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2018

Proteomics

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Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu Dec 2018

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …


Investigating The Role Of Carotenoids In Membrane Organization Of Pantoea Sp. Yr343, Sushmitha Vijaya Kumar Dec 2018

Investigating The Role Of Carotenoids In Membrane Organization Of Pantoea Sp. Yr343, Sushmitha Vijaya Kumar

Doctoral Dissertations

Bacterial cell membranes are complex mixtures of lipids and proteins, the combination of which confers biophysical properties to the membrane and allows it to respond to environmental conditions. Pantoea sp. YR343 is a plant-associated gram-negative gamma-proteobacteria characterized by the presence of carotenoids in the membrane. Pantoea sp. YR343 mutants lacking phytoene synthase (encoded by crtB), which catalyzes the first step in carotenoid biosynthesis, failed to produce carotenoids and displayed enhanced sensitivity to reactive oxygen species. The crtB mutant also displayed unexpected defects in biofilm formation, secretion of indole-3-acetic acid, and root colonization compared to wildtype cells. We hypothesized that …


Progress On Identifying And Characterizing The Human Proteome: 2018 Metrics From The Hupo Human Proteome Project., Gilbert S Omenn, Lydie Lane, Christopher M Overall, Fernando J Corrales, Jochen M Schwenk, Young-Ki Paik, Jennifer E Van Eyk, Siqi Liu, Michael Snyder, Mark S Baker, Eric W Deutsch Dec 2018

Progress On Identifying And Characterizing The Human Proteome: 2018 Metrics From The Hupo Human Proteome Project., Gilbert S Omenn, Lydie Lane, Christopher M Overall, Fernando J Corrales, Jochen M Schwenk, Young-Ki Paik, Jennifer E Van Eyk, Siqi Liu, Michael Snyder, Mark S Baker, Eric W Deutsch

Articles, Abstracts, and Reports

The Human Proteome Project (HPP) annually reports on progress throughout the field in credibly identifying and characterizing the human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2018-01-17, the baseline for this sixth annual HPP special issue of the Journal of Proteome Research, contains 17 470 PE1 proteins, 89% of all neXtProt predicted PE1-4 proteins, up from 17 008 in release 2017-01-23 and 13 975 in release 2012-02-24. Conversely, the number of neXtProt PE2,3,4 missing proteins has been reduced from 2949 to 2579 to 2186 over the past …


Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst Dec 2018

Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst

Articles, Abstracts, and Reports

The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level …


Integrated Proteotranscriptomics Of Breast Cancer Reveals Globally Increased Protein-Mrna Concordance Associated With Subtypes And Survival, Wei Tang, Ming Zhou, Tiffany H Dorsey, Darue A Prieto, Xin W Wang, Eytan Ruppin, Timothy Veenstra, Stefan Ambs Dec 2018

Integrated Proteotranscriptomics Of Breast Cancer Reveals Globally Increased Protein-Mrna Concordance Associated With Subtypes And Survival, Wei Tang, Ming Zhou, Tiffany H Dorsey, Darue A Prieto, Xin W Wang, Eytan Ruppin, Timothy Veenstra, Stefan Ambs

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis.

METHODS: We applied a quantitative liquid chromatography/mass spectrometry-based proteome analysis using an untargeted approach and analyzed protein extracts from 65 breast tumors and 53 adjacent non-cancerous tissues. Additional gene expression data from Affymetrix Gene Chip Human Gene ST Arrays were available …


Venom Composition Of Little Known Mountain Rattlesnakes And Predator-Prey Interactions Of Crotalus Pricei Pricei And Its Natural Prey, Sceloporus Jarrovii, Emily Grabowsky Dec 2018

Venom Composition Of Little Known Mountain Rattlesnakes And Predator-Prey Interactions Of Crotalus Pricei Pricei And Its Natural Prey, Sceloporus Jarrovii, Emily Grabowsky

Master's Theses

The Crotalus intermedius clade is a small group composed of four species: C. intermedius, C. transversus, C. pricei, and the recently identified C. tancitarensis (Alvarado-Díaz and Campbell, 2004; Reyes-Valesco et al. 2013). Though these species are restricted to high elevations of Sky Islands of southern Arizona and throughout México, little has been reported about their natural history and basic biology, including venom composition. Specifically, the Western Twin-spotted Rattlesnake (C. pricei pricei) is a small lizard specialist restricted to the more northern Sky Islands of México, with isolated populations in southern Arizona, where they are a protected species. …


Molecular Response Of Retinal Pigment Epithelial Cells To Oxidized Lipoproteins: Global And Targeted Studies, Diwa Koirala Dec 2018

Molecular Response Of Retinal Pigment Epithelial Cells To Oxidized Lipoproteins: Global And Targeted Studies, Diwa Koirala

Theses and Dissertations (ETD)

Global-scale examinations of biological systems at the molecular level complement targeted approaches to scientific inquiry that focus on specific subsets of biomolecules, or on a single molecule of interest. In this dissertation, we utilized both the discovery-based approach to evaluate the proteomics workflows centered around mass spectrometry as the key technology, and the targeted approach to examine the molecular response of RPE due to oxidized lipoproteins (oxLDL) treatments. A crucial aspect in proteomics studies is the design of bioanalytical strategies that maximize coverage of the complex repertoire of a proteome. A comprehensive, unbiased examination of the proteome represents a powerful …


Imass Time: The Future, In Future!, Qingwei Ma, Eric Adua, Mary C. Boyce, Xingang Li, Guang Ji, Wei Wang Nov 2018

Imass Time: The Future, In Future!, Qingwei Ma, Eric Adua, Mary C. Boyce, Xingang Li, Guang Ji, Wei Wang

Research outputs 2014 to 2021

Joseph John Thomson discovered and proved the existence of electrons through a series of experiments. His work earned him a Nobel Prize in 1906 and initiated the era of mass spectrometry (MS). In the intervening time, other researchers have also been awarded the Nobel Prize for significant advances in MS technology. The development of soft ionization techniques was central to the application of MS to large biological molecules and led to an unprecedented interest in the study of biomolecules such as proteins (proteomics), metabolites (metabolomics), carbohydrates (glycomics), and lipids (lipidomics), allowing a better understanding of the molecular underpinnings of health …


Redox Regulation Of Type-I Inositol Trisphosphate Receptors In Intact Mammalian Cells., Suresh K. Joseph, Michael P. Young, Kamil Alzayady, David I. Yule, Mehboob Ali, David M. Booth, György Hajnóczky Nov 2018

Redox Regulation Of Type-I Inositol Trisphosphate Receptors In Intact Mammalian Cells., Suresh K. Joseph, Michael P. Young, Kamil Alzayady, David I. Yule, Mehboob Ali, David M. Booth, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by alterations in the redox state of critical thiols in the IP3R, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We found that under basal conditions, ∼5 of the 60 cysteines are oxidized in IP3R1. Cell treatment with 50 μm thimerosal altered gel shifts, indicating oxidation of ∼20 cysteines. …


Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt Nov 2018

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …


Egfr Signaling From The Early Endosome., Julie A. Gosney Aug 2018

Egfr Signaling From The Early Endosome., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue …


Hypoxia-Derived Exosomes Induce Putative Altered Pathways In Biosynthesis And Ion Regulatory Channels In Glioblastoma Cells, Rajshekhar A. Kore, Jacob L. Edmondson, Samir V. Jenkins, Azemat Jamshidi-Parsian, Ruud P.M. Dings, Nathan S. Reyna, Robert J. Griffin Jul 2018

Hypoxia-Derived Exosomes Induce Putative Altered Pathways In Biosynthesis And Ion Regulatory Channels In Glioblastoma Cells, Rajshekhar A. Kore, Jacob L. Edmondson, Samir V. Jenkins, Azemat Jamshidi-Parsian, Ruud P.M. Dings, Nathan S. Reyna, Robert J. Griffin

Articles

Hypoxia, a hallmark characteristic of glioblastoma (GBM) induces changes in the transcriptome and the proteome of tumor cells. We discovered that hypoxic stress produces significant qualitative and quantitative changes in the protein content of secreted exosomes from GBM cells. Among the proteins found to be selectively elevated in hypoxic exosomes were protein-lysine 6-oxidase (LOX), thrombospondin-1 (TSP1), vascular derived endothelial factor (VEGF) and a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), well studied contributors to tumor progression, metastasis and angiogenesis. Our findings demonstrate that hypoxic exosomes induce differential gene expression in recipient glioma cells. Glioma cells stimulated with hypoxic exosomes …


Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator Jun 2018

Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator

Electronic Thesis and Dissertation Repository

Cancers exist within complex microenvironments formed by heterogeneous cell types. This diversity creates significant challenges for detection, diagnosis and treatment. Mass spectrometry-based proteomics is a powerful approach capable of characterizing complex biological systems which are characteristic of cancer biology. In this thesis, proteomics was utilized to answer several questions related to ovarian cancer diagnosis and detection, and the effects of NODAL, an embryonic morphogen, on the breast cancer secretome and stromal cell recruitment. First, I compared multiple sample preparation techniques and found high-pH/low-pH fractionation to yield the greatest proteome coverage over commonly used approaches. Second, I compared the proteomes from …


Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins Jun 2018

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins

Arshad M. Khan, Ph.D.

This article, which includes novel unpublished data along with commentary and analysis,
focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from
brain tissue to the original locations within the brain that they are derived from using digital atlas
mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic
analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we
highlight studies that have mined biochemical and molecular information from the hypothalamus
and then lay out a strategy for how these data can be linked spatially to the mapped locations in a
canonical brain atlas …


A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi Jun 2018

A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi

USF Tampa Graduate Theses and Dissertations

Lung cancer is the second most common cancer type and is associated with high mortality rates. The survival rate for lung cancer patients has increased slowly in the last decade mainly as the result of the development of novel targeted and immune therapies. However, non-small cell lung cancer patients lacking known or actionable driver mutations and small cell lung cancer patients with recurrent disease are still in urgent need of new therapies. Drug repurposing is an efficient way to identify new therapies since it uses clinically relevant small molecule drugs. Determination of off-targets of small molecules is a novel approach …


A Systems Biology Approach For Studying Heterotopic Ossification: Proteomic Analysis Of Clinical Serum And Tissue Samples, Erin Crowgey, Jennifer Wyffels, Patrick Osborn, Thomas Wood, Laura Edsberg Jun 2018

A Systems Biology Approach For Studying Heterotopic Ossification: Proteomic Analysis Of Clinical Serum And Tissue Samples, Erin Crowgey, Jennifer Wyffels, Patrick Osborn, Thomas Wood, Laura Edsberg

Articles & Book Chapters

Heterotopic ossification (HO) refers to the abnormal formation of bone in soft tissue. Although some of the underlying processes of HO have been described, there are currently no clinical tests using validated biomarkers for predicting HO formation. As such, the diagnosis is made radiographically after HO has formed. To identify potential and novel biomarkers for HO, we used isobaric tags for relative and absolute quantitation (iTRAQ) and high-throughput antibody arrays to produce a semi-quantitative proteomics survey of serum and tissue from subjects with (HO+) and without (HO−) heterotopic ossification. The resulting data were then analyzed using a systems biology approach. …


Mitochondrial Proteome Disruption In The Diabetic Heart Through Targeted Epigenetic Regulation At The Mitochondrial Heat Shock Protein 70 (Mthsp70) Nuclear Locus, Danielle L. Shepherd, Quincy A. Hathaway, Cody E. Nichols, Andrya J. Durr, Mark V. Pinti, Kristen M. Hughes, Amina Kunovac, Seth M. Stine, John M. Hollander Jun 2018

Mitochondrial Proteome Disruption In The Diabetic Heart Through Targeted Epigenetic Regulation At The Mitochondrial Heat Shock Protein 70 (Mthsp70) Nuclear Locus, Danielle L. Shepherd, Quincy A. Hathaway, Cody E. Nichols, Andrya J. Durr, Mark V. Pinti, Kristen M. Hughes, Amina Kunovac, Seth M. Stine, John M. Hollander

Clinical and Translational Science Institute

Greater than 99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor. Type 2 diabetes mellitus (T2DM) disrupts mitochondrial proteomic signature which is associated with decreased protein import efficiency. The goal of this study was to manipulate the mitochondrial protein import process through targeted restoration of mtHsp70, in an effort to restore proteomic signature and mitochondrial function in the T2DM heart. A novel line of cardiac-specific mtHsp70 …


Ms Analysis Of A Dilution Series Of Bacteria: Phytoplankton To Improve Detection Of Low Abundance Bacterial Peptides, Emma Timmins-Schiffman, Molly P. Mikan, Ying Sonia Ting, H. Rodger Harvey, Brook L. Nunn Jun 2018

Ms Analysis Of A Dilution Series Of Bacteria: Phytoplankton To Improve Detection Of Low Abundance Bacterial Peptides, Emma Timmins-Schiffman, Molly P. Mikan, Ying Sonia Ting, H. Rodger Harvey, Brook L. Nunn

OES Faculty Publications

Assigning links between microbial activity and biogeochemical cycles in the ocean is a primary objective for ecologists and oceanographers. Bacteria represent a small ecosystem component by mass, but act as the nexus for both nutrient transformation and organic matter recycling. There are limited methods to explore the full suite of active bacterial proteins largely responsible for degradation. Mass spectrometry (MS)-based proteomics now has the potential to document bacterial physiology within these complex systems. Global proteome profiling using MS, known as data dependent acquisition (DDA), is limited by the stochastic nature of ion selection, decreasing the detection of low abundance peptides. …


A Protein Standard That Emulates Homology For The Characterization Of Protein Inference Algorithms., Matthew The, Fredrik Edfors, Yasset Perez-Riverol, Samuel H Payne, Michael R Hoopmann, Magnus Palmblad, Björn Forsström, Lukas Käll May 2018

A Protein Standard That Emulates Homology For The Characterization Of Protein Inference Algorithms., Matthew The, Fredrik Edfors, Yasset Perez-Riverol, Samuel H Payne, Michael R Hoopmann, Magnus Palmblad, Björn Forsström, Lukas Käll

Articles, Abstracts, and Reports

A natural way to benchmark the performance of an analytical experimental setup is to use samples of known composition and see to what degree one can correctly infer the content of such a sample from the data. For shotgun proteomics, one of the inherent problems of interpreting data is that the measured analytes are peptides and not the actual proteins themselves. As some proteins share proteolytic peptides, there might be more than one possible causative set of proteins resulting in a given set of peptides and there is a need for mechanisms that infer proteins from lists of detected peptides. …


Inhibition Of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells With Vascular Regenerative Function, Tyler T. Cooper, Stephen E. Sherman, Miljan Kuljanin, Gillian I. Bell, Gilles A. Lajoie, David A. Hess May 2018

Inhibition Of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells With Vascular Regenerative Function, Tyler T. Cooper, Stephen E. Sherman, Miljan Kuljanin, Gillian I. Bell, Gilles A. Lajoie, David A. Hess

Paediatrics Publications

Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH hi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDH hi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDH hi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during …


Determination Of Adamts13 Susceptibility In Type Iia Von Willebrand Disease, Monica Buselli May 2018

Determination Of Adamts13 Susceptibility In Type Iia Von Willebrand Disease, Monica Buselli

Dissertations, Masters Theses, Capstones, and Culminating Projects

von Willebrand Disease (vWD) is a bleeding disorder caused by a deficiency in von Willebrand Factor (vWF), a large glycoprotein that assists in coagulation. Specifically, large vWF multimers in the blood stream are key components in starting the coagulation cascade. vWF is cleaved by the metalloprotease ADAMTS13, regulating the multimers size, which hinders vWF’s ability to function properly. The three main types of vWD —Type I, II, and III— are not well defined, and as a result are all similarly treated with plasma-derived vWF replacement therapy. Plasma-derived vWF is a treatment that does not cure the problem but relieves the …


The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin Apr 2018

The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin

USF Tampa Graduate Theses and Dissertations

Chronic liver diseases, which includes alcoholic liver disease (ALD), are consistently among the top 15 leading causes of death in the United States. ALD is characterized by progression from a normal liver to fatty liver disease (hepatic steatosis), which can lead to cirrhosis, alcoholic hepatitis, and liver failure. We have identified a novel role of phosphohistidine signaling, mediated through phosphohistidine phosphatase 1 (PHPT1), in the onset of hepatic steatosis. We have identified PHPT1 as a target of selective oxidation following acute ethanol exposure as well as being downregulated following chronic ethanol exposure. We mapped the oxidative modification site and developed …


Neural Mechanisms Of Transcranial Magnetic Stimulation In The Treatment Of Tinnitus, Andrea S. Lowe Apr 2018

Neural Mechanisms Of Transcranial Magnetic Stimulation In The Treatment Of Tinnitus, Andrea S. Lowe

USF Tampa Graduate Theses and Dissertations

Millions of people suffer from tinnitus, a disorder for which there is currently no effective treatment or cure. My dissertation work provides insight into the neural correlates of this pervasive hearing disorder and examines how a newly emerging therapy, transcranial magnetic stimulation (TMS), affects the central auditory system in the generation of the tinnitus percept. This work has a multifold focus of: i) developing and modeling the function of a miniature magnetic coil that can be used for TMS in rodents, ii) establishing a reliable mouse model of tinnitus that can be used for assessing TMS treatment-induced changes, iii) measuring …


A Holistic Computational Approach To Boosting The Performance Of Protein Search Engines, Majdi Ahmad Mosa Maabreh Apr 2018

A Holistic Computational Approach To Boosting The Performance Of Protein Search Engines, Majdi Ahmad Mosa Maabreh

Dissertations

Despite availability of several proteins search engines, due to the increasing amounts of MS/MS data and database sizes, more efficient data analysis and reduction methods are important. Improving accuracy and performance of protein identification is a main goal in the community of proteomic research. In this research, a holistic solution for improvement in search performance is developed.

Most current search engines apply the SEQUEST style of searching protein databases to define MS/MS spectra. SEQUEST involves three main phases: (i) Indexing the protein databases, (ii) Matching and Ranking the MS/MS spectra and (iii) Filtering the matches and reporting the final proteins. …


Transcriptional Regulatory Networks Underlying Gene Expression Changes In Huntington's Disease., Seth A Ament, Jocelynn R Pearl, Jeffrey P Cantle, Robert M Bragg, Peter J Skene, Sydney R Coffey, Dani E Bergey, Vanessa C Wheeler, Marcy E Macdonald, Nitin S Baliga, Jim Rosinski, Leroy E Hood, Jeffrey B Carroll, Nathan D Price Mar 2018

Transcriptional Regulatory Networks Underlying Gene Expression Changes In Huntington's Disease., Seth A Ament, Jocelynn R Pearl, Jeffrey P Cantle, Robert M Bragg, Peter J Skene, Sydney R Coffey, Dani E Bergey, Vanessa C Wheeler, Marcy E Macdonald, Nitin S Baliga, Jim Rosinski, Leroy E Hood, Jeffrey B Carroll, Nathan D Price

Articles, Abstracts, and Reports

Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in


Comparative Proteomics: Assessing The Variation In Molecular Physiology Within The Adductor Muscle Between Mytilus Galloprovincialis And Mytilus Trossulus In Response To Acute Heat Stress, Joshua Scott Mier Mar 2018

Comparative Proteomics: Assessing The Variation In Molecular Physiology Within The Adductor Muscle Between Mytilus Galloprovincialis And Mytilus Trossulus In Response To Acute Heat Stress, Joshua Scott Mier

Master's Theses

Increases in seawater temperatures have imposed physiological constraints which are partially thought to contribute to recently observed shifts in biogeographic distribution among closely related intertidal ectotherms. For instance, Mytilus galloprovincialis an introduced warm-adapted species from the Mediterranean, has displaced the native cold-adapted congener, M. trossulus, over large latitudinal expanses off the California coast. Several comparative physiological studies have revealed interspecific differences in thermal tolerance, including variation in aerobic metabolism and gape behavior, which suggest the invasive congener is better adapted to acclimate to increasing seawater conditions as predicted due to climate change. However, current analyses seek to discover the …


Applying Genomics In Heart Transplantation., Brendan J Keating, Alexandre C Pereira, Michael Snyder, Brian D. Piening Mar 2018

Applying Genomics In Heart Transplantation., Brendan J Keating, Alexandre C Pereira, Michael Snyder, Brian D. Piening

Articles, Abstracts, and Reports

While advances in patient care and immunosuppressive pharmacotherapies have increased the lifespan of heart allograft recipients, there are still significant comorbidities post-transplantation and 5-year survival rates are still significant, at approximately 70%. The last decade has seen massive strides in genomics and other omics fields, including transcriptomics, with many of these advances now starting to impact heart transplant clinical care. This review summarizes a number of the key advances in genomics which are relevant for heart transplant outcomes, and we highlight the translational potential that such knowledge may bring to patient care within the next decade.


The Human Brainome: Network Analysis Identifies Hspa2 As A Novel Alzheimer’S Disease Target, Vladislav A. Petyuk, Rui Chang, Manuel Ramirez-Restrepo, Noam D. Beckmann, Marc Y. R. Henrion, Paul D. Piehowski, Kuixi Zhu, Sven Wang, Jennifer L. Clarke, Matthew J. Huentelman, Fang Xie, Victor Andreev, Anzhelika Engel, Toumy Guettoche, Loida Navarro, Philip De Jager, Julie A. Schneider, Christopher M. Morris, Ian G. Mckeith, Robert H. Perry, Simon Lovestone, Randall L. Woltjer, Thomas G. Beach, Lucia I. Sue, Geidy E. Serrano, Andrew P. Lieberman, Roger L. Albin, Isidre Ferrer, Deborah C. Mash, Christine M. Hulette, John F. Ervin, Eric M. Reiman, John A. Hardy, David A. Bennett, Eric Schadt, Richard D. Smith, Amanda J. Myers Jan 2018

The Human Brainome: Network Analysis Identifies Hspa2 As A Novel Alzheimer’S Disease Target, Vladislav A. Petyuk, Rui Chang, Manuel Ramirez-Restrepo, Noam D. Beckmann, Marc Y. R. Henrion, Paul D. Piehowski, Kuixi Zhu, Sven Wang, Jennifer L. Clarke, Matthew J. Huentelman, Fang Xie, Victor Andreev, Anzhelika Engel, Toumy Guettoche, Loida Navarro, Philip De Jager, Julie A. Schneider, Christopher M. Morris, Ian G. Mckeith, Robert H. Perry, Simon Lovestone, Randall L. Woltjer, Thomas G. Beach, Lucia I. Sue, Geidy E. Serrano, Andrew P. Lieberman, Roger L. Albin, Isidre Ferrer, Deborah C. Mash, Christine M. Hulette, John F. Ervin, Eric M. Reiman, John A. Hardy, David A. Bennett, Eric Schadt, Richard D. Smith, Amanda J. Myers

Department of Food Science and Technology: Faculty Publications

Our hypothesis is that changes in gene and protein expression are crucial to the development of late-onset Alzheimer’s disease. Previously we examined how DNA alleles control downstream expression of RNA transcripts and how those relationships are changed in late-onset Alzheimer’s disease. We have now examined how proteins are incorporated into networks in two separate series and evaluated our outputs in two different cell lines. Our pipeline included the following steps: (i) predicting expression quantitative trait loci; (ii) determining differential expression; (iii) analysing networks of transcript and peptide relationships; and (iv) validating effects in two separate cell lines. We performed all …


Proteogenomic Study Of Nitrogen-Fixing Cyanobacterium Anabaena Cylindrica, Yeyan Qiu Jan 2018

Proteogenomic Study Of Nitrogen-Fixing Cyanobacterium Anabaena Cylindrica, Yeyan Qiu

Electronic Theses and Dissertations

Cyanobacteria are gram-negative photosynthetic bacteria. In some filamentous cyanobacteria such as Anabaena cylindrica, every 10th to 20th vegetative cells can differentiate into nitrogen fixing heterocysts. Heterocyst can induce the neighboring cells developing into spore-like akinetes. The specialized cell functions and resourceful networks have contributed to the prosperity of cyanobacteria for over 2 billion years, but the genetic mechanisms for multi-cellular differentiation are barely known, especially for akinete formation. The heterocysts, akinetes and vegetative cells of Anabaena cylindrica were isolated for proteomic study. This study identified a total of 1395 proteins, including 664 proteins from akinetes, 751 proteins from …


Quantification Of Mouse Cardiac Troponin I And Myosin Binding Protein C Phosphorylation By Liquid Chromatography-Mass Spectrometry (Lc-Ms), Praveena Nukareddy Jan 2018

Quantification Of Mouse Cardiac Troponin I And Myosin Binding Protein C Phosphorylation By Liquid Chromatography-Mass Spectrometry (Lc-Ms), Praveena Nukareddy

Graduate College Dissertations and Theses

Heart failure is a major public health issue, with its prevalence estimated to be 6.5 million adults in the USA. Of the hospitalized heart failure (HF) cases, 50% are characterized by preserved ejection function (HFpEF). In HFpEF, the heart pumps a normal proportion of blood that enters it. However, thickening of the ventricular walls inhibits the chamber filling to normal volume. The direct basis of HFpEF is a slowed elongation of the cardiac muscle during the diastolic phase of the cardiac cycle. Elucidation of mechanisms that mediate relaxation of cardiac muscle could help understand the pathogenic mechanisms in HFpEF.

Myocardial …