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title: «Home»,
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notification: {
visible: false,
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dismiss: () => {
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rightNavigation: {
item: {
title: «Profile»,
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item: {
item: {
title: «My Chats»,
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Bandicam V41.1.3.757 Reg Key
.This proposal is designed to advance the understanding of the molecular mechanism of action of thiamin in a human disease. The long-term objective of this proposal is to understand the molecular events that occur in thiamin deficiency and the mechanisms by which thiamin promotes recovery. Our emphasis will be on questions that relate to the function of thiamin in the regulation of carbohydrate metabolism, particularly the regulation of pyruvate dehydrogenase (PDH) kinase and pyruvate dehydrogenase (PDH), and the possible protection of the carbon flux into the pentose phosphate pathway, the biosynthesis of NADPH, and the activity of pyruvate dehydrogenase phosphatase (PDP) by thiamin. Our specific aims are: 1) to characterize the regulatory region of the human PDH kinase gene and to elucidate its potential functions as a regulatory element in carbohydrate metabolism; 2) to identify the protein kinase(s) and phosphatase(s) that are involved in thiamin’s regulation of the activity of PDH kinase; 3) to elucidate the molecular mechanism of thiamin’s regulation of PDP and to identify the enzyme that functions as a thiamin sensor in thiamin deficiency; 4) to characterize the structural changes that thiamin-deficient patients experience and to characterize the metabolic pathways that are affected; and 5) to develop a methodology to monitor changes in human thiamin status in vivo. These experiments will be carried out using the human cell cultures and biopsy samples of patients with thiamin-deficient diseases, a variety of molecular biological approaches, and metabolic profiling of relevant metabolites. The results will be analyzed using a systems biology approach. Molecular information will be integrated with metabolic information to elucidate the molecular mechanism of thiamin’s regulation of carbohydrate metabolism. In particular, this proposal will identify a new target of thiamin and a new subunit of PDH kinase, and elucidate the interrelationships between PDH kinase, pyruvate dehydrogenase, and PDP that are regulated by thiamin. The proposed experiments will also elucidate the cellular and biochemical changes that occur in thiamin deficiency and will lead to more effective therapies for thiamin-deficient diseases.// This file is part of libigl, a simple c++ geometry processing library.
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