A5067077021- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Malaria Research and Control
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Immunology Research
- Mosquito-borne diseases and control
- COVID-19 Clinical Research Studies
- Trypanosoma species research and implications
- Biosensors and Analytical Detection
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
- Bacillus and Francisella bacterial research
- Cytomegalovirus and herpesvirus research
- Genomic variations and chromosomal abnormalities
- Genetics, Bioinformatics, and Biomedical Research
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Legionella and Acanthamoeba research
- Genomics and Phylogenetic Studies
- Water Treatment and Disinfection
- Hydrogen's biological and therapeutic effects
- E-commerce and Technology Innovations
- Computational Drug Discovery Methods
Chan Zuckerberg Initiative (United States)
2019-2025
University of California, San Francisco
2014-2024
Stanford University
2023
Washington University in St. Louis
2023
Methodist Hospital
2023
Hong Kong Polytechnic University
2010-2022
Veterans Health Administration
2022
University of California System
2021
Neurology, Inc
2020
Howard Hughes Medical Institute
2016
Abstract Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report general protein language models can efficiently evolve human antibodies by mutations are evolutionarily plausible, despite providing the model with no information about target antigen, binding specificity or structure. We performed language-model-guided affinity...
Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses cerebrospinal fluid (CSF) blood from individuals COVID-19 we find compartmentalized, CNS-specific T cell activation B responses. All affected had CSF anti-severe acute respiratory syndrome 2 (SARS-CoV-2) antibodies whose target epitopes diverged serum antibodies. In...
Abstract We evaluated the performance of Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless symptoms, at a public plaza site ongoing community transmission. Titration with cultured severe acute respiratory syndrome 2 yielded human observable threshold between 1.6 × 104-4.3 104 viral RNA copies (cycle [Ct], 30.3–28.8). Among 878 subjects tested, 3% (26 878) were positive by reverse-transcription polymerase chain reaction,...
Antibody detection of prior SARS-CoV-2 infection depends on severity, assay, and timing with implications for serosurveillance.
Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in non-major histocompatibility complex (MHC)-restricted manner, can penetrate tissues more thoroughly than mAbs. However, previous study indicated that anti-CD19 CAR-T cells paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested B-cell-dependent EAE model responsive to anti-CD20...
Abstract Science frequently benefits from teams of interdisciplinary researchers. However, most scientists don’t have access to experts multiple fields. Fortunately, large language models (LLMs) recently shown an impressive ability aid researchers across diverse domains by answering scientific questions. Here, we expand the capabilities LLMs for science introducing Virtual Lab, AI-human research collaboration perform sophisticated, research. The Lab consists LLM principal investigator agent...
Delivery by Trojan horse: A water-soluble derivative of the chemotherapeutic agent taxol was synthesized with bioconjugation functionality and attached to capsids bacteriophage MS2 (see picture). The modified retained their form released when incubated MCF-7 cells. resulting cell-viability levels were similar those observed upon treatment free in solution. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited...
In MRI, anatomical structures are most often differentiated by variations in their bulk magnetic properties. Alternatively, exogenous contrast agents can be attached to chemical moieties that confer affinity molecular targets; the distribution of such imaged resonance. Xenon-based sensors imaging rely on reversible exchange hyperpolarized xenon between and a specifically targeted host-guest complex. We have incorporated approximately 125 sensor molecules interior an MS2 viral capsid,...
The apicoplast is an essential plastid organelle found in Plasmodium parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the "Malaria Box" library of growth-inhibitory antimalarial compounds as having specific activity against apicoplast. inhibition blood-stage falciparum growth stereospecific and potent, with most active diastereomer demonstrating a 50% effective concentration (EC50) 110 nM. Whole-genome...
Balamuthia mandrillaris is a pathogenic free-living amoeba that causes rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE). Two distinct forms B. mandrillaris-a proliferative trophozoite form and nonproliferative cyst form, which highly resistant to harsh physical chemical conditions-have been isolated from environmental samples worldwide are both observed in infected tissue. Patients suffering GAE typically treated with...
ABSTRACT We evaluated the performance of Abbott BinaxNOW™ Covid-19 rapid antigen test to detect virus among persons, regardless symptoms, at a public plaza site ongoing community transmission. Titration with cultured clinical SARS-CoV-2 yielded human observable threshold between 1.6×10 4 -4.3×10 viral RNA copies (cycle (Ct) 30.3-28.8 in this assay). Among 878 subjects tested, 3% (26/878) were positive by RT-PCR, which 15/26 had Ct<30, indicating high load. 40% (6/15) Ct<30...
Abstract The spread of coronavirus disease 2019 (COVID-19) has affected both physical health and mental well-being around the world. Stress-related reactions, if prolonged, may result in problems. We examined consequences COVID-19 pandemic on a multinational study explored effects government responses to outbreak. sampled 18,171 community adults from 35 countries/societies, stratified by age, gender, region residence. Across societies, 26.6% participants reported moderate extremely severe...
Genetic manipulation of the deadly malaria parasite Plasmodium falciparum remains challenging, but rise CRISPR/Cas9-based genome editing tools is increasing feasibility altering this parasite's in order to study its biology. Of particular interest investigation drug targets and resistance mechanisms, which have major implications for fighting malaria. We present a new method introducing mutations P. without use plasmids or need cloning homologous recombination templates. demonstrate by edits...
ABSTRACT Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance antibody assays to detect seroreactivity over time individuals with different clinical presentations. We measured longitudinal responses plasma samples from a diverse cohort 128 160 days using 14 binding neutralization assays. For all assays, we found consistent strong effect disease severity on...
Infection by Trypanosoma cruzi , the agent of Chagas disease, can irreparably damage cardiac and gastrointestinal systems during decades parasite persistence related inflammation in these tissues. Diagnosis chronic disease requires confirmation multiple serological assays due to imperfect performance existing clinical tests. Current serology tests utilize antigens discovered over three ago with small specimen sets predominantly from South America, lower test has been observed patients who...
Benzoxaboroles are under study as potential new drugs to treat malaria. One benzoxaborole, AN13762, has potent activity and promising features, but its mechanisms of action resistance unknown. To gain insights into these mechanisms, we cultured malaria parasites with nonlethal concentrations AN13762 generated varied levels resistance. Parasites low-level had mutations in PfPARE, which processes an active metabolite; PfPARE prevented this processing. high-level any a number enzymes, mostly...
<h3>Objective</h3> In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection characterization. <h3>Methods</h3> RNA was extracted from (n = 20), plasma 9), stool 15), nasopharyngeal samples 16) 10 children with meningitis or encephalitis. Pathogens...
Abstract Serosurveillance provides a unique opportunity to quantify the proportion of population that has been exposed pathogens. Here, we developed and piloted for Continuous, ActionabLe Epidemiologic Intelligence Transmission (SCALE-IT), platform through which systematically tested remnant samples from routine blood draws in two major hospital networks San Francisco SARS-CoV-2 antibodies during early months pandemic. Importantly, SCALE-IT allows algorithmic sample selection rich data on...
COVID-19 has drastically changed human behaviors and posed a threat to globalism by spurring resurgence of nationalism. Promoting prosocial behavior within across borders is paramount importance for global cooperation combat pandemics. To examine both self-report actual behavior, we conducted the first empirical test consciousness theory in multinational study 35 cultures ( N = 18,171 community adults stratified age, gender, region residence). Global encompassed cosmopolitan orientation,...
A multiplexed enzyme-linked immunosorbent assay (ELISA) that simultaneously measures antibody binding to multiple antigens can extend the impact of serosurveillance studies, particularly if approaches simplicity, robustness, and accuracy a conventional single-antigen ELISA. Here, we report on development multiSero, an open-source multiplex ELISA platform for measuring responses viral infection. Our consists three parts: (1) against array proteins in 96-well format; (2) automated imaging each...
The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight mutations enabling immune escape. Understanding how these affect the dynamics antibody-antigen interactions is crucial to development broadly protective antibodies vaccines. Here we report characterization a potent neutralizing antibody (N3-1) identified from COVID-19 patient during first disease wave. Cryogenic electron microscopy revealed quaternary binding mode...
Abstract We identify a mutation in the N gene of SARS-CoV-2 that adversely affects annealing commonly used RT-PCR primer; epidemiologic evidence suggests virus retains pathogenicity and competence for spread. This reinforces importance using multiple targets, preferably at least 2 genes, robust detection. Article Summary Line A variant occurs worldwide has spread California significantly diagnostic sensitivity an assay, highlighting need to employ viral targets