Cholesterol inhibits human voltage-gated proton channel hHv1.

Although human sperm is morphologically mature in the epididymis, it cannot fertilize eggs before capacitation. Cholesterol efflux from the sperm plasma membrane is a key molecular event essential for cytoplasmic alkalinization and hyperactivation, but the underlying mechanism remains unclear. The human voltage-gated proton (hHv1) channel functions as an acid extruder to regulate intracellular pHs of many cell types, including sperm. Aside from voltage and pH, Hv channels are also regulated by distinct ligands, such as Zn2+ and albumin. In the present work, we identified cholesterol as an inhibitory ligand of the hHv1 channel and further investigated the underlying mechanism using the single-molecule fluorescence resonance energy transfer (smFRET) approach. Our results indicated that cholesterol inhibits the hHv1 channel by stabilizing the voltage-sensing S4 segment at resting conformations, a similar mechanism also utilized by Zn2+. Our results suggested that the S4 segment is the central gating machinery in the hHv1 channel, on which voltage and distinct ligands are converged to regulate channel function. Identification of membrane cholesterol as an inhibitory ligand provides a mechanism by which the hHv1 channel regulates fertilization by linking the cholesterol efflux with cytoplasmic alkalinization, a change that triggers calcium influx through the CatSper channel. These events finally lead to hyperactivation, a remarkable change in the mobility pattern indicating fertilization competence of human sperm.

Food Security and Diet Quality Improvements among At-Risk, Low-Income, Older Adults following a Free Meal Pilot Program.

Older adults are at a greater risk for food insecurity compared to the general population. This study aimed to describe changes in diet quality and food insecurity following a free meal program at low-income, older adult housing complexes. Study participants were recruited from two low-income older adult public housing complexes in Kentucky. Fifty participants were enrolled and received 1-4 free weekly meals across 3 months as part of the Meals on Wings pilot program. Surveys and a 24 h dietary recall were completed at baseline and 3 months. Participants were predominately female, 69 years of age, and Black or African American race. Food security status (FSS) and dietary quality through the Healthy Eating Index (HEI) were assessed as primary measures. Participants were placed in "at-risk" categories of the (1a) lower quartile of the HEI and (1b) lower than 51% HEI, or (2) "low" or "very low" food security status based on the USDA Household Food Security Screener (FSS). Multiple linear regression (MLR) models were conducted for HEI and FSS scores to include time, group, time*group interaction, and control of meal utilization percentage (i.e., dose). The MLR for the HEI quartile had a significant time by quartile interaction that was present for an increase in the HEI in Q1 (n = 12; 32.42 ± 5.95% to n = 6; 46.10 ± 10.62%; p < 0.0001) and a decrease in the HEI for Q4 (n = 12; 70.68 ± 7.13% to n = 9; 52.36 ± 11.57%; p < 0.0001). For those low food security participants (n = 24; 48.0%), the average food insecurity score from the 6-item USDA screener improved from 4.09 ± 1.62 at baseline to 2.63 ± 2.41 at 3 months (p = 0.0064). The MLR for the FSS had a significant group*time interaction (p = 0.0071). In our population, particularly those vulnerable with lowest dietary quality and food insecurity status, we did see improvements across the free meal pilot program. However, a small sample, limited generalizability, and limited data collection measures urge caution when using these results to extrapolate for the general population. However, the current results are promising and should encourage further investigation of the effects of meal assistance programs on the health and well-being of older adults.