A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel.

Pseudohypoaldosteronism type 1 (PHA-1) is an inherited disease characterized by severe neonatal salt-wasting and caused by mutations in subunits of the amiloride-sensitive epithelial sodium channel (ENaC). A missense mutation (G37S) of the human ENaC beta subunit that causes loss of ENaC function and PHA-1 replaces a glycine that is conserved in the N-terminus of all members of the ENaC gene family. We now report an investigation of the mechanism of channel inactivation by this mutation. Homologous mutations, introduced into alpha, beta or gamma subunits, all significantly reduce macroscopic sodium channel currents recorded in Xenopus laevis oocytes. Quantitative determination of the number of channel molecules present at the cell surface showed no significant differences in surface expression of mutant compared with wild-type channels. Single channel conductances and ion selectivities of the mutant channels were identical to that of wild-type. These results suggest that the decrease in macroscopic Na currents is due to a decrease in channel open probability (P(o)), suggesting that mutations of a conserved glycine in the N-terminus of ENaC subunits change ENaC channel gating, which would explain the disease pathophysiology. Single channel recordings of channels containing the mutant alpha subunit (alphaG95S) directly demonstrate a striking reduction in P(o). We propose that this mutation favors a gating mode characterized by short-open and long-closed times. We suggest that determination of the gating mode of ENaC is a key regulator of channel activity.

Chicken BAFF--a highly conserved cytokine that mediates B cell survival.

Members of the tumor necrosis factor (TNF) family play key roles in the regulation of inflammation, immune responses and tissue homeostasis. Here we describe the identification of the chicken homologue of mammalian B cell activating factor of the TNF family (BAFF/BLyS). By searching a chicken EST database we identified two overlapping cDNA clones that code for the entire open reading frame of chicken BAFF (chBAFF), which contains a predicted transmembrane domain and a putative furin protease cleavage site like its mammalian counterparts. The amino acid identity between soluble chicken and human BAFF is 76%, considerably higher than for most other known cytokines. The chBAFF gene is most strongly expressed in the bursa of Fabricius. Soluble recombinant chBAFF produced by human 293T cells interacted with the mammalian cell-surface receptors TACI, BCMA and BAFF-R. It bound to chicken B cells, but not to other lymphocytes, and it promoted the survival of splenic chicken B cells in culture. Furthermore, bacterially expressed chBAFF induced the selective expansion of B cells in the spleen and cecal tonsils when administered to young chicks. Our results suggest that like its mammalian counterpart, chBAFF plays an important role in survival and/or proliferation of chicken B cells.

Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation.

Site-directed mutagenesis and molecular dynamics simulations of the alpha 1B-adrenergic receptor (AR) were combined to explore the potential molecular changes correlated with the transition from R (inactive state) to R (active state). Using molecular dynamics analysis we compared the structural/dynamic features of constitutively active mutants with those of the wild type and of an inactive alpha 1B-AR to build a theoretical model which defines the essential features of R and R. The results of site-directed mutagenesis were in striking agreement with the predictions of the model supporting the following hypothesis. (i) The equilibrium between R and R depends on the equilibrium between the deprotonated and protonated forms, respectively, of D142 of the DRY motif. In fact, replacement of D142 with alanine confers high constitutive activity to the alpha 1B-AR. (ii) The shift of R143 of the DRY sequence out of a conserved 'polar pocket' formed by N63, D91, N344 and Y348 is a feature common to all the active structures, suggesting that the role of R143 is fundamental for mediating receptor activation. Disruption of these intramolecular interactions by replacing N63 with alanine constitutively activates the alpha 1B-AR. Our findings might provide interesting generalities about the activation process of G protein-coupled receptors.

An Integral Abutment Bridge with Precast Concrete Piles, May 2007

The use of precast, prestressed concrete piles in the foundation of bridge piers has long been recognized as a valuable option for bridge owners and designers. However, the use of these precast, prestressed concrete piles in integral abutment bridges has not been widespread because of concerns over pile flexibility and the potential for concrete cracking and deterioration of the prestressing strands due to long-term exposure to moisture. This report presents the details of the first integral abutment bridge in the state of Iowa that utilized precast, prestressed concrete piles in the abutment. The bridge, which was constructed in Tama County in 2000, consists of a 110 ft. long, 30 ft. wide, single-span PC girder superstructure with a left-side-ahead 20º skew angle. The bridge was instrumented with a variety of strain gages, displacement sensors, and thermocouples to monitor and help in the assessment of structural behavior. The results of this monitoring are presented, and recommendations are made for future application of precast, prestressed concrete piles in integral abutment bridges. In addition to the structural monitoring data, this report presents the results of a survey questionnaire that had been mailed to each of the 50 state DOT chief bridge engineers to ascertain their current practices for precast, prestressed concrete piles and especially the application of these piles in integral abutment bridges.

SIS: Sistema Integral Sanitario

Desarrollo de una aplicación para responder a la necesidad del ministerio de Sanidad de informatizar todo el sistema sanitario, desde hospitales hasta farmacias.

Sistema de Talleres Dirigido a la Superación Profesional de los Docentes de la Enseñanza Básica Integral en la Atención a la Diversidad de Niños con Necesidades Educativas Especiales en la República de Cabo Verde

La presente tesis abordó un tema de gran actualidad y pertinencia social: la superación profesional de los docentes de la Enseñanza Básica Integral en atención a la diversidad de niños con necesidades educativas especiales en la República de Cabo Verde, da una respuesta encaminada a la atención a la diversidad en la escuela regular, esta como la diferencia entre culturas, lenguas, valores, sexualidad, género, religión, desarrollo y necesidades educativas especiales asociadas a una discapacidad. Esta necesidad ha sido reconocida en documentos nacionales e internacionales como la Ley General de Educación la Declaración Universal de la UNESCO. Se asume como el proceso de atención psicopedagógica encaminada a los alumnos con necesidades educativas especiales y se considera como uno de los principales retos que la sociedad actual, creciente en su pluralidad, plantea al sistema educativo, y en concreto a las instituciones escolares. Es objetivo del trabajo proponer un sistema de talleres dirigido a la superación profesional de los docentes en la atención a la diversidad de niños con necesidades educativas especiales. Desde el enfoque general dialéctico materialista y los métodos teóricos y empíricos de investigación se modela la solución del problema. Los datos obtenidos revelan las posibilidades de cambios y transformación en el objeto de estudio: la superación de los docentes en la atención a la diversidad necesidades educativas especiales regular.

Aprovechamiento de la materia prima en la elaboración de harina de pescado tipo integral

Estudio técnico y económico de dos métodos del aprovechamiento de la materia prima en la elaboración de harina de pescado tipo integral. Contiene el balance de materia y la composición de la materia prima y sus rendimientos.

Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken.

The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in birds.

A consulta pré-concepcional: um desafio à assistência integral à saúde da mulher em Idade Reprodutiva

Neste trabalho académico tivemos como objectivo verificar/conhecer a importância que as mulheres em idade reprodutiva atribuem à consulta pré-concepcional porque é uma consulta determinante para assegurar a qualidade da assistência à mulher em idade reprodutiva, porque permite obter informações incentivadoras de atitudes saudáveis no pré, durante o período de desenvolvimento fetal e no pós. Isto porque, cada vez mais a consulta pré-concepcional tem um papel fundamental na prevenção da gravidez de risco e acima de tudo na prevenção das anomalias fetais e patologias materno-fetais. A nossa pesquisa foi desenvolvida num centro de saúde de gestão pública, o Centro de Saúde Reprodutiva da Bela Vista (CSRBV), abrangendo tanto a abordagem quantitativa como a qualitativa, uma vez que os métodos de recolha e os instrumentos de recolha das informações foram: um inquérito por questionário fechado aplicado a uma amostra constituída por 52 grávidas; e ainda entrevistas exploratórias dirigidas aos enfermeiros que trabalham nesse centro. Os resultados obtidos apontam que: as gestantes não fizeram planeamento familiar; as grávidas não consideram as consultas pré-concepcionais pertinentes; 37 revelaram não ter ido à consulta pré-concepcional: as intervenções dos enfermeiros incidem sobre a avaliação de risco pré-concepcional e ainda aconselham-nas a terem cuidados com a alimentação, a praticarem exercício físico e a evitarem o consumo de bebidas alcoólicas, drogas ilícitas e tabaco. Embora a consulta pré-concepcional seja importante, ela aparece incluída nas consultas de planeamento familiar e o CSRBV revela que existe uma fraca adesão na procura da consulta pré-concepcional, chegando mesmo a não existir dados estatísticos que confirmam a realização dessa consulta no CSRBV, e ainda, não dispor de uma ficha para o atendimento de mulheres em idade reprodutiva que pretendam esse serviço. Ora, isso revela: a necessidade de ser divulgada e que as mulheres sejam sensibilizadas para que procurem esse tipo de serviços; que o CSRBV crie um sistema de atendimento próprio para as consultas pré-concepcionais; criar as condições adequadas para que haja mais adesão de mulheres para as consultas pré-concepcionais; identificar as razões pelas quais as mulheres que procuram o CSRBV não vão às consultas pré-concepcionais. Palavras-

Visión integral del problema "El Niño": Introducción

Prefacio sobre el monitoreo sobre el impacto del El Niño desde 1982 hasta 1983 cuando su nivel fue extremadamente intenso.

Comparison of human chromosome 21 conserved nongenic sequences (CNGs) with the mouse and dog genomes shows that their selective constraint is independent of their genic environment.

The analysis of conservation between the human and mouse genomes resulted in the identification of a large number of conserved nongenic sequences (CNGs). The functional significance of this nongenic conservation remains unknown, however. The availability of the sequence of a third mammalian genome, the dog, allows for a large-scale analysis of evolutionary attributes of CNGs in mammals. We have aligned 1638 previously identified CNGs and 976 conserved exons (CODs) from human chromosome 21 (Hsa21) with their orthologous sequences in mouse and dog. Attributes of selective constraint, such as sequence conservation, clustering, and direction of substitutions were compared between CNGs and CODs, showing a clear distinction between the two classes. We subsequently performed a chromosome-wide analysis of CNGs by correlating selective constraint metrics with their position on the chromosome and relative to their distance from genes. We found that CNGs appear to be randomly arranged in intergenic regions, with no bias to be closer or farther from genes. Moreover, conservation and clustering of substitutions of CNGs appear to be completely independent of their distance from genes. These results suggest that the majority of CNGs are not typical of previously described regulatory elements in terms of their location. We propose models for a global role of CNGs in genome function and regulation, through long-distance cis or trans chromosomal interactions.

A Derivada de um Integral

O cálculo do valor da derivada de um integral ocorre com certa frequência na vida profissional de físicos, químicos, engenheiros, economistas ou biólogos. É frequente, contudo, surgir alguma dificuldade no decurso da sua aprendizagem. Este texto, assente na doutrina essencial e desenvolvido através de um conjunto vasto de exemplos significativos, visa, precisamente, ajudar os estudantes universitários de cursos de licenciatura diversos a ultrapassar os obstáculos referidos, assim conseguindo dominar um tema que é tão simples quão importante.