20 results match your criteria: "CA (K.G.A.); and Howard Hughes Medical Institute[Affiliation]"
Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience.
Nat Genet
December 2024
Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location, University of Amsterdam, Amsterdam, the Netherlands.
Article Synopsis
- * A large study involving nearly 10,000 DCM cases and close to a million controls identified 70 significant genetic locations linked to the disease, revealing the importance of heart muscle cells in its development.
- * The research also indicates that factors like higher body weight and blood pressure may contribute to DCM, and genetic risk scores can help predict the condition across different populations.
Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic.
Cell
September 2024
Institut d'Écologie et des Sciences de l'Environnement (IEES-Paris, UMR 7618), CNRS, Sorbonne Université, UPEC, IRD, INRAE, Paris, France. Electronic address:
Article Synopsis
- Zoonotic viruses, like SARS-CoV-2, can spill over from animals to humans, often linked to animal trade, with COVID-19 traced back to the Huanan Seafood Wholesale Market.
- Analysis of environmental samples from the market in early 2020 shows high genetic diversity of SARS-CoV-2, especially near a wildlife stall that had a variety of wildlife DNA, including potential intermediate hosts.
- The research combines genomic techniques to identify specific animal species and suggest which ones should be prioritized for further research on their role in transmitting the virus.
Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex.
Immunity
September 2024
Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address:
Article Synopsis
- - Lassa virus, which is linked to thousands of deaths annually, primarily spreads from Mastomys rodents to humans, highlighting the need for effective vaccines and treatments.
- - Researchers conducted experiments using pseudovirus deep mutational scanning to analyze mutations in the virus's glycoprotein complex (GPC) that impact its ability to enter cells and be neutralized by antibodies.
- - The study identified how mutations in GPC can escape neutralization by existing antibodies and proposed a method to better understand these variations, which could improve the development of future vaccines and therapies.
Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus glycoprotein complex.
bioRxiv
February 2024
Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus's glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization.
View Article and Find Full Text PDFGenomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.
Cell
December 2023
Department of Immunology and Microbiology, Scripps Research, La Jolla, CA, USA. Electronic address:
The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions.
View Article and Find Full Text PDFGenetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic.
bioRxiv
September 2023
Institut d'Écologie et des Sciences de l'Environnement (IEES-Paris, UMR 7618), CNRS, Sorbonne Université, UPEC, IRD, INRAE, Paris, France.
Article Synopsis
- Zoonotic virus spillovers, including the COVID-19 pandemic, are linked to animal trade, with the Huanan Seafood Market in Wuhan being a focal point of investigation.
- Analysis of environmental samples from this market showed a specific wildlife stall with high SARS-CoV-2 positivity and identified various animal DNA, including raccoon dogs, which can transmit the virus.
- The study used genetic data to suggest potential intermediate hosts for SARS-CoV-2, aiming to guide future testing and viral sampling efforts.
Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program.
Nat Genet
July 2023
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Article Synopsis
- A genome-wide association study (GWAS) was conducted on thoracic aortic aneurysms and dissections (TAAD) involving nearly 450,000 participants, identifying 21 genetic risk loci, 17 of which are new findings.
- The study utilized various analytical methods to pinpoint specific genes and cell types linked to TAAD, reinforcing that it is a unique condition not caused by the usual vascular disease factors.
- The research highlights that the genetic basis of TAAD is complex, similar to other traits, and is not only influenced by significant protein-altering gene variants.
Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations.
Nat Methods
April 2023
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Article Synopsis
- The global scientific community has sequenced over 11 million SARS-CoV-2 genomes by May 2022, allowing real-time tracking of virus evolution.
- Outbreak.info is a platform that monitors over 40 million variants and mutations across 7,000 locations, providing valuable insights for researchers and public health officials.
- The platform features user-friendly visualizations and robust infrastructure for data ingestion and dissemination, supporting genomic surveillance and hypothesis generation regarding the pandemic.
Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources.
Nat Methods
April 2023
Department of Integrative, Structural and Computational Biology, the Scripps Research Institute, La Jolla, CA, USA.
Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources.
View Article and Find Full Text PDFImmune checkpoint expression on HIV-specific CD4+ T cells and response to their blockade are dependent on lineage and function.
EBioMedicine
October 2022
Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada; Université de Montréal, Montreal, Quebec, Canada. Electronic address:
Article Synopsis
- The study explores how immune checkpoint blockade (ICB) affects HIV-specific CD4+ T cells, focusing on expression of dysfunction-related molecules in individuals with varying levels of HIV viral load.
- Researchers found that the responsiveness of T helper cell subsets to ICB varied based on infection status and specific T cell functions, indicating that the functional state of the cells affects their reaction to treatment.
- The findings suggest that different CD4+ T cell subsets show varying sensitivities to PD-1 inhibition, which could influence the effectiveness of ICB in improving T cell function in HIV and potentially other diseases.
Deep Learning Detects Changes Indicative of Axial Spondyloarthritis at MRI of Sacroiliac Joints.
Radiology
December 2022
From the Institute for Radiology (K.K.B., L.C.A., K.G.A.H., T.D., S.M.N., B.H., J.L.V.) and Department of Gastroenterology, Infectious Diseases and Rheumatology (including Nutrition Medicine) (F.P., L.S., M.P., V.R.R., H.H., J.R., M.T., D.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany (K.K.B., L.C.A., J.R.); Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Technical University of Munich, Munich, Germany (M.R.M.); Department of Medicine, University of Alberta, Edmonton, Alberta, Canada (R.G.L., W.P.M.); Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Germany (X.B.); and Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany (D.P.).
Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection.
View Article and Find Full Text PDFWastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Nature
September 2022
Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Article Synopsis
- Effective detection of SARS-CoV-2 variants through wastewater analysis can complement existing clinical testing methods, especially in resource-limited areas where traditional testing may be biased.* -
- The study implemented improved virus concentration techniques and software to enhance the sequencing of multiple virus strains from wastewater, resulting in high-resolution data over 295 days at a university and its surrounding county.* -
- Wastewater surveillance identified emerging variants up to 14 days earlier than clinical methods and revealed instances of virus spread that clinical testing missed, highlighting its potential for public health monitoring.*
Emergence of an early SARS-CoV-2 epidemic in the United States.
Cell
September 2021
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Research Translational Institute, La Jolla, CA 92037, USA. Electronic address:
Article Synopsis
- The COVID-19 epidemic in the U.S. went largely unnoticed due to a lack of testing, with New Orleans experiencing one of the earliest outbreaks during Mardi Gras.
- Researchers sequenced SARS-CoV-2 genomes in Louisiana and found that the virus had limited diversity, indicating a single introduction led to most early cases.
- The study revealed that SARS-CoV-2 was likely present in New Orleans before Mardi Gras, and the event significantly contributed to the rapid spread of the virus, highlighting the impact of large gatherings on epidemics.
The origins of SARS-CoV-2: A critical review.
Cell
September 2021
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK. Electronic address:
Article Synopsis
- A new virus similar to other viruses called coronaviruses was first noticed in Wuhan, China, in December 2019.
- Scientists are trying to figure out how this virus, named SARS-CoV-2, started spreading among people.
- There are two main ideas: one suggests it accidentally escaped from a lab, and the other says it came from animals.
Global genome analysis reveals a vast and dynamic anellovirus landscape within the human virome.
Cell Host Microbe
August 2021
Ring Therapeutics, Cambridge, MA 02139, USA. Electronic address:
Anelloviruses are a ubiquitous component of healthy human viromes and remain highly prevalent after being acquired early in life. The full extent of "anellome" diversity and its evolutionary dynamics remain unexplored. We employed in-depth sequencing of blood-transfusion donor(s)-recipient pairs coupled with public genomic resources for a large-scale assembly of anellovirus genomes and used the data to characterize global and personal anellovirus diversity through time.
View Article and Find Full Text PDFEmergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.
Cell
May 2021
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92122, USA. Electronic address:
The highly transmissible B.1.1.
View Article and Find Full Text PDFEbola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease.
N Engl J Med
April 2021
From the Institut National de Recherche Biomédicale (P.M.-K., A.N.-N., E.K.-L., A.A., D.M., N.B., D.K., B.N., M.A., O.T., S.M, S.A.-M., J.-J.M.T.), the University of Kinshasa (P.M.-K., A.N.-N., F.M., F.E., M.M., J.B.B., S.A.-M., J.-J.M.T.), and Ministère de la Santé (F.B., V.E., E.S.-P., Y.T.T.N.) - all in Kinshasa, Democratic Republic of Congo; the University of Nebraska Medical Center, Omaha (C.P., B.W., M.R.W.); International Medical Corps (M.M.-R.) and the University of California, Los Angeles (A.W.R., M.A.S.), Los Angeles, and the Scripps Research Institute, La Jolla (M.G.P., K.G., E.S., A.T., K.G.A.) - all in California; the Fred Hutchinson Cancer Research Center, Seattle (A.B., J.H., T.B.); the Institut Pasteur de Dakar, Dakar, Senegal (M.F., M.M.D., O.F., A.S.); the Vaccine Research Center, National Institutes of Health, Bethesda (J.M., A.P., N.J.S.), and the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research (I.C.), and the Integrated Research Facility at Fort Detrick, National Institutes of Health (L.H.), Frederick - all in Maryland; the World Health Organization, Geneva (B.D., M.K., M.R.D.B., I.S.F., A.Y.); and the University of Edinburgh, Edinburgh, United Kingdom (A.R.).
During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died.
View Article and Find Full Text PDFMolecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas.
Cancers (Basel)
February 2021
Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients.
View Article and Find Full Text PDFTransethnic Transferability of a Genome-Wide Polygenic Score for Coronary Artery Disease.
Circ Genom Precis Med
February 2021
Centre for Genomic Medicine, Department of Medicine (A.C.F., A.V.K.), Massachusetts General Hospital.
Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018.
N Engl J Med
November 2018
From the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University (K.J.S., K.G.B., S.M., S.F.S., S.M.W., R.R.S., J.Q., S.W., P.B., S.Y., B.C., D.K., A.C., A.G.-Y., C.A.F., D.J.P., N.L.Y., B.L.M., P.C.S.), the Center for Systems Biology, Department of Organismic and Evolutionary Biology (K.J.S., K.G.B., S.F.S., S.W., B.C., D.K., C.A.F., N.L.Y., P.C.S.), and the Faculty of Arts and Sciences (M.N.), Harvard University, Harvard University Extension School (R.R.S.), and Harvard-MIT Health Sciences and Technology, MIT (S.Y., P.C.S.), Cambridge, and the Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health (K.G.B., S.F.S., B.L.M., P.C.S., C.T.H.), and Beth Israel Deaconess Medical Center, Division of Infectious Diseases (S.M.), Boston - all in Massachusetts; the African Center of Excellence for Genomics of Infectious Diseases (P.E., J.U.O., E.U., T.K., F.A., J.U., A.G., M.M., I.N., P.O., O.T., O.A.F., C.T.H.) and the Department of Biological Sciences, College of Natural Sciences (J.U.O., E.U., T.K., F.A., J.U., P.O., O.A.F., C.T.H.), Redeemer's University, Ede, the Institute of Lassa Fever Research and Control (I.O., C. Iruolagbe, J.A., E.U., P.A., G.O., O.O., B.O., E.B.M., M.A., R.E., B.E., E.O.-E., G.A., S.O., P.O.O., C.T.H.) and the Department of Medicine (P.O.O.), Irrua Specialist Teaching Hospital, Irrua, the Nigeria Center for Disease Control, Abuja (C. Ihekweazu), and the Department of Medicine, Faculty of Clinical Sciences, Ambrose Alli University, Ekpoma (P.O.O.) - all in Nigeria; the Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, Dakar, Senegal (A.G.); Kenema Government Hospital, Kenema, Sierra Leone (M.M.); Tulane Health Sciences Center, Tulane University, New Orleans (R.F.G.); the Departments of Immunology and Microbial Science and Integrative Structural and Computational Biology, Scripps Research Institute, and the Scripps Translational Science Institute, La Jolla, CA (K.G.A.); and Howard Hughes Medical Institute, Chevy Chase, MD (P.C.S.).
During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time.
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