The Impact of Social-Emotional Learning in the Elementary Classroom

The purpose of this action research project was to investigate whether a correlation exists between stronger social-emotional learning (SEL) skills and attendance records and behaviors at school. The participants included four males ages five to seven in kindergarten and first grade in an early elementary building in a suburban school district in Iowa, USA. The research focuses on the effects of the targeted behavior intervention plan for each student based on their pre-Social, Academic, Emotional, Behavior Risk Screener (SAEBRS) assessment; SAEBRS scores determine which SEL skills are most needed for students. This study discusses the helpfulness of various SEL skills reported by students in an interview. Researchers found no correlations to better attendance and behavior to stronger SEL skills. Future research with more students, all genders represented, and longer interventions would provide more data and understanding of the impact on SEL in the elementary classroom

Inhibition of GSK3 by lithium, from single molecules to signaling networks

For more than 60 years, the mood stabilizer lithium has been used alone or in combination for the treatment of bipolar disorder, schizophrenia, depression, and other mental illnesses. Despite this long history, the molecular mechanisms trough which lithium regulates behavior are still poorly understood. Among several targets, lithium has been shown to directly inhibit glycogen synthase kinase 3 alpha and beta (GSK3α and GSK3β). However in vivo, lithium also inhibits GSK3 by regulating other mechanisms like the formation of a signaling complex comprised of beta-arrestin 2 (βArr2) and Akt. Here, we provide an overview of in vivo evidence supporting a role for inhibition of GSK3 in some behavioral effects of lithium. We also explore how regulation of GSK3 by lithium within a signaling network involving several molecular targets and cell surface receptors [e.g., G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs)] may provide cues to its relative pharmacological selectivity and its effects on disease mechanisms. A better understanding of these intricate actions of lithium at a systems level may allow the rational development of better mood stabilizer drugs with enhanced selectivity, efficacy, and lesser side effects

Mise au point d'une méthode de détection des composés pharmacologiquement actifs sur la voie D2R-AKT-GSK3

Les maladies mentales sont un phénomène en pleine expansion dans nos sociétés occidentales. Des estimations de l'Organisation Mondiale de la Santé (O.M.S) prévoient que d'ici 2020, la dépression mesurée en DALYs (déficience ajustée par année de survie qui est un indicateur d'années de vie avec une déficience et des années perdues par une mort prématurée) [1] sera la deuxième cause d'invalidité tout âge ou sexe confondu dans le monde ce qui entraînerait un coût exorbitant pour nos sociétés [2]. Investir dans la découverte des causes des maladies mentales ainsi que dans leur traitement représente par conséquent un élément crucial pour conserver la cohésion sociale. Aujourd'hui, l'une des causes les plus probables à l'origine des pathologies mentales semble impliquer une dérégulation de la voie de signalisation neuronale D2R-AKT-GSK-3 au sein du striatum. La première étape de l'étude préclinique des médicaments est le criblage pharmaceutique in-vitro c'est-à-dire un criblage sur cellules et en laboratoire. Ainsi, l'objet de ma maîtrise concerne le développement de modèles d'études in vitro permettant l'étude de la voie de signalisation neuronale D2R-AKT-GSK-3. Compte tenu du manque d'expertise de mon laboratoire d'accueil à l'époque, mon mémoire sera à dominante méthodologique. Tout d'abord, j'ai mis au point un modèle de culture cellulaire de striatum de souris transgéniques sur lamelles. Ceci pour m'assurer que la culture est viable et qu'elle présente les différentes populations neuronales en proportions similaires à ce que l'on trouve chez l'animal. J'ai utilisé cette même culture dans le cadre d'un article édité en 2011 (Swift et al., 2011) afin de prouver que les récepteurs dopaminergiques endogènes peuvent transactiver les récepteurs TrkB endogènes dans les neurones du striatum, phénomène visible via la technique d'Analyse de Distribution d'Intensité Spatiale (SpEDA). Une fois assurée par ces deux résultats que le modèle fonctionne bien et est utilisable dans le cadre d'une étude de stimulation, la seconde étape entreprise a été la mise au point d'une technique de criblage pharmacologique à moyen débit en plaque de 96 puits. Ces résultats me permettent d'envisager que ce modèle est développable et a un véritable potentiel dans le criblage pharmaceutique qui souffre actuellement de nombreuses limitations concernant l'étude des protéines G. En effet, il assure une certaine flexibilité dans l'examen des variables utilisées sans avoir à modifier la trousse de réactifs expérimentale

Actinomycosis of the Gallbladder Mimicking Carcinoma: a Case Report with US and CT Findings

We describe a case of actinomycosis of the gallbladder mimicking carcinoma. Sonography showed a hypoechoic mass replacing gallbladder lumen and engulfing a stone; contrast-enhanced computed tomography showed a heterogeneously enhanced thickened gallbladder wall with subtle, disrupted luminal surface enhancement, which formed a mass. As a result of the clinical and radiologic presentation, our impression was of gallbladder carcinoma. Actinomycosis should be included in the differential diagnosis when sonography and computed tomography findings show a mass engulfing the stone in the gallbladder and extensive pericholecystic infiltration with extension to neighboring abdominal wall muscle

Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP and analyzed the consequence of plasmalogen deficiency in peripheral nerves. We determined that plasmalogens are crucial for Schwann cell development and differentiation and that plasmalogen defects impaired radial sorting, myelination, and myelin structure. Plasmalogen insufficiency resulted in defective protein kinase B (AKT) phosphorylation and subsequent signaling, causing overt activation of glycogen synthase kinase 3β (GSK3β) in nerves of mutant mice. Treatment with GSK3β inhibitors, lithium, or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) restored Schwann cell defects, effectively bypassing plasmalogen deficiency. Our results demonstrate the requirement of plasmalogens for the correct and timely differentiation of Schwann cells and for the process of myelination. In addition, these studies identify a mechanism by which the lack of a membrane phospholipid causes neuropathology, implicating plasmalogens as regulators of membrane and cell signaling.We thank Paula Sampaio for microscopy support, Paula Magalhdes for genotyping, and Isabel Carvalho, Sofia Lamas, and Fatima Martins for excellent animal care. We are grateful to P. Brophy (University of Edinburgh) for the DRP2 antibody and to M. Baes (K.U. Leuven) for providing the Gnpat mouse strain. This work was funded by the Research Foundation of the European Leukodystrophy Association (ELA 2008-009C4, ELA 2010-042C5), by FEDER Funds through the Operational Competitiveness Program - COMPETE, and by national funds through the FCT - Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-015970 (PTDS/SAU-ORG/112406/2009). P. Brites is an FCT Investigator, and T. Ferreira da Silva was supported by the FCT (SFRH/BD/88160/2012)

Evaluation of physical activity programmes for the elderly - exploring the lessons from other sectors and examining the general characteristics of the programmes

<p>Abstract</p> <p>Background</p> <p>In Portugal, there are several physical activity (PA) programmes for elderly people developed by the local government. The importance of these programmes has been increasing since the evidence has shown that this type of health promotion interventions may reduce the deleterious effects of the ageing process. However, no study has already identified the general characteristics of these programmes nor if they use any scheme to assess the quality of the service provided. A widely-used scheme is the EFQM Excellence Model, which will be in the core of our present work. Thus, the main aims of this preliminary study were 1) to identify the general characteristics of the PA programmes developed by the Portuguese Local Public Administration 2) to determine the extent of implementation of quality initiatives in these programmes.</p> <p>Methods</p> <p>Data were collected by an on-line questionnaire sent to all Continental Municipalities (n = 278). Categorical data were expressed as absolute counts and percentages. Continuous data were expressed as the mean and SD. An open-ended question was analysed using qualitative content analysis with QSR NVivo software. Associations between categorical variables were tested by the use of contingency tables and the calculation of chi-square tests. Significance level was set at p ≤ 0.05.</p> <p>Results</p> <p>Results showed: i) a total of 125 PA programmes were identified in the 18 districts of the Portugal mainland; ii) the main goal of the majority (95.2%) was the participants' health promotion; iii) different characteristics of the programmes were found according to different regions of the country; iv) certain characteristics of the programmes were associated to the existence of other features; v) only one PA programme developed quality initiatives.</p> <p>Conclusions</p> <p>In conclusion, although there are many PA programmes for elderly people spread throughout the country, aiming at improving the health of participants, the overwhelming majority does not adopt quality control initiatives. Considering that the quality of a service increases customer satisfaction, the continuous quality improvement of the PA programmes for elderly people should therefore be implemented since they can be useful and critical for elderly satisfaction and adherence.</p

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney functio

Lymphoid development and function in MHC class I deficient mice

MHC class I molecules present short peptide fragments, derived from proteins synthesized in the cytosol, to specific CTL. The MHC class I molecule is a heterotrimer encompassed of a polymorphic transmembrane glycoprotein (heavy chain), ß2-microglobulin (ß2m), and a peptide. In the first study (Paper I), we carried out an in depth analysis with respect to the requirement of the ß2m and TAPtransported peptides for proper MHC class I assembly, and intracellular transport. We show that properly conformed class I heavy chains can be detected in a terminally glycosylated form indicative of cell surface expression in H-2b, H-2d and H-2s ß2m -/- ConA-stimulated splenocytes incubated at reduced temperature. Furthermore, we demonstrate the presence of Kb molecules at the surface of ß2m -/- cells cultured at 37o C. We provide evidence for a role of peptide in intracellular transport of free MHC class I heavy chains, through analysis of ConA-stimulated splenocytes from TAP1 -/-, ß2m -/- double mutant TAP1/ß2m -/- mice. Studies of MHC class I -deficient mice have also provided insights into the role of MHC class I molecules in the development of CD8+ T lymphocytes and NK cells. Although ß2m -/- mice were initially thought to be devoid of MHC class I molecules and CD8+ T cells, it is now clear that they express low levels of MHC class I molecules on the cell surface, and studies by others have provided evidence for the selection of a small pool of CD8+ T cells in these mice. The latter is true also for TAP1 -/- as well as for TAP1/ Min -/- mice. In Paper II, we addressed the ability of TAP1 -/-, ß2m -/- and TAP1/ ß2m -/- mice to mount responses against allogeneic and syngeneic MHC class I-positive tumor grafts, and against MHC class I-deficient tumor grafts. The results demonstrated a potent ability of TAP1 -/-, ß2m -/- as well as TAP1/ Win -/- mice to reject allogeneic tumors. In contrast to published data, rejection of syngeneic MHC class I expressing tumors was also observed. This response was specific for the MHC class I deficient mice. Finally, MHC class I deficient tumor grafts were accepted in MHC class I deficient mice while similar grafts were rejected in wild type mice. To directly address the potential role of CD8+ T cell responses in ß2m -/- mice, we introduced a CD8 null mutation into ß2m -/- mice (Paper III). ß2m/CD8 -/- mice and corresponding control mice were primed, and challenged with syngeneic tumor grafts. While ß2m -/- mice readily cleared such tumor grafts, similar tumor grafts grew progressively in a dose dependent manner in ß2m/CD8 -/- mice. This study provided formal proof for the dependence of CD8+ T cells in the tumor rejection responses studied. The present results suggest that studies using ß2m -/- as a model of CD8+ T cell deficiency must be regarded with caution. NK cells recognize MHC class I molecules with specific receptors. In the mouse, MHC class I-specific inhibitory receptors are dimeric C-type lectins that belong to the Ly49 family. In an attempt to re-express a functional ß2m gene in ß2m -/- mice, we generated a panel of founder mice with an unexpected mosaic expression of MHC class I molecules (Paper IV). This allowed us to study lymphocyte development in an environment where MHC class Ipositive and -negative cells had co-evolved, and to examine of the influence of MHC class I on the expression of the Ly49C inhibitory receptor on NK cells. This receptor binds to H-2Kb. It is expressed at low levels on NK cells in wild type mice of the H-2b haplotype, but at markedly higher levels on NK cells in ß2m -/- mice and other strains of mice lacking expression of H-2Kb. Through the analysis of the present MHC class I mosaic mice, we demonstrate that the expression levels of Ly49C on NK cells is a consequence not only of MHC class I expression in the environment, but also of the expression of MHC class I molecules by the NK cells themselves