Orientador: Rogério Martins Amorim / Banca: Marcos Jun Watanabe / Banca: Maria Verônica de Souza / Resumo: As fibras musculares esqueléticas são entidades versáteis, capazes de alterar seus fenótipos de acordo com a demanda energética. Para avaliar os efeitos do exercício de enduro no músculo esquelético, foram utilizados neste estudo 36 equinos da raça Puro Sangue Árabe divididos em dois grupos: treinados e não treinados para enduro. Foram obtidos fragmentos musculares da região profunda do músculo glúteo médio e processados para técnicas histoquímicas e imunoistoquímica, utilizando-se anticorpos específicos contra isoformas de cadeia pesada de miosina (MyHC) lenta e rápida. As fibras identificadas pela histoquímica e imunoistoquímica foram analisadas uma a uma. Determinou-se a porcentagem dos diferentes tipos de fibras musculares, e avaliou-se que, a porcentagem das fibras do tipo IIA foi significativamente mais alta do que a porcentagem das fibras dos tipos I e IIX no grupo não treinado (P<0,05). Em contra partida, a porcentagem das fibras do tipo I foi significativamente mais alta do que a porcentagem das fibras dos tipo IIA e IIX no grupo treinado (P<0,05). Também foram analisados, a média da área de corte transversal e o menor diâmetro da fibra e observou-se que, a média de corte transversal das fibras do tipo IIX foi significativamente maior comparada à média de corte de transversal das fibras dos tipos I e IIA em ambos os grupos. Em conclusão pode-se afirmar que, o exercício de enduro em equinos aumenta a população das fibras de contração lenta, em detrimento da população de fibras de contração rápida / Abstract: The skeletal muscle fibers are versatile entities capable to change their phonotype according to energy demand. To evaluate the effects of exercise over equine skeletal muscle in this study, 36 Arabian horses divided in 2 groups trained and untrained for endurance were used. The samples was obtained from de deep region of the gluteus medius muscle and processed for histochemistry and immunohistochemistry using specific monoclonal antibodies to selected fast and slow isoforms myosin heavy chain (MyHC). The histochemical and immunohistochemical categorization of the muscle fiber types were compared fiber by fiber. It was analyzed the percentage of different fiber types where, in the untrained group, the percentage of the fiber type IIA was higher significantly than the percentage of fiber types I and IIX (P<0.05). Unlike, the group trained showed a higher proportion of fiber type I than the fiber type IIX (P<0.05). The cross section area and lesser fiber diameter were also analyzed, and showed that, CSA of fiber type IIX was higher significantly than fibers I and IIA (P<0.05) in both groups. In conclusion, endurance exercise in equines increase the population of slow-twitch fibers in detriment of fast-twitch fibers / Mestre

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Le cancer est la plus grande cause de mortalité après les maladies cardiaques. Les cellules cancéreuses sont issues des cellules saines dont les systèmes de multiplications et de régulations ont été annihilés. Elles se multiplient anarchiquement et forment des tumeurs. Nous nous sommes donc intéressés au cancer de la vessie qui en termes d’incidences dans les pays industrialisés est le quatrième cancer chez l’homme et le neuvième chez la femme. Parmi les nombreux récepteurs surexprimés dans les cellules tumorales de vessie, la kinase Tyro3 s’est révélée indispensable à la survie de ces cellules tumorales. Le premier objectif de cette thèse est de synthétiser un inhibiteur sélectif de Tyro3 possédant un noyau purine. Une première stratégie est orienté vers la synthèse d’un inhibiteur de type I alors que la seconde stratégie est menée vers la synthèse d’un inhibiteur de type II. Deux composés montrent une activité intéressante à 1 µM sur Tyro3 et semblent adopter un profil d’inhibition de type II. Le second objectif de la thèse présente une approche méthodologique pour la substitution de la position 2 et 8 du noyau purine. Une première partie présente la double lithiation des positions 2 et 8 de la 6-chloro-9-(tétrahydro-2H-pyran-2-yl)-9H-purine suivie d’une substitution avec différents électrophiles. Le dérivé 2,8-diodé obtenu est engagé dans une réaction de Sonogashira conduisant à des dérivés 2-alcynyl-8-iodo ou 2,8-dialcynyle. Une seconde partie traite de l’amidation et amination pallado-catalysées de la 8-iodo-6-(phénylsulfanyl)-9-(tétrahydro-2H-pyran-2-yl)-9H-purine. / After heart diseases, cancer is the most important cause of death. Cancerous cells are normal cells which multiplication and regulation system have been affected. They anarchically grow and give tumors. We have investigated in bladder cancer which is fourth cancer among men and ninth cancer among women in industrial countries. Amongst overexpressed receptors in bladder cancerous cells, Tyro3 seems to be essential for the survival of bladder cancerous cells. First goal of this thesis is to synthesize a potent and selective inhibitor of Tyro3 with a purine scaffold. Two approaches have done. The first approach is the synthesis of a type I inhibitor whereas the second approach is the synthesis of a type II inhibitor. Two compounds have shown an interesting activity against Tyro3 at 1 µM and they seem to be type II inhibitors. The second part of the thesis was the functionalization of position 2 and 8 of purine scaffold. We show first the double deprotonation by lithium species of 6-chloro-9-(tétrahydro-2H-pyran-2-yl)-9H-purine following by substitution with different electrophiles. Obtained 2,8-di-iodine compound is engaged in Sonogashira reaction which gives 2-alkyne or 2,8-di-alkyne compunds. And, we investigate in palladium catalyzed amidation and amination of 8-iodo-6-(phénylsulfanyl)-9-(tétrahydro-2H-pyran-2-yl)-9H-purine.

Yip Mei Po. / "April 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 170-197). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Made available in DSpace on 2014-06-11T19:30:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-08Bitstream added on 2014-06-13T21:01:45Z : No. of bitstreams: 1 coan_ai_dr_rcla.pdf: 17033809 bytes, checksum: 1ae8df7113d96a44c82c828cd54a77c3 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / The embryology and the seed development of Eriocaulaceae and Cyperaceae were studied here in order to contribute to the taxonomy and phylogeny of both families. The results given by different genera of Eriocaulaceae allowed us to strengthen the embryological uniformity of the family. The endothecial thickenings of the baseplate-type, the spiraperturate pollen grains, the antipodal cyst closely associated to the hypostase, and the operculated endotestal seeds are synapomorphies of Eriocaulaceae within Poales. The use of the character number of microsporangia of anthers in genera delimitation is not consistent, while those related to the seed coat seem to be more stable in establishing relationships between genera. The overall embryological features pointed out the necessity of a taxonomic revision in Eriocaulaceae, aiming at a more natural classification of its taxa. In Cyperaceae, the embryology and the fruit development were investigated in species of Hypolytrum and Rhynchospora, showing that most of these aspects are also uniform within the family. The endothecial thickenings of the spiral type, the Cyperaceous-type of simultaneous microsporogenesis, the trinucleate pollen grain of the pseudomonad type, the formation of a funicular obturator closely associated with the hypostase of the ovule, the Onagrad-Juncus variation embryogeny, and the fruit of the achene type with silica deposition clearly distinguish this family amongst the other Poales. Hypolytrum differs from Rhynchospora as well as from the other genera of Cyperaceae already studied for the spherical pseudomonads, with reticulate exine and central arrangement in the microsporangia, the micropyle formed by both the integuments, and the conspicuous parietal tissue which indicate its position as a basal group in the family. Moreover, the number and the ...(Complete abstract, click electronic address below).

The protein Poly was first discovered in Drosophila melanogaster, during a screening for third chromosome lethal mutations. Drosophila poly mutant larvae exhibit a slower rate of development. However, they reach the third instar larval stage and remain at that stage for 21 days before they die without reaching pupation. This phenotype is attributed to developmental impairment of the imaginal discs, therefore suggesting defects in cell growth and/or proliferation. During that stage, the mutant larvae develop melanotic masses. Poly is conserved and its homolog, Elp6, is one of the small subunits of the Elongator Complex, a complex involved in many cellular functions including transcription and translation. Drosophila larvae mutated at the Elp3 gene, the gene encoding the catalytic subunit of the Elongator complex, develop melanotic masses, a phenotype very similar to that of poly. The Heck laboratory published that Poly is a positive mediator of the Insulin Receptor/TOR (InR/TOR) pathway, which leads to protein, glycogen and fatty acid synthesis, regulates cell growth and apoptosis. It was shown that Poly interacts with InR, at least in some cases, therefore promoting cell growth and metabolism (Bolukbasi et al., 2012). The Drosophila genome shares 60% similarity to the human, with 77% of the genes attributed to a human disease having a Drosophila counterpart (Chien et al., 2002). In 2011, an intriguing study by Musselman et al. reported that feeding wild type Drosophila larvae with excessive amounts of sucrose led to the development of an insulin resistance phenotype similar to that of Type 2 Diabetes (T2D), thus rendering Drosophila an easily accessible T2D model. The phenotype included impaired metabolism, slower rate of development, and excessive accumulation of triglycerides (TAG) in the larval fat body. In my thesis research, I examined the involvement of Poly in insulin resistance - T2D using Drosophila as a model. The understanding of the connection between the protein and the disease came upon the discovery of a new form of Poly, Poly14. Poly14 is enriched in the Drosophila fat body, the equivalent of the human fat tissue and liver and its protein levels are significantly decreased when larvae are fed a high sucrose diet, compared to other types of diets – potentially linking the protein to the onset of T2D. Poly mRNA levels were also lower. To examine whether the overexpression of poly might be able to rescue the insulin resistance phenotype, two new Drosophila transgenes were generated with the ability to express the gene in a tissue of interest. In these two new transgenes, Poly is tagged with tRFP (Red Fluorescence Protein) at the N’- (UAS_N’RFPpoly) or the C’-terminus (UAS_polyC’RFP). Overexpression of Poly rescued the insulin resistance phenotype, therefore implicating Poly as a possible important regulator in the development of the insulin resistance phenotype. All of the above findings suggest a vital role of Poly in metabolism and the development of the insulin resistance/diabetic phenotype in Drosophila, providing us the opportunity for new tools in this very medically-relevant field of research.

There has been an increased interest in optimization for the analysis of large-scale data sets which require gigabytes or terabytes of data to be stored. A variety of applications originate from the fields of signal processing, machine learning and statistics. Seven representative applications are described below. - Magnetic Resonance Imaging (MRI): A medical imaging tool used to scan the anatomy and the physiology of a body. - Image inpainting: A technique for reconstructing degraded parts of an image. - Image deblurring: Image processing tool for removing the blurriness of a photo caused by natural phenomena, such as motion. - Radar pulse reconstruction. - Genome-Wide Association study (GWA): DNA comparison between two groups of people (with/without a disease) in order to investigate factors that a disease depends on. - Recommendation systems: Classification of data (i.e., music or video) based on user preferences. - Data fitting: Sampled data are used to simulate the behaviour of observed quantities. For example estimation of global temperature based on historic data. Large-scale problems impose restrictions on methods that have been so far employed. The new methods have to be memory efficient and ideally, within seconds they should offer noticeable progress towards a solution. First-order methods meet some of these requirements. They avoid matrix factorizations, they have low memory requirements, additionally, they sometimes offer fast progress in the initial stages of optimization. Unfortunately, as demonstrated by numerical experiments in this thesis, first-order methods miss essential information about the conditioning of the problems, which might result in slow practical convergence. The main advantage of first-order methods which is to rely only on simple gradient or coordinate updates becomes their essential weakness. We do not think this inherent weakness of first-order methods can be remedied. For this reason, the present thesis aims at the development and implementation of inexpensive higher-order methods for large-scale problems.

Barley row-type describes the number of grains present at a node on the barley spike. Two forms exist amongst cultivated barley: two-rowed with only the central of three spikelets fertile producing a single grain at a node and six-rowed with all three spikelets fertile, producing three grain at a node. Twelve regions of the barley genome have been associated with the row-type character with specific genes identified at three loci, <i>VRS1</i>, <i>VRS4</i> and <i>INT-C</i>. Advancements in the understanding of the genetic control underpinning barley row-type enables the identification of potential mechanisms for improving yield and yield architecture within the cereals.  This study used genetic linkage mapping in segregating F2 populations to refine the genetic location of the row-type locus, <i>VRS3</i>, to 16 candidate genes on barley chromosome 1H. Sequencing candidate loci in 32 <i>vrs3</i> induced mutant alleles identified <i>VRS3</i> to be a highly conserved JmjC histone demethylase, with two natural alleles within European cultivated barley. <i>VRS3</i> was further characterised as a potential means of improving grain uniformity within cultivated six-rowed barley, through phenotypic assessment of grain size in varying allele combinations of <i>VRS3</i>, <i>VRS1</i> and <i>INT-C</i>. The addition of six-rowed alleles at these loci was found to improve balance between central and lateral grain parameters, resulting in a more uniform grain sample. Analysis of gene expression found <i>Vrs3</i> to be constitutively expressed across a diverse panel of barley tissues. Moreover, detailed study within the developing inflorescence suggests a role for <i>Vrs3</i> in the regulation of the row-type genes <i>VRS1</i> and <i>INT-C. </i>

Endocytosis is the process in which a cell engulfs extracellular cargo by creating invaginations within its plasma membrane. The cargo that has entered the cell enters an endosome and then is delivered to either the trans-Golgi network for recycling to the plasma membrane or to the lysosome for its degradation (Trousdale & Kim, 2015). Retromer is a peripheral membrane protein complex that plays a key role in sorting of these cargo molecules (Collins, 2008). More specifically, retromer deliver cargo from the endosome to the trans-Golgi Network, the process which is called retrograde transport of cargo molecules. Retromer dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease. However, recent Genome Wide Association Studies suggest that a mutation in retromer subunit VPS26a, has been linked to Type II Diabetes (Trousdale & Kim, 2015). A 2016 study published in The Faseb Journal attempts to characterize the role of retromer in adipocyte differentiation and insulin-stimulated uptake of glucose through transporter GLUT4 (Yang et al., 2016). The aim of this study is to further investigate the role of retromer in adipogenesis and to determine whether retromer plays a role at the transcriptional level or translational level. In this study, retromer’s VPS35 subunit was knocked down in four mouse 3T3-L1 fibroblast cell lines using the CRISPR-Cas9 approach. These cell lines were differentiated into mature adipocytes and analyzed by Oil-Red O staining, Western Blotting and quantitative PCR. The knockdown of retromer produced varying effects on adipocyte differentiation. In two of the knockdown cell lines, adipocyte differentiation was downregulated whereas adipocyte differentiation was upregulated in the other two cell lines. Although the results from Oil-Red O staining and Western Blot analyses complemented each other, results obtained from qPCR were not as straightforward and further analysis is needed to fully comprehend how retromer acts at the transcriptional level of cell differentiation. Based on the results of this study, retromer is involved in adipogenesis at both the transcriptional and translational level, however it’s mechanism of action remains unclear as both cases of impaired differentiation and upregulated differentiation were observed. Further studies are necessary to determine retromer’s exact role in adipogenesis.

Thesis (M Med (Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / Introduction: Diabetes Mellitus still remains an important non- communicable disease globally. The burden of the disease continues to rise even in the sub-Saharan Africa. Aim: The study aimed to assess and describe the dietary practices and the prevalence of obesity among type 2 diabetic patients seen at Scott Hospital. Methods: A descriptive cross- sectional study was conducted among type 2 diabetic patients at Scott Hospital, Morija, Lesotho. A simple random sample of 50 participants was selected and each completed an interviewer administered questionnaire. The administration of the questionnaire was done by the researcher and a research assistant. Socio- demographic characteristics of the participants were obtained, anthropometric measurements were height and weight of each participant with subsequent determination of the BMI. Dietary intake was assessed using questions from a modified food frequency questionnaire of 16 food groups that reflect the commonest food items available. Results: The results showed that 86% (43/50) of the participants were females and 14% (7/50) were males with a female: male ratio of 6:1. The majority (72%) were above age 50 years and with regards to educational status, 62% had primary school education as the highest level attained. Four percent (4%) had no formal education. Fifty percent (50%) of the participants were unemployed. The mean weight of the participants was 84.22 ± 13.51 kg and the mean height was 157.76 ± 6.10 cm. The mean BMI was 33.97 ± 4.99 kg/m². Seventy-eight percent (38/50) of the participants were obese, and 14% (7/50) of the participants who were females, were morbidly obese with BMIs ≥ 40kg/m². The prevalence of obesity when stratified by gender showed that 57% (4/7) of male participants and 81% (35/43) of female participants were obese. According to the dietary assessments, food groups with the highest reported consumption per unit per month were; maize meals, breakfast-cereals and bread respectively. Conclusion: The study showed a predominantly female and elderly population of type 2 diabetics at Scott Hospital, Morija, Lesotho. The prevalence of obesity was high (78%) among the participants and this further supports the view that obesity is a major risk factor for type 2 diabetes. Reported dietary intake showed a higher consumption of carbohydrates and a very low intake of dietary fibre as represented by legumes. Keywords: Type 2 diabetes mellitus, dietary habits and obesity.