Background: Post-translational modification activates bacterial elongation factor P (EF-P) in several Gram-negative bacteria.Results: The addition of ␤-lysine alone is sufficient for activation of EF-P to function in translation. Conclusion: Modified EF-P acts by regulating translation of a subset of mRNAs. Significance: EF-P can post-transcriptionally regulate gene expression by controlling translation elongation.

Metastasis is the leading cause of breast cancer-related death and poses a substantial clinical burden owing to a paucity of targeted treatment options. The clinical manifestations of metastasis occur years-to-decades after initial diagnosis and treatment because disseminated tumor cells readily evade detection and resist therapy, ultimately giving rise to recurrent disease. Using an unbiased genetic screen, we identified SLX4-interacting protein (SLX4IP) as a regulator of metastatic recurrence and established its relationship in governing telomere maintenance mechanisms (TMMs). Inactivation of SLX4IP suppressed alternative lengthening of telomeres (ALT), coinciding with activation of telomerase. Importantly, TMM selection dramatically influenced metastatic progression and survival of patients with genetically distinct breast cancer subtypes. Notably, pharmacologic and genetic modulation of TMMs elicited telomere-dependent cell death and prevented disease recurrence by disseminated tumor cells. This study illuminates SLX4IP as a potential predictive biomarker for breast cancer progression and metastatic relapse. SLX4IP expression correlates with TMM identity, which also carries prognostic value and informs treatment selection, thereby revealing new inroads into combating metastatic breast cancers.

Exercise-trained men consuming a P diet combined with multi-component exercise training (PRISE) enhance muscular power, strength, aerobic performance, and flexibility which are not likely related to GH or BDNF but possibly to IGF-1 response.

The ideal exercise time of day (ETOD) remains elusive regarding simultaneous effects on health and performance outcomes, especially in women.Purpose: Given known sex differences in response to exercise training, this study quantified health and performance outcomes in separate cohorts of women and men adhering to different ETOD.Methods: Thirty exercise-trained women (BMI = 24 ± 3 kg/m2; 42 ± 8 years) and twenty-six men (BMI = 25.5 ± 3 kg/m2; 45 ± 8 years) were randomized to multimodal ETOD in the morning (0600–0800 h, AM) or evening (1830–2030 h, PM) for 12 weeks and analyzed as separate cohorts. Baseline (week 0) and post (week 12) muscular strength (1-RM bench/leg press), endurance (sit-ups/push-ups) and power (squat jumps, SJ; bench throws, BT), body composition (iDXA; fat mass, FM; abdominal fat, Abfat), systolic/diastolic blood pressure (BP), respiratory exchange ratio (RER), profile of mood states (POMS), and dietary intake were assessed.Results: Twenty-seven women and twenty men completed the 12-week intervention. No differences at baseline existed between groups (AM vs PM) for both women and men cohorts. In women, significant interactions (p < 0.05) existed for 1RM bench (8 ± 2 vs 12 ± 2, ∆kg), pushups (9 ± 1 vs 13 ± 2, ∆reps), BT (10 ± 6 vs 45 ± 28, ∆watts), SJ (135 ± 6 vs 39 ± 8, ∆watts), fat mass (−1.0 ± 0.2 vs −0.3 ± 0.2, ∆kg), Abfat (−2.6 ± 0.3 vs −0.9 ± 0.5, ∆kg), diastolic (−10 ± 1 vs−5 ± 5, ∆mmHg) and systolic (−12.5 ± 2.7 vs 2.3 ± 3, mmHg) BP, AM vs PM, respectively. In men, significant interactions (p < 0.05) existed for systolic BP (−3.5 ± 2.6 vs −14.9 ± 5.1, ∆mmHg), RER (−0.01 ± 0.01 vs −0.06 ± 0.01, ∆VCO2/VO2), and fatigue (−0.8 ± 2 vs −5.9 ± 2, ∆mm), AM vs PM, respectively. Macronutrient intake was similar among AM and PM groups.Conclusion: Morning exercise (AM) reduced abdominal fat and blood pressure and evening exercise (PM) enhanced muscular performance in the women cohort. In the men cohort, PM increased fat oxidation and reduced systolic BP and fatigue. Thus, ETOD may be important to optimize individual exercise-induced health and performance outcomes in physically active individuals and may be independent of macronutrient intake.