Toxin-antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role in physiology and virulence. Nine of these TA systems belong to the mazEF family, encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce bacteriostasis. The construction of various single-, double-and triple-mutant Mtb strains reveals that these MazF ribonucleases contribute synergistically to the ability of Mtb to adapt to conditions such as oxidative stress, nutrient depletion and drug exposure. Moreover, guinea pigs infected with the triple-mutant strain exhibits significantly reduced bacterial loads and pathological damage in infected tissues in comparison with parental strain-infected guinea pigs. The present study highlights the importance of MazF ribonucleases in Mtb stress adaptation, drug tolerance and virulence.

Drought stress negatively affects crop performance and weakens global food security. It triggers the activation of downstream pathways, mainly through phytohormones homeostasis and their signaling networks, which further initiate the biosynthesis of secondary metabolites (SMs). Roots sense drought stress, the signal travels to the above-ground tissues to induce systemic phytohormones signaling. The systemic signals further trigger the biosynthesis of SMs and stomatal closure to prevent water loss. SMs primarily scavenge reactive oxygen species (ROS) to protect plants from lipid peroxidation and also perform additional defense-related functions.Moreover, drought-induced volatile SMs can alert the plant tissues to perform drought stress mitigating functions in plants. Other phytohormone-induced stress responses include cell wall and cuticle thickening, root and leaf morphology alteration, and anatomical changes of roots, stems, and leaves, which in turn minimize the oxidative stress, water loss, and other adverse effects of drought. Exogenous applications of phytohormones and genetic engineering of phytohormones signaling and biosynthesis pathways mitigate the drought stress effects. Direct modulation of the SMs biosynthetic pathway genes or indirect via phytohormones' regulation provides drought tolerance. Thus, phytohormones and SMs play key roles in plant development under the drought stress environment in crop plants. | INTRODUCTIONA large segment of the population is going to face food scarcity due to climate change and the gradually decreasing arable land area. Plants are confronted to a variable environment while growing from seedling to mature plant. Different abiotic and biotic stresses affect plant growth and development (Cramer et al., 2011;Fujita et al., 2006;Tuteja & Sopory, 2008). Abiotic stress includes drought, submergence, osmotic stress, salinity stress, oxidative stress, ultra-violet irradiation, wounding, and nutrient depletion. The extremity of optimum factors such as high temperature or low temperature and freezing-thawing is also included in abiotic stresses. Biotic stresses include viruses, bacteria, fungi, algae, worms, nematodes, insects, herbivores, and parasitic plants. Plants have to combat these stressors due to their sessile lifestyle (Cramer et al., 2011;Fujita et al., 2006). More than 50% reduction in average yields of major cereal crops has been reported because of various abiotic stresses. Drought is one of the most important abiotic stresses that negatively influence plant performance and causes harsh effects on biomass and yield (Fahad et al., 2017). A

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Early administration of intravenous heparin, specifically before transseptal puncture, decreases the incidence of left atrial thrombi.

BackgroundHyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain.MethodsTo assess the effects of non–calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.ResultsA total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.ConclusionsIn patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.Clinical Trial registry name and registration numberAustralian Clinical Trials Registry, ACTRN12610000650099