5,167 results match your criteria: "Gladstone|UCSF Center for Cell Circuitry[Affiliation]"
Science
September 2024
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
BMC Bioinformatics
September 2024
Stanford University, 1265 Welch Road, x327, Stanford, CA, 94305, USA.
Genomics methods have uncovered patterns in a range of biological systems, but obscure important aspects of cell behavior: the shapes, relative locations, movement, and interactions of cells in space. Spatial technologies that collect genomic or epigenomic data while preserving spatial information have begun to overcome these limitations. These new data promise a deeper understanding of the factors that affect cellular behavior, and in particular the ability to directly test existing theories about cell state and variation in the context of morphology, location, motility, and signaling that could not be tested before.
View Article and Find Full Text PDFbioRxiv
August 2024
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
While often represented as static entities, gene networks are highly context-dependent. Here, we developed a multi-task learning strategy to yield context-specific representations of gene network dynamics. We assembled a corpus comprising ~103 million human single-cell transcriptomes from a broad range of tissues and diseases and performed a two stage pretraining, first with non-malignant cells to generate a foundational model and then with continual learning on cancer cells to tune the model to the cancer domain.
View Article and Find Full Text PDFNat Rev Endocrinol
January 2025
Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis.
View Article and Find Full Text PDFN Engl J Med
January 2025
From Duke Clinical Research Institute, Duke University School of Medicine (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, S.J.E., F.W.R., J.H.A.), and Duke University Medical Center (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, F.W.R., J.H.A.) - both in Durham, NC; Hirslanden Clinic Zurich, Zurich, Switzerland (J.S.); the School of Medicine, Tulane University, New Orleans (K.F.); the University Medical Center, University of Groningen, Groningen (I.C.V.G., M.R.), Radboud University Medical Center, Nijmegen (M.H.), Rijnstate Hospital, Arnhem (M.H.), and the Dutch Network for Cardiovascular Research, Utrecht (M.H.) - all in the Netherlands; Cooper Medical School of Rowan University, Camden (A.M.R.), and Bayer U.S., Whippany (R.C.) - both in New Jersey; the Cardiology Center of Beijing, Anzhen Hospital No. 2, Beijing (C.-S.M.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael's Hospital, Unity Health Toronto, and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto - all in Canada (S.G.G.); the Uppsala Clinical Research Center and the Department of Medical Sciences, Uppsala University, Uppsala, Sweden (J.O.); the Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia (C.H.); the Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); the School of Cardiology, University of Pisa, and the Cardiology Division, Pisa University Hospital, Pisa (R.D.C.), and Santa Maria della Misericordia Hospital, University of Perugia, Perugia (V.C.) - all in Italy; the Department of Cardiology, University Heart and Vascular Center Hamburg, and the German Center for Cardiovascular Research, Hamburg (P.K.), and Bayer, Wuppertal (C.N., T.V., H.M.) - all in Germany; the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (P.K.), the Faculty of Medicine, National Heart and Lung Institute, Imperial College, London (D.A.G.), the Centre for Health Services and Clinical Research, Faculty of Life and Medical Sciences, University of Hertfordshire, Hatfield (D.A.G.), and the Liverpool Centre for Cardiovascular Science at University of Liverpool and John Moores University and Liverpool Heart and Chest Hospital, Liverpool (G.Y.H.L.) - all in the United Kingdom; the Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark (G.Y.H.L.); and Bayer, São Paulo (J. Hung).
Background: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.
Methods: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban.
Nat Microbiol
September 2024
Africa Health Research Institute, Durban, South Africa.
Nature
September 2024
Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Cell
October 2024
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address:
Animal and bacterial cells sense and defend against viral infections using evolutionarily conserved antiviral signaling pathways. Here, we show that viruses overcome host signaling using mechanisms of immune evasion that are directly shared across the eukaryotic and prokaryotic kingdoms of life. Structures of animal poxvirus proteins that inhibit host cGAS-STING signaling demonstrate architectural and catalytic active-site homology shared with bacteriophage Acb1 proteins, which inactivate CBASS anti-phage defense.
View Article and Find Full Text PDFNat Cardiovasc Res
December 2023
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions.
View Article and Find Full Text PDFNat Cardiovasc Res
March 2024
Cardiovascular Institute, Epigenetics Institute, and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Human induced pluripotent stem cell (hiPSC) to cardiomyocyte (CM) differentiation has reshaped approaches to studying cardiac development and disease. In this study, we employed a genome-wide CRISPR screen in a hiPSC to CM differentiation system and reveal here that BRD4, a member of the bromodomain and extraterminal (BET) family, regulates CM differentiation. Chemical inhibition of BET proteins in mouse embryonic stem cell (mESC)-derived or hiPSC-derived cardiac progenitor cells (CPCs) results in decreased CM differentiation and persistence of cells expressing progenitor markers.
View Article and Find Full Text PDFNPJ Vaccines
August 2024
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.
Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity.
View Article and Find Full Text PDFCJEM
October 2024
School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Objectives: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus).
View Article and Find Full Text PDFNature
September 2024
Gladstone-UCSF Institute of Data Science and Biotechnology, San Francisco, CA, USA.
The rapid evolution of viruses generates proteins that are essential for infectivity and replication but with unknown functions, due to extreme sequence divergence. Here, using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are structurally distinct and lack homologues in the AlphaFold database. Among the remaining 38% of viral proteins, many have non-viral structural analogues that revealed surprising similarities between human pathogens and their eukaryotic hosts.
View Article and Find Full Text PDFInt J Infect Dis
November 2024
Vitalant Research Institute, San Francisco, California, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA; Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.
Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).
Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users.
Cancer Immunol Res
November 2024
Ragon Institute of Mass General, MIT, and Harvard, Cambridge, Massachusetts.
Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses.
View Article and Find Full Text PDFbioRxiv
August 2024
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge.
View Article and Find Full Text PDFMaternal diabetes mellitus is among the most frequent environmental contributors to congenital birth defects, including heart defects and craniofacial anomalies, yet the cell types affected and mechanisms of disruption are largely unknown. Using multi-modal single cell analyses, here we show that maternal diabetes affects the epigenomic landscape of specific subsets of cardiac and craniofacial progenitors during embryogenesis. A previously unrecognized cardiac progenitor subpopulation expressing the homeodomain-containing protein ALX3 showed prominent chromatin accessibility changes and acquired a more posterior identity.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
February 2025
Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; The Department of Radiation Oncology and Applied Sciences, Dartmouth Cancer Center, Dartmouth Health, Lebanon, New Hampshire.
Lancet Microbe
October 2024
Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway; Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK; Helsinki Institute for Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. Electronic address:
J Am Chem Soc
September 2024
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
The envelope (E) protein of SARS-CoV-2 is the smallest of the three structural membrane proteins of the virus. E mediates budding of the progeny virus in the endoplasmic reticulum Golgi intermediate compartment of the cell. It also conducts ions, and this channel activity is associated with the pathogenicity of SARS-CoV-2.
View Article and Find Full Text PDFNucleic Acids Res
September 2024
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
bioRxiv
August 2024
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.
SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses.
View Article and Find Full Text PDFbioRxiv
August 2024
Gladstone|UCSF Center for Cell Circuitry, University of California, San Francisco, CA 94158.
Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise, remains unclear. Here we utilize a small-molecule perturbation (IdU) to amplify noise and assess noise quantification from numerous scRNA-seq algorithms on human and mouse datasets, and then compare to noise quantification from single-molecule RNA FISH (smFISH) for a panel of representative genes.
View Article and Find Full Text PDFBioinform Adv
August 2024
Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN 46556, United States.