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Full-Text Articles in Molecular Biology
Examining The Biotic And Abiotic Degradation Of Simple Phenols, Madeline Gruenberg
Examining The Biotic And Abiotic Degradation Of Simple Phenols, Madeline Gruenberg
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Plant secondary metabolites are a diverse class of compounds that encompass small phenols to large polymeric structures such as tannins. Smaller compounds such as phenolic acids can serve as substrates for soil microbes and enzymes. We monitored the degradation of three small phenols pyrogallol, gallic acid, and benzoic acid in biotic and abiotic conditions. They were chosen to observe the impacts of specific functional groups on both degradation processes and act as model compounds to mimic larger tannin reactivity. Both abiotic and biotic degradation of pyrogallol resulted in the formation of a stable quinone, while abiotic degradation of gallic acid …
The Role Of Fbxl16 In Regulating Erk3 Stability And Cell Migration, Seth Charles Murdock
The Role Of Fbxl16 In Regulating Erk3 Stability And Cell Migration, Seth Charles Murdock
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Extracellular signal-regulated kinase 3 (ERK3) is a member of the atypical mitogen-activated protein kinase (MAPK) family. While ERK3’s role in promoting cell migration and invasion in multiple types of cancer has been well-documented, its activation and regulation remain poorly understood. Unlike other typical MAPK proteins, whose activation is regulated via the phosphorylation of an upstream kinase, ERK3 is regulated through its abundance, as it is constitutively phosphorylated when present in the cell. While USP20 has been established as a deubiquitinating protein that stabilizes ERK3 by preventing its degradation, both TRIM21 and FBXW7 have been identified as E3 ligases that target …
Long-Read Mdm4 Isoform Sequencing Reveals Aberrant Isoform Landscape In Metastatic Melanomas, Nehaal Rooha Patrick
Long-Read Mdm4 Isoform Sequencing Reveals Aberrant Isoform Landscape In Metastatic Melanomas, Nehaal Rooha Patrick
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The changes in splicing of MDM4 in human melanomagenesis are critical to p53 activity and represent potential therapeutic targets. Genomic characteristics of melanoma and precursor lesions, such as copy number variation and gene expression, have been investigated in detail. However, there has never been a detailed survey of splicing changes that occur during melanomagenesis. Splicing changes can be a very early event in melanoma tumor progression, with characteristic changes in the p53 pathway already in place in early nevi. MDM4 is upregulated in a strong majority of melanoma cases and has been described as a “key therapeutic target in cutaneous …
Exploring The Effects Of Choline Treatment On Dystrophic Phenotype, Brooklyn Morris
Exploring The Effects Of Choline Treatment On Dystrophic Phenotype, Brooklyn Morris
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Duchenne Muscular Dystrophy (DMD) is a devastating progressive muscular disorder caused by a mutation in the dystrophin gene affecting approximately 1 in 3,500 males. However, despite its prevalence, there is currently no cure for this disease. Mutations in dystrophin lead to enhanced inflammation, fibrosis, cell death, development, and decreased skeletal muscle function. Phosphatidylcholine, synthesized by choline, is a major phospholipid that functions in maintaining and synthesizing cell membranes and has previously been found to be decreased in DMD patients. This led us to hypothesize that the dystrophic phenotype could be improved through treatment with choline. In this study, we used …
Comparing The Performance Of A Targeted Pull-Down Assay To Shotgun Sequencing For Improving Respiratory Infectious Disease Surveillance, Monica R. Christian
Comparing The Performance Of A Targeted Pull-Down Assay To Shotgun Sequencing For Improving Respiratory Infectious Disease Surveillance, Monica R. Christian
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Current surveillance focuses on well characterized pathogens such as influenza. Since 2000, there have been multiple outbreaks of respiratory disease. These outbreaks have demonstrated the need for robust and collaborative global efforts to identify, monitor, and contain novel respiratory viruses. This study aims to improve the ability of public health agencies to monitor and respond to respiratory disease outbreaks. Using five respiratory pathogens, this study compares a molecular capture technology from Twist Biosciences to the shotgun sequencing approach of whole transcriptome amplification (WTA, Qiagen) with the goal of determining which method is most effective using cost, usability, and sequencing quality …
Regulation Of Erk3 By Kras Signalling And Its Role In The Growth Of Lung Adenocarcinoma (Luad) Cells, Shreya Akunapuram
Regulation Of Erk3 By Kras Signalling And Its Role In The Growth Of Lung Adenocarcinoma (Luad) Cells, Shreya Akunapuram
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Extracellular signal related kinase 3 (ERK3) is one of the atypical mitogen activated protein kinases (MAPK). It is expressed ubiquitously and plays a role in a variety of cellular processes, including cell growth and differentiation. ERK3’s role in promoting migration and invasion in various cancers has been well established. ERK3 is upregulated in non-small cell lung cancers (NSCLCs) and has been shown to promote NSCLC tumor growth and progression. However, the regulation of ERK3 in lung cancers remains largely unclear. A recent study indicates that ERK3 phosphorylation at S189, an indicator of ERK3 activity, is upregulated by KRAS in NSCLCs. …
The Effect Of Pomegranate Consumption On The Gut Microbiome, Brant Bandow
The Effect Of Pomegranate Consumption On The Gut Microbiome, Brant Bandow
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Pomegranate is known to have antioxidant and prebiotic qualities that have been shown to promote the growth of beneficial bacteria while reducing inflammation in the gut. Inflammation in the gut is an issue that results in many health problems including obesity and colon cancer. In this study, an experimental group received a daily pomegranate supplement for three weeks where a control group did not receive any supplement. After sequencing gDNA isolated from fecal samples from both before and after the trial period there was a significant difference between the two groups. The largest amount of variability is attributed to the …
A Novel Role Of Lipin1 In The Regulation Of Expression And Function Of Nnos, Ayat Azzam
A Novel Role Of Lipin1 In The Regulation Of Expression And Function Of Nnos, Ayat Azzam
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Duchenne muscular dystrophy (DMD) is a severe and progressive muscular dystrophy that develops in the skeletal muscles because of mutations in the dystrophin gene. Dystrophin stabilizes sarcolemma and assembles neuronal nitric oxide synthase (nNOS) into the dystrophin-associated protein complex on the sarcolemma. The absence of dystrophin triggers the delocalization of nNOS and contributes to the misregulation of muscle development, blood flow, muscle fatigue, and inflammation. Lipin1 was reduced in the skeletal muscles of patients with DMD and the mdx mouse model of DMD. In this study, we explored the role of lipin1 in the regulation of nNOS expression and function. …
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 …
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. …
Effects Of Lipin1 Deficiency & Restoration In The Dystrophic Diaphragm, Alexandra Brown
Effects Of Lipin1 Deficiency & Restoration In The Dystrophic Diaphragm, Alexandra Brown
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Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder that is characterized by severe and progressive muscle wasting (Venugopal & Pavlakis, 2021). This disease is caused by a mutation in the largest known human gene which encodes the protein, dystrophin (Gao & McNally, 2015). Dystrophin connects the inner cytoskeleton to the extracellular matrix and is critical for maintaining the structural stability of muscle cells during contraction (Venugopal & Pavlakis, 2021). Mutations to the dystrophin gene result in myocyte membrane instability, contributing to the structural deterioration of the muscle tissue (Venugopal & Pavlakis, 2021). Progressive muscle degeneration and the replacement of …
The Role Of Pi4kb In Cellular Localization Of Small Gtpases, Parisa Sadrpour
The Role Of Pi4kb In Cellular Localization Of Small Gtpases, Parisa Sadrpour
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Constitutively active oncogenic mutant K-Ras is one the principal contributors to human cancers including 90% of pancreatic, 50% of colorectal and 32% of non-small cell lung cancers. However, except for K-Ras G12C oncogenic mutant, which only presents in about 13% of non-small cell lung cancer patients, there is no anti-K-Ras therapy for a considerable subset of K-Ras mutations in human tumors, reflecting challenges for targeting oncogenic K-Ras activity. K-Ras is a membrane-bound small GTPase; when active, it triggers multiple signaling pathways regulating a variety of key cellular functions such as cell growth, proliferation and survival. To initiate these signaling cascades, …
Reconstruction Of Gut Microbiome Via Intermittent Feeding, Kourtney Sprague
Reconstruction Of Gut Microbiome Via Intermittent Feeding, Kourtney Sprague
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The benefits of intermittent fasting have been studied across many facets of health. It is known that physiologically fasting results in a metabolic switch from liver-derived glucose to adipose cell derived ketones to be used as energy and signaling molecules. Fasting down-regulates inflammation, increases expression of antioxidant defenses, and activates pathways for DNA repair and autophagy. While fasting or intermittent feeding effects on host physiology have been identified, the relationship between fasting and gut microbiome is not as well known. In times of gut rest, resident microbes undergo detoxication and motility, and in times of activity, gut microbes undergo DNA …
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 …
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 …
The F-Box Protein Fbw7 Negatively Regulates The Stability Of Erk3 Protein, Nicole Walters
The F-Box Protein Fbw7 Negatively Regulates The Stability Of Erk3 Protein, Nicole Walters
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Extracellular signal-regulated kinase 3 (ERK3) is a member of the atypical mitogen-activated protein kinase (MAPK) subfamily, whose members have been shown to play important roles in a number of cellular processes including proliferation, differentiation, migration, and apoptosis. While signals regulating ERK3 kinase activity remain unclear, ERK3 is known to be an unstable protein with function tightly regulated via ubiquitination and proteasomal turnover. The deubiquitinating enzyme USP20 has been shown to regulate ERK3 by stabilizing the kinase, but presently, no destabilizing ubiquitin ligases have been identified. The SKP1-CUL1-F-box protein (SCF) E3 ligases are a subfamily of ubiquitin E3 ligases composed of …
Enzymatic Post-Translational Halogenation For Adding Functionality To Biomaterials, Alexander L. Compean
Enzymatic Post-Translational Halogenation For Adding Functionality To Biomaterials, Alexander L. Compean
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Silk fibroin from the silkworm, Bombyx mori, is a unique biomaterial that has been extensively studied for a variety of applications due to its promising properties such as controllable self-assembly, robust mechanical properties, and biological compatibility. Previously, there have been numerous methods describing the chemical modification of silk fibroin that utilize synthetic or enzymatic means that do not use halogens as a means of functionalization. Herein, a halogenation strategy is presented to modify silk fibroin with the aim of developing a novel functional material through the carbon-halogen (C-X) bond. Modification with NaX (X = Cl, Br, and I) salts, hydrogen …
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 …
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 …
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 …
Erk3 Negatively Regulates The Il-6/Stat3 Signaling Via Socs3, Astha Shakya
Erk3 Negatively Regulates The Il-6/Stat3 Signaling Via Socs3, Astha Shakya
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Mitogen activated protein kinases (MAPKs) are Ser/Thr kinases that relay the extracellular signal into intracellular responses and regulate several biological responses. They are classified into conventional MAPKs and atypical MAPKs. Extracellular signal regulated kinase 3 (ERK3) is an atypical MAPK that has a single phospho-acceptor site (Ser 189) in its activation motif instead of the canonical Thr-Xaa-Tyr (TXY) motif of conventional MAPK like ERK1/2. ERK3 comprises of a unique C terminal tail and a central C34 domain that further distinguishes it from ERK1/2. Moreover, compared to ERK1/2, much less is known about the upstream activators and the downstream targets of …
Genotyping For Response To Physical Training, Stacy Simmons
Genotyping For Response To Physical Training, Stacy Simmons
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Understanding the inter-individual variability in physical fitness performance has been the focus of scientific research for decades especially in the United States military. Injury and physical inadequacy cost the U.S military millions of dollars every year. The project PHITE (Precision High Intensity Training through Epigenetics) was funded to investigate this personal complex trait by combing the genetic and epigenetic (non-shared environmental factors) contributions into a single model for physical training response. This project is set up as having 150 male and female recruits between the ages of 18-27 years old. Each participant is randomly put blind into either a high …
∆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 …
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 …
A Novel Method To Analyze Dna Breaks And Repair In Human Cells, Caitlin Elizabeth Goodman
A Novel Method To Analyze Dna Breaks And Repair In Human Cells, Caitlin Elizabeth Goodman
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Microsatellites repeat sequences are prone to forming non-canonical DNA structures and mutations. These areas of the genome can undergo expansions and contractions and are responsible for a variety of inherited neurological and neuromuscular disorders. Hairpin structures formed by trinucleotide repeats can lead to replication fork stalling, and fork collapse causing DNA double strand breaks. Various mechanisms are involved in processing microsatellites including mismatch repair, base excision repair, and crossover junction endonuclease cleavage. These processes, which are supposed to protect the genome, could also be the culprits which are causing mutations. In order to test and study this hypothesis, the use …
Availability Of Fermentable Nutrients Affect Gut Microbiota Composition, Trupthi Mehta
Availability Of Fermentable Nutrients Affect Gut Microbiota Composition, Trupthi Mehta
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Recent studies have increasingly established the role of gut microbiota in human health and disease. Diseases such as inflammatory bowel disease, colon cancer, cardiovascular disease and many neurological disorders have been linked to specific gut microbiota composition and disturbances. There have also been attempts in recent years to modulate gut microbial composition with the use of prebiotics and probiotics to promote healthy gut and prevent diseases. This thesis investigates whether the availability of fermentable nutrients high in fiber and antioxidants such as found in green coffee, roasted coffee, and salami infused with various prebiotics altered the composition and abundance of …
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 …
Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity, Sarah E. Kovar
Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity, Sarah E. Kovar
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Ras proteins were the first human oncogenes discovered. Although Ras has been found to be the most frequently mutated oncogene, there are currently no anti-Ras-specific drugs available in the clinic. Ras is responsible for initiating cellular pathways that include proliferation, survival, and apoptosis. There are three ubiquitously expressed Ras isoforms in mammalian cells: H-, N-, and K-Ras. Interaction with the plasma membrane is required for Ras biological activity. When Ras interaction with the plasma membrane is blocked, Ras activity is inhibited. Two compounds (from Dr. Ketcha, WSU Chemistry Department) were tested and shown to dissociate K-Ras, but not H-Ras from …
Erk3 As A Braf-Regulated Tumor Suppressor Is A New Potential Cancer Target In Melanoma, Minyi Chen
Erk3 As A Braf-Regulated Tumor Suppressor Is A New Potential Cancer Target In Melanoma, Minyi Chen
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Melanoma is the highest mortality rate skin cancer and the sixth most common cancer in the U.S..[1, 2] Arising from melanocytes, melanoma is known for frequent mutation of BRAF to its constitutive activation state BRAFV600E, thus over-activating its downstream MAPK targets ERK1/2 and contributing to melanoma progression.[3, 4, 5] ERK3, a less studied MAPK family protein which contributes to promoting lung, breast, cervical, head and neck (HNC) cancer metastasis, has also shown a correlation with upregulation of BRAF.[6, 7, 8, 9] However, the BRAF-ERK3 regulatory mechanism and the function of ERK3 in melanoma are still unclear. Here, we first elucidate …