Determinants of synaptobrevin regulation in membranes

Neuronal exocytosis is driven by the formation of SNARE complexes between synaptobrevin 2 on synaptic vesicles and SNAP-25/syntaxin 1 on the plasma membrane. It has remained controversial, however, whether SNAREs are constitutively active or whether they are down-regulated until fusion is triggered. We now show that synaptobrevin in proteoliposomes as well as in purified synaptic vesicles is constitutively active. Potential regulators such as calmodulin or synaptophysin do not affect SNARE activity. Substitution or deletion of residues in the linker connecting the SNARE motif and transmembrane region did not alter the kinetics of SNARE complex assembly or of SNARE-mediated fusion of liposomes. Remarkably, deletion of C-terminal residues of the SNARE motif strongly reduced fusion activity, although the overall stability of the complexes was not affected. We conclude that although complete zippering of the SNARE complex is essential for membrane fusion, the structure of the adjacent linker domain is less critical, suggesting that complete SNARE complex assembly not only connects membranes but also drives fusion.     

Salicylic Acid Modulates Antioxidant System,Defense Metabolites,and Expression of Salt Transporter Genes in Pisum sativum Under Salinity Stress

At present plants continuously exposed to salinity stress due to the challenging environment that has reduced the crop growth and productivity worldwide. Application of phytohormones by using seed priming method emerges as one of the most reliable and cost effective to alleviate the toxic effect of salinity stress. In this study, we evaluate the effect of seed-primed salicylic acid (SA) to reduce the adverse effect of different salt concentrations (0, 100, 200, and 300 mM NaCl) in pea (Pisum sativum L.) seedlings. After seedling emergence, percent seed germination was calculated; however, after 60 days; plants were sampled for studying the growth and photosynthetic traits, lipid peroxidation level, antioxidant activities, ions accumulation, and its sequestration. The results depicted that salinity treatments hampered overall growth performance and induced oxidative stress in a dose-dependent manner. Salinity also has negatively influence on ion accumulation as Na⁺ ion increased while K⁺ ion decreased. On the other hand, seed priming with SA significantly reduced the salinity-induced effects on the overall performance of plants, including growth and photosynthetic attributes. SA alleviated the adverse effect of salinity even at higher salinity level by inducing enzymatic and non-enzymatic antioxidant systems, soluble sugars, and proline accumulation, and regulating ion homeostasis along with up-regulation of Na⁺/H⁺ antiporters (SOS1 and NHX1). Thus, seed priming with SA shows a comprehensive role in mitigation of salinity stress and can be used as a model for promising salinity tolerant cultivation.

     

Salicylic Acid Improves Nitrogen Fixation,Growth, Yield and Antioxidant Defence Mechanisms in Chickpea Genotypes Under Salt Stress

Journal of Plant Growth Regulation - Salinization of farming soils is a major abiotic stress hampering crop growth and productivity globally. Chickpea is a vital legume crop, being cultivated...     

Halotolerant Plant Growth-Promoting Rhizobacteria Induce Salinity Tolerance in Wheat by Enhancing the Expression of SOS Genes

Journal of Plant Growth Regulation - Soil salinity is one of the main yield-limiting factors in various crops. Under different environmental stresses, many rhizobacteria have demonstrated...     

Crystal structure and metal binding properties of the periplasmic iron component EfeM from Pseudomonas syringae EfeUOB/M iron-transport system

BioMetals - EfeUOB/M has been characterised in Pseudomonas syringae pathovar. syringae as a novel type of ferrous-iron transporter, consisting of an inner-membrane protein (EfeUPsy) and three...     

Nanovehicles in the improved treatment of infections due to brain-eating amoebae

International Microbiology - Pathogenic free-living amoebae are known to cause fatal central nervous system infections with extremely high mortality rates. High selectivity of the blood–brain...     

Cancer drug resistance: A fleet to conquer

Cancer is a disease that claims millions of lives each year across the world. Despite advancement in technologies and therapeutics for treating the disease, these modes are often found to turn ineffective during the course of treatment. The resistance against drugs in cancer patients stems from multiple factors, which constitute genetic heterogeneity like gene mutations, tumor microenvironment, exosomes, miRNAs, high rate of drug efflux from cells, and so on. This review attempts to collate all such known and reported factors that influence cancer drug resistance and may help researchers with information that might be useful in developing better therapeutics in near future to enable better management of several cancers across the world.     

Pyrazinamide resistance and mutations L19R,R140H,and E144K in Pyrazinamidase of Mycobacterium tuberculosis

Pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid. Mutations in the pncA gene have been recognized as the major cause of PZA resistance. We detected some novel mutations, Leucine19Arginine (L19R), Arginine140Histidine (R140H), and Glutamic acid144 Lysine (E144K), in the pncA gene of PZA-resistant isolates in our wet lab PZA drug susceptibility testing and sequencing. As the molecular mechanism of resistance of these variants has not been reported earlier, we have performed multiple analyses to unveil different mechanisms of resistance because of PZase mutations L19R, R140H, and E144K. The mutants and native PZase structures were subjected to comprehensive computational molecular dynamics (MD) simulations at 100 nanoseconds in apo and drug-bound form. Mutants and native PZase binding pocket were compared to observe the consequence of mutations on the binding pocket size. Hydrogen bonding, Gibbs free energy, and natural ligand Fe ⁺² effect were also analyzed between native and mutants. A significant variation between native and mutant PZase structure activity was observed. The native PZase protein docking score was found to be the maximum, showing strong binding affinity in comparison with mutants. MD simulations explored the effect of the variants on the biological function of PZase. Hydrogen bonding, metal ion Fe ⁺² deviation, and fluctuation also seemed to be affected because of the mutations L19R, R140H, and E144K. The variants L19R, R140H, and E144K play a significant role in PZA resistance, altering the overall activity of native PZase, including metal ion Fe ⁺² displacement and free energy. This study offers valuable evidence for better management of drug-resistant tuberculosis.