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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Trinucleotide Repeat Instability Modulated By Dna Repair Enzymes And Cofactors, Yaou Ren May 2018

Trinucleotide Repeat Instability Modulated By Dna Repair Enzymes And Cofactors, Yaou Ren

FIU Electronic Theses and Dissertations

Trinucleotide repeat (TNR) instability including repeat expansions and repeat deletions is the cause of more than 40 inherited incurable neurodegenerative diseases and cancer. TNR instability is associated with DNA damage and base excision repair (BER). In this dissertation research, we explored the mechanisms of BER-mediated TNR instability via biochemical analysis of the BER protein activities, DNA structures, protein-protein interaction, and protein-DNA interaction by reconstructing BER in vitro using synthesized oligonucleotide TNR substrates and purified human proteins. First, we evaluated a germline DNA polymerase β (pol β) polymorphic variant, pol βR137Q, in leading TNR instability-mediated cancers or neurodegenerative diseases. We find ...


Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia Apr 2018

Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia

Graduate Theses and Dissertations

Mitochondria plays a crucial role in cells by maintaining energy metabolism and directing cell death mechanisms by buffering calcium (Ca2+ )from cytosol. Therefore, the Ca2+ overload of mitochondria due to the upregulated cytosolic Ca2+ , observed in many neurological disorders is hypothesized to be a key pathway leading to mitochondrial dysfunction and cell death. In particular, Ca2+ homeostasis disruptions due to Alzheimer’ s disease (AD)-causing presenilins (PS1/PS2) and oligomeric forms of β-amyloid peptides Aβ commonly found in AD patients are presumed to cause detrimental effects on the mitochondria and its ability to function properly. We ...


Understanding The Structure Of Amyloid Fibrils Using Atomic Force Microscopy (Afm) To Design New Therapeutic Strategies For Neurodegenerative Diseases, Sumeyra Gokalp, Michelle Foster May 2017

Understanding The Structure Of Amyloid Fibrils Using Atomic Force Microscopy (Afm) To Design New Therapeutic Strategies For Neurodegenerative Diseases, Sumeyra Gokalp, Michelle Foster

UMass Center for Clinical and Translational Science Research Retreat

Amyloid fibrils are misfolded proteins that are irreversible once they are formed. In human beings, there are different kinds of proteins that form into amyloid fibrils and are associated with several degenerative diseases. For example, insulin, Huntington, Amyloid β-42 and α- synuclein proteins are linked with Type-2 Diabetes, Huntington’s, Alzheimer’s and Parkinson’s diseases, respectively. The mechanism for the misfolding and creation of the fibrils is thought to be the same for all of these proteins. Hen Egg White Lysozyme (HEWL) is a low-cost and widely recognized model protein to work with to help us understand the mechanisms ...


Sensing And Mapping Of Surface Hydrophobicity Of Proteins By Fluorescent Probes, Nethaniah Dorh Jan 2016

Sensing And Mapping Of Surface Hydrophobicity Of Proteins By Fluorescent Probes, Nethaniah Dorh

Dissertations, Master's Theses and Master's Reports

Surface hydrophobic interactions in proteins play a critical role in molecular recognition, influence biological functions, and play a central role in many protein misfolding diseases. As significance of surface hydrophobic interactions in age-related proteinopathies is becoming clear; it has led to an increased demand for better probes and tools to sense and characterize protein surface hydrophobicity. Current commercially available fluorescent probes such as 8-anilino-1-naphthalene sulfonic acid (ANS), 4,4′ -dianilino-1,1′-binaphthyl-5,5′-disulfonic acid (Bis-ANS), 6-propionyl-2-(N,N-dimethylamino)naphthalene (PRODAN), tetraphenylethene derivative, and Nile Red can sense proteins average hydrophobicity. However, probe limitations prevents their application for measuring the ...


Effect Of Disulfide Bond Scrambling On Protein Stability, Aggregation, And Cytotoxicity, Colina Dutta Jan 2016

Effect Of Disulfide Bond Scrambling On Protein Stability, Aggregation, And Cytotoxicity, Colina Dutta

Dissertations, Master's Theses and Master's Reports

Proteins are nano-machines that carry out majority of the cellular functions. Thermodynamically they are functional and stable within a very narrow range (1 kcal/mol). External perturbations in the form of pH change, thermal, or oxidative/reducing stress can destabilize the protein resulting in misfolding and aggregation. Prolonged environmental stress can affect the cells adaptive response resulting in loss of ability to refold or recycle proteins. This can lead to accumulation of misfolded or aggregated proteins within the cell. Such accumulation of aggregated proteins have been associated with neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), Parkinson’s, Huntington’s ...


Development Of A Maldi-Tof-Ms Method For The Analysis Of Cyanobacterial Neurotoxin Β-N-Methylamino-L-Alanine (Bmaa) In Search Of Bmaa Incorporation In Biological Samples, Laura M. Conklin Nov 2015

Development Of A Maldi-Tof-Ms Method For The Analysis Of Cyanobacterial Neurotoxin Β-N-Methylamino-L-Alanine (Bmaa) In Search Of Bmaa Incorporation In Biological Samples, Laura M. Conklin

FIU Electronic Theses and Dissertations

Beta-N-methylamino-L-alanine (BMAA) is a non-protein amino acid produced by many cyanobacteria, and thought to induce neurotoxic effects through excitotoxicity, contributing to neurodegenerative diseases such as Amyotrophic Lateral Sclerosis/Parkinsonism-dementia complex (ALS-PDC) and Alzheimer’s. The ubiquitous nature of cyanobacteria, and evidence of biomagnification through our food web, creates a dire need for the development of an analytical platform that will provide accurate identification and quantification of BMAA amounts in our ecosystem and potential food supply. The present study evaluated the ability of a MALDI-ToF-MS method to detect and quantify BMAA in a variety of biological matrices. Through validation ...


Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope Aug 2014

Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope

UT GSBS Dissertations and Theses (Open Access)

The majority of proteins require molecular chaperones to assist their folding into tertiary and quaternary structures. Certain stresses can compromise the weak hydrophobic forces responsible for these structures and lead to protein unfolding, misfolding, and aggregation. Aggregates of proteins are hallmarks of devastating diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Fortunately, bacteria, plants, and fungi have a potent disaggregase, named Hsp104 in Saccharomyces cerevisiae. Recently, heat-induced aggregates, termed Q-bodies, were found to contain three molecular chaperones: Hsp70, Hsp104, and Hsp42. Their coalescence from small puncta into larger inclusions required Hsp104. During glucose deprivation, a stress that ...


Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich Sep 2012

Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich

Open Access Dissertations

Locomotion in vertebrates depends on proper formation and maintenance of neuronal networks in the hind-brain and spinal cord. Malformation or loss of factors required for proper maintenance of these networks can lead to severe neurodegenerative diseases limiting or preventing locomotion. A powerful tool to investigate the genetic and cellular requirements for development and/or maintenance of these networks is a collection of zebrafish mutants with defects in motility. The zebrafish mutant quetschkommode (que) harbors a previously unknown gene defect leading to abnormal locomotor behavior. Here I show that the que mutants display a seizure-like behavior starting around four days post ...


Structural Polymorphism In Tau Filaments: An Implication For Neurodegenerative Diseases, Ayisha Siddiqua Jan 2012

Structural Polymorphism In Tau Filaments: An Implication For Neurodegenerative Diseases, Ayisha Siddiqua

Electronic Theses and Dissertations

Tau filaments are the pathological hallmark of >20 neurodegenerative diseases including Alzheimer's disease, Pick's disease, and progressive supranuclear palsy. In the adult human brain, six isoforms of tau are expressed that differ by presence or absence of the second of the four semiconserved repeats. As a consequence, half of the tau isoforms have three repeats (3R tau), whereas the other half has four repeats (4R tau).

Site-directed spin labeling of recombinant tau in conjunction with electron paramagnetic resonance spectroscopy was used to obtain structural insights into tau filaments. The studies showed that the filaments of 4R tau and ...


Evaluation Of Mitochondrial Dysfunction And Α-Synuclein Aggregation In Yeast Models Of Parkinson’S Disease, Michael Zorniak Apr 2008

Evaluation Of Mitochondrial Dysfunction And Α-Synuclein Aggregation In Yeast Models Of Parkinson’S Disease, Michael Zorniak

Eukaryon

Parkinson's disease (PD) is characterized by the progressive death of dopaminergic neurons in the human brain. The misfolding and aggregation of alpha-synuclein, as well as the presence of reactive oxygen species (ROS), are throught to contribute to the cytoxicity. The mechanism of interaction between these two pathways is unknown. Mitochondrial dysfunction, specifically, incomplete respiratory metabolism and loss of antioxidants, has long been implicated as the culprit of ROS accumulation. Our lab has previously developed budding and fission yeast models to study genetic regulation of alpha-synuclein misfolding and toxicity. My thesis is composed of two studies. For my first goal ...