Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory.

Immune protection from intracellular pathogens depends on the generation of terminally differentiated effector and of multipotent memory precursor CD8 T cells, which rapidly regenerate effector and memory cells during recurrent infection. The identification of factors and pathways involved in CD8 T cell differentiation is of obvious importance to improve vaccination strategies. Here, we show that mice lacking T cell factor 1 (Tcf-1), a nuclear effector of the canonical Wingless/Integration 1 (Wnt) signaling pathway, mount normal effector and effector memory CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV). However, Tcf-1-deficient CD8 T cells are selectively impaired in their ability to expand upon secondary challenge and to protect from recurrent virus infection. Tcf-1-deficient mice essentially lack CD8 memory precursor T cells, which is evident already at the peak of the primary response, suggesting that Tcf-1 programs CD8 memory cell fate. The function of Tcf-1 to establish CD8 T cell memory is dependent on the catenin-binding domain in Tcf-1 and requires the Tcf-1 coactivators and Wnt signaling intermediates beta-catenin and gamma-catenin. These findings demonstrate that the canonical Wnt signaling pathway plays an essential role for CD8 central memory T cell differentiation under physiological conditions in vivo. They raise the possibility that modulation of Wnt signaling may be exploited to improve the generation of CD8 memory T cells during vaccination or for therapies designed to promote sustained cytotoxic CD8 T cell responses against tumors.

Can we continue to neglect genomic variation in introgression rates when inferring the history of speciation? A case study in a Mytilus hybrid zone.

The use of molecular data to reconstruct the history of divergence and gene flow between populations of closely related taxa represents a challenging problem. It has been proposed that the long-standing debate about the geography of speciation can be resolved by comparing the likelihoods of a model of isolation with migration and a model of secondary contact. However, data are commonly only fit to a model of isolation with migration and rarely tested against the secondary contact alternative. Furthermore, most demographic inference methods have neglected variation in introgression rates and assume that the gene flow parameter (Nm) is similar among loci. Here, we show that neglecting this source of variation can give misleading results. We analysed DNA sequences sampled from populations of the marine mussels, Mytilus edulis and M. galloprovincialis, across a well-studied mosaic hybrid zone in Europe and evaluated various scenarios of speciation, with or without variation in introgression rates, using an Approximate Bayesian Computation (ABC) approach. Models with heterogeneous gene flow across loci always outperformed models assuming equal migration rates irrespective of the history of gene flow being considered. By incorporating this heterogeneity, the best-supported scenario was a long period of allopatric isolation during the first three-quarters of the time since divergence followed by secondary contact and introgression during the last quarter. By contrast, constraining migration to be homogeneous failed to discriminate among any of the different models of gene flow tested. Our simulations thus provide statistical support for the secondary contact scenario in the European Mytilus hybrid zone that the standard coalescent approach failed to confirm. Our results demonstrate that genomic variation in introgression rates can have profound impacts on the biological conclusions drawn from inference methods and needs to be incorporated in future studies.

Incidència de l’entorn educatiu, familiar i social en les actituds lingüístiques i identitàries dels joves d’origen xinès i llatinoamericà a Catalunya

From an interdisciplinary perspective, the present investigation undertaken by the GREILI-UPF research group has expanded a previous study aiming at explaining how young secondary school students of Latin American and Chinese origin in Catalonia construct their linguistic and cultural identity. Here we analyze the relationship between these youngsters and their social environment in order to determine how these relationships and the socialization process that derives from them influence language attitudes and practices. We focus on two spaces of socialization: (1) the school, where youngsters from diverse cultural and linguistic backgrounds coexist and interact, and (2) the neighborhood, a geographic and symbolic space where social identity is constructed and, consequently, where young newcomers construct their perceptions regarding the host society, including its linguistic reality. We have collected several sets of data in three public secondary schools and three neighborhoods from Barcelona’s metropolitan area with a high index of immigrant population: (1) interviews with secondary school students, (2) interviews with teachers, (3) social discourses in newspapers that consolidate the social image of the neighborhood, (4) narratives from immigrant families in relation to their neighborhood, (5) participant observation in schools, and (5) observation in the neighborhood. The results of the thematic and, when appropriate, discursive analysis of the data allow us to reach conclusions regarding: (a) the social image of the neighborhoods, (b) the socialization of young newcomers in the schools and the neighborhoods, (c) the identity games, and (d) the language and cultural practices and attitudes of young people, in relation to their countries and languages of origin as well as the school and the neighborhood investigated.

Trajectòries d'èxit de joves immigrants a l'ensenyament superior i al món professional

L’educació dels immigrants és un tema prioritari a les agendes polítiques de molts països de la OCDE. En molts casos, els governs s’han preocupat especialment de la seva integració al món del treball però creix l’interès en els seus resultats al sistema educatiu i en la revisió de les polítiques adreçades a respondre a les seves necessitats educatives i formatives. La majoria d’aquests estudis es situen a l’esfera de l’educació infantil, primària, secundaria i formació professional, per això resulta pràcticament impossible trobar estudis que analitzin el baix percentatge d’accés d’estudiants immigrants extracomunitaris a la universitat (al voltant de 3,3% en el cas de Catalunya); que contribueixin a entendre els factors que configuren les trajectòries d’èxit escolar i d’integració laboral dels estudiants immigrants que accedeixen i completen els estudis universitaris; que puguin donar pautes per desenvolupar polítiques educatives que millorin els resultats d’aprenentatge dels estudiants immigrants; i que puguin servir com a mirall i incentiu per a altres persones immigrants i, perquè no, també del país. Aquest projecte ha estudiat el conjunt d’elements que condicionen l’accés dels joves immigrants als estudis universitaris, i a l’estatus laboral que els hauria de possibilitar la seva formació universitària. L’estudi ha consistit en una metaanàlisi dels documents existents sobre el tema i en la realització de 8 narratives biogràfiques; quatre de persones cursant diferents estudis a les universitats catalanes i quatre que ja s’han incorporat al món del professional. Aquestes narratives venen acompanyades de 8 vídeos que exploren noves maneres de visibilització d’aquesta població i es transformen en una pràctica d’autoria. Aquest material visual pot servir com a recurs educatiu, en la mida que pugui ser un mirall i un incentiu per a altres persones immigrants i del país. Finalment, presenta un seguit de recomanacions per als responsables de les polítiques i dels centres educatius.

Evaluation de la qualité de vie après prélèvement de la veine fémorale superficielle lors de reconstructions infra-inguinales [Quality of life after superficial femoral vein harvest for infra-inguinal reconstructions]

BACKGROUND: The superficial femoral vein (SFV) is a well-established alternative conduit for infra-inguinal reconstructivenous hypertension after SFV harvest may however result in significant morbidity. This study reports the efficiency of SFV as conduit for infra-inguinal reconstructions and characterize the anatomic and physiologic changes in harvest limbs and their relationship to the development of venous complications. METHODS: From May 1999 through November 2003, 23 SFV were harvested from 21 patients undergoing infra-inguinal reconstructions. Bypasses were controlled by regular duplex-ultrasound. The venous morbidity was assessed by measurements of leg circumferences, strain-gauge plethysmography and quality of life, investigated by the VEINES-QOL scale. RESULTS: At a mean follow-up of 10.4 months (range 1-56), primary, secondary patency and limb salvage rates of infra-inguinal bypasses using SFV are 71.4%, 76.2% and 85.7% respectively. No patient had major venous claudication. Oedema was significantly present in nine patients. Strain-gauge plethysmography showed outflow obstruction in all patients. The VEINES-QOL assessment showed no limitation in social and domestic activity, moderate complain about leg heaviness despite presence of oedema. CONCLUSION: The SFV harvest is a reliable conduit for infra-inguinal reconstructions and results in moderate venous morbidity in terms of functional consequences and quality of life.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Avaliação de necessidades de formação em professores do ensino secundário em Cabo Verde

II Resumo Cabo Verde é um país que tem acompanhado as grandes mudanças políticas, sociais, económicas e educativas, atribuindo um papel preponderante aos professores na educação/formação dos indivíduos. Neste sentido a formação inicial não pode constituir um acto “acabado” que não tem em linha de conta as mudanças que decorrem no seu seio. A formação contínua aparece com um processo de construção da mudança, apoiado no desenvolvimento profissional dos professores. A avaliação de necessidade de formação em professores do ensino secundário em Cabo Verde é o tema do trabalho de investigação, realizado nas escolas secundárias da ilha de Santo Antão, em Cabo Verde, no sentido de identificar questões problemáticas na formação inicial e contínua de professores e as suas implicações na qualidade educativa. Neste sentido, ao longo de 5 capítulos apresentamos os pontos desta investigação, estruturados de forma a se poder acompanhar a sua evolução. No 1º capítulo, apresenta-se a Problemática de Investigação, que constitui a parte inicial da dissertação, pela exposição do quadro conceptual do ensino secundário em Cabo Verde através da contextualização e identificação do problema, da formulação dos objectivos e questões de investigação. No 2º capítulo faz-se o percurso histórico/educativo de Cabo Verde, desde a época colonial, passando pela educação após a independência em 1975, à constituição da Lei de Bases do Sistema Educativo e a Reforma Educativa dos anos 90. No 3º capítulo, intitulado “A Formação Inicial e Continua de Professores em Cabo Verde”, é abordado o enquadramento teórico desta investigação, com referência à contextualização geral da formação e modelos de formação de professores, evoluindo para a realidade Cabo-verdiana, tendo em consideração as instituições de formação de professores e o contexto actual do ensino secundário em Cabo Verde. No 4º capítulo faz-se a apresentação da Metodologia de Investigação, adoptada num estudo extensivo, do qual abordamos a natureza da investigação e caracterizamos a amostra e respondentes. Como técnicas de recolha de dados, são utilizados: o inquérito por questionário (n=77), a professores do ensino secundário e o inquérito por entrevista (n=9), aos directores das escolas secundárias da ilha de Santo Antão e a formadores de professores em São Vicente. Como técnica de análise de dados, são utilizados diversos procedimentos estatísticos e a análise de conteúdo. O 5º capítulo corresponde a apresentação e discussão dos resultados da investigação desses três públicos analisados. Para finalizar, apresenta-se uma conclusão que corresponde a síntese dos resultados obtidos, propostas de sugestões de melhoria e limitações do estudo. Cabo Verde is a country willing to follow the great political, social, economic and educational changes. This important role have attributed to teachers to educate and train individuals. In this sense the initial training cannot be considered as a “finished” task without taking into consideration those changes. The in service training appears as a scientific and pedagogic autonomization towards the growing change. The Evaluation of Secondary School teacher training Needs in Cabo Verde constitutes an investigation work, carried out in Santo Antão's island Secondary schools, aiming to identify problems in initial and continuous teachers' training and their implications in the educational quality. In this sense, along five chapters we will present the points of this investigation, structured to facilitate the understanding of its evolution. In the first chapter we present the Problem of Investigation which is an introductory part of the dissertation, the conceptual theory of the Cabo Verde secondary education through the contextualization and identification of the problem, the formulation of the objectives and investigation issues. In the second chapter we present the Cabo Verde historical/educational background, from the colonial time, going through after independence in 1975, to the constitution of the Basic Educational Law of the System and the nineties Educational Reform. In the third chapter entitled “The Initial and in-service Teacher´s Training in Cabo Verde” brings the theoretical framework of this investigation, where we present a general contextualization of teachers' training and models, developed from the reality of Cabo Verde. In this regard we will consider the teachers' training institutions and the current secondary education context in Cabo Verde. In the fourth chapter we present the Research Methodology, adopted in an extensive study, of which we draw the nature of the investigation and we characterized the sample. We carried out questionnaire (n=77) to teachers, interviews (n=9) to headmasters from Santo Antão's island secondary schools and trainers from São Vicente. We used statistical analyses and content analyses as data analyse techniques. The fifth chapter deals with presentation the discussion of results of those three analyzed publics' investigation. Finally, we present a summary of the obtained results, suggestions for improvement and limitations of study.

O Sistema de Normalização Contabilística e de Relato Financeiro e a Tributação sobre o Rendimento das Empresas

O presente trabalho tem como propósito evidenciar os efeitos da introdução do SNCRF na elaboração das contas nas empresas cabo-verdianas, num ambiente fiscal desactualizado. O tema escolhido justifica-se pelas implicações do novo normativo contabilístico nas sociedades comerciais e, sobretudo, da necessidade de se fazer uma contraposição de um sistema contabilístico moderno com um sistema fiscal antigo. O método utilizado foi estudo de caso. A recolha de dados foi feita através da aplicação de entrevistas estruturadas e não estruturadas, de recursos a fontes secundárias e análise documental. Os resultados do estudo apontam as dificuldades na adaptação do novo sistema contabilístico num ambiente fiscal, que não acompanhou as reformas do sistema contabilístico. The principal objective of this research is to evidence the effects of the introduction of SNCRF in the elaboration of the accounts at the capeverdian enterprises with antiquated fiscal environment. The chosen theme is justified by the involvement of the new accountancy normative at the commercial societies and, especially, of the requirement to make a contraposition of an accountancy and modern system with an antiquated fiscal system. The method utilized is the study of a case. The gathering is made by application of structured and no structured interviews, recourse to secondary sources and documental analysis. The results of this study appoint to incertitudes and difficulties of the adaptation of the new accountancy system in a fiscal environment which didn’t follow the reforms of the accountancy system.

RsmY, a small regulatory RNA, is required in concert with RsmZ for GacA-dependent expression of biocontrol traits in Pseudomonas fluorescens CHA0.

In the plant-beneficial soil bacterium and biocontrol model organism Pseudomonas fluorescens CHA0, the GacS/GacA two-component system upregulates the production of biocontrol factors, i.e. antifungal secondary metabolites and extracellular enzymes, under conditions of slow, non-exponential growth. When activated, the GacS/GacA system promotes the transcription of a small regulatory RNA (RsmZ), which sequesters the small RNA-binding protein RsmA, a translational regulator of genes involved in biocontrol. The gene for a second GacA-regulated small RNA (RsmY) was detected in silico in various pseudomonads, and was cloned from strain CHA0. RsmY, like RsmZ, contains several characteristic GGA motifs. The rsmY gene was expressed in strain CHA0 as a 118 nt transcript which was most abundant in stationary phase, as revealed by Northern blot and transcriptional fusion analysis. Transcription of rsmY was enhanced by the addition of the strain's own supernatant extract containing a quorum-sensing signal and was abolished in gacS or gacA mutants. An rsmA mutation led to reduced rsmY expression, via a gacA-independent mechanism. Overexpression of rsmY restored the expression of target genes (hcnA, aprA) to gacS or gacA mutants. Whereas mutants deleted for either the rsmY or the rsmZ structural gene were not significantly altered in the synthesis of extracellular products (hydrogen cyanide, 2,4-diacetylphloroglucinol, exoprotease), an rsmY rsmZ double mutant was strongly impaired in this production and in its biocontrol properties in a cucumber-Pythium ultimum microcosm. Mobility shift assays demonstrated that multiple molecules of RsmA bound specifically to RsmY and RsmZ RNAs. In conclusion, two small, untranslated RNAs, RsmY and RsmZ, are key factors that relieve RsmA-mediated regulation of secondary metabolism and biocontrol traits in the GacS/GacA cascade of strain CHA0.

Gut symbionts from distinct hosts exhibit genotoxic activity via divergent colibactin biosynthetic pathways.

Secondary metabolites produced by nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways are chemical mediators of microbial interactions in diverse environments. However, little is known about their distribution, evolution, and functional roles in bacterial symbionts associated with animals. A prominent example is "colibactin", a largely unknown family of secondary metabolites produced by Escherichia coli via a hybrid NRPS-PKS biosynthetic pathway, inflicting DNA damage upon eukaryotic cells and contributing to colorectal cancer and tumor formation in the mammalian gut. Thus far, homologs of this pathway have only been found in closely related Enterobacteriaceae, while a divergent variant of this gene cluster was recently discovered in a marine alphaproteobacterial Pseudovibrio strain. Herein, we sequenced the genome of Frischella perrara PEB0191, a bacterial gut symbiont of honey bees, and identified a homologous colibactin biosynthetic pathway related to those found in Enterobacteriaceae. We show that the colibactin genomic island (GI) has conserved gene synteny and biosynthetic module architecture across F. perrara, Enterobacteriaceae and the Pseudovibrio strain. Comparative metabolomics analyses of F. perrara and E. coli further reveal that these two bacteria produce related colibactin pathway-dependent metabolites. Finally, we demonstrate that F. perrara, like E. coli, causes DNA damage in eukaryotic cells in vitro in a colibactin pathway-dependent manner. Together, these results support that divergent variants of the colibactin biosynthetic pathway are widely distributed among bacterial symbionts, producing related secondary metabolites and likely endowing its producer with functional capabilities important for diverse symbiotic associations.

Nouvelles thérapies pour les maladies osseuses de l'enfant [New therapies for children affected by bone diseases].

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

Status of Iowa Women Report, 2006

The Iowa Commission on the Status of Women (ICSW) is a state agency that seeks to assure equality for Iowa women. As an advocacy agency, the Commission works to equalize women's opportunities and to promote full participation by women in the economic, political, and social life of the state. This is the tenth edition of the Status of Iowa Women Report. Many positive changes toward women's full participation in all aspects of society are evident in this edition: more women than ever are getting a post-secondary education and they have made significant inroads into some traditionally male-dominated work domains. Still, much remains to be done. The 2006 report also shows that girls, by and large, are not enrolling in upper-level high-school computer courses, a necessity for the 21st century; women's earnings lag behind men's; and women continue to be raped, beaten, and battered at staggering rates. Much work needs to be done at the community and state levels to address those and other challenges addressed in this publication.

Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells.

Engineering of fetal tissue has a high potential for the treatment of acute and chronic wounds of the skin in humans as these cells have high expansion capacity under simple culture conditions and one organ donation can produce Master Cell Banks which can fabricate over 900 million biological bandages (9 x 12cm). In a Phase 1 clinical safety study, cases are presented for the treatment of therapy resistant leg ulcers. All eight patients, representing 13 ulcers, tolerated multiple treatments with fetal biological bandages showing no negative secondary effects and repair processes similar to that seen in 3rd degree burns. Differential gene profiling using Affymetrix gene chips (analyzing 12,500 genes) were accomplished on these banked fetal dermal skin cells compared to banked dermal skin cells of an aged donor in order to point to potential indicators of wound healing. Families of genes involved in cell adhesion and extracellular matrix, cell cycle, cellular signaling, development and immune response show significant differences in regulation between banked fetal and those from banked old skin cells: with approximately 47.0% of genes over-expressed in fetal fibroblasts. It is perhaps these differences which contribute to efficient tissue repair seen in the clinic with fetal cell therapy.

Open to closed system transition traced through the TDIC isotopic signature at the aquifer recharge stage, implications for groundwater 14C dating

14C dating models are limited when considering recent groundwater for which the carbon isotopic signature of the total dissolved inorganic carbon (TDIC) is mainly acquired in the unsaturated zone. Reducing the uncertainties of dating thus implies a better identification of the processes controlling the carbon isotopic composition of the TDIC during groundwater recharge. Geochemical interactions between gas, water and carbonates in the unsaturated zone were investigated for two aquifers (the carbonate-free Fontainebleau sands and carbonate-bearing Astian sands, France) in order to identify the respective roles of CO2 and carbonates on the carbon isotopic signatures of the TDIC; this analysis is usually approached using open or closed system terms. Under fully open system conditions, the seasonality of the 13C values in the soil CO2 can lead to important uncertainties regarding the so-called "initial 14C activity" used in 14C correction models. In a carbonate-bearing unsaturated zone such as in the Astian aquifer, we show that an approach based on fully open or closed system conditions is not appropriate. Although the chemical saturation between water and calcite occurs rapidly within the first metre of the unsaturated zone, the carbon isotopic contents (δ13C) of the CO2 and the TDIC evolve downward, impacted by the dissolution-precipitation of the carbonates. In this study, we propose a numerical approach to describe this evolution. The δ13C and the A 14C (radiocarbon activity) of the TDIC at the base of the carbonate-hearing unsaturated zone depends on (i) the δ13C and the A 14C of the TDIC in the soil determined by the soil CO2, (ii) the water's residence time in the unsaturated zone and (iii) the carbonate precipitation-dissolution fluxes. In this type of situation, the carbonate δ13C-A 14C evolutions indicate the presence of secondary calcite and permit the calculation of its accretion flux, equal to ~ 4.5 ± 0.5 x 10-9 mol grock-1 yr-1. More generally, for other sites under temperate climate and with similar properties to the Astian sands site, this approach allows for a reliable determination of the carbon isotopic composition at the base of the unsaturated zone as the indispensable "input function" data of the carbon cycle into the aquifer.

Posttranscriptional repression of GacS/GacA-controlled genes by the RNA-binding protein RsmE acting together with RsmA in the biocontrol strain Pseudomonas fluorescens CHA0.

In the plant-beneficial soil bacterium Pseudomonas fluorescens CHA0, the production of biocontrol factors (antifungal secondary metabolites and exoenzymes) is controlled at a posttranscriptional level by the GacS/GacA signal transduction pathway involving RNA-binding protein RsmA as a key regulatory element. This protein is assumed to bind to the ribosome-binding site of target mRNAs and to block their translation. RsmA-mediated repression is relieved at the end of exponential growth by two GacS/GacA-controlled regulatory RNAs RsmY and RsmZ, which bind and sequester the RsmA protein. A gene (rsmE) encoding a 64-amino-acid RsmA homolog was identified and characterized in strain CHA0. Overexpression of rsmE strongly reduced the expression of target genes (hcnA, for a hydrogen cyanide synthase subunit; aprA, for the main exoprotease; and phlA, for a component of 2,4-diacetylphloroglucinol biosynthesis). Single null mutations in either rsmA or rsmE resulted in a slight increase in the expression of hcnA, aprA, and phlA. By contrast, an rsmA rsmE double mutation led to strongly increased and advanced expression of these target genes and completely suppressed a gacS mutation. Both the RsmE and RsmA levels increased with increasing cell population densities in strain CHA0; however, the amount of RsmA showed less variability during growth. Expression of rsmE was controlled positively by GacA and negatively by RsmA and RsmE. Mobility shift assays demonstrated specific binding of RsmE to RsmY and RsmZ RNAs. The transcription and stability of both regulatory RNAs were strongly reduced in the rsmA rsmE double mutant. In conclusion, RsmA and RsmE together account for maximal repression in the GacS/GacA cascade of strain CHA0.