Biochemistry Commons^™

Huntingtin Aggregation At Interfaces Associated With Membranes And Organelles, Adewale Vincent Adegbuyiro

Graduate Theses, Dissertations, and Problem Reports

Huntington’s Disease (HD) is a genetic neurodegenerative disease caused by the expansion of polyglutamine (polyQ) domain within the first exon (exon1) of the huntingtin (htt) protein. Due to this mutation within the polyQ domain, htt aggregates into various toxic species such as oligomers, fibrils, and other amorphous aggregates. While the aggregation of htt strongly correlates with polyQ length, other factors, e.g. interaction with membranes or organelles and posttranslational modifications (PTMs), modulate aggregation. The first 17 N-terminal amino acids (Nt17) that precede the polyQ in htt-exon1 enhances aggregation and facilitated binding of htt to membranous organelles, promoting morphological changes and disfunction. …

Understanding The Relationship Between Local Environmental Changes And The Function Of The Ph Low Insertion Peptide, Violetta Burns Casamayor

Graduate Theses, Dissertations, and Problem Reports

Cancer is the second leading cause of death in the US with over 1.7 million new cases each year. Current cancer treatments tend to also target healthy tissues due to similarities with cancerous ones, resulting in acute side effects. Early detection is the best approach towards defeating cancer, however, modern imaging techniques require sizeable samples, often implying a late stage in the disease. One common attribute of tumors is their acidic microenvironment, which can be taken advantage of.

The pH Low Insertion Peptide (pHLIP) is a membrane-active peptide that can take advantage of the acidic microenvironment surrounding cancer cells. pHLIP …

Biocompatible And Multifunctional Trityl Spin Probes For Electron Paramagnetic Resonance Spectroscopy, Teresa D. Gluth

Graduate Theses, Dissertations, and Problem Reports

The primary objective of my thesis was to develop and utilize a biocompatible multifunctional trityl spin probe for concurrent measurement of pO₂, pH_e, and [P_i] in vivo by electron paramagnetic resonance (EPR) spectroscopy (Chapter 2). My first goal was to synthesize the proposed probe we are terming HOPE71. Secondly, HOPE71 was characterized by X-band and L-band EPR spectroscopy. Next, the biocompatibility of HOPE71 was assessed through an albumin binding test, cytotoxicity assays, and in vivo intravenous tolerance. Then, the use of HOPE71 to measure the target parameters was demonstrated in a breast cancer …

Protein/Peptide Characterization Using Mass Spectrometry And Molecular Dynamics Simulations, Ahmad Kiani Karanji

Graduate Theses, Dissertations, and Problem Reports

Mass spectrometry (MS) based-techniques and molecular dynamics (MD) simulations have been used to characterize protein/peptide structure as well as their interactions with lipid vesicles and detergents. Chapter 1 introduces an introduction to the concepts and tools that were used in this work. In Chapter 2, the dominant gas-phase conformer of [M+3H]3+ ions of the model peptide Acetyl-PSSSSKSSSSKSSSSKSSSSK are examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. This section furthers the development of a protein structural prediction tool by providing information about gas-phase ion conformers of two model peptides having different solution conformational …

The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation, Maryssa Beasley

Graduate Theses, Dissertations, and Problem Reports

Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by an expanded glutamine repeat region (polyQ) within the huntingtin protein (htt). As a result of the expanded polyQ domain, htt associates into a variety of toxic aggregate species. The polyQ domain of htt is flanked at the N-terminal end by 17 amino acids (Nt17) that adopt an amphipathic α-helical structure in the presence of binding partners such as lipid membranes. In addition to comprising a lipid binding domain, the Nt17 amphipathic α -helix has been directly implicated in htt aggregation initiation via self-association with other Nt17 α -helices. Due to …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Graphene Nanoplatelets-Sericin Surface-Modified Gum Alloy For Improved Biological Response, Valentina Mitran, Valentina Dinca, Raluca Ion, Vasile D. Cojocaru, Patricia Neacsu, Cerasela Zoica Dinu, Laurentiu Rusen, Simona Brajnicov, Anca Bonciu, Maria Dinescu, Doina Raducanu, Ioan Dan

Faculty & Staff Scholarship

In this study a “Gum Metal” titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young's modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP–SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), …

Enhanced Hot Electron Lifetimes In Quantum Wells With Inhibited Phonon Coupling, Hamidreza Esmaielpour, Vincent R. Whiteside, Herath P. Piyathilaka, Sangeetha Vijeyaragunathan, Bin Wang, Echo Adcock-Smith, Kenneth P. Roberts, Tetsuya D. Mishima, Michael B. Santos, Alan D. Bristow, Ian R. Sellers

Faculty & Staff Scholarship

Hot electrons established by the absorption of high-energy photons typically thermalize on a picosecond time scale in a semiconductor, dissipating energy via various phonon-mediated relaxation pathways. Here it is shown that a strong hot carrier distribution can be produced using a type-II quantum well structure. In such systems it is shown that the dominant hot carrier thermalization process is limited by the radiative recombination lifetime of electrons with reduced wavefunction overlap with holes. It is proposed that the subsequent reabsorption of acoustic and optical phonons is facilitated by a mismatch in phonon dispersions at the InAs-AlAsSb interface and serves to …