<p> There has been an increasing value in the ability to describe the world's diversity for the purpose of enhancing research and conservatory efforts. Characterizing the level of heterogeneity of particular molecular markers and verifying its suitability as an identifier of new specimens provides a way of quantifying biodiversity. One such molecular marker is the mitochondrial cytochrome c oxidase subunit I (COl). An analysis of the evolutionary rates among and within taxonomic groupings of 13,641 insect COl sequences revealed that the evolutionary rate of some species increased or decreased, sometimes by an order of a magnitude. Furthermore, the increased evolutionary rates of two species, from the Lepidopteran and Orthopteran orders, may be explained by the influence of positive selection but further analyses would be required to rule out other explanations. Overall, we deem that the rate of substitution generates enough change for COl to work sufficiently as a barcode marker in insects. As COl is not suitable for specimen identification in plants, it would be useful to be able to quickly determine if there is enough variation in COl or other molecular markers for specimen identification. In response, a visualization tool, Fingerprint, was developed to graphically depict 11 different types of sequence diversity. An application of the tool to Lepidopteran COl data verified the genetic diversity in insect COl and the tool's ability to sensitively detect different types of heterogeneity. </p> / Thesis / Master of Science (MSc)

Thèse doctorat : Biologie Moléculaire : Strasbourg 1 : 2006. / Thèse soutenue sur un ensemble de travaux. Titre provenant de l'écran-titre. Bibliogr. 23 p.

La réversion tumorale est un processus de transformation cellulaire peu fréquent qui s’explique par le rétablissement du contrôle de la croissance cellulaire aboutissant au phénotype cellulaire normal. Plusieurs agents sélectifs (virus, produits chimiques, interféron) peuvent être utilisés pour provoquer ce phénomène. L’efficacité de ces thérapies dépend de l’agressivité des cellules à traiter et les gènes qui sont bloqués. Les cellules HeLa et SiHa sont des lignées cellulaires utilisées fréquemment comme modèle in vitro pour étudier le cancer du col utérin. Ces deux lignées cellulaires comportent des oncogènes E6 et E7 du virus du papillome humain (VPH) à haut risque de type 18 pour les cellules HeLa et de type 16 pour les cellules SiHa. Les oncoprotéines virales E6 et E7 bloquent les protéines suppresseurs de tumeur p53 et pRb respectivement ce qui entraîne la transformation en cellules cancéreuses. La réactivation de la protéine p53 et/ou de la protéine pRb ou d’autres types de protéines effectuée par des agents sélectifs oncosuppressifs peut renormaliser le cycle cellulaire. L’étude proposée pour cette thèse vise à étoffer la littérature scientifique afin d’expliquer la faisabilité d’établir un modèle in vitro qui serait exploité pour 1) déterminer si la réversion tumorale a lieu de manière spontanée dans les cellules HeLa et SiHa, 2) comprendre les effets de différentes thérapies pouvant entraîner la réversion tumorale des cellules cancéreuses du col utérin et 3) comprendre le mécanisme d’action des thérapies oncosuppressives dans le contexte de la réversion tumorale du cancer du col utérin.

Thesis (Ph. D.)--Columbia University, 1916. / Vita. "Reprinted from the Romanic review, vol. VII, no. 4, 414-457, 1916; vol. VIII, no. 2, 145-165, and no. 3, 290-306, 1917." Bibliography: p. 95-101.

Most studies of plant hybridisation are concerned with documenting its occurrence in different plant groups. Many flowering plants are polyploids and seeds developed from crosses between individuals of different ploidies usually show abnormal features and often abort. The success or failure of interploidy crosses is very important to understanding the evolution of plants as well as to agriculture, but much remains to be learned about the nature of hybridisation barriers. Several mechanisms have been proposed to explain postzygotic barriers, including negative interactions between diverged sequences, global genome rearrangements, and widespread epigenetic reprogramming. Some recent advances in our understanding of the process of hybridisation are derived from different experimental studies on a series of A. thaliana ecotypes. Crosses between diploid (2x) and tetraploid (4x) individuals of the same ecotype can result in F1 lethality, and this dosage-sensitive incompatibility plays a major role in polyploidy speciation research. We have performed interploidy crosses between different diploid maternal A. thaliana ecotypes and tetraploid paternal Col-0 ecotype and identified a genetic variation in F1 lethality. We also found that maternal parents of some ecotypes such as Tsu-1 suppressed the F1 lethality caused by paternal-excess interploidy cross of Col-0 ecotype. A preliminary mapping exercise produced advanced backcross populations that are suitable for mapping maternal modifiers and for the identification of modifier genes. Furthermore, we studied the killer effect caused by Col-0 and identified three additive QTL that affect the rate of postzygotic lethality in F1 during interploidy crosses. This information will facilitate the identification of paternal genes that cause F1 lethality and contribute to reproductive isolation. The moa-1 (mosaic aneuploidy 1) mutant of A. thaliana was obtained in a screen of chemically (EMS) mutagenised seeds of Landsberg erecta (Ler). moa-1 has various phenotypic differences to wild type; the preliminary karyotype analysis showed that the cells of individual moa-1 mutant plants have a variable number of chromosomes (usually between 11-18). In contrast, the cells of wild type Arabidopsis plants and conventional aneuploids have a fixed number of chromosomes in each somatic cell. This data showed that all moa-1 plants have an abnormal number of chromosomes and thus they were termed as mosaic aneuploids.

The proteins tyrosine kinases (PTKs) and the proteins tyrosine phosphatases (PTPs) are very important proteins implicated in the regulation of the cell cycle and numerous human diseases including cancer. VHR is a dual-specific phosphatase whose principles substrats are the MAPKs ERK and JNK. Previous studies of our laboratory showed that this phosphatase is regulated during the cell cycle. Its level is low during the G1 phase and increases during S and G2 phases to reach a top at the G2/M phases. The low level of VHR during the G1 phase is probably due to an alteration of the protein stability demonstrated by a decreased half-life (after treatment of the cell with cycloheximide). In addition, VHR deletion by RNA interference in HeLa cells induces a cell cycle arrest during G1/S and G2/M transitions [1]. In the first part of our work, we show that the dual-specificity phosphatase VHR is overexpressed in cervix cancer cell lines compared to primary keratinocytes. These cell lines are infected (HeLa, CaSki and SiHa) or not (C33 and HT3) by HPV, suggesting that VHR overexpression is HPV independent, virus which is responsible of cervix cancer. We show that VHR overexpression is associated with a differential subcellular localization. Indeed, VHR is localized in the cytoplasm of normal keratinocytes while it localizes in both cytoplasm and nucleus of the cell lines studied. This observed overexpression is not associated with an increased expression of its mRNA but with a stabilization of the protein. CHX chase showed us that VHR half life is about 2 hours in primary keratinocytes and longer than 8 hours in cervix cancer cell lines. The TMA technique allowed us to study a large number of preneoplasic and neoplasic cervical lesions. Interestingly, we observe that VHR is significantly overexpressed in CIN III (Cervical intraepithelial Lesions III) (n=18) and in SCCs (Squamous Cell Carcinoma) (n=12) compared to normal exocols (n=16) and although in ADCs (Adenocarcinoma) (n=12) and AISs (Adenocarcinoma in situ) (n=9) compared to normal endocols (n=19). The differential subcellular localization is also observed in CIN III and SCCs compared to normal exocols but not in ADCs and AISs compared to normal endocols. In the second part of our work, we analyzed the effect of small selectif inhibitors of VHR developped by Dr. L. Tautz from Burnham Institute in La Jolla, CA on cervical cell lines, HeLa and CaSki. We show that these small sulfonic acids induced a decreased number and a decreased proliferation of HeLa and CaSki cells. These effects are similar to those induced by RNA interference. We also show that these inhibitors induced an increased level of ERK phosphorylation. Since ERK is a specific substrat of VHR, these results suggest that the small inhibitors developped by L. Tautz et al. are specific for VHR.

Thèse d'exercice : Médecine. Gynécologie obstétrique : Nantes : 2007. / Bibliogr.

Reproduction de : Thèse d'exercice : Médecine. Médecine générale : Nantes : 2009. / Bibliogr.

Reproduction de : Thèse d'exercice : Médecine. Médecine générale : Nantes : 2009. / Bibliogr.

Reproduction de : Thèse d'exercice : Pharmacie : Nantes : 2008. / Bibliogr.