Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains vii, 51 p. : ill. Includes abstract. Includes bibliographical references.

Thesis (M.BmedSc.)--Victoria University of Wellington, 2010. / Includes bibliographical references.

Thesis (MSc.(Physiology)--Faculty of Health Sciences)-University of Pretoria, 2004. / Also available on the Internet via the World Wide Web.

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Edward M. Marcotte. Vita. Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.

Inflammatory bowel disease (IBD) is associated with an inappropriate immune response to the gut microbiota and disruption of intestinal homeostasis. IBD patients and experimental animal models have consistently shown alterations in the gut microbiota composition. However, these studies have mainly focused on faecal microbiota samples taken after the onset of inflammation and IBD establishment. The colonic microbiota inhabits both the gut lumen and the mucus layer covering the intestinal epithelium. Thus, information about mucus-resident microbiota is not necessarily conveyed in the routine microbiota analyses of faecal samples. To address potential changes in microbial composition and function before the onset of IBD, we compared both mucus and faecal microbiota in the mdr1a-/- spontaneous model of colitis over times that we histologically defined as before onset of colitis, during and after colitis onset. We showed that alterations in microbiota composition preceded the onset of intestinal inflammation and that these changes were evident in the mucus, but not in faeces. This altered microbiota composition was coupled with a reduced inner mucus layer, indicating a compromised mucus barrier prior to colitis development. Upon emergence of inflammation, compositional differences were found in both mucus and faecal microbial communities. Spatial segregation of microbiota with intestinal mucosa was also disrupted on disease onset which we hypothesise contributes to a more severe intestinal pathology. Therefore, our data indicate that microbial changes start locally in the mucus and then proceed to the faecal matter concomitantly with colitis development. Next, we examined whether microbial gene functional potential and endogenous metabolite profiles followed alterations in gut microbiota taxonomic composition. Our findings showed that the microbial gene content was similar between mdr1a-/- mice and wild-type littermate controls, demonstrating stability of the gut microbiome at the face of ensuing gut inflammation. In further support of these findings, urinary metabolite analysis revealed that metabolite profiles were unaffected by intestinal inflammation. Metabolites previously reported to change in IBD were similar between mdr1a-/- and wild-type mice at stages preceding and during inflammation. We also found that changes in metabolite profiles did not correlate with colitis scores. However, metabolite changes could discriminate mdr1a-/- mice from wild-type controls, suggesting they could have value in predicting risk of IBD with a potential clinical use in at least a subset of individuals with MDR1A polymorphisms. To assess whether changes in antimicrobial proteins (AMPs) accounted for observed differences in mucus microbiota composition, we also investigated the expression of regenerating islet-derived protein 3 γ (Reg3γ), angiogenin 4 (Ang4), β-defensin 1 and resistin-like molecule beta (Relm-β) in the colon. We found similar levels of these AMPs as well as IgA-producing plasma cells between mdr1a-/- and wild-type mice, suggesting that other factors contribute to alterations in microbiota composition. Overall, our data indicate that the mdr1a-/- is a good model of colitis, as it enables us to look at pre-clinical changes in the gut microbiota. This work suggests the importance of mucus sampling for sensitive detection of microbiota changes. Furthermore, metabolite profiling may be a helpful way to discriminate genetic susceptibility to disease.

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Cancer-related diseases are mostly associated with reduced or inappropriate cell death. This thesis focuses on secondary cyanobacterial metabolites which induce apoptosis in human cancer cells in vitro and thus may serve as potential drug hits. Screening and selection of active natural extracts clearly precede activity-guided isolation of a bioactive compound itself. Summarizing the results of phenotypic screening of cyanobacterial extracts for inducers of apoptosis, I show that adjustment of measurement the activity of key apoptotic enzymes, caspases, per cell significantly enlarges the pool of detected hits. This could be of particular importance, since this correction is relevant for complex natural extracts as well as chemical libraries of pure compounds, and moreover applicable all the way from small-sized screens to high-throughput ones. Further, I investigated the apoptosis inducing activity of nocuolin A (NoA) a new cyanobacterial compound isolated and described by our group. NoA shows remarkable characteristics regarding its structure (1,2,3-oxadiazine heterocycle), biosynthetic origin and also its biological activity. It induces caspase-dependent apoptosis and shows potency against a panel of nine human cancer cell lines, which makes NoA a pharmaceutically interesting compound. I also bring the first insights into elucidation of its mode of action in cancer cells in vitro.

BRANCO, Karoliny Farias Castelo. Impacto da restrição alimentar sobre os parâmetros biometricos, hormonais e metábolicos de ovinos Santa Inês. 2015. 51 f. Dissertação (mestrado em zootecnia)- Universidade Federal do Ceará, Fortaleza-CE, 2015. / Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-04-05T19:38:55Z No. of bitstreams: 1 2016_dis_kfcbranco.pdf: 1130996 bytes, checksum: fbd5efcef36975da8442760b524bad9c (MD5) / Approved for entry into archive by José Jairo Viana de Sousa (jairo@ufc.br) on 2016-05-24T22:47:00Z (GMT) No. of bitstreams: 1 2016_dis_kfcbranco.pdf: 1130996 bytes, checksum: fbd5efcef36975da8442760b524bad9c (MD5) / Made available in DSpace on 2016-05-24T22:47:00Z (GMT). No. of bitstreams: 1 2016_dis_kfcbranco.pdf: 1130996 bytes, checksum: fbd5efcef36975da8442760b524bad9c (MD5) Previous issue date: 2015 / The present study aimed to evaluate biometric measurements and blood and hormonal parameters of Santa Ines lambs. Thirty lambs with an average live weight of 13.0 ± 1.49 kg and 60 days of age were used to estimate glucose, cholesterol, β-hydroxybutyrate, urea N, total protein, albumin, globulin, chloride, calcium, phosphorus, magnesium, and leptin, insulin, and thyroxine (T4) hormones. Lambs were assigned to a randomized complete design in a 3 × 2 factorial arrangement consisting of three levels of food restriction (FR) (control, 30%, and 60%), three collection periods corresponding the age of the animals (14, 18, and 23 weeks of age), and two sex categories (castrated and uncastrated). Blood was collected by jugular venipuncture in the three collection periods. For biometric measurements, a randomized complete design in a 3 × 2 factorial arrangement was adopted, taking into account restriction levels and sex categories. Measurements were taken every two weeks throughout the experimental period. The hormone thyroxine was not influenced by age, diet, or sex category. Leptin and insulin increased with the animal age (P <0.01). Glucose concentrations decreased as the FR level were increased (P <0.001). β-hydroxybutyrate concentrations increased as the food restriction was increased (P <0.001). Urea nitrogen was influenced by age and experimental diet (P <0.001), and there was an age × sex category interaction effect (P <0.01). Concentrations of total cholesterol and total proteins were not influenced by experimental treatments (P <0.05), but albumin and globulin were influenced by age (P <0.001, P <0.01). Plasma concentrations of chloride, calcium, magnesium, and phosphorus varied significantly according to age. Animals subjected to FR grew at a slower rate, and the negative influence was more pronounced at 60% FR. At 30% FR, the growth rate decline was more noticeable at 100 days of age for body weight (BW); at 130 days for body condition score (BCS) and chest girth (CG); at 145 days for rump height (RH); and at 160 days for rump length (RL) and breast width (BW). Pearson's correlation analysis showed biometric measurements are co-dependent on the feeding level because correlations were high and significant in control animals (r = 0.61 to 0.95). It is concluded that the metabolic parameters were more influenced by age than by diet, and food restriction affects the metabolic and hormonal profiles, in particular β-hydroxybutyrate and insulin. Body condition score, body weight, and breast width were the most significantly affected by FR parameters. / Objetivou-se com o presente estudo avaliar a biometria, parâmetros sanguíneos e hormonais de cordeiros Santa Inês. Foram utilizados 30 cordeiros com peso vivo médio inicial de 13,0 ± 1,49 kg e aproximadamente 60 dias de idade para estimativa daglicose, colesterol, β- hidroxibutirato, N- ureico, proteínas totais, albumina, globulina, cloreto, cálcio, fósforo, magnésio e os hormônios leptina, insulina e tiroxina (T4). Utilizou-se o delineamento inteiramente casualizado em esquema fatorial 3 x 3 x 2, que consistia detrês níveis de restrição alimentar (RA) (controle, 30% e 60%), três períodos de coleta correspondente à idade dos animais (14, 18 e 23 semanas de idade) e duas classes sexuais (castrados e não castrados). O sangue foi coletado por punção da veia jugular nos três períodos de coleta. Para as medidas biométricas utilizou-se o delineamento inteiramente casualizado em esquema fatorial 3 x 2, levando-se em consideração os níveis de restrição e as classes sexuais. As medidas foram realizadas quinzenalmente durante todo período experimental.O hormônio Tiroxina não foi influenciado pela idade, dieta ou classe sexual. Já a leptina e a insulina aumentaram com a idade dos animais (P<0,01). As concentrações de glicose diminuíram de acordo com o aumento do nível de RA (P<0,001). As concentrações de BHB foram maiores à medida que se aumentou a restrição alimentar (P<0,001). O N-ureico foi influenciado pela idade e dieta experimental (P< 0,001) e houve interação idade X classe sexual (P<0,01). As concentrações de colesterol total e proteínas totais não foram influenciadas pelos tratamentos experimentais (P<0,05), entretanto a albumina e globulina foram influenciadas pela idade (P<0,001; P<0,01). As concentrações plasmáticas de cloretos, cálcio, magnésio e fósforo variaram significativamente em função da idade. Os animais submetidos à RA cresceram em ritmo mais lento, sendo que, a influencia negativa foi mais acentuada no R60 (60% de RA). No R30 (30% de RA), o ritmo de crescimento diminuído foi mais perceptível com 100 dias de idade no peso corporal (PC), com 130 dias no escore de condição corporal (ECC) e perímetro torácico (PT), com 145 dias na altura de garupa (AG) e com 160 dias no comprimento de garupa (CG) e largura de peito (LP). A análise da correlação de Pearson mostra que as medidas biométricas são co-dependentes do nível de alimentação do animal, pois as correlações foram altas e significativas nos animais controle (r= + 0,61 a 0,95). Conclui-se que os parâmetros metabólicos foram influenciados mais pela idade do que pela dieta e que a restrição alimentar afeta o perfil metabólico e hormonal, em especial o β-hidroxibutirato e a insulina. O escore de condição corporal, peso corporal e largura de peito foram os parâmetros mais sensivelmente influenciados pela RA.

No description available.