715 results match your criteria: "School of Systems Biology[Affiliation]"

Trust forms the basis of virtually all interpersonal relationships. Although significant individual differences characterize trust, the driving neuropsychological signatures behind its heterogeneity remain obscure. Here, we applied a prediction framework in two independent samples of healthy participants to examine the relationship between trust propensity and multimodal brain measures.

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Functional analysis of BRCA1 RING domain variants: computationally derived structural data can improve upon experimental features for training predictive models.

Integr Biol (Camb)

September 2020

School of Systems Biology, College of Science, George Mason University, 10900 University Blvd, MS 5B3, Manassas, Virginia 20110, USA.

Advancements in the interpretation of variants of unknown significance are critical for improving clinical outcomes. In a recent study, massive parallel assays were used to experimentally quantify the effects of missense substitutions in the RING domain of BRCA1 on E3 ubiquitin ligase activity as well as BARD1 RING domain binding. These attributes were subsequently used for training a predictive model of homology-directed DNA repair levels for these BRCA1 variants relative to wild type, which is critical for tumor suppression.

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Venezuelan equine encephalitis virus (VEEV), a mosquito transmitted alphavirus of the family, can cause a highly inflammatory and encephalitic disease upon infection. Although a category B select agent, no FDA-approved vaccines or therapeutics against VEEV currently exist. We previously demonstrated NF-κB activation and macromolecular reorganization of the IKK complex upon VEEV infection in vitro, with IKKβ inhibition reducing viral replication.

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Accurate and efficient structure-based computational mutagenesis for modeling fluorescence levels of Aequorea victoria green fluorescent protein mutants.

Protein Eng Des Sel

September 2020

Laboratory for Structural Bioinformatics, School of Systems Biology, George Mason University, 10900 University Boulevard MS 5B3, Manassas, VA 20110, USA.

A computational mutagenesis technique was used to characterize the structural effects associated with over 46 000 single and multiple amino acid variants of Aequorea victoria green fluorescent protein (GFP), whose functional effects (fluorescence levels) were recently measured by experimental researchers. For each GFP mutant, the approach generated a single score reflecting the overall change in sequence-structure compatibility relative to native GFP, as well as a vector of environmental perturbation (EP) scores characterizing the impact at all GFP residue positions. A significant GFP structure-function relationship (P < 0.

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A significant impediment to the improvement of clinical outcomes in treating breast and ovarian cancers rests with the lack of available interpretations for BRCA1 variants of unknown significance. Two research groups recently implemented large-scale functional assays for quantifying effects of single missense mutations on homology-directed DNA repair activity of BRCA1 variants, which is critical for tumor suppression and strongly correlates with cancer risk, and their results are significantly concordant with each other as well as with known pathogenic and benign variant clinical data. In this work, we implemented an established computational mutagenesis procedure to characterize structural impacts of single residue replacements to the BRCA1 RING domain.

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Background: Head-to-head comparison of BeadChip and WGS/WES genotyping techniques for their precision is far from straightforward. A tool for validation of high-throughput genotyping calls such as Sanger sequencing is neither scalable nor practical for large-scale DNA processing. Here we report a cross-validation analysis of genotyping calls obtained via Illumina GSA BeadChip and WGS (Illumina HiSeq X Ten) techniques.

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Janzen's influential "mountain passes are higher in the tropics" hypothesis predicts restricted gene flow and genetic isolation among populations spanning elevational gradients in the tropics. Few studies have tested this prediction, and studies that focus on population genetic structure in Southeast Asia are particularly underrepresented in the literature. Here, we test the hypothesis that mountain treeshrews (Tupaia montana) exhibit limited dispersal across their broad elevational range which spans ~2,300 m on two peaks in Kinabalu National Park (KNP) in Borneo: Mt Tambuyukon (MT) and Mt Kinabalu (MK).

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Introduction: The COVID-19 pandemic raises the question of strategic readiness for emergent pathogens. The current case illustrates that the cost of inaction can be higher in the future. The perspective article proposes a dedicated, government-sponsored agency developing anti-viral leads against all potentially dangerous pathogen species.

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Medical genomics relies on next-gen sequencing methods to decipher underlying molecular mechanisms of gene expression. This special issue collects materials originally presented at the "Centenary of Human Population Genetics" Conference-2019, in Moscow. Here we present some recent developments in computational methods tested on actual medical genetics problems dissected through genomics, transcriptomics and proteomics data analysis, gene networks, protein-protein interactions and biomedical literature mining.

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Nutritional status impacts dengue virus infection in mice.

BMC Biol

August 2020

Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.

Background: Dengue virus (DENV) is estimated to infect 390 million people annually. However, few host factors that alter disease severity are known. Malnutrition, defined as both over- and undernutrition, is a growing problem worldwide and has long been linked to dengue disease severity by epidemiological and anecdotal observations.

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Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies.

Cancers (Basel)

August 2020

Leroy T. Canoles Jr. Cancer Research Center, Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA.

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S.

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HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.

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An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients.

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To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included.

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Preeclampsia (PE) confers a significant risk for subsequent diagnosis with autism spectrum disorder (ASD), with the mechanisms underlying this observation being largely unknown. To identify molecular networks affected by both PE and ASD, we conducted a large-scale literature data mining and a gene set enrichment analysis (GSEA), followed by an expression mega-analysis in 13 independently profiled ASD datasets. Sets of genes implicated in ASD and in PE significantly overlap (156 common genes; = 3.

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With the advent of high-resolution and cost-effective genomics and bioinformatics tools and methods contributing to a large database of both human (HAdV) and simian (SAdV) adenoviruses, a genomics-based re-evaluation of their taxonomy is warranted. Interest in these particular adenoviruses is growing in part due to the applications of both in gene transfer protocols, including gene therapy and vaccines, as well in oncolytic protocols. In particular, the re-evaluation of SAdVs as appropriate vectors in humans is important as zoonosis precludes the assumption that human immune system may be naïve to these vectors.

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Neural signatures of prosocial behaviors.

Neurosci Biobehav Rev

November 2020

School of Systems Biology, George Mason University, Fairfax, VA, USA; Department of Psychology, George Mason University, Fairfax, VA, USA.

Prosocial behaviors are hypothesized to require socio-cognitive and empathic abilities-engaging brain regions attributed to the mentalizing and empathy brain networks. Here, we tested this hypothesis with a coordinate-based meta-analysis of 600 neuroimaging studies on prosociality, mentalizing and empathy (∼12,000 individuals). We showed that brain areas recruited by prosocial behaviors only partially overlap with the mentalizing (dorsal posterior cingulate cortex) and empathy networks (middle cingulate cortex).

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Category A and B biothreat agents are deemed to be of great concern by the US Centers for Disease Control and Prevention (CDC) and include the bacteria Francisella tularensis, Yersinia pestis, Burkholderia mallei, and Brucella species. Underscored by the impact of the 2020 SARS-CoV-2 outbreak, 2016 Zika pandemic, 2014 Ebola outbreak, 2001 anthrax letter attacks, and 1984 Rajneeshee Salmonella attacks, the threat of future epidemics/pandemics and/or terrorist/criminal use of pathogenic organisms warrants continued exploration and development of both classic and alternative methods of detecting biothreat agents. Volatile organic compounds (VOCs) comprise a large and highly diverse group of carbon-based molecules, generally related by their volatility at ambient temperature.

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Using an all-atom explicit water model and replica exchange umbrella sampling simulations, we investigated the molecular mechanisms of benzoic acid partitioning into two model lipid bilayers. The first was formed of 1,2-dimyristoyl--glycero-3-phosphocholine (DMPC) lipids, whereas the second was composed of an equimolar mixture of DMPC, 1,2-dimyristoyl--glycero-3-phosphoethanolamine, palmitoylsphingomyelin, and cholesterol to constitute a blood-brain barrier (BBB) mimetic bilayer. Comparative analysis of benzoic acid partitioning into the two bilayers has revealed qualitative similarities.

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Correction: Multi-trait analysis for genome-wide association study of five psychiatric disorders.

Transl Psychiatry

July 2020

Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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A few studies suggested the contribution of PPARs to the etiology of schizophrenia (SCZ). However, it is still not clear whether variants in PPAR-encoding genes have a direct association with SCZ. The potential linkage between SCZ and the variants within PPAR encoding genes (PPARA, PPARD, and PPARG) was tested in a large cohort genome-wide association study (GWAS).

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Trust plays a critical role in nearly every aspect of social life. Parental investment theory and social role theory predict that women trust less than men due to a higher sensitivity to risk and betrayal, while men trust more than women to maximize resources and to signal their willingness to lose something. However, the underlying neuropsychological underpinnings for this gender difference are still obscure.

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