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

Acetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contribute to cellular development and aging. In particular, enzymatic cleavage of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the ⍺7 nicotinic acetylcholine receptor (nAChR) at synapses.

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Tissues comprise ordered arrangements of cells that can be surprisingly disordered in their details. How the properties of single cells and their microenvironment contribute to the balance between order and disorder at the tissue-scale remains poorly understood. Here, we address this question using the self-organization of human mammary organoids as a model.

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T14 modulates calcium influx via the α-7 nicotinic acetylcholine receptor to regulate cell growth. Inappropriate triggering of this process has been implicated in Alzheimer's disease (AD) and cancer, whereas T14 blockade has proven therapeutic potential in in vitro, ex vivo and in vivo models of these pathologies. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth, however its hyperactivation is implicated in AD and cancer.

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Artificial intelligence and emerging data science techniques are being leveraged to interpret medical image scans. Traditional image analysis relies on visual interpretation by a trained radiologist, which is time-consuming and can, to some degree, be subjective. The development of reliable, automated diagnostic tools is a key goal of radiomics, a fast-growing research field which combines medical imaging with personalized medicine.

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Objective: COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate the causal associations and genetic overlap between COVID-19 and intelligence.

Methods: We performed Mendelian randomization (MR) analyses to assess potential associations between three COVID-19 outcomes and intelligence (N = 269 867).

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A recent neuropsychoeconomic model of trust propensity argues that an individual uses economic (executive functions) and social (social cognition) rationality strategies to transform the risk of treachery (affect) into positive expectations of reciprocity, promoting trust in another person. Previous studies have shown that the trust of older adults is associated with affect and social cognition. However, little is known about the intrinsic functional connectivity correlated with trust propensity or whether trust propensity is associated with executive functions in older adults.

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Zoonotic pathogens that are vector-transmitted have and continue to contribute to several emerging infections globally. In recent years, spillover events of such zoonotic pathogens have increased in frequency as a result of direct contact with livestock, wildlife, and urbanization, forcing animals from their natural habitats. Equines serve as reservoir hosts for vector-transmitted zoonotic viruses that are also capable of infecting humans and causing disease.

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Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections.

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Generation of Human Embryonic Stem Cell-Derived Lung Organoids for Modeling Infection and Replication Differences between Human Adenovirus Types 3 and 55 and Evaluating Potential Antiviral Drugs.

J Virol

May 2023

Cancer Research Institute, School of Basic Medical Sciences, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of Education), Southern Medical University, Guangzhou 510515, China.

Human adenoviruses type 3 (HAdV-3) and type 55 (HAdV-55) are frequently encountered, highly contagious respiratory pathogens with high morbidity rate. In contrast to HAdV-3, one of the most predominant types in children, HAdV-55 is a reemergent pathogen associated with more severe community-acquired pneumonia (CAP) in adults, especially in military camps. However, the infectivity and pathogenicity differences between these viruses remain unknown as models are not available.

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Background: We aimed to evaluate whether major depressive disorder (MDD) could aggravate the outcomes of coronavirus disease 2019 (COVID-19) or whether the genetic liability to COVID-19 could trigger MDD.

Aims: We aimed to assess bidirectional causal associations between MDD and COVID-19.

Methods: We performed genetic correlation and Mendelian randomisation (MR) analyses to assess potential associations between MDD and three COVID-19 outcomes.

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Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the US.The first HPV vaccine was introduced in 2006. There are three different HPV vaccines that commonly target high-risk HPV types.

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Article Synopsis
  • The study focuses on how the Mayaro virus (MAYV) adapts to urban mosquito vectors like Ae. aegypti, which could influence its transmission and emergence as a health threat.
  • Researchers discovered a specific mutation (E2-T179N) that enhances MAYV replication in mosquitoes, improving its transmission after passing through the mosquito's gut, but it reduces its ability to replicate in human cells.
  • The findings suggest that while this mutation may increase the virus's ability to spread through mosquitoes, it compromises its efficiency in human hosts, indicating a complex trade-off in virus adaptation that might lead to future emergence of outbreaks.
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Although Venezuelan equine encephalitis virus (VEEV) is a life-threatening pathogen with a capacity for epidemic outbreaks, there are no FDA-approved VEEV antivirals for humans. VEEV cytotoxicity is partially attributed to the formation of a tetrameric complex between the VEEV capsid protein, the nuclear import proteins importin-α and importin-β, and the nuclear export protein CRM1, which together block trafficking through the nuclear pore complex. Experimental studies have identified small molecules from the CL6662 scaffold as potential inhibitors of the viral nuclear localization signal (NLS) sequence binding to importin-α.

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New World alphaviruses including Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) are mosquito-transmitted viruses that cause disease in humans and equines. There are currently no FDA-approved therapeutics or vaccines to treat or prevent exposure-associated encephalitic disease. The ubiquitin proteasome system (UPS)-associated signaling events are known to play an important role in the establishment of a productive infection for several acutely infectious viruses.

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To evaluate the genetic relationship between hypertension and COVID-19 and explore the molecular pathways linking hypertension to COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess potential associations between hypertension and hospitalized COVID-19. We compared genome-wide association signals to reveal shared genetic variation between hypertension and hospitalized COVID-19.

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Background: Type 2 diabetes (T2D) is a chronic metabolic disorder with high comorbidity with mental disorders. The genetic links between attention-deficit/hyperactivity disorder (ADHD) and T2D have yet to be elucidated.

Aims: We aim to assess shared genetics and potential associations between ADHD and T2D.

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Venezuelan equine encephalitis virus E1 protein interacts with PDIA6 and PDI inhibition reduces alphavirus production.

Antiviral Res

April 2023

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24060, USA; Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24060, USA. Electronic address:

Venezuelan equine encephalitis virus (VEEV) is an alphavirus transmitted by mosquitos that can cause a febrile illness and induce severe neurological complications in humans and equine populations. Currently there are no FDA approved vaccines or antiviral treatments to combat VEEV. Proteomic techniques were utilized to create an interactome of the E1 fusion glycoprotein of VEEV.

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Endocrine therapy (ET) in combination with CDK4/6 inhibition is routinely used as first-line treatment for HR+/HER2- metastatic breast cancer (MBC) patients. However, 30-40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven protein/phosphoprotein-based approach to identify predictive markers of response to ET plus CDK4/6 inhibition in pre-treatment tissue biopsies.

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Tea ingredients can effectively inhibit SARS-CoV-2 infection at adequate concentrations. It is not known whether tea intake could impact the susceptibility to COVID-19 or its severity. We aimed to evaluate the causal effects of tea intake on COVID-19 outcomes.

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Detection of high-grade cervical neoplasia using extended genotyping: Performance data from the longitudinal phase of the Onclarity trial.

Gynecol Oncol

March 2023

Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, 7 Loveton Circle, Sparks, MD 21152, USA. Electronic address:

Objectives: The Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data.

Methods: At baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results.

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Calsequestrin Type 2 (CASQ2) is a high-capacity, low-affinity, Ca-binding protein expressed in the sarcoplasmic reticulum (SR) of the cardiac myocyte. Mutations in CASQ2 have been linked to the arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT2) that occurs with acute emotional stress or exercise can result in sudden cardiac death (SCD). CASQ2 is a 16 bp (339-354) deletion CASQ2 mutation that prevents the protein expression due to premature stop codon.

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Mutations in the calcium-sensing protein calmodulin () have been linked to two cardiac arrhythmia diseases, Long QT Syndrome 14 (LQT14) and Catecholaminergic Polymorphic Ventricular Tachycardia Type 4 (CPVT4), with varying degrees of severity. Functional characterization of the mutants most strongly associated with LQT14 show a clear disruption of the calcium-dependent inactivation (CDI) of the L-Type calcium channel (LCC). CPVT4 mutants on the other hand are associated with changes in their affinity to the ryanodine receptor.

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The impact of Lys28 acetylation on Alzheimer's Aβ peptide binding to the lipid bilayer has not been previously studied, either experimentally or computationally. To probe this common post-translational modification, we performed all-atom replica exchange molecular dynamics simulations targeting binding and aggregation of acetylated acAβ25-35 peptide within the DMPC bilayer. Using the unmodified Aβ25-35 studied previously as a reference, our results can be summarized as follows.

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Neuroinflammation caused by COVID-19 negatively impacts brain metabolism and function, while pre-existing brain pathology may contribute to individuals' vulnerability to the adverse consequences of COVID-19. We used summary statistics from genome-wide association studies (GWAS) to perform Mendelian randomization (MR) analyses, thus assessing potential associations between multiple sclerosis (MS) and two COVID-19 outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and COVID-19 hospitalization). Genome-wide risk genes were compared between the GWAS datasets on hospitalized COVID-19 and MS.

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The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae.

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