Chronic ethanol attenuates centrally-mediated hypotension elicited via α2-adrenergic,but not I1-imidazoline,receptor activation in female rats

AimsThis study dealt with the effect of chronic ethanol administration on hemodynamic responses elicited by α₂-adrenergic (α-methyldopa) or I₁-imidazoline (rilmenidine) receptor activation in telemetered female rats.Main methodsThe effects of α-methyldopa or rilmenidine on blood pressure (BP), heart rate (HR) and their variability were investigated in rats that received liquid diet without or with ethanol (5% w/v) for 12 weeks. To evaluate the effect of each drug on cardiovascular autonomic control (BP and HR variability) in the absence or presence of ethanol, three time-domain indices of hemodynamic variability were measured: (i) standard deviation of mean arterial pressure (SDMAP), (ii) standard deviation of beat-to-beat intervals, and (iii) root mean square of successive differences in R–R intervals.Key findingsIn liquid diet-fed control rats, i.p. rilmenidine (600 µg/kg) or α-methyldopa (100 mg/kg) reduced BP along with decreases and increases, respectively, in HR. Both drugs had no effect on HR variability but reduced BP variability (SDMAP), suggesting a reduced vasomotor sympathetic tone. Ethanol feeding attenuated reductions in BP and SDMAP evoked by α-methyldopa but not by rilmenidine.SignificanceWe conclude that chronic ethanol preferentially compromises α₂- but not I₁-receptor-mediated hypotension in female rats probably via modulation of vasomotor sympathetic activity. These findings highlight the adequacy of rilmenidine use to lower BP in hypertensive alcoholic females.     

Function of the nuclear receptor FTZ‐F1 during the pupal stage in Drosophila melanogaster

The nuclear receptor βFTZ‐F1 is expressed in most cells in a temporally specific manner, and its expression is induced immediately after decline in ecdysteroid levels. This factor plays important roles during embryogenesis, larval ecdysis, and early metamorphic stages. However, little is known about the expression pattern, regulation and function of this receptor during the pupal stage. We analyzed the expression pattern and regulation of ftz‐f1 during the pupal period, as well as the phenotypes of RNAi knockdown or mutant animals, to elucidate its function during this stage. Western blotting revealed that βFTZ‐F1 is expressed at a high level during the late pupal stage, and this expression is dependent on decreasing ecdysteroid levels. By immunohistological analysis of the late pupal stage, FTZ‐F1 was detected in the nuclei of most cells, but cytoplasmic localization was observed only in the oogonia and follicle cells of the ovary. Both the ftz‐f1 genetic mutant and temporally specific ftz‐f1 knockdown using RNAi during the pupal stage showed defects in eclosion and in the eye, the antennal segment, the wing and the leg, including bristle color and sclerosis. These results suggest that βFTZ‐F1 is expressed in most cells at the late pupal stage, under the control of ecdysteroids and plays important roles during pupal development.     

Phylogenomics of life-or-death switches in multicellular animals: Bcl-2, BH3-Only, and BNip families of apoptotic regulators

In this report, we conducted a comprehensive survey of Bcl-2 family members, a divergent group of proteins that regulate programmed cell death by an evolutionarily conserved mechanism. Using comparative sequence analysis, we found novel sequences in mammals, nonmammalian vertebrates, and in a number of invertebrates. We then asked what conclusions could be drawn from phyletic distribution, intron/exon structures, sequence/structure relationships, and phylogenetic analyses within the updated Bcl-2 family. First, multidomain members having a sequence pattern consistent with the conservation of the Bcl-X(L)/Bax/Bid topology appear to be restricted to multicellular animals and may share a common ancestry. Next, BNip proteins, which were originally identified based on their ability to bind to E1B 19K/Bcl-2 proteins, form three independent monophyletic branches with different evolutionary history. Lastly, a set of Bcl-2 homology 3-only proteins with unrelated secondary structures seems to have evolved after the origin of Metazoa and exhibits diverse expansion after speciation during vertebrate evolution.     

A non-parametric approach for identifying differentially expressed genes in factorial microarray experiments

We introduce a non-parametric approach using bootstrap-assisted correspondence analysis to identify and validate genes that are differentially expressed in factorial microarray experiments. Model comparison showed that although both parametric and non-parametric methods capture the different profiles in the data, our method is less inclined to false positive results due to dimension reduction in data analysis.     

Evaluation of superoxide dismutase and glutathione peroxidase enzymes and their cofactors in Egyptian children with Down's syndrome

The present work investigated the activity of Cu/Zn superoxide dismutase enzyme (SOD) in red blood cells and glutathione peroxidase enzyme (GPx) in whole blood by spectrophotometric methods. Plasma levels of the cofactors copper and zinc and whole-blood selenium were evaluated using atomic absorption spectrophotometer. The study included a population of 18 Down's syndrome (DS) patients with complete trisomy 21 (group 1), translocations (group 2), and mosaicism (group 3), and their 15 matched controls. The purpose of this work was to study the gene dosage effect of SOD and its consequence on GPx enzyme and the various cofactors, and to find out correlations with developmental fields. Our results showed that in the population with complete trisomy 21 and translocations, SOD and GPx activities were increased, whereas in cases with mosaicism, the enzymes activities were within normal limits. Plasma copper concentrations were increased, whereas whole-blood selenium concentrations were significantly decreased in the three DS groups. Plasma zinc levels were within normal in all patients. We concluded that changes in trace elements and enzyme activities were not related to age or sex. Also, there was no correlation between the enzyme levels and the developmental activities. Our results are useful tools for identifying nutritional status and guiding antioxidant intervention.     

Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells

This study was designed to investigate the molecular changes that may develop during exposure of breast cancer cells to anticancer agents and that may lead to acquired resistance. We used two breast cancer cell lines, a parental (MCF7/WT) and a doxorubicin-resistant (MCF7/DOX) one. Cell survival, cell cycle distribution and RT-PCR expression level of genes involved in DNA damage response, MDR1, GST and TOPOIIα were measured. MCF7/DOX cells were five-fold more resistant to doxorubicin (DOX) than the MCF7/WT cells. DOX treatment causes arrest of MCF7/DOX cells in G1 and G2 phases of cell cycle whereas MCF7/WT cells were arrested in S-phase. The molecular changes in both cell lines due to DOX treatment could be classified into: (1) the basal level of p53, p21, BRCA1, GST and TOPOIIα mRNA was higher in MCF7/DOX than MCF7/WT. During DOX treatment, the expression level of these genes decreased in both cell lines but the rate of down-regulation was faster in MCF7/WT than MCF7/DOX cells. (2) The expression level of MDR1 was the same in both cell lines but 48 and 72 h of drug treatment, MDR1 disappeared in MCF7/WT but still expressed in MCF7/DOX. (3) There was no change in the expression level of BAX, FAS and BRCA2 in both cell lines. Conclusively, after validation in clinical samples, overexpression of genes like BRCA1, p53, p21, GST, MDR1 and TOPOIIα could be used as a prognostic biomarker for detection of acquired resistance in breast cancer and as therapeutic targets for the improvement of breast cancer treatment strategies.     

An experiment of fish spillover from a marine reserve in Cuba

Several studies on adult fish movement from marine protected areas to zones open to fishing activity conclude spillover is present, but most of these investigations use indirect evidence and small-sized species of little commercial importance. This paper reports the effects of manipulating a density gradient on movements of large-sized and commercially-important fish across “Jardines de la Reina” Marine Reserve boundaries, using tagging methods and visual census. Tagging was carried out using dart tags and modified spearguns at an experimental and a control site. Density of fish was experimentally manipulated on the unprotected side of the boundary. Before experimental manipulation, fish density was similar in both experimental and control sites and on both sides of the boundaries. After manipulation, fish density in the unprotected side of experimental site declined dramatically and a strong gradient was established through the boundary. One month later, this forced gradient disappeared, returning to the situation at the beginning of the study. This last result is due to spillover effect: the mean distance traveled by fish increased 1.5 times (mean from below 200 m to more than 300 m), the mean emigration rate doubled and the immigration rate decreased, allowing density levels to recover after manipulation.