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Full-Text Articles in Life Sciences
Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh
Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh
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Huntington’s disease (HD) is a genetic disorder associated with progressive cognitive and motor decline. Recent studies in HD models suggest primary peripheral pathologies arise independent of changes in the central nervous system. Our lab found defects in skeletal muscle occurring early in the progression of disease in transgenic R6/2 HD mice, resulting in membrane hyperexcitability. Additionally, there is evidence of decreased quantal content in late-stage R6/2 mice. Here, we investigate pre-synaptic and post-synaptic function at single neuromuscular junctions (NMJ) to make direct comparisons of disease progression in the muscle membrane and motor nerve terminal. We hypothesize that muscle membrane defects …
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 …
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
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To study microsatellites instability and their repair pathways a dual fluorescent (DF2) and selectable (ganciclovir sensitive/ thymidine kinase (TK) expressing) cell system was assayed using replication fork stalling agents hydroxyurea and telomestatin. These cell lines carried ectopically integrated microsatellites derived from the Dystrophia Myotonica Protein Kinase (DMPK) gene ((CTG)102 microsatellite), or an 88 bp polypurine/ polypyrimidine (Pu/Py) repeat from the PKD-1 locus, inserted into a FLP recombinase target site. These microsatellites form non-B DNA structures in -vivo and in-vitro causing replication fork stalling and double strand breaks. DF2 myc (CTG)102 -TK cells treated with hydroxyurea were assayed for mutagenesis of …
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
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To study microsatellites instability and their repair pathways a dual fluorescent (DF2) and selectable (ganciclovir sensitive/ thymidine kinase (TK) expressing) cell system was assayed using replication fork stalling agents hydroxyurea and telomestatin. These cell lines carried ectopically integrated microsatellites derived from the Dystrophia Myotonica Protein Kinase (DMPK) gene ((CTG)102 microsatellite), or an 88 bp polypurine/ polypyrimidine (Pu/Py) repeat from the PKD-1 locus, inserted into a FLP recombinase target site. These microsatellites form non-B DNA structures in -vivo and in-vitro causing replication fork stalling and double strand breaks. DF2 myc (CTG)102 -TK cells treated with hydroxyurea were assayed for mutagenesis of …
Divalent Metal Cation Entry And Cytotoxicity In Jurkat T Cells: Role Of Trpm7 Channels, Alayna N. Mellott
Divalent Metal Cation Entry And Cytotoxicity In Jurkat T Cells: Role Of Trpm7 Channels, Alayna N. Mellott
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Humans are exposed daily to a variety of metals that can be harmful to our immune system. Although certain divalent metal cations are essential for numerous cellular functions and are critical trace elements in humans, the uptake mechanisms of these ions remain mostly unknown. Transient receptor potential melastatin 7 (TRPM7), which is expressed in a variety of human cell types, including lymphocytes and macrophages, conducts many divalent metal cations. TRPM7 channels are largely inactive under normal physiological conditions due to cytoplasmic magnesium acting as a channel inhibitor. Magnesium is a cofactor for many biochemical reactions. Low serum levels of magnesium, …
Identification Of A Hybrid Lethal Gene On The X Chromosome Of Caenorhabditis Briggsae, John Kelly Dougherty
Identification Of A Hybrid Lethal Gene On The X Chromosome Of Caenorhabditis Briggsae, John Kelly Dougherty
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Two closely related Caenorhabditis species, C. briggsae and C. nigoni are cross fertile and produce viable adult progeny. From C. nigoni mothers, F1 adult females are viable and fertile, F1 males are viable but sterile. In crosses that utilize C. nigoni males and C. briggsae hermaphrodites produce viable adult F1 females but F1 males arrest during embryogenesis. A mutation in the Cbr-him-8 gene is a recessive maternal-effect suppressor of male-specific lethality. Hybrid crosses with cbr-him-8 mutant mothers produce viable adult male progeny. The HIM-8 protein in C. elegans is required for the pairing of X-chromosomes during meiosis. This function is …
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 …
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 …
Early Increase Of Cd11c In Human Monocyte-Derived Dendritic Cells In The Presence Of A/California/07/2009 (H1n1pdm), Amber M. Braddock
Early Increase Of Cd11c In Human Monocyte-Derived Dendritic Cells In The Presence Of A/California/07/2009 (H1n1pdm), Amber M. Braddock
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Influenza A continues to cause significant morbidity and mortality. Vaccine production time, viral antigenic variability and low vaccine efficacy contribute to the annual pandemics and seasonal epidemics. A better understanding of human immune responses to influenza A could result in more effective vaccines. Dendritic cells (DCs) play an important role in the initiation of immune responses. Populations of B lymphocytes secrete protective antibodies but the role of different populations of B cells in the protective response is unknown. In this thesis we developed assays to determine subclasses of influenza specific antibodies. Mononuclear cells were assessed using flow cytometry to identify …
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 …