Inhibition of the post-translational processing of microvillar hydrolases is associated with a specific decreased expression of sucrase-isomaltase and an increased turnover of glucose in Caco-2 cells treated with monensin

AbstractThe biosynthesis and post-translational processing of sucrase-isomaltase and dipeptidylpeptidase IV were studied by L-[35S]methionine labeling, immunoisolation with monoclonal antibodies and SDS-PAGE in post-confluent Caco-2 cells treated with monensin (10 μM, 48 h). In addition to its classical effect on the post-translational processing of both hydrolases, i.e. an inhibition of the conversion of the high-mannose to the complex glycosylated form of the enzymes, monensin was found to have two other effects: a marked decrease of sucrase-isomaltase expression, but not of dipeptidylpeptidase IV; an increased turnover of glucose, as substantiated by increased rates of glucose consumption and lactic acid production and a decreased glycogen content. Whether these two effects are related to the particular differentiation and metabolic status of Caco-2 cells is discussed, as well as a possible role for the drug-induced modifications of glucose turnover on the decreased expression of sucrase-isomaltase

Needs analysis for an online learning service

International audienceThe development of fully or partially online training, as well as the provision of digital learning materials for students, requires the development of systems that provide students with innovative services tailored to their needs. We are interested in students who perform all or part of their course in a foreign language and who face difficulties due to language understanding. Our goal is to provide them, on demand, online and in their native language, with a document similar to the one that troubles them. In this paper we present the needs analysis phase, related to the engineering process of the online service

Analyse de besoins pour un service en ligne

National audienceLe développement des formations totalement ou partiellement en ligne, ainsi que la mise à disposition de documents numériques pour les étudiants nécessitent de fournir des services innovants adaptés aux besoins induits. Nous nous intéressons ici aux étudiants qui effectuent tout ou partie de leur cursus dans une langue étrangère et qui rencontrent des difficultés dues à la langue. Notre objectif est de leur fournir, à la demande, en ligne et dans leur langue maternelle, un document similaire à celui qui fait difficulté pour eux. Nous présentons dans ce papier la phase d'analyse des besoins relative à l'ingénierie de ce service en ligne. Mots-clés. Ressources numériques de formation, fourniture de ressources dans une autre langue, service en ligne, analyse de besoins Abstract. The development of training fully or partially online, as well as the provision of digital materials for students, requires providing innovative services adapted to new needs identified. We focus on students who complete all or part of their course in a foreign language and who encounter difficulties due to language. Our goal is to provide on-demand, online and in their native language, a document similar to the one that troubles them. We present in this paper the needs analysis phase, relating to the engineering of this online servic

Producing cabbage seeds for organic agriculture

This tool is a data sheet that can be used by French farmers who produce or want to produce cabbage seeds in organic conditions. It provides advice starting from the contract signing to the seed drying, going through the specificities of the crop, the sowing, irrigation, specific pests and their management, and the harvest

Relação entre o acúmulo de serapilheira sobre o solo e variáveis dendrométricas em povoamento híbrido de Eucalyptus urophylla x E. globulus maidenii, em Eldorado do Sul/RS

In a 5.5 years old Eucalyptus urophylla x E. globulus maidenii stand with 5.5 years old, in Eldorado do Sul, Rio Grande do Sul/Brazil, the litter accumulation and its relation with dendrometric variables were studied. In 4 (four) plots (20 m x 20 m each), 3 (three) sub-plots (3 m x 2 m each) were installed for branches (diameter > 1 cm) and the fine litter (leaves, branches with diameter ≤ 1 cm, barks, fruits, seeds, etc.) collection. The dendrometric variables were obtained (Diameter at breast height-DBH, and the total height-TH 3 (three) plots (20 m x 30 m each). Fine litter accumulated was 18.4 Mg ha-1 (CV% 29.6%). Coarse branches accumulation was 1.06 Mg ha-1 (CV% 49.5%), totalizing 19.5 Mg ha-1 of organic material accumulated. The average DBH was 17 cm and the TH 21.6 m, with basal area of 22.7 m² ha-1. The correlation between litter accumulation, coarse branches and total organic matter was positive to the number of trees and negative to DBH and Ht and out to the basal area. It demonstrates the higher litter accumulation in areas with more trees (even smaller ones), which can be related to higher litter production in these areas and to low decomposition rate, in general associated to low productivity sites.Em um povoamento de Eucalyptus urophylla x E. globulus maidenii, com 5,5 anos, no município de Eldorado do Sul, Rio Grande do Sul/Brasil, estudou-se o acúmulo de serapilheira e sua relação com parâmetros dendrométricos. Na área de estudo foram alocadas 4 (quatro) parcelas de 20 m x 20 m e dentro destas 3 (três) sub-parcelas de 3 m x 2 m cada, coletando-se todos os galhos (diâmetro > 1 cm) e a serapilheira fina (folhas, galhos com diâmetro ≤ 1 cm, cascas, frutos, sementes, etc.) em 04 amostras/parcela. As variáveis dendrométricas foram medidas (Diâmetro a Altura do Peito (DAP) e a altura total (Ht)) em 03 parcelas de 20 m x 30 m. A serapilheira acumulada alcançou 18,4 Mg ha-1 (CV% 29,6%). O acúmulo de galhos grossos foi de 1,06 Mg ha-1 (CV% 49,5%), totalizando 19,5 Mg ha-1 de material orgânico acumulado. O DAP médio foi de 17,0 cm, a altura total média 21,6 m e a área basal de 22,7 m2 ha-1. A correlação entre acúmulo de serapilheira, galhos grossos e material orgânico total foi positiva quanto ao número de árvores/ha, negativa em relação ao DAP e Ht e inexistente para área basal. Isso demonstra maior acúmulo de serapilheira em locais com mais árvores, porém menores, o que pode estar relacionado a uma maior produção de serapilheira nestes locais e uma menor velocidade de decomposição, geralmente associada a sítios de menor produtividade. DOI: http://dx.doi.org/10.13086/2316-980x.v01n01a0

Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis

<p>Abstract</p> <p>Background</p> <p>Previously we reported that mice deficient in toll-like receptor 4 (TLR-4) signalling were protected from diet-induced non-alcoholic steatohepatitis (NASH). Another member of the toll-like receptor family, TLR-2, has been shown to play a role in lipid trafficking via uptake of diacylated lipoproteins. However, a role for TLR-2 in NASH has not been elucidated. The objectives of the current study were to examine the influence of dietary fat quality and TLR-2 on NASH pathogenesis.</p> <p>Methods</p> <p>Steatohepatitis was induced in male Db, C57BL/6 and TLR-2^-/-mice by feeding an L-amino acid-defined diet that was deficient in methionine and choline (MCDD). Mice fed the base diet supplemented with methionine and choline (control diet; CD) were used as controls. To determine the role of fat quality, MCDD was enriched with polyunsaturated corn oil (PUFA) or coconut oil that is comprised mostly of saturated fat (SAFA); the total amount of each fat was 112.9 g/kg of diet. After 8 weeks of feeding CD or MCDD, hepatic steatosis, inflammation and necrosis were evaluated in histological sections. Total RNA was extracted from frozen liver samples and mRNA expression of TNFα, collagen α1, IL-10, peroxisome proliferator-activated receptor-γ (PPAR-γ), TLR-4, and CD14, was analyzed via real-time PCR. Protein levels of TLR-2 were analyzed by western blot.</p> <p>Results</p> <p>Panlobular macrovessicular steatosis and diffuse leukocyte infiltration were noted in PUFA-fed Db mice. Histological scores demonstrated significantly less steatosis, inflammation and necrosis in SAFA-fed mice of all mouse strains. However, compared to wild type mice, hepatocellular damage was notably more severe in TLR-2^-/-mice. Consistent with histological findings, mRNA expression of TNFα was elevated by approximately 3-fold in TLR-2^-/-mice; PPAR-γ expression was blunted in this strain compared to wild type. Expression of the matrix protein collagen αI was also significantly higher in TLR-2^-/-mice, indicating a pro-fibrogenic state. Sensitivity to steatohepatitis due to dietary fat or TLR-2 deficiency correlated significantly with alterations in the expression of TLR-4 as well as the co-receptor CD-14.</p> <p>Conclusions</p> <p>Our findings suggest that dietary saturated fat plays a protective role against MCDD-induced steatohepatitis, whereas TLR-2 deficiency exacerbated NASH. The mechanism underlying the response to dietary fat and TLR-2 likely involves altered signalling via the TLR-4 pathway.</p

A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy

G. Bruck, Die Spätromische Kupferprägung. Ein Bestimmungsbuch für schlecht erhaltene Münzen.

Mainjonet Monique. G. Bruck, Die Spätromische Kupferprägung. Ein Bestimmungsbuch für schlecht erhaltene Münzen. In: Revue numismatique, 6e série - Tome 4, année 1962 pp. 333-334