Ezetimibe Enhances Lipid Droplet and Mitochondria Contact Formation, Improving Fatty Acid Transfer and Reducing Lipotoxicity in Alport Syndrome Podocytes.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alport syndrome (AS), contributing to podocyte injury and disease progression. Ezetimibe, a lipid-lowering drug, is known to inhibit cholesterol and fatty acid uptake and to reduce triglyceride content in the kidney cortex of mice with AS. However, its effects on lipid droplet (LD) utilization by mitochondria have not been explored.

Human Herpes Virus-8 Oral Shedding Heterogeneity is Due to Varying Rates of Reactivation from Latency and Immune Containment.

Unlabelled: Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission.

Ensemble modeling of SARS-CoV-2 immune dynamics in immunologically naïve rhesus macaques predicts that potent, early innate immune responses drive viral elimination.

Introduction: An unprecedented breadth of longitudinal viral and multi-scale immunological data has been gathered during SARS-CoV-2 infection. However, due to the high complexity, non-linearity, multi-dimensionality, mixed anatomic sampling, and possible autocorrelation of available immune data, it is challenging to identify the components of the innate and adaptive immune response that drive viral elimination. Novel mathematical models and analytical approaches are required to synthesize contemporaneously gathered cytokine, transcriptomic, flow cytometry, antibody response, and viral load data into a coherent story of viral control, and ultimately to discriminate drivers of mild versus severe infection.

Input Pose is Key to Performance of Free Energy Perturbation: Benchmarking with Monoacylglycerol Lipase.

Free energy perturbation (FEP) methodologies have become commonplace methods for modeling potency in hit-to-lead and lead optimization stages of drug discovery. The conformational states of the initial poses of compounds for FEP+ calculations are often set up by alignment to a cocrystal structure ligand, but it is not clear if this method provides the best result for all proteins or all ligands. Not only are ligand conformational states potential variables in modeling compound potency in FEP but also the selection of crystallographic water molecules for inclusion in the FEP input structures can impact FEP models.