The Relationship of Alcohol Consumption and HDL Metabolism in the Multiethnic Dallas Heart Study.

BACKGROUND: Small studies have suggested that moderate alcohol consumption increases HDL cholesterol (HDL-C) levels and cholesterol efflux capacity (CEC), a main anti-atherosclerotic HDL function. OBJECTIVES: This study aimed to understand the degree to which alcohol intake is associated with various HDL markers in a large, multiethnic population cohort, the Dallas Heart Study (DHS), and whether alcohol modifies the link between HDL markers and atherosclerotic cardiovascular disease (ASCVD). METHODS: Participants of the DHS were included if they had self-reported alcohol intake and CEC measurements (N=2,919). Alcohol intake was analyzed continuously (grams/week) and as an ordered categorical variable (never, past, light, moderate, heavy, and binge drinkers). HDL-C, CEC, HDL particle number (HDL-P), HDL particle size (HDL-size), and ApoA-I were the primary HDL measures. RESULTS: After adjustment for confounding variables, increasing continuous measure of alcohol intake was associated with increased levels of all HDL markers. Moreover, as compared to moderate drinkers, light drinkers had decreased levels of the HDL markers. CONCLUSION: In a large, multiethnic cohort, increased alcohol intake was associated with increased levels of multiple markers of HDL metabolism. However, the association of HDL markers with ASCVD risk as modified by alcohol consumption is unable to be determined in this low-risk cohort.

Pharmacokinetic tuning of protein-antigen fusions enhances the immunogenicity of T-cell vaccines.

The formulations of peptide-based antitumour vaccines being tested in clinical studies are generally associated with weak potency. Here, we show that pharmacokinetically tuning the responses of peptide vaccines by fusing the peptide epitopes to carrier proteins optimizes vaccine immunogenicity in mice. In particular, we show in immunized mice that the carrier protein transthyretin simultaneously optimizes three factors: efficient antigen uptake in draining lymphatics from the site of injection, protection of antigen payloads from proteolytic degradation and reduction of antigen presentation in uninflamed distal lymphoid organs. Optimizing these factors increases vaccine immunogenicity by up to 90-fold and maximizes the responses to viral antigens, tumour-associated antigens, oncofetal antigens and shared neoantigens. Protein-peptide epitope fusions represent a facile and generalizable strategy for enhancing the T-cell responses elicited by subunit vaccines.

Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.

The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP.