Les éléments transposables (ETs) sont des acteurs majeurs de la dynamique des génomes. Ils regroupent l’ensemble des séquences d’ADN capables de se déplacer et de se propager dans les génomes. L’objectif de cette thèse a été d’estimer la contribution des ETs dans la dynamique du génome de la microalgue Tisochrysis lutea (Haptophyte). Dans ce but, le séquençage et l’assemblage de novo du génome de cette espèce ont été réalisés. Afin de détecter, classer et annoter les ETs présents dans le génome de T. lutea, un pipeline bio-informatique nommé PiRATE (Pipeline to Retrieve and Annotate Transposable Elements) a été développé. Suite à cette annotation, l’activité de deux familles d’ETs candidates baptisées Luffy et Ace a été mise en évidence à l’aide de données transcriptomiques et protéomiques. L’étude de la dynamique des ETs a ensuite été conduite chez deux souches domestiquées de cette espèce. La comparaison de leur génome respectif à celui de la souche d’origine a permis la prédiction d’insertions et délétions associées aux ETs. Les deux familles d’ETs identifiées précédemment ainsi qu’une troisième, appelée Shanks, participent de façon prépondérante à ces variations génétiques et semblent ainsi fortement impliquées dans la dynamique du génome de T. lutea. Ce travail apporte les premières connaissances de l’activité des ETs chez les Haptophytes attestant ainsi de l’importance de ces éléments dans la dynamique des génomes de microalgues. / Transposable elements (TEs) are known as key drivers of the genome dynamics. They are defined as DNA sequences able to move and spread in genomes. The objective of this thesis was to estimate the contribution of TEs in the genome dynamics of the microalgae Tisochrysis lutea (Haptophyte). For this purpose, a new genome assembly of this species was performed. In order to detect, classify and annotate TEs, a new pipeline named PiRATE (Pipeline to Retrieve and Annotate Transposable Elements) was developed. Following this annotation, the activity of two candidate TE families named Luffy and Ace was revealed using transcriptomic and proteomic data. The study of the TE dynamics was then conducted in two domesticated strains of T. lutea. Comparative analysis between the domesticated and the originated strains genomes highlighted insertions and deletions predictions associated to TEs. The two families previously identified, together with a third one that was called Shanks, mainly participate in these genetic variations and seem to be strongly involved in the genome dynamics of T. lutea. This work provides the first knowledges regarding the activity of TEs in Haptophyte and demonstrate their importance in the genome dynamics of microalgae.

Thesis (Ph. D.)--University of Chicago, Dept. of Botany, August 1922. / Description based on print version record. Fifteen plates in pocket. Includes bibliographical references.

Thesis (M. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Purpose: To compare the safety and efficacy of intravitreal (IVT) and sub-Tenon (ST) triamcinolone acetonide for the treatment of refractory diffuse diabetic macular oedema. Method: 29 eyes of 22 patients with long-standing, diffuse diabetic macular oedema refractory to argon laser treatment were randomly assigned to a single 4mg injection of IVT triamcinolone acetonide or a 40mg sub-Tenon injection. Patients were subsequently monitored for six to nine months. Outcome measures were visual acuity, intraocular pressure, macular thickness on optical coherence tomography and adverse effects. Results: There was no significant improvement in visual acuity in either group. A transient decrease in macular thickness was found in the IVT group but not in the ST group. There were no significant adverse effects apart from a mild to moderate intra-ocular pressure rise found more frequently in the IVT group. Conclusion: IVT and ST triamcinolone acetonide injections for refractory diffuse diabetic macular oedema appear relatively safe and well-tolerated. IVT injection produces a significant temporary decrease in macular thickness in patients with long-standing diffuse diabetic macular oedema while ST injection does not. Neither intervention was shown to significantly improve visual acuity in this group of patients.

Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008. / Full text also available online. Scroll down for electronic link.

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

BEZERRA, S. B. Avaliação da segurança e eficácia farmacológica não-clínica das Gotas Arthur de Carvalho®: validação do uso medicinal nos distúrbios gastrointestinais. 2015. 163 f. Tese (Doutorado em Ciências Farmacêuticas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015. / Submitted by Erika Fernandes (erikaleitefernandes@gmail.com) on 2017-03-10T16:32:43Z No. of bitstreams: 1 2015_tese_sbbezerra.pdf: 1474995 bytes, checksum: ba23171bc8e1dd553d181b5028516865 (MD5) / Approved for entry into archive by Erika Fernandes (erikaleitefernandes@gmail.com) on 2017-03-10T16:32:53Z (GMT) No. of bitstreams: 1 2015_tese_sbbezerra.pdf: 1474995 bytes, checksum: ba23171bc8e1dd553d181b5028516865 (MD5) / Made available in DSpace on 2017-03-10T16:32:53Z (GMT). No. of bitstreams: 1 2015_tese_sbbezerra.pdf: 1474995 bytes, checksum: ba23171bc8e1dd553d181b5028516865 (MD5) Previous issue date: 2015-05-22 / The herbal medicine Gotas Arthur de Carvalho® (GAC) produced from Matricaria recutita (chamomile), Gentiana lutea (gentian) and Foeniculum vulgare (fennel) tinctures, has indication use as antispasmodic and stomachic, and despite being on the market more than 70 years, does not have scientific studies proving its quality, stability, safety and therapeutic efficacy in gastrointestinal disorders. This study aims to validate the use of GAC in functional gastrointestinal disorders, determining the safety and efficacy of product, to meet the requirements of ANVISA and thus, contribute to the product registration renovation. Firts, were carried out the preclinical toxicity test (acute and repeated-doses toxicity) in rodents, cytotoxicity on human neutrophils and HepG2 cells and evaluation of the pharmacological activity of the herbal medicine to treat gastrointestinal disorders. Initially, the herbal medicine was standardized on the content of active markers (7-glucosídio apigenin, gentiopicrosídio and anethole) determined by the use of validated analytical method - RE 899 (BRAZIL, 2003) with the aid of Liquid Chromatography System with High Efficiency array detector diiodo (HPLC-DAD). In vitro toxicological evaluations (culture neutrophils and HepG2 cells) was investigated the determination of lactate dehydrogenase activity and / or the MTT test, and GAC (10-200 ug / ml) was shown to be not cytotoxic. Continuing toxicity studies in rodents, the estimated LD50 of the product was above 2 g / kg when administered orally. Moreover, in repeated-doses toxicity study (250-1000 mg / kg, p.o.) in rats confirmed the low toxicity of the product through biochemical, haematological and histopathological evaluations. In pharmacological evaluation, the herbal GAC (100 - 400 mg / kg, p.o.) showed activity on dyspepsia, demosntrated by reduction of intestinal transit induced by bethanechol, besides the laxative effect. Moreover, the antinociceptive effect of GAC founded in visceral pain model induced by mustard oil in mice where both opioid and adrenergic systems, in addition to potassium channels appear to have an important role in action, which is not related to a possible central effect, because sedation or decreased motor activity was not observed. Finally, the herbal medicine Arthur de Carvalho showed a safety standard which confirms its use as medicine, in addition to its potential in the treatment of gastrointestinal disorders, proving its antinociceptive activities / visceral pain and role in dyspepsia. However, further studies are still needed, especially related to determine the pharmacological mechanism of action as well as clinical studies, seeking registration as herbal medicine in Brazil. Also, is important valorize the importance of this study of university-industry partnership / Pharmaceutical Industry, which made work something concretely applied to social and economic needs of the region. / O fitoterápico Gotas Arthur de Carvalho produzido a partir das tinturas de Matricaria recutita (camomila), Gentiana lutea (genciana) e Foeniculum vulgare (funcho), possui como indicação o uso como anti-espasmódico e estomáquico e, apesar de estar no mercado a mais de 70 anos, não possui ainda estudos científicos que comprovem a sua qualidade, estabilidade, segurança e eficácia terapêutica nas desordens gastrointestinais. O presente trabalho tem como principal objetivo validar o uso do fitoterápico nas desordens gastrintestinais, determinando a segurança e eficácia do produto padronizado, para atender as exigências da ANVISA e assim, contribuir para a renovação de registro do produto. Foram então realizados os testes de toxicidade pré-clínica (toxicidade aguda e de doses repetidas) em roedores, citotoxicidade em neutrófilos humano e células HepG2 e avaliação da atividade farmacológica do fitoterápico para desordens gastrintestinais. Inicialmente, fitoterápico foi padronizado quanto ao teor de marcadores ativos (apigenina 7-glucosídio, gentiopicrosídio e anetol) determinados pelo emprego de método analítico validado - RE 899 (BRASIL, 2003) com auxílio de sistema de Cromatografia Líquida de Alta Eficiência com detector de arranjo diiodo (CLAE-DAD). Nas avaliações toxicológicas in vitro (cultura de neutrófilos e células HepG2) investigada pela determinação da atividade da lactato desidrogenase e/ou teste do MTT, o fitoterápico GAC (10-200 µg/mL) não mostrou-se citotóxico. Prosseguindo os estudos de toxicidade em roedores, a estimativa da DL50 do produto foi acima de 2g/kg, quando administrado por via oral. Ademais, estudo de toxicidade de dose repetida (250-1000 mg/Kg, v.o.) em ratos ratificou a baixa toxicidade do produto através de avaliações bioquímica, hematológica e histopatológica. Na avaliação farmacológica, o fitoterápico GAC (100 – 400 mg/Kg, v.o.) mostrou potencial antidispéptico, reduziu o trânsito intestinal induzido por betanecol, além do efeito laxativo. Ainda, o fitoterápico apresentou efeito antinociceptivo no modelo de dor visceral induzido pelo óleo de mostarda em camundongos, tanto nos sistemas opióide e adrenérgico, além dos canais de potássio, que parecem possuir um papel importante nessa ação, que não está relacionada a um possível efeito central, como sedação ou diminuição da atividade motora. Por fim, o fitoterápico Gotas Arthur de Carvalho mostrou um padrão de segurança que ratifica o seu emprego como medicamento, além do seu potencial no tratamento de desordens gastrointestinal, destacando suas atividades anti-dispéptica e antinociceptiva/dor visceral. Contudo, estudos adicionais são ainda necessários relacionados especialmente à determinação mais aprofundada do mecanismo de ação farmacológico, bem como a realização de estudos clínicos, vislumbrando seu registro como fitoterápico no país. Ainda, destaca-se a importância do presente estudo que envolveu parceria universidade-empresa/Indústria Farmacêutica, o que tornou o trabalho algo concretamente aplicada às necessidades sociais e econômicas da região.

Steroid and eicosanoid metabolism occurs in two phases and primarily within hepatic tissues, but localized metabolism has been examined in several extra-hepatic tissues in humans and rodents. Phase I of metabolism is performed by Cytochrome P450s (CYP) that add hydroxyl groups to the carbon ring structure which is further metabolized by phase II UDP-glucuronosyltransferase (UGT). The overall objectives of the following experiments were to: 1) determine the amount of extra-hepatic steroid metabolism within reproductive tissues of cattle across the estrous cycle; 2) determine the amount of extra-hepatic steroid metabolism and an oxylipin profile within reproductive tissues of cattle based on pregnancy status; and 3) determine the amount of endometrial blood perfusion in cattle using a novel laser Doppler technique. Activity of CYP1A was found within corpora lutea (CL) tissues of both pregnant and non-pregnant cattle, but not within endometrial tissues. Endometrial perfusion, measured using a novel laser Doppler technique, was also validated by measuring angiogenic factors in close proximity to the location of perfusion. A positive correlation (r = 0.28; P = 0.04) was observed between endometrial perfusion and nitrite concentration, an angiogenic factor. Endometrial blood perfusion was affected by the proximity to the CL, but not by the proximity of the dominant follicle. In addition, UGT was categorized across the estrous cycle and the activity was dependent upon the proximity of the CL. Oxylipins, including eicosanoids, were also profiled in CL of cattle that were non-pregnant and pregnant with 5 out of 39 oxylipins differentially expressed. The activity and oxylipin products of steroid and eicosanoid enzymes were not correlated with serum or luteal progesterone. Through these experiments, we have verified that there is localized metabolism of steroids and eicosanoids within reproductive tissues of cattle as well as fetal tissues. Also, we have achieved a full oxylipin profile of non-pregnant and pregnant cattle CL with five oxylipins contained in various amounts between pregnancy status.

Limitations from reduced light and increasing water depth on Nelumbo lutea seedlings were determined in tank experiments. Survival was high in all tested light levels. Total biomass increased significantly with increasing light. Biomass allocation shifted significantly to root production between 3 and 6 weeks in the 10 and 24% levels. Survival decreased with increasing planting depth, and biomass of survivors reduced significantly between 0.5, 1.0, and 1.5 m depths. Nelumbo lutea and Myriophyllum spicatum populations were monitored for one season in a 0.7 ha pond to track changes in species dominance. Myriophyllum spicatum dominated early, and N. lutea dominated from July through October, suppressing M. spicatum at all depths. Competitive interactions between N. lutea and M. spicatum were investigated for two seasons in a container experiment situated within a pond. Where established, N. lutea dominated in the presence of M. spicatum. However, N. lutea could not be established in depths greater than 1 meter.

Chen, Tingting. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 100-109). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.