Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation.

Notch1 (N1) receptor signaling is essential and sufficient for T cell development, and recently developed in vitro culture systems point to members of the Delta family as being the physiological N1 ligands. We explored the ability of Delta1 (DL1) and DL4 to induce T cell lineage commitment and/or maturation in vitro and in vivo from bone marrow (BM) precursors conditionally gene targeted for N1 and/or N2. In vitro DL1 can trigger T cell lineage commitment via either N1 or N2. N1- or N2-mediated T cell lineage commitment can also occur in the spleen after short-term BM transplantation. However, N2-DL1-mediated signaling does not allow further T cell maturation beyond the CD25(+) stage due to a lack of T cell receptor beta expression. In contrast to DL1, DL4 induces and supports T cell commitment and maturation in vitro and in vivo exclusively via specific interaction with N1. Moreover, comparative binding studies show preferential interaction of DL4 with N1, whereas binding of DL1 to N1 is weak. Interestingly, preferential N1-DL4 binding reflects reduced dependence of this interaction on Lunatic fringe, a glycosyl transferase that generally enhances the avidity of Notch receptors for Delta ligands. Collectively, our results establish a hierarchy of Notch-Delta interactions in which N1-DL4 exhibits the greatest capacity to induce and support T cell development.

Peroxisome proliferator-activated receptors beta/delta: emerging roles for a previously neglected third family member.

PURPOSE OF REVIEW: Peroxisome proliferator-activated receptors alpha, beta/delta and gamma are members of the nuclear receptor superfamily. They mediate the effects of fatty acids and their derivatives at the transcriptional level, and are considered to be lipid sensors that participate in the regulation of energy homeostasis. Compared with the alpha and gamma peroxisome proliferator-activated receptor isotypes, peroxisome proliferator-activated receptor beta functions have long remained an enigma. In this review, we focus on emerging knowledge about peroxisome proliferator-activated receptor beta activation and roles. RECENT FINDINGS: We review recent data that suggest key roles in basic cell functions, such as proliferation, differentiation and survival, and in embryonic development and lipid metabolism in peripheral tissues. SUMMARY: The newly unveiled roles of peroxisome proliferator-activated receptor beta in important basic cell functions certainly justify a further exploration of its potential as a therapeutic target in pathologies such as metabolic syndrome X or skin diseases.

Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism.

We have described previously a transcription-dependent induction of glycogen resynthesis by the vasoactive intestinal peptide (VIP) or noradrenaline (NA) in astrocytes, which is mediated by cAMP. Because it has been postulated that the cAMP-mediated regulation of energy balance in hepatocytes and adipocytes is channeled at least in part through the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, we tested the hypothesis that C/EBP isoforms could be expressed in mouse cortical astrocytes and that their level of expression could be regulated by VIP, by the VIP-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), or by NA. We report in this study that in these cells, C/EBP beta and C/EBP delta are induced by VIP, PACAP, or NA via the cAMP second-messenger pathway. Induction of C/EBP beta and -delta mRNA by VIP occurs in the presence of a protein synthesis inhibitor. Thus, c/ebp beta and c/ebp delta behave as cAMP-inducible immediate-early genes in astrocytes. Moreover, transfection of astrocytes with expression vectors selectively producing the transcriptionally active form of C/EBP beta, termed liver-enriched transcriptional activator protein, or C/EBP delta enhance the glycogen resynthesis elicited by NA, whereas an expression vector producing the transcriptionally inactive form of C/EBP beta, termed liver-enriched transcriptional inhibitory protein, reduces this resynthesis. These results support the idea that C/EBP beta and -delta regulate gene expression of energy metabolism-related enzymes in astrocytes.

Prevalence of Helicobacter pylori infection in Warao lineage communities of Delta Amacuro State, Venezuela

The purpose of this study was the evaluation of Helicobacter pylori infections in children and adults from two indigenous communities of Delta Amacuro State, Venezuela, that differ in hygienic conditions of the housing. The evaluation was performed in 98 children (mean age 7 ± 3.37 years) and their mothers (33.96 ± 13.77 years) from two communities of Warao lineage. Anti-H. pylori serum IgG and secretory anti-H. pylori IgA antibodies were de-termined, as well as total secretory IgA and H. pylori antigens in feces. Serological prevalence of H. pylori infection was 38% in children and 84% their in mothers. Children from the community that had the most deficient sanitary and hygienic conditions had significantly lower titers of specific IgG antibodies and total secretory IgA (P < 0.0001) and a high percentage of them had H. pylori antigens in their feces (P < 0.0001). The levels of specific IgA were similar in both groups. The results indicate that in these populations there is a high prevalence of H. pylori infection and that poor hygienic conditions can increase the risk of infection and damage to the gastrointestinal tract.

Histopathological and ultrastructural effects of delta-endotoxins of Bacillus thuringiensis serovar israelensis in the midgut of Simulium pertinax larvae (Diptera, Simuliidae)

The bacterium Bacillus thuringiensis (Bt) produces parasporal crystals containing delta-endotoxins responsible for selective insecticidal activity on larvae. Upon ingestion, these crystals are solubilized in the midgut lumen and converted into active toxins that bind to receptors present on the microvilli causing serious damage to the epithelial columnar cells. We investigated the effect of these endotoxins on larvae of the Simulium pertinax, a common black fly in Brazil, using several concentrations during 4 h of the serovar israelensis strain IPS-82 (LFB-FIOCRUZ 584), serotype H-14 type strain of the Institute Pasteur, Paris. Light and electron microscope observations revealed, by time and endotoxin concentration, increasing damages of the larvae midgut epithelium. The most characteristic effects were midgut columnar cell vacuolization, microvilli damages, epithelium cell contents passing into the midgut lumen and finally the cell death. This article is the first report of the histopathological effects of the Bti endotoxins in the midgut of S. pertinax larvae and the data obtained may contribute to a better understanding of the mode of action of this bacterial strain used as bioinsecticide against black fly larvae.

Desarrollo detallado de la fase de aprobación de un proyecto informático : De la idea al proyecto.

Aquest treball exposa les fases del cicle de vida d'un projecte, especialment d'enginyeria informàtica. Qualsevol tipus de projecte està subjecte a una planificació i un control, cosa que porta a una evolució ordenada del projecte mitjançant fases, les quals constitueixen el cicle de vida del projecte.

Millora de l'enfocament més comercial de la fase de definició d'un projecte informàtic

Aquest PFC mira d'analitzar els aspectes comercials d'un projecte informàtic en les seves fases inicials, la fase d'aprovació i la fase de definició; en aquesta segona fase s'estudiarà amb més profunditat com hi influeix l'aspecte comercial.

Enfocament comercial de la fase d'aprovació i definició d'un projecte informàtic

Amb aquest estudi es volen analitzar els aspectes comercials que es poden fer intervenir en les fases inicials dels projectes informàtics, concretament en les d'aprovació i definició. Aquestes fases són les més importants a l'hora de gestionar projectes, ja que és quan es decideix si la proposta del projecte es porta a terme i té viabilitat.

Fase Zero de qualsevol projecte informàtic : l'acció comercial

El propòsit d'aquest TFC és presentar una metodologia lleugera per a aplicar en aquesta anomenada

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine.

Epoetin-delta (Dynepo Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-delta injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-alpha and epoetin-beta, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

Mejora del enfoque comercial en la fase de definición de un proyecto informático

Aquest TFC mira d'analitzar els aspectes comercials que intervenen en les fases inicials de l'execució de projectes informàtics, concretament en la fase d'aprovació i, encara més detingudament, en la fase de definició. Aquestes fases són les mes crítiques per a les entitats dedicades a la gestió de projectes, perquè és on es decideix si són viables.

Enfoque comercial de la fase de definición de un proyecto informático

Projecte que estudia amb detall cadascun dels processos que cal seguir per a portar a terme el desenvolupament de la fase de definició d'un projecte informàtic. Aquest estudi ens ha ajudat a obtenir els coneixements necessaris sobre les diferents característiques d'aquests processos. Una vegada hem acabat el desenvolupament del projecte, es pot dir que el resultat que podem obtenir és la necessitat que tenen les empreses d'incorporar a la fase de definició d'un procés informàtic un enfocament més comercial que el que tenen avui dia. Aquest enfocament més comercial s'ha anat incorporant al llarg dels anys i a poc a poc al desenvolupament dels projectes en general i, en particular, a la fase que ens ocupa, la fase de definició. Tot i així, la realitat és que no està tan estès ni és tan emprat com es podria pensar. Moltes empreses encara no l'entenen com un pas necessari i imprescindible dins la fase de definició d'un projecte informàtic. La majoria no l'empren com un procés que calgui seguir en la definició de tots els seus projectes i continuen pensant que es pot arribar a l'objectiu sense aplicar aquest enfocament.

Gestión de proyectos : enfoque más comercial de la fase de definición de un proyecto informático

El desarrollo de este Trabajo, identificado por los diferentes capítulos que lo componen, se ha definido siguiendo un hilo conductor que nos permite desgranar la Gestión de Proyectos informáticos, y de esta manera poder hacer una mejor penetración en su fase de definición, para poder aportar mejoras en su enfoque más comercial.Esta fase engloba áreas tales como definir el objeto del proyecto, fijar objetivos, acordar presupuestos, etc., es decir, esta fase de definición del proyecto representa su mismo fundamento. Por lo tanto, la manera en qué se lleve a cabo, marcará la pauta para el resto del proyecto. Profundizando en la gestión de Proyectos podemos evidenciar que la fase de definición se puede considerar una de las fases más importante de cualquier proyecto. A menos que se lleve a cabo correctamente, el proyecto tiene pocas probabilidades de éxito.Por lo tanto, el planteamiento de este Trabajo, está basado en un guión que da una visión general de la Gestión de Proyectos, para posteriormente profundizar en el enfoque más comercial de la fase de definición, de una manera natural.

Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures.

Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 microM in single treatment and of 1 microM and 2 microM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 microM of THC or JWH 015, whereas the expression of TNF-alpha remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.