Characterization of MAP1B heavy chain interaction with actin.

Microtubule-associated protein 1B is an essential protein during brain development and neurite outgrowth and was studied by several assays to further characterize actin as a major interacting partner. Tubulin and actin co-immunoprecipitated with MAP1B at similar ratios throughout development. Their identity was identified by mass spectrometry and was confirmed by Western blots. In contrast to previous reports, the MAP1B-actin interaction was not dependent on the MAP1B phosphorylation state, since actin was precipitated from brain tissue throughout development at similar ratios and equal amounts were precipitated before and after dephosphorylation with alkaline phosphatase. MAP1B heavy chain was able to bind actin directly and therefore the N-terminal part of MAP1B heavy chain must also contain an actin-binding site. The binding force of this interaction was measured by atomic force microscopy and values were in the same range as those of MAP1B binding to tubulin or that measured in MAP1B self-aggregation. Aggregation was confirmed by negative staining and electron microscopy. Experiments including COS-7 cells, PC12 cells, cytochalasin D and immunocytochemistry with subsequent confocal laser microscopy, suggested that MAP1B may bind to actin but has no obvious microfilament stabilizing effect. We conclude, that the MAP1B heavy chain has a microtubule-stabilization effect, and contains an actin-binding site that may play a role in the crosslinking of actin and microtubules, a function that may be important in neurite elongation.

The Arts (Music, Arts&Crafts and Drama) as a procedure for learning pre-school content: Grupo Edebé Project

There is nothing as amazing and fascinating as children learning process. Between 0 and 6 years old, a child brain develops in a waythat will never be repeated. At this age, children are eager to discover and they have great potential of active and affective life.Because of this, their learning capacity in this period is incalculable. (Jordan-Decarbo y Nelson, 2002; Wild, 1999).Pre-school Education is a unique and special stage, with self identity, which aims are:attending children as a whole,motivate them to learn,give them an affective and stable environment in which they can grow up and get to be balanced and confident people and inwhich they can relate to others, learn, enjoy and be happy.Arts, Music, Visual Arts and Drama (Gardner, 1994) can provide a framework of special, even unique, personal expression.With the aim of introducing qualitative improvements in the education of children and to ensure their emotional wellbeing, and havingnoticed that teachers had important needs and concerns as regards to diversity in their student groups, we developed a programbased on the detection of needs and concerns explained by professionals in education.This program of Grupo edebé, object of our research, is a multicultural, interdisciplinary and globalizing project the aims of which are:developing children's talent and personality,keeping their imagination and creativity and using these as a learning resource,promoting reasoning, favouring expression and communication,providing children with the tools to manage their emotions,and especially, introducing Arts as a procedure to increase learning.We wanted to start the research by studying the impact (Brice, 2003) that this last point had on the learning of five-year-old childrenschooled in multicultural environments.Therefore, the main goal of the research was the assessment of the implementation of a child education programme attending todiversity in a population of five-year-old children, specifically in the practice of procedures based on the use of Arts (music, arts andcrafts and theatre) as a vehicle or procedure for learning contents in Pre-school stage.Because children emotional welfare was a subject of our concern, and bearing in mind that the affective aspects are of vitalimportance for learning and child development (Parke and Gauvain, 2009), Grupo Edebé has also evaluated the starting, evolving andfinal impact in five-year-old children given that they finish Pre-school education at that age.

Des services adaptés aux adolescents, à quel prix. [What services do we adapt to adolescents and at what price?].

http://rms.medhyg.ch/numero-253-page-1227.htm

Roles of transient guidepost neurons in corpus callosum formation and guidance

RESUMENeurones transitoires jouant un rôle de cibles intermédiaires dans le guidage des axones du corps calleuxLe guidage axonal est une étape clé permettant aux neurones d'établir des connexions synaptiques et de s'intégrer dans un réseau neural fonctionnel de manière spécifique. Des cellules-cibles intermédiaires appelées « guidepost » aident les axones à parcourir de longues distances dans le cerveau en leur fournissant des informations directionnelles tout au long de leur trajet. Il a été démontré que des sous-populations de cellules gliales au niveau de la ligne médiane guident les axones du corps calleux (CC) d'un hémisphère vers l'autre. Bien qu'il fût observé que le CC en développement contenait aussi des neurones, leur rôle était resté jusqu'alors inconnu.La publication de nos résultats a montré que pendant le développement embryonnaire, le CC contient des glies mais aussi un nombre considérable de neurones glutamatergiques et GABAergiques, nécessaires à la formation du corps calleux (Niquille et al., PLoS Biology, 2009). Dans ce travail, j'ai utilisé des techniques de morphologie et d'imagerie confocale 3D pour définir le cadre neuro-anatomique de notre modèle. De plus, à l'aide de transplantations sur tranches in vitro, de co-explants, d'expression de siRNA dans des cultures de neurones primaires et d'analyse in vivo sur des souris knock-out, nous avons démontré que les neurones du CC guident les axones callosaux en partie grâce à l'action attractive du facteur de guidage Sema3C sur son récepteur Npn- 1.Récemment, nous avons étudié l'origine, les aspects dynamiques de ces processus, ainsi que les mécanismes moléculaires impliqués dans la mise en place de ce faisceau axonal (Niquille et al., soumis). Tout d'abord, nous avons précisé l'origine et l'identité des neurones guidepost GABAergiques du CC par une étude approfondie de traçage génétique in vivo. J'ai identifié, dans le CC, deux populations distinctes de neurones GABAergiques venant des éminences ganglionnaires médiane (MGE) et caudale (CGE). J'ai ensuite étudié plus en détail les interactions dynamiques entre neurones et axones du corps calleux par microscopie confocale en temps réel. Puis nous avons défini le rôle de chaque sous-population neuronale dans le guidage des axones callosaux et de manière intéressante les neurones GABAergic dérivés de la MGE comme ceux de la CGE se sont révélés avoir une action attractive pour les axones callosaux dans des expériences de transplantation. Enfin, nous avons clarifié la base moléculaire de ces mécanismes de guidage par FACS sorting associé à un large criblage génétique de molécules d'intérêt par une technique très sensible de RT-PCR et ensuite ces résultats ont été validés par hybridation in situ.Nous avons également étudié si les neurones guidepost du CC étaient impliqués dans son agénésie (absence de CC), présente dans nombreux syndromes congénitaux chez 1 humain. Le gène homéotique Aristaless (Arx) contrôle la migration des neurones GABAergiques et sa mutation conduit à de nombreuses pathologies humaines, notamment la lissencéphalie liée à IX avec organes génitaux anormaux (XLAG) et agénésie du CC. Fait intéressant, nous avons constaté qu'ARX est exprimé dans toutes les populations GABAergiques guidepost du CC et que les embryons mutant pour Arx présentent une perte drastique de ces neurones accompagnée de défauts de navigation des axones (Niquille et al., en préparation). En outre, nous avons découvert que les souris déficientes pour le facteur de transcription ciliogenic RFX3 souffrent d'une agénésie du CC associé avec des défauts de mise en place de la ligne médiane et une désorganisation secondaire des neurones glutamatergiques guidepost (Benadiba et al., submitted). Ceci suggère fortement l'implication potentielle des deux types de neurones guidepost dans l'agénésie du CC chez l'humain.Ainsi, mon travail de thèse révèle de nouvelles fonctions pour ces neurones transitoires dans le guidage axonal et apporte de nouvelles perspectives sur les rôles respectifs des cellules neuronales et gliales dans ce processus.ABSTRACTRole of transient guidepost neurons in corpus callosum development and guidanceAxonal guidance is a key step that allows neurons to build specific synaptic connections and to specifically integrate in a functional neural network. Intermediate targets or guidepost cells act as critical elements that help to guide axons through long distance in the brain and provide information all along their travel. Subpopulations of midline glial cells have been shown to guide corpus callosum (CC) axons to the contralateral cerebral hemisphere. While neuronal cells are also present in the developing corpus callosum, their role still remains elusive.Our published results unravelled that, during embryonic development, the CC is populated in addition to astroglia by numerous glutamatergic and GABAergic guidepost neurons that are essential for the correct midline crossing of callosal axons (Niquille et al., PLoS Biology, 2009). In this work, I have combined morphological and 3D confocal imaging techniques to define the neuro- anatomical frame of our system. Moreover, with the use of in vitro transplantations in slices, co- explant experiments, siRNA manipulations on primary neuronal culture and in vivo analysis of knock-out mice we have been able to demonstrate that CC neurons direct callosal axon outgrowth, in part through the attractive action of Sema3C on its Npn-1 receptor.Recently, we have studied the origin, the dynamic aspects of these processes as well as the molecular mechanisms involved in the establishment of this axonal tract (Niquille et al., submitted). First, we have clarified the origin and the identity of the CC GABAergic guidepost neurons using extensive in vivo cell fate-mapping experiments. We identified two distinct GABAergic neuronal subpopulations, originating from the medial (MGE) and caudal (CGE) ganglionic eminences. I then studied in more details the dynamic interactions between CC neurons and callosal axons by confocal time-lapse video microscopy and I have also further characterized the role of each guidepost neuronal subpopulation in callosal guidance. Interestingly, MGE- and CGE-derived GABAergic neurons are both attractive for callosal axons in transplantation experiments. Finally, we have dissected the molecular basis of these guidance mechanisms by using FACS sorting combined with an extensive genetic screen for molecules of interest by a sensitive RT-PCR technique, as well as, in situ hybridization.I have also investigated whether CC guidepost neurons are involved in agenesis of the CC which occurs in numerous human congenital syndromes. Aristaless-related homeobox gene (Arx) regulates GABAergic neuron migration and its mutation leads to numerous human pathologies including X-linked lissencephaly with abnormal genitalia (XLAG) and severe CC agenesis. Interestingly, I found that ARX is expressed in all the guidepost GABAergic neuronal populations of the CC and that Arx-/- embryos exhibit a drastic loss of CC GABAergic interneurons accompanied by callosal axon navigation defects (Niquille et al, in preparation). In addition, we discovered that mice deficient for the ciliogenic transcription factor RFX3 suffer from CC agenesis associated with early midline patterning defects and a secondary disorganisation of guidepost glutamatergic neurons (Benadiba et al., submitted). This strongly points out the potential implication of both types of guidepost neurons in human CC agenesis.Taken together, my thesis work reveals novel functions for transient neurons in axonal guidance and brings new perspectives on the respective roles of neuronal and glial cells in these processes.

Climate Change or Land Use Dynamics: Do We Know What Climate Change Indicators Indicate?

Different components of global change can have interacting effects on biodiversity and this may influence our ability to detect the specific consequences of climate change through biodiversity indicators. Here, we analyze whether climate change indicators can be affected by land use dynamics that are not directly determined by climate change. To this aim, we analyzed three community-level indicators of climate change impacts that are based on the optimal thermal environment and averagelatitude of the distribution of bird species present at local communities. We used multiple regression models to relate the variation in climate change indicators to: i) environmental temperature; and ii) three landscape gradients reflecting important current land use change processes (land abandonment, fire impacts and urbanization), all of them having forest areas at their positive extremes. We found that, with few exceptions, landscape gradients determined the figures of climate change indicators as strongly as temperature. Bird communities in forest habitats had colder-dwelling bird species with more northerndistributions than farmland, burnt or urban areas. Our results show that land use changes can reverse, hide or exacerbate our perception of climate change impacts when measured through community-level climate change indicators. We stress the need of an explicit incorporation of the interactions between climate change and land use dynamics to understand what are current climate change indicators indicating and be able to isolate real climate change impacts

Faut-il traiter l'osteoporose liee a la thalassemie majeure: deux cas cliniques [Should we treat thalassemia-induced osteoporosis: two case reports].

We report two cases of beta-thalassemia-induced osteoporosis. A man and a woman presented an osteoporosis at the densitometry and were treated with bisphoshonate iv. All the studies analysed the efficacity of bisphosphonate, in particular zoledronate seems to be effective. Concerning the pathogenesis, the RANK-RANK-Ligand and OPG play a major role in bone-resorption and seem to be the principal implicated mechanism for the development of osteoporosis in BTM. At the moment there is no study evaluating the efficacity of denosumab in the BTM.

How early can we predict Alzheimer's disease using computational anatomy?

Computational anatomy with magnetic resonance imaging (MRI) is well established as a noninvasive biomarker of Alzheimer's disease (AD); however, there is less certainty about its dependency on the staging of AD. We use classical group analyses and automated machine learning classification of standard structural MRI scans to investigate AD diagnostic accuracy from the preclinical phase to clinical dementia. Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative were stratified into 4 groups according to the clinical status-(1) AD patients; (2) mild cognitive impairment (MCI) converters; (3) MCI nonconverters; and (4) healthy controls-and submitted to a support vector machine. The obtained classifier was significantly above the chance level (62%) for detecting AD already 4 years before conversion from MCI. Voxel-based univariate tests confirmed the plausibility of our findings detecting a distributed network of hippocampal-temporoparietal atrophy in AD patients. We also identified a subgroup of control subjects with brain structure and cognitive changes highly similar to those observed in AD. Our results indicate that computational anatomy can detect AD substantially earlier than suggested by current models. The demonstrated differential spatial pattern of atrophy between correctly and incorrectly classified AD patients challenges the assumption of a uniform pathophysiological process underlying clinically identified AD.

What can we learn from international comparisons of costs by DRG ?

OBJECTIVES: The objective of this study was to compare costs data by diagnosis related group (DRG) between Belgium and Switzerland. Our hypotheses were that differences between countries can probably be explained by methodological differences in cost calculations, by differences in medical practices and by differences in cost structures within the two countries. METHODS: Classifications of DRG used in the two countries differ (AP-DRGs version 1.7 in Switzerland and APR-DRGs version 15.0 in Belgium). The first step of this study was to transform Belgian summaries into Swiss AP-DRGs. Belgian and Swiss data were calculated with a clinical costing methodology (full costing). Belgian and Swiss costs were converted into US$ PPP (purchasing power parity) in order to neutralize differences in purchasing power between countries. RESULTS: The results of this study showed higher costs in Switzerland despite standardization of cost data according to PPP. The difference is not explained by the case-mix index because this was similar for inliers between the two countries. The length of stay (LOS) was also quite similar for inliers between the two countries. The case-mix index was, however, higher for high outliers in Belgium, as reflected in a higher LOS for these patients. Higher costs in Switzerland are thus probably explained mainly by the higher number of agency staff by service in this country or because of differences in medical practices. CONCLUSIONS: It is possible to make international comparisons but only if there is standardization of the case-mix between countries and only if comparable accountancy methodologies are used. Harmonization of DRGs groups, nomenclature and accountancy is thus required.

Resistance of Candida spp. to antifungal drugs in the ICU: where are we now?

Current increases in antifungal drug resistance in Candida spp. and clinical treatment failures are of concern, as invasive candidiasis is a significant cause of mortality in intensive care units (ICUs). This trend reflects the large and expanding use of newer broad-spectrum antifungal agents, such as triazoles and echinocandins. In this review, we firstly present an overview of the mechanisms of action of the drugs and of resistance in pathogenic yeasts, subsequently focusing on recent changes in the epidemiology of antifungal resistance in ICU. Then, we emphasize the clinical impacts of these current trends. The emergence of clinical treatment failures due to resistant isolates is described. We also consider the clinical usefulness of recent advances in the interpretation of antifungal susceptibility testing and in molecular detection of the mutations underlying acquired resistance. We pay particular attention to practical issues relating to ICU patient management, taking into account the growing threat of antifungal drug resistance.

Trastornos de identidad de género: evaluación de la competencia para el cuidado

En este documento se realiza una descripción de los trastornos de identidad de género (TIG) y de su situación a nivel nacional e internacional, teniendo en cuenta la legislación y epidemiología, con el objetivo de consolidar así una base teórica para el estudio. Se diferencian también otras patologías similares para evitar confusión o errores. Se propone un estudio cuantitativo, observacional, transversal, descriptivo y correlacional que tiene como objetivos principales evaluar los conocimientos, habilidades y actitudes necesarios del personal de enfermería para el cuidado de las personas con TIG y comparar las competencias de la enfermería de distintos niveles asistenciales. Como método de recogida de datos se utiliza un cuestionario de elaboración propia, de preguntas cerradas con múltiples opciones de respuesta. El análisis de los datos será inferencial y descriptivo, ya que el objetivo es realizar una estimación a partir de los resultados obtenidos de la muestra sobre el conjunto total de la población con la finalidad de realizar el contraste de la hipótesis formulada; para ello, se realizará la prueba no paramétrica de Chi-­‐ cuadrado.

Building a Better Future.... Together, We Can: Iowa's Program and Budget Fiscal Years 2016-2017, January 2015

Governor Terry E. Branstad's FY2016-17 budget report.

"Aunque lea poco, yo sé que soy listo”. Estudio de caso sobre un adolescente que no lee literatura

Exploramos con un estudio de caso la lectura como práctica social en la vida de un adolescente que acaba de abandonar los estudios en 1º de Bachillerato. Desde el prisma teórico de los Nuevos Estudios de Literacidad, analizamos su punto de vista y sus creencias sobre las prácticas lectoras dominantes y vernáculas en las que participa, dentro y fuera del Instituto. A pesar de su fuerte desinterés por la lectura académica, nuestro informante ha construido una vida lectora variada y activa al margen de la escuela.