Digital Commons Network^™

First-Generation And Continuing-Generation College Graduates' Application, Acceptance, And Matriculation To U.S. Medical Schools: A National Cohort Study, Hyacinth R C Mason, Ashar Ata, Mytien Nguyen, Sunny Nakae, Devasmita Chakraverty, Branden Eggan, Sarah Martinez, Donna B Jeffe

Open Access Publications

Many U.S. medical schools conduct holistic review of applicants to enhance the socioeconomic and experiential diversity of the physician workforce. The authors examined the role of first-generation college-graduate status on U.S. medical school application, acceptance, and matriculation, hypothesizing that first-generation (vs. continuing-generation) college graduates would be less likely to apply and gain acceptance to medical school.Secondary analysis of de-identified data from a retrospective national-cohort study was conducted for individuals who completed the 2001-2006 Association of American Medical Colleges (AAMC) Pre-Medical College Admission Test Questionnaire (PMQ) and the Medical College Admissions Test (MCAT). AAMC provided medical school application, acceptance, and matriculation …

'I Need Time To Start Antiretroviral Therapy': Understanding Reasons For Delayed Art Initiation Among People Diagnosed With Hiv In Lusaka, Zambia, Chanda Mwamba, Laura K Beres, Stephanie M Topp, Njekwa Mukamba, Sandra Simbeza, Kombatende Sikombe, Aaloke Mody, Elvin Geng, Charles B Holmes, Caitlin E Kennedy, Izukanji Sikazwe, Julie A Denison, Carolyn Bolton Moore

Open Access Publications

INTRODUCTION: Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately.

METHODS: We conducted a qualitative study to inform interventions supporting rapid initiation in the 'Test and Start' era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation.

RESULTS: Drawing on messages gleaned from facility-based counselling and community information, many …

The Microbial One-Hit Wonder, Brigida A. Rusconi, Rodney D. Newberry

Open Access Publications

Intestinal inflammation, in the absence of infection, occurs from contributions by genetics and environment. Chen et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210324) challenge this concept by demonstrating that a dominant transmissible dysbiotic microbial community predisposes to intestinal inflammation in absence of genetic alterations.

Making An Impact On Kidney Disease In People With Type 2 Diabetes: The Importance Of Screening For Albuminuria, Janet B Mcgill, Hermann Haller, Prabir Roy-Chaudhury, Andrea Cherrington, Takashi Wada, Christoph Wanner, Linong Ji, Peter Rossing

Open Access Publications

Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review …

Multisite Learning Of High-Dimensional Heterogeneous Data With Applications To Opioid Use Disorder Study Of 15,000 Patients Across 5 Clinical Sites, Xiaokang Liu, Rui Duan, Chongliang Luo, Alexis Ogdie, Jason H Moore, Henry R Kranzler, Jiang Bian, Yong Chen

Open Access Publications

Integrating data across institutions can improve learning efficiency. To integrate data efficiently while protecting privacy, we propose A one-shot, summary-statistics-based, Distributed Algorithm for fitting Penalized (ADAP) regression models across multiple datasets. ADAP utilizes patient-level data from a lead site and incorporates the first-order (ADAP1) and second-order gradients (ADAP2) of the objective function from collaborating sites to construct a surrogate objective function at the lead site, where model fitting is then completed with proper regularizations applied. We evaluate the performance of the proposed method using both simulation and a real-world application to study risk factors for opioid use disorder (OUD) using …

Large Comparative Analyses Of Primate Body Site Microbiomes Indicate That The Oral Microbiome Is Unique Among All Body Sites And Conserved Among Nonhuman Primates, Abigail E Asangba, Lawrence Mugisha, Joshua Rukundo, Rebecca J Lewis, Ali Halajian, Liliana Cortés-Ortiz, Randall E Junge, Mitchell T Irwin, Johan Karlson, Andrew Perkin, Mrinalini Watsa, Gideon Erkenswick, Karen L Bales, Dorothy L Patton, Anna J Jasinska, Eduardo Fernandez-Duque, Steven R Leigh, Rebecca M Stumpf

Open Access Publications

The study of the mammalian microbiome serves as a critical tool for understanding host-microbial diversity and coevolution and the impact of bacterial communities on host health. While studies of specific microbial systems (e.g., in the human gut) have rapidly increased, large knowledge gaps remain, hindering our understanding of the determinants and levels of variation in microbiomes across multiple body sites and host species. Here, we compare microbiome community compositions from eight distinct body sites among 17 phylogenetically diverse species of nonhuman primates (NHPs), representing the largest comparative study of microbial diversity across primate host species and body sites. Analysis of …

Genomic Surveillance Of Clinical Pseudomonas Aeruginosa Isolates Reveals An Additive Effect Of Carbapenemase Production On Carbapenem Resistance, Luke Diorio-Toth, Sidra Irum, Robert F Potter, Meghan A Wallace, Muhammad Arslan, Tehmina Munir, Saadia Andleeb, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Carbapenem resistance in Pseudomonas aeruginosa is increasing globally, and surveillance to define the mechanisms of such resistance in low- and middle-income countries is limited. This study establishes the genotypic mechanisms of β-lactam resistance by whole-genome sequencing (WGS) in 142 P. aeruginosa clinical isolates recovered from three hospitals in Islamabad and Rawalpindi, Pakistan between 2016 and 2017. Isolates were subjected to antimicrobial susceptibility testing (AST) by Kirby-Bauer disk diffusion, and their genomes were assembled from Illumina sequencing data. β-lactam resistance was high, with 46% of isolates resistant to piperacillin-tazobactam, 42% to cefepime, 48% to ceftolozane-tazobactam, and 65% to at least one …

Comparability Of Clinical Trials And Spontaneous Reporting Data Regarding Covid-19 Vaccine Safety, Chongliang Luo, Jingcheng Du, Adam Cuker, Ebbing Lautenbach, David A Asch, Gregory A Poland, Cui Tao, Yong Chen

Open Access Publications

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports …

Detection Of Bourbon Virus-Specific Serum Neutralizing Antibodies In Human Serum In Missouri, Usa, Gayan Bamunuarachchi, Houda Harastani, Paul W Rothlauf, Ya-Nan Dai, Ali Ellebedy, Daved Fremont, Sean P J Whelan, David Wang, Adrianus C M Boon

Open Access Publications

Bourbon virus (BRBV) was first discovered in 2014 in a fatal human case. Since then it has been detected in the tick Amblyomma americanum in the states of Missouri and Kansas in the United States. Despite the high prevalence of BRBV in ticks in these states, very few human cases have been reported, and the true infection burden of BRBV in the community is unknown. Here, we developed two virus neutralization assays, a vesicular stomatitis virus (VSV)-BRBV pseudotyped rapid assay and a BRBV focus reduction neutralization assay, to assess the seroprevalence of BRBV neutralizing antibodies in human sera collected in …

Paris And Sparta: Finding The Achilles' Heel Of Sars-Cov-2, Viviana Simon, Ali H Ellebedy, Et Al

Open Access Publications

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators.

Structure Of A Vaccine-Induced, Germline-Encoded Human Antibody Defines A Neutralizing Epitope On The Sars-Cov-2 Spike N-Terminal Domain, Clara G Altomare, Daniel C Adelsberg, Juan Manuel Carreno, Iden A Sapse, Fatima Amanat, Ali H Ellebedy, Viviana Simon, Florian Krammer, Goran Bajic

Open Access Publications

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy …

Invl, An Invasin-Like Adhesin, Is A Type Ii Secretion System Substrate Required For Acinetobacter Baumannii Uropathogenesis, Clay D Jackson-Litteken, Gisela Di Venanzio, Nguyen-Hung Le, Nichollas E Scott, Bardya Djahanschiri, Jesus S Distel, Evan J Pardue, Ingo Ebersberger, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type II secretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Here, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify …

Isolation Of A Potently Neutralizing And Protective Human Monoclonal Antibody Targeting Yellow Fever Virus, Michael P Doyle, Joseph R Genualdi, Adam L Bailey, Nurgun Kose, Christopher Gainza, Jessica Rodriguez, Kristen M Reeder, Christopher A Nelson, Prashant N Jethva, Rachel E Sutton, Robin G Bombardi, Michael L Gross, Justin G Julander, Daved H Fremont, Michael S Diamond, James E Crowe

Open Access Publications

Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus. Recent advances in monoclonal antibody (mAb) technology have allowed the identification of numerous candidate therapeutics targeting highly pathogenic viruses, including many flaviviruses. Here, we sought to identify …

Human Metapneumovirus Phosphoprotein Independently Drives Phase Separation And Recruits Nucleoprotein To Liquid-Like Bodies, Kerri Beth Boggs, Kearstin Edmonds, Nicolas Cifuentes-Munoz, Farah El Najjar, Conny Ossandón, Mckenna Roe, Chao Wu, Carole L Moncman, Trevor P Creamer, Gaya K Amarasinghe, Daisy W Leung, Rebecca Ellis Dutch

Open Access Publications

Human metapneumovirus (HMPV) inclusion bodies (IBs) are dynamic structures required for efficient viral replication and transcription. The minimum components needed to form IB-like structures in cells are the nucleoprotein (N) and the tetrameric phosphoprotein (P). HMPV P binds to the following two versions of the N protein in infected cells: N-terminal P residues interact with monomeric N (N

The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic And Oxidative Stress Responses In Acinetobacter, Anna J Hooppaw, Jenna C Mcguffey, Gisela Di Venanzio, Juan C Ortiz-Marquez, Brent S Weber, Tasia Joy Lightly, Tim Van Opijnen, Nichollas E Scott, Silvia T Cardona, Mario F Feldman

Open Access Publications

The opportunistic pathogen Acinetobacter baumannii is responsible for a wide range of infections that are becoming increasingly difficult to treat due to extremely high rates of multidrug resistance. Acinetobacter's pathogenic potential is thought to rely on a "persist and resist" strategy that facilitates its remarkable ability to survive under a variety of harsh conditions. The

Cancer Cells Dying From Ferroptosis Impede Dendritic Cell-Mediated Anti-Tumor Immunity, Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S Ravichandran, Peter Vandenabeele

Open Access Publications

Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process-'initial' associated with lipid peroxidation, 'intermediate' correlated with ATP release and 'terminal' recognized by HMGB1 release and loss of plasma membrane integrity-that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals …

Dissociation Between Individual Differences In Self-Reported Pain Intensity And Underlying Fmri Brain Activation, M E Hoeppli, H Nahman-Averbuch, W A Hinkle, E Leon, J Peugh, M Lopez-Sola, C D King, K R Goldschneider, R C Coghill

Open Access Publications

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related …

68ga-Labeled Benzothiazole Derivatives For Imaging Aβ Plaques In Cerebral Amyloid Angiopathy, Truc T Huynh, Yujue Wang, Karna Terpstra, Hong-Jun Cho, Liviu M Mirica, Buck E Rogers

Open Access Publications

Timely diagnostic imaging plays a crucial role in managing cerebral amyloid angiopathy (CAA)-the condition in which amyloid β is deposited on blood vessels. To selectively map these amyloid plaques, we have designed amyloid-targeting ligands that can effectively complex with

The Challenges Of Interrogating Adipose Tissue Extracellular Vesicle Functions In Physiology, Clair Crewe

Open Access Publications

No abstract provided.

Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Michael A. Province, Et Al

Open Access Publications

No abstract provided.

A Long-Acting Interleukin-7, Rhil-7-Hyfc, Enhances Car T Cell Expansion, Persistence, And Anti-Tumor Activity, Miriam Y Kim, Reyka Jayasinghe, Jessica M Devenport, Julie K Ritchey, Michael P Rettig, Julie O'Neal, Karl W Staser, Krista M Kennerly, Alun J Carter, Feng Gao, Byung Ha Lee, Matthew L Cooper, John F Dipersio

Open Access Publications

Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free …

Antigen Glycosylation Regulates Efficacy Of Car T Cells Targeting Cd19, Amanda Heard, Jack H Landmann, Ava R Hansen, Yu-Sung Hsu, Mehmet Emrah Selli, John M Warrington, John Lattin, Jufang Chang, Helen Ha, Balraj Doray, Abby M Green, Nathan Singh, Et Al

Open Access Publications

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance …

Phase I Study Of Safety, Tolerability, And Efficacy Of Tebentafusp Using A Step-Up Dosing Regimen And Expansion In Patients With Metastatic Uveal Melanoma, Richard D Carvajal, Paul Nathan, Joseph J Sacco, Marlana Orloff, Leonel F Hernandez-Aya, Jessica Yang, Jason J Luke, Marcus O Butler, Sarah Stanhope, Laura Collins, Cheryl Mcalpine, Chris Holland, Shaad E Abdullah, Takami Sato

Open Access Publications

PURPOSE: This phase I study aimed to define the recommended phase II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using a three-week step-up dosing regimen, and to assess its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in patients with metastatic uveal melanoma (mUM).

METHODS: In this open-label, international, phase I/II study, HLA-A*02 or HLA-A*02:01+ patients with mUM received tebentafusp 20 μg once in week 1 and 30 μg once in week 2. Dose escalation (starting at 54 μg) began at week 3 in a standard 3 + 3 design to define RP2D. Expansion-phase patients were treated at …

Blimp-1 Molds The Epigenetic Architecture Of Il-21-Mediated Autoimmune Diseases Through An Autoregulatory Circuit, Yu-Wen Liu, Shin-Huei Fu, Ming-Wei Chien, Chao-Yuan Hsu, Ming-Hong Lin, Jia-Ling Dong, Rita Jui-Hsien Lu, Yi-Jing Lee, Pao-Yang Chen, Chih-Hung Wang, Huey-Kang Sytwu

Open Access Publications

Positive regulatory domain 1 (PRDM1) encodes B lymphocyte-induced maturation protein 1 (BLIMP1), also known as a master regulator of T cell homeostasis. We observed a negative relationship between Blimp-1 and IL-21 based on our previous data that Blimp-1 overexpression in T cells suppresses autoimmune diabetes while Blimp-1-deficient T cells contribute to colitis in NOD mice. Reanalysis of published data sets also revealed an inverse correlation between PRDM1 and IL21 in Crohn's disease. Here, we illustrate that Blimp-1 repressed IL-21 by reducing chromatin accessibility and evicting an IL-21 activator, c-Maf, from the Il21 promoter. Moreover, Blimp-1 overexpression-mediated reduction in permissive chromatin …

Estrogen Hormone Is An Essential Sex Factor Inhibiting Inflammation And Immune Response In Covid-19, Fuhai Li, Adrianus C M Boon, Andrew P Michelson, Randi E Foraker, Ming Zhan, Philip R O Payne

Open Access Publications

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality of COVID-19 patients already infected with SARS-CoV-2. The global data on COVID-19 showed that men have a higher mortality rate than women. We further observed that the proportion of mortality of females increases starting from around the age of 55 significantly. Thus, sex is an essential factor associated with COVID-19 mortality, and sex related genetic factors could be interesting mechanisms and targets for COVID-19 treatment. However, the associated sex factors and signaling pathways remain unclear. Here, we propose …

Political Environment And Mortality Rates In The United States, 2001-19: Population Based Cross Sectional Analysis, Haider J Warraich, Pankaj Kumar, Khurram Nasir, Karen E Joynt Maddox, Rishi K Wadhera

Open Access Publications

OBJECTIVE: To assess recent trends in age adjusted mortality rates (AAMRs) in the United States based on county level presidential voting patterns.

DESIGN: Cross sectional study.

SETTING: USA, 2001-19.

PARTICIPANTS: 99.8% of the US population.

MAIN OUTCOME MEASURES: AAMR per 100 000 population and average annual percentage change (APC).

METHODS: The Centers for Disease Control and Prevention WONDER database was linked to county level data on US presidential elections. County political environment was classified as either Democratic or Republican for the four years that followed a November presidential election. Additional sensitivity analyses analyzed AAMR trends for counties that voted only …

The Aryl Hydrocarbon Receptor Instructs The Immunomodulatory Profile Of A Subset Of Clec4a4, Wei-Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Jennifer K Bando, Stanley Ching-Cheng Huang, Kentaro Yomogida, Steven J Van Dyken, Marina Cella, Marco Colonna, Et Al

Open Access Publications

SignificanceEosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4

Raising Is A High-Performance Method For Identifying Random Transgene Integration Sites, Yusaku Wada, Ariella L G Coler-Reilly, Et Al

Open Access Publications

Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes …

Evolutionarily Stable Gene Clusters Shed Light On The Common Grounds Of Pathogenicity In The Acinetobacter Calcoaceticus-Baumannii Complex, Bardya Djahanschiri, Gisela Di Venanzio, Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann, Beate Averhoff, Stephan Göttig, Gottfried Wilharm, Mario F. Feldman, Ingo Ebersberger

Open Access Publications

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in …

An Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Disrupts The Spike Trimer, Naveenchandra Suryadevara, Laura A. Vanblargan, Rita E. Chen, James Brett Case, Michael S. Diamond, Et Al

Open Access Publications

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope ("supersite") on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, …