Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase

Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ～80% at 2?h when dosed in mice orally at 50?mg/kg.     

Effect of Supplemental Trace Minerals on Hsp-70 mRNA Expression in Commercial Broiler Chicken

The effects of supplementing the organic forms of selenium (Se), chromium (Cr), and zinc (Zn) on Hsp-70 mRNA expression and body weight in broiler chickens were evaluated. 200 chicks were equally distributed into stainless steel battery brooders at the rate of 5 birds per pen and reared under heat stress condition up to 42^nd day. The chicks were fed with three experimental diets supplemented with organic forms of Se (0.30?mg/kg), Cr (2?mg/kg), and Zn (40?mg/kg) during the starter and finisher phases and a control diet without any supplementation. On the 21st and 42nd day, 20 birds from each period were sacrificed and samples were collected for analysis. Organic Se, Cr, and Zn supplementation significantly (P?Hsp-70 mRNA levels. The Hsp-70 mRNA expression levels were significantly (P?Hsp-70 mRNA expression level was not affected by age of the birds. The study concluded that organic trace mineral (oTM) supplementation resulted in low Hsp-70 mRNA expression, indicating reduced heat stress in broilers.     

Detection of filarial antigen by inhibition enzyme linked immunosorbent assay using fractionatedBrugia malayi microfilarial excretory secretory antigen

Detection of filarial antigen in blood or urine samples would provide an accurate indication of active infection. The absence of a simple, well established animal model and limitations in getting the required amount of parasite material from human sources have been the main obstacles for the diagnosis ofWuchereria bancrofti infection. An inhibition ELISA has been developed for detection of filarial antigen using a partially purifiedBrugia malayi mf ES antigen (BmE DE1) and its affinity purified antibodies. Filarial antigen was detected in the sera of 88% of microfilaraemic, 60% of chronic filarial, 17% of endemic normal and none of the non- endemic normal subjects. The sensitivity and specificity of the assay were 88% and 89% respectively. Moreover, undiluted urine samples from 82% of microfilaraemic and 17% of endemic normal, but none of the non- endemic normal samples showed the presence of filarial antigen. With the limitations on the availability of sufficient homologous parasite materials, the inhibition ELISA using BmE DE1 and anti BmE DE1 antibodies shows promise for the detection of active infection in bancroftian filariasis in man. Moreover, its detection in urine makes it more possible to test patients in field areas.     

Does RU486 modify hormonal responses to handling stressor and cortisol treatment in fed and fasted rainbow trout?

This study examines the effect of the steroid analogue, RU486, on the physiological responses of fed and chronically fasted rainbow trout to an acute handling stressor. This potent ligand of the glucocorticoid receptor was administered as a slow-release implant either alone, or in combination with cortisol. There were temporal changes in plasma cortisol concentrations following administration of cortisol implants in both fed and fasted trout. By day 14, plasma cortisol levels in fed fish were similar in all treatment groups, but in fasted fish, the effect of cortisol administration on plasma cortisol concentrations was still evident; RU486 administered with cortisol, did not affect this response. Cortisol administration also elicited a small, but significant increase in plasma GH concentrations in fed rainbow trout and in plasma glucose concentrations in fasted animals. RU486-treatment prevented these responses. Conversely, whereas RU486 alone had no effect on hepatic 5'-monodeiodinase activity, when administered with cortisol it enhanced the marked suppressive effect of cortisol evident in both fed and fasted groups, suggesting that it may exert an interactive effect with cortisol on this process. Stressor-related changes in plasma cortisol, glucose, GH and thyroid hormone concentrations were evident in both fed and fasted groups; however, there was no evidence of a suppressive effect of RU486 treatment on any of the measured plasma parameters. Although RU486 did not prevent the stressor-related changes, the post-stressor cortisol profiles in RU-treated trout were extremely erratic compared with the oil-treated controls. This implies a disturbance of the normal interactions of the components of the hypothalamus-pituitary-interrenal tissue axis.     

Distribution and homology of plasmids in several strains of Cyanothece

The plasmid distribution of several clonal isolates of the unicellular, diazotrophic, cyanobacterium Cyanothece sp. has been analyzed. The Cyanothece isolates contain three to four plasmids ranging in size from 4.8 kb to 40 kb. The plasmid profiles of three Cyanothece strains (BH63, BH68, BH93) indicated that strains BH68 and BH93 were closely related and that strain BH63 may be more distantly related. A small 4.8-kb plasmid (pSE480), from the clonal isolate Cyanothece sp. strain BH68F, has been subcloned and restriction mapped. Ten restriction sites have been mapped, five of which are unique and suitable for further subcloning. Southern hybridization revealed that this plasmid was present in two out of five clonal isolates of strain BH68 and in one isolate of strain BH93. A 10-kb plasmid from strain BH68F (pSE1000) was found in all of the BH68 isolates and was absent in the BH93 isolate, Cyanothece sp. strain BH93A. No notable physiological changes were observed in the absence of either the 4.8-kb or 10-kb plasmids. Therefore, these plasmids remain cryptic. Further analysis of these plasmids may provide insight into the function of these plasmids and will allow the construction of shuttle vectors for gene transfer experiments.     

Effect of C/N ratio and moisture content on the composting of poplar wood

Summary Milled poplar wood (1.7 mm mesh size) was composted in lab-scale reactors. Initial C/N ratios were adjusted to 10:1, 30:1, and 50:1 using urea as the nitrogen source. At each C/N ratio, three moisture levels (30, 50, and 70%) were tested. C/N ratios of 50:1 or 30:1 and moisture content of 70% favored more effective composting as indicated by higher levels of mineralization of the poplar wood to CO₂.     

Differential expression of esterase and MDH isozymes during in vitro culture in maize (Zea mays L.)

Isozyme patterns of esterase and malate dehydrogenase were analyzed at different stages of in vitro culture of immature embryos and glumes of Zea mays L. viz. explant, callus formation, root formation and shoot formation. Significant changes in isoenzyme patterns of esterase and MDH were observed besides the appearance of specific and new isozymes. Specific fast migrating isozymes were noted in differentiating calli of embryo and glume calli which were absent at other stages suggesting a possible association of these isozyme patterns with in vitro differentiation.     

Localization of a kinesin-like calmodulin-binding protein in dividing cells of Arabidopsis and tobacco

The cloning and characterization of a novel kinesin-like protein ( k inesin-like c almodulin- b inding p rotein, KCBP) from Arabidopsis and other plants has recently been described. Unlike all other known kinesin-like proteins, KCBP interacts with calmodulin in the presence of micromolar calcium. An antibody specific to KCBP was raised using a calmodulin-binding synthetic peptide that is unique to KCBP. The KCBP antibody detected a single protein of about 140 kDa in Arabidopsis and tobacco, the size predicted from cDNA sequences. In synchronized cell cultures, the amount of KCBP was abundant during M-phase and very low in interphase. To get some insight into the function of this novel motor protein, KCBP in Arabidopsis and tobacco cells was localized by indirect immunofluorescence microscopy using affinity-purified anti-KCBP antibody. The KCBP was localized to the pre-prophase band, the mitotic spindle and the phragmoplast. The association of KCBP with microtubule arrays in dividing cells suggests that this minus-end-directed microtubule motor protein is likely to be involved in the formation of these microtubule arrays and/or functions associated with these structures.     

Furanoid sugar amino acids as dipeptide mimics in design of analogs of vasoactive intestinal peptide receptor binding inhibitor.

In this study we describe the development of peptidomimetic analogs of the potent vasoactive intestinal peptide receptor binding inhibitor, Leu(1) -Met(2) -Tyr(3) -Pro(4) -Thr(5) -Tyr(6) -Leu(7) -Lys(8) -OH 1, by incorporating furanoid sugar amino acids (SAAs) 2-4 into the molecule. The furanoid SAAs 2-4 were used as dipeptide isosteres to replace Tyr(3) -Pro(4) or Pro(4) -Thr(5) in sequence 1. The resulting analogs 5-9 were tested for their anti-cancer activities in vitro, following the standard MTT assay on a panel of human cancer cell lines. One of the potent analogs, 6a was tested in vivo for tumor regression on primary colon tumor xenografted nude mice. Our experimental results suggest that many of these analogs show either retention or enhancement of biological activity.