No description available.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

by Julia Luen-wah Woo. / Thesis (M.Ph.) -- Chinese University of Hong Kong, 1988. / Bibliography: leaves 90-94.

Entre le XIème et le XVIème siècle, la Mer des Indes fut le théâtre de nombreux mouvements populationnels aux fins essentiellement commerciales ou coloniales. Madagascar se trouve à la croisée des mondes asiatiques et africains. La côte sud-est malgache a vu l'arrivée de plusieurs migrations : la dernière, probablement vers la fin du XVème siècle, serait celle des Antemoro dont une partie d'entre eux se réclame d'une origine arabe et se rattache à La Mecque. L'éthnie des Antemoro a fait l'objet de nombreuses études anthropologiques et linguistiques. Néanmoins, le débat sur l'origine des migrants fait toujours l'objet d'hypothèses contradictoires. Leurs origines génétiques pourraient ainsi être l'Arabie, l'Afrique de l'Est, l'Inde ou encore l'Asie du Sud-Est à une époque où ces régions étaient déjà islamisées. Ce travail a consisté à étudier la diversité génétique d'une population Antemoro afin d'apporter des éléments de réponse à la question de leur origine biologique. Ce projet interdisciplinaire a pour objectif de mettre en relation l'anthropologie culturelle et sociale avec l'anthropologie biologique. Le polymorphisme du chromosome Y a été étudié afin de rechercher les origines des lignées paternelles par l'analyse de 17 marqueurs microsatellites ainsi que des mutations ponctuelles de l'ADN de la partie non recombinante du chromosome Y. De même, la variabilité génétique des lignées maternelles a été analysée par séquençage des régions hypervariables I et II de l'ADN mitochondrial, et par la définition de polymorphismes bialléliques dans sa région codante. Nous avons mis en évidence la présence de deux haplogroupes du chromosome Y chez certains groupes Antemoro, qui les différencient de la diversité habituellement rencontrée dans les populations malgaches. Bien que la majeure partie des Antemoro entre dans la diversité observée en Afrique sub-Saharienne et en Asie du Sud-Est, quelques haplotypes, des lignées paternelles, les lieraient au Moyen-Orient. Les lignées maternelles, quant à elles, ne les différencient pas de celles des autres populations malgaches. L'isolat génétique formé par certaines « pseudo-castes » Antemoro confirme bien l'isolat culturel. Ce travail apporte une nouvelle vision de la diversité génétique humaine à Madagascar. / Between the 11th and 16th century, the Indian Ocean was the scene of many population movements notably for commercial and colonial purposes. Madagascar is located at the crossroads of the Asian and African continents. Several migrations have occurred in this region; the last one during the late 15th century involved the Antemoro population who claimed an Arabian origin in Mecca. Many anthropological and linguistic studies have been carried out on this ethnic group, but the origin of these migrants remains contentious. It is uncertain whether their origins were in Arabia, East Africa, India or Southeast Asia, when these regions were Islamized. In this study we assessed the genetic diversity of an Antemoro population from villages between Manakara and Vohipeno, to determine their biological origin. The aim of our interdisciplinary study was to link cultural and social anthropology with biological anthropology. Y-chromosome polymorphisms were studied by analyzing 17 microsatellites markers and some SNPs in the non-recombining region of the Y-chromosome to determine the biological origins of the paternal lineages. In addition, genetic variability of maternal lineages was analyzed by sequencing hypervariables regions I and II, and by defining bi-allelic polymorphisms in the coding region of mitochondrial DNA. We found two Y-chromosome haplogroups in some Antemoro groups that differentiated them from the typical genetic variability found in other Malagasy populations. Although most of the Antemoro showed a genetic diversity similar to that observed in sub-Saharan Africa and Southeast Asia, few haplotypes associated to paternal lineages linked them to the Middle East. Maternal lineages did not differ from those found in other Malagasy populations. The genetic isolate formed by some Antemoro groups confirmed their cultural isolation. This study provides a new view of the human genetic diversity in Madagascar.

Thesis (Ph. D.)--University of Michigan, 1971. / Includes bibliographical references (leaves 106-110).

<p>The current research is directed towards dissection of host genetic factors involved in host immune response and the malaria disease outcome. A possible association between FcγRIIa polymorphism and anti-malarial antibody (A.M.A) responses were investigated in Sudanese patients in relation to clinical outcome of falciparum malaria. The frequency of the R/R131 genotype was significantly higher in patients with severe malaria as compared with mild malaria. A.M.A IgG3 was shown to be associated with reduced risk of clinical malaria in individuals carrying the H/H131 genotype. Low levels of IgG2 reactive with the Pf332-C231 antigen were associated with lower risk of severe malaria in individuals carrying the H131 allele. </p><p>Fulani and Masaleit, two sympatric ethnic groups in Sudan, are characterized by marked differences in susceptibility to falciparum malaria. We investigated whether the two populations differ in the frequency of GM/KM allotypes. The distribution of GM/KM phenotypes differed significantly among the two groups, with Gm 6 being significantly lower among the Fulani, and the combined frequency of Km 1,3 and Gm 1,17 5,6,13,14 phenotypes was found to be higher among Masaleit.</p><p> In interethnic study we investigated whether the two groups differ in the frequency of FcγRIIa and HbAS genotypes. The frequency of the H/H131, R/R13 and HbAS genotypes differed significantly among the two groups. Moreover, the Fulani showed higher levels of A.M.A IgG2 and lower IgG1 and IgG3 when compared to their sympatric non-Fulani neighbours.</p><p>A tri-allelic SNP (C/T/A) in the CRP gene was investigated for possible ethnic associations. The A allele, which is associated with higher basal CRP levels, was found to be less frequent in the Fulani compared with non-Fulani ethnic groups both in Sudan and Mali. </p><p>In conclusion, our results suggest possible associations between FcγRIIa, CRP genotypes, GM/KM allotypes, and anti-malarial antibody responses and the clinical outcome of falciparum malaria.</p>

The current research is directed towards dissection of host genetic factors involved in host immune response and the malaria disease outcome. A possible association between FcγRIIa polymorphism and anti-malarial antibody (A.M.A) responses were investigated in Sudanese patients in relation to clinical outcome of falciparum malaria. The frequency of the R/R131 genotype was significantly higher in patients with severe malaria as compared with mild malaria. A.M.A IgG3 was shown to be associated with reduced risk of clinical malaria in individuals carrying the H/H131 genotype. Low levels of IgG2 reactive with the Pf332-C231 antigen were associated with lower risk of severe malaria in individuals carrying the H131 allele. Fulani and Masaleit, two sympatric ethnic groups in Sudan, are characterized by marked differences in susceptibility to falciparum malaria. We investigated whether the two populations differ in the frequency of GM/KM allotypes. The distribution of GM/KM phenotypes differed significantly among the two groups, with Gm 6 being significantly lower among the Fulani, and the combined frequency of Km 1,3 and Gm 1,17 5,6,13,14 phenotypes was found to be higher among Masaleit. In interethnic study we investigated whether the two groups differ in the frequency of FcγRIIa and HbAS genotypes. The frequency of the H/H131, R/R13 and HbAS genotypes differed significantly among the two groups. Moreover, the Fulani showed higher levels of A.M.A IgG2 and lower IgG1 and IgG3 when compared to their sympatric non-Fulani neighbours. A tri-allelic SNP (C/T/A) in the CRP gene was investigated for possible ethnic associations. The A allele, which is associated with higher basal CRP levels, was found to be less frequent in the Fulani compared with non-Fulani ethnic groups both in Sudan and Mali. In conclusion, our results suggest possible associations between FcγRIIa, CRP genotypes, GM/KM allotypes, and anti-malarial antibody responses and the clinical outcome of falciparum malaria.

Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 153-162). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Pas de résumé fourni. / No summary available.

O carrapato do boi, Rhipicephalus microplus, é o principal empecilho para o avanço da produção pecuária, causando enormes prejuízos econômicos. Durante a infestação, o carrapato acaba ingerindo uma grande quantidade de imunoglobulinas presentes no soro do hospedeiro. Desse modo, como mecanismo de defesa e com o objetivo de auxiliar o repasto sanguíneo realizado pelas fêmeas, carrapatos machos Ixodidae, secretam proteínas ligantes de IgG (IGBPs) contidas em sua saliva, teoricamente interferindo na ligação específica de anticorpos com antígenos do carrapato, bem como nas funções efetoras da IgG. Raças bovinas taurinas e zebuínas possuem uma peculiar distribuição de alótipos de IgG e, ao mesmo tempo, frente às infestações por carrapatos, tais raças se comportam de maneira distinta, sendo taurinas susceptíveis e zebuínas resistentes a esse ectoparasita. Uma vez que já é relatado na literatura existir diferença na ligação entre as IGBPs de diversos patógenos e os diferentes alótipos de IgG, o presente trabalho teve por objetivo avaliar a natureza das interações entre a IGBP-C de R. microplus e os alótipos de IgG bovina de animais suscetíveis ou resistentes a carrapatos. Para isso, foi feita a genotipagem por sequenciamento da região CH1-CH3 de IgG1 e IgG2, de 40 bovinos da raça taurina Holandesa (Holandês preto e branco - HPB) e 40 bovinos zebuínos da raça Nelore, com posterior purificação do alótipo de IgG1 e IgG2 mais comum em cada raça a partir do soro dos animais homozigotos. Curiosamente, verificou-se que havia uma associação entre os genótipos da região constante da cadeia pesada de IgG1 e IgG2 com os fenótipos de infestação por carrapato observados nos animais estudados. Em seguida, foram realizados ensaios em sistema de Ressonância Plasmônica de Superfície (Biacore T200 - GE Healthcare) para avaliar a afinidade de ligação entre a proteína recombinante IGBP-C e os alótipos de IgG1 e IgG2 bovinas, de uma forma não cognata. Por meio do ensaio em Biacore, observou-se uma maior afinidade de ligação da IGBP-C com alótipos de IgG2 de ambas as raças estudadas em relação aos alótipos de IgG1 e apesar de ligar em mais moléculas do alótipo de IgG2 mais frequente em bovinos Nelore (resistente a carrapato), apresentou uma afinidade maior para o alótipo de IgG2 mais frequente na raça HPB (suscetível a carrapato). Além disso, foi possível confirmar a porção Fc como o sítio de ligação preferencial da IGBP-C na IgG. Por fim, para um maior entendimento da sua função, foi feita a modelagem por homologia da IGBP-C e em ensaios adicionais, visto que essa proteína também interfere no processo de angiogênese, bem como na ativação da via clássica do complemento. Em suma, no presente trabalho foi possível descrever algumas funções promovidas pela IGBP-C, demonstrando assim, a sua importância em compor mecanismos de escape do carrapato R. microplus em relação a resposta imune do hospedeiro / The cattle tick, Rhipicephalus microplus, is the main impediment to the advance of livestock production, causing enormous economic losses. During infestation, the tick ingests a large amount of immunoglobulins present in the host\'s serum. Consequently as a defense mechanism and for assisting the blood meal performed by females, male Ixodidae ticks secrete IgG binding proteins (IGBPs) contained in their saliva, theoretically interfering in the specific binding of antibodies with tick antigens and in the effector functions of IgG. The taurine and zebu bovine breeds have a peculiar distribution of IgG allotypes and also present different phenotypes of tick infestation, being susceptible taurines and zebuines resistant to this ectoparasite. Since it is reported in the literature that there is a difference in the binding between the IGBPs of different pathogens and the different IgG allotypes, the present work aimed to evaluate the nature of the interactions between the IGBP-C of R. microplus and the IgG from susceptible or tick resistant animals. For this, was done genotyping by sequencing of the CH1-CH3 region of IgG1 and IgG2 from forty Holstein taurine and forty Nelore zebu cattle, with subsequent purification of the more common IgG allotypes in each breed, from the serum of homozygous animals. Interestingly, there was an association between IgG1 and IgG2 heavy chain constant region genotypes with tick infestation phenotypes. Subsequently, assays were performed in Surface Plasmon Resonance System (Biacore T200) to evaluate the binding affinity between the recombinant IGBP-C protein and the bovine IgG1 and IgG2 allotypes in a non-cognate manner. Through the Biacore assay, was observed that IGBP-C binding more affinity with IgG2 than IgG1 allotypes of both breeds, and although IGBP-C binds more molecules of the most frequent IgG2 allotype in Nelore tick resistant cattle, showed a higher affinity for the most frequent IgG2 allotype in the HPB, tick susceptible cattle. In addition, it was possible to confirm the Fc portion as the preferred binding site of IGBP-C in IgG. The homology modeling of this protein was done for a better understanding of its function and finally, IGBP-C has also been shown to interfere with the angiogenesis process, as well as in the activation of the classical complement pathway. In short, in the present work it was possible to describe some of the functions promoted by the IGBP-C, thus demonstrating its importance in composing escape mechanisms of the R. microplus tick to the host immune response