Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

Prioritization of causal genes from genome-wide association studies by Bayesian data integration across loci.

Motivation: Genome-wide association studies (GWAS) have identified genetic variants, usually single-nucleotide polymorphisms (SNPs), associated with human traits, including disease and disease risk. These variants (or causal variants in linkage disequilibrium with them) usually affect the regulation or function of a nearby gene. A GWAS locus can span many genes, however, and prioritizing which gene or genes in a locus are most likely to be causal remains a challenge.

Loading of Extracellular Vesicles with Nucleic Acids via Hybridization with Non-Lamellar Liquid Crystalline Lipid Nanoparticles.

The translation of cell-derived extracellular vesicles (EVs) into biogenic gene delivery systems is limited by relatively inefficient loading strategies. In this work, the loading of various nucleic acids into small EVs via their spontaneous hybridization with preloaded non-lamellar liquid crystalline lipid nanoparticles (LCNPs), forming hybrid EVs (HEVs) is described. It is demonstrated that LCNPs undergo pH-dependent structural transitions from inverse hexagonal (H) phases at pH 5 to more disordered non-lamellar phases, possibly inverse micellar (L) or sponge (L) phases, at pH 7.

Macrophages make "sense" of obesity-driven acidity in the TME.

Obesity is a leading risk factor and a negative prognostic indicator for many cancers. In a recent issue of Science Immunology, Bagchi et al. identified that tumor-associated macrophages upregulate GPR65 in response to obesity-driven intratumor acidity resulting in reduced effector function to promote tumor growth.

The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging.

In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan.