Thesis (Ph.D.)--Indiana University, Dept. of Biochemistry, 2009. / Title from PDF t.p. (viewed on Jul 20, 2010). Source: Dissertation Abstracts International, Volume: 70-12, Section: B, page: 7377. Advisers: Martin J. Stone; Carl E. Bauer.

Thesis (Ph.D.)--Indiana University, Dept. of Biochemistry, 2009. / Title from PDF t.p. (viewed on Jul 22, 2010). Source: Dissertation Abstracts International, Volume: 70-12, Section: B, page: 7367. Adviser: Lingling Chen.

Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 70-10, Section: B, page: 5992. Adviser: Kaveh Ashrafi.

Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Geeta Narlikar.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3586. Adviser: Byron W. Kemper. Includes bibliographical references (leaves 103-120) Available on microfilm from Pro Quest Information and Learning.

Obesity is characterized by two major events: systemic low-grade inflammation and energy metabolism imbalance. Adiponectin, an adipocyte-derived protein, has insulin-sensitizing properties in muscle and liver. Its expression and plasma concentrations are decreased in obesity. Our studies examined the role of interleukin-6 (IL-6), an important obesity-related cytokine, on adiponectin gene expression. IL-6 decreased adiponectin expression in a time- and dose-dependent manner in both human primary adipocytes and 3T3-L1 cells through a p44/42 MAP kinase-dependent pathway. In vivo studies demonstrated that IL-6 KO mice have increased plasma adiponectin levels on both a chow and a high fat/high glucose diet. Acyl-CoA: diacylglycerol acyltransferase (DGAT) is a key enzyme in triglyceride biosynthesis. Although many studies have demonstrated the role of DGAT in rodents, very little is known about its role in humans. Our studies identified a novel stop codon in the DGAT2 gene, which results in decreased DGAT2 mRNA expression in adipocytes and is associated with decreased triglyceride levels.

The objective of this study was to test the hypothesis that "During fatigue development there is greater ATP utilization in the absence than in the presence of KATP channel activity". Flexor digitorum brevis (FDB) muscle bundles were fatigued with one tetanic contraction every sec for 3 min. KATP channel activity was abolished pharmacologically using glibenclamide or genetically using Kir6.2-/- FDB muscle bundles; pinacidil was used to activate the channel. Abolishing KATP channel activity had no effect on the decrease in phosphocreatine (PCr), but pinacidil significantly reduced its depletion. Kir6.2-/- FDB showed greater and faster ATP depletion compared to wild type control, but glibenclamide did not reproduce the effect. In the presence of pinacidil ATP content remained significantly above that of control wild type. Unexpectedly Kir6.2-/- FDB muscles generated less lactate than those of wild type. During the first half of the fatigue period, lactate production in wild type FDB were unexpectedly in the order of pinacidil > control > glibenclamide, with the reverse order for the second half of the fatigue period. In conclusion, not all the data supported the hypothesis because the effects of modulating KATP channel activity appeared complicated by difference between acute (pharmacological) and chronic (genetical) approaches, such as changes in ATP and lactate; as well as by time dependent effects, such as observed with lactate.

Breast Cancer Resistance Protein, BCRP, is highly expressed in many different tumor tissues conferring multi-drug resistance against many chemotherapy drugs. BCRP has also been reported to be present in normal tissues including the human placenta during pregnancy. It is believed that in the placenta, BCRP controls the levels of toxins, drugs and xenobiotics that may cross maternal circulation into fetal circulation. The expression of BCRP was examined in the human placenta and in placental membranes (amnion and chorion leave) and attached decidua. In addition, the effect of cytokines and hypoxia on BCRP expression in placental cells was examined in vitro. BCRP was found to be highly expressed in the placenta throughout pregnancy as well as in the amnion, chorion laeve and attached decidua. Our data suggest that increased cytokine expression and reduced oxygen levels may not have any effect on BCRP mRNA or protein levels in the placental syncytiotrophoblast cells. This may suggest that BCRP is stably expressed in the placenta, even under adverse conditions, and may imply that activity of this transporter protein is essential for normal placental function.

Type II Diabetes Mellitus (DM) is a common metabolic disorder that affects millions of people worldwide. Elevated blood glucose levels in type II DM is associated with altered sympathetic nervous system (SNS) activity and enhanced noradrenaline (NA). Persistent NA release, in turn, leads to alterations in beta-adrenergic receptor (betaAR) density and downstream signalling. A common complication of diabetes is cardiovascular disease. In this project, myocardial betaAR density was evaluated in hyperglycaemic streptozotocin (STZ)-treated rats fed high fat diet (HFD), using betaAR antagonist (S)-[3H]CGP12177. At 30 minutes post injection, the radiotracer exhibited specific binding in myocardial regions, brown adipose tissue and kidney, and was capable of measuring reduced binding to betaARs. A subset of HFD moderate-STZ treated rats became hyperglycaemia, whereas the remainder maintained euglycaemia. At 10 days post-STZ, no alteration was observed in tracer binding in either sub-group. At 56 days, hyperglycaemic rats displayed a significant reduction in specific binding to betaARs in myocardial regions (30-40%), while no alteration was observed in euglycaemics or controls. This finding suggests a strong association between sustained hyperglycaemia and alterations in SNS activity and PAR binding.

In a screen for genes differentially expressed during fin regeneration in adult zebrafish, two novel genes, 2-H06 and 2-F11, belonging to the same family coding for secreted proteins with unknown function, were identified. Besides their expression during fin regeneration, they are specifically expressed in the embryonic fins of zebrafish. During development, their expression is restricted to the developing fin folds of both paired and unpaired fins. Searches of the current genomic databases did not reveal any orthologs of 2-H06 or 2-F11 genes in tetrapods, plants and invertebrates species. However, orthologs of the genes are found in other teleost fish like the puffer fish Takifugu rubripes (fugu), Tetraodon nigroviridis and the Medaka fish (Oryzias latipes), and in the cartilaginous fish, elephant shark (Callorhinchus milii). In zebrafish embryos, around hatching time, the first component of the fin exoskeleton is seen. It is made of two layers of collagenous fibrils called actinotrichia. These fibrils are only present in fish fins and their appearance correlates with the onset of the developmental divergence between fish paired fin buds and higher vertebrate limb buds. Functional analysis was performed using the gene "knock-down" approach by injection of morpholino oligonucleotides in 1-cell-stage zebrafish embryos. It revealed no significant defects when the morpholino of each gene was injected individually but co-injection of both of the morpholinos induced a complete absence of the actinotrichia, which led to the fin fold losing its structural integrity. Moreover, rescue analysis performed by co-injecting single stranded mRNA (2-H06 or 2-F11) with the two morpholinos in embryos confirmed that the absence of actinotrichia was a defect specific to the knockdown of the 2-H06 and 2-F11 genes. The results of this study suggest that these two genes encode structural proteins of the actinotrichia and loss of this gene family in species other than fish may be one of the causes or consequences of the evolutionary transition from fins to limbs.