Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions

Polyalanine expansions in the PHOX2B gene have been detected in the vast majority of patients affected with congenital central hypoventilation syndrome, a neurocristopathy characterized by absence of adequate control of breathing, especially during sleep, with decreased sensitivity to hypoxia and hypercapnia. The correlation between length of the alanine expanded tracts and severity of congenital central hypoventilation syndrome respiratory phenotype has been confirmed by length-dependent cytoplasmic PHOX2B retention with formation of aggregates. To deepen into the molecular mechanisms mediating the effects of PHOX2B polyalanine expansions, we have set up experiments aimed at assessing the fate of cells characterized by PHOX2B polyalanine aggregates. In particular, we have observed that activation of the heat shock response by the drug geldanamycin is efficient both in preventing formation and in inducing clearance of PHOX2B pre-formed polyalanine aggregates in COS-7 cells expressing PHOX2B-GFP fused proteins, and ultimately also in rescuing the PHOX2B ability to transactivate the Dopamine-beta-Hydroxilase promoter. In addition, we have demonstrated elimination of PHOX2B mutant proteins by the proteasome and autophagy, two cellular mechanisms already been involved in the clearance of proteins containing expanded polyglutamine and polyalanine tracts. Moreover, our data suggest that geldanamycin effects on PHOX2B aggregates may be also mediated by the proteasome pathway. Finally, analysis of cellular toxicity due to polyalanine aggregates has confirmed the occurrence of cell apoptosis consequent to expression of PHOX2B carrying the longest expanded alanine tract and shown that geldanamycin can delay cell progression toward the most advanced apoptotic stages.     

Chromium removal from a real tanning effluent by autochthonous and allochthonous fungi

Heavy metals represent an important ecological and health hazard due to their toxic effects and their accumulation throughout the food chain. Conventional techniques commonly applied to recover chromium from tanning wastewaters have several disadvantages whereas biosorption has good metal removal performance from large volume of effluents. To date most studies about chromium biosorption have been performed on simulated effluents bypassing the problems due to organic or inorganic ligands present in real industrial wastewaters that may sequestrate the Cr(III) ions. In the present study a tanning effluent was characterized from a mycological point of view and different fungal biomasses were tested for the removal of Cr(III) from the same tanning effluent in which, after the conventional treatments, Cr(III) amount was very low but not enough to guarantee the good quality of the receptor water river. The experiments gave rise to promising results with a percentage of removed Cr(III) up to 40%. Moreover, to elucidate the mechanisms involved in biosorption process, the same biomasses were tested for Cr(III) removal from synthetic aqueous solutions at different Cr(III) concentrations.     

Cunninghamella elegans biomass optimisation for textile wastewater biosorption treatment: an analytical and ecotoxicological approach

The effect of pre-treatments on the composition of Cunninghamella elegans biomass and on its biosorption yields in the treatment of simulated textile wastewaters was investigated. The inactivated biomass was subjected to physical treatments, such as oven drying and lyophilisation, and chemical treatments using acid or alkali. The wastewater colour, COD and toxicity variations were evaluated. The lyophilisation sped up the biosorption process, whereas the chemical pre-treatment changed the affinity of biomass for different dyes. The alkali per-treated biomass achieved the highest COD reduction in the treatment of alkali wastewaters, probably because no release of alkali-soluble biomass components occurred under the alkaline pH conditions. Accordingly, only the acid pre-treated biomass decreased the COD of the acidic effluent. The ecotoxicity test showed significant toxicity reduction after biosorption treatments, indicating that decolourisation corresponds to an actual detoxification of the treated wastewaters. Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analyses of biomasses allowed highlighting their main chemical and physical properties and the changes induced by the different pre-treatments, as well as the effect of the chemical species adsorbed from wastewaters.     

Argentine population genetic structure: large variance in Amerindian contribution

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.     

Influence of Culture Medium on Fungal Biomass Composition and Biosorption Effectiveness

Zygomycetes such as Cunninghamella elegans seem to be promising biosorbents for pollutants removal from wastewaters because of their particular cell wall characteristics. In this article the effect of ten culture media on C. elegans biomass composition was investigated by means of Fourier transform infra red spectroscopy (FTIR). Biomasses grown on starches from potatoes and cereals were characterised by high amount of chitin and polysaccharides, the glucose gave rise to a biomass rich in acidic polysaccharides and lipids. By contrast, biomasses grown on corn steep liquor were poor in acidic polysaccharides and, when N sources and micronutrients were added, rich in proteins. The lipid content of the biomass generally increased by halving nutrients. Biosorption yields of these biomasses towards four wastewater models were assessed in terms of colour, salts and toxicity reduction. The biomasses rich in proteins and acid polysaccharides were less effective in removing reactive and direct dyes, whereas those rich in cationic polysaccharides showed a higher affinity for these dyes. Both chromatography and FTIR analyses showed that biomasses cultured in halved C and N had the highest affinity for salts. The wastewaters detoxification was quite always achieved, with values often lower that the Italian legal threshold limit.     

Decolorization and detoxication of reactive industrial dyes by immobilized fungi <Emphasis Type="Italic">Trametes pubescens</Emphasis> and <Emphasis Type="Italic">Pleurotus ostreatus</Emphasis>

Trametes pubescens and Pleurotus ostreatus, immobilized on polyurethane foam cubes in bioreactors, were used to decolorize three industrial and model dyes at concentrations of 200, 1000 and 2000 ppm. Five sequential cycles were run for each dye and fungus. The activity of laccase, Mn-dependent and independent peroxidases, lignin peroxidase, and aryl-alcohol oxidase were daily monitored during the cycles and the toxicity of media containing 1000 and 2000 ppm of each dye was assessed by the Lemna minor (duckweed) ecotoxicity test. Both fungi were able to efficiently decolorize all dyes even at the highest concentration, and the duckweed test showed a significant reduction (p 相似文献