Mechanism of impaired skin collagen maturity in riboflavin or pyridoxine deficiency

To elucidate the biochemical basis of impaired skin collagen maturity in pyridoxine-or riboflavin-deficient rats the following two mechanistic possibilities were tested: (i) Reduction in the activity of skin lysyl oxidase (EC 1·4·3·13) which initiates the cross-linking of collagen and (ii) putative rise in homocysteine level leading to neutralization of allysine (α-aminoadipic acid δ-5-semialdehyde)or hydroxyallysine (hydroxy α-aminoadepic acid (δ-semialdehyde) in collagen by the formation of thiazine complexes. Skin lysyl oxidase activity was not affected in pyridoxine deficiency suggesting that pyridoxal phosphate may not be its cofactor. In riboflavin deficiency, lysyl oxidase activity was not altered in the newly regenerated rat skin but a slight reduction was observed in the skin of 18-day-old rat pups. This could be related to the body weight deficit rather than deficiencyper se. Aldehyde content of purified salt soluble collagen of regenerated skin was significantly reduced in both the deficiencies. A 2 to 4-fold increase in the concentration of skin homocysteine was observed in both the deficiencies. The results suggest that increase in skin homocysteine level may be responsible for the impaired skin collagen maturity in riboflavin or pyridoxine deficiency.     

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2^Tyr1007/1008 phosphorylation, and inhibits its downstream STAT3^Tyr705 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.

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Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis

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NeeMDB: Convenient Database for Neem Secondary Metabolites

Indian Neem tree is known for its pesticidal and medicinal properties for centuries. Structure elucidation of large number of secondary metabolites responsible for its diverse properties has been achieved. However, this data is spread over various books, scientific reports and publications and difficult to access. We have compiled and stored structural details of neem metabolites in NeeMDB, a database which can be easily accessed, queried and downloaded. NeeMDB would be central in dissipating structural information of neem secondary metabolites world over.     

Mechanisms of resistance to Helicoverpa armigera and introgression of resistance genes into F1 hybrids in chickpea

The noctuid pod borer, Helicoverpa armigera is a major pest of chickpea, and host plant resistance is an important component for managing this pest. We evaluated a set of diverse chickpea genotypes with different levels of resistance to H. armigera, and their F₁ hybrids for oviposition non-preference, antibiosis, and tolerance components of resistance under uniform insect infestation under greenhouse/laboratory conditions. The genotypes ICC 12476, ICC 12477, ICC 12478, ICC 12479, and ICC 506EB were non-preferred for oviposition under no-choice, dual-choice, and multi-choice conditions, and also suffered lower leaf damage in no-choice tests as compared to the susceptible check, ICCC 37. Antibiosis expressed in terms of low larval weights was observed in insects reared on ICC 12476, ICC 12478, and ICC 506EB. Weight gain by the third-instars was also low on ICC 12476, ICC 12477, ICC 12478, ICC 12479, and ICC 506EB at the podding stage. Non-preference for oviposition and antibiosis (poor larval growth) were also expressed in hybrids based on ICC 12477, ICC 12476, ICC 12478, ICC 12479, and ICC 506EB as compared to the hybrids based on the susceptible check, ICCC 37, indicating that oviposition non-preference and antibiosis in the F₁ hybrids is influenced by the parent genotype. Loss in grain yield was lower in ICC 12477, ICC 12478, ICC 12479, and ICC 506EB compared to that on ICCC 37. The genotypes ICC 12477, ICC 12478, ICC 12479, and ICC 506EB showing antixenosis, antibiosis, and tolerance mechanism of resistance to H. armigera can be used for developing chickpea cultivars for resistance to this pest.     

A colorimetric micro method for the determination of formyl groups

The characteristic purple colour formed by N-formyl-N'-2,4-dinitrophenyl-hydrazine in the presence of piperidine and acetone was made the basis of a new quantitative method for the determination of formyl groups. Samples containing N-formyl groups (up to 0.4mumole) are hydrazinolysed at 97-98 degrees for 1hr. and are dinitrophenylated after the removal of excess of hydrazine. Interference from 2,4-dinitrophenylhydrazine is eliminated by subjecting the dinitrophenylated samples to chromatography on an alumina column. Interference arising from the formation of N-acetyl-N'-2,4-dinitrophenylhydrazine, when determining formyl groups in samples containing acetyl, can be avoided by a paper-chromatographic separation before analysis. A standard procedure is described. The method gives satisfactory results when applied to N-formyl-amino acids. Gramicidin, when analysed by this method, was found to contain 0.89 mole of formyl group/mole for a molecular weight of 1880. The method indicated the absence of formyl groups from lysozyme, a protein known not to contain such groups. Generally, the analytical values obtained by the method are within 100+/-4% of theory.