Molecular Biology Commons^™

Apoptosis And Necrosis Drive Muscle Fiber Loss In Lipin1 Deficient Skeletal Muscle, Sandhya Ramani Sattiraju

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Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children, however, the molecular mechanism involved in the regulation of myofiber death by lipin1 is not known. In this study, we utilized the skeletal muscle from cell-type-specific lipin1 knockout (Lipin1Myf5cKO) mice to define cell death pathways involved in lipin1 deficient muscles. We observed a significant increase in centrally nucleated fibers and embryonic myosin heavy chain (EMyHC)-positive regenerating fibers in Lipin1Myf5cKO mice compared to wild-type (WT) mice, indicating an increased cycle of degeneration and regeneration in lipin1 deficient muscles. Lipin1 deficient muscles had significantly elevated pro-apoptotic …

Alternative Splicing Of Mdm4 In Human Melanomas, Abdullah Salem S. Alatawi

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Melanoma is a potentially lethal type of skin cancer and regarded to be the third most common type of skin cancer. Although melanoma is not as common as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), it is more likely to metastasize than BCC and SCC. Interestingly, the incidence of melanoma continues to go up (expected 2% in 2020), but the deaths continue to decrease (-5.3% in 2020) due to improvements in detection and treatment. The treatment of melanoma depends on several aspects but most importantly the tumor's stage and the location. In the early stages, melanoma can be …

A Proteomic Analysis Of Corydoras Sterbai Secretions And Tissues, Erik Powell Wictor

University of the Pacific Theses and Dissertations

Defensive mechanisms vary widely in the animal kingdom ranging from physical defenses like spines to chemical defenses such as toxins. Toxins in these secretions and tissues can fluctuate from enzymes to lipids to uncharacterized chemicals. Next generation -omics technology and mass spectrometry are extremely important in analyzing these samples because of their ability to distinguish minute amounts of toxic substance within a complicated sample. The goal of this experiment was to look at secretions and tissues from Corydoras sterbai. All samples in this study were proteolyzed using a mixture of Trypsin and Lys-C, fractionated, and run through nanoLC-MS/MS analysis using …

Peroxiredoxin 6 And Inflammation In Alzheimer's Disease, Jared Ferrell-Penniman

Biological Sciences Theses and Dissertations

Alzheimer’s disease (AD) is known for its debilitating symptoms and poor prognosis. However, despite intense research into neurodegenerative diseases, there are few therapies targeted at the underlying mechanisms of the disease. Oxidative stress (OS) and inflammation are cellular phenomena thought to be key to the progression of the disease. Critically, peroxiredoxin 6 (Prx6), an antioxidant protein with multiple functions, has been identified from mammalian studies as a potential regulator of both OS and inflammation that may have a specific effect on AD. This project seeks to elucidate the role of Prx6 in AD as well as the underlying mechanisms. Drosophila …

How A Cell Knows Where To Divide: Oscillation Of Mind In Vivo, Colby Ferreira

Senior Honors Projects

Over two-million people in the United States are infected by antibiotic resistant bacteria each year. Of this number 23,000 die from these infections and other complications. Due to this, novel antibiotic targets are constantly being investigated. One process in prokaryotes that holds promise is cellular division. Bacterial cells grow and reproduce using a series of proteins known as the cell division machinery. This machinery enables the division of the parental cell into two identical daughter cells. The cell division machinery is similar between bacterial taxa, making it an ideal target for new classes of antibiotics. Therefore, understanding the molecular mechanisms …

∆Np63Α Positively Regulates Erk3 Expression In Non-Melanoma Skin Cancer, Eid Salem Alshammari

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Non-melanoma skin cancer (NMSC) is a group of skin cancer that includes basal cell carcinoma of the skin (BCC), squamous cell carcinoma of the skin (SCC), actinic keratoses, a precursor to SCC, and other rare cutaneous carcinomas. p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α, a main isoform of p63, is highly expressed in NMSC and plays essential roles in NMSCs development. Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the MAPK family. It possesses a single phosphorylation site (serine 189) in its activation loop, which makes …

Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido

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Ras proteins are small GTPases that regulate cell growth, differentiation and apoptosis. There are three main isoforms: H-, N-, and K-Ras in mammalian cells, and they cycle between an active GTP- and inactive GDP-bound states. Constitutively active Ras mutations are found in ~15% of all human cancers. Of those, oncogenic K-Ras is found in ~98% of pancreatic, ~52% colorectal, and ~32% of lung cancers. In nearly 30 years since its discovery, there are no anti-K-Ras drugs currently available for clinical use. Since K-Ras must be localized to the plasma membrane (PM) for its full biological activity, targeting K-Ras PM interaction …

Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway, Abdulrahman M. Jama

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Our previous characterization of global lipin1-deficient (fld) mice demonstrated that lipin1 played a novel role in skeletal muscle (SM) regeneration. The clinical relevance of lipin1 has been observed in patients with lipin1 null mutations where they exhibited severe rhabdomyolysis with aggregated and dysfunctional mitochondria. Lipin1 is a key gene that plays an important role in lipid biosynthesis and metabolism. It has dual functions as it contains a phosphatase activity that converts phosphatidic acid (PA) to diacylglycerol (DAG), the penultimate step in triglycerides (TAG) biosynthesis as well as transcriptional co-activator function. In the cytosol and ER, lipin1 carries out its lipid …

Phylogenetic Diversity Of The Bacterial Communities In Craft Beer, Lindsey Rodhouse

Graduate Theses and Dissertations

The craft beer industry is increasing in popularity in the United States. The craft brewing process typically does not use a pasteurization step, therefore the boiling process is the primary critical control step. Any microorganisms introduced after boiling, or those that are not killed during boiling, are likely to participate in fermentation and persist in the final product. Previous culture-based studies have isolated bacteria and yeast from craft beers at specific time points, but little research has been done on the process as a whole. The objectives of this research are to (1) track bacteria development throughout the brewing process …

Novel Insight Into The Role Of Lxrα In Metabolic Regulation Via Dna Binding As A Heterodimer With Pparα And As A Homodimer, Andrea M. Klingler

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Liver X receptor a (LXRa) plays a critical role in the maintenance of energy homeostasis within a cell through tight transcriptional regulation of genes involved in metabolism of lipids, glucose, and cholesterol. Although LXRa has been established to function as a heterodimer with the retinoid X receptor a (RXRa), recent studies have determined that LXRa also interacts directly with peroxisome proliferator-activated receptor a (PPARa). However, little is known regarding the functionality of this heterodimer, if any exists at all. This study determined that a heterodimer of PPARa and LXRa is capable of binding to candidate response elements in vitro with …

A Bioluminescence Sensor Of Nlrp3 Inflammasome Activation, Michael Alexander Winek

Master's Theses

The innate immune system is many organisms first line of defense against pathogenic insult or tissue damage. This defense strategy is intent on restoring homeostasis upon perturbation. Upon activation of the innate immune system in humans, an oligomeric protein complex termed the “Inflammasome” forms in myeloid cells. The canonical output of activation of any subset of inflammasome is Caspase-1-mediated secretion of pro-inflammatory cytokines IL1β and IL18. Chronic or uncontrolled inflammasome activation is at the core of myriad economically burdening diseases. In many of these diseases, endogenous factors chronically engage the innate immune system. To study these diseases in in vivo, …

Emetine As An Anti-Cancer Therapeutic In Bladder Cancer, Valerie Davidson

Master's Theses

Bladder cancer is a serious health concern among the older population, as it is responsible for thousands of deaths annually in the United States. Patients that are diagnosed with muscle-invasive disease have a 5-year survival rate of only 20 percent. Additionally, muscle-invasive disease has a high metastatic potential; half of all patients develop metastatic disease within 3 years. Patients with muscle-invasive disease are presented with few treatment options aside from surgery. The current standard of care is a chemotherapeutic combination therapy of cisplatin and gemcitabine. This therapy is highly toxic, and due to the high instance of co-morbidities in these …

Y- Box Protein 2 (Ybx2) Is A Major Mrna Specific Regulator Of Translation In Spermatogenesis And The Translational Regulation Of The Sperm Mitochondria Associated Cysteine Rich Protein (Smcp) Mrna, Tamjid A. Chowdhury

Graduate Doctoral Dissertations

Spermatogenesis is the process by which diploid stem cells differentiate into haploid male gametes, spermatozoa. As haploid cells differentiate into spermatozoa, they undergo profound changes in morphology and physiology, including total reorganization of chromatin in the nucleus which results in the inability to synthesize new mRNAs about one week before the differentiation of sperm is complete. Consequently, many mRNAs, such as the protamine 1 (Prm1) mRNA and sperm mitochondria-associated cysteine rich-protein (Smcp) mRNA, are transcribed in early haploid spermatogenic cells and stored as translationally inactive messenger ribonucleoprotein particles (free-mRNPs) for several days to a week before the mRNA is translated …

Elucidating The Role Of Dopamine In The Avoidance Response Of Caenorhabditis Elegans Utilizing Microfluidics, Patricia Frances Turturro

Theses Digitization Project

This study looks at dopamine modulation of ASH neurons, which are part of the avoidance circuit of C. elegans, and their response to water soluble stimuli. Because nematodes such as Caenorhabditis elegans utilize dopamine at the molecular and cellular level in much the same way as mammals, they offer researchers a unique opportunity to study the mechanisms of dopamine signaling.

Generation And Characterization Of Sequence-Independent Sumoylated Lens Epithelium-Derived Growth Factor (Ledgf) Protein P75 Chimeras., Alfredo Roman, Denisse Gutierrez, Manuel Llano

COURI Symposium Abstracts, Summer 2012

LEDGF/p75 is a transcriptional coactivator required for efficient lentiviral cDNA integration. LEDGF/p75 has been found to be SUMOylated at four lysine residues, and mutation of these residues to arginine inhibits LEDGF/p75 SUMOylation and impairs the HIV-cofactor activity of this protein. However, we still do not understand how SUMOylation influences the HIV cofactor activity of LEDGF/p75. It has been demonstrated that attachment of SUMO to transcription factors in a non-sequence specific fashion recapitulates the effect of sequence-specific SUMOylation on the activity of these proteins. These results have suggested that is SUMO per se and not the modification of the target protein …

Lipase-Kinase Associations Involving Pld2, Jak3 And Fes That Underlie Cancer Cell Proliferation And Invasion, Qing Ye

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Phospholipase D (PLD) is an enzyme that breaks down phospholipids in the cell membrane. It has been suggested that PLD may play a role during cell proliferation and cell invasion of cancer cells. The objective of this thesis was to define new molecular signaling pathways in which PLD2 might be involved in terms of cell proliferation (first part) and cell invasion (second part). To this, I compared molecular and biochemical aspects between untransformed cell lines with highly invasive, transformed breast cancer cells. In the first part, I investigated the interaction of two tyrosine kinases with PLD2 and the effect of …

The Mitospecific Region Of Mrp20 And Its Importance For The Assembly Of Mitochondrial Ribosomes In Saccharomyces Cerevisiae, Jasvinder Kaur

Dissertations (1934 -)

Yeast mitochondrial ribosomes are composed of an rRNA scaffold, encoded by the mitochondrial genome and many different proteins, which, with the exception of one, are encoded by nuclear genes. These ribosomal proteins are imported into the mitochondrial matrix following their synthesis in the cytosol, however, little is known about the subsequent events which result in an assembled, translationally-competent ribosome. Many of the mitochondrial ribosomal proteins bear homology to bacterial ancestors. In addition to the acquisition of mitochondrial targeting signals, a number of these nuclearly-encoded ribosomal proteins have acquired additional domains, often at their C-termini, which are termed "mitochondrial-specific domains". The …

Quantifying Agonist Activity At G Protein-Coupled Receptors, Frederick J. Ehlert, Hinako Suga, Michael T. Griffin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When an agonist activates a population of G protein-coupled receptors (GPCRs), it elicits a signaling pathway that culminates in the response of the cell or tissue. This process can be analyzed at the level of a single receptor, a population of receptors, or a downstream response. Here we describe how to analyze the downstream response to obtain an estimate of the agonist affinity constant for the active state of single receptors.

Receptors behave as quantal switches that alternate between active and inactive states (Figure 1). The active state interacts with specific G proteins or other signaling partners. In the absence …