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

The impact of radiation dread on mass casualty medical management during a radiological or nuclear event.

Am J Disaster Med

August 2021

Associate Professor, Center for Social Complexity, Department of Computational and Data Science, College of Science, George Mason University, Fairfax, Virginia.

Since the events of 9/11, a concerted interagency effort has been undertaken to create comprehensive emergency planning and preparedness strategies for management of a radiological or nuclear event in the US. These planning guides include protective action guidelines, medical countermeasure recommendations, and systems for diagnosing and triaging radiation injury. Yet, key areas such as perception of risk from radiation exposure by first responders have not been addressed.

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Using all-atom explicit solvent replica exchange molecular dynamics simulations, we studied the aggregation of oxidized (ox) Aβ25-35 peptides into dimers mediated by the zwitterionic dimyristoylphosphatidylcholine (DMPC) lipid bilayer. By comparing oxAβ25-35 aggregation with that observed for reduced and phosphorylated Aβ25-35 peptides, we elucidated plausible impact of post-translational modifications on cytotoxicity of Aβ peptides involved in Alzheimer's disease. We found that Met35 oxidation reduces helical propensity in oxAβ25-35 peptides bound to the lipid bilayer and enhances backbone fluctuations.

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Classifying major mental disorders genetically.

Prog Neuropsychopharmacol Biol Psychiatry

January 2022

Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China. Electronic address:

Typically, mental disorders are defined and classified based on clinical symptoms and syndromes. Although clinically useful, current diagnostic systems for psychiatry cause concerns due to the lack of biological mechanisms. Deciphering the relationships among psychiatric traits according to their genetic basis may facilitate understanding the biological mechanisms of psychiatric disorders.

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Humans are motivated to give norm violators their just deserts through costly punishment even as unaffected third parties (i.e., third-party punishment, TPP).

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We aimed to investigate the genetic mechanisms associated with coronavirus disease of 2019 (COVID-19) outcomes in the host and to evaluate the possible associations between smoking and drinking behavior and three COVID-19 outcomes: severe COVID-19, hospitalized COVID-19 and COVID-19 infection. We described the genomic loci and risk genes associated with the COVID-19 outcomes, followed by functional analyses of the risk genes. Then, a summary data-based Mendelian randomization (SMR) analysis, and a transcriptome-wide association study (TWAS) were performed for the severe COVID-19 dataset.

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A microfluidic array was constructed for trapping single cell and loading identical dynamic biochemical stimulation for gain a better understanding of Ca2+ signaling at single cell resolution in the present study. This microfluidic array consists of multiple radially aligned flow channels with equal intersection angles, which was designed by a combination of stagnation point flow and physical barrier. Numerical simulation results and trajectory analysis have shown the effectiveness of this single cell trapping device.

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CD27CD38 B cells accumulated in early HIV infection exhibit transitional profile and promote HIV disease progression.

Cell Rep

July 2021

NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou 310003, China. Electronic address:

Although peripheral B cell dysfunction in early HIV infection is established, how B cell subsets are altered by HIV infection is poorly understood. While investigating B cell subsets among individuals recently infected with HIV, we observe an accumulation of CD27CD38 B cells and find that these cells can directly facilitate HIV infection of primary CD4 T cells in vitro. Comprehensive analyses of the phenotype, function, and transcriptome of the CD27CD38 B cell subset is conducted compared with memory and naive B cells.

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Correction to: Causal influences of neuroticism on mental health and cardiovascular disease.

Hum Genet

September 2021

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China.

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Article Synopsis
  • SARS-CoV-2 is the virus responsible for COVID-19, leading to severe cases that can cause serious lung damage, often requiring mechanical ventilation due to conditions like acute lung injury and ARDS.
  • The study highlighted that infection with SARS-CoV-2 results in an inflammatory response marked by elevated levels of specific chemokines (CXCL9, CXCL10, CXCL11) and cytokines (IL-6, TNFα, IFN-γ) in lung cells and infected mouse models.
  • It found that blocking certain signaling pathways, particularly the AKT pathway, significantly reduces the expression of these harmful chemokines, suggesting potential therapeutic targets to mitigate inflammation and improve outcomes in COVID-19 patients.
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Background: Many pathogens, including Yersinia pestis, cannot be consistently and reliably cultured from blood. New approaches are needed to facilitate the detection of proteins, nucleic acid and microorganisms in whole blood samples to improve downstream assay performance. Detection of biomarkers in whole blood is difficult due to the presence of host proteins that obscure standard detection mechanisms.

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Background: Colorectal cancer (CRC) represents the fourth leading cause of cancer-related deaths. The heterogeneity of CRC identity limits the usage of cell lines to study this type of tumor because of the limited representation of multiple features of the original malignancy. Patient-derived colon organoids (PDCOs) are a promising 3D-cell model to study tumor identity for personalized medicine, although this approach still lacks detailed characterization regarding molecular stability during culturing conditions.

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Schizophrenia Plays a Negative Role in the Pathological Development of Myocardial Infarction at Multiple Biological Levels.

Front Genet

June 2021

The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

It has shown that schizophrenia (SCZ) is associated with a higher chance of myocardial infarction (MI) and increased mortality. However, the underlying mechanism is largely unknown. Here, we first constructed a literature-based genetic pathway linking SCZ and MI, and then we tested the expression levels of the genes involved in the pathway by a meta-analysis using nine gene expression datasets of MI.

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Adult patients with atopic dermatitis (AD) present relatively higher rates of major depressive disorder (MDD). However, the underlying mechanism is largely unknown. Here, we first conducted a systematic literature-based data mining to identify entities linking AD and MDD, including proteins, cells, functional classes, and small molecules.

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The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor.

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X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin.

Cells

May 2021

School of Systems Biology and The Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA.

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling.

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PERK Is Critical for Alphavirus Nonstructural Protein Translation.

Viruses

May 2021

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.

Article Synopsis
  • Venezuelan equine encephalitis virus (VEEV) infection leads to cell death through the early growth response 1 (EGR1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway.
  • Inhibition of PERK in human astrocytes significantly decreased VEEV and eastern equine encephalitis virus (EEEV) replication, while showing no effect on replication in certain transformed cell lines.
  • This research suggests that targeting PERK could be a promising strategy for developing antiviral therapies against various RNA viruses, including VEEV, Rift Valley fever virus, and Zika virus.
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Identification of the SHREK Family of Proteins as Broad-Spectrum Host Antiviral Factors.

Viruses

May 2021

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.

Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123) that share similar structural characteristics with PSGL-1.

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Genetic Determinants of Antibiotic Resistance in .

Front Microbiol

May 2021

School of Systems Biology, George Mason University, Manassas, VA, United States.

Tularemia, caused by , is endemic to the northern hemisphere. This zoonotic organism has historically been developed into a biological weapon. For this Tier 1, Category A select agent, it is important to expand our understanding of its mechanisms of antibiotic resistance (AMR).

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Background: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 128 million people and has caused over 2.8 million deaths as of April 2021 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality.

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Predictive Models to Identify Small Molecule Activators and Inhibitors of Opioid Receptors.

J Chem Inf Model

June 2021

Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, Maryland 20850, United States.

Opioid receptors (OPRs) are the main targets for the treatment of pain and related disorders. The opiate compounds that activate these receptors are effective analgesics but their use leads to adverse effects, and they often are highly addictive drugs of abuse. There is an urgent need for alternative chemicals that are analgesics and to reduce/avoid the unwanted effects in order to relieve the public health crisis of opioid addiction.

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Brain networks involved in the influence of religion on empathy in male Vietnam War veterans.

Sci Rep

May 2021

Cognitive Neuroscience Laboratory, Brain Injury Research, Shirley Ryan AbilityLab, Chicago, IL, USA.

Humans all over the world believe in spirits and deities, yet how the brain supports religious cognition remains unclear. Drawing on a unique sample of patients with penetrating traumatic brain injuries (pTBI) and matched healthy controls (HCs) we investigate dependencies of religious cognition on neural networks that represent (1) others agents' intentions (Theory of Mind, ToM) and (2) other agents' feelings (Empathy). Extending previous observations that ToM networks are recruited during prayer, we find that people with vmPFC damage report higher scores on the personal relationship with God inventory even when they are not praying.

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We propose a biosphere model of convergent interactions between nicotine and neonicotinoids (neonics) within a related framework of nicotinic receptor targeting agents (NrTA) across the globe. We explore how rising global trends in the use nicotine as well as neonics impacts vulnerability, within and across species, and posit that evolutionary conservation at the nicotinic acetylcholine receptor (nAChR) provides an operational strategy map for pathogens and disease. Furthermore, we examine the effects of NrTA exposure on balance within extant and developing ecological niches, food chains, and human societies.

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Omics community detection using multi-resolution clustering.

Bioinformatics

October 2021

Biostatistics and Research Decision Sciences, Merck & Co., Inc, Rahway, NJ 07065, USA.

Motivation: The discovery of biologically interpretable and clinically actionable communities in heterogeneous omics data is a necessary first step toward deriving mechanistic insights into complex biological phenomena. Here, we present a novel clustering approach, omeClust, for community detection in omics profiles by simultaneously incorporating similarities among measurements and the overall complex structure of the data.

Results: We show that omeClust outperforms published methods in inferring the true community structure as measured by both sensitivity and misclassification rate on simulated datasets.

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