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Biology

Washington University in St. Louis

Obesity

Publication Year

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Full-Text Articles in Life Sciences

Ketone Body Metabolism Preserves Hepatic Function During Adaptation To Birth And In Overnutrition, David Graham Cotter May 2015

Ketone Body Metabolism Preserves Hepatic Function During Adaptation To Birth And In Overnutrition, David Graham Cotter

Arts & Sciences Electronic Theses and Dissertations

Mammalian ketone body metabolism partially oxidizes hepatic acyl-chains to ketone body intermediates, which can serve as alternative fuels in extrahapetic tissues during carbohydrate restricted states. Ketone body production (ketogenesis) occurs primarily in liver, due to hepatocyte-specific expression of the fate committing ketogenic enzyme, mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2). In contrast, the fate committing enzyme of ketone body oxidation, mitochondrial Succinyl-CoA:3-oxoacid CoA Transferase (SCOT), is expressed ubiquitously, except in liver. Here I demonstrate novel roles for ketone body metabolism during a classically ketogenic period, the transition to birth, and in a classically `non-ketogenic' state, overnutrition, using novel genetic mouse models, high-resolution measures …


A Ranksum Statistics Based Framework To Decipher Transcription Regulation, Iuan-Bor Chen Aug 2012

A Ranksum Statistics Based Framework To Decipher Transcription Regulation, Iuan-Bor Chen

Arts & Sciences Electronic Theses and Dissertations

The unbiased generation of specific and meaningful hypotheses from the deluge of data generated by modern genomic methods remains a challenge. These datasets require increasing level of expertise to analyze fully, and are often underutilized even in the originating lab. It would be desirable to have a computational strategy that is easy to implement, robust against outliers and missing data, and broadly applicable to diverse experimental designs. In this dissertation, I present a set of ranksum statistics-based analytical methods as a framework to extract testable hypotheses from large and complex datasets. To illustrate its utility, this framework was applied to …