A Metalloproteinase Secreted by Streptococcus pneumoniae Removes Membrane Mucin MUC16 from the Epithelial Glycocalyx Barrier

The majority of bacterial infections occur across wet-surfaced mucosal epithelia, including those that cover the eye, respiratory tract, gastrointestinal tract and genitourinary tract. The apical surface of all these mucosal epithelia is covered by a heavily glycosylated glycocalyx, a major component of which are membrane-associated mucins (MAMs). MAMs form a barrier that serves as one of the first lines of defense against invading bacteria. While opportunistic bacteria rely on pre-existing defects or wounds to gain entry to epithelia, non opportunistic bacteria, especially the epidemic disease-causing ones, gain access to epithelial cells without evidence of predisposing injury. The molecular mechanisms employed by these non opportunistic pathogens to breach the MAM barrier remain unknown. To test the hypothesis that disease-causing non opportunistic bacteria gain access to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and 16, were exposed to a non encapsulated, non typeable strain of Streptococcus pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain SP168 to induce MAM ectodomain release from epithelia was compared to that of other strains of S. pneumoniae, as well as the opportunistic pathogen Staphylococcus aureus. The experiments reported herein demonstrate that the epidemic disease-causing S. pneumoniae species secretes a metalloproteinase, ZmpC, which selectively induces ectodomain shedding of the MAM MUC16. Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of the glycocalyx barrier function and enhanced internalization of the bacterium. These data suggest that removal of MAMs by bacterial enzymes may be an important virulence mechanism employed by disease-causing non opportunistic bacteria to gain access to epithelial cells to cause infection

Effect of pre-milling treatment on protein and carbohydrate content in tribal pulses

69-71Non-traditional pulses (tribal pulses) namely Kandulo and Bailo treated with different pre-treatments like water soaking, oil treatment, and chemical treatment and the changes in nutritive value of protein content and carbohydrate content both in manually dehulled and finished product (dhal) were assessed over untreated manually dehulled sample. Dhal yield ranged from 68.34% to 80.76% in Kandulo and 66.90% to 81.89% in Bailo; maximum dhal yield was in chemical treatment and minimum in oil pre-treated sample. All the premilling treatments except sodium bicarbonate treatment caused significant loss in protein content in cotyledon over untreated sample. Oil treated finished product resulted maximum loss in protein content in both the samples over untreated manually dehulled sample. In manually dehulled sample, maximum carbohydrate loss was found in oil treated sample than untreated finished dhal sample

Modulation of the mitochondrial voltage dependent anion channel (VDAC) by curcumin

Voltage dependent anion channel (VDAC) of mitochondria plays a crucial role in apoptosis. Human VDAC-1, reconstituted in planar lipid bilayer showed reduced conductance when treated with curcumin. Curcumin interacts with residues in the alpha helical N-terminus of VDAC and in the channel wall, as revealed by molecular docking, followed by mutational analysis. N-terminus mimicking peptide showed conformational changes in circular dichroism, upon curcumin treatment. We propose that the interaction of curcumin with amino acids in N-terminus and in channel wall fixes the alpha helix in closed conformation. This restricts its movement which is required for the opening of the channel. (C) 2014 Elsevier B.V. All rights reserved

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Not AvailableInsect pests and diseases are the major biotic constraints in rice production. According to the ecosystem, the incidence of insect pests and diseases vary. The degree of loss due to different biotic stresses differ widely depending upon the predominant factors of abundance of these pests in a particular year, season or locality. Though around 800 insect species damaging rice in one way or another, the majority of them do very little damage. In India, about a dozen of insect species are of major pest status. Farmers bear an estimated average of 37% losses in rice crop due to insect pests and diseases every year. This review focuses on status of insect pests and diseases, extent of losses, different tools used in pest monitoring and management in rice. Among the important pest management tools used in rice pest and diseases management are forecasting model for real-time pest-advisory services, light trap, hyper-spectral remote sensing, computer-based decision support system, disruptive technologies (mobile apps).Not Availabl

Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor

Catestatin (CST), a chromogranin-A-derived peptide, is a potent endogenous inhibitor of the neuronal nicotinic acetylcholine receptor (nAChR). It exerts an anti-hypertensive effect by acting as a 'physiological brake' on transmitter release into the circulation. However, the mechanism of interaction of CST with nAChR is only partially understood. To unravel molecular interactions of the wild-type human CST (CST-WT) as well as its naturally occurring variants (CST-364S and CST-370L, which have Gly -> Ser and Pro -> Leu substitutions, respectively) with the human alpha 3 beta 4 nAChR, we generated a homology-modeled human alpha 3 beta 4 nAChR structure and solution structures of CST peptides. Docking and molecular dynamics simulations showed that similar to 90% of interacting residues were within 15 N-terminal residues of CST peptides. The rank order of binding affinity of these peptides with nAChR was: CST-370L > CST-WT > CST-364S; the extent of occlusion of the receptor pore by these peptides was also in the same order. In corroboration with computational predictions, circular dichroism analysis revealed significant differences in global structures of CST peptides (e. g. the order of alpha-helical content was: CST-370L > CST-WT > CST-364S). Consistently, CST peptides blocked various stages of nAChR signal transduction, such as nicotine-or acetylcholine-evoked inward current, rise in intracellular Ca2+ and catecholamine secretion in or from neuron-differentiated PC12 cells, in the same rank order. Taken together, this study shows molecular interactions between human CST peptides and human alpha 3 beta 4 nAChR, and demonstrates that alterations in the CST secondary structure lead to the gain of potency for CST-370L and loss of potency for CST-364S. These findings have implications for understanding the nicotinic cholinergic signaling in humans

Functional Genetic Variants of the Catecholamine-Release-Inhibitory Peptide Catestatin in an Indian Population ALLELE-SPECIFIC EFFECTS ON METABOLIC TRAITS

Catestatin (CST), a chromogranin A (CHGA)-derived peptide, is a potent inhibitor of catecholamine release from adrenal chromaffin cells and postganglionic sympathetic axons. We re-sequenced the CST region of CHGA in an Indian population (n = 1010) and detected two amino acid substitution variants: G364S and G367V. Synthesized CST variant peptides (viz. CST-Ser-364 and CST-Val-367) were significantly less potent than the wild type peptide (CST-WT) to inhibit nicotine-stimulated catecholamine secretion from PC12 cells. Consistently, the rank-order of blockade of nicotinic acetylcholine receptor (nAChR)-stimulated inward current and intracellular Ca2+ rise by these peptides in PC12 cells was: CST-WT > CST-Ser-364 > CST-Val-367. Structural analysis by CD spectroscopy coupled with molecular dynamics simulations revealed the following order of alpha-helical content: CST-WT > CST-Ser-364 > CST-Val-367; docking of CST peptides onto a major human nAChR subtype and molecular dynamics simulations also predicted the above rank order for their binding affinity with nAChR and the extent of occlusion of the receptor pore, providing a mechanistic basis for differential potencies. The G364S polymorphism was in strong linkage disequilibrium with several common CHGA genetic variations. Interestingly, the Ser-364 allele (detected in similar to 15% subjects) was strongly associated with profound reduction (up to similar to 2.1-fold) in plasma norepinephrine/epinephrine levels consistent with the diminished nAChR desensitization-blocking effect of CST-Ser-364 as compared with CST-WT. Additionally, the Ser-364 allele showed strong associations with elevated levels of plasma triglyceride and glucose levels. In conclusion, a common CHGA variant in an Indian population influences several biochemical parameters relevant to cardiovascular/metabolic disorders