L’héritage épigénétique transgénérationnelle est un phénomène très controversé, selon lequel un phénotype non-génétiquement déterminé peut être transmis à la génération suivante. Jusqu'à présent, ce mode de transmission a été décrit dans quelques cas et il a été suggéré que les composants de la chromatine peuvent être impliqués, y compris des protéines du groupe Polycomb, qui agissent comme des répresseurs de gènes clés du développement et coordonnent la différenciation cellulaire et la prolifération. Les mécanismes moléculaires à la base du rôle de la répression génique Polycomb-dépendante à hérédité épigénétique transgénérationnelle sont loin d'être compris. Par conséquent, j’ai développé un système expérimental chez Drosophila melanogaster pour induire un héritage épigénétique transgénérationnelle stable, dans lequel des états d'expression génique alternatifs peuvent être transmis en présence de la même séquence d'ADN. A partir de ces « épilignes » stables, j’ai pu disséquer certaines des propriétés génétiques des épiallèles induits, tels que leur héritage quantitatif et leur capacité à communiquer à longue distance. En outre, les épiallèles montrent une synergie dans leur expression et transmission héréditaire. L'une des signatures moléculaires des épiallèles est une différence de répression médiée par les complexes Polycomb et par leur marque d’histone caractéristique. Cette distribution différente est indépendante de l’activité transcriptionnelles des gènes en aval, au moins dans un stade de développement précoce, et pourrait influer l'organisation tridimensionnelle du locus impliqué. Curieusement Ago2, un composant de la voie ARNi, a été montré interagir avec les épiallèles génétiquement et la protéine Ago2 se fixe directement à leur chromatine, ce qui indique un rôle possible pour le ncRNAs dans l'expression des épiallèles et éventuellement dans leur transmission. Ces résultats plaident en faveur e l’existence d’une hérédité épigénétique transgénérationnelle stable chez les métazoaires et fournissent un modèle qui se prête à une dissection moléculaire de ce phénomène. / Transgenerational epigenetic inheritance is a hotly debated phenomenon whereby a non-genetically determined phenotype can be transmitted to the next generation. So far, this mode of inheritance has been described in few cases and it was suggested that chromatin components might be involved, including Polycomb group proteins, which act as repressors of key developmental genes and coordinate cell differentiation and proliferation. The molecular mechanisms linking Polycomb-mediated silencing to transgenerational epigenetic inheritance are far from being understood. Therefore, I developed an experimental system in Drosophila melanogaster to induce stable transgenerational epigenetic inheritance, in which alternative gene expression states can be transmitted in the presence of the same DNA sequence. Starting from these highly stable “epilines”, I could dissect some of the genetic properties of the induced epialleles, such as their quantitative inheritance and their ability to trans-communicate. Moreover, the epialleles displayed synergy in their expression and transmission. One of the molecular signatures of the epialleles is the differential presence of the Polycomb repressive complexes and their related epigenetic marks. This different distribution is independent of the transcriptional activity of the downstream genes, at least in an early developmental stage, and could influence the three-dimensional organization of the locus involved. Intriguingly Ago2, an RNAi pathway component, has been found to genetically interact with the epialleles and to be directly bound on their chromatin, indicating a possible role for the ncRNAs in the expression of the epialleles and possibly in their transmission. These results make a case for strong and stable transgenerational epigenetic inheritance in metazoan and provide a model that is amenable for the molecular dissection of this phenomenon.

The thesis deals with the problems of inheritance law. The main goal is the comparison of its legal form in the current Civil Code and in the new Civil Code, followed by the analyzing and the evaluating of the changes. The thesis concentrates on both legal forms of inheritance law to fulfil this goal. These legal forms are compared after and the changes are analyzed to answer the question, whether these changes are beneficial for citizens, why this part of law was changed and what its deficiency and correction is.

Cette étude vise à décrire le rôle de l’héritage et de la segmentation associés au rifting pour la réactivation ainsi qu’à étudier l’importance de l’asymétrie tectonique sur l’évolution thermique syn-rift, en utilisant le système pyrénéo-cantabrique comme laboratoire naturel. L’étude de la jonction entre les segments pyrénéen et cantabrique infirme l’hypothèse d’une faille transformante de Pampelune et met en évidence une zone d’accommodation où les segments de rifts se propagent au nord et au sud des massifs basques, associée à une direction d’extension nord-sud. Lors de la convergence, cette segmentation et le niveau de découplage associé aux évaporites triasiques contrôlent fortement la réactivation ainsi que l’architecture orogénique locale. Enfin, cette étude démontre que l’asymétrie lors de l’hyper-étirement est associée à une évolution thermique asymétrique et diachrone, et souligne l’importance de l’évolution tectonique pour l’architecture thermique. / This study aims to describe the role of rift-inheritance and segmentation for reactivation and to investigate the influence of asymmetric rifting on the syn-rift thermal evolution, using the Pyrenean-Cantabrian system as a natural laboratory. The study of the Pyrenean-Cantabrian junction discards the existence of a Pamplona transform fault between the two rift segments and argues for an accommodation zone where rift segments overlap north and south of the Basque massifs in relation with north-south direction of extension. During convergence, rift segmentation and the Triassic evaporite decoupling horizon controlled the reactivation and the local orogenic architecture. Finally, this study shows that asymmetric hyperextension is associated with asymmetric and diachronous thermal evolution, and highlights the importance of understanding the tectonic evolution to define the thermal architecture.

During recent years the principles of Mendelism have been used extensively in the production of the new types of plants possessing resistance to various diseases. Results of this mode of attacking the disease problem have been very favorable. Old varieties are gradually giving way to newer types equal to or exceeding in quality and productivity as well as possessing resistance to one or more diseases. Loose smut (U. tritici) in wheat, while not as serious a problem in Utah as the covered smut (T. tritici), according to Tapke (14) has caused an average annual loss of between 50,000 and 100,000 bushels of wheat. these data shown in figure 1 are for the period 1917 to 1926, inclusive. The various methods advocated for the control of loose smut (U. tritici), with the exception of the use of resistant varieties and hot water treatments, either have been impradtical of application or have been ineffective in control or both (14). The modified hot water treatment of Freeman and Johnson (4), has generally been the method recommended. While this method is effective if properly executed, it is rather complicated and tedious to apply, especially for farmers who are not usually properly equipped. Because of this and the fact that the disease frequently escapes observation, seed treatment for the control of loose smut (U. tritici) is seldom practiced; as a result the smut is allowed to go unchecked. The development of a resistant variety possessing the adaptability and desirable characteristics of our locally-grown spring wheats would be a decided advantage to the farmers in combating the disease.

This paper is devoted principally to the presentation and discussion of the results obtained when certain contrasting characters were brought together in a wheat cross between Ridit and Sevier 59. this is one of the crosses made in an attempt to develop a wheat adapted to this region with the following desirable qualities: Bunt resistance, strong straw, hard kernels, and heavy yield. How near this ideal is approached in succeeding generations can be told only by extensive tests. The genetic study herein presented was made to hasten the time when some of the progeny of this cross may become of economic value.

Wheat is the most important cereal crop of the world, and one of the most serious diseases affecting it over much of its range is covered smut or bunt (57). The word "bunt", according to Heald (48), is a contraction of an old English term, "burnt ear", which fittingly describes the ravages of covered smut.

Os tumores de endométrio fazem parte do espectro de tumores de inúmeras síndromes neoplásicas hereditárias (SNH). Entretanto, tais tumores, quando proficientes para o sistema de reparo incorreto de DNA (MMR), geralmente são classificados como cânceres esporádicos. Contudo, mesmo diante de uma provável classificação esporádica, a história familiar (HF) de portadoras dessas neoplasias pode apresentar indícios de componentes genéticos hereditários associados ao seu desenvolvimento. Para tanto, tivemos como objetivo principal, caracterizar a HF de mulheres diagnosticadas com tumores de endométrio, com estabilidade de microssatélites, proficientes para o sistema de reparo de pareamento incorreto de DNA, com a finalidade de avaliar o seu risco para síndromes neoplásicas hereditárias. Trata-se de um estudo descritivo de caráter populacional. A amostra inicial (n=58) foi acessada e caracterizada por meio da colaboração com um estudo maior, que investigou tumores de endométrio, quanto à proficiência do sistema de reparo MMR em uma casuística brasileira, a partir de dados coletados no biobanco do Serviço de Patologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. A coleta da HF teve início em abril de 2018 e foi finalizada em julho do mesmo ano. Nossa casuística final foi composta por 42 mulheres que atenderam aos critérios de inclusão/exclusão. Por meio de contato telefônico foi aplicado o Questionário de Rastreamento Primário e, posteriormente, desenhado o heredogramas das famílias, com a utilização do software PedigreeDraw. Após a coleta e o registro da HF, os heredogramas foram analisados pela pesquisadora principal deste trabalho e as famílias foram classificadas quanto ao seu risco de possuírem uma SNH. Nosso estudo possibilitou a identificação de 27 mulheres (64% da nossa casuística) que podem estar em risco para SNH. Dentre essas, no que se refere às SNH que têm o câncer colorretal no seu espectro de tumores, 26% preencheram critérios de Bethesda e 15% preencheram critérios de Amsterdam, sendo que 4% preencheram critérios para FAP atenuada. Já 11% preencheram critérios para síndrome de Câncer de Mama e Ovário Hereditários e 22% preencheram critérios para síndrome Li-Fraumeni Like tipo 1. Ressaltamos que 33% apresentaram história pessoal de câncer abaixo dos 50 anos. Os resultados aqui apresentados reforçam a importância da HF e precisam encorajar os profissionais de saúde a realizar com maior frequência a coleta e o registro da HF, ainda que seja autorreferida. Mesmo diante das novas tecnologias genômicas e do crescente conhecimento dos aspectos genéticos e de testes, a HF continua a destacar informações de risco, extremamente significativas, que vão além da suscetibilidade genética. Portanto, os indivíduos e suas famílias devem ser acompanhados com base na história pessoal e familiar para identificação de suspeitas de SNH / Endometrial tumors are part of the spectrum of tumors of innumerable hereditary neoplastic syndromes (SNH). However, such tumors, when proficient for the DNA mismatch repair (MMR), are usually classified as sporadic cancers. However, even though they are characterized as sporadic, the family history (HF) of carriers of these neoplasms may present evidence of hereditary genetic components associated with its onset and development. In order to study such evidences, we aimed to characterize the HF of women diagnosed with endometrial tumors and microsatellite stability, proficient for the DNA mismatch repair system, in order to evaluate their risk for hereditary neoplastic syndromes. This is a descriptive population-based study. The initial sample (n = 58) was reached and characterized by collaboration with a larger study, which investigated endometrial tumors, regarding the proficiency of the MMR system in a Brazilian sample. We collected data in the Pathology Center of the Hospital das Clínicas of the Medical School of Ribeirão Preto of the University of São Paulo. The HF collection began in April 2018 and was completed in July of the same year. Our final sample consisted of 42 women who met the inclusion / exclusion criteria. By telephone, the Primary Tracking Questionnaire was applied and, afterwards, the families\' pedigrees were drawn using the PedigreeDraw software. After HF collection and registration, the pedigrees were analyzed by the main researcher of this study and the families were classified according to their risk of having an NHS. Our study allowed the identification of 27 women (64% of our sample) who may be at risk for SNH. For samples who have colorectal cancer in their tumor spectrum and suspicion for NHS, 26% met Bethesda criteria and 15% met Amsterdam criteria, and 4% met criteria for attenuated FAP. 11% of our sample met criteria for Hereditary Breast and Ovarian Cancer syndrome and 22% met criteria for Li-Fraumeni Like type 1 syndrome. We pointed out that 33% had a personal history of cancer under 50 years. The results presented here support the importance of HF and the need to encourage health professionals to perform HF collection and registration more frequently, even if it is self-referenced. Even in the face of new genomic technologies and growing knowledge of genetic and testing aspects, HF continues to highlight extremely significant risk information beyond genetic susceptibility. Therefore, not only the individuals but also their families should be monitored on the basis of personal and family history to identify suspected SNH

No description available.

<p>Familial primary hyperparathyroidism (HPT) is a rare disorder that is treated surgically and mostly occurs in association with tumor-susceptibility syndromes, like multiple endocrine neoplasia and the hyperparathyroidism-jaw tumor syndrome. Familial hypercalciuric hypercalcemia (FHH) is another cause of hereditary hypercalcemia that generally is considered to require no treatment and is genetically and pathophysiologically distinct from HPT. Inactivating mutations in the calcium receptor gene cause FHH, whereas the down-regulated expression of the CaR in HPT never has been coupled to CaR gene mutations. </p><p>Family screening revealed a hitherto unknown familial condition with characteristics of both FHH and HPT. The hypercalcemia was mapped to a point mutation in the intracellular domain of the CaR gene that was coupled to relative calcium resistance of the PTH release by transient expression in HEK 294 cells. Unusually radical excision of parathyroid glands was required to normalise the hypercalcemia. The mildly enlarged parathyroid glands displayed hyperplasia with nodular components. Frequent allelic loss on especially 12q was found and contrasts to findings in HPT. Allelic loss was also seen in loci typical for primary HPT like 1p, 6q and 15q, but not 11q13. Quantitative mRNA analysis showed that the glands had mild increase in a proliferation index (PCNA/GAPDH mRNA ratio) and mild reduction in genes important to parathyroid cell function, like CaR, PTH, VDR and LRP2. </p><p>A previously unrecognized variant of hypercalcemia is explored that could be one explanation for persistent hypercalcemia after apparently typical routine operations for HPT. It also raises the issue of possibilities to treat FHH with parathyroidectomy provided it is radical enough.</p>

Familial primary hyperparathyroidism (HPT) is a rare disorder that is treated surgically and mostly occurs in association with tumor-susceptibility syndromes, like multiple endocrine neoplasia and the hyperparathyroidism-jaw tumor syndrome. Familial hypercalciuric hypercalcemia (FHH) is another cause of hereditary hypercalcemia that generally is considered to require no treatment and is genetically and pathophysiologically distinct from HPT. Inactivating mutations in the calcium receptor gene cause FHH, whereas the down-regulated expression of the CaR in HPT never has been coupled to CaR gene mutations. Family screening revealed a hitherto unknown familial condition with characteristics of both FHH and HPT. The hypercalcemia was mapped to a point mutation in the intracellular domain of the CaR gene that was coupled to relative calcium resistance of the PTH release by transient expression in HEK 294 cells. Unusually radical excision of parathyroid glands was required to normalise the hypercalcemia. The mildly enlarged parathyroid glands displayed hyperplasia with nodular components. Frequent allelic loss on especially 12q was found and contrasts to findings in HPT. Allelic loss was also seen in loci typical for primary HPT like 1p, 6q and 15q, but not 11q13. Quantitative mRNA analysis showed that the glands had mild increase in a proliferation index (PCNA/GAPDH mRNA ratio) and mild reduction in genes important to parathyroid cell function, like CaR, PTH, VDR and LRP2. A previously unrecognized variant of hypercalcemia is explored that could be one explanation for persistent hypercalcemia after apparently typical routine operations for HPT. It also raises the issue of possibilities to treat FHH with parathyroidectomy provided it is radical enough.