164 research outputs found

    Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease.

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    Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field <sup>1</sup> H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability

    Phage-dependent variability of Candidatus ‘Accumulibacter phosphatis’ populations in aerobic granular sludge

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    During the past 20 years, aerobic granular sludge (AGS) has been extensively studied with the aim to develop an attractive alternative to conventional activated sludge for wastewater treatment. The phosphate-accumulating organism (PAO) Candidatus ‘Accumulibacter phosphatis’ is often found with significant abundance in AGS as well as in other enhanced biological phosporus removal (EPBR) systems. Although they have never been isolated in pure culture, members of this bacterial genus appear to be genetically and physiologically more diversified than initially expected. Impaired EBPR performances observed in lab- and full-scale reactors have often been correlated to a decrease in Accumulibacter populations. This phenomenon has mainly been linked to the presence of bacterial competitors such as glycogen-accumulating organisms (GAO), and bacteriophages have only rarely been suspected to be responsible for this depletion (1). In the present study, the metagenome of 46 individual granules from a lab-scale AGS sequencing batch reactor was sequenced. The results showed a surprisingly variable relative abundance of Accumulibacter populations amongst the different granules that could only be partially explained by the “phenotype” of these granules. A co-occurrence analysis revealed a strong negative correlation between the number of Accumulibacter sequencing reads with the relative abundance of two bacteriophages, namely EBPR podovirus 1 (EPV1) and EBPR podovirus 3 (EPV3), that have been previously detected in a lab-scale EBPR reactor (2). These results suggest that these phages are the major reason for the variability of Accumulibacter relative abundance in the sampled granules which raises the question whether the Accumulibacter populations in the different granules have different sensitivities towards these phages. (1) Barr et al., 2010, Fems Microbiology Ecology, 631-642 (2) Skennerton et al., 2011, Plos On

    Multicenter analysis of sputum microbiota in tuberculosis patients.

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    The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment

    Fifteen years SIB Swiss Institute of Bioinformatics: life science databases, tools and support.

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    The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) was created in 1998 as an institution to foster excellence in bioinformatics. It is renowned worldwide for its databases and software tools, such as UniProtKB/Swiss-Prot, PROSITE, SWISS-MODEL, STRING, etc, that are all accessible on ExPASy.org, SIB's Bioinformatics Resource Portal. This article provides an overview of the scientific and training resources SIB has consistently been offering to the life science community for more than 15 years

    Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review

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    BACKGROUND: Malaria is almost invariably ranked as the leading cause of morbidity and mortality in Africa. There is growing evidence of a decline in malaria transmission, morbidity and mortality over the last decades, especially so in East Africa. However, there is still doubt whether this decline is reflected in a reduction of the proportion of malaria among fevers. The objective of this systematic review was to estimate the change in the Proportion of Fevers associated with Plasmodium falciparum parasitaemia (PFPf) over the past 20 years in sub-Saharan Africa. METHODS: Search strategy. In December 2009, publications from the National Library of Medicine database were searched using the combination of 16 MeSH terms.Selection criteria. Inclusion criteria: studies 1) conducted in sub-Saharan Africa, 2) patients presenting with a syndrome of 'presumptive malaria', 3) numerators (number of parasitologically confirmed cases) and denominators (total number of presumptive malaria cases) available, 4) good quality microscopy.Data collection and analysis. The following variables were extracted: parasite presence/absence, total number of patients, age group, year, season, country and setting, clinical inclusion criteria. To assess the dynamic of PFPf over time, the median PFPf was compared between studies published in the years ≀2000 and > 2000. RESULTS: 39 studies conducted between 1986 and 2007 in 16 different African countries were included in the final analysis. When comparing data up to year 2000 (24 studies) with those afterwards (15 studies), there was a clear reduction in the median PFPf from 44% (IQR 31-58%; range 7-81%) to 22% (IQR 13-33%; range 2-77%). This dramatic decline is likely to reflect a true change since stratified analyses including explanatory variables were performed and median PFPfs were always lower after 2000 compared to before. CONCLUSIONS: There was a considerable reduction of the proportion of malaria among fevers over time in Africa. This decline provides evidence for the policy change from presumptive anti-malarial treatment of all children with fever to laboratory diagnosis and treatment upon result. This should insure appropriate care of non-malaria fevers and rationale use of anti-malarials

    N-3 PUFA Supplementation Triggers PPAR-α Activation and PPAR-α/NF-ÎșB Interaction: Anti-Inflammatory Implications in Liver Ischemia-Reperfusion Injury

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    Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to rats preconditions the liver against ischemia-reperfusion (IR) injury, with reduction of the enhanced nuclear factor-ÎșB (NF-ÎșB) functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation and interference with NF-ÎșB activation. For this purpose we evaluated the formation of PPAR-α/NF-ÎșBp65 complexes in relation to changes in PPAR-α activation, IÎșB-α phosphorylation and serum levels and expression of interleukin (IL)-1ÎČ and tumor necrosis factor (TNF)-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion) or sham laparotomy (controls) in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) or isovolumetric amounts of saline (controls). Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology) was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-ÎșB activation was paralleled by generation of PPAR-α/NF-ÎșBp65 complexes, in concomitance with normalization of the IR-induced IÎșB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox) and Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-ÎșB-controlled cytokines IL-lÎČ and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-ÎșB-controlled transcription of pro-inflammatory mediators. This effect is associated with the formation of PPAR-α/NF-ÎșBp65 complexes and enhanced cytosolic IÎșB-α stability, as major preconditioning mechanisms induced by n-3 PUFA supplementation against IR liver injury
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