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Full-Text Articles in Physical Sciences and Mathematics

Using Quantitative And Kinetic Proteomics To Explore Proteostasis, Nathan Raul Zuniga Pina Dec 2023

Using Quantitative And Kinetic Proteomics To Explore Proteostasis, Nathan Raul Zuniga Pina

Theses and Dissertations

Every cell consists of carefully orchestrated biomolecules such as lipids, carbohydrates, and proteins. To maintain internal stability (homeostasis), cells maintain the right amount of these molecules at the right time and at the right place. This process is especially true for proteins since they are the foundation functional units within the cell. Proteins form structures and perform chemistry that bestows cells overarching functional roles. Cells maintain protein homeostasis (proteostasis) by modulating synthesis, folding, and degradation processes (turnover) to maintain the abundance levels for all proteins. This is the foundational kinetic model of proteostasis that is covered in this work, and …


Monitoring Brain Region-Specific Control Of Protein Turnover And Concentration Using Proteomics, Rebecca Suzanne Burlett Nov 2023

Monitoring Brain Region-Specific Control Of Protein Turnover And Concentration Using Proteomics, Rebecca Suzanne Burlett

Theses and Dissertations

Regulation of metabolism is vital to health and lies at the core of many different diseases. The breakdown of metabolisms' regulation within the brain can lead to neurological disease like Alzheimer's Disease (AD). AD is known to affect brain regions responsible for memory and memory processing like the hippocampus and entorhinal cortex. The regulation of these regions' protein quality, synthesis, and degradation deviate from 'normal' or 'healthy' levels when AD is happening. It is known there is a breakdown of regulation in those regions; however, little is known about the specifics of regulation in healthy brains regions or how it …


Soft Contact Lens Tear Film Proteomics For Clinical Diagnostic Biomarker Discovery, Robert Kimball Roden Jun 2023

Soft Contact Lens Tear Film Proteomics For Clinical Diagnostic Biomarker Discovery, Robert Kimball Roden

Theses and Dissertations

Human tear film is an accessible biospecimen rich with useful biological information. As tear protein biomarkers for both ocular and systemic diseases have been identified in tears, efforts are being made to create point-of-care tests useful for clinical diagnoses. However, there are significant obstacles to tear diagnostics, including inadequate sampling methods and biomarkers with insufficient sensitivity and specificity. Furthermore, tear film diagnostics are particularly challenging for dry eye disease (DED) patients, where low tear volume makes sampling more difficult and the multifactorial nature of DED makes identifying the exact pathological subtype very complex. As soft contact lenses (SCLs) are designed …


Quantifying Protein Quality To Understand Protein Homeostasis, Hsien-Jung Lavender Lin Jul 2022

Quantifying Protein Quality To Understand Protein Homeostasis, Hsien-Jung Lavender Lin

Theses and Dissertations

Proteins are the center of all biochemical reactions in living organisms. Proteins need to be present at the right time, in the right place, with the correct concentration and have the right shape to carry their designated function. Protein homeostasis is when all proteins in the proteome are in functional balance, and such balance is maintained by synthesis, folding, and degradation machinery. When protein homeostasis is lost, organisms start to age and develop diseases. To truly unveil disease mechanisms and provide more efficient means for treatment and prevention, we need a holistic understanding of the mechanism of protein homeostasis. Currently, …


Sd2 Ptov1 Interactomics, Joshua Andersen Aug 2021

Sd2 Ptov1 Interactomics, Joshua Andersen

ScholarsArchive Data

PTOV1 interactome data


Sd1 14-3-3 Interactome For Ptov1 Manuscript, Joshua Andersen Aug 2021

Sd1 14-3-3 Interactome For Ptov1 Manuscript, Joshua Andersen

ScholarsArchive Data

14-3-3 interactome


Investigation Of Dynamic Biological Systems Using Direct Injection And Liquid Chromatography Mass Spectrometry, Adam Clayton Swensen Dec 2016

Investigation Of Dynamic Biological Systems Using Direct Injection And Liquid Chromatography Mass Spectrometry, Adam Clayton Swensen

Theses and Dissertations

In biological systems, small changes can have significant impacts. It is, therefore, very important to be able to identify these changes in order to understand what is occurring in the organism. In many cases, this is not an easy task. Mass spectrometry has proven to be a very useful tool in elucidating biological changes even at a very small scale. Several different mass spectrometry based techniques have been developed to discover and investigate complex biological changes. Some of these techniques, such as proteomics, have been through years of development and have advanced to the point that anyone can complete complex …


Discovery Of Low-Molecular Weight Novel Serum Biomarkers For Diagnosing Preeclampsia And Alzheimer's Disease, Swati Anand Mar 2016

Discovery Of Low-Molecular Weight Novel Serum Biomarkers For Diagnosing Preeclampsia And Alzheimer's Disease, Swati Anand

Theses and Dissertations

Preeclampsia (PE), a life threatening pregnancy-related disorder, is characterized mainly by new onset of hypertension and proteinuria after 20 weeks of gestation. Currently, PE cannot be predicted prior to onset of symptoms and there is no cure for the disease. There is a clear value in having biomarkers able, early in a pregnancy, to identify women at risk for PE so that proper treatment therapies could be developed. Although a number of serum candidate markers have been proposed to be altered in PE patients, their use is limited due to poor sensitivity and specificity. Therefore, there is ongoing need for …


Mass Spectrometry Based Proteomics And Lipidomics Studies, Huan Kang Oct 2015

Mass Spectrometry Based Proteomics And Lipidomics Studies, Huan Kang

Theses and Dissertations

Mass spectrometry has emerged as having a vital role in various applications to biochemical fields. In this thesis, we have utilized a variety of mass spectrometry techniques for both bacteriophage proteomics and colostrum and milk lipidomics studies. Our first study was the proteome characterization of Great Salt Lake bacteriophage NS01 with SDS-PAGE GEL to separate the viral proteins and high performance liquid chromatography (HPLC) coupled with an LTQ Orbitrap to identify the proteins after in-gel digestion. In this project, we have successfully identified 11 proteins with high confidence, p-values < 0.01, including coat protein gp88 with a coverage of 91% and tail protein gp86 with a coverage of 40.96%, which facilitated the classification of NS01 as a T7-like phage. Our second study was the discovery of colostrum and milk biomarkers that can be used to predict the likelihood of development of production-related metabolic diseases (PRMDs) in dairy cows through a lipidomics approach. In this study, an electrospray ionization, time-of-flight mass spectrometer was applied to lipid profiling, quantification and significant biomolecule selection. A Q-Star quadrupole, orthogonal time-of-flight mass spectrometer and an Agilent 6530 accurate-mass quadrupole/time-of flight mass spectrometer were both used for lipid biomarker fragmentation and identification. According to linear discriminative statistical modeling, three panels of biomarkers were defined. A combination of 2 milk lipid predictors, including DG18:0/18:0 and TG 18:0/18:0/18:1, provided PRMD predictions with 75.0% sensitivity at 90.0% specificity. A combination of 3 colostrum lipid predictors, including TG16:0/18:1/18:3, DG16:0/16:0 and C40H60NO, provided PRMD prediction with 90.0% sensitivity at …


Ribosome Component Turnover Kinetics Describes A Two-Pool Kinetic Model In Dietary Restriction That Suggests Rpl10 Is Exchanged During Ribosome Lifespan, Andrew David Mathis Aug 2015

Ribosome Component Turnover Kinetics Describes A Two-Pool Kinetic Model In Dietary Restriction That Suggests Rpl10 Is Exchanged During Ribosome Lifespan, Andrew David Mathis

Theses and Dissertations

The eukaryotic ribosome is a large molecular machine consisting of ~80 ribosomal proteins and 4 rRNAs. The 40S and 60S ribosomal subunits are assembled in the nucleolus by ~200 helper proteins then shipped into the cytoplasm or to the endoplasmic reticulum where protein translation takes place. Eventually ribosomes are removed from the cytoplasm and recycled through ribophagy, however, very is little is known about ribosomal protein exchange after assembly but before ribophagy. Using kinetic turnover measurements of ribosomal proteins and rRNA in vivo we determined ribosomal protein replacement rates are diverse suggesting ribosomal components may be replaced without destruction of …


Bioinformatic Solutions To Complex Problems In Mass Spectrometry Based Analysis Of Biomolecules, Ryan M. Taylor Jul 2014

Bioinformatic Solutions To Complex Problems In Mass Spectrometry Based Analysis Of Biomolecules, Ryan M. Taylor

Theses and Dissertations

Biological research has benefitted greatly from the advent of omic methods. For many biomolecules, mass spectrometry (MS) methods are most widely employed due to the sensitivity which allows low quantities of sample and the speed which allows analysis of complex samples. Improvements in instrument and sample preparation techniques create opportunities for large scale experimentation. The complexity and volume of data produced by modern MS-omic instrumentation challenges biological interpretation, while the complexity of the instrumentation, sample noise, and complexity of data analysis present difficulties in maintaining and ensuring data quality, validity, and relevance. We present a corpus of tools which improves …


A Top-Down Proteomic Approach For The Discovery Of Novel Serum Biomarkers Of Pregnancy-Related Disease, Karen Merrell Jul 2009

A Top-Down Proteomic Approach For The Discovery Of Novel Serum Biomarkers Of Pregnancy-Related Disease, Karen Merrell

Theses and Dissertations

The serum fraction of blood is an ideal material in which to search for novel biomarkers for disease. It is easily obtained through relatively non-invasive means, routinely collected, and a rich treasure-trove of information about the health of an individual. Cells react to signal molecules, take up nutrients, and release waste products, fragments that are the result of proteolysis, and other molecules out into the bloodstream. If these components are unique to the cells in question, that part of the complex mixture that is the blood stream can potentially characterize the health of the tissue or organ those cells are …


Study Of The Reproducibility Of Proteomics Methods And Variability Of Fruit Fly Proteomes., Thomas Franklin Culwell Dec 2007

Study Of The Reproducibility Of Proteomics Methods And Variability Of Fruit Fly Proteomes., Thomas Franklin Culwell

Theses and Dissertations

The reliability of biomarker discovery by means of proteomics has been called into question. It was speculated that "background noise" variation resulting from differences in preparation and handling of samples and proteome dynamics may mask subtle, yet important, differences due to the biological condition. Little is understood about complex proteomes and their variability. A critical aspect of proteomic biomarker research that is largely unexplored is the comparative reproducibility of certain methods such as two-dimensional gel electrophoresis and liquid chromatography/mass spectrometry. In particular, with liquid chromatography/mass spectrometry, it is not known whether variability in peptide quantitation is dependent on any of …


Biochemical Investigations Of Macular Degeneration: The Significance Of Protein Oxidation Including Novel Methods For Its Study, Sarah Warburton Nov 2006

Biochemical Investigations Of Macular Degeneration: The Significance Of Protein Oxidation Including Novel Methods For Its Study, Sarah Warburton

Theses and Dissertations

The retinal pigment epithelium (RPE) is a monolayer of cells located directly behind the photoreceptor cells in the retina. These cells are involved in a variety of functions that support the visual process in the eye, namely 1) they form a blood-retina barrier which separates the neural retina from the choroid's blood supply, 2) the apical processes of RPE cells diurnally phagocytose the outer segments of photoreceptor cells, and 3) they participate in the renewal of the photopigment 11-cis retinal. Age-related macular degneration (AMD) is the leading cause of blindness in people over the age of 50 years in North …


Sources Of Variability In A Proteomic Experiment, Scott Daniel Crawford Aug 2006

Sources Of Variability In A Proteomic Experiment, Scott Daniel Crawford

Theses and Dissertations

The study of proteomics holds the hope for detecting serious diseases earlier than is currently possible by analyzing blood samples in a mass spectrometer. Unfortunately, the statistics involved in comparing a control group to a diseased group are not trivial, and these difficulties have led others to incorrect decisions in the past. This paper considers a nested design that was used to quantify and identify the sources of variation in the mass spectrometer at BYU, so that correct conclusions can be drawn from blood samples analyzed in proteomics. Algorithms were developed which detect, align, correct, and cluster the peaks in …


Ip Algorithm Applied To Proteomics Data, Christopher Lee Green Nov 2004

Ip Algorithm Applied To Proteomics Data, Christopher Lee Green

Theses and Dissertations

Mass spectrometry has been used extensively in recent years as a valuable tool in the study of proteomics. However, the data thus produced exhibits hyper-dimensionality. Reducing the dimensionality of the data often requires the imposition of many assumptions which can be harmful to subsequent analysis. The IP algorithm is a dimension reduction algorithm, similar in purpose to latent variable analysis. It is based on the principle of maximum entropy and therefore imposes a minimum number of assumptions on the data. Partial Least Squares (PLS) is an algorithm commonly used with proteomics data from mass spectrometry in order to reduce the …