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You searched for subject:( Betatrophin). Showing records 1 – 3 of 3 total matches.

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ETH Zürich

1. Harmand, Thibault J.R. Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation.

Degree: 2017, ETH Zürich

Proteins are involved in and perform a myriad of biological functions. Understanding their structures, functions and interactions with small molecules or other proteins is essential for modern day science. In recent years, proteins as therapeutics have become more and more relevant in the pharmaceutical industry, because of their low toxicity, low risk of side effects as well as their high specificity. Hence, obtaining pure and homogenous samples of proteins has become an important field of research. Although recombinant production allows access to a large number of proteins, it does present limitations: incorporation of unnatural amino acids and the highly sought after posttranslational modifications (PTMs) – that are often critical for the biological activity of the protein of interest – are difficult, if not impossible, to implement. Chemical protein synthesis appears to be a good alternative to the recombinant approach, as it can easily bypass the mentioned limitations. It can deliver homogenous protein samples with almost any kind of amino acid component, without biological contaminants. In 2006, the Bode group developed a method called the -ketoacid–hydroxylamine ligation (KAHA ligation) which allows the chemical synthesis of proteins by ligating two unprotected peptide segments. The KAHA ligation proceeds via the decarboxylative condensation of an -ketoacid with a hydroxylamine to form an amide bond under acidic organic buffering conditions at slightly elevated temperature. Since its discovery, the KAHA ligation has been subject to constant development, allowing the Bode group to synthesize proteins like SUMO2, SUMO3, irisin, AS48, NP4, betatrophin, interleukin-2 proteins and IFITM3. This dissertation describes, in the first chapter, the synthetic improvements made for two main building blocks: the cyanosulfur ylide linker and the (S)-N-Boc-5-oxaproline, used for the preparation of -ketoacid peptide segments and hydroxylamine peptide segments respectively. The new procedures enable the production of these monomers on a multigram scale, allowing our group to scale up the synthesis of synthetic proteins. The second chapter describes the usage of the KAHA ligation for the preparation of multimilligram quantities of the protein hormone betatrophin. This protein had attracted attention after primary results claimed it had direct effects on the proliferation of -cells, giving rise to hope for a new approach to treat diabetes. This synthesis represents the first report of a synthetic protein assembled via five peptide segments by KAHA ligation. Integral membrane proteins are, because of their hydrophobicity, challenging to obtain both by recombinant overexpression and chemical synthesis. In a third chapter, the KAHA ligation was used to synthesize one of these challenging molecules: the antiviral transmembrane protein IFITM3. The unique features of the KAHA ligation – acidic organic solvents and the formation of a depsi-peptide at the ligation site – appeared to be ideally suited for the synthesis of… Advisors/Committee Members: Bode, Jeffrey W., Hilvert, Donald.

Subjects/Keywords: Betatrophin; IFITM3; Chemical protein synthesis; KAHA ligation; Membrane proteins; Protein modifications; info:eu-repo/classification/ddc/540; Chemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Harmand, T. J. R. (2017). Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/209686

Chicago Manual of Style (16th Edition):

Harmand, Thibault J R. “Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation.” 2017. Doctoral Dissertation, ETH Zürich. Accessed July 20, 2019. http://hdl.handle.net/20.500.11850/209686.

MLA Handbook (7th Edition):

Harmand, Thibault J R. “Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation.” 2017. Web. 20 Jul 2019.

Vancouver:

Harmand TJR. Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2019 Jul 20]. Available from: http://hdl.handle.net/20.500.11850/209686.

Council of Science Editors:

Harmand TJR. Chemical Synthesis of Betatrophin and the Integral Membrane Protein IFITM3 by KAHA Ligation. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/209686


Kyoto University

2. Izumi, Ryouta. CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats .

Degree: 2019, Kyoto University

Subjects/Keywords: ANGPTL8; Betatrophin; Lipid metabolism; Glucose metabolism; Lipoprotein lipase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Izumi, R. (2019). CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/242910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Izumi, Ryouta. “CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats .” 2019. Thesis, Kyoto University. Accessed July 20, 2019. http://hdl.handle.net/2433/242910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Izumi, Ryouta. “CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats .” 2019. Web. 20 Jul 2019.

Vancouver:

Izumi R. CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats . [Internet] [Thesis]. Kyoto University; 2019. [cited 2019 Jul 20]. Available from: http://hdl.handle.net/2433/242910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Izumi R. CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats . [Thesis]. Kyoto University; 2019. Available from: http://hdl.handle.net/2433/242910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Jiao, Yang. Regulators of Mouse and Human Beta Cell Proliferation.

Degree: 2013, University of Pennsylvania

Diabetes mellitus is an increasingly prevalent metabolic disorder that is estimated to affect over 300 million people by 2025. Common to either type 1 or type 2 diabetes is a progressive inadequacy of functional beta-cell mass. Recent studies have shown that during times of prolonged metabolic demand for insulin, the endocrine pancreas can respond by increasing beta-cell mass by beta-cell proliferation. Advances that further our knowledge of the molecular factors that control beta-cell proliferation will be crucial for understanding the homeostasis of beta-cell mass during adulthood, and are pivotal for any attempt to use instructive cues to induce the proliferation of terminally differentiated fully functional insulin-producing beta-cells that are suitable for transplantation. In the first part of my thesis, I investigated the role of CISH on beta cell proliferation in pregnant mice by using a pancreas-specific Cish-ablation mouse model. My results demonstrated that CISH is not required for beta cell proliferation or glucose homeostasis before, during, and after pregnancy. Socs2 expression is up-regulated in Cish-ablation islets at pregnant day 9.5, indicating that SOCS2 might be compensating for CISH deficiency. In the second part of my thesis, I studied the role of HNF4-alpha in beta cell proliferation during obesity by inducing beta-cell-specific Hnf4-alpha ablation in ob/ob mice. My results indicated that HNF4-alpha is required for beta-cell proliferation during obesity. Furthermore, I also demonstrated that overexpression of Hnf4-alpha in beta cells had no protective effect in glucose homeostasis in high-fat-diet fed obese mice. In the third part of my thesis, I investigated the role of betatrophin on human beta cell replication by transplanting human islets under kidney capsule of immunodeficient mice and induce betatrophin overexpressing in the liver. In spite of the mitogenic role of betatrophin on mouse beta-cells, it does not promote replication in human beta cells. In summary, my thesis work furthered the understanding of the role of CISH, HNF4-alpha, and betatrophin on beta-cell proliferation.

Subjects/Keywords: Beta cell proliferation; Betatrophin; CISH; Diabetes; HNF4-alpha; SOCS2; Cell Biology; Genetics; Molecular Biology

…mice and induce betatrophin overexpressing in the liver. In spite of the mitogenic role… …of betatrophin on mouse beta-cells, betatrophin does not promote replication in human beta… …betatrophin on beta-cell proliferation… …133 Chapter 4 Elevated hepatic betatrophin expression does not… …142 Elevated betatrophin expression does not stimulate replication of human beta cells… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jiao, Y. (2013). Regulators of Mouse and Human Beta Cell Proliferation. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/877

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Jiao, Yang. “Regulators of Mouse and Human Beta Cell Proliferation.” 2013. Thesis, University of Pennsylvania. Accessed July 20, 2019. https://repository.upenn.edu/edissertations/877.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Jiao, Yang. “Regulators of Mouse and Human Beta Cell Proliferation.” 2013. Web. 20 Jul 2019.

Vancouver:

Jiao Y. Regulators of Mouse and Human Beta Cell Proliferation. [Internet] [Thesis]. University of Pennsylvania; 2013. [cited 2019 Jul 20]. Available from: https://repository.upenn.edu/edissertations/877.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jiao Y. Regulators of Mouse and Human Beta Cell Proliferation. [Thesis]. University of Pennsylvania; 2013. Available from: https://repository.upenn.edu/edissertations/877

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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