Chez les mammifères, la détermination du sexe permet à un organe bipotentiel, la gonade, de se différencier en ovaire ou en testicule. Nrg1 (Neuregulin 1) est un facteur de croissance qui agit par phosphorylation de protéines cibles. Chez la souris, Nrg1 est nécessaire à la fertilité des adultes. Les mutants perte de fonction présente une hypoplasie testiculaire. Cependant, Nrg1 est exprimé dans la gonade embryonnaire, ce qui suggère son rôle précoce dans le développement de cet organe. Son rôle durant la gonadogenèse restait encore à établir. Mes travaux ont montré que Nrg1 est impliqué dans la prolifération des précurseurs des cellules de Sertoli chez le mâle, dans l’établissement de la vascularisation et par conséquent l’organisation des cordons testiculaires. Ce phénotype est aggravé en l’absence d’expression du gène Rspo1, un facteur qui stimule également la prolifération des précurseurs des cellules de Sertoli. Cela suggère une fonction additive entre les voies de signalisation contrôlées par Nrg1 et Rspo1 au cours du développement testiculaire. Chez les femelles, les mutants Nrg1 présentent une hypoplasie ovarienne et une réduction de la fertilité. Cela est associé à des cellules germinales atypiques. L’impact de ce phénotype sur la fertilité reste à déterminer. Mmd2 est spécifiquement exprimé dans le testicule mais son rôle est encore inconnu. Pour le déterminer durant la gonadogenèse, j’ai généré des modèles murins de perte de fonction par le système CRISPR-Cas9. Les premiers résultats montrent des cellules somatiques apoptotiques dans les testicules de ce modèle murin. Ces études restent cependant préliminaires et les causes de ce phénotype à élucider. / In mammals, sex determination allows a bipotential organ, the gonad, to differentiate into either an ovary or a testis. NRG1 (Neuregulin 1) is a growth factor that promotes phosphorylation of target proteins. In mice, Nrg1 is required for adult fertility. Loss-of-function mutants exhibit testicular hypoplasia. Nrg1 is expressed in embryonic gonads, suggesting an early role in the formation of this organ. However this role remained to be analysed. Here I show that Nrg1 is involved in the proliferation of precursors of Sertoli cells in male. It is also involved in the establishment of the vasculature and in turn partitioning of testis cords. This phenotype is more severe in the absence of Rspo1 expression. RSPO1 signalling also enhances proliferation of precursors of Sertoli cells. This suggests an additive function between the signalling pathways controlled by Nrg1 and Rspo1 during testicular development. In female, Nrg1 mutant ovaries exhibit hypoplasia and reduced fertility. This is associated with atypical germ cells. The relevance of this phenotype on fertility remains to be determined. Mmd2 is specifically expressed in testis but its role is still unknown. To investigate Mmd2 function, I have generated loss-of-function mouse models using the CRISPR-cas9 system. Preliminary results show apoptotic somatic cells in the testes of these mice. However, the causes of this phenotype remain to be clarified.

No description available.

Thesis (doctoral)--University of Göteborg, 1983. / Extra t.p. with thesis statement inserted. Includes the author's seven published papers. Includes bibliographical references.

Thesis (doctoral)--University of Göteborg, 1983. / Extra t.p. with thesis statement inserted. Includes the author's seven published papers. Includes bibliographical references.

Orientador: Maria Valeriana Leme de Moura-Ribeiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T01:57:00Z (GMT). No. of bitstreams: 1 Franco_KatiaMariaDmytraczenko_M.pdf: 2999636 bytes, checksum: 50217c1194a5170e4458815b3e813e2b (MD5) Previous issue date: 2007 / Resumo: O objetivo deste estudo observacional com grupo controle foi: a) verificar a presença de defeitos de desenvolvimento do esmalte (DDE) em dentes decíduos de crianças nascidas pré-termo (PT) e com baixo peso, e um grupo controle de nascidos a termo e com peso normal; b) investigar possíveis fatores etiológicos pré-natais e neonatais associados à presença dos DDE; c) situar as hipoplasias, de acordo com sua localização, como pré-natais ou pós-natais, segundo tabelas de cronologia de mineralização. Cada grupo foi formado por 61 crianças, examinadas entre 18 ¿ 35 meses de idade; todas nascidas no Centro de Atenção Integral à Saúde da Mulher ¿ Universidade Estadual de Campinas. Foi adotado o critério da FDI para a avaliação odontológica. Os dados da história médica foram colhidos retrospectivamente do prontuário do hospital. A análise estatística dos dados foi realizada através dos testes de Mann-Whitney, qui-quadrado e exato de Fisher. A freqüência encontrada entre pré-termos foi 57.4% de DDE, 52.5 % de opacidades e 21.3 % de hipoplasia. No grupo controle, 24.6% apresentaram DDE, 24.6% tiveram opacidades e 3.3%, hipoplasia. Os DDE estiveram significativamente associados com o nascimento PT e com baixo peso (p <0.001). Após a regressão logística multivariada, a apnéia permaneceu como a variável mais associada aos DDE. Pode-se concluir que crianças nascidas PT e com baixo peso apresentaram maior prevalência de DDE que aquelas nascidas a termo e com peso normal. O fator neonatal apnéia teve associação significativa com DDE. No entanto, cumpre ressaltar que utilizando os DDE como marcadores biológicos, estes defeitos localizados na porção de esmalte formado no período pré-natal indicam uma agressão sistêmica ocorrida neste período. Existem muitos aspectos a serem considerados na prematuridade ou no recém-nascido submetido a um processo hipóxico-isquêmico. Os DDE, utilizados como marcadores biológicos, podem ser um dado a mais na compreensão dos fatores sistêmicos envolvidos na prematuridade ou na lesão do SNC e suas conseqüências / Abstract: The purpose of this observational study with control group was: a) verify the presence of developmental enamel defects (DDE) in deciduous teeth of infants born preterm (PT) and with low birthweight and in a control group of infants born full term and with normal birthweight; b) investigate possible prenatal and postnatal etiologic factors associated with DDE; c) classify hypoplasias according to their location as prenatal or postnatal, following mineralization tables. Each group was formed by 61 children, examined between 18 and 35 months of age; all born at the Center for Integral Assistance to Women¿s Health ¿ State University of Campinas. FDI criteria were followed for dental examination. Medical data was collected retrospectively from hospital records. The statistic analysis was performed with the Mann-Whitney, chi-square and Fisher¿s exact test, wherever appropriate. Among preterms, 57.4% had some type of DDE, 52.5 % had opacities and 21.3 % presented hypoplasia. Among full terms, 24.6% presented DDE, 24.6% had opacities and 3.3% had hypoplasia. DDE were significantly associated with preterm birth and low birth weight (p< 0.001). After the multivariate logistic regression, apnea remained as the variable most strongly associated with DDE. Concluding, infants born preterm and with low birthweight presented a higher prevalence of DDE than those born full term and with normal birth weight. The neonatal variable apnea presented a statistically significant association with DDE. Nevertheless, using DDE as biological markers, the defects observed in the tooth enamel formed during the neonatal period indicate that a systemic insult occurred in this period. There are many aspects that must be considered in prematurity and in infants that suffered hypoxic ischemic insults. DDE, used as biological markers, may be an additional element in the study of the variety of factors involved in prematurity or insults to the Central Nervous System and its consequences / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

Although human congenital cerebellar malformations are common, their molecular and developmental basis is still poorly understood. Recently, cilia-related gene deficiencies have been implicated in several congenital disorders that exhibit cerebellar abnormalities such as Joubert syndrome, Meckel-Gruber syndrome, Bardet-Biedl syndrome, and Orofaciodigital syndrome. The association of cilia gene mutations with these syndromes suggests that cilia may be important for cerebellar development, but the nature of cilia involvement has not been elucidated. To assess the importance of cilia-related proteins during cerebellar development, we studied the effects of CNS-specific inactivation of two mouse genes whose protein products are critical for cilia formation and maintenance, IFT88, (also known as polaris or Tg737), which encodes intraflagellar transport 88 homolog, and Kif3a, which encodes kinesin family member 3a. We showed that loss of either of these genes caused severe cerebellar hypoplasia and foliation abnormalities, primarily attributable to a failure of expansion of the neonatal granule cell progenitor population. In addition, granule cell progenitor proliferation was sensitive to partial loss of IFT function in a hypomorphic mutant of IFT88 (IFT88orpk), an effect that was modified by genetic background. IFT88 and Kif3a were not required for the specification and differentiation of most other cerebellar cell types, including Purkinje cells. Together, our observations constitute the first demonstration that cilia proteins are essential for normal cerebellar development and suggest that granule cell proliferation defects may be central to the cerebellar pathology in human cilia-related disorders.

Indiana University-Purdue University Indianapolis (IUPUI) / Microabrasion with PREMA Compound (Premier Dental Product Co., King of Prussia, Penn.) has been advocated for the removal of superficial enamel stains. This procedure eliminates stains by removing a microscopic layer of enamel. The objective of this study was to determine whether the use of PREMA microabrasion prior to orthodontic bonding affects the tensile bond strength of an adhesive precoated stainless steel orthodontic bracket. Sixty noncarious extracted human premolar teeth were randomly divided into three groups of 20 and stored in 3-percent buffered formalin solution. Group I was a control group that was etched and bonded in the usual manner. Group II received PREMA Compound microabrasion immediately prior to bonding. Group III received PREMA microabrasion followed by a six-week storage period prior to bonding. After bonding, specimens were thermocycled and stored in distilled water at 37 °C for 14 days. The specimens were then loaded to failure in the tensile mode of an Instron testing machine (Instron Corp., Canton, Mass.). A stress-breaking apparatus was utilized to minimize all forces other than tensile. The data was statistically analyzed using one-way analysis of variance at the 0.05 level. No statistically significant differences were found among the three groups. From these results it was concluded that microabrasion with PREMA did not affect bond strength. Enamel microabrasion can be provided prior to orthodontic treatment without any detriment to bracket bond strength.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21650号 / 医博第4456号 / 新制||医||1034(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 斎藤 通紀, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

No description available.