Durant ma thèse, j’ai étudié l’implication d’un variant du récepteur aux œstrogènes α, ERα36, dans l’initiation et la progression du cancer du sein. Au laboratoire, son expression dans les cancers testiculaires avait été montrée comme étant inductrice de la prolifération cellulaire in vitro et in vivo après une exposition à un mélange de polluants environnementaux, considérés comme perturbateurs endocriniens oestrogéno-mimétique : les alkylphénols. Une analyse rétrospective d’échantillons de tumeurs mammaires a montré, par la modélisation de réseaux d’interactions géniques, que l’expression d’ERα36 était corrélée avec l’expression de marqueurs de migration cellulaire, caractéristiques de la progression tumorale. La surexpression d’ERα36 par transfection in vitro et dans un modèle unique de souris Knocked In exprimant ERalpha36 dans la glande mammaire ont montré qu’ERα36 est suffisant pour altérer le phénotype épithélial des cellules mammaires saines. Une exposition aux alkylphénols qui stimulent son expression endogène accentue les altérations cellulaires observées et contribue à l’acquisition transgénérationnelle de propriétés relatives à une transformation tumorale. Les analyses de ce projet pluridisciplinaire se sont appuyées sur des expertises biologiques, mathématiques et bioinformatiques et ont permis de mettre en évidence pour la première fois le rôle potentiel d’ERα36 dans l’initiation tumorale et de confirmer son implication dans la progression du cancer du sein. Enfin, nous avons montré que l’exposition à des doses environnementales d’alkylphénols lors de la période de périnatalité peut conduire à une modification transgénérationnelle de la différenciation de la glande mammaire sous le contrôle d’ERα36 et ainsi augmenter le risque de cancer mammaire / This work was dedicated to study how a variant of estrogen receptor α, ERα36, acts in initiation and progression of breast cancer. In the laboratory, his expression in testicular cancer was shown to stimulate cell proliferation in vitro and in vivo after environmental pollutant exposure. The compounds studied, the alkylphenols, are endocrine disruptors, interfering with normal estrogen signaling. Gene interaction network modelling from retrospective analysis of breast cancer samples showed that ERα36 expression was correlated with the expression of cell migration markers, typical of tumor progression. In vitro ERα36 overexpression and in a unique mouse Knocked In model, expressing ERα36 in the mammary gland, showed that ERα36 is sufficient to alter epithelial phenotype of normal breast cells. Alkylphenols exposure, that stimulated ERα36 endogenous expression, increased cellular alterations and contributed to transgenerational acquisition of properties related to neoplastic transformation. Analysis of this multidisciplinary project were based on biological expertise, mathematics and bioinformatic tools. These results enabled to highlight for the first time the potential role of ERα36 in tumor initiation and confirmed his involvement in breast cancer progression. Finally, we showed that exposure to environmental doses of alkylphenols during the perinatal period can lead to transgenerational modification of mammary gland differentiation under ERα36 control and eventually may increase breast cancer risk

O estudo aborda os sentimentos e as expectativas dos pais com relação ao ingresso do primogênito na escola de ensino fundamental. Refere-se às questões transgeracionais que se fazem presentes na história escolar do filho, que antes pertenceram à história escolar dos pais. Constrói-se seguindo a abordagem qualitativa, de natureza exploratória centrada na abordagem sistêmica, que permite ultrapassar o modelo linear de causa e efeito em favor de um modelo circular. O eixo básico da investigação versa sobre sentimentos e expectativas de pais de primogênitos que ingressam na escola de educação fundamental. A história da relação com a criança, enfocando o apego, os cuidados e a separação entre pais e filhos, foram questões norteadoras na entrevista semi estruturada, que foi o instrumento utilizado para a coleta de informações. O método que possibilitou se chegar aos resultados foi o de estudo de caso coletivo, que num primeiro momento, privilegiou as questões singulares e posteriormente os aspectos comuns aos quatro casos. Os sujeitos que participaram diretamente do estudo foram quatro casais de pais de primogênitos que freqüentam pela primeira vez a primeira série na escola de ensino fundamental e, sendo sujeitos indiretos, as quatro crianças e suas respectivas professoras. Todas as crianças têm entre seis e sete anos da idade, freqüentavam a mesma escola de ensino particular na zona urbana. Todos os casais são pais biológicos e estão no primeiro casamento Os resultados encontrados evidenciam que se pode encontrar a presença das histórias das famílias de origem de ambos os pais na história escolar de cada caso estudado. Os pais conservam o registro de como seus pais os educaram - os valores, as crenças, os legados e a arte de educar naquela família - bem como carregam até seus filhos expectativas de seus pais em relação aos filhos não cumpridas por eles em suas infâncias. A mãe e o pai são espelhos extremamente importantes na vida do filho. No entanto, às vezes, são necessários alguns ajustes nesses espelhos, os quais passam a refletir mais a história dos pais, do que a dos filhos em sua individualidade. Com esse estudo, foi possível evidenciar que a própria evolução da criança na escola foi um fator que propiciou um ajuste das expectativas dos pais em relação ao desempenho escolar do filho . Quanto à escola, pôde ser confirmada a necessidade da articulação entre ela e a família para privilegiar junto com o cognitivo, também os aspectos emocionais dos alunos. Os profissionais da educação necessitam ter clareza de que, ao cumprir a função de transmissora de conhecimentos, lidam paralelamente com outros aspectos do desenvolvimento, como por exemplo, o emocional, que está diretamente relacionado ao aspecto cognitivo. / The study on parenta! feelings and explications conceming the first-bom child's entry in formal school. It refers to transgenerational questions in the child's school story, which before belong to the parents school story. It follows a qualitative approach, of an exploratory nature, which enables to overcome a causal linear model in favor of a circular model. The basic investigative axis is centered on parental feelings and expectations regarding their first-bom child who was starting formal education. The father's and mother's school history, as well as the history of the relationship with the child, focusing on attachment, care and separation between parents and child were the main questions of a semi-structured interview. The method used was collective case study wich explored first the particular and then the common aspects of ali cases. The subjects took part in the study were four couples of firstbom who were in first grade of formal education, and indirectly the four children and their teachers. Ali children were around six and seven years old were in the same private school in an urban area. Ali couples were biological parents and were and the first marriage. The results show that it is possible to find features of the parents family of origin history in the school history of each case studied. The parents keep a record o f how they were educated by their parents - the values, beliefs, legacies and art o f educating in that family - and bring to their children their own parents unfulfilled expectations regarding their children The mother and the father are very important mirrors in the child's life. However, sometimes it is necessary to make some readjustment I these mirrors as they star to reflect more the parents' expectations conceming the child's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account the child 's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account child 's emotional apart from the cognitives aspects. The education professionals need to be aware that, in transmitting knowledge, they deal with other developmental features, such as for example, the emotional, wich is directly associated with the cognitive.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A exposição materna durante o período gestacional a uma dieta restrita em proteínas (LP) prejudica o desenvolvimento do pâncreas endócrino em sua prole e aumenta a susceptibilidade à hipertensão, diabetes e obesidade na vida adulta. Há evidências de que esse fenômeno pode persistir em gerações subsequentes. Objetivou-se avaliar o efeito da restrição proteica sobre o metabolismo da glicose e morfometria pancreática na prole F3 de camundongos ao nascimento e ao desmame. Para tanto, fêmeas virgens de camundongos Suíços (F0) foram acasaladas e receberam dieta normo-proteica (19% de proteína - NP) ou uma dieta isocalórica restrita em proteínas (5% de proteína - LP) durante toda a gravidez. Durante a lactação e o restante do experimento, todos os grupos receberam a dieta NP. Os filhotes machos foram nomeados F1 (NP1 e LP1). As fêmeas F1 e F2 foram acasaladas para produzir F2 e F3 (NP2, LP2, NP3 e LP3), respectivamente. Semanalmente, os filhotes foram pesados e calculada a taxa de crescimento alométrico (log [massa corporal] = log a + log b [idade]). Os animais foram sacrificados nos dias 1 e 21 de idade, a glicemia foi determinada e o pâncreas retirado, pesado e analisado por estereologia e imunofluorescência; a insulina foi mensurada aos 21 dias. Como resultados, os filhotes restritos na primeira geração (LP1) foram menores ao nascer, mas apresentaram um crescimento acelerado nos primeiros sete dias de vida, mostrando catch-up com os controles; a prole LP2 demonstrou a maior massa corporal ao nascimento e tiveram uma taxa de crescimento mais lenta durante a lactação; não houve diferença na massa corporal e na taxa de crescimento na geração F3. A massa de pâncreas foi diminuída em LP1-LP3 ao nascimento, contudo foi aumentada em LP2 ao desmame. A densidade de volume e o diâmetro das ilhotas foram menores em todos os grupos restritos no dia 1 e 21, somente LP1 teve o menor número de ilhotas. Ao nascer, a massa de células beta foi menor em LP1-LP3 e permaneceu baixa durante a lactação. No dia 1 e 21, os filhotes foram normoglicêmicos, entretanto foram hipoinsulinêmicos ao desmame. Portanto, a restrição de proteínas em camundongos durante a gestação produz alterações morfológicas nas ilhotas pancreáticas, sugerindo que a homeostase da glicose foi mantida por um aumento da sensibilidade à insulina durante os primeiros estágios de vida na prole ao longo de três gerações consecutivas. / Exposure of pregnant mice to a low-protein (LP) diet impairs endocrine pancreas development in their offspring and increases susceptibility to hypertension, diabetes and obesity in adulthood. There is evidence that this phenomenon may persist in subsequent generations. We sought to evaluate the effect of protein restriction on glucose metabolism and pancreatic morphometry in the F3 offspring of mice at birth and weaning. Virgin female Swiss mice (F0) were mated and received normal protein diet (19% protein - NP) or an isocaloric low protein diet (5% protein - LP) throughout pregnancy. Lactation and the rest of the experimental groups received NP diet. The male pups were named F1 (NP1 and LP1). F1 and F2 females were mated to produce F2 and F3 (NP2, LP2, NP3 and LP3). Weekly, pups were weighted and calculated the growth rate by allometry (log [body mass] = log a + b log [age]). The mice were sacrificed on days 1 and 21 of age, blood glucose was measured and the pancreas removed, weighed and analyzed by stereology and immunofluorescence, insulin was measured at 21 days. LP pups in the first generation (LP1) were smaller at birth, but had an accelerated growth and within 7 days catch-up growth with controls; LP2 offspring had higher body mass at birth and had a slower growth rate within 21 days; but there was no difference in body mass and growth rate in the F3 generation. The pancreatic mass decreased in LP1 through LP3 at birth but increased in LP2 at weaning. The islet volume density and diameter were smaller in all restricted groups at day 1 and 21, and LP1 had the lowest islet number; at birth, beta cell mass was smaller in LP1 through LP3 and remained low throughout suckling. At day 1 and 21, pups were normoglycemic, but were hypoinsulinemic at weaning. Thus, protein restriction in mice during pregnancy produces morphologic changes in pancreatic islets, suggesting that glucose homeostasis is maintained by an increased sensitivity to insulin during the early stages of life in offspring over three consecutive generations.

Pour les descendants des survivants du génocide arménien de 1915, les traumatismes actuels, liés à la confrontation aux épreuves du vieillissement et à l’hospitalisation, ont un effet attracteur des traumatismes transgénérationnels. Ces traumatismes génocidaires non subjectivés, transmis au travers des générations, tentent de prendre forme et sens, trouvant dans le présent du vieillissement une « correspondance hallucinatoire » (après-coup). Ces patients ont en commun d’avoir vécu une accumulation de traumas au cours de leurs vies : le deuil, la dépendance, la passivation, la crainte de mourir, rencontrés aujourd’hui, ont déjà fait partie de leur histoire individuelle et ont déjà induit dans le passé d’autres après-coups des traumatismes transgénérationnels. À l’heure du vieillissement, dans la psyché du patient, on assiste à un processus de « feuilletage traumatique », où les différents temps traumatiques présents, passés et transgénérationnels, résonnent et s’intriquent. Les entretiens cliniques sont l’occasion pour ces sujets de retrouver et de partager les mythes familiaux dont ils sont porteurs : en appui sur cet héritage mythique, ce feuilletage peut se « dé-collapser », la psyché réussissant alors à s’approprier l’expérience traumatique qui s’inscrit dans une histoire. Du feuilletage traumatique, d’abord inerte, peuvent advenir des remaniements psychiques remobilisés par la fonction transformatrice du mythe. Dans d’autres cas, les mythes familiaux ont, dans la psyché, une fonction davantage protectrice que transformatrice et le travail thérapeutique consiste à ranimer ce mythe figé, pour le réinscrire dans un mouvement dynamique. Ailleurs, on assiste aux efforts du sujet pour créer un mythe, à défaut de pouvoir en retrouver dans la mémoire. Les transferts parentaux et filiaux permettent de remettre au travail et de relancer, dans la relation thérapeutique, la transmission entre les générations. Les patients peuvent ainsi redonner vie, retrouver du sens à leur fin de vie et continuer à s’inscrire dans une « co-transmission » avec leur descendance. / For the descendants of the survivors of the 1915 Armenian genocide, the current traumas connected with the painful experience of ageing and hospital care have a drawing power on transgenerational trauma. Such traumas, passed on through generations, attempt to take shape finding a “hallucinatory correspondence” in the present ageing experience (deferred action). These subjects share the common experience of superposition of traumas that they have gone through all along their lives: bereavement, dependence, the constraint passivity, the fear of death, which are confronted with today, have already been part of their individual history and have already induced, in the past, other deferred actions ascribable to transgenerational traumas. When comes the time of ageing, in the patient’s psyche, we witness a process of “traumatic superposition” whereby the interplay of various traumatic times-present, past, and transgenerational resonate and become closely enmeshed. Psychological interviews conducted by the practitioner provide such subjects with the opportunity to revisit and to share the family myths which they carry within themselves. Relying on this mythical legacy, the superposition may “de-collapse itself”, the psyche succeeding in appropriating the traumatic experience that lies within the scope of a history. From the traumatic superposition, which is initially inert, there can happen psychic reorganisations which are mobilized anew by the transforming function of the myth. In other cases, family myths have within the psyche, a function more protective than transforming and the therapy consists in reviving this frozen myth in order to place it again within the frame of a dynamic movement. In other cases, what we may observe is the subject’s endeavour to create myth of his or her own for lack of being able to trace it backing his or her memory. Parental or filial transference makes it possible to start up and to stimulate again the transmission between generations within the therapeutic relationship. So doing, the patients can restore life; give back significance to the end of their lives and keep in line with a co-transmission with their descendants.

Les facteurs environnementaux, tels que les pesticides, peuvent induire des changements phénotypiques dans une variété d'organisme incluant les mammifères. Nous avons étudié chez la souris les effets d'un pesticide largement utilisé, l'atrazine (ATZ), sur la méiose, une étape clé du processus de spermatogenèse. L'utilisation des méthodes de puces à ADN (Gene-Chip) et de séquençage de chromatine immunoprécipité (ChIP-seq) nous a permis de mettre en évidence l'effet de l'ATZ sur une variété de fonctions cellulaires, incluant l'activité GTPase, la fonction mitochondriale et le métabolisme des hormones stéroïdes. De plus, les souris traitées présentent un enrichissement des marques d'histone H3K4me3 au niveau des régions de forte recombinaison (sites de cassures double brin) de gènes très long et une réduction de ces mêmes marques au niveau des régions pseudo-autosomal du chromosome X. Nos données démontrent que l'exposition à l'ATZ interfère avec le déroulement normal de la méiose, ceci affectant la production des spermatozoïdes. Nous avons trouvé que les marques H3K4me3, chez la souris mâle, sont largement affectées par l'ATZ grâce à l'utilisation de technique de séquençage du génome entier. La reprogrammation embryonnaire nécessite l'action coordonnée d'un grand nombre de gène et de facteurs épigénétiques afin de permettre la transition de cellules somatique en cellules germinales. Les modifications épigénétiques imposées pendant la transition des cellules somatiques en cellules germinales et affectées par des expositions nocives, peuvent être héritées et transmises aux générations suivantes via les gamètes. Dans cette étude, nous avons examiné l'héritage des histones modifié aux générations suivantes. Nous avons exposés des femelles gestantes CD1 non consanguines à l'ATZ et les mâles issus de ces femelles ont été croisés pendant trois générations avec des femelles non traitées. Nous avons démontré ici que l'exposition à l'ATZ réduit le nombre de spermatozoïdes sans affecter la morphologie cellulaire ou la proportion des différents types cellulaires constituant l'épithélium séminifère chez les individus issus de la 3ème génération après traitement. Beaucoup de gènes associés avec la réparation de l'ADN, la reproduction et les fonctions mitochondriales sont dérégulés chez les mâles issus de la 3ème génération après traitement. De façon importante, l'exposition à l'ATZ change dramatiquement l'initiation de la transcription, l'épissage et la polyadénylation alternative des ARN. Nous avons aussi observé chez les mâles F3 issus de souris traitées à l'ATZ une altération de la localisation des marques H3K4me3 dans le promoteur de gène associé à la régulation de processus métaboliques cellulaires, à la régulation de la transcription et à la mitose. Les changements de localisation des marques H3K4me3 chez les mâles F3 issus de souris traitées à l'ATZ correspondent à des changements de la localisation de ces marques au niveau de gènes impliqués dans la différenciation des cellules de type souche de la génération F1.Nos données suggèrent que l'héritage transgénérationnel est permis grâce à de multiples voies et repose sur le statut épigénétique de gènes impliqués dans la différenciation des cellules de type souches tels que Pou5f1 et Sox2, l'action des facteurs de transcription et la rétention d'histones dans le sperme. / Environmental factors such as pesticides can cause phenotypic changes in various organisms, including mammals. We studied the effects of the widely used herbicide atrazine (ATZ) on meiosis, a key step of gametogenesis, in male mice. We demonstrate that exposure to ATZ reduces testosterone levels and the number of spermatozoa in the epididymis and delays meiosis. Using Gene-Chip and ChIP-Seq analysis of H3K4me3 marks, we found that a broad range of cellular functions, including GTPase activity, mitochondrial function and steroid-hormone metabolism, are affected by ATZ. Furthermore, treated mice display enriched histone H3K4me3 marks in regions of strong recombination (double-strand break sites), within very large genes and reduced marks in the pseudoautosomal region of X chromosome. Our data demonstrate that atrazine exposure interferes with normal meiosis, which affects spermatozoa production.We found that the H3K4me3 marks in male mice are broadly affected by the widely used herbicide atrazine with genome wide ChIP-sequencing. Embryonic reprogramming requires the coordinated action of many genes and epigenetic factors to perform somatic to germline transition. The epigenetic modifications imposed during somatic to germline transition and affected by harmful exposure can be inherited and transferred to subsequent generations via the gametes. In this study, we examine the inheritance of altered histone modifications by subsequent generations. We exposed pregnant outbred CD1 female mice to the widely used herbicide atrazine (ATZ), and the male progeny were crossed for three generations with untreated females. We demonstrate here that exposure to ATZ reduces the number of spermatozoa without changing the cell morphology or types in testis tissue in the third generation after treatment. Many genes associated with DNA repair, reproduction and mitochondrial function became dysregulated in the third generation (F3) of males after treatment. Importantly, exposure to ATZ dramatically changes the transcription initiation, splicing and alternative polyadenylation of RNA. We also observed altered occupancy of H3K4me3 markers in the F3 generation of ATZ-derived males in gene promoters associated with the regulation of cellular metabolic processes, transcriptional regulation and mitosis. The changes in H3K4me3 occupancy in F3 ATZ-derived males correspond to changes in the H3K4me3 occupancy of stem cell differentiation genes in the F1 generation. Our data suggest that transgenerational inheritance is accomplished through multiple pathways and relies on the epigenetic state of stem cell differentiation genes such as Pou5f1 and Sox2, transcription factor action and sperm histone retention.

Childhood sexual abuse (CSA) has been linked to a number of adverse effects in adulthood including higher levels of depression, shame, guilt, self-blame, somatic concerns, anxiety, dissociation, repression, denial, relationship problems, and sexual problems. Little is known, however, about the influence CSA has on parenting, specifically among African American mothers, as previous researchers have primarily focused on the trauma experienced by survivors. Examining the impact of CSA on African American mothers' parenting is important as those children of survivors will often also experience the impact of the long-term sequelae associated with CSA. Guided by womanist theory, the purpose of this hermeneutic phenomenological qualitative inquiry was to explore the lived experiences in relation to parenting of African American mothers who survived CSA. Experiential anecdotes of data collected from interviews with 7 participants were hand coded for emergent themes; analysis generated 4 essential themes and 10 subthemes of experience. Themes included impact of abuse, bonding, efforts to protect, spirituality, and desires. This study's implications for positive social change include contributing to the knowledge base about the process of parenting experienced by African American female survivors of CSA. Findings may add insight shedding light on cultural nuances in parenting and coping with trauma and inform culturally-competent practice. Using study findings, mental health providers may be able to develop tailored treatment interventions and better support services for the prevention of adverse long-term effects of CSA in African American women.

La psychanalyse est-elle épistémologiquement dans l’impasse ? Les «Japonais» (Lacan) ou encore les Arabes ne sont-ils pas «psychanalysables» ? Ce sont deux malaises qui ont concomitamment motivé cette recherche. Celle-ci découvre alors la «psychanalyse du lien» à laquelle elle suppose un potentiel de résolution de la double crise de la psychanalyse : celle qui lui est intrinsèque et a trait à sa longévité et celle de la rencontre entre cette dernière et des champs opérationnels d’accueil. Analyser les liens plutôt que des sujets en lien révolutionne la métapsychologie classique en la décentrant du pur intrapsychique, lénifiant ainsi son panindividualisme et promettant une «rencontre équitable» entre la psychanalyse et son terrain d’accueil, le tunisien en l’occurrence. La pratique de ce paradigme auprès de couples et de familles tunisiens en situations de recherche et de consultation, alternant au besoin, entretiens individuel, de couple et de famille, génosociogramme commenté, FAT ou encore TAT, permet de déceler des configurations liennaires récurrentes et caractéristiques colorant, par l’Instance culturelle (Kaës, 1998), l’espace du lien. Sont alors identifiés et définis les Objets-reliques, la Co-maternité et le Bel-Oedipe comme émergents du contexte informant respectivement sur les liens généalogique, parento-filial et de couple. C’est ainsi qu’une psychanalyse des liens de couple et de famille ouvre la voie à une lecture conjointe de trois espaces intra, inter et transsubjectif où le travail de subjectivation «se déroule» en même temps qu’elle incite à s’interroger sur les liens, leur nouage et défaillances aux prises avec le contexte culturel. / Is psychoanalysis epistemologically deadlocked? Aren’t the "Japanese" (Lacan) or the Arabs "psychoanalysable"? These are two discomforts that simultaneously motivated this research. It found out the "link psychoanalysis" in which it supposes a potential to resolve the double crisis of psychoanalysis: the intrinsic one related to its longevity and that of the encounter between the latter and the operational hosting fields. Analysing the link rather than subjects in link revolutionized classical metapsychology by offsetting the pure intrapsychic thus soothing its panindividualism and promising an « equitable encounter » between psychoanalysis and its host ground, the Tunisian one in this case. The practice of this « paradigm » with tunisian couples and families in contexts of research and consultation, alternating, on need, individual, couple and family interviews, commented genosociograms, FAT or TAT allowed to detect recurrent and characteristic link configurations, in which Cultural Instance (Kaës, 1998) colours neatly the link space. Thus, could be identified and defined the Relic objects, Co-motherhood and Oedipus-in-law as context emergents informing respectively about genealogical, parental-filial and couple links. That is how a couple and family link psychoanalysis paves the way to a joint reading of three spaces: intra, inter and transsubjective where the subjectivation work occurs. At the same time, it raises questions about link-knitting and failures dealing with the cultural context.

O estudo aborda os sentimentos e as expectativas dos pais com relação ao ingresso do primogênito na escola de ensino fundamental. Refere-se às questões transgeracionais que se fazem presentes na história escolar do filho, que antes pertenceram à história escolar dos pais. Constrói-se seguindo a abordagem qualitativa, de natureza exploratória centrada na abordagem sistêmica, que permite ultrapassar o modelo linear de causa e efeito em favor de um modelo circular. O eixo básico da investigação versa sobre sentimentos e expectativas de pais de primogênitos que ingressam na escola de educação fundamental. A história da relação com a criança, enfocando o apego, os cuidados e a separação entre pais e filhos, foram questões norteadoras na entrevista semi estruturada, que foi o instrumento utilizado para a coleta de informações. O método que possibilitou se chegar aos resultados foi o de estudo de caso coletivo, que num primeiro momento, privilegiou as questões singulares e posteriormente os aspectos comuns aos quatro casos. Os sujeitos que participaram diretamente do estudo foram quatro casais de pais de primogênitos que freqüentam pela primeira vez a primeira série na escola de ensino fundamental e, sendo sujeitos indiretos, as quatro crianças e suas respectivas professoras. Todas as crianças têm entre seis e sete anos da idade, freqüentavam a mesma escola de ensino particular na zona urbana. Todos os casais são pais biológicos e estão no primeiro casamento Os resultados encontrados evidenciam que se pode encontrar a presença das histórias das famílias de origem de ambos os pais na história escolar de cada caso estudado. Os pais conservam o registro de como seus pais os educaram - os valores, as crenças, os legados e a arte de educar naquela família - bem como carregam até seus filhos expectativas de seus pais em relação aos filhos não cumpridas por eles em suas infâncias. A mãe e o pai são espelhos extremamente importantes na vida do filho. No entanto, às vezes, são necessários alguns ajustes nesses espelhos, os quais passam a refletir mais a história dos pais, do que a dos filhos em sua individualidade. Com esse estudo, foi possível evidenciar que a própria evolução da criança na escola foi um fator que propiciou um ajuste das expectativas dos pais em relação ao desempenho escolar do filho . Quanto à escola, pôde ser confirmada a necessidade da articulação entre ela e a família para privilegiar junto com o cognitivo, também os aspectos emocionais dos alunos. Os profissionais da educação necessitam ter clareza de que, ao cumprir a função de transmissora de conhecimentos, lidam paralelamente com outros aspectos do desenvolvimento, como por exemplo, o emocional, que está diretamente relacionado ao aspecto cognitivo. / The study on parenta! feelings and explications conceming the first-bom child's entry in formal school. It refers to transgenerational questions in the child's school story, which before belong to the parents school story. It follows a qualitative approach, of an exploratory nature, which enables to overcome a causal linear model in favor of a circular model. The basic investigative axis is centered on parental feelings and expectations regarding their first-bom child who was starting formal education. The father's and mother's school history, as well as the history of the relationship with the child, focusing on attachment, care and separation between parents and child were the main questions of a semi-structured interview. The method used was collective case study wich explored first the particular and then the common aspects of ali cases. The subjects took part in the study were four couples of firstbom who were in first grade of formal education, and indirectly the four children and their teachers. Ali children were around six and seven years old were in the same private school in an urban area. Ali couples were biological parents and were and the first marriage. The results show that it is possible to find features of the parents family of origin history in the school history of each case studied. The parents keep a record o f how they were educated by their parents - the values, beliefs, legacies and art o f educating in that family - and bring to their children their own parents unfulfilled expectations regarding their children The mother and the father are very important mirrors in the child's life. However, sometimes it is necessary to make some readjustment I these mirrors as they star to reflect more the parents' expectations conceming the child's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account the child 's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account child 's emotional apart from the cognitives aspects. The education professionals need to be aware that, in transmitting knowledge, they deal with other developmental features, such as for example, the emotional, wich is directly associated with the cognitive.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A exposição materna durante o período gestacional a uma dieta restrita em proteínas (LP) prejudica o desenvolvimento do pâncreas endócrino em sua prole e aumenta a susceptibilidade à hipertensão, diabetes e obesidade na vida adulta. Há evidências de que esse fenômeno pode persistir em gerações subsequentes. Objetivou-se avaliar o efeito da restrição proteica sobre o metabolismo da glicose e morfometria pancreática na prole F3 de camundongos ao nascimento e ao desmame. Para tanto, fêmeas virgens de camundongos Suíços (F0) foram acasaladas e receberam dieta normo-proteica (19% de proteína - NP) ou uma dieta isocalórica restrita em proteínas (5% de proteína - LP) durante toda a gravidez. Durante a lactação e o restante do experimento, todos os grupos receberam a dieta NP. Os filhotes machos foram nomeados F1 (NP1 e LP1). As fêmeas F1 e F2 foram acasaladas para produzir F2 e F3 (NP2, LP2, NP3 e LP3), respectivamente. Semanalmente, os filhotes foram pesados e calculada a taxa de crescimento alométrico (log [massa corporal] = log a + log b [idade]). Os animais foram sacrificados nos dias 1 e 21 de idade, a glicemia foi determinada e o pâncreas retirado, pesado e analisado por estereologia e imunofluorescência; a insulina foi mensurada aos 21 dias. Como resultados, os filhotes restritos na primeira geração (LP1) foram menores ao nascer, mas apresentaram um crescimento acelerado nos primeiros sete dias de vida, mostrando catch-up com os controles; a prole LP2 demonstrou a maior massa corporal ao nascimento e tiveram uma taxa de crescimento mais lenta durante a lactação; não houve diferença na massa corporal e na taxa de crescimento na geração F3. A massa de pâncreas foi diminuída em LP1-LP3 ao nascimento, contudo foi aumentada em LP2 ao desmame. A densidade de volume e o diâmetro das ilhotas foram menores em todos os grupos restritos no dia 1 e 21, somente LP1 teve o menor número de ilhotas. Ao nascer, a massa de células beta foi menor em LP1-LP3 e permaneceu baixa durante a lactação. No dia 1 e 21, os filhotes foram normoglicêmicos, entretanto foram hipoinsulinêmicos ao desmame. Portanto, a restrição de proteínas em camundongos durante a gestação produz alterações morfológicas nas ilhotas pancreáticas, sugerindo que a homeostase da glicose foi mantida por um aumento da sensibilidade à insulina durante os primeiros estágios de vida na prole ao longo de três gerações consecutivas. / Exposure of pregnant mice to a low-protein (LP) diet impairs endocrine pancreas development in their offspring and increases susceptibility to hypertension, diabetes and obesity in adulthood. There is evidence that this phenomenon may persist in subsequent generations. We sought to evaluate the effect of protein restriction on glucose metabolism and pancreatic morphometry in the F3 offspring of mice at birth and weaning. Virgin female Swiss mice (F0) were mated and received normal protein diet (19% protein - NP) or an isocaloric low protein diet (5% protein - LP) throughout pregnancy. Lactation and the rest of the experimental groups received NP diet. The male pups were named F1 (NP1 and LP1). F1 and F2 females were mated to produce F2 and F3 (NP2, LP2, NP3 and LP3). Weekly, pups were weighted and calculated the growth rate by allometry (log [body mass] = log a + b log [age]). The mice were sacrificed on days 1 and 21 of age, blood glucose was measured and the pancreas removed, weighed and analyzed by stereology and immunofluorescence, insulin was measured at 21 days. LP pups in the first generation (LP1) were smaller at birth, but had an accelerated growth and within 7 days catch-up growth with controls; LP2 offspring had higher body mass at birth and had a slower growth rate within 21 days; but there was no difference in body mass and growth rate in the F3 generation. The pancreatic mass decreased in LP1 through LP3 at birth but increased in LP2 at weaning. The islet volume density and diameter were smaller in all restricted groups at day 1 and 21, and LP1 had the lowest islet number; at birth, beta cell mass was smaller in LP1 through LP3 and remained low throughout suckling. At day 1 and 21, pups were normoglycemic, but were hypoinsulinemic at weaning. Thus, protein restriction in mice during pregnancy produces morphologic changes in pancreatic islets, suggesting that glucose homeostasis is maintained by an increased sensitivity to insulin during the early stages of life in offspring over three consecutive generations.

O estudo aborda os sentimentos e as expectativas dos pais com relação ao ingresso do primogênito na escola de ensino fundamental. Refere-se às questões transgeracionais que se fazem presentes na história escolar do filho, que antes pertenceram à história escolar dos pais. Constrói-se seguindo a abordagem qualitativa, de natureza exploratória centrada na abordagem sistêmica, que permite ultrapassar o modelo linear de causa e efeito em favor de um modelo circular. O eixo básico da investigação versa sobre sentimentos e expectativas de pais de primogênitos que ingressam na escola de educação fundamental. A história da relação com a criança, enfocando o apego, os cuidados e a separação entre pais e filhos, foram questões norteadoras na entrevista semi estruturada, que foi o instrumento utilizado para a coleta de informações. O método que possibilitou se chegar aos resultados foi o de estudo de caso coletivo, que num primeiro momento, privilegiou as questões singulares e posteriormente os aspectos comuns aos quatro casos. Os sujeitos que participaram diretamente do estudo foram quatro casais de pais de primogênitos que freqüentam pela primeira vez a primeira série na escola de ensino fundamental e, sendo sujeitos indiretos, as quatro crianças e suas respectivas professoras. Todas as crianças têm entre seis e sete anos da idade, freqüentavam a mesma escola de ensino particular na zona urbana. Todos os casais são pais biológicos e estão no primeiro casamento Os resultados encontrados evidenciam que se pode encontrar a presença das histórias das famílias de origem de ambos os pais na história escolar de cada caso estudado. Os pais conservam o registro de como seus pais os educaram - os valores, as crenças, os legados e a arte de educar naquela família - bem como carregam até seus filhos expectativas de seus pais em relação aos filhos não cumpridas por eles em suas infâncias. A mãe e o pai são espelhos extremamente importantes na vida do filho. No entanto, às vezes, são necessários alguns ajustes nesses espelhos, os quais passam a refletir mais a história dos pais, do que a dos filhos em sua individualidade. Com esse estudo, foi possível evidenciar que a própria evolução da criança na escola foi um fator que propiciou um ajuste das expectativas dos pais em relação ao desempenho escolar do filho . Quanto à escola, pôde ser confirmada a necessidade da articulação entre ela e a família para privilegiar junto com o cognitivo, também os aspectos emocionais dos alunos. Os profissionais da educação necessitam ter clareza de que, ao cumprir a função de transmissora de conhecimentos, lidam paralelamente com outros aspectos do desenvolvimento, como por exemplo, o emocional, que está diretamente relacionado ao aspecto cognitivo. / The study on parenta! feelings and explications conceming the first-bom child's entry in formal school. It refers to transgenerational questions in the child's school story, which before belong to the parents school story. It follows a qualitative approach, of an exploratory nature, which enables to overcome a causal linear model in favor of a circular model. The basic investigative axis is centered on parental feelings and expectations regarding their first-bom child who was starting formal education. The father's and mother's school history, as well as the history of the relationship with the child, focusing on attachment, care and separation between parents and child were the main questions of a semi-structured interview. The method used was collective case study wich explored first the particular and then the common aspects of ali cases. The subjects took part in the study were four couples of firstbom who were in first grade of formal education, and indirectly the four children and their teachers. Ali children were around six and seven years old were in the same private school in an urban area. Ali couples were biological parents and were and the first marriage. The results show that it is possible to find features of the parents family of origin history in the school history of each case studied. The parents keep a record o f how they were educated by their parents - the values, beliefs, legacies and art o f educating in that family - and bring to their children their own parents unfulfilled expectations regarding their children The mother and the father are very important mirrors in the child's life. However, sometimes it is necessary to make some readjustment I these mirrors as they star to reflect more the parents' expectations conceming the child's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account the child 's school performance. As far as school is concemed, it is important that school recognizes the importance of its articulation with the family so as to take into account child 's emotional apart from the cognitives aspects. The education professionals need to be aware that, in transmitting knowledge, they deal with other developmental features, such as for example, the emotional, wich is directly associated with the cognitive.