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.

Stereospecific Properties and Intracellular Transport of Novel Intrinsically Fluorescent Neurosteroids.

Allopregnanolone (AlloP) is an example of neuroactive steroids (NAS), which is a potent allosteric activator of the γ-aminobutyric acid A (GABA) receptor. The mechanisms underlying the biological activity of AlloP and other NAS are only partially understood. Here, we present intrinsically fluorescent analogs of AlloP (MQ-323) and its 3β-epimer, epi-allopregnanolone (E-AlloP) (YX-11), and show, by a combination of spectroscopic and computational studies, that these analogs mimic the membrane properties of AlloP and E-AlloP very well.