The chromogranin/secretogranin proteins are costored and coreleased with catecholamines from secretory vesicles in chromaffin cells and noradrenergic neurons. Chromogranin A (CHGA) regulates catecholamine storage and release through intracellular (vesiculogenic) and extracellular (catecholamine release-inhibitory) mechanisms. CHGA is a candidate gene for autonomic dysfunction syndromes, including intermediate phenotypes that contribute to human hypertension. Here, we show a surprising pattern of CHGA variants that alter the expression and function of this gene, both in vivo and in vitro. Functional variants include both common alleles that quantitatively alter gene expression and rare alleles that qualitatively change the encoded product to alter the signaling potency of CHGA-derived catecholamine release-inhibitory catestatin peptides.

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Significance and Impact of the Study: The water-soluble metabolite sulfonoquinovosyldiacylglyceride (SQDG) isolated from Azadirachta indica (Neem) possess significant antibacterial as well as anti-HSV activity. The efficacies as well as the solubility factor of SQDG substantiate a greater attention for its use as phytotherapeutic drug for controlling microbial infections as most consumers have better acceptance of phytomedicines than synthetic drugs. AbstractAssessment of antibacterial as well as antiherpes virus activity of sulfonoquinovosyldiacylglyceride (SQDG), a glycolipid, isolated from the leaves of Azadirachta indica has been described. Antimicrobial activity was evaluated against Gram-positive, Gram-negative bacteria and herpes simplex virus. SQDG showed significant inhibitory activity against Salmonella typhi and two isolates of Shigella dysenteriae with MIC values 32 lg ml À1 , while three isolates of Salm. typhi, Escherichia coli and Vibrio cholerae were inhibited at 64 lg ml À1and have shown zone diameter ranging from 6Á2 to 12Á3 mm. The growth kinetics study of SQDG on Salm. typhi and Sh. dysenteriae revealed that the growths were completely inhibited at their MIC values within 24 h of exposure. Interestingly, SQDG inhibits herpes simplex virus (HSV) type 1 and 2 with the EC 50 of 9Á1 and 8Á5 lg ml À1 , compared with acyclovir (2Á2 and 2Á8 lg ml À1 against HSV-1 and HSV-2). The selectivity index (SI) was found to be 12Á4 against HSV-1 and 13Á41 with HSV-2. Furthermore, the expression of proinflammatory cytokines of HSV-infected and SQDG-treated macrophages using ELISA kit revealed that SQDG significantly downregulated the production of TNF-a, IL-1b, IL-12 and IL-6.

The molecular basis of neuroendocrine-specific expression of chromogranin B gene (Chgb) has remained elusive. Utilizing wild-type and mutant Chgb promoter/luciferase reporter constructs, this study established a crucial role for the cAMP response element (CRE) box at )102/)95 bp in endocrine [rat pheochromocytoma (chromaffin) cell line (PC12) and rat pituitary somatotrope cell line (GC)] and neuronal [rat dorsal root ganglion/mouse neuroblastoma hybrid cell line (F-11), cortical and hippocampal primary neurons] cells. Additionally, G/C-rich domains at )134/)127, )125/)117 and )115/)110 bp played especially important roles for endocrine-specific expression of the Chgb gene. Co-transfection of expression plasmids for CREB, activator protein-2 (transcription factor) (AP-2), early growth response protein (transcription factor) (Egr-1) or specificity protein 1 (transcription factor) (Sp1) with the Chgb promoter constructs trans-activated expression of the Chgb gene. Nuclear extracts from either PC12 or F-11 cells formed specific complexes with the Chgb ()110/)87 bp) (CRE) oligonucleotide, which were either supershifted or disrupted by anti-CREB antibodies. In addition PC12 nuclear extracts also formed a specific complex with a Chgb ()140/)104-bp) oligonucleotide containing three G/C-rich regions, which was dose-dependently disrupted by anti-AP-2, anti-Egr-1 or antiSp1 antibodies; indeed, any one of these three antibodies completely abolished the complex, suggesting that all three factors bind the region simultaneously, at least in vitro. Chromatin immunoprecipitation assays documented the binding of the transcription factors CREB, AP-2, Egr-1 and Sp1 to the chromosomal Chgb gene promoter in vivo in PC12 cells within the context of chromatin. We conclude that the neuroendocrine-specific expression of Chgb is mediated by the CRE and G/C boxes in cis and the transcription factors CREB, AP-2, Egr-1 and Sp1 in trans.

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Lump lime is presently being used as a fluxed material in basic oxygen steel making process. However, problems are often encountered in operation due to its high melting point, poor dissolution property, fines generation and hygroscopic property. Binary CaO-Fe 2 O 3 has a eutectic point (1 200°C) with 22 % CaO. An agglomerate of lime and iron oxide under BOF condition would thus generate low melting oxidizing slag at the beginning of blow and would facilitate refining process. In this study, lime fluxed iron oxide pellet has been prepared using waste iron oxides and its strength was developed by CO 2 /CO 2 containing gas treatment at room temperature, while no separate binders has been used. Industrial waste gases, say, blast furnace gas (BFG) may suitably be used as CO 2 source. The pellet making process parameters such as composition of pellets, grain size of iron ore fines, treatment conditions etc. have been optimized through physical characterization like cold compressive strength, drop strength, abrasive resistance etc. Up to around 30 kg/pellet cold compressive strength, around 150 drop strength and excellent abrasive property have been achieved.

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