical Science Unversity of Bergen Bergen Norway. Nuffield Department of Population Health University of Oxford Oxford UK. MRC Population Health Research Unit University of Oxford Oxford UK. Department of Epidemiology and Biostatistics School of Public Health Peking University Health Science Center Beijing China. Department of Respiratory Diseases Ghent Universital Hospital Ghent Belgium. Department of Bioanalysis Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium. Department of Epidemiology Eramus Medical Center Rotterdam The Netherlands. Department of Internal Medicine Eramus Medical Center Rotterdam The Netherlands. Center for Public Health Genomics University of Virginia Charlottesville VA USA. Department of Medicine Columbia University Medical Center New York NY USA. Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK. Human Genetics Center Department of Epidemiology Human Genetics and Environmental Sciences School of Public Health The University of Texas Health Science Center at Houston Houston TX USA. MRC Centre for Environment and Health Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK. Department of Epidemiology and Public Health Swiss Tropical

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In vitro activity of imipenem/relebactam, meropenem/vaborbactam and comparators against Enterobacterales causing urinary tract infection in Taiwan: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2020

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International journal of antimicrobial agents 2023年第6期61卷 106815页

作者： Chih-Yen Chang Yu-Lin Lee Yu-Tsung Huang Wen-Chien Ko Mao-Wang Ho Po-Ren Hsueh Department of Internal Medicine Yuanlin Christian Hospital Changhua Taiwan. Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan and Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan. Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan. Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan. Division of Infectious Diseases Department of Internal Medicine China Medical University Hospital China Medical University Taichung Taiwan. Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan Division of Infectious Diseases Department of Internal Medicine China Medical University Hospital China Medical University Taichung Taiwan Center of Laboratory Medicine China Medical University Hospital China Medical University Taichung Taiwan PhD Program for Aging School of Medicine China Medical University Taichung Taiwan. Electronic address: hsporen@***.

OBJECTIVES:Antimicrobial resistance due to β-lactamase production is a worldwide issue, and β-lactamase inhibitors have been developed to overcome the growing problem. This study aimed to evaluate the in vitro activities of two recently introduced carbapenem/β-lactamase inhibitor combinations - imipenem/relebactam and meropenem/vaborbactam - and their comparators against Enterobacterales from patients with urinary tract infections (UTIs). METHODS:Enterobacterales isolates from patients with UTIs in Taiwan and participating in the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2020 were included. Minimum inhibitory concentrations (MICs) for various antibiotics were determined using the broth microdilution method. Susceptibility was interpreted based on the MIC breakpoints of the Clinical and Laboratory Standards Institute 2022. Genes encoding common β-lactamases, including extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases, were detected using multiplex polymerase chain reaction. RESULTS:A total of 309 Enterobacterales isolates were included, against which both imipenem/relebactam and meropenem/vaborbactam exerted excellent efficacy (275 of 309, 95% and 288 of 309, 99.3%, respectively). Among imipenem non-susceptible isolates, 17 of 43 (39.5%) and 39 of 43 (90.7%) were susceptible to imipenem/relebactam and meropenem/vaborbactam, respectively. CONCLUSION:Imipenem/relebactam and meropenem/vaborbactam may be appropriate choices for treating UTIs due to Enterobacterales resistant to commonly used antibiotics. Continuous monitoring of antimicrobial resistance is crucial.

关键词： Carbapenem resistance Cross-resistance Enterobacterales Multidrug resistance Novel β-lactam combination agents

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Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq

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Nature communications 2025年第1期16卷 4785页

作者： Hefei Zhang Xuhang Li Dongyuan Song Onur Yukselen Shivani Nanda Alper Kucukural Jingyi Jessica Li Manuel Garber Albertha J M Walhout Department of Systems Biology University of Massachusetts Chan Medical School Worcester MA USA. Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles CA USA. Department of Genetics and Genome Sciences University of Connecticut Health Center Farmington CT USA. Via Scientific Inc. Cambridge MA USA. Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA. Department of Genomics and Computational Biology University of Massachusetts Chan Medical School Worcester MA USA. Department of Statistics and Data Science Department of Biostatistics Department of Computational Medicine and Department of Human Genetics University of California Los Angeles CA USA. Department of Genomics and Computational Biology University of Massachusetts Chan Medical School Worcester MA USA. manuel.garber@umassmed.edu. Department of Systems Biology University of Massachusetts Chan Medical School Worcester MA USA. marian.walhout@umassmed.edu.

Transcriptomes provide highly informative molecular phenotypes that, combined with gene perturbation, can connect genotype to phenotype. An ultimate goal is to perturb every gene and measure transcriptome changes, however, this is challenging, especially in whole animals. Here, we present 'Worm Perturb-Seq (WPS)', a method that provides high-resolution RNA-sequencing profiles for hundreds of replicate perturbations at a time in living animals. WPS introduces multiple experimental advances combining strengths of Caenhorhabditis elegans genetics and multiplexed RNA-sequencing with a novel analytical framework, EmpirDE. EmpirDE leverages the unique power of large transcriptomic datasets and improves statistical rigor by using gene-specific empirical null distributions to identify DEGs. We apply WPS to 103 nuclear hormone receptors (NHRs) and find a striking 'pairwise modularity' in which pairs of NHRs regulate shared target genes. We envision the advances of WPS to be useful not only for C. elegans, but broadly for other models, including human cells.

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PCC-hippocampal functional connectivity associated with stress biomarker changes after meditation training for healthy adults

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Neuroscience letters 2025年 138272页

作者： Diane Joss Gunes Sevinc John W Denninger Sat Bir Singh Khalsa Elizabeth A Hoge Manoj Bhasin Jeffery A Dusek Eric Macklin Towia A Libermann Gregory L Fricchione Herbert Benson Sara W Lazar Department of Psychiatry Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA. Electronic address: djoss@cha.harvard.edu. Department of Psychiatry Massachusetts General Hospital Boston MA USA. Harvard Medical School Boston MA USA Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital Boston MA USA. Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital Boston MA USA Department of Medicine Brigham and Women's Hospital Harvard Medical School USA. Department of Psychiatry Georgetown University Medical Center Washington DC USA. Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA. Susan Samueli Integrative Health Institute University of California-Irvine Irvine CA USA School of Medicine University of California-Irvine Irvine CA USA. Harvard Medical School Boston MA USA. Genomics Proteomics Bioinformatics and Systems Biology Center Beth Israel Deaconess Medical Center Boston MA USA.

Meditation training has been shown to improve physical and mental health and promote neural plasticity, but more research is needed on the relationships between these effects. This study analyzed the Resting State Functional Connectivity (RSFC) of posterior cingulate cortex (PCC) among 94 chronically stressed but otherwise healthy adults randomized 1:1:1 to receive eight weeks of in-person one-on-one interventions focused either on meditation (n = 32), yoga (n = 31), or stress education (n = 31). We found only in the meditation arm, there was a significant reduction of PCC RSFC with the left hippocampus (p < 0.05, FWE corrected). Post-intervention changes of PCC-hippocampal RSFC were significantly (all p ≤ 0.01) correlated with changes of perceived stress (r = 0.54), allostatic load index (r = 0.58), and NF-κB anti-inflammatory gene expression (r = -0.55), suggesting the neural effects of meditation are closely associated with biomarkers of physical wellness. No significant changes with PCC RSFC were observed within the yoga or stress education arm, suggesting this neurobiological mechanism might be unique to meditation training.

关键词： Biomarker Inflammation MRI Meditation Wellbeing Wellness Yoga

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