Medicine and Health Sciences Commons^™

Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas M. Ruden, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

Conrad Waddington published an influential model for evolution in his 1942 paper, Canalization of Development and Inheritance of Acquired Characters. In this classic, albeit controversial, paper, he proposed that an unknown mechanism exists that conceals phenotypic variation until the organism is stressed. Recent studies have proposed that the highly conserved chaperone Hsp90 could function as a “capacitor,” or an “adaptively inducible canalizer,” that masks silent phenotypic variation of either genetic or epigenetic origin. This review will discuss evidence for, and arguments against, the role of Hsp90 as a capacitor for morphological evolution, and as a key component of what …

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …

Detection Of Forces And Body Load In Standing And Walking In The American Cockroach, J. Adam Noah

Theses, Dissertations and Capstones

Sense organs in the legs that detect body weight are an important component in the regulation of posture and locomotion. This thesis seeks to gain an understanding of how body weight is detected by sense organs of the legs, and determine how this information influences muscle activities in standing and walking. The first study tested the ability of tibial campaniform sensilla (receptors that monitor forces in the cockroach leg) to encode variations in body load using magnets attached to the thorax. Recordings of sensory activities in freely standing animals showed that proximal tibial sensilla (oriented perpendicular to the leg long …

The Neural Connectivity Of The Torus Semicircularis In The Cave Dwelling Form Of Astyanax Fasciatus, Timothy B. Angel

Theses, Dissertations and Capstones

Afferent projections of the torus semicircularis were traced in the blind cave form of Astyanax fasciatus using HRP tract-tracing techniques, and the results were compared to those found in previous studies of closely related sighted teleosts.

Following unilateral injections of tracer to the nucleus centralis of the torus semicircularis, retrogradely labeled cells were found in two octaval nuclei of the medulla. The descending octavolateralis nucleus was labeled bilaterally and the anterior octaval nucleus was labeled primarily on the ipsilateral side. Both the descending and anterior octavolateralis nuclei are known to receive auditory input from CN VIII in sighted fish. In …

The Characterization Of Two Differentially Expressed Plasma Proteins In Obese Versus Lean Rats In Two Rodent Models Of Obesity, Roger D. Boggs

Theses, Dissertations and Capstones

Zucker fa and La/N faf rats are widely studied models of genetic obesity and its complications. These two rodent models of obesity were utilized to search for a circulating protein marker for obesity. Plasma samples from both of these models of obesity were collected and analyzed via SDS-PAGE analysis. Two proteins were found which demonstrate differential expression between lean and obese rats. Both proteins demonstrated increased expression in the obese rats compared to the lean. One differentially expressed protein migrated on SDS-PAGE gels at 116 KD while the second migrated at 22 KD compared to molecular weight markers. The 22 …

A Mechanistic Study In The Nephrotoxicity Of P-Aminophenol, R. Christopher Harmon

Theses, Dissertations and Capstones

The acetaminophen metabolite, p-aminophenol (PAP), is a known nephrotoxicant. The current study is directed at understanding the mechanism of this nephrotoxicity. Renal cortical slices isolated from F344 rats were incubated with 0 – 0.5 mM PAP with or without pretreatments. Renal slices exposed to PAP showed toxicity as measured by increased lactate dehydrogenase leakage (LDH), decreased pyruvate-stimulated gluconeogenesis, and decreased total adenine nucleotides. There was, however, an increase in ATP as percent of total, implying maintained mitochondrial function. These data show that PAP is directly toxic to renal cortical slices. Pretreatment with EDTA or EGTA provided protection from PAP- induced …

The Role Of Ap-1 Transcription Complex In Retinoic Acid-Dependent B16 Melanoma Cell Growth Arrest And Differentiation, Ying Huang

Theses, Dissertations and Capstones

Our laboratory has been studying the effects of all-trans retinoic acid (atRA) on the growth and differentiation of the B16 mouse melanoma cells. RA inhibits both anchorage-dependent and –independent growth and stimulates melanin production in B16 cells, which are accompanied by an increase in AP-1 activity. To further investigate the RA-induced AP-1 activity, I established clones of B16 stably expressing an AP-1-luciferase reporter gene. Treatment of these clones with phorbol dibutyrate (PDB), a known activator of AP-1, rapidly increased AP-1 activity which reached its maximum level at 2-4 h and returned to baseline level by 24 h. In contrast, RA …