Sec15, a component of the exocyst, promotes notch signaling during the asymmetric division of Drosophila sensory organ precursors

Asymmetric division of sensory organ precursors (SOPs) in Drosophila generates different cell types of the mature sensory organ. In a genetic screen designed to identify novel players in this process, we have isolated a mutation in Drosophila sec15, which encodes a component of the exocyst, an evolutionarily conserved complex implicated in intracellular vesicle transport. sec15(-) sensory organs contain extra neurons at the expense of support cells, a phenotype consistent with loss of Notch signaling. A vesicular compartment containing Notch, Sanpodo, and endocytosed Delta accumulates in basal areas of mutant SOPs. Based on the dynamic traffic of Sec15, its colocalization with the recycling endosomal marker Rab11, and the aberrant distribution of Rab11 in sec15 clones, we propose that a defect in Delta recycling causes cell fate transformation in sec15(-) sensory lineages. Our data indicate that Sec15 mediates a specific vesicle trafficking event to ensure proper neuronal fate specification in Drosophila.     

Interruption of antifungal secondary prophylaxis in AIDS-related histoplasmosis

The clinical data of 21 patients, suffering AIDS-related histoplasmosis, who were able to interrupt antifungal secondary prophylaxis, after achieving a partial restoration of the cell mediated immunity by HAART administration, are presented. They were 16 males and five females, whose ages varied between 32 and 54 years (mean = 38.5 years). All of them presented disseminated progressive forms of histoplasmosis, with multiple locations (skin, mucous membranes, liver, spleen, lymph nodes and lungs). The majority of the cases suffered other concomitant diseases (specially tuberculosis and Kaposi sarcoma), 66.6 % of the patients had less than 50 CD4+ cells/microl at the start of treatment and the average viral burden was 278,385 RNA copies/ml. The initial treatment consisted in 400 mg/day of itraconazole, by oral route, in 14 cases and the remaining seven patients were treated with amphotericin B, intravenously, at a daily dose of 0.7 mg/kg of body weight. One patient who did not tolerate amphotericin B and presented a partial response to itraconazole, was treated with posaconazole orally at a daily dose of 800 mg. Fourteen patients received oral itraconazole at a daily dose of 200 mg as a secondary prophylaxis, the remaining three patients were treated with intravenous amphotericin B, 50 mg twice a week. After HAART for an average lapse of 16.7 months (10 to 32 months), five cases showed CD4+ cells counts above 150 cells/microl and the remaining 16 presented more than 200 cells/microl; 18 of them had undetectable viral burden and all cases were asymptomatic. The follow up after secondary prophylaxis discontinuation varied between six months and six years (mean= 33.6 months). Twenty out of 21 patients (95 %) were clinically stable, without any manifestation of relapses, including two patients who abandoned HAART. One patient, who discontinued HAART, contracted a fatal bacterial pneumonia. Even though the limited number of cases, the data presented in this study seem to suggest that it is possible to interrupt antifungal secondary prophylaxis of histoplasmosis, when the patient is clinically asymptomatic and the CD4+ cells counts are above 150 cells/microl.     

Production of structured lipids by acidolysis of an EPA-enriched fish oil and caprylic acid in a packed bed reactor: analysis of three different operation modes

Structured triacylglycerols (ST) enriched in eicosapentaenoic acid (EPA) in position 2 of the triacylglycerol (TAG) backbone were synthesized by acidolysis of a commercially available EPA-rich oil (EPAX4510, 40% EPA) and caprylic acid (CA), catalyzed by the 1,3-specific immobilized lipase Lipozyme IM. The reaction was carried out in a packed bed reactor (PBR) operating in two ways: (1) by recirculating the reaction mixture from the exit of the bed to the substrate reservoir (discontinuous mode) and (2) in continuous mode, directing the product mixture leaving the PBR to a product reservoir. By operating in these two ways and using a simple kinetic model, representative values for the apparent kinetic constants (kX) for each fatty acid (native, Li or odd, M) were obtained. The kinetic model assumes that the rate of incorporation of a fatty acid into TAG per amount of enzyme, rX (mole/(h g lipase)) is proportional to the extent of the deviation from the equilibrium for each fatty acid (i.e., the difference of concentration between the fatty acid in the triacylglycerol and the concentration of the same fatty acid in the triacylglycerol once the equilibrium of the acidolysis reaction is reached). The model allows comparing the two operating modes through the processing intensity, defined as mLt/(V[TG]0) and mL/(q[TG]0), for the discontinuous and continuous operation modes, respectively. In discontinuous mode, ST with 59.5% CA and 9.6% EPA were obtained. In contrast, a ST with 51% CA and 19.6% EPA were obtained when using the continuous operation mode. To enhance the CA incorporation when operating in continuous mode, a two-step acidolysis reaction was performed (third operation mode). This continuous two-step process yields a ST with a 64% CA and a 15% EPA. Finally, after purifying the above ST in a preparative silica gel column, impregnated with boric acid, a ST with 66.9% CA and 19.6% EPA was obtained. The analysis by reverse phase and Ag+ liquid chromatography of the EPA-enriched ST demonstrated that the CA was placed in positions 1 and 3 and the EPA was occupying position 2 of the final ST.     

Modulation by substrates of the protective effect of cyclosporin A on mitochondrial damage

The influence of substrates on the role of cyclosporin A, to promote the closure of the permeability transition pore, was studied. It was found that in succinate-oxidizing mitochondria, cyclosporin inhibited pore opening as induced by carboxyatractyloside. The opposite occurred when mitochondrial respiration was supported by malate-glutamate, i.e., cyclosporin A was unable to block pore opening promoted by carboxyatractyloside. We propose that the failure of cyclosporin A to induce pore closure could be due to a low NADH matrix content.     

The flavoenzyme ferredoxin (flavodoxin)-NADP(H) reductase modulates NADP(H) homeostasis during the soxRS response of Escherichia coli

Escherichia coli cells from strain fpr, deficient in the soxRS-induced ferredoxin (flavodoxin)-NADP(H) reductase (FPR), display abnormal sensitivity to the bactericidal effects of the superoxide-generating reagent methyl viologen (MV). Neither bacteriostatic effects nor inactivation of oxidant-sensitive hydrolyases could be detected in fpr cells exposed to MV. FPR inactivation did not affect the MV-driven soxRS response, whereas FPR overexpression led to enhanced stimulation of the regulon, with concomitant oxidation of the NADPH pool. Accumulation of a site-directed FPR mutant that uses NAD(H) instead of NADP(H) had no effect on soxRS induction and failed to protect fpr cells from MV toxicity, suggesting that FPR contributes to NADP(H) homeostasis in stressed bacteria.     

Song perception in the European starling: hemispheric specialisation and individual variations

Hemispheric specialisation for speech in humans has been well documented. The lateralisation for song production observed in songbirds is reminiscent of this hemispheric dominance. In order to investigate whether song perception is also lateralised, we made multiunit recordings of the neuronal activity in the field L of starlings during the presentation of species-specific and artificial non-specific sounds. We observed a systematic stronger activation in one hemisphere than in the other one during the playback of species-specific sounds, with inter-subject variability in the predominant hemisphere for song perception. Such an asymmetry was not observed for artificial non-specific sounds. Thus, our results suggest that, at least at the individual level, the two hemispheres of the starlings' brain perceive and process conspecific signals differently.     

Proteomics analysis of the neurodegeneration in the brain of tau transgenic mice

Protein tau, a major microtubule-binding protein in the brain, comprises six isoforms generated through alternative mRNA splicing. A dysfunctional form of mutant and normal tau is associated or implicated in the pathogenesis of several neurodegenerative disorders. The neuropathological hallmark of these tau-opathies are intraneuronal depositions of fibrillary aggregates of which neurofibrillary tangles are most common. Several distinct transgene mouse models confirmed that tau protein can cause neurodegeneration directly. This study was aimed at identifying proteins that might play a role in the cellular disturbances caused by overexpression of the longest isoform of human tau in the brain of transgenic mice. We found 34 proteins which differed in integrated intensity by a factor of at least 1.5. These proteins could be sorted into several categories. Some of the phenotypic characteristics found in the htau transgenic mice could be related to proteins found in this study. Several proteins are linked to processes involving apoptosis and neuronal death and have been discussed in papers describing neurodegenerative disorders.     

(Co)variance components, genetic parameters and annual trends for calf weights in a Brahman herd kept on floodable savanna

(Co)variance components and genetic parameters were estimated for body weights of an elite Brahman herd under a designed, supervised management and genetic program, including strategic artificial insemination (AI). Restricted maximum likelihood methods were used with a univariate animal model for birth weight (BW) and a bivariate model for weaning weight (205-day weight, 205W) and 18-month weight (548-day weight, 548W). Models included random animal direct and maternal genetic effects, maternal permanent environmental effect (c2), and sex-year-month of birth-age of dam and genetic group (identified and unidentified paternity), as fixed effects. Analysis A1 included all calves and analysis A2 included only those with identified sires. Of the 8,066 calves born, 36% were progeny of AI, 11% from single sire and 53% from multi-sire herds. They were born from 1985 to 1998, from 2559 dams and 146 sires (78 identified). Estimates of direct, maternal and total heritabilities from A1 for BW, 205W and 548W were: 0.23, 0.07 and 0.30; 0.08, 0.14 and 0.16; 0.16, 0.04 and 0.28, respectively. Corresponding estimates of direct maternal genetic correlations were 0.22, 0.07 and 0.86, and c2 estimates were 0.04, 0.14 and 0.04, respectively. Estimates of direct and maternal genetic, and permanent environmental correlations between 205W and 548W were: 0.66, 0.70 and 1.00. Variances and genetic parameters from A1 and A2 were, in general, very similar. Estimates of phenotypic, and direct and maternal genetic trends per year from A1 were: 0.393, 0.004 and 0.003 kg (BW), 3.367, 0.142 and 0.115 kg (205W), 1.813, 0.263 and 0.095 kg (548W). Estimates of direct and maternal genetic trends from A2 were: 0.033 and -0.002 kg (BW); 0.186 and 0.276 kg (205W); 0.471 and 0.136 kg (548W). The modern selection methods that have been used recently should be continued, with emphasis on the improvement of cow efficiency for sustainable beef production on floodable savanna combined with improved pasture.