No description available.

Lactate dehydrogenase A (LDHA) is hormonally regulated in rodents, and increased expression of LDHA is observed during mammary gland tumorigenesis. The mechanisms of hormonal regulation of LDHA were investigated in breast cancer cells using a series of deletion and mutant reporter constructs derived from the rat LDHA gene promoter. Results of transient transfection studies showed that the -92 to -37 region of the LDHA promoter was important for basal and estrogen-induced transactivation, and mutation of the consensus CRE motif (-48/-41) within this region resulted in significant loss of basal activity and hormone-responsiveness. Gel mobility shift assays using nuclear extracts from MCF-7 cells indicated that CREB family proteins interacted with the CRE. Studies with kinase inhibitors showed that estrogen-induced activation of this CRE was dependent on protein kinase C, and these data show that LDHA is induced through a nongenomic (extranuclear) pathway of estrogen action. Estrogen activates several nongenomic pathways in MCF-7 cells, and this study investigated the effects of structurally diverse estrogenic compounds on activation of mitogen activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), protein kinase A (PKA), and calcium/calmodulin-dependent protein kinase IV (CaMKIV). Activation of kinases was determined by specific substrate phosphorylation and transactivation assays that were diagnostic for individual kinases. The compounds investigated in this study include E2, diethylstilbestrol (DES), the phytoestrogen resveratrol, and the following synthetic xenoestrogens: bisphenol-A (BPA), nonylphenol, octylphenol, endosulfan, kepone, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), and 2',3',4',5'-tetrachloro-4-biphenylol (HO-PCB-Cl4). With theexception of resveratrol, all the compounds activated PI3K and MAPK whereas activation of PKC by the xenoestrogens was structure-dependent and resveratrol, kepone and HO-PCB-Cl4 were inactive. Only minimal estrogen/xenoestrogen-dependent activation of PKA was observed. CaMKIV was activated only by E2 and DES, and HO-PCB-Cl4 was a potent inhibitor of CaMKIV-dependent activity. These results demonstrate that activation of nongenomic pathways by estrogenic compounds in MCF-7 cells is structure-dependent.

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: Charles B. Swanik, Dept. of Health, Nutrition, & Exercise Sciences. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 122-165).

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references. Available also from UMI/Dissertation Abstracts International.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 126-134). Available also in a digital version from Dissertation Abstracts.

Not available / text

This study was designed to test the claim that a deficit in low-level visual processing is a major factor in the etiology of developmental dyslexia. The transient and sustained pathways are neuro-anatomical pathways which underlie low level visual processing. Dyslexics are hypothesized to suffer from a transient pathway deficit which manifests itself in reading difficulties. Normal and disabled adult readers were compared on two visual processing tasks. One task measured the contrast threshold of subjects for flickering sinewave gratings; normal and disabled readers did not differ in contrast sensitivity. On the second task--a visual search task--disabled readers were consistently slower than normal readers, rather than showing the pattern of performance predicted by the transient deficit model; the results provide little evidence for a transient pathway deficit. The results of this and related studies are discussed; it is concluded that empirical evidence for a transient pathway deficit in dyslexia is equivocal.

No description available.

The aim of this study was to investigate the role of Ca²⁺ signalling pathways in the growth, morphogenesis and hyphal reorientation responses of <i>C. albicans</i>. The genes <i>CCH1</i> and <i>MID1</i> were identified in <i>S. cerevisiae</i> as encoding putative Ca²⁺ channels. These genes have since been shown to compose a Ca²⁺ channel complex. Homologues of these genes were identified and cloned from <i>C. albicans</i>. <i>CaMID1</i> was disrupted by the Ura-blaster method, and the resulting mutant characterised. The <i>C. albicans</i> <i>mid1</i> mutant strain was sensitive to the depletion of Ca²⁺ the presence of cell wall perturbing compounds such as SDS and Calcofluor. It formed hyphae more rapidly in the presence of serum, and had a propensity to grow as elongated cells or pseudohyphae in Ca²⁺-depleted medium, on SD, or on medium containing cell wall perturbing compounds. This suggests that depletion of Ca²⁺-uptake perturbs yeast-hypha morphogenesis, perhaps by inducing a nutrient starvation stress response. The <i>mid1</i> mutant and a number of other <i>C. albicans</i> Ca²⁺ signalling mutants were defective in chlamydospore formation, suggesting a role for Ca²⁺ in two morphogenetic genesises: the hyphae and of chlamydospores. The role of Mid1p in the thigmotropic reorientation responses of <i>C. albicans</i> hyphae was investigated. The <i>mid1</i> mutant strain displayed reduced ability to reorientate growth upon contact with ridges on an etched quartz slide. Suggesting that Mid1p may function as stretch-activated Ca²⁺ channel in <i>C. albicans</i>. The ability of <i>C. albicans</i> <i>mid1</i> mutants to respond to an electric field was also attenuated, suggesting that Mid1p may form part of a voltage-sensitive Ca²⁺ channel in <i>C. albicans</i> that plays a central role in the steering mechanism of <i>C. albicans</i> hyphae. The <i>C. albicans </i>kinase Cst20p may function downstream of Mid1p in growth reorientation responses.