No description available.

Amylin is a 37 amino acid long peptide that aggregates into toxic oligomers and fibrils. Since amylin is secreted by and also acts on pancreatic beta cells, type II diabetes is classified as an amyloidogenic disease. This study focuses on the development of a cost effective chemical synthetic strategy for amylin synthesis as previous studies relied on extremely expensive pseudoproline derivatives. Furthermore, commercially available amylin varies between batches and also contains impurities that could generate anomalies and affect reproducibility of experiments. Secondly, chemically synthesized non-methylated and N-methylated derivatives of amylin were shown to inhibit toxicity of full length amylin. A fluorescentlylabeled chemically synthesized derivative of amylin was used to track cellular localization of amylin via confocal microscopy. Amylin aggregation kinetics was established using a surface plasmon resonance (SPR) biosensor. In addition, nanoparticle tracking analysis (NTA) was used as a novel technique to determine the size of oligomers over real time. This technology indicated that the size range of the toxic species of amylin is between 200-300 nm. Furthermore, it can be suggested that NTA could potentially be developed into a screening tool for inhibitors of amylin-mediated cytotoxicity. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2012.

1,2-Dibromo-4-(1,2 dibromoethyl)cyclohexane or tetrabromoethylcyclohexane (TBECH) is an additive bromine based flame retardant used primarily in expandable polystyrene beads that are used mainly to produce thermal insulation for housing. Secondary uses include extrusion into polystyrene foam, adhesive in fabric and vinyl lamination, electrical cable coatings and construction materials. The technical formulation contains two diastereoisomers, α- and β-, which are present in equimolar amounts. Under elevated temperatures two other isomers, γ- and δ-, can be formed. The recent detection of TBECH in the environment and suggestions that all four isomers are androgenic prompted me to examine the bioaccumulation and biochemical effects of one of the isomers, β-, in a controlled laboratory environment. I purposely chose to examine this isomer as it has been detected in biota. Juvenile brown trout (Salmo trutta) were exposed to three different amounts of the β-isomer via their to three different amounts of the β-isomer via their food for 56 days (uptake phase). This was followed by a depuration phase in which all fish were exposed to unfortified food for 77 days. A fourth group of fish were exposed to unfortified food for the duration of the experiment. On days 0, 7, 14, 35, 49, 56, 63, 77, 91, 105, and 133 eight fish from each treatment group were sacrificed and liver, plasma, thyroid and gonad gland were collected and whole-fish (carcass minus tissues above) were collected. Residues of β-isomer were analyzed in the whole-fish and in liver extracts by gas chromatography mass spectrometry in the electron ionization while estradiol (E2), 11-ketotestosterone (11-KT) and testosterone (T) were extracted from plasma and analysed by liquid chromatography tandem mass spectrometry. The bioaccumulation of β-isomer was similar in fish from all treatment groups with steady-state occurring before the end of the uptake phase. Depuration of the β-isomer from fish obeyed first order kinetics and there were no statistically significant differences in the depuration half life (t1/2) among the treatment groups: 22.5 ± 10.4 (low), 13.5 ± 5.9 (med) and 13.8 ± 2.2 (high) days. Steady-state biomagnification factors were much smaller than 1 for fish in all treatment groups. I was unable to detect debrominated metabolites in liver or whole-fish extracts and I also found no evidence of isomerization of the β-isomer to other isoforms in vivo. While there were some differences in E2, T and 11-KT levels in plasma of fish from the treated groups relative to plasma in fish from the control group there were no clear, consistent, discerning trends.

Adult mammopoiesis occurs in close synchronization with reproductive development when the hypothalamic-pituitary-ovarian axis delivers integral systemic hormone cues to propel mammary morphogenesis during puberty, remodeling during reproductive cycles and functional differentiation following pregnancy. While hormones remain the driving force behind normal glandular development, increased life-time hormone exposure is a strong risk factor for breast cancer. Breast cancer heterogeneity has been attributed to different cells of origin and/or different mutation repertoires. Stem/progenitor cells are intensely investigated as cells of origin given their regenerative and self-renewal properties that provide conceivable advantage in cancer. Although hormones have a fundamental influence in breast cancer, their capacity to regulate stem/progenitor cells was unknown, and presents the central directive in this thesis. Employing mouse models, we show that mammary epithelial subpopulations and in particular, stem cells, are highly responsive to ovarian hormones and depend on key molecular events. A progesterone peak during the luteal phase of reproductive cycles results in a significant increase in stem cell-enriched basal cells and an expansion of stem cells measured by in vivo transplantation assays, with rapid development of lobuloalveoli. Progesterone was found to stimulate expression of mitogenic ligands, RANKL and Wnt4, in ER+PR+ luminal epithelial niche cells concomitant with increased expression of their receptors and target genes in the ER-PR- basal stem cell population, suggesting a cross-talk between luminal and basal cells that elicits stem cell expansion within the niche. The requirement of RANKL signaling for hormone-induced mammary stem cell dynamics was further explored utilizing mice deficient for its receptor, RANK, and by pharmacological inhibition of RANKL. Disruption of RANKL/RANK signaling resulted in abrogated activation of the basal stem cell-enriched population and alveolar progenitor cells in response to progesterone. This was accompanied by a marked reduction in cell proliferation, cell cycle regulators, alveolar lineage determinants and notably, in epithelial Wnt responsiveness. Thus, progesterone orchestrates a series of molecular events in the mammary stem cell niche where RANK is effectively positioned to deliver instructive signals to stem cells, culminating in stem cell recruitment and alveolar regeneration, processes which when deregulated have considerable potential to promote breast cancer pathogenesis.

No description available.

This study was desined to measure the effect of various intensities of leg-press exercise and squat exercise on hGH release. Young, 24 ± .7 yrs of age, male lifters (n=3) served as subjects for this study. After a 1 RM was established on the weight sled and squat rack they completed a 3 RM, 10 RM, or 25 RM workout using a 3 set protocol. Each workout (3, 10, squat exercises were separated by 2 weeks. Blood was taken from an antecubital vein prior to exercise (pre-exercise, after warm-up, and post-exercise 4, 8, 16 MIN). The serum was measured for hGH levels. The results indicate that 1) High intensity exercise of a short duration will not elicit a hGH response indicating that exercise duration is more important than exercise intensity, 2) The hGH output, in part, depends on exercise intensity when exercise duration is sufficient to elicit hGH response, and 3) The increased lactic acid during resistance exercise did not relate to hGH levels. / School of Physical Education

The relative distribution of dry matter over shoot and tuberous roots is an important factor in determining the yield of cassava. Under sub-tropical conditions the dry matter distribution pattern is not always efficient. During the summer the vegetative growth is generally excessive due to long days and high temperatures. Furthermore, it was found that a reduction of tuberous root mass occurs shortly after the winter period when the new canopy is formed. The role of endogenous hormones, in particular abscisic acid and cytokinins, in dry matter distribution and tuberization was studied. Furthermore, experiments were conducted on the effect of exogenous applied plant growth regulators on the growth of cassava. Inhibitor activity present in plant extracts, was tentatively identified as cis-abscisic acid. A high level of inhibitor activity, co-eluting with abscisic acid, was found throughout the tuberous roots. The highest level of inhibitor activity was detected under conditions which caused a high rate of tuberous root growth, ego with a low level of nitrogen fertilization. Gibberellic acid application to the leaves promoted shoot growth and led to a decrease in inhibitor activity of the tuberous roots. Shoot removal, however, stopped tuberous root growth without leading to changes in inhibitor activity. No clear correlation was found between inhibitor activity of tuberous roots and the rate of tuberous root growth of plants harvested from the field tentatively identified as the major cytokinins in tuberous root extracts. Cytokinin activity was concentrated in the meristematic region of the xylem. The level of cytokinin activity in the roots was much higher than in primary roots of the same plants. Gibberellic acid application to the leaves and shoot removal resulted in a reduction of the cytokinin level of tuberous roots. The nitrogen application to the plants had no clear effect on the cytokinin levels. In field-grown plants the highest level of cytokinin activity was found shortly after tuber initiation. Applications of Alar caused satisfactory reduction of shoot growth of young cassava plants grown in the greenhouse. The internodes were shortened, the leaf area generally reduced, while a relatively larger part of the dry matter was allocated to storage roots. The effect of Alar was further studied in field experiments. A growth analysis showed that a reduction of tuberous root mass occured shortly after the winter period, in September. Later in the second growing season, shoot and tuberous root mass increased at a relatively constant rate. Alar application (up to 4,5 grammes per Iitre) early in the second season failed to bring about major changes in dry matter distribution. Shoot removal at the end of the winter period was followed by excessive vegetative growth. Alar application reduced the internode length but the reduction of shoot growth was insufficient to cause a significant increase in yield. A nitrogen topdressing at the start of the second season increased the vegetative growth. However, Alar application, later in the season, did not inhibit shoot growth at any of the nitrogen levels applied. RSW 0411 which caused good reduction of shoot growth in the greenhouse, was not effective in the field. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1984.

1,2-Dibromo-4-(1,2 dibromoethyl)cyclohexane or tetrabromoethylcyclohexane (TBECH) is an additive bromine based flame retardant used primarily in expandable polystyrene beads that are used mainly to produce thermal insulation for housing. Secondary uses include extrusion into polystyrene foam, adhesive in fabric and vinyl lamination, electrical cable coatings and construction materials. The technical formulation contains two diastereoisomers, α- and β-, which are present in equimolar amounts. Under elevated temperatures two other isomers, γ- and δ-, can be formed. The recent detection of TBECH in the environment and suggestions that all four isomers are androgenic prompted me to examine the bioaccumulation and biochemical effects of one of the isomers, β-, in a controlled laboratory environment. I purposely chose to examine this isomer as it has been detected in biota. Juvenile brown trout (Salmo trutta) were exposed to three different amounts of the β-isomer via their to three different amounts of the β-isomer via their food for 56 days (uptake phase). This was followed by a depuration phase in which all fish were exposed to unfortified food for 77 days. A fourth group of fish were exposed to unfortified food for the duration of the experiment. On days 0, 7, 14, 35, 49, 56, 63, 77, 91, 105, and 133 eight fish from each treatment group were sacrificed and liver, plasma, thyroid and gonad gland were collected and whole-fish (carcass minus tissues above) were collected. Residues of β-isomer were analyzed in the whole-fish and in liver extracts by gas chromatography mass spectrometry in the electron ionization while estradiol (E2), 11-ketotestosterone (11-KT) and testosterone (T) were extracted from plasma and analysed by liquid chromatography tandem mass spectrometry. The bioaccumulation of β-isomer was similar in fish from all treatment groups with steady-state occurring before the end of the uptake phase. Depuration of the β-isomer from fish obeyed first order kinetics and there were no statistically significant differences in the depuration half life (t1/2) among the treatment groups: 22.5 ± 10.4 (low), 13.5 ± 5.9 (med) and 13.8 ± 2.2 (high) days. Steady-state biomagnification factors were much smaller than 1 for fish in all treatment groups. I was unable to detect debrominated metabolites in liver or whole-fish extracts and I also found no evidence of isomerization of the β-isomer to other isoforms in vivo. While there were some differences in E2, T and 11-KT levels in plasma of fish from the treated groups relative to plasma in fish from the control group there were no clear, consistent, discerning trends.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 116-131). / Microfiche. / xvi, 131 leaves, bound ill. (some col.) 29 cm

Typescript. / Bibliography: leaves 158-169. / Photocopy. / Microfilm. / xviii, 169 leaves, bound ill. 29 cm