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Full-Text Articles in Life Sciences
Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan
Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan
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We have previously documented our evidence of genetic instabilities at the (Pu/Py)78 and (ATTCT)47 sequences and our reasoning for identifying break-induced replication (BIR) as the mode of repair responsible for the mutations in the DNA flanking the unstable inserts. Now, as our lab investigates the protein mechanisms at play in the BIR pathway taking place at these sites, we are also expanding our knowledge of how this mechanism extends into the pathways responsible for forming extrachromosomal circular DNA (eccDNA) molecules. We have documented the phenomena posed as the driving factors for eccDNA formation in our systems containing (Pu/Py)78 and (ATTCT)47. …
Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada
Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada
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Microsatellite repeat sequences have been shown to induce replication stalling, fork collapse, double-strand breaks (DSBs), and possibly stimulate break-induced replication. In this study we use a dual-fluorescent HeLa model that is designed to monitor recombination at an ectopic site through use of flow cytometry and inverse PCR with a microsatellite in the lagging strand for DNA synthesis. To test the stability of the 78 bp polypurine/pyrimidine repeat from the PDK1 locus, we subjected cells to replication stress drugs designed to induce DSBs and measure break-induced replication (BIR). The study revealed that polypurine repeat cells undergo endogenous stress contributing to instability …
Quantitated Effects Of Nutritional Supplementation On Exercise Induced Sweat, Andrew Blake Austin Browder
Quantitated Effects Of Nutritional Supplementation On Exercise Induced Sweat, Andrew Blake Austin Browder
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Discovery studies have identified many metabolites contained in human sweat. However, quantitative analysis of the sweat metabolome content remains mostly unknown. Furthermore several attributes, including rate, have been defined to affect sweat metabolite content, while other effectors, like diet, remain unknown. This study works to quantitatively define the metabolite impact caused by nutritional supplementation. To better understand the effect diet plays, a LC-MS method was developed focusing on improving resolution and peak width. While the literature provided examples of how diet affected sweat metabolite concentrations, the long-term effects of diet have not been explored. The experiment described here attempts to …
Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti
Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti
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The functions of Ataxia telangiectasia and Rad-3 related protein (ATR) is very much important in a cell, as it is a DNA damage response protein, which plays an important role in cell division, DNA repair and apoptosis. This protein helps in proliferation in the actively DNA dividing normal cells and in cancer cells. The functions of ATR in a proliferating cell are well studied and known to involve regulation of replication fork and cell cycle progression after DNA damage. Whereas, in a non-replicating cell, the functions of ATR are not so well known. In the human body, most of the …
Functional Characterization Of Infectious Hematopoietic Necrosis Virus Matrix Protein In Host Cellular Responses, Jeffery Ringiesn
Functional Characterization Of Infectious Hematopoietic Necrosis Virus Matrix Protein In Host Cellular Responses, Jeffery Ringiesn
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Infectious hematopoietic necrosis virus (IHNV) is a deadly fish pathogen that poses a global threat to aquatic ecosystems and the aquaculture industry. For decades, research has focused on developing vaccine therapeutics utilizing a variety of techniques and strategies. While these studies have met with some success in identifying potential vaccine targets that provided protective immunity, a commercially viable IHNV vaccine is currently unavailable. Here we explore the relationship between the structure and function of the IHNV matrix (M) protein through the introduction of mutations that reduce anti-host effects, with the goal of developing a novel recombinant IHNV with reduced pathogenicity …
Potential Drug Treatment For Duchenne Muscular Dystrophy Which Could Be Through Upregulation Of Lipin1, Rajsi Y. Thaker
Potential Drug Treatment For Duchenne Muscular Dystrophy Which Could Be Through Upregulation Of Lipin1, Rajsi Y. Thaker
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Duchenne muscular dystrophy (DMD) is a genetic disorder leading to progressive muscle degeneration and weakness due to mutation in dystrophin gene, which is very important for maintaining muscle membrane integrity. Dystrophin is the largest gene in the human genome therefore more prone to mutation. There is currently no cure for DMD. Our lab recently found that Lipin1 deficient myofibers showed upregulation of necroptosis correlated with the loss of muscle membrane integrity. Our primary approach for ameliorating dystrophic phenotype in DMD is through reduction of necroptosis using drugs which can potentially upregulate Lipin1 expression. In this study, we identified two drugs …
Alternative Splicing Of Mdm4 In Human Melanomas, Abdullah Salem S. Alatawi
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 …
Apoptosis And Necrosis Drive Muscle Fiber Loss In Lipin1 Deficient Skeletal Muscle, Sandhya Ramani Sattiraju
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 …
Genetic Study Of Checkpoint Defects Of The Mus81-1 Mutant In The Fission Yeast Schizosaccharomyces Pombe, Darlington Osei Abrefa
Genetic Study Of Checkpoint Defects Of The Mus81-1 Mutant In The Fission Yeast Schizosaccharomyces Pombe, Darlington Osei Abrefa
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In response to various perturbations of DNA replication, the DNA replication checkpoint is activated in eukaryotes to stimulate a cascade of cellular responses that are crucial for maintaining genome stability and cell survival. Defects in the checkpoint pathway result in mutations and genome instability, which is a hallmark for cancers. This study used a genetic approach to identify a mutation in the MMS (methyl methanesulfonate) and UV-sensitive protein Mus81, a DNA repair enzyme that resolves aberrant DNA structures through the homologous recombination pathway. We show that a single missense mutation, identified in fission yeast mus81-1, causes moderate reduction in the …
Differing Functions Of Atr Kinase In Human Epidermal Keratinocytes Exposed To Ultraviolet B Radiation, Kavya Shaj
Differing Functions Of Atr Kinase In Human Epidermal Keratinocytes Exposed To Ultraviolet B Radiation, Kavya Shaj
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Ataxia-telangiectasia and Rad-3 related (ATR) is a DNA damage response protein kinase that is upregulated in various cancer cell types and has key roles in cell cycle progression, DNA repair and apoptosis. Small molecule ATR kinase inhibitors are of importance as antineoplastic agents because they sensitize cancer cells to DNA damaging chemotherapy drugs. However, only a few studies have looked at the effects of ATR kinase inhibitors on non-replicating cells, which constitute the majority of cells in the human body and have suggested an opposite, pro-apoptotic role for ATR kinase signaling in non-replicating cells in comparison to a pro-survival function …
Identification Of New Metabolic Mutations That Enhance The Cell-Killing Effect Of Hydroxyurea, A Clinically Used Drug With Multiple Implications, Rittu Elsa Samuel
Identification Of New Metabolic Mutations That Enhance The Cell-Killing Effect Of Hydroxyurea, A Clinically Used Drug With Multiple Implications, Rittu Elsa Samuel
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Cancer is one of the leading causes of death and a worldwide health issue. Intensive studies have been conducted in the past to unearth new anti-cancer agents. One such anti-proliferative drug is hydroxyurea (HU). HU has been used in clinics for ≥ 100 years to treat various neoplastic and non-neoplastic diseases. Although newer agents have been developed, as a WHO-enlisted essential medicine, it remains the staple drug for the management of chronic myeloproliferative disorders and sickle cell anemia. A better understanding of the HU-induced cell death may improve or expand the therapeutic spectrum of this clinically important drug. HU arrests …
∆Np63Α Positively Regulates Erk3 Expression In Non-Melanoma Skin Cancer, Eid Salem Alshammari
∆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 …
Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway, Abdulrahman M. Jama
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 …
Osmotic Activation Of Sperm Motility Via Water Flow Through Aquaporins In The Freeze-Tolerant Cope's Gray Treefrog, Dryophytes Chrysoscelis, Deja Miller
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Gametes of gray treefrogs, Dryophytes chrysoscelis, are deposited into freshwater ponds. Sperm undergo spermatogenesis and maturation beginning in the seminiferous tubules and migrating to the lumen. In mammals and fishes, these cells are immotile within the isosmotic fluid of the testes and have motility activated by exposure to a hyper- or hypoosmotic medium. Water flows into or out of the sperm cell, altering intracellular ionic concentrations, and ultimately stimulates flagellar movement. We tested the hypothesis that exposure to a hypotonic environment activates motility of gray treefrog sperm. We also hypothesized that osmotic water uptake is facilitated by expression of water …
Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido
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 …
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
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 …
N-Glycosylation, Localization And Trafficking Of Endogenous Nkcc1 In Cos7 Cells, Richa Singh
N-Glycosylation, Localization And Trafficking Of Endogenous Nkcc1 In Cos7 Cells, Richa Singh
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The Na+K+2Cl- co-transporter-1 (NKCC1) effects the electroneutral movement of Na+, K+ and 2Cl- ions across plasma membranes. NKCC1 is considered a widely distributed, highly N-glycosylated ion transporter involved in the regulation of the intracellular chloride concentration ([Cl-]i), cell volume and salt secretion. NKCC1 locates in the plasma membrane of all cells studied so far, particularly on the basolateral side of most polarized cells. However, the majority of immunoreactive NKCC1 distributes in intracellular compartments of unknown nature whereas a small proportion of the transporter appears to be located in the plasma membrane. Here, we identified and characterized …
Use Of Phage Display Libraries To Select For B-Cell Receptor-Specific Peptides Of Chronic Lymphocytic Leukemia Cells, Richard M. Chou
Use Of Phage Display Libraries To Select For B-Cell Receptor-Specific Peptides Of Chronic Lymphocytic Leukemia Cells, Richard M. Chou
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Peptides with high affinity to the B-cell receptor (BCR) fused to a toxin could be an effective therapy for Chronic Lymphocytic Leukemia (CLL) patients. We screened captured BCR of a CLL patient with peptides from 7 and 12-mer phage display libraries, using two strategies. Lymphocytes from two patients diagnosed with CLL expressing two different unmutated VH genes (VH 1-3 and VH4-34, respectively) were used. Membrane BCRs were obtained from patient CLL cells by lysis, identified by western blot, semi-quantified and screened with phage libraries. The first strategy involved using patient VH4-34 BCRs which were captured using goat anti-human IgM to …
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 …