Life Sciences Commons^™

Mitochondrial Dynamics And Respiration Within Cells With Increased Open Pore Cytoskeletal Meshes, David H. Jang, Sarah C. Seeger, Martha E. Grady, Frances S. Shofer, David M. Eckmann

Mechanical Engineering Faculty Publications

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and …

Toxicity And Mitochondrial Delivery Of Flavonol-Based Carbon Monoxide-Releasing Molecules, Hector Jose Esquer Heredia

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Despite the reputation of carbon monoxide (CO) as a silent killer, new evidence suggests that this gaseous molecule has anti-inflammatory, anti-cancer and vasoprotective properties. Unfortunately, little is known about the role of CO in the body. However, proteins present in mitochondria are believed to be important targets. We previously synthesized a class of novel and structurally modifiable flavonol-based CO-releasing molecules (CORMs). Flavonols are commonly found in fruits and vegetables. The base structure, Flav-1, is fluorescent, exhibits low toxicity, and releases CO after exposure to visible light. Previous reports indicate that addition of a triphenylphosphonium (TPP) tail allows chemical structures to …

Mechanism Of Transcription Anti-Termination In Human Mitochondria., Hauke S Hillen, Andrey V Parshin, Karen Agaronyan, Yaroslav I Morozov, James J Graber, Aleksandar Chernev, Kathrin Schwinghammer, Henning Urlaub, Michael Anikin, Patrick Cramer, Dmitry Temiakov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp," providing high processivity to the EC. …

The Landscape Of Mtdna Modifications In Cancer: A Tale Of Two Cities, Kate L. Hertweck, Santanu Dasgupta

Biology Faculty Publications and Presentations

Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

Hne-Modified Proteins In Down Syndrome: Involvement In Development Of Alzheimer Disease Neuropathology, Eugenio Barone, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Sanders-Brown Center on Aging Faculty Publications

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylating in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as …

Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose …

Ydj1 Governs Fungal Morphogenesis And Stress Response, And Facilitates Mitochondrial Protein Import Via Mas1 And Mas2, Jinglin L. Xie, Iryna Bohovych, Erin O.Y. Wong, Jean-Philippe Lambert, Anne-Claude Gingras, Oleh Khalimonchuk, Leah E. Cowen, Michelle D. Leach

Department of Biochemistry: Faculty Publications

Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and …

Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh

Electronic Thesis and Dissertation Repository

Maintenance of telomere length during cell division is dependent on the catalytic subunit telomerase reverse transcriptase (TERT), which adds TTAGGG repeats to the ends of chromosomes to prevent telomere shortening during DNA replication. However, non-telomeric roles of TERT have emerged under oxidative stress whereby TERT translocates from the nucleus to the mitochondria and protects against mitochondrial dysfunction through a poorly defined mechanism. A major pathological feature of Alzheimer’s Disease (AD) is the progressive accumulation of amyloid-beta (Aβ) peptide within the cortex and hippocampus. Aβ can directly interfere with mitochondrial respiration and promote mitochondrial dysfunction, ROS production, and neuronal cell death. …

Metalloproteases Of The Inner Mitochondrial Membrane, Roman M. Levytskyy, Iryna Bohovych, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

The inner mitochondrial membrane (IM) is among most protein-rich cellular compartments. The metastable IM sub-proteome where the concentration of proteins is approaching oversaturation creates a challenging protein folding environment with high probability for protein malfunction or aggregation. Failure to maintain protein homeostasis in such a setting can impair functional integrity of the mitochondria and drive clinical manifestations. The IM is equipped with a series of highly conserved, proteolytic complexes dedicated to the maintenance of normal protein homeostasis within this mitochondrial sub-compartment. Particularly important is a group of membrane-anchored metallopeptidases commonly known as m-AAA and i-AAA proteases, and the ATP-independent Oma1 …

Defining The Immune Response And Cellular Pathologies In Multiple System Atrophy, Annamarie Valenti

Masters Theses

Multiple System Atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (α-Syn) in oligodendrocytes of the central nervous system (CNS). A previous study in our lab used Affymetrix DNA microarray analysis to show the downregulation of various mitochondrial related genes, as well as the upregulation of genes involved in inflammatory/immune responses in MSA brain tissue. Therefore, it is hypothesized that an increased presence of immune proteins exists in the MSA brain accompanied by glial cell pathology including decreases in cell metabolism and cell viability. This study uses immunohistochemistry (IHC) to show the increased presence of CD68 …

Effects Of Curcumin And Ursolic Acid On The Mitochondrial Coupling Efficiency And Hydrogen Peroxide Emission Of Intact Skeletal Myoblasts, Daniel J. Tueller

Theses and Dissertations

Curcumin is a natural compound that improves blood glucose management. While some evidence from isolated mitochondria indicates that curcumin uncouples electron transport from oxidative phosphorylation, the effects of curcumin on mitochondrial respiration and hydrogen peroxide emission in intact skeletal muscle cells are not known. By assessing rates of oxygen consumption, we demonstrated for the first time that curcumin (40 µM) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption that supports ATP synthesis) of intact skeletal muscle cells. A 30-minute incubation with curcumin decreased mitochondrial coupling efficiency by 17.0 ± 0.4% relative to vehicle (p < 0.008). Curcumin also decreased the rate of hydrogen peroxide emission by 43 ± 13% compared to vehicle (p < 0.05). Analysis of cell respiration in the presence of curcumin revealed a 40 ± 4% increase in the rate of oxygen consumption upon curcumin administration (p < 0.05 compared to vehicle). In additional experiments, no difference in mitochondrial coupling efficiency was observed between vehicle- and curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The possibility of synergistic …

Oxidative Insults Disrupt Mitochondrial Dynamics, Iraselia A. Garcia

Theses and Dissertations

Mitochondria form an organellar network to provide ATP to the cell. Mitochondrial DNA (mtDNA) combines with nuclear DNA to encode polypeptides critical to forming the complexes of oxidative phosphorylation in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. This ΔΨm is required to maintain mitochondria fission/fusion dynamics: organellar fusion (mediated by OPA1) and fission events (mediated by DRP1) coordinately regulate mitochondrial dynamics. While oxidative stress correlates with mitochondrial dysfunction, it is unclear how oxidants affect mitochondrial structure/function homeostasis. This project seeks to establish and examine the impact of reactive oxygen species (ROS) on mitochondrial dynamics. …

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as …

Temperature Induces Significant Changes In Both Glycolytic Reserve And Mitochondrial Spare Respiratory Capacity In Colorectal Cancer Cell Lines, Mihail I. Mitov, Jennifer W. Harris, Michael Alstott, Yekaterina Y. Zaytseva, B. Mark Evers, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach.

This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32°C, 37°C and 42°C using assay …

Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures

Arts & Sciences Electronic Theses and Dissertations

The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Electronic Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Publications and Research

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …

Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr

Theses and Dissertations

The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …

Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr

Theses and Dissertations

The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …

Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius

David M. Ojcius

Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the …

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca²⁺]_i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca²⁺]_i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca²⁺ channels.

Results

In CA3 pyramidal neurons, kainic …

Mutational Analysis Of The Qrrq Motif In The Yeast Hig1 Type 2 Protein Rcf1 Reveals A Regulatory Role For The Cytochrome C Oxidase Complex, Joshua Garlich, Valentina Strecker, Ilka Wittig, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc₁(complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown. Hig1 type 2 isoforms, which include the Rcf1 protein, are characterized in part by the presence …

Reduced Mitochondrial Efficiency Explains Mismatched Growth And Metabolic Rate At Supraoptimal Temperatures., Eloy Martinez, Michael A. Menze, Salvatore J. Agosta

Faculty Scholarship

The relationship between whole-organism growth and metabolism is generally assumed to be positive and causative; higher metabolic rates support higher growth rates. In Manduca sexta, existing data demonstrate a deviation from this simple prediction: at supraoptimal temperatures for larval growth, metabolic rate keeps increasing while growth rate is decreasing. This mismatch presumably reflects the rising “cost of maintenance” with temperature. Precisely what constitutes this cost is not clear, but we suspect the efficiency with which mitochondria harness oxygen and organic substrates into cellular energy (ATP) is key. We tested this by integrating existing data on M. sexta growth and …

Organelle_Pba, A Pipeline For Assembling Chloroplast And Mitochondrial Genomes From Pacbio Dna Sequencing Data, Aboozar Soorni, David Haak, David Zaitlin, Aureliano Bombarely

Kentucky Tobacco Research and Development Center Faculty Publications

Background: The development of long-read sequencing technologies, such as single-molecule real-time (SMRT) sequencing by PacBio, has produced a revolution in the sequencing of small genomes. Sequencing organelle genomes using PacBio long-read data is a cost effective, straightforward approach. Nevertheless, the availability of simple-to-use software to perform the assembly from raw reads is limited at present.

Results: We present Organelle-PBA, a Perl program designed specifically for the assembly of chloroplast and mitochondrial genomes. For chloroplast genomes, the program selects the chloroplast reads from a whole genome sequencing pool, maps the reads to a reference sequence from a closely related species, and …

Peixoto Studies, Teaches The Powerhouses Of Life., Aldemaro Romero Jr.

Publications and Research

Sometimes great things come from small ones. Among the smallest structures we find in almost all cells are the mitochondria. Not only are they very small (about 0.001of an inch), but they are also very numerous (some of our cells have more than 2,000 of them each). And their role in life is enormous: they generate the energy molecules we use to make our bodies work.

Pablo Peixoto studies these microscopic structures. Born in Brasilia, the capital of Brazil, he became interested in science early in life. “I was one of those annoying kids who always wanted to know the …

Effect Of Trehalose As An Additive To Dimethyl Sulfoxide Solutions On Ice Formation, Cellular Viability, And Metabolism., Jason Solocinski, Quinn Osgood, Mian Wang, Aaron Connolly, Michael A. Menze, Nilay Chakraborty

Faculty Scholarship

Cryopreservation is the only established method for long-term preservation of cells and cellular material. This technique involves preservation of cells and cellular components in the presence of cryoprotective agents (CPAs) at liquid nitrogen temperatures (−196 °C). The organic solvent dimethyl sulfoxide (Me₂SO) is one of the most commonly utilized CPAs and has been used with various levels of success depending on the type of cells. In recent years, to improve cryogenic outcomes, the non-reducing disaccharide trehalose has been used as an additive to Me₂SO-based freezing solutions. Trehalose is a naturally occurring non-toxic compound found in bacteria, …

Exploring The Role Of Lipin1 In Mitophagy Process Using Lipin1 Deficient-Egfp Tagged Lc3 Transgenic Mice, Abdullah Ali Alshudukhi

Browse all Theses and Dissertations

Lipin1 (phosphatidic acid phosphatase) is a key molecule in the cells with two functions: first, it converts phosphatidic acid into diacylglycerol in the cytosol which in turn makes triglycerides. Second, in nucleus lipin1 acts as a transcriptional factor which regulates the expression of genes involved in the fatty acid oxidation and lipid metabolism. Clinically, Lpin1 gene mutations have been detected in patients with severe rhabdomyolysis accompanied with aggregated and dysfunctional mitochondria in their type II muscle fiber. Previously, we have observed that mice with lipin1 deficiency had aggregated mitochondria and abnormal autophagosomes formations by electron microscopy. The mechanism underlying the …

Short-Term Succinic Acid Treatment Mitigates Cerebellar Mitochondrial Oxphos Dysfunction, Neurodegeneration And Ataxia In A Purkinje-Specific Spinocerebellar Ataxia Type 1 (Sca1) Mouse Model, Austin Ferro, Emily Carbone, Jenny Zhang, Evan Marzouk, Monica Villegas, Asher Siegel, Donna Nguyen, Thomas Possidente, Jessilyn Hartman, Kailen Polley, Melissa A. Ingram, Berry Georgia, Thomas H. Reynolds,, Bernard Possidente, Kimberley Frederick, Stephen J. Ives, Sarita Lagalwar

Health and Human Physiological Sciences

Mitochondrial dysfunction plays a significant role in neurodegenerative disease including ataxias and other movement disorders, particularly those marked by progressive degeneration in the cerebellum. In this study, we investigate the role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse. Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen consumption assays, we report that in the presence of mutant polyglutamine-expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of symptom onset and upregulation persists into late …

The Prohibitin Protein Complex Promotes Mitochondrial Stabilization And Cell Survival In Hematologic Malignancies, Elisa Robles Escajeda

Open Access Theses & Dissertations

Lymphocyte proliferation and differentiation is coordinated with high precision in healthy humans and is vital to maintaining a normal immune system. Imbalance of these events can result in the development of autoimmune diseases, immunodeficiencies and hematopoietic malignancies. These pathologies, specifically leukemia and lymphoma have a high incidence of relapse and mortality due to limited treatment options. Therefore, there is a critical need to characterize the signal transduction pathways and understand molecular hallmarks that mediate T cell activation in order to develop new strategies for diagnosis and treatments of these diseases.

Prohibitins (PHB1 and PHB2) have been proposed to play important …

Proteome Basis Of Muscle‐Specific Beef Color Stability, Mahesh Narayanan Nair

Theses and Dissertations--Animal and Food Sciences

Fresh beef color is critical to consumers’ purchase decisions, and beef color stability is muscle-specific. Sarcoplasmic proteome plays a critical role in beef color stability. This dissertation focuses on the proteome basis of inter- and intra-muscular variations in beef color.

The first experiment examined the sarcoplasmic proteome of three beef muscles with differential color stability, i.e., longissimus lumborum (LL), psoas major (PM), and semitendinosus (ST), during wet-aging. LL, PM, and ST (n = 8) were subjected to wet-aging for 0, 7, 14, and 21 days. On each aging day, steaks were fabricated, and color and other biochemical attributes were evaluated …