Thesis (Ph.D.) - James Cook University, 2003. / Typescript (photocopy) Bibliography: leaves 223-257.

Instability characterizes the taxonomy of the African rodent subfamily Otomyinae. Two genera, Otomys and Parotomys, and 14 species are currently recognized, but the generic subdivision is equivocal. Between two and five cytotypes are delimited within O. irroratus, which illustrate a rapid rate of karyotypic evolution, and may reflect incipient speciation. In an attempt to resolve the group's phylogeny, the mitochondrial cyt b (complete) and 12S rRNA (802 bp) genes were analyzed using parsimony, distance and maximum likelihood methods. Alternative models of evolutionary change were compared to determine the best-fit model for each data set. Both genes failed to resolve deeper evolutionary associations, but the cyt b gene proved useful in resolving relationships among closely related taxa. Robust associations consistently retrieved include: (1) the O. irroratus cytotypes form a monophyletic group with O. laminatus basal. (2) an exclusively East African clade comprises two representatives of O. anchietae lacustris (not sister taxa), O. tropicalis with O. denti basal~ (3) Otomys angoniensis and O. maximus from southern Africa are monophyletic sister taxa with O. typus jacksoni and O. typus successively basal, making the East African Otomyinae non-monophyletic. (4) Parotomys brantsii and P. Wtledalei cluster within Otomys, but with no clear sister relationships. These results question some of the nomenclatural divisions in current use. First, the paraphyly of Otomys renders the recognition of two distinct genera unsupported. Second, the strongly supported monophyletic clustering of O. angoniensis and O. maximus coupled with the comparatively small genetic distance separating them, disputes the status of O. maximus. Third, the paraphyletic associations shown for representatives of O. typus and O. anchietae might imply that distinct evolutionary lineages are contained within these species. Otomys irroratus is phylogenetically distant from other Otomys species previously considered conspecifics. Moreover, a sister association between the Band C cytotypes to the exclusion of Al and A2, corroborate the delimitation of two major cytogenetic groups within O. irroratus. The major clades form an unresolved polytomy suggesting that the Otomyinae experienced a rapid radiation approximately 5 Myr ago. A biogeographical scenario is presented in light of palaeo-climatic changes during the late Miocene and Plio-Pleistocene epochs. / Thesis (DPhil (Zoology))--University of Pretoria, 2005. / Zoology and Entomology / unrestricted

Made available in DSpace on 2015-11-11T12:13:54Z (GMT). No. of bitstreams: 2 raul_dias_ioc_dout_2014.pdf: 7886227 bytes, checksum: accba0e5a6fdc7af44ece1654e72921c (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2015-04-14 / O tecido linfóide das mucosas apresenta estruturas especializadas contendo células imunorreguladoras e mecanismos capazes de determinar indução de tolerância ou resposta inflamatória após a administração oral de um antígeno. Diversos agentes causadores de doenças utilizam a via oral como rota de infecção, dentre eles o Toxoplasma gondii. A infecção por T. gondii pode gerar diversas manifestações patológicas, como por exemplo, a doença inflamatória intestinal, que envolve diferentes tipos celulares, diversas citocinas, bem como a participação da microbiota intestinal. Para melhor compreender o envolvimento dos diversos tipos celulares e elementos humorais na toxoplasmose, elegemos como modelos experimentais as linhagens de camundongos geneticamente selecionados para tolerância oral: TR (resistentes à tolerância) e TS (susceptíveis à tolerância). Os camundongos TS se caracterizam por baixa resposta inflamatória e maior quantidade de células T regulatórias produtoras de IL-10. Em contraste, os camundongos TR produzem fortes reações inflamatórias. A caracterização da toxoplasmose experimental nos camundongos TR e TS infectados por gavagem com T. gondii foi feita por análise histológica e imunohistoquímica de cortes do intestino, fígado e baço, dosagem de citocinas e quimiocinas, além da caracterização da microbiota intestinal Nossos resultados confirmam o estabelecimento de uma resposta inflamatória intestinal aguda nos camundongos TR, que ocorre durante os 14 dias iniciais da infecção. As lesões apresentam macrófagos e, em menor número, células dendríticas. Além disso, o perfil de citocinas corrobora essas observações, com alta produção de citocinas pró-inflamatórias, tanto sistêmica quanto localizada. Os camundongos TS, por outro lado, apresentaram um perfil característico voltado para a regulação, inibindo a infecção intestinal e produção de citocinas inflamatórias, ao mesmo tempo em que favorece um aumento da quantidade de parasitos nos órgãos. O perfil da microbiota intestinal não apresentou diferenças qualitativas entre as linhagens TS e TR, porém os camundongos TS possuem maior presença de bactérias do gênero Prevotella, enquanto nos camundongos TR predomina a família Enterobacteriaceae. Esses enterotipos observados não exibiram mudanças significativas ao longo do período de infecção de 21 dias dentro das mesmas linhagens / The mucosal lymphoid tissue has specialized structures containing immunoregulatory cells and mechanisms to determine the induction of tolerance or inflammatory response following oral administration of an antigen. Several agents causative of diseases uses the oral route as a form of infection, including Toxoplasma gondii . T. gondii infection can lead to various pathological manifestations , such as inflammatory bowel disease, involving various cell types, several cytokines, as well as the involvement of the intestinal microbiota. To better understand the involvement of different cell types and humoral elements in the toxoplasmosis , we choose as experimental models two lineages of mice genetically selected for oral tolerance: TR (tolerance resistant) and TS (tolerance susceptible) . TS mice are characterized by low inflammatory response and increased amount of regulatory T cells producing IL - 10 . In contrast, the TR mice produce strong inflammatory reactions. Characterization of experimental toxoplasmosis in TR and TS mice infected by gavage with T. gondii was made by histological and immunohistochemical analysis of sections of the intestine, liv er and spleen , dosage of cytokines and chemokines, in addition to characterization of intestinal microbiota. Our results confirm the setting of an acute inflamm atory response in the intestines of TR mice , which occurs during the initial 14 days from infect ion. Lesions presented macrophages and to a lesser number, dendritic cells. Moreover, the cytokine profile supports these observations, with a high production of pro - inflammatory cytokines, either systemic or localized. TS mice, on the other hand, showed a characteristic profile directed to regulati on , inhibiting intestinal infection and production of inflammatory cytokines at the same time it promotes an increase in the number of parasites in the organs . The intestinal microbiota profile did not differ qua litatively between the TS and TR lineages , but TS mice have greater presence of bacteria of genus Prevotella , while in TR mice pre dominates the Enterobacteriaceae family . The se enterotip e s showed no significant changes during the 21 day period within the same lineages

Phylogeographic mitochondrial DNA (mtDNA) population structure was determined for Aethomys namaquensis and A. ineptus from southern Africa and Swaziland. It was evident from the study that A. namaquensis reflected a pattern of phylogenetic discontinuity with and without spatial separation between populations. Previously documented mtDNA phylogeographic patterns recorded in the rock hyrax, Procavia capensis and the red rock rabbit species, Pronolagus rupestris and P. randensis, coincided with the phylogeographic break that was detected in one of the mtDNA lineages (C) within A. namaquensis. Similar vicariant events may have been responsible for shaping evolutionary processes in the independent Procavia, Pronolagus and Aethomys lineages. In contrast, A. ineptus showed a pattern of shallow phylogeographic structuring. The marked genetic differences detected in A. namaquensis and A. ineptus may reflect the influences of habitat specificity, its fragmentation and the effects of life history on mtDNA gene flow. The study also revealed three genetically well-supported lineages within A. namaquensis: a lineage (A) found in the Limpopo valley, a lineage (B) widely distributed across the Karoo and a lineage (C) found across the grasslands of the North-West, Limpopo and Mpumalanga Provinces. These spatial distributions broadly coincided with the ranges of four previously proposed morphologically defined subspecies. From the present sample sizes, there is only good support, from a molecular point of view, for the subspecies A. n. lehocla (lineage B). In addition to the three well-supported lineages, six geographically restricted lineages were identified that could not be assigned to any of the four previously proposed subspecies, A. n. namaquensis, A. n. monticularis, A. n. alborarius and A. n. lehocla. Molecular techniques, specifically the analysis of the mtDNA cytochrome b gene, have been useful in the identification of sibling species. This technique has also proved to be useful in the identification of two cryptic species, A. chrysophilus and A. ineptus in this study. Phylogenetic analysis revealed two maternal groups corresponding to A. chrysophilus and A. ineptus. Distributional data of these two species, suggest that A. chrysophilus occupies the low elevations of the Limpopo River drainage, while A. ineptus occupies the remainder of South Africa at higher elevations, but expands into lower elevations in the southern portion of its range. Phylogenetic relationships among four southern African species of Aethomys suggest the presence of two clades that included: 1) A. chrysophilus and A. ineptus and 2) A. namaquensis and A. granti. This study, however, revealed that Aethomys may be paraphyletic, suggesting that the allocation of A. namaquensis and A. granti to the subgenus Micaelamys needs to be investigated further. / Dissertation (MSc (Genetics))--University of Pretoria, 2006. / Genetics / unrestricted

Part of Thesis (Ph. D.)--University of Florida, 1964. / Cover title. Includes bibliographical references (p. 41-42).

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [154]-164).

This work sets out to describe the socio-ecological niches of otonya irroratus, Rhabdomys pumilio and Praomys natalensis in the Natal midlands. This objective necessitated a broad-based approach in which aspects of the ecological niches, and the social behaviour and social organization of the three species were investigated in field (habitat and trapping) and laboratory (experimental and observational) studies, during the period January 1976-May 1978. To test the assumption that the commonly sympatric O. irroratus, R. pumilio and P. natalensis are primarily adapted to habitats which differ mainly in respect of water availability, an attempt was made to define their positions on a mesic/xeric continuum. The results suggest that in terms of the parameters measured (responses to water and cover availability, and to food and water deprivation), O. irroratus is more nearly mesically adapted than is R. pumilio, with P. natalensis positioned between the two extremes. However, in the case of P. natalensis it is apparently of overriding importance that this species is adapted to disturbed habitats. The mesic habitats preferred by O. irroratus are often of limited size, but resource availability within these areas is apparently high and stable. Extensive areas of suitable habitat are available to R. pumilio, but availability of resources is seasonally variable. The disturbed habitats preferred by P. natalensis arise unpredictably in nature and, depending on the rate of ecological succession, may be short-lived; hence availability of resources to this species is highly unpredictable. Social behaviour was studied by means of dyadic encounters in the laboratory. Communication in O. irroratus, R. pumilio and P. natalensis appears to be dominated by auditory, visual and olfactory signals respectively, although O. irroratus also has well developed visual signals in its communicatory repertoire. These differences are explained mainly in terms of patterns of diel activity and habitat preferences: R. pumilio is adapted to bright light, and its visual signals are subtle; O. irroratus is adapted to dim light, and its visual signals involve gross changes in posture, while the use of loud, low frequency vocalizations would allow conspecifics to know their precise location in relation to one another in dense vegetation; P. natalensis is nocturnal, and hence appears to emphasize olfactory (and possibly ultrasonic) communication, which would permit transfer of information in the dark. O. irroratus is overtly highly aggressive, but agonism is ritualized; ritualization of aggression has probably evolved to allow high densities of this species to exploit limited areas of prime habitat. R. pumilio is less overtly aggressive than O. irroratus, but aggression tends to be unritualized; direct aggression probably acts as a spacing mechanism, and is possible in view of the large areas of habitat available to this species. Agonism is poorly developed and ritualized in P. natalensis, permitting high sociability and group formation in this species, and maximum exploitation of locally abundant resources. Social organization was studied in the field (trapping studies) and by means of dyadic encounters in the laboratory. The social system of O. irroratus appears to include temporal territoriality, which would permit animals to live in close spatial association (in small areas of habitat) while seldom actually meeting. Hierarchical ranking occurs in male O. irroratus and R. pumilio, with competition in both most likely being for mating opportunities. Breeding females of these two species are intrasexually territorial, in the case of Q. irroratus thereby providing dispersing young with adequate space for establishment of a home-range in prime habitat, and in R. pumilio protecting the young against conspecific female aggression until dispersal. R. pumilio tends to aggregate in mesic refuge habitats in winter, which apparently reflects the seasonality of resource availability to this species in drier environments. P. natalensis is colonial, an adaptation facilitating maximum exploitation of temporarily abundant resources in transitory disturbed habitats. In response to intense courtship by the male, female R. pumilio appear to undergo reflex ovulation; this strategy would maximize the chances of fertilization occurring during occasional meetings between males and females. Courtship intensity is low in P. natalensis, and presumably because the colonial social system of this species ensures frequent association between potential mates, females appear to ovulate spontaneously. Sexual activity was not observed in O. irroratus. The life-history tactics of the three species are such that o. irroratus and P. natalensis respectively appear to be K- and r-selected, with R. pumilio falling between these two extremes on an r-K continuum. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1982.

Made available in DSpace on 2016-05-02T13:06:59Z (GMT). No. of bitstreams: 2 edson_oliveira_ioc_dout_2014.pdf: 7681363 bytes, checksum: d1541a9340bac4e63312fb02768ab622 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / A dengue é considerada uma grande ameaça em um vasto território mundial que resulta em cerca de 20 mil mortes ao ano. Modelos animais para o estudo da dengue constituem uma ferramenta importante não somente para o desenvolvimento de estratégias anti-dengue como vacinas e antivirais, mas também para o estudo da resposta imune induzida após a infecção. Uma abordagem amplamente utilizada para testes de candidatos vacinais é o uso de camundongos BALB/c infectados por via intracerebral (i.c.) com um vírus DENV neuroadaptado. Como este modelo envolve um desafio letal, inúmeros trabalhos fizeram uso apenas deste parâmetro para avaliar a eficácia de vacinas anti-dengue. Sendo assim, pouco se sabe a respeito da dinâmica da resposta imune primária em animais infectados pela via intracerebral, bem como os mecanismos pelos quais uma vacina pode exercer proteção contra a infecção sob tais condições. Neste contexto, o presente estudo objetivou analizar a resposta imune anti-dengue no modelo BALB/c infectado por via i.c. com o vírus DENV neuroadaptado, investigando a participação de subpopulações celulares na imunidade primária e também durante a imunidade adaptativa induzida por vacinas de DNA. Com relação à resposta imune primária, observamos que apesar da via de inoculação não natural empregada, foi possível observar efeitos periféricos decorrentes da infecção com DENV2, como ativação e migração de células T para órgãos alvo, bem como produção de anticorpos e citocinas Com relação à resposta imune adaptativa aos antígenos do DENV, detectamos que vacinas de DNA que codificam as proteínas NS1, NS3 ou E de DENV2 produzem efeitos peculiares quanto à ativação de células T. Vimos que os antígenos E e NS3, principalmente NS3, induzem ativação de células T mais acentuada do que o antígeno NS1, segundo a expressão reduzida de CD45RB na superfície destas células. Experimentos de transferência de células T utilizando CFSE como sonda mostraram que após o desafio com DENV, animais protegidos pela vacinação com pcTPANS1 apresentaram ativação marcante de células T com proliferação e migração destas células para diversos locais no hospedeiro, incluindo tecido hepático e cerebral. Durante a resposta imune adaptativa ao antígeno NS1, foram encontrados alguns possíveis correlatos de proteção, como por exemplo, os fenótipos TCD4+CD44hi e TCD8+CD44hiCD69- presentes no baço. Além disso, uma população celular de alta granulosidade B220hiCD19+CD11clow presente no sangue de camundongos BALB/c após o desafio com DENV parece estar relacionada a uma melhor condição clínica destes animais. Em conclusão, este estudo contribuiu para a compreensão da dinâmica da resposta imune em animais infectados pela via i.c. Além disso, o estudo forneceu novos insights na compreensão dos mecanismos envolvidos na proteção induzida por vacinas de DNA anti-dengue / Dengue is considered a major threat worldwide that results in approximately 20000 deaths every year. Animal models for dengue disease represent an important tool not only to delelop anti-dengue strategies, such as vaccines and antivirals, but also to investigate the immune response incuced during the infection. A commonly used appoach to evaluate vaccine candidates is the BALB/c mouse model infected with a neuroadapted DENV by the intracerebral (i.c.) route. Since the animals succumb to the infection in this model, many groups consider only the survival as the endpoint in the evaluation of anti-dengue vaccine efficacy. Therefore, little is known about the primary immune response dynamics of these animals infected by the i.c. route, as well as the mechanisms through which the vaccine may protect the host under such conditions. In this context, the present study aimed to analyse the primary immune response against DENV in the BALB/c mouse model, investigating the role of cellular subpopulations in the primary immunity and also during the adaptative immunity induced by DNA vaccines. Concerning the primary immune response, eventhough the inoculation route applied was not natural, peripheral effects caused by DENV infection, like T cell activation and migration to target organs, as well as the production of antibodies and cytokines were observed. With respect to the adaptive immune response to DENV antigens, DNA vaccines that encode the NS1, NS3 or E DENV proteins produced peculiar effects once considering the activation of T cells. We found that E and NS3 antigens, mainly NS3, induced more pronounced T cell activation in comparison to NS1 protein, as measured by the surface membrane expression of CD45RB. Transference experiments of T cells obtained from vaccinated animals and traced by CFSE showed evident T lymphocytes activation, proliferation and migration to different sites in the host, including hepatic and brain tissue, after DENV challenge. During the adaptive immune response to NS1 antigen we found possible cell-fenotypes related to protection, such as TCD4+CD44hi and TCD8+CD44hiCD69- detected in the spleen. Besides, a cell population B220hiCD19+CD11clow, showing high granulosity, detected in blood samples after DENV challenge seemed also to be related with a better clinical condition of these animals. In conclusion, this study contributed for the elucidation of the immune response dynamics in animals infected with DENV by the i.c. route. Moreover, this work provided new insights in the comprehension of the mechanisms involved in the protection induced by anti-dengue DNA vaccines. / 2017-10-16

Thesis (M. Sc.)--York University, 2000. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 111-119). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ59179.

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