Prevention by free radical scavenger AD5 of prooxidant effects of choline deficiency

This study was designed to explore the possible preventive effects of a novel radicophile, N-p-methoxyphenylacetyl-dehydroalanine (AD5) and three other antioxidants, N,N'-diphenyl-p-phenylenediamine (DPPD), butylated hydroxyanisole (BHA) and a water-soluble analogue of vitamin E, trolox C, on the acute effects of the liver of feeding a choline-deficient (CD) diet. It has been suggested that some of the acute effects of a CD diet are related to free radicals, the generation or metabolism of which is disturbed in this acute dietary model. AD5 was found to be very effective in preventing nuclear lipid peroxidation, DNA damage and cell death induced by a CD diet but to have little effect on triglyceride accumulation ("fatty liver"). DPPD, BHA, and trolox C were ineffective. These results add strength to the hypothesis that oxygen free radicals might be an important component in the early events during carcinogenesis induced by feeding a CD diet.     

Comparative morphology of the stomach of some laboratory mammals

Histomorphology of the stomach of mouse, rat, hamster, guineapig, gerbil, and rabbit was studied. Although a common structural basis existed in the stomach between these species, the occurrence and distribution of various cells in gastric glands differed considerably between them. In mice, rats, hamsters and gerbils, the lower one-third of the glandular lamina propria was seemingly occupied by a varying proportion of parietal and chief cells. In rabbits, the predominantly occurring chief cells were distributed in the lower three-quarters of the glands intermingling with parietal cells, but in guinea-pigs the chief cells were not discernible. In hamsters, there was, however, a gradual increase of chief cells from the junction between nonglandular-glandular stomach toward the pyloric region. In all these species, parietal cells were the predominant cell type in the upper half to upper one-third of the gastric glands, often extending up to the neck of the glands interspersing between mucus neck cells and occasionally between chief cells.     

Reversible HuR‐microRNA binding controls extracellular export of miR‐122 and augments stress response

microRNAs (miRNAs), the tiny but stable regulatory RNAs in metazoan cells, can undergo selective turnover in presence of specific internal and external cues to control cellular response against the changing environment. We have observed reduction in cellular miR‐122 content, due to their accelerated extracellular export in human hepatic cells starved for small metabolites including amino acids. In this context, a new role of human ELAV protein HuR has been identified. HuR, a negative regulator of miRNA function, accelerates extracellular vesicle (EV)‐mediated export of miRNAs in human cells. In stressed cells, HuR replaces miRNPs from target messages and is both necessary and sufficient for the extracellular export of corresponding miRNAs. HuR could reversibly bind miRNAs to replace them from Ago2 and subsequently itself gets freed from bound miRNAs upon ubiquitination. The ubiquitinated form of HuR is predominantly associated with multivesicular bodies (MVB) where HuR‐unbound miRNAs also reside. These MVB‐associated pool of miRNAs get exported out via EVs thereby delimiting cellular miR‐122 level during starvation. Therefore, by modulating extracellular export of miR‐122, HuR could control stress response in starved human hepatic cells.     

Clastogenic effects of dietary supplement--Spirulina alga, and some medicinal plant products from Boswellia serrata, Withania somnifera on mice

Pretreatment of aqueous extracts of Zyrulina (Spirulina), Aswagandha (Withania) and Nopane (Boswellia) on colchicine induced chromosome damage showed weakness of clastogenic activity in Swiss albino mice. None of the treatments increased significantly the number of chromosome aberrations.     

Simultaneous storage of medical images in the spatial and frequency domain: A comparative study

Background  

Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images, to reduce storage and transmission overheads.     

Randomly distributed crossovers may generate block-like patterns of linkage disequilibrium: an act of genetic drift

There is considerable interest in identifying and characterizing block-like patterns of linkage disequilibrium (LD; haplotype blocks) in the human genome as these may facilitate the identification of complex disease genes via genome-wide association studies. Although recombination hot-spots have been suggested as the primary mechanism to explain the block-like pattern of LD, other forces, such as genetic drift, may also be important. To this end, we have studied the effect of various recombination models on patterns of LD by using extensive simulations. As expected, haplotype blocks were observed under a model allowing recombination hot-spots. However, we also observed similar block-like patterns in the models where recombination crossovers are randomly and uniformly distributed, and we demonstrate that these blocks are generated by genetic drift. We caution that genetic drift may be an alternative mechanism (in addition to recombination hot-spots) that can lead to block-like patterns of LD. Our findings highlight the necessity of characterizing haplotype blocks in world-wide populations.     

Azide and acetate complexes plus two iron-depleted crystal structures of the di-iron enzyme delta9 stearoyl-acyl carrier protein desaturase. Implications for oxygen activation and catalytic intermediates

Delta9 stearoyl-acyl carrier protein (ACP) desaturase is a mu-oxo-bridged di-iron enzyme, which belongs to the structural class I of large helix bundle proteins and that catalyzes the NADPH and O2-dependent formation of a cis-double bond in stearoyl-ACP. The crystal structures of complexes with azide and acetate, respectively, as well as the apoand single-iron forms of Delta9 stearoyl-ACP desaturase from Ricinus communis have been determined. In the azide complex, the ligand forms a mu-1,3-bridge between the two iron ions in the active site, replacing a loosely bound water molecule. The structure of the acetate complex is similar, with acetate bridging the di-iron center in the same orientation with respect to the di-iron center. However, in this complex, the iron ligand Glu196 has changed its coordination mode from bidentate to monodentate, the first crystallographic observation of a carboxylate shift in Delta9 stearoyl-ACP desaturase. The two complexes are proposed to mimic a mu-1,2 peroxo intermediate present during catalytic turnover. There are striking structural similarities between the di-iron center in the Delta9 stearoyl-ACP desaturase-azide complex and in the reduced rubrerythrin-azide complex. This suggests that Delta9 stearoyl-ACP desaturase might catalyze the formation of water from exogenous hydrogen peroxide at a low rate. From the similarity in iron center structure, we propose that the mu-oxo-bridge in oxidized desaturase is bound to the di-iron center as in rubrerythrin and not as reported for the R2 subunit of ribonucleotide reductase and the hydroxylase subunit of methane monooxygenase. The crystal structure of the one-iron depleted desaturase species demonstrates that the affinities for the two iron ions comprising the di-iron center are not equivalent, Fe1 being the higher affinity site and Fe2 being the lower affinity site.     

Anti-angiogenic activity of BIM (bio-immunomodulator)

Angiogenesis and immune suppression are the two important factors responsible for embryo implantation and development of tumor. Therefore, disruption of angiogenesis and upliftment of immune function is essential for control of tumor growth as well as to regulate the activity of post coital contraceptives. BIM is an immunomodulatory cytokine obtained from rodent bone marrow that showed anti-implantation and anti-tumor activities. It also improved T/B cell and monocyte macrophage functions. In this communication the anti-angiogenic property of BIM is demonstrated in pregnant rat model. BIM induced disintegration of uterine myometrium and blood vessels. No implantation was observed compared to control. It is proposed that depending upon the physiological condition of the host BIM could modulate host immune function and exert its anti-angiogenic effect.     

Exposing culprit organic pollutants: a review

There is a continuing need for monitoring the health of the environment due to the presence of pollutants. Here, we review the development and attributes of biosensors by which bacteria have been genetically modified to express the luminescence genes, i.e. to glow, in a quantified manner, in response to pollutants. We have concentrated on the detection of organic hydrocarbon pollutants and discussed the molecular mechanisms by which some of these chemicals act as effector molecules on the respective regulatory systems. The future of environmental biosensors is predictably bright. As more knowledge is gathered on the sensing regulatory component, the possibility of developing targeted or pollutant-specific biosensors is promising. Moreover, the repertoire of biosensors for culprit organic pollutants is expected to be enlarged through advances in genomics technology and identification of new sensory or receptor molecules. The need for pollutant detection at concentrations in the parts per trillion range or biosensors configured in a nanoscale is anticipated.