The role of I-FABP as a biomarker of intestinal barrier dysfunction driven by gut microbiota changes in obesity

Financial support from Fundacao para Ciencia e Tecnologia (PTDC/AGR-TEC/2227/2012 and SFRH/BD/93073/2013) is gratefully acknowledged.Background: Intestinal fatty-acid binding protein (I-FABP) is expressed in epithelial cells of the mucosal layer of the small intestine tissue. When intestinal mucosal damage occurs, I-FABP is released into the circulation and its plasma concentration increases. In the context of obesity, the gut barrier integrity can be disrupted by dietary fat while intestinal permeability increases. Objective: To investigate whether intestinal fatty acid binding protein (I-FABP) is a suitable plasma marker of intestinal injury and inflammation in obesity. Methods: Twelve male Wistar rats were randomly divided into two groups of six animals each: standard (St) and high-fat (HF) diet fed groups for 12 weeks. Results: HF fed animals developed obesity, insulin resistance and seemed to present increased plasma levels of proinflammatory cytokines (MCP-1 and IL1 beta). The gut microbiota composition of these animals was also altered, with lower number of copies of Bacteroidetes, Prevotella spp. and Lactobacillus spp., in comparison with those from St diet group. Fecal lipopolysaccharide (LPS) concentrations tended to be increased in HF fed animals. Intestinal expression of TLR4 seemed to be also increased in HF fed animals suggesting that HF diet-induced dysbiosis may be behind the systemic inflammation observed. However, in contrast to other intestinal inflammatory diseases, plasma I-FABP levels were decreased in HF fed rats whereas I-FABP expression in jejunum tended to be increased. Conclusions: HF diet-induced obesity is characterized by dysbiosis, insulin resistance and systemic inflammation. In this context, plasmatic I-FABP should not be used as a marker of the intestinal barrier dysfunction and the low-grade chronic inflammatory status.publishersversionpublishe

Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics

Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4oC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37oC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from similar to 1.5 hours to more than 13 hours. Notably, ex-miRNA half-lives calculated in two different biofluids (murine serum and C2C12 mouse myotube conditioned medium) were highly similar, suggesting that intrinsic sequence properties are a determining factor in miRNA stability. By contrast, ex-miRNAs associated with extracellular vesicles (isolated by size exclusion chromatography) were highly stable. The release of ex-miRNAs from C2C12 myotubes was measured over time, and mathematical modelling revealed miRNA-specific release kinetics. While some ex-miRNAs reached the steady state in cell culture medium within 24 hours, the extracellular level of miR-16 did not reach equilibrium, even after 3 days in culture. These findings are indicative of miRNA-specific release and degradation kinetics with implications for the utility of ex-miRNAs as biomarkers, and for the potential of ex-miRNAs to transfer gene regulatory information between cells

First report on methicillin-resistant Staphylococcus aureus of Spa type T037, Sequence type 239, SCCmec type III/IIIA in Malaysia

Methicillin-resistant Staphylococcus aureus (MRSA) from Malaysia were shown to possess staphylococcal cassette chromosome mec (SCCmec)-III and IIIA. Spa sequencing and multi-locus sequence typing (MLST) documented t037 and ST 239 (CC8) for 83.3% of the isolates. This confirms observations in several other Far Eastern countries and corroborates the epidemicity of this clone

Gene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype 2 by modulating AR transcriptional activity:AR isoform 2 counteracts polyglutamine AR toxicity

Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset neuromuscular condition caused by an abnormal polyglutamine (polyQ) tract expansion in androgen receptor (AR) protein. SBMA is a disease with high unmet clinical need. Recent studies have shown that mutant AR-altered transcriptional activity is key to disease pathogenesis. Restoring the transcriptional dysregulation without affecting other AR critical functions holds great promise for the treatment of SBMA and other AR-related conditions; however, how this targeted approach can be achieved and translated into a clinical application remains to be understood. Here, we characterized the role of AR isoform 2, a naturally occurring variant encoding a truncated AR lacking the polyQ-harboring domain, as a regulatory switch of AR genomic functions in androgen-responsive tissues. Delivery of this isoform using a recombinant adeno-associated virus vector type 9 resulted in amelioration of the disease phenotype in SBMA mice by restoring polyQ AR-dysregulated transcriptional activity

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazonia Sustentavel, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.Keywords: Social–ecological systems, Tropical forests, Land use, Interdisciplinary research, Sustainability, Trade-off

Binary Solid-liquid Equilibrium Systems Containing Fatty Acids, Fatty Alcohols And Triolein By Differential Scanning Calorimetry

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The solid-liquid phase diagrams of six binary mixtures composed of triolein plus fatty acids (triolein (1) + capric acid (2), triolein (1) + lauric acid (3) and triolein (1) + myristic acid (4)) and triolein plus fatty alcohols (triolein (1) + 1-decanol (5), triolein (1) + 1-dodecanol (6) and triolein (1) + 1-tetradecanol (7)) were studied by differential scanning calorimetry (DSC). Experimental results clearly show that systems formed by triolein + capric acid, triolein + 1-decanol and triolein + 1-dodecanol show eutectic behavior, while for the other binary systems, the occurrence of an eutectic point very close to the melting temperature of pure triolein was observed. Experimental data were used to adjust the parameters of the three-suffix Margules and NRTL models. (C) 2015 Elsevier B.V. All rights reserved.40418Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2008/56258-8, 2012/05027-1]CNPq [483340/2012-0, 479533/2013-0, 309780/2014-4, 308616/2014-6, 305870/2014-9