Phosphorylation of the gastric tumor suppressor RUNX3 following H. pylori infection results in its localization to the cytoplasm

As H. pylori infection progresses, intestinal metaplasia (IM), a key event in gastric carcinogenesis, develops in the stomach. The mechanism by which H. pylori infection causes the trans-differentiation of gastric cells to intestinal-type cells remains an important question. In the current study, we found that RUNX3 is deregulated in all human IM specimens examined by either down regulation or mislocalization; Aberrant localization of a gastric tumor suppressor RUNX3 is observed in most human cases of IM with concurrent H. pylori infection, and RUNX3 is down-regulated in most cases of IM without H. pylori-infection. The cytoplasmic mislocalization of a RUNX3 was associated with H. pylori-induced c-Src activation and RUNX tyrosine phosphorylation. Moreover, gastric epithelial cells of Runx3(-/-) mice expressed the intestinal markers Muc2 and Li-Cadherin, which suggests that the deregulation of Runx3 is a key event in the intestinalization of the gastric epithelium. Collectively, the results of the current study suggest that RUNX3 deregulation is associated with H. pylori-induced pathogenesis and the development of IM.     

STUDIES ON THE TISSUE AND SUBCELLULAR DISTRIBUTION OF β-N-OXALYL-l-α, β-DIAMINOPROPIONIC ACID, THE LATHYRUS SATIVUS NEUROTOXIN

Abstract— β- N -Oxalyl- l -α, β-diaminopropionic acid (ODAP), the Lathyrus sativus neurotoxin can be detected in significant concentrations in the synaptosomal fractions isolated from young rat brain and adult monkey spinal cord, when these animals manifest neurological symptoms after ODAP administration. However, isolated synaptosomes fail to exhibit any transport system for ODAP uptake. ODAP administered in vivo appears to get localized in a population of synaptosomes which exhibit a high affinity uptake system for glutamate.     

Risk modulation of GSTM1–GSTT1 interactions to head and neck cancer in tobacco users

Tobacco use and environmental air pollution are the established etiological factors in head and neck cancer (HNC) progression. Nevertheless, not all the inhabitants with high usage of tobacco from the same polluted locality are suffering with HNC and this is due to the existence of factors like inter-individual genetic polymorphisms, life time exposure to tobacco and the rate of xenobiotic metabolism enzyme (XME) activity. The present study investigates the polymorphic genotypes of the most important XME, glutathione-S-transferase Mu 1 (GST M1) and Theta 1 (GST T1) as the risk modulator to HNC among tobacco-habituated inhabitants of Saurashtra in Gujarat, a region in western India. A population based case–control study was done in 252 HNC patients and 504 healthy controls. Blood samples were collected from the subjects and investigated for polymorphic genotypes of GST M1 and GST T1. Estimation of the odds of risks was done by logistic regressions. Among the subjects with high usage of tobacco, M1 not null-T1 null genotypes presence was found as risk reducing factor to HNC with 0.334 folds (95 % CI; 0.170–0.659). The presence of M1 null-T1 not null genotypes was found with susceptibility to HNC among the subjects with no habit of tobacco chewing, adjusted odds ratio (AOR) 3.170 (1.128–8.913) and no habit of smoking, AOR of 2.544 (1.094–5.963). The present study reveals the finding of significantly increased risk to HNC by interactions of GST M1 null-GST T1 not null polymorphic genotypes among the subjects with nil or less tobacco usage shed some light for the insights of biomarker application in early detection of HNC.     

Aromatic-aromatic interactions: analysis of π-π interactions in interleukins and TNF proteins

Aromatic-aromatic hydrogen bonds are important in many areas of chemistry, biology and materials science. In this study we have analyzed the roles played by the π-π interactions in interleukins (ILs) and tumor necrosis factor (TNF) proteins. Majority of π-π interacting residues are conserved in ILs and TNF proteins. The accessible surface area calculations in these proteins reveal that these interactions might be important in stabilizing the inner core regions of these proteins. In addition to π-π interactions, the aromatic residues also form π-networks in ILs and TNF proteins. The results obtained in the present study indicate that π-π interactions and π-π networks play important roles in the structural stability of ILs and TNF proteins.     

The relationship between δ-aminolaevulinate synthetase induction and the concentrations of cytochrome P-450 and catalase in rat liver

The porphyrinogenic drug 2-allyl-2-isopropylacetamide causes the degradation of microsomal cytochrome P-450 and inhibits the synthesis of catalase in rat liver. The inhibition of catalase synthesis follows the induction of delta-aminolaevulinate synthetase and the consequent overproduction of haem. The allylisopropylacetamide-mediated breakdown of cytochrome P-450 is a rapid event and has a reciprocal relationship to the pattern of delta-aminolaevulinate synthetase induction. Breakdown of cytochrome P-450 appears to be one of the conditions leading to the ;derepression' of delta-aminolaevulinate synthetase.     

Haem synthesis during mitochondrogenesis in yeast

The activities of delta-aminolaevulate synthetase and delta-aminolaevulate dehydratase have been assayed in Saccharomyces cerevisiae during glucose repression and de-repression. delta-Aminolaevulate dehydratase increased concomitantly with the increase in oxygen uptake during the de-repression phase caused by the depletion of glucose in the medium. delta-Aminolaevulate synthetase showed an oscillatory behaviour and a spurt in its activity always preceded the increase in oxygen uptake. The activity of both the enzymes was lowered if the cells were incubated with glucose or cycloheximide, but not with chloramphenicol.