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Full-Text Articles in Physical Sciences and Mathematics
Using Quantitative And Kinetic Proteomics To Explore Proteostasis, Nathan Raul Zuniga Pina
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
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 …
Developing Methods For Measuring In Vivo Lipid Metabolism, Russell L. Denton
Developing Methods For Measuring In Vivo Lipid Metabolism, Russell L. Denton
Theses and Dissertations
Lipid metabolism is critically important to the normal function of individual cells and for signaling between tissues of the human body. There is a great need to quantify changes in lipid metabolism because of its implications in both normal healthy conditions and during disease development. In our first study, we developed a liquid chromatography mass spectrometry based workflow to assess in vivo metabolism of murine brain lipids. This involved sample preparation, data acquisition, and analysis software development and improvements. Regarding sample preparation, we maintained the mice at 5% body water for the duration of the experiment. As mouse metabolism proceeds, …
Quantifying Protein Quality To Understand Protein Homeostasis, Hsien-Jung Lavender Lin
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, …
Instrumentation And Application Of Image-Charge Detection Of Electrospray-Charged Microparticles And Microdroplets, Jiuzhi Gao
Theses and Dissertations
Image-charge detection is emerging as an important tool to analyze heavy and heterogeneous samples because of its unique advantages in measuring highly charged microparticles. Conventional image-charge detection instruments include at least three fundamental components: an ionization source, an aerodynamic particle delivery system, and an image-charge detector. Here I report research efforts that investigated the mechanisms of image-charge detection and proposed some instrumental developments of these components to suit specific research purposes. In Chapter 2, I report an investigation of the electrospray ionization (ESI) mechanism based on an observation that a certain portion of charged particles generated with an ESI source …
Computational Regiospecific Analysis Of Brain Lipidomic Profiles, Austin Ahlstrom
Computational Regiospecific Analysis Of Brain Lipidomic Profiles, Austin Ahlstrom
Undergraduate Honors Theses
Mass spectrometry provides an extensive data set that can prove unwieldy for practical analytical purposes. Applying programming and machine learning methods to automate region analysis in DESI mass spectrometry of mouse brain tissue can help direct and refine such an otherwise unusable data set. The results carry promise of faster, more reliable analysis of this type, and yield interesting insights into molecular characteristics of regions of interest within these brain samples. These results have significant implications in continued investigation of molecular processes in the brain, along with other aspects of mass spectrometry, collective analysis of biological molecules (i.e. omics), and …
Development And Use Of Lipidomics And Proteomics Methods To Identify And Measure Pro-Survival Metabolic Pathways In Cancer, Monique Merilyn Speirs
Development And Use Of Lipidomics And Proteomics Methods To Identify And Measure Pro-Survival Metabolic Pathways In Cancer, Monique Merilyn Speirs
Theses and Dissertations
Throughout society’s continual war against cancer, we have attempted pharmacological intervention only to find that tumors develop modes of resistance. It is well known that genetics play an integral role in cancer. Technological advances have greatly improved our ability to study cancer biochemistry beyond the genome by measuring changes in the expression and activity of RNA, proteins, and lipids in experimental models and human patients. As our techniques and technology to perform cancer research progresses, it is becoming more evident that cancer cells develop stress tolerance mechanisms at multiple levels within the central dogma, including altering mRNA expression, enzyme concentrations, …
Fundamental Studies And Applications Of Ambient Plasma Ionization Sources For Mass Spectrometry, Wade C. Ellis
Fundamental Studies And Applications Of Ambient Plasma Ionization Sources For Mass Spectrometry, Wade C. Ellis
Theses and Dissertations
The field of ambient desorption/ionization mass spectrometry (ADI-MS) has existed for over a decade. ADI-MS is a technique that offers benefits including fast analysis time, simple ionization sources that are easily constructed, and little to no required sample preparation. The research presented here describes efforts to better understand plasma-based ADI-MS sources and to explore the use of hydrogen-doped plasma gases with these sources. The use of hydrogen-doped argon (H2/Ar) and hydrogen-doped helium (H2/He) as plasma gases for a dielectric barrier discharge (DBD) and an AC glow discharge is presented first. When using the DBD, the intensity …
Desorption Electrospray Ionization (Desi) Mass Spectrometric Imaging Of Spatially Regulated In Vivo Metabolic Rates, Charlotte Reininger Lewis
Desorption Electrospray Ionization (Desi) Mass Spectrometric Imaging Of Spatially Regulated In Vivo Metabolic Rates, Charlotte Reininger Lewis
Theses and Dissertations
Desorption electrospray ionization (DESI) is an ambient ionization technique used for mass spectrometric imaging of biological samples. When coupled with isotopic ratio measurements of deuterium-labeled tissues, DESI provides a means of measuring metabolic rates on a spatially resolved basis. In vivo metabolic rates are desired to better understand diseases such as Alzheimer's, Parkinson's, Huntington's, and various forms of cancer that negatively impact metabolic rates within different organs of the human body. Although DESI has been used to image lipids and metabolites of a variety of tissues and other imaging techniques, such as NIMS, have been used to study kinetic turnover …
Investigation Of Dynamic Biological Systems Using Direct Injection And Liquid Chromatography Mass Spectrometry, Adam Clayton Swensen
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
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 …
Image-Charge Detection  Novel Instrumentation And Applications, Brandon Lee Barney
Image-Charge Detection  Novel Instrumentation And Applications, Brandon Lee Barney
Theses and Dissertations
Image-charge detection is an analytical technique in which a highly-charged particle is detected by the magnitude of the image current that it generates in a detecting electrode. This current is represented as a voltage between the charged particle and the sensing electrode. It is a single particle detection method, ideal for the analysis of large, variable mass particles such as biological cells. Some of the physical properties of Bacillus subtilis spores were explored using different applications of image-charge detection. B. subtilis is a gram-negative spore-forming bacteria that has been shown to exhibit extremophile behavior. The particular extremophile behavior that was …
Mass Spectrometry Based Proteomics And Lipidomics Studies, Huan Kang
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
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
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 …
Elucidation And Improvement Of Algorithms For Mass Spectrometry Isotope Trace Detection, Robert Anthony Smith
Elucidation And Improvement Of Algorithms For Mass Spectrometry Isotope Trace Detection, Robert Anthony Smith
Theses and Dissertations
Mass spectrometry facilitates cutting edge advancements in many fields. Although instrumentation has advanced dramatically in the last 100 years, data processing algorithms have not kept pace. Without sensitive and accurate signal segmentation algorithms, the utility of mass spectrometry is limited. In this dissertation, we provide an overview and analysis of mass spectrometry data processing. A tutorial to ease the learning curve for those outside the field is provided. We draw attention to the lack of critical evaluation in the field and describe the resulting effects, including a glut of algorithm contributions of questionable novel contribution. To facilitate increased critical evaluation, …
Bacterial Spores Remain Viable After Electrospray Charging And Desolvation, Sara Nielson Pratt
Bacterial Spores Remain Viable After Electrospray Charging And Desolvation, Sara Nielson Pratt
Theses and Dissertations
The electrospray survivability of B. subtilis spores and E. coli was tested in atmospheric mobility experiments. E. coli did not survive electrospray charging and desolvation, but B. subtilis did. Experimental conditions ensured that any surviving bacteria were charged, desolvated, and de-agglomerated. B. subtilis was also found to survive both positive and negative electrospray and subsequent introduction into vacuum conditions. Attempts were made to measure the charge distribution of viable B. subtilis spores using electrostatic deflection. From those experiments, it was found that either the spores do not become highly charged under the electrospray conditions used or only spores in a …
Novel Ion Trap Made Using Lithographically Patterned Plates, Ying Peng
Novel Ion Trap Made Using Lithographically Patterned Plates, Ying Peng
Theses and Dissertations
A new approach of making ion trap mass analyzers was developed in which trapping fields are created in the space between two ceramic plates. Based on microfabrication technology, a series of independently-adjustable electrode rings is lithographically patterned on the facing surfaces of each ceramic plate. The trapping field can be modified or fine-tuned simply by changing the RF amplitude applied to each electrode ring. By adjusting the potential function applied to the plates, arbitrary trapping fields can be created using the same set of ceramic plates. Unlike conventional ion traps, the electrodes of planar ion traps have a non-equipotential surface, …
Halo Ion Trap Mass Spectrometry: Design, Instrumentation, And Performance, Miao Wang
Halo Ion Trap Mass Spectrometry: Design, Instrumentation, And Performance, Miao Wang
Theses and Dissertations
New ion trap mass spectrometry (ITMS) instrumentation, the toroidal IT and halo IT, were developed to meet the significant growth in on-site analysis applications. The miniature toroidal IT mass analyzer was operated with radio frequency (RF) trapping voltages of 3 kVp-p or less. Despite its reduced dimensions, it has roughly the same ion trapping capacity as conventional 3D quadrupole ITs. Unit-mass resolved spectra for n-butylbenzene, xenon, and naphthalene were obtained. The desired linear mass scale was obtained using conventional mass-selective instability scan combined with resonance ejection. The halo IT was also based on toroidal trapping geometry and microfabrication technology, consisting …
Gas Phase Chiral Recognition, Characterization Of Porous Polymer Monolith Nanospray Ionization, And The Negative Mode Crafti Method Using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, Nannan Fang
Theses and Dissertations
Our group has been studying chiral recognition in gas phase using mass spectrometry for more than 10 years. We are interested in gas phase studies of fundamental interactions because the gas phase avoids complications and masking effects that may arise upon solvation. Therefore, the results of gas phase experiments can be directly compared with those of high-level computational studies. In chapter 2, I studied the roles of hydrogen bonding and pi stacking in gas phase chiral recognition between aromatic crown molecules and aromatic amines. High affinity between host and guest doesn't necessarily result in better recognition. If the affinity is …
A Top-Down Proteomic Approach For The Discovery Of Novel Serum Biomarkers Of Pregnancy-Related Disease, Karen Merrell
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 …
Development Of Methods For The Study Of Phosphoproteins, Zhaoyuan Chen
Development Of Methods For The Study Of Phosphoproteins, Zhaoyuan Chen
Theses and Dissertations
Characterization of phosphoproteins-including detection, identification of phosphoproteins and identification of phosphorylation sites-is mostly done with radiolabeling and proteomic techniques. Three main topics related to phosphoprotein characterization are included in this dissertation. First, large-scale characterization of the CHO (Chinese hamster ovary) cell phosphoproteome was done using two dimensional gel electrophoresis (2DE) separation, visualization of phosphoproteins by radiolabeling or a phosphoprotein specific dye, followed by MALDI-TOF identification. Because radiolabeling of phosphoproteins is very sensitive and straightforward to quantify, such analysis can give a clear picture of the relative phosphosphorylation of proteins present in a sample. But there are also limitations to this …
Biochemical Investigations Of Macular Degeneration: The Significance Of Protein Oxidation Including Novel Methods For Its Study, Sarah Warburton
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 …
Enhanced Electrospray Ionization For Mass Spectrometry And Ion Mobility Spectrometry, Li Zhou
Enhanced Electrospray Ionization For Mass Spectrometry And Ion Mobility Spectrometry, Li Zhou
Theses and Dissertations
Electrospray ionization (ESI) has become one of the most commonly used ionization techniques for mass spectrometry (MS) and ion mobility spectrometry (IMS), and efforts continue to improve its performance. ESI-MS is most recognized for its wide application to biomacromolecules where high sensitivity is of paramount importance. However, the major limitation in sensitivity with ESI-MS is due to its low ion transmission efficiency from the ESI source into the sampling orifice and through any stages utilized for transfer of ions from atmosphere to vacuum in the MS. A series of atmospheric pressure ion focusing interfaces were designed and implemented to enhance …
Ip Algorithm Applied To Proteomics Data, Christopher Lee Green
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 …