Highlights d HI.fate reports HIV-1 fate in target cells by using sensitive fluorescent proteins d Alternative fates of HIV-1 infection are linked to differential gene expression d Small molecules can modulate the fate of HIV-1 infection d Extra-cellular environment contributes to the fate of HIV-1 in vivo
Many HIV strains downregulate the levels of CD4 receptor on the surface of infected cells to prevent superinfection. In contrast, the rare HIV-2 UC1 strain is noncytopathic and has no effect on CD4 expression in infected cells but still replicates as efficiently as more cytopathic strains in peripheral blood mononuclear cells (PBMCs). Here, we show that HIV-2 UC1 Env interactions with the CD4 receptor exhibit slow association kinetics, whereas the dissociation kinetics is within the range of cytopathic strains. Despite the resulting 10to 100-fold decrease in binding affinity, HIV-2 UC1 Envs exhibit long-lived activation state and efficient fusion activity. These observations suggest that HIV-2 UC1 Envs evolved to balance low affinity with an improved and readily triggerable molecular machinery to mediate entry. Resistance to cold exposure, similar to many primary HIV-1 isolates, and to sCD4 neutralization suggests that HIV-2 UC1 Envs preferentially sample a closed Env conformation. Our data provide insights into the mechanism of HIV entry.
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
HIV-1 entry into host cells leads to one of three alternative fates: 1) HIV-1 elimination by restriction factors, 2) establishment of HIV-1 latency, or 3) active viral replication in target cells. Here we developed an improved system for monitoring HIV-1 fate and provide evidence for the differential contribution of the intracellular environment as well as extracellular environment found in organs of BLT humanized mouse to the fate of HIV-1 infection.
Introduction: Pathogenesis of high blood pressure or hypertension is associated with microbial imbalance or dysbiosis of the gut microbiome. Previous research suggests probiotic consumption may reduce elevated blood pressure, possibly through manipulation of the gut microbiome, and may offer a future potential therapy for hypertension. Aim:The aim of this research was to critically evaluate current research evidence to assess whether probiotic supplements may reduce high blood pressure and formulate recommendations regarding their use as an intervention to support hypertensive clients in a Nutritional Therapy context. The objectives were to outline the possible association between gut dysbiosis and hypertension, and to explore possible mechanisms by which probiotics may influence blood pressure.Methods: A systematic review of the literature based upon PRISMA protocol was conducted. Four databases were searched: Cochrane Library (Central), CINAHL, Medline and TRIP from January 2014 until July 2020. Five eligible randomised controlled trials, including 453 participants, were identified and critically appraised to assess the quality of their evidence [1].Results: Of the three highest quality studies, two supported probiotic supplements to be effective in reducing blood pressure, one study reported no effect. The remaining two studies were appraised to be of lesser methodological quality so were given less weighting for quality of evidence. This research study found moderate evidence that probiotic supplementation can significantly reduce blood pressure in individuals with borderline hypertension. No effect was reported in normotensives. Conclusion:Probiotic supplementation may offer a convenient and effective adjunct for hypertensives to reduce high blood pressure alongside other dietary/lifestyle/medical interventions.Recommendation: Further large-scale trials of longer duration on hypertensives are recommended to establish functional pathways, bacterial strain, dosage and required timescale.
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