The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.
View Article and Find Full Text PDFArgonaute proteins are best known for their role in microRNA-mediated post-transcriptional gene silencing. Here, we show that AGO3 and AGO4, but not AGO2, localize to the sex chromatin of pachytene spermatocytes where they are required for transcriptional silencing of XY-linked genes, known as Meiotic Sex Chromosome Inactivation (MSCI). Using an mouse, we show that AGO3 and AGO4 are key regulators of spermatogenesis, orchestrating expression of meiosis-related genes during prophase I while maintaining silencing of spermiogenesis genes.
View Article and Find Full Text PDFA 64-year-old man participated in a 13.1-mile half marathon in San Diego, CA on April 23, 2023. The ambient temperature when he started the race was 54°F, which increased to 64°F on his completing the race 3 hours and 58 minutes later.
View Article and Find Full Text PDFBackground: Use of sodium-glucose co-transporter 2 inhibitors (SGLT-2 inhibitors) falls short of their cardiorenal protective benefits. Patient and provider-level barriers hinder the adoption of these life-saving medications. Innovative practices to provide primary care providers (PCP) with added clinical-decision support via a dedicated remote interdisciplinary diabetes rounds (IDR) team could promote SGLT-2 inhibitor selection.
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