Digital Commons Network^™

Elevated Mrna Expression And Defective Processing Of Cathepsin D In Hela Cells Lacking The Mannose 6-Phosphate Pathway, Lin Liu, Balraj Doray

2020-Current year OA Pubs

Disruption of the mannose 6-phosphate (M-6-P) pathway in HeLa cells by inactivation of the GNPTAB gene, which encodes the α/β subunits of GlcNAc-1-phosphotransferase, results in missorting of newly synthesized lysosomal acid hydrolases to the cell culture media instead of transport to the endolysosomal system. We previously demonstrated that the majority of the lysosomal aspartyl protease, cathepsin D, is secreted in these GNPTAB

Malda, Accelerating Malaria Drug Discovery, Tuo Yang, Eva S. Istvan, Daniel E. Goldberg, Et Al.

2020-Current year OA Pubs

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of …

The Azithromycin To Prevent Wheezing Following Severe Rsv Bronchiolitis-Ii Clinical Trial: Rationale, Study Design, Methods, And Characteristics Of Study Population, Mythili Srinivasan, Leonard B Bacharier, Charles W Goss, Yanjiao Zhou, Jonathan Boomer, Sarah Bram, Dana Burgdorf, Carey-Ann Burnham, Timothy Casper, Mario Castro, Andrea Coverstone, Matthew Haslam, Watcharoot Kanchongkittiphon, Cadence Kuklinski, Qinghua Lian, Kenneth Schechtman, Gregory A Storch, Kelly True, Meghan A Wallace, Huiqing Yin-Declue, Elizabeth Ahrens, Jinli Wang, Avraham Beigelman

2020-Current year OA Pubs

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 …

Integration Of Immunotherapy Into Adjuvant Therapy For Resected Non-Small-Cell Lung Cancer: Alchemist Chemo-Io (Accio), Jacob M Sands, Ramaswamy Govindan, Jhanelle Gray, Et Al

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study …

A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez

2020-Current year OA Pubs

Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the …

Transfer Transcriptomic Signatures For Infectious Diseases, Julia Di Iulio, Istvan Bartha, Roberto Spreafico, Herbert W Virgin, Amalio Telenti

2020-Current year OA Pubs

The modulation of the transcriptome is among the earliest responses to infection. However, defining the transcriptomic signatures of disease is challenging because logistic, technical, and cost factors limit the size and representativeness of samples in clinical studies. These limitations lead to a poor performance of signatures when applied to new datasets. Although the study focuses on infection, the central hypothesis of the work is the generalization of sets of signatures across diseases. We use a machine learning approach to identify common elements in datasets and then test empirically whether they are informative about a second dataset from a disease or …

Safety And Efficacy Of Umbilical Cord-Derived Wharton's Jelly Compared To Hyaluronic Acid And Saline For Knee Osteoarthritis: Study Protocol For A Randomized, Controlled, Single-Blind, Multi-Center Trial, Ashim Gupta, Nicola Maffulli, Hugo C Rodriguez, Eric W Carson, Randa A Bascharon, Kristin Delfino, Howard J Levy, Saadiq F El-Amin

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of …

Hypergraph Models Of Biological Networks To Identify Genes Critical To Pathogenic Viral Response, Song Feng, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al

2020-Current year OA Pubs

BACKGROUND: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets.

RESULTS: We compiled a novel data set of transcriptional …

Exome Sequencing Revealed Pde11a As A Novel Candidate Gene For Early-Onset Alzheimer's Disease, Wei Qin, Aihong Zhou, Xiumei Zuo, Longfei Jia, Fangyu Li, Qi Wang, Ying Li, Yiping Wei, Hongmei Jin, Carlos Cruchaga, Bruno A Benitez, Jianping Jia

2020-Current year OA Pubs

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (AD), whole-exome sequencing was performed in 215 early-onset AD (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOAD. Both variants are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation and are classified as pathogenic. Furthermore, we found significantly decreased protein levels of …

Spontaneous Neural Synchrony Links Intrinsic Spinal Sensory And Motor Networks During Unconsciousness, Jacob Graves Mcpherson, Maria F. Bandres

Open Access Publications

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al., 2014 used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection …

Cellular, Circuit And Transcriptional Framework For Modulation Of Itch In The Central Amygdala, Vijay K. Samineni, Jose G. Grajales-Reyes, Gary E. Grajales-Reyes, Eric Tycksen, Bryan A. Copits, Christian Pedersen, Edem S. Ankudey, Julian N. Sackey, Sienna B. Sewell, Michael R. Bruchas, Robert W. Gereau

Open Access Publications

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral …

Common Dna Methylation Dynamics In Endometriod Adenocarcinoma And Glioblastoma Suggest Universal Epigenomic Alterations In Tumorigenesis, Jennifer A Karlow, Benpeng Miao, Xiaoyun Xing, Ting Wang, Bo Zhang

Open Access Publications

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated …

Semi-Supervised Peak Calling With Span And Jbr Genome Browser, Oleg Shpynov, Aleksei Dievskii, Roman Chernyatchik, Petr Tsurinov, Maxim N Artyomov

2020-Current year OA Pubs

UNLABELLED: The widespread application of ChIP-seq led to a growing need for consistent analysis of multiple epigenetics profiles, for instance, in human studies where multiple replicates are a common element of design. Such multisamples experimental designs introduced analytical and computational challenges. For example, when peak calling is done independently for each sample, small differences in signal strength/quality lead to a very different number of peaks for individual samples, making group-level analysis difficult. On the other side, when samples are pooled together for joint analysis, individual-level statistical differences are averaged out. Recently we have demonstrated that a semi-supervised peak calling approach …

Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad

Open Access Publications

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The …

Tofacitinib, An Oral Janus Kinase Inhibitor: Analysis Of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across The Ulcerative Colitis Clinical Program, Gary R Lichtenstein, Gerhard Rogler, Matthew A Ciorba, Chinyu Su, Gary Chan, Ronald D Pedersen, Nervin Lawendy, Daniel Quirk, Chudy I Nduaka, Andrew J Thorpe, Julian Panés

2020-Current year OA Pubs

BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]).

METHODS: Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events …

A Genetic Screen For Regulators Of Muscle Morphogenesis In Drosophila, Tiffany Ou, Gary Huang, Beth Wilson, Paul Gontarz, James B Skeath, Aaron N Johnson

Open Access Publications

The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developing Drosophila body wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis (Johnson et al., 2013; Williams et al., 2015; Yang et al., 2020a; Yang et al., 2020b). Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact dependent interactions between muscles and tendon cells. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far …

Stroma-Targeting Strategies In Pancreatic Cancer: Past Lessons, Challenges And Prospects, Faran Polani, Patrick M Grierson, Kian-Huat Lim

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is projected to emerge as the second leading cause of cancer-related death after 2030. Extreme treatment resistance is perhaps the most significant factor that underlies the poor prognosis of PDAC. To date, combination chemotherapy remains the mainstay of treatment for most PDAC patients. Compared to other cancer types, treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and shorter-lived. Aside from typically harboring genetic alterations that to date remain un-druggable and are drivers of treatment resistance, PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting …

Bundle-Specific Associations Between White Matter Microstructure And Aβ And Tau Pathology In Preclinical Alzheimer's Disease, Alexa Pichet Binette, Tammie Benzinger, John Morris, Randall Bateman, Et Al

Open Access Publications

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau …

Presepsin As A Diagnostic And Prognostic Biomarker In Sepsis, Dimitrios Velissaris, Nicholas Zareifopoulos, Vasileios Karamouzos, Evangelos Karanikolas, Charalampos Pierrakos, Ioanna Koniari, Menelaos Karanikolas

2020-Current year OA Pubs

Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited …

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …

Recovery Of Consciousness And Cognition After General Anesthesia In Humans, George A. Mashour, Ben J.A. Palanca, Wei Wang, Nan Lin, Maxwell Muench, Hannah Maybrier, Michael S. Avidan, Et Al

Open Access Publications

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, …

Neurological Diseases And Covid-19: Prospective Analyses Using The Uk Biobank, Nicola Veronese, Lee Smith, Mario Barbagallo, Gianluigi Giannelli, Maria Gabriella Caruso, Anna Maria Cisternino, Maria Notarnicola, Chao Cao, Thomas Waldhoer, Lin Yang

2020-Current year OA Pubs

COVID-19 (Coronavirus disease-19) may present with neurological signs, but whether people already affected by neurological conditions are at a higher risk of contracting COVID-19 is still not known. We, therefore, aimed to investigate the association of previously diagnosed neurological conditions with COVID-19. 502,536 community-dwelling UK Biobank participants (54.4% male, mean age 56.6 ± 10.3 years) were included. Among these, 57,463 participants had a diagnosis of neurological conditions (11.43%) and a total of 1326 COVID-19-positive cases were identified (0.26%). Neurological conditions were identified through medical history and linkage to data on hospital admissions (ICD-10 code G00-G99). COVID-19 presence was diagnosed using …

Quantitative Signal Properties From Standardized Mris Correlate With Multiple Sclerosis Disability, Matthew R Brier, Abraham Z Snyder, Aaron Tanenbaum, Richard A Rudick, Elizabeth Fisher, Stephen Jones, Joshua S Shimony, Anne H Cross, Tammie L S Benzinger, Robert T Naismith

Open Access Publications

OBJECTIVE: To enable use of clinical magnetic resonance images (MRIs) to quantify abnormalities in normal appearing (NA) white matter (WM) and gray matter (GM) in multiple sclerosis (MS) and to determine associations with MS-related disability. Identification of these abnormalities heretofore has required specialized scans not routinely available in clinical practice.

METHODS: We developed an analytic technique which normalizes image intensities based on an intensity atlas for quantification of WM and GM abnormalities in standardized MRIs obtained with clinical sequences. Gaussian mixture modeling is applied to summarize image intensity distributions from T1-weighted and 3D-FLAIR (T2-weighted) images from 5010 participants enrolled in …

Placental Sampling For Understanding Viral Infections - A Simplified Protocol For The Covid-19 Pandemic, Guilherme De Moraes Nobrega, José Paulo Siqueira Guida, Rodolfo Rosa Japecanga, Arthur Antolini-Tavares, Indira Mysorekar, Maria Laura Costa

Open Access Publications

OBJECTIVE:  The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections.

METHODS:  A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings. …

Bacterial Sepsis Increases Hippocampal Fibrillar Amyloid Plaque Load And Neuroinflammation In A Mouse Model Of Alzheimer's Disease, Jacob M Basak, Aura Ferreiro, Lucy S Cohen, Patrick W Sheehan, Collin J Nadarajah, Michael F Kanan, Kimberley V Sukhum, Gautam Dantas, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might …

A Blood-Based Diagnostic Test Incorporating Plasma Aβ42/40 Ratio, Apoe Proteotype, And Age Accurately Identifies Brain Amyloid Status: Findings From A Multi Cohort Validity Analysis, Tim West, Kristopher M Kirmess, Matthew R Meyer, Mary S Holubasch, Stephanie S Knapik, Yan Hu, John H Contois, Erin N Jackson, Scott E Harpstrite, Randall J Bateman, David M Holtzman, Philip B Verghese, Ilana Fogelman, Joel B Braunstein, Kevin E Yarasheski

2020-Current year OA Pubs

BACKGROUND: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

METHODS: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic …

Oncolytic Hsv-1 G207 Immunovirotherapy For Pediatric High-Grade Gliomas, Gregory K Friedman, Mohamed S Abdelbaki, Et Al

Open Access Publications

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement …

Increasing Metadata Coverage Of Sra Biosample Entries Using Deep Learning-Based Named Entity Recognition, Adam Klie, Brian Y Tsui, Shamim Mollah, Dylan Skola, Michelle Dow, Chun-Nan Hsu, Hannah Carter

2020-Current year OA Pubs

High-quality metadata annotations for data hosted in large public repositories are essential for research reproducibility and for conducting fast, powerful and scalable meta-analyses. Currently, a majority of sequencing samples in the National Center for Biotechnology Information's Sequence Read Archive (SRA) are missing metadata across several categories. In an effort to improve the metadata coverage of these samples, we leveraged almost 44 million attribute-value pairs from SRA BioSample to train a scalable, recurrent neural network that predicts missing metadata via named entity recognition (NER). The network was first trained to classify short text phrases according to 11 metadata categories and achieved …

Phenotype Of Peripheral Nk Cells In Latent, Active, And Meningeal Tuberculosis, José Alberto Choreño-Parra, Shabaana A. Khader, Et Al

Open Access Publications

No abstract provided.

Sars-Cov-2 Requires Cholesterol For Viral Entry And Pathological Syncytia Formation, David W. Sanders, Alex S. Holehouse, Et Al

Open Access Publications

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with quantitative cell biology …