Fatty acid 2-hydroxylase facilitates rotavirus uncoating and endosomal escape.

Despite the clinical significance of many nonenveloped viruses, the molecular mechanisms of their internalization and membrane penetration are not well understood. Rotaviruses (RVs) are nonenveloped double-stranded RNA viruses and the leading cause of severe dehydrating diarrhea in infants and young children. We identified fatty acid 2-hydroxylase (encoded by ) in the fatty acid 2-hydroxylation pathway as a proviral gene that supports RV infection.

Type 2 diabetes polygenic risk score demonstrates context-dependent effects and associations with type 2 diabetes-related risk factors and complications across diverse populations.

Polygenic risk scores (PRS) hold prognostic value for identifying individuals at higher risk of type 2 diabetes (T2D). However, further characterization is needed to understand the generalizability of T2D PRS in diverse populations across various contexts. We characterized a multi-ancestry T2D PRS among 244,637 cases and 637,891 controls across eight populations from the Population Architecture Genomics and Epidemiology (PAGE) Study and 13 additional biobanks and cohorts.

Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants.

Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method And Results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program.

Premorbid predictors of death at initial presentation of coronary heart disease in the Women's Health Initiative study.

Background: Premorbid health traits that increase the risk of dying at the time of initial presentation of coronary heart disease (CHD) remain poorly characterized.

Methods: We followed 148,230 post-menopausal participants in the Women's Health Initiative for a median of 13.3 years.

Entry inhibitors as arenavirus antivirals.

Arenaviruses belonging to the Arenaviridae family, genus mammarenavirus, are enveloped, single-stranded RNA viruses primarily found in rodent species, that cause severe hemorrhagic fever in humans. With high mortality rates and limited treatment options, the search for effective antivirals is imperative. Current treatments, notably ribavirin and other nucleoside inhibitors, are only partially effective and have significant side effects.

Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS) for 5 genetic ancestry groups.

Methods: We derived ancestry-specific and multi-ancestry PRS based on pruning and thresholding (PRS) and ancestry-based continuous shrinkage priors (PRS) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.

HIV-1 replication requires optimal activation of the unfolded protein response.

Several human diseases including viral infections activate the unfolded protein response (UPR) due to abnormal accumulation of unfolded/misfolded proteins. However, UPR modulation and its functional relevance in HIV-1 infection lack comprehensive elucidation. This study reveals that HIV-1 activates IRE1, PERK, and ATF6 signaling pathways of UPR.

Identification of 5' upstream sequence involved in HSPBP1 gene transcription and its downregulation during HIV-1 infection.

The Human Immunodeficiency Virus-1 (HIV-1) is known to modulate the host environment for successful replication and propagation like other viruses. The virus utilises its proteins to interact with or modulate host factors and host signalling pathways that may otherwise restrict the virus. A previous study from our lab has shown that the host heat shock protein 70 (HSP70) binding protein (HSPBP1) is a co-chaperone that inhibits viral replication.

Diversity in heat shock protein families: functional implications in virus infection with a comprehensive insight of their role in the HIV-1 life cycle.

Heat shock proteins (HSPs) are a group of cellular proteins that are induced during stress conditions such as heat stress, cold shock, UV irradiation and even pathogenic insult. They are classified into families based on molecular size like HSP27, 40, 70 and 90 etc, and many of them act as cellular chaperones that regulate protein folding and determine the fate of mis-folded or unfolded proteins. Studies have also shown multiple other functions of these proteins such as in cell signalling, transcription and immune response.

Comparative analysis of differential gene expression of HSP40 and HSP70 family isoforms during heat stress and HIV-1 infection in T-cells.

Heat shock proteins (HSPs) are a family of cellular proteins involved in a variety of biological functions including chaperone activity. HSPs are classified based on their molecular weight and each family has several isoforms in eukaryotes. HSP40 is the most diverse family acting as a co-chaperone for the highly conserved HSP70 family.

Targeted deep sequencing of the PEAR1 locus for platelet aggregation in European and African American families.

Coronary artery disease (CAD) remains a major cause of mortality and morbidity worldwide. The aggregation of activated platelets on a ruptured atherosclerotic plaque is a critical step in most acute cardiovascular events like myocardial infarction. Platelet aggregation both at baseline and after aspirin is highly heritable.