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

Cement pastes with UV-irradiated polypropylene: Fracture energy and the benefit of adding metakaolin

Adding fine plastic-based aggregates to cement pastes can allow for recycling waste while increasing the tensile strength and fracture toughness of the paste. However, the hydrophobicity of plastic causes poor cohesion with the cement paste, affecting the mechanical properties of the composite. Pre-irradiation with UV-C light reduces the hydrophobicity of the plastic, thus increasing the tensile strength of the paste while preserving compressive strength. This paper presents new experimental results, mainly showing that: (i) UV-C irradiated micro-sized polypropylene powder increases the tensile strength and fracture energy of CEM-I cement pastes; (ii) blending cement with metakaolin amplifies the positive effect of polypropylene addition in both untreated and UV-treated forms. These findings indicate that cement-metakaolin pastes containing UV-irradiated polypropylene may be an asset when crack resistance is key, such as in nuclear waste storage and oil/gas well cementing