TY - JOUR AU - Vardalakis, N. AU - Aussel, A. AU - Rougier, N.P. AU - Wagner, F.B. TI - A dynamical computational model of theta generation in hippocampal circuits to study theta-gamma oscillations during neurostimulation JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.87356 UR - https://m2.mtmt.hu/api/publication/34816859 ID - 34816859 LA - English DB - MTMT ER - TY - JOUR AU - Verma, A. AU - Hawes, C.E. AU - Elizaldi, S.R. AU - Smith, J.C. AU - Rajasundaram, D. AU - Pedersen, G.K. AU - Shen, X. AU - Williams, L.D. AU - Tomaras, G.D. AU - Kozlowski, P.A. AU - Amara, R.R. AU - Iyer, S.S. TI - Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.89395 UR - https://m2.mtmt.hu/api/publication/34815033 ID - 34815033 N1 - Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States Graduate Group in Immunology, University of California, Davis, Davis, United States California National Primate Research Center, University of California, Davis, Davis, United States Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, United States Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, United States Bioinformatics Core, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, United States Statens Serum Institute, Copenhagen, Denmark Center for Human Systems Immunology, Durham, United States Department of Surgery, Duke University Medical Center, Durham, United States Duke Human Vaccine Institute, Duke University Medical Center, Durham, United States Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States Department of Integrative Immunobiology, Duke University Medical Center, Durham, United States Department of Microbiology and Immunology, Emory University, Atlanta, United States Yerkes National Primate Research Center, Emory University, Atlanta, United States Export Date: 23 April 2024 Correspondence Address: Iyer, S.S.; Department of Pathology, United States; email: siyer.3@pitt.edu Chemicals/CAS: chemokine receptor CCR6, 287981-77-5; gamma interferon, 82115-62-6; immunoglobulin G, 97794-27-9, 308067-58-5; interleukin 21, 251100-02-4, 510787-82-3, 542817-56-1; lapretolimod, 88598-53-2, 960324-04-3; saponin, 8047-15-2; DNA, 9007-49-2; gamma interferon inducible protein 10, 97741-20-3; AIDS Vaccines; Chemokine CXCL10; DNA; HIV Antibodies Tradenames: Bioplex 200, Biorad; FACS Symphony., Becton Dickinson; GeoMx Digital Spatial Profiler, NanoString; NovaSeq S4, Illumina, United States; Prism v.9.5.1, Graphpad; Qubit 2.0, Thermo, United States; RNeasy, Qiagen; Spectramax 5 plate reader, Molecular Devices Manufacturers: Statens Serum Institut, Denmark; VanguardAgilent; Becton Dickinson; Biorad; Graphpad; Illumina, United States; Molecular Devices; NanoString; Novus Biologicals, United States; Qiagen; Thermo, United States Funding details: National Institute of Allergy and Infectious Diseases, NIAID Funding details: California National Primate Research Center, CNPRC Funding details: National Institutes of Health, NIH, R56AI150409, P30 AI064518, HHSN272201800004C, AI126683, OD10976 Funding text 1: The authors are grateful to Dennis Christensen, previously at the SSI, for provision of CAF01 adjuvant for the studies. The authors are grateful to Brian Schmidt for technical assistance with the LAMV study; Wilhelm Von Morgenland and Miles Christensen and the CNPRC SAIDS team for coordination of macaque studies; Stephenie Liu at the UC Davis Genomics Resource for optimization of morphological markers for spatial profiling, and Daniel Newhouse at the Spatial Data Analysis Service (sDAS) for analysis of spatial proteomics data. We thank Robert L Wilson for excellent technical assistance in processing secretions and measuring mucosal antibodies. The authors thank Aloki Patel for technical assistance with BAMA-AI assays, Kelly Seaton and Angelina Sharak for BAMA-AI data selection/ consultation, and Lu Zhang for data analysis and visualization (Center for Human Systems Immunology, Duke University). The authors acknowledge funding support from NIAID, NIH R56AI150409 (SSI) and contract # HHSN272201800004C (XS); Duke CFAR Grant P30 AI064518 (GDT). Reagents for measurement of rhesus IgG subclasses were obtained from the NIH Nonhuman Primate Reagent Resource supported by AI126683 and OD10976. NIH Office of the Director K01OD023034 Smita S Iyer National Institutes of Health R56AI150409 Smita S Iyer National Institutes of Health HHSN272201800004C Xiaoying Shen National Institutes of Health P30 AI064518 Georgia D Tomaras The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding text 2: The authors are grateful to Dennis Christensen, previously at the SSI, for provision of CAF01 adjuvant for the studies. The authors are grateful to Brian Schmidt for technical assistance with the LAMV study; Wilhelm Von Morgenland and Miles Christensen and the CNPRC SAIDS team for coordination of macaque studies; Stephenie Liu at the UC Davis Genomics Resource for optimization of morphological markers for spatial profiling, and Daniel Newhouse at the Spatial Data Analysis Service (sDAS) for analysis of spatial proteomics data. We thank Robert L Wilson for excellent technical assistance in processing secretions and measuring mucosal antibodies. The authors thank Aloki Patel for technical assistance with BAMA-AI assays, Kelly Seaton and Angelina Sharak for BAMA-AI data selection/ consultation, and Lu Zhang for data analysis and visualization (Center for Human Systems Immunology, Duke University). The authors acknowledge funding support from NIAID, NIH R56AI150409 (SSI) and contract # HHSN272201800004C (XS); Duke CFAR Grant P30 AI064518 (GDT). Reagents for measurement of rhesus IgG subclasses were obtained from the NIH Nonhuman Primate Reagent Resource supported by AI126683 and OD10976. AB - CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced compa-rable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml-MPLA; 5500; CAF01, 2155; p<0.05). Notably, interferon γ+Env-specific Tfh responses were consistently higher with gp140 in MPLA +QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction promote persistent Env anti-bodies, important for protective immunity against HIV. © 2024, eLife Sciences Publications Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Mainali, R. AU - Buechler, N. AU - Otero, C. AU - Edwards, L. AU - Key, C.-C. AU - Furdui, C. AU - Quinn, M.A. TI - Itaconate stabilizes CPT1a to enhance lipid utilization during inflammation JF - ELIFE J2 - ELIFE VL - 12 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.92420 UR - https://m2.mtmt.hu/api/publication/34805068 ID - 34805068 N1 - Export Date: 22 April 2024 LA - English DB - MTMT ER - TY - JOUR AU - Chuang, C.-N. AU - Liu, H.-C. AU - Woo, T.-T. AU - Chao, J.-L. AU - Chen, C.-Y. AU - Hu, H.-T. AU - Hsueh, Y.-P. AU - Wang, T.-F. TI - Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.91405 UR - https://m2.mtmt.hu/api/publication/34801422 ID - 34801422 N1 - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan Export Date: 19 April 2024 Correspondence Address: Wang, T.-F.; Institute of Molecular Biology, Taiwan; email: tfwang@gate.sinica.edu.tw LA - English DB - MTMT ER - TY - JOUR AU - Zhu, Yi-jun AU - Deng, Cai-yun AU - Fan, Liu AU - Wang, Ya-Qian AU - Zhou, Hui AU - Xu, Hua-tai TI - Combinatorial expression of γ-protocadherins regulates synaptic connectivity in the mouse neocortex JF - ELIFE J2 - ELIFE VL - 12 PY - 2024 PG - 22 SN - 2050-084X DO - 10.7554/eLife.89532 UR - https://m2.mtmt.hu/api/publication/34799824 ID - 34799824 N1 - Funding Agency and Grant Number: National Natural Science Foundation of China [91632101]; Training Program of the Major Research Plan of the National Natural Science Foundation of China [XDB32010100]; Strategic Priority Research Program of the Chinese Academy of Sciences [31671113]; National Natural Science Foundation of China [2018SHZDZX05]; Shanghai Municipal Science and Technology Major Project [LG-GG-202201-01]; State Key Laboratory of Neuroscience Funding text: We thank Dr. Yifeng Zhang for providing the Pcdhgfcon3/fcon3 mouse line and Dr. Zilong Qiu for Neurod6-cre (also known as Nex-cre) mouse line, Dr. Jun Chu for sharing plasmids with mNeongreen and mRuby3, and other members in Xu lab for their discussions and technique supports. We are grateful to Prof. Mu-ming Poo and Song-hai Shi for critical reading of the manuscript. This work was supported by grants from the Training Program of the Major Research Plan of the National Natural Science Foundation of China, grant no. 91632101; Strategic Priority Research Program of the Chinese Academy of Sciences, grant no. XDB32010100; National Natural Science Foundation of China project 31671113; Shanghai Municipal Science and Technology Major Project, grant no. 2018SHZDZX05, the State Key Laboratory of Neuroscience and the Lingang Laboratory, grant no. LG-GG-202201-01. AB - In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (gamma-PCDH) expression in orchestrating synaptic connectivity in the mouse neocortex. Through 5' end single-cell sequencing, we unveiled the intricate combinatorial expression patterns of gamma-PCDH variable isoforms within neocortical neurons. Furthermore, our whole-cell patch-clamp recordings demonstrated that as the similarity in this combinatorial pattern among neurons increased, their synaptic connectivity decreased. Our findings elucidate a sophisticated molecular mechanism governing the construction of neural networks in the mouse neocortex. LA - English DB - MTMT ER - TY - JOUR AU - Grob, A.-M. AU - Heinbockel, H. AU - Milivojevic, B. AU - Doeller, C.F. AU - Schwabe, L. TI - Causal role of the angular gyrus in insight-driven memory reconfiguration JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.91033 UR - https://m2.mtmt.hu/api/publication/34798723 ID - 34798723 N1 - Export Date: 18 April 2024 Correspondence Address: Schwabe, L.; Department of Cognitive Psychology, Germany; email: lars.schwabe@uni-hamburg.de LA - English DB - MTMT ER - TY - JOUR AU - Wagstyl, K. AU - Adler, S. AU - Seidlitz, J. AU - Vandekar, S. AU - Mallard, T.T. AU - Dear, R. AU - Decasien, A.R. AU - Satterthwaite, T.D. AU - Liu, S. AU - Vértes, P.E. AU - Shinohara, R.T. AU - Alexander-Bloch, A. AU - Geschwind, D.H. AU - Raznahan, A. TI - Transcriptional cartography integrates multiscale biology of the human cortex JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.86933 UR - https://m2.mtmt.hu/api/publication/34795243 ID - 34795243 N1 - Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom UCL Great Ormond Street Institute for Child Health, Holborn, United Kingdom Department of Psychiatry, University of Pennsylvania, Philadelphia, United States Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, United States Department of Biostatistics, Vanderbilt University, Nashville, United States Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, United States Department of Psychiatry, Harvard Medical School, Boston, United States Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom Section on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United States Lifespan Informatics and Neuroimaging Center, University of Pennsylvania School of Medicine, Philadelphia, United States Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States Center for Autism Research and Treatment, Semel Institute, Program in Neurogenetics, Department of Neurology and Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States Export Date: 17 April 2024 Correspondence Address: Wagstyl, K.; Wellcome Centre for Human Neuroimaging, United Kingdom; email: k.wagstyl@ucl.ac.uk LA - English DB - MTMT ER - TY - JOUR AU - Rickelton, K. AU - Zintel, T.M. AU - Pizzollo, J. AU - Miller, E. AU - Ely, J.J. AU - Raghanti, M.A. AU - Hopkins, W.D. AU - Hof, P.R. AU - Sherwood, C.C. AU - Bauernfeind, A.L. AU - Babbitt, C.C. TI - Tempo and mode of gene expression evolution in the brain across primates JF - ELIFE J2 - ELIFE VL - 13 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.70276 UR - https://m2.mtmt.hu/api/publication/34793009 ID - 34793009 N1 - Department of Biology, University of Massachusetts Amherst, Amherst, United States Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, United States Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, United States MAEBIOS Epidemiology Unit, Alamogordo, United States Department of Anthropology, School of Biomedical Sciences, and Brain Health Research Institute, Kent State University, Kent, United States Department of Comparative Medicine, Michale E. Keeling Center for Comparative Medicine, The University of Texas M D Anderson Cancer Centre, Bastrop, United States New York Consortium in Evolutionary Primatology, New York, United States Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States Department of Neuroscience, Washington University School of Medicine, St. Louis, United States Department of Anthropology, Washington University in St. Louis, St. Louis, United States Export Date: 16 April 2024 Correspondence Address: Rickelton, K.; Department of Biology, United States; email: krickelton@umass.edu Correspondence Address: Babbitt, C.C.; Department of Biology, United States; email: cbabbitt@bio.umass.edu Funding details: BCS-1750377 T32 GM135096 Funding details: National Science Foundation, NSF, BCS-1750377 Funding details: National Institutes of Health, NIH, NS092988, T32 GM135096 Funding details: James S. McDonnell Foundation, JSMF, 220020293, SMA-1542848 Funding details: Wenner-Gren Foundation, WGF Funding text 1: The sample includes brain tissue from human and nonhuman primates. All samples were obtained from adult individuals free from known neurological disease. If available, the right hemisphere was preferentially sampled. Human brain samples were obtained from the National Institute for Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland (Baltimore, MD). Chimpanzee brain tissue was obtained from the National Chimpanzee Brain Resource (https://www.chimpanzeebrain.org, supported by NIH grant NS092988). All other sources of brain tissue are listed in Supplementary file 1. Funding text 2: We would also like to acknowledge our funding from NSF BCS-1750377, the Wenner Gren Foundation, James S McDonnell Foundation (220020293), NSF INSPIRE (SMA-1542848), NIH (NS-092988), and a fellowship to KR from NIH T32 GM135096. https://doi.org/10.37717/220020293. Funding text 3: We would also like to acknowledge our funding from NSF BCS-1750377, the Wenner Gren Foundation, James S McDonnell Foundation (220020293), NSF INSPIRE (SMA-1542848), NIH (NS-092988), and a fellowship to KR from NIH T32 GM135096. https://doi.org/10.37717/220020293. National Science Foundation National Institutes of Health James S. McDonnell Foundation National Institutes of Health National Science Foundation BCS-1750377 T32 GM135096 https://doi.org/10.37717/ 220020293 NS-092988 SMA-1542848 Courtney C Babbitt Katherine Rickelton Chet C Sherwood Chet C Sherwood Chet C Sherwood. AB - Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our samples that represent a 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size. Our study extensively broadens the phylogenetic context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for the study of genetic regulation of brain evolution. © Rickelton et al. LA - English DB - MTMT ER - TY - JOUR AU - Zhang, Y. AU - Lauder, G.V. TI - Energy conservation by collective movement in schooling fish JF - ELIFE J2 - ELIFE VL - 12 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.90352 UR - https://m2.mtmt.hu/api/publication/34790638 ID - 34790638 N1 - Export Date: 15 April 2024 Correspondence Address: Zhang, Y.; Department of Organismic and Evolutionary Biology, United States; email: yangfan_zhang@fas.harvard.edu LA - English DB - MTMT ER - TY - JOUR AU - Grandits, Thomas AU - Augustin, Christoph M AU - Haase, Gundolf AU - Jost, Norbert László AU - Mirams, Gary R AU - Niederer, Steven A AU - Plank, Gernot AU - Varró, András AU - Virág, László AU - Jung, Alexander TI - Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies JF - ELIFE J2 - ELIFE VL - 12 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.91911 UR - https://m2.mtmt.hu/api/publication/34786266 ID - 34786266 AB - Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies. LA - English DB - MTMT ER -