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Full-Text Articles in Molecular Biology
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 …
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 …
∆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 …
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 …
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 …