Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Narrativa autobiográfica como prática de formação e de atualização de si : os grupos referência e o grupo reflexivo na mediação da constituição identitária docente

The thesis: "autobiographical narrative as practical continuous training and updating of itself: the groups-reference and the reflexive group in the mediation of identity construction of teaching" begins in the founder matter: "What are the implications of groups-reference in the process of identity formation and the teaching role of teachers which is participating of the research? This object of study deals with the continuing education of teachers of Basic Education and the role of the reflective group as space-time of (re) construction of educational knowledge, for the recognition of yourself. The thesis defends that the autobiographical narrative, as a pedagogical tool and research, for the initial and continuous training, is presented as theoretical and methodological foundation necessary for identity formation of the teacher. The research is limited to the qualitative approach with a focus on the autobiographical narrative. The participants are six teachers, three teachers and three students-teachers. The corpus comprises six autobiographical narratives, six reports of successful experiences, two studies on the biographical work, and six individual testimonials about the impact in personal and professional life. The data analysis was to reference Dausien and Alheit (2006), Bruner (1997), Contreras (2002), Delory-Momberger (2007), Freire (2005), Giddens (2002), Josso (2004), new (1988, 2002), Passeggi (2001, 2002), Pineau (2004), Ricoeur (2004), Souza (2006), Tardif (2002) and Vygotsky (2005). The research revealed that the formation of identity as a teachers of the educators occurred in the reference group, involving the formal, non-formal and informal of the processes of knowledge , in a movement of alternation training that includes yourself, the other and the ambient. Also revealed that the pedagogical choices of the teachers studied aimed at minimizing educational gaps that were lived in both field personal and social; that the personal identity is configured as an identity narrative and the methodology of the biographical work, through the mimesis of continuing education, provided the passage from the group reflective to the group of reference

Navegando nas ondas dos saberes do ser: uma conversa com a sexualidade à luz da corporeidade.

This study aimed to provide a continuing education towards raising teachers for reflection and effective sexual education within the school environment as a possible route of self-education and training of teachers of elementary school. More specifically aim to facilitate through the Continuing Education to discuss the knowledge of the body and knowledge of human sexuality, presenting them as core knowledge in the integral formation of individuals and promote discussion of a Human-centered education Teaching in a vocational training and human .In this sense, we dialogue with the human teaching preconized by Arroyo (2002, 2004) along with the humanization (hominization) of the individuals through education, under Freire´s perspective of the being more (2003) as well as his ideas, Pineau´s (2003) and Josso´s (2004) about the educational practice understanding as a way to build up the autonomy of the individuals who we intend to educate. We defend the inclusion of the body as an essential learning element according to the principles of corporeity presented by Assman (2001), whose comprehension is that every learning experience has a corporal inscription. Furthermore, the knowledge about human sexuality cannot be excluded from this process since the sexuality is inherent of individuals and is constructed and reconstructed during their existence. Our view of the world and of man is supported by the knowledge of the complexity (Morim, 2004) trying to surpass the mechanist view that sees them through the duality view, fragmenting them. For the discussion and construction of knowledge that search for the confluence of these knowledges about the being and the educational practice, aiming at the individual integral formation starting from the process of self-formation/self-knowledge, we´ve directed our research-action-formation having as compass the theoretical-methodological postulate of the research-action (Barbier, 2002; Morin, 2004; Thiollent, 2004) because it makes the participation of all the involved people in the process of resolution or surpassing of problem solving possible. We´ve used the continuing formation as a way of access for data collection, applying a questionnaire with open questions for the ones involved in the research. Based on the findings it´s been possible to infer that for the teaching formation it is necessary the inclusion of the Human sexuality and corporeity theme, so that the teacher can surpass the biological view of sexuality and also the expansion of the mechanist view of the body. To do so, we suggest that the teaching formation happens supported by the teaching capacitation and formation according to Maturana (2004), bringing teaching knowledges (Tardiff, 2002), which contribute effectively for the responsibility to educate people for life.

Memorial de formação: um dispositivo de pesquisa ação - formação

La recherche prend comme point de départ la dimension formative du mémoire de formation, considerée comme constitutive de l´écriture de soi, et cherche à problématiser cette dimension au tour du questionnement suivant: Comment le mémoire de formation devient-il un instrument de recherche-action-formation? Les analyses s´appuient sur les principes théoriques du paradigme anthropoformateur, proposé par Pineau (2005), les études réalisées par Passeggi (2006ª, 2006b, 2007, 2008ª, 2008b) sur les mémoires, les travaux de recherche de Nóvoa (1988, 1995), de Josso (2004), de Souza (2006) et de Fontana (2000), qui conçoivent la formação du point de vue de l´ apprenant. L´univers de la recherche s´est circonscrit à la situation de formation des éducateurs de la zone rurale, étudiants en Pédagogie dans le PROFORMAÇÃO (CAMEAM), à l´Univeristé de l´Etat du Rio Grande du Nord (UERN), pendant le second semestre de 2005. La recherche a croisé diférents types de démarche pour recueillir les données empiriques: l´observation du processus d´élaboration des mémoires; un questionnaire; des entretiens informels avec les enseignants en formation et avec les formateurs; et 09 mémoires, écrits par les participants de la recherche. Les analyses des données empiriques montrent que l´écriture des mémoires, en tant que démarche de recherche-action-formation, révelent que la dimension formative se dédouble en d´autres dimensions: etnosociologique, heuristique, herméneutique, social et afective, autopoiétique et politique. Dans la quête de soi (recherche), mise en oeuvre dans et par l´écriture (action), chaque narrateur construit de nouveaux sens à la vie et (re)signifient les représentations de soi (formation). Les résultats confirment la richesse et les potentialités du mémoire, même dans des conditions non ideal, ce qui permet d´affirmer as valeur travail académique important dans la formation des enseignants

A videobiografia como dispositivo de pesquisa-ação-formação: uma prática educativa com adolescentes abrigados

The focus of this thesis is a production of video biographies with/by sheltered teenagers. The general objective is discuss the potential production of video biographies while a device of research-action-formation. From de point of view of research, the study interrogates cultural practices that demarcates the passage of teenagers in shelter institutional; From the point of view of action, seeks to identify the modes of appropriation of space for audiovisual creation by teenagers; and, from the point of view of formation, asks the potentiality of audiovisual language while the way from which teenagers can auto-configure themselves responsibly, in the reinvention of places and others worlds for them. The research falls in the intersection of qualitative approach of ethnographic and of research-action-formation. Is anchored theoretically in autobiographical approaches - Pineau (2005); Passeggi (2008); Delory-Momberger (2008); Josso (2010) e Bertaux (2010) - and in the filmic method - Ramos (2003); Wohlgemuth (2005) and Comoli (2009). Participated in the research eleven teenagers members of the production cycle of biographical traces, among these, the three teenagers who advanced to cycles of audiovisual recording life narratives and reflective exercises around produced reports, procedures of which we extract the set of empirical material analyzed The analysis revealed that teens use in under three types of practices: the practices of mess , as way of expression; the practices of evasion , as resistance to restraint the right to come and go, and the practices of claim a regime of "truth" to the institutional environment, which emerge as a survival tactic in the face of paths desvínculos, family abandonment and neglect. The study also showed the appropriation of spaces of audio-visual creation meaningful expression through music by teenagers and encourage dialogue between and with the teenagers and the achievement of reflective exercises focused for awareness of their stories in becoming. These findings show a broader sense the thesis that visual language is a potent mobilizer artifact reflections and empowerment of individuals in situations of social exclusion

Tessituras poéticas da corporeidade na formação humana do educador infantil

Cette étude a comme sujet principal la formation humaine de l instituteur. L objectif général est d analyser et décrire les conditions créées par les vécus d un atelier corps biographique pour la resignification de la corporéité de l instituteur, fixant les questions suivantes pour l investigation : Quelles sont les implications du vécu de l atelier corps biographique dans la vie des instituteurs ? La recherche a été exposée sur l approche qualitative, suivant les principes de la recherche-action reliée à la méthode des histoires de vie. Pour révéler la beauté et la complexité du processus poïétique de la formation humaine, nous nous sommes servi de la métaphore du "dessus de lit en patchwork" comme opérateur cognitif en attachant les principes de la corporéité fondés sur la Théorie de la complexité (MORIN, 2005), la Théorie autopoïétique (MATURANA ; VARELA, 2001), la Théorie du flux (CSIKSZENTMIHALYI, 1999), les approches de transdisciplinarité (LA TORRE; MORAES, 2008), et d autobiographie (JOSSO, 2004; PINEAU, 2003; PASSEGGI, 2000;), joignant la conception de l éducation comme pratique d autonomie, de liberté, d espoir et de l enchantement (FREIRE, 1996, 1992; ASSMANN, 1995). Nous avons eu comme scène du développement de la recherche, l Unidade Educacional Infantil (UEI), la garderie qui accueille les enfants des fonctionnaires de l Université Fédérale du Rio Grande do Norte. Treise élèves (enfants), des institutrices titulaires, vacataires, boursières ont participé de l'investigation. En conptant sur eux, nous avons développé un atelier corps biographique, dans lequel nous avons réalisé 10 vécus dans la période qui a couvert le deuxième semestre de 2007 jusqu au deuxième semestre de 2008, en manifestant la réflexivité autobiographique, le ludique, la créativité, la sensibilité et la réflexivité du vécu. Nous avons utilisé comme instruments pour la construction des donnés, l observation participante, les propres vécus, le port folio, la technique du jeu de sable et l'enregistrement photographique. L analyse a montré que le vécu de la formation humaine à partir des principes de la corporéité, implique dans un parcours vers soi-même dans lequel émergent les expériences qui nous ont constitués en tant qu êtres existentiels. Pour finaliser, nous avons aperçu les répercussions dans la vie professionnelle et personnelle de ces institutrices, qui comme moi pensaient avoir besoin d exposer leur luminosité intérieure pour que l on la redécouvre. Lors des vécus des tissages, les institutrices se sont montrées impliquées aux moments de jeux, de création, de réalisation, d afection et d action réflexive, dans lesquelles la teneur humaine cachée, a été révélée, en ouvrant les possibilités pour le sentiment du mouvement de naissance de l humanisation intérieure. Pour conclure, le corps joyeux de savoir et de beauté a été révélé, et dans sa rencontre avec soi-même et avec l autre, a pu être auto- recréé

Memória lúdica de infância de educadores que atuam em contextos rurais no município de Araraquara-SP: referências para formação e ação docente

Pós-graduação em Educação Escolar - FCLAR

Programas de formação de alfabetizadores em Portugal e no Brasil: representações de professores

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

European outbreak of atypical myopathy in the autumn 2009

BACKGROUND: Atypical myopathy is an acute, severe rhabdomyolysis occurring in grazing horses. In the beginning of October 2009, a new outbreak occurred in several European countries. Geographic, demographic and clinical data of the reported cases in the month October 2009 are described. KEY FINDINGS: The survival rate in this outbreak was 25%. The most frequently observed clinical signs were congested mucous membranes, dyspnea, tachycardia, depression, weakness, stiffness, recumbency, trembling, sweating, and myoglobinuria. Nonsurvivors were significantly more likely to be recumbent than survivors. Prognostic factors, symptomatic treatment, and preventive measures are discussed. SIGNIFICANCE: Differences were encountered during the described outbreak of atypical myopathy in October 2009 compared with previous outbreaks reported. Equine practitioners should be aware that previous epidemiological studies have shown that after a high prevalence in the autumn, new cases are likely to occur in the following spring.

Optimal target localization for subthalamic stimulation in patients with Parkinson disease

OBJECTIVE To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). METHODS Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. RESULTS Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. CONCLUSION In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location.

Chloroplast DNA footprints of postglacial recolonization by oaks

Recolonization of Europe by forest tree species after the last glaciation is well documented in the fossil pollen record. This spread may have been achieved at low densities by rare events of long-distance dispersal, rather than by a compact wave of advance, generating a patchy genetic structure through founder effects. In long-lived oak species, this structure could still be discernible by using maternally transmitted genetic markers. To test this hypothesis, a fine-scale study of chloroplast DNA (cpDNA) variability of two sympatric oak species was carried out in western France. The distributions of six cpDNA length variants were analyzed at 188 localities over a 200 × 300 km area. A cpDNA map was obtained by applying geostatistics methods to the complete data set. Patches of several hundred square kilometers exist which are virtually fixed for a single haplotype for both oak species. This local systematic interspecific sharing of the maternal genome strongly suggests that long-distance seed dispersal events followed by interspecific exchanges were involved at the time of colonization, about 10,000 years ago.

Cytochrome P450 CYP1B1 determines susceptibility to 7,12-dimethylbenz[a]anthracene-induced lymphomas

CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans.

Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2.

Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals. This protein is primarily involved in oxidative metabolism of xenobiotics and is capable of metabolically activating numerous procarcinogens including aflatoxin B1, arylamines, heterocyclic amine food mutagens, and polycylic aromatic hydrocarbons. Expression of CYP1A2 is induced after exposure to certain aromatic hydrocarbons (i.e., 2,3,7,8-tetrachlorodibenzo-p-dioxin). Direct evidence for a role of CYP1A2 in any physiological or developmental pathway has not been documented. We now demonstrate that mice homozygous for a targeted mutation in the Cyp1a-2 gene are nonviable. Lethality occurs shortly after birth with symptoms of severe respiratory distress. Mutant neonates display impaired respiratory function associated with histological signs of lung immaturity, lack of air in alveoli at birth, and changes in expression of surfactant apoprotein in alveolar type II cells. The penetrance of the phenotype is not complete (19 mutants survived to adulthood out of 599 mice). Surviving animals, although lacking expression of CYP1A2, appear to be normal and are able to reproduce. These findings establish that CYP1A2 is critical for neonatal survival by influencing the physiology of respiration in neonates, thus offering etiological insights for neonatal respiratory distress syndrome.