A5088832021- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Mosquito-borne diseases and control
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Transgenic Plants and Applications
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Inflammasome and immune disorders
- Respiratory Support and Mechanisms
- vaccines and immunoinformatics approaches
- COVID-19 and healthcare impacts
- Vector-borne infectious diseases
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- HIV-related health complications and treatments
- Viral gastroenteritis research and epidemiology
- Parasitic Infections and Diagnostics
- Connexins and lens biology
- Toxin Mechanisms and Immunotoxins
Boston VA Research Institute
2020-2024
Harvard University
2020-2024
Northwest University
2023
NHS Lothian
2022
Edinburgh Royal Infirmary
2022
University of Virginia Health System
2021
University of Virginia
2020
Oregon State University
2014-2018
<h3>Importance</h3> In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low volume ventilation, may improve outcomes. <h3>Objective</h3> To determine whether lower using extracorporeal carbon dioxide removal improves outcomes failure. <h3>Design, Setting, and Participants</h3> This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult receiving...
Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they become dominant strains. Here, we evaluate consequences further viral evolution. We demonstrate mechanisms through which SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers simultaneous escape mutations and show that pseudotypes containing up to seven mutations, as opposed one three found in previously studied concern, are...
SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in a minority of patients. Although severe COVID-19 disease is linked exuberant inflammation, how triggers inflammation not understood. Monocytes macrophages are sentinel immune cells the blood tissue, respectively, sense invasive infection form inflammasomes activate caspase-1 gasdermin D (GSDMD) pores, leading inflammatory (pyroptosis) processing release IL-1 family cytokines, potent mediators....
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
Abstract Eastern equine encephalitis virus (EEEV) is the most virulent alphavirus that infects humans, and many survivors develop neurological sequelae, including paralysis intellectual disability. Alphavirus spike proteins comprise trimers of heterodimers glycoproteins E2 E1 mediate binding to cellular receptors fusion host cell membranes during entry. We recently identified very-low density lipoprotein receptor (VLDLR) apolipoprotein E 2 (ApoER2) as for EEEV a distantly related alphavirus,...
Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub Rsa4, direct substrate force-generating ATPase Rea1. We show Rsa4 connected central protuberance by binding Rpl5 and ribosomal RNA (rRNA) helix 89 peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds before relocation PTC....
LC8 is a dimeric hub protein involved in large number of interactions central to cell function. It binds short linear motifs—usually containing Thr-Gln-Thr (TQT) triplet—in intrinsically disordered regions its binding partners, some which have several recognition motifs tandem. Hallmarks the 7–10 amino acid motif are high variability affinity and extensive sequence permutation outside TQT triplet. To elucidate molecular basis recognition, we use 69-residue segment human Chica spindle adaptor...
Abstract The SARS-CoV-2 viral spike (S) protein mediates attachment and entry into host cells is a major target of vaccine drug design. Potent neutralizing antibodies derived from closely related antibody heavy chain genes (IGHV3-53 or 3-66) have been isolated multiple COVID-19 convalescent individuals. These usually contain minimal somatic mutations bind the S receptor-binding domain (RBD) to interfere with cellular receptor angiotensin-converting enzyme 2 (ACE2). We used antigen-specific...
Abstract The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent clones owing to the powerful evolutionary process of somatic hypermutation. However, immunization is inherently slow, has poor compatibility with certain antigens ( e . g ., integral membrane proteins), suffers from self-tolerance immunodominance, limit functional spectrum antibodies that be obtained. Here, we describe A utonomous H ypermutation y E ast...
Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary replicate. Using murine herpesvirus 68 (MHV-68) as a model system understand how similar human gammaherpesviruses cause cancer, we profiled changes that occur during lytic MHV-68 infection replication.
Many methods of protein structure generation such as NMR-based solution determination and template-based modeling do not produce a single model, but an ensemble models consistent with the available information. Current strategies for comparing ensembles lose information because they use only representative structure. Here, we describe ENSEMBLATOR its novel strategy to directly compare two containing same atoms identify significant global local backbone differences between them on per-atom...
Clinical trials are underway to evaluate the safety and efficacy of transcatheter mitral valve replacement in intermediate high surgical risk patients. We analyzed outcomes a regional consortium provide benchmark data for emerging alternative therapies.All patients undergoing with Society Thoracic Surgeons predicted mortality (STS PROM) from 2001 2017 were analyzed. Patients endocarditis excluded. stratified by STS PROM into low (<4%), moderate (4%-8%), (>8%) cohorts. Mortality,...
ABSTRACT Oncogenic virus infections are estimated to cause ∼15% of all cancers. Two prevalent human oncogenic viruses members the gammaherpesvirus family: Epstein Barr Virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV EBV, as a model system study lytic replication. Viruses implement distinct metabolic programs support their life cycle, such increasing supply lipids, amino acids, nucleotide materials...
Alphaviruses are arthropod-borne enveloped RNA viruses that include several important human pathogens with outbreak potential. Among them, eastern equine encephalitis virus (EEEV) is the most virulent, and many survivors develop neurological sequelae, including paralysis intellectual disability. The spike proteins of alphaviruses comprise trimers heterodimers their envelope glycoproteins E2 E1 mediate binding to cellular receptors fusion host cell membranes during entry. We recently...