Naloxone influences ultrasonic calling in young mice

The ultrasonic calls produced by three day old mice when separated from the nest mother and siblings increase in number when naloxone is injected.     

Plasma uric acid levels in ethanol-fed turkey poults treated with allopurinol

Plasma uric acid levels were determined in ethanol-fed poults following administration of allopurinol. In young poults, allopurinol at a dose of 50 mg/kg significantly depressed plasma uric acid levels 6 hr post-dosing. At 11 hr post-dosing, plasma uric acid levels were significantly elevated in the allopurinol-treated poults when compared with control poults. During a period of ethanol abstinence, allopurinol at a dose of 40 mg/kg significantly depressed plasma uric acid levels up to 8 hr post-dosing. At a dose of 30 mg/kg, plasma uric acid levels were similar to control values at 4 and 6 hr post-dosing. Data suggest that plasma uric acid levels can be depressed in ethanol poults when allopurinol is administered every 8 hr at a dose of 40-50 mg/kg of body weight.     

Evaluation of allopurinol as a cardioprotectant in ethanol-fed turkey poults

Cardioprotectant effects of allopurinol were investigated in ethanol-fed poults during induction of cardiomyopathy and during a period of ethanol abstinence. In young poults fed ethanol, allopurinol has an additive effect on depression of growth but has little or no effect on caloric consumption. Allopurinol significantly depresses heart weight and heart weight to body weight ratios in young poults. In poults 5 weeks and older, allopurinol depresses significantly body weight and caloric consumption. Although allopurinol depresses heart weight in older poults, it appears to have little or no effect on heart weight to body weight ratios. Cardioprotective effect of allopurinol is more apparent during the inductive process than during the recovery phase.     

Accumulation and secretion of exoglucanase activity in yeast secretory mutants

Representative conditional yeast secretory mutants, blocked in transport of secretory and plasma membrane proteins from the endoplasmic reticulum (sec 18), from the Golgi body (sec 7) and in transport of secretory vesicles (sec 1), accumulated exoglucanase, a constitutive yeast activity, when incubated at the restrictive temperature (37°C). Different proportions of the accumulated activity were released by mutant cells under permissive conditions. The presence or absence of cycloheximide during the secretion period made no differences in the results. More than 90% of the internal activity was bound to membrane in wild type cells. However, only the soluble pool underwent changes during the accumulation or secretion periods. The bulk of secretory invertase accumulated by sec 1 was also soluble. By contrast sec 7 and sec 18 accumulated membrane-bound as well as soluble invertase forms and both were secreted in similar proportions in each mutant. More than 90% of the accumulated invertase was secreted at the permissive temperature in sec 18 cells. That percentage was significantly lower for exoglucanase (<65%). Concomitantly, invertase accumulated by this mutant exited from the cells with a lower half time (t 1/2=150 min). These results may be interpreted assuming that exoglucanase is exported by a passive flow of the soluble pool.Non-standard abbreviations p-NPG p-nitrophenyl--d-glucopyranoside - Con A concanavalin A - Tris tris(hydroxymethyl)-amino-methane     

Effects of some aldehydes on brain microtubular protein

4-Hydroxynonenal is one of the main breakdown products of lipid peroxidation. It has an antiproliferative effect, which may partly be the consequence of an interaction with cytoskeletal structures. Its effects on microtubular protein are compared with those of homologous aldehydes with the same number of carbon atoms, and with that of benzaldehyde. Unlike the other aliphatic aldehydes, this latter aldehyde does not impair microtubular functions at every concentration in the range. Nonanal has the greatest effect on tubulin polymerization, whereas it only slightly impairs colchicine binding activity. 2-Nonenal and 4-hydroxynonenal have less inhibiting effect on tubulin polymerization; their effect on colchicine binding activity is dose-dependent. The targets of 4-hydroxynonenal on tubulin are -SH groups; the action mechanism of other aldehydes has not yet been identified.     

Effects of starvation on haemolymphatic glucose levels, glycogen contents and nucleotidase activities in different tissues of Helix aspersa (Müller, 1774) (Mollusca, Gastropoda)

In the present study, the glucose concentration in the haemolymph and glycogen levels were determined in the various body parts of the Helix aspersa snail after feeding lettuce ad libitum and after various periods of starvation. To characterize the effect of starvation on nucleotidase activity, enzyme assays were performed on membranes of the nervous ganglia and digestive gland. Results demonstrated the maintenance of the haemolymph glucose concentration for up to 30 days of starvation, probably due to the consumption of glycogen from the mantle. In the nervous ganglia, depletion of glycogen occurs progressively during the different periods of starvation. No significant changes were observed on ATP and ADP hydrolysis in the membranes of nervous ganglia and no alterations in Ca2+ -ATPase and Mg2+ -ATPase occurred in the membranes of the digestive gland of H. aspersa during the different periods of starvation. Although there were no changes in the enzyme activities during starvation, they could be modulated by effectors in situ with concomitant changes in products/reactants during starvation.     

Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of PI3-kinase

Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model.     

Structurally conserved interaction of Lgl family with SNAREs is critical to their cellular function

The Lethal giant larvae (Lgl) tumor suppressor family is conserved from yeast to mammals and plays a critical yet controversial role in cell polarity. Studies on Drosophila Lgl suggest that its function in polarity is through regulation of the acto-myosin cytoskeleton. In contrast, studies on the yeast Lgl homologs, Sro7/Sro77, suggest a function in exocytosis through interaction with the t-SNARE Sec9. Using yeast/mammalian Lgl chimeras, we demonstrate that the overall architecture of Lgl proteins is highly conserved and that the C-terminal domain is the major site of SNARE interaction within both yeast and mammalian homologs. Importantly, we find that the ability of Lgl chimeras to function as the only source of Lgl in yeast correlates precisely with the ability to interact with the yeast t-SNARE. We report a novel interaction between Sro7 and the yeast myosin V, Myo2. However, we find that interactions with either Myo2 or Myo1 (myosin II) cannot account for the dramatic functional differences observed for these chimeras in yeast. These results provide the first demonstration that the interaction of an Lgl family member with a specific effector is critical to its function in vivo. These data support the model that the Lgl family functions in cell polarity, at least in part, by regulating SNARE-mediated membrane delivery events at the cell surface.     

Transcriptional signatures of normal human mammary epithelial cells in response to benzo[a]pyrene exposure: a comparison of three microarray platforms

Microarrays are used to study gene expression in a variety of biological systems. A number of different platforms have been developed, but few studies exist that have directly compared the performance of one platform with another. The goal of this study was to determine array variation by analyzing the same RNA samples with three different array platforms. Using gene expression responses to benzo[a]pyrene exposure in normal human mammary epithelial cells (NHMECs), we compared the results of gene expression profiling using three microarray platforms: photolithographic oligonucleotide arrays (Affymetrix), spotted oligonucleotide arrays (Amersham), and spotted cDNA arrays (NCI). While most previous reports comparing microarrays have analyzed pre-existing data from different platforms, this comparison study used the same sample assayed on all three platforms, allowing for analysis of variation from each array platform. In general, poor correlation was found with corresponding measurements from each platform. Each platform yielded different gene expression profiles, suggesting that while microarray analysis is a useful discovery tool, further validation is needed to extrapolate results for broad use of the data. Also, microarray variability needs to be taken into consideration, not only in the data analysis but also in specific probe selection for each array type.