3 resultados para SERK


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This r\.~et.lrch examined ho\\' ~ight \\'omen artists \\'ho t~ach at the uni versity and college level, balance thcir artistic practic~ and their institu tional responsibilities as tcachers. This thesis reprt.~ents the culmination of \\'ork for my second graduate degree. For my first degrCt! on th~ grad uat~ level, I concentratoo on d~veloping my artistic practice. This ~Iaster's Degree in Education is no k~ important to m~. In pursuing studies in the field of education I \\'anted to understand my rol~ as both an educator and an artist and in the process I uncovered the interplay of race, class, and gender at \\'ork in th~ classroom. Coming from a \\'orking-class, immigrant background \\'here higher education \vas vie\\'cd as a stepping stone that \"ould enable my siblings and me a greater spectrum of opportunities, I \\'as at last able to understand my o\\'n educational experiences, more clearly. I discovered ho\\' d\.~ply I internalized the racism, sexism and class discrimination, I submitted to in my history as a student. Becoming a\\'are about the social forc\.~ at "'ork \\'ithin my day to day life has provided me \\'ith instruments \\'hich I can usc to examine and respond to these inequities as I confront them in th~ future. This \,'ork exists as a serk'S of responses and further av~nues for investigation on some themes I first began to explor~, albeit very tentati\'~ly, during my first incarnation as a graduate student and so though the h\'o bound volum~s rna-\' one da.v sit si.d~ b\' s id~ on the bookshelf, th~\-' exist in the context of my life as a set of brackets surrounding a series of qUl'Stions about being a \\'Onlan, a teachcr and an artist.

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The physiological and molecular processes controlling zygotic and somatic embryo development in angiosperms are mediated by a hierarchically organized program of gene expression. Despite the overwhelming information available about the molecular control of the embryogenic processes in angiosperms, little is known about these processes in gymnosperms. Here we describe the cloning and characterization of the expression pattern of the Araucaria angustifolia putative homolog of a SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) gene family member, designated as AaSERK1. The Araucaria AaSERK1 gene encodes a leucine-rich repeat receptor-like kinase showing significant similarity to angiosperm homologs of SERK1, known to be involved in early somatic and zygotic embryogenesis. Accordingly, RT-PCR results showed that AaSERK1 is preferentially expressed in Araucaria embryogenic cell cultures. Additionally, in situ hybridization results showed that AaSERK1 transcripts initially accumulate in groups of cells at the periphery of the embryogenic calli and then are restricted to the developing embryo proper. Our results indicate that AaSERK1 might have a role during somatic embryogenesis in Araucaria, suggesting a potentially conserved mechanism, involving SERK-related leucine-rich repeat receptor-like kinases, in the embryogenic processes among all seed plants.

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Aberrant expression and/or activation of Src Family of non-receptor protein tyrosine kinases (SFKs) occur frequently during progressive stages of multiple types of human malignancies, including prostate cancer. Two SFKs, Src and Lyn, are expressed and implicated in prostate cancer progression. Work in this dissertation investigated the specific roles of Src and Lyn in the prostate tumor progression, and the effects of SFK inhibition on prostate tumor growth and lymph node metastasis in pre-clinical mouse models. ^ Firstly, using a pharmacological inhibitor of SFKs in clinical trials, dasatinib, I demonstrated that SFK inhibition affects both cellular migration and proliferation in vitro. Systemic administration of dasatinib reduced primary tumor growth, as well as development of lymph node metastases, in both androgen-sensitive and -resistant orthotopic prostate cancer mouse models. Immunohistochemical analysis of the primary tumors revealed that dasatinib treatment decreased SFK phosphorylation but not expression, resulting in decreased cellular proliferation and increased apoptosis. For this analysis of immunohistochemical stained tissues, I developed a novel method of quantifying immunohistochemical stain intensity that greatly reduced the inherent bias in analyzing staining intensity. ^ To determine if Src and Lyn played overlapping or distinct roles in prostate cancer tumor growth and progression, Src expression alone was inhibited by small-interfering RNA. The resulting stable cell lines were decreased in migration, but not substantially affected in proliferation rates. In contrast, an analogous strategy targeting Lyn led to stable cell lines in which proliferation rates were significantly reduced. ^ Lastly, I tested the efficacy of a novel SFK inhibitor (KX2-391) targeting peptide substrate-binding domain, on prostate cancer growth and lymph node metastasis in vivo. I demonstrated that KX2-391 has similar effects as dasatinib, an ATP-competitive small molecular inhibitor, on both the primary tumor growth and development of lymph node metastasis in vivo, work that contributed to the first-in-man Phase I clinical trial of KX2-391. ^ In summary, studies in this dissertation provide the first demonstration that Src and Lyn activities affect different cellular functions required for prostate tumor growth and metastasis, and SFK inhibitors effectively reduce primary tumor growth and lymph node metastasis. Therefore, I conclude that SFKs are promising therapeutic targets for treatment of human prostate cancer. ^