Thesis (M.Sc.). / Written for the Institute of Parasitology. Title from title page of PDF (viewed 2009/08/07). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 111-119).

Schistosome is the causative agent of schistosomiasis which is one of the world's most prevalent tropical diseases. In the skin of infected host, significant inflammatory response to the parasite is not observed. Previous studies from Schistosoma mansoni showed that this subdued inflammatory response was due to a 16-KDa protein, Sm16, which is present abundantly in the secretions of schistosomulae. Provided that Schistosoma japonicum shares the same infective pathway as S. mansoni by penetrating the skin, it seems logical that S. japonicum has a protein with a similar role to Sm16 to down-regulate host immune responses. According to the cDNA sequence of Sm16, a corresponding gene (designated Sj16) of Sm16 has previously been amplified and cloned from the cercarial cDNA of S. japonicum. Sequence analysis showed that Sj16 shares 99% identity with Sm16 in its nucleotide sequence, and 100% identity in its protein sequence. While previous studiers reported their failure in obtaining the soluble recombinant protein of Sm16, we expressed and purified the recombinant Sj16 (rSj16) from E. coli in the present study. Western blot and ELISA analysis showed that S. japonicum-infected rabbit sera could not recognize rSj16, indicating that native Sj16 might fail to induce circulating antibodies during S. japonicum infection. In the in vivo study, rSj16 dramatically suppressed not only the recruitment of leukocytes to the peritoneal cavity of BALB/c mice injected with thioglycollate, but also the maturation of thioglycollate-induced peritoneal macrophages. The suppression effect was accompanied by a marked up-regulation of IL-10 and IL-1RA transcripts, and down-regulation of IL-12p35, IL-1beta and MIP-2 transcripts in peritoneal cells. Further analysis revealed that rSj16 also inhibited both humoral and cellular immune responses to heterologous antigens. In addition, rSj16 was found to induce macrophage differentiation of the murine myeloid leukemia WEHI-3B (JCS) cells, and regulate the differentiation of mouse hematopoietic cells towards the macrophage lineage. Although previous studies indicated the involvement of endogenous IL-1alpha, IL-1beta and TNF-alpha in the macrophage differentiation of JCS cells, the results from this study suggested that rSj16-induced JCS cell differentiation do not rely on the endogenous production of these three cytokines. This is the first study to successfully express and purify sufficient soluble rSj16, and demonstrate the anti-inflammatory and immunomodulatory effects of the rSj16. / Hu, Shaomin. / Adviser: Ming Chiu Fung. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0210. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 139-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Diss. (sammanfattning) Umeå : Univ., 2009. / Härtill 4 uppsatser.

In a 4-cell C. elegans embryo the ventral blastomere EMS requires polarity signaling from its posterior sister cell, P2. This signaling event enables EMS to orient its division spindle along the anterior-posterior (A/P) axis and to specify the endoderm fate of its posterior daughter cell, E. Wnt pathway components have been implicated in mediating P2/EMS signaling. However, no single mutants or various mutant combinations of the Wnt pathway components disrupt EMS polarity completely. Here we describe the identification of a pathway that is defined by two tyrosine kinase related proteins, SRC-1 and MES-1, which function in parallel with Wnt signaling to specify endoderm and to orient the division axis of EMS. We show that SRC-1, a C. elegans homolog of c-Src, functions downstream of MES-1 to specifically enhance phosphotyrosine accumulation at the P2/EMS junction in order to control cell fate and mitotic spindle orientation in both the P2 and EMS cells. In the canonical Wnt pathway, GSK-3 is conserved across species and acts as a negative regulator. However, in C. elegans we find that GSK-3 functions in a positive manner and in parallel with other components in the Wnt pathway to specify endoderm during embryogenesis. In addition, we also show that GSK-3 regulates C. elegans germline development, a function of GSK-3 that is not associated with Wnt signaling. It is required for the differentiation of somatic gonadal cells as well as the regulation of meiotic cell cycle in germ cells. Our results indicate that GSK-3 modulates multiple signaling pathways to regulate both embryogenesis and germline development in C. elegans.