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Articles 1 - 30 of 42
Full-Text Articles in Life Sciences
Life History Analysis Of James River Atlantic Sturgeon (Acipenser Oxyrinchus Oxyrinchus) With Implications For Management And Recovery Of The Species, Matthew Balazik
Life History Analysis Of James River Atlantic Sturgeon (Acipenser Oxyrinchus Oxyrinchus) With Implications For Management And Recovery Of The Species, Matthew Balazik
Theses and Dissertations
Sturgeon species (family Acipenseridae) are threatened globally due to habitat destruction, pollution, and overfishing. The Atlantic sturgeon Acipenser oxyrinchus oxyrinchus was listed as a federally endangered species in 2012. Atlantic sturgeon have a complex life history that utilizes a wide range of habitats. Timing of life history varies in different areas requiring each population to be studied. Very little work has been published on Atlantic sturgeon reproduction in the James River, Virginia. To aid the recovery of James River Atlantic sturgeon, aspects of life history need to be addressed. To increase understanding of Atlantic sturgeon life history a length at …
Growth Gone Awry: Exploring The Role Of Embryonic Liver Development Genes In Hcv Induced Cirrhosis And Hepatocellular Carcinoma, Martha K. Behnke
Growth Gone Awry: Exploring The Role Of Embryonic Liver Development Genes In Hcv Induced Cirrhosis And Hepatocellular Carcinoma, Martha K. Behnke
Theses and Dissertations
Introduction and methods: Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Metabolic and cell-cycle perturbations are known, large changes in tumors that add little to our understanding of the development of tumors, but generate “noise” that obscures potentially important smaller scale expression changes in “driver genes”. Recently, some researchers have suggested that HCC shares pathways involving the master regulators of embryonic development. Here, we investigated the involvement and specificity of developmental genes in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared …
Novel Strategies To Improve Metabolic Parameters And Precondition Diabetic Hearts Against Ischemia/Reperfusion Injury, Amit Varma
Theses and Dissertations
Insulin resistance and chronic hyperglycemia promote vascular damage, increase circulating levels of inflammatory cytokines and lead to increased morbidity and mortality. MicroRNAs (miRs) -103/107 have been shown to negatively regulate insulin sensitivity and glucose homeostasis. Based on complimentary binding profiles, the downstream target gene of miR-103/107 is caveolin-1 (Cav-1). We hypothesized that daily administration of the phosphodiesterase-5 inhibitor tadalafil (TAD) ± the curcumin analogue (HO-3867) will attenuate inflammation, improve metabolic parameters and reduce infarct size after ischemia/reperfusion injury (IRI). Furthermore, we propose that TAD therapy will reduce myocardial expression of miR-103/107 and increase mRNA and protein levels of its target …
Regulation Of Excitation-Contraction And Excitation-Transcription Coupling In Gastrointestinal Smooth Muscle By Caveolin-1, Sayak Bhattacharya
Regulation Of Excitation-Contraction And Excitation-Transcription Coupling In Gastrointestinal Smooth Muscle By Caveolin-1, Sayak Bhattacharya
Theses and Dissertations
Caveolae are integral part of the smooth muscle membrane and caveolins, the defining proteins of caveolae, act as scaffolding proteins for several G protein-coupled receptor signaling molecules and regulate cellular signaling through direct and indirect interactions with signaling proteins. Caveolin-1 is the predominant isoform in the smooth muscle and drives the formation of caveolae. However, little is known about the role of caveolin-1 in the regulation of excitation-contraction and excitation-transcription coupling in gastrointestinal smooth muscle. In the present study we have characterized muscarinic m2 and m3 receptor signaling in gastric smooth muscle and tested the hypothesis that caveolin-1 positively regulates …
Mutant P53 Regulation Of Cxc-Chemokine Expression In Head And Neck Squamous Cell Carcinoma, Brittany Field
Mutant P53 Regulation Of Cxc-Chemokine Expression In Head And Neck Squamous Cell Carcinoma, Brittany Field
Theses and Dissertations
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common type of cancer in the western hemisphere with a five-year survival rate of only 50% for patients with a localized tumor, which decreases significantly to as low as 5% for those patients with tumors that have metastasized to distant sites of the body. It has been found that both mutant p53 and epidermal growth factor receptor (EGFR) signaling pathways function to increase the expression of CXCL5, which has been identified as a key mediator in the process of tumor metastasis. Previous data from our lab suggested that the …
Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan
Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan
Theses and Dissertations
Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …
Characterization Of Microsatellite Loci And Pilot Population Genetic Analysis In Hickory Shad, Alosa Mediocris, Fnu Vishakha
Characterization Of Microsatellite Loci And Pilot Population Genetic Analysis In Hickory Shad, Alosa Mediocris, Fnu Vishakha
Theses and Dissertations
The hickory shad (Alosa mediocris) is a relatively understudied species of the anadromous fish sub-family Alosinae. This study, the first population genetic analysis of this species, employed 12 neutral microsatellite loci to estimate genetic diversity and population structure in tributaries of lower Chesapeake Bay, Virginia including James River and its tributaries (Appomattox and Chickahominy Rivers), Rappahannock River, and Pamunkey River. Genetic variation was extremely low. Estimates of observed heterozygosity were lower than expected heterozygosity. Significant population structure was detected among the six samples (FST = 0.093, p = 0.01). Effective population sizes were low (Ne ranged from 2 to 134). …
Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim
Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim
Theses and Dissertations
The human dopamine transporter (hDAT) provides the primary mechanism for dopamine clearance in synapses and thus facilitates the regulation of dopaminergic functions in cognition and reward. It is the molecular target of many centrally-active agents including amphetamines and cocaine. Therefore, an understanding of hDAT function and its modulation by these therapeutic drugs and drugs of abuse can provide insight into the mechanisms of abuse and addiction. In the presented studies, hDAT is tagged with a hexahistidine construct and heterologously expressed in Xenopus laevis oocytes. The plasma membranes are isolated, solubilized, and applied to a Nickel affinity column to obtain purified …
Combinatorial Analysis Of Tumorigenic Micrornas Driving Prostate Cancer, William Budd
Combinatorial Analysis Of Tumorigenic Micrornas Driving Prostate Cancer, William Budd
Theses and Dissertations
Prostate cancer is the leading non-cutaneous malignancy affecting men in the United States. One in every six men will be affected by prostate cancer. Due to the high incidence of prostate cancer, there is a need to develop biomarkers capable of identifying tumors from benign prostatic lesions. miRNAs are small molecules that regulate protein translation and impact cellular integrity when dysregulated. It is widely thought that miRNAs have the potential to serve as biomarkers. This study utilizes a unique combinatorial analysis of miRNA dysregulation to identify key miRNAs involved in prostate tumor initiation, progression and metastasis. Numerous dysregulated miRNAs potentially …
Sorafenib Enhances Pemetrexed-Induced Cytotoxicity Through And Autophagy-Dependent Mechanism In Cancer Cells, Bareford Mary
Sorafenib Enhances Pemetrexed-Induced Cytotoxicity Through And Autophagy-Dependent Mechanism In Cancer Cells, Bareford Mary
Theses and Dissertations
Acquired cellular resistance to traditional chemotherapeutics is a common obstacle in the treatment of most cancer cell types. This resistance occurs as a result of changes in the underlying molecular mechanisms of disease progression. The development of novel chemotherapeutic approaches designed to enhance the efficacy of protypical anti-cancer drugs is important in order to overcome this issue. Such approaches will aid in understanding the biomolecular phenomena responsible for drug resistance and disease progression. Combining signaling pathway inhibitors has become an effective strategy for enhancing tumor cell death by targeting multiple pathways known to regulate cell survival. Pemetrexed, an FDA-approved anti-folate …
Ocean Acidification: Understanding The Coastal Carbon Pump In A High Co2 World, Rachel Cooper
Ocean Acidification: Understanding The Coastal Carbon Pump In A High Co2 World, Rachel Cooper
Theses and Dissertations
Since the 1800s, carbon dioxide emissions due to human activities have contributed significantly to the amount of carbon in the atmosphere. Approximately a third of this carbon is absorbed by the ocean, through air-sea fluxes at the ocean surface (Sabine, 2004). Increased CO2 has changed the carbon chemistry of the ocean and hence the pH. pH is expected to drop by 0.4 by the year 2100. It is unclear how this lower pH will affect carbon cycling and sequestration with respect to the biological carbon pump. Most studies have focused on open ocean phytoplankton or bacterial communities in large, stationary …
Spag16 Is A Bifunctional Gene Regulating Male Fertility, David R. Nagarkatti-Gude
Spag16 Is A Bifunctional Gene Regulating Male Fertility, David R. Nagarkatti-Gude
Theses and Dissertations
SPAG16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the “9 + 2” axoneme. The “9 + 2” axoneme provides the cytoskeletal core of all eukaryotic motile cilia and flagella. In Chlamydomonas, the Pf20 gene encodes a single protein present in the central pair of the axoneme. Loss of Pf20 prevents central pair assembly and results in flagellar paralysis. The murine Spag16 gene encodes two proteins. While 71 kDa SPAG16L is found in all murine cells with motile cilia or flagella, 35 kDa SPAG16S transcript and protein are …
Effects Of Leaf Litter Diversity On Nutrients And Mosquito Communities In Neotropical Artificial Tree Holes, Rachel Komosinski
Effects Of Leaf Litter Diversity On Nutrients And Mosquito Communities In Neotropical Artificial Tree Holes, Rachel Komosinski
Theses and Dissertations
Inputs from terrestrial habitats to aquatic habitats are important for structuring aquatic communities. Terrestrial producer diversity in the tropics may decline due to anthropogenic causes. I investigated how tree diversity affects aquatic communities. We used leaves from three timber-producing species (Dalbergia retusa, Pachira quinata, and Tectona grandis) to test the effects of leaf litter species composition and richness on invertebrate aquatic communities in Gamboa, Panama. We quantified macroinvertbrate species richness and abundances, leaf litter mass loss, and dissolved carbon to nitrogen ratios (C:N) after 4 weeks. We found that litter types differed in breakdown and C:N. Tectona grandis had lower …
Characterizing The Interaction Between Ve-Ptp, Tie2 And Ve-Cadherin, Sharif Ossai Muhammad
Characterizing The Interaction Between Ve-Ptp, Tie2 And Ve-Cadherin, Sharif Ossai Muhammad
Theses and Dissertations
Many signaling pathways have been shown to be involved in the formation of the vascular system. Among them are the endothelial specific receptor families such as VEGF, Ang/Tie, as well as other signaling pathways such as semaphorins, which are also involved, in axonal guidance. It is known that the interaction between receptor tyrosine kinase, Tie2, VE-Cadherin, and VE-PTP mediate endothelial cell quiescence and adhesion. However, the structural basis of these interactions is not well understood. The aim of our study is to characterize the binding interactions between these players. Another important part of our study is describing the cross-talk between …
Using Next Generation Sequencing (Ngs) To Identify And Predict Micrornas (Mirnas) Potentially Affecting Schizophrenia And Bipolar Disorder, Vernell Williamson
Using Next Generation Sequencing (Ngs) To Identify And Predict Micrornas (Mirnas) Potentially Affecting Schizophrenia And Bipolar Disorder, Vernell Williamson
Theses and Dissertations
The last decade has seen considerable research focusing on understanding the factors underlying schizophrenia and bipolar disorder. A major challenge encountered in studying these disorders, however, has been the contribution of genetic, or etiological, heterogeneity to the so-called “missing heritability” [1-6]. Further, recent successes of large-scale genome-wide association studies (GWAS) have nonetheless seen only limited advancements in the delineation of the specific roles of implicated genes in disease pathophysiology. The study of microRNAs (miRNAs), given their ability to alter the transcription of hundreds of targeted genes, has the potential to expand our understanding of how certain genes relate to schizophrenia …
Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai
Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai
Theses and Dissertations
Head and Neck Squamous Cell Carcinoma (HNSCC) is an epithelial skin cancer of the upper aerodigestive tract, and is the sixth most common malignancy in the U.S. HNSCC patients undergoing chemotherapy commonly develop anemia, a condition in which the body lacks mature red blood cells (RBCs). Erythropoietin (EPO) is a systemically circulating hormone in the body that regulates the production of RBCs and is applied to treat anemia. Recently, several studies implicated shortened life expectancy of cancer patients by EPO administration. It may be due to an unexpected activation of survival and proliferation pathways of cancer cells by EPO because …
Sex-Specific Habitat Use And Responses To Fragmentation In An Endemic Chameleon Fauna, Philip Shirk
Sex-Specific Habitat Use And Responses To Fragmentation In An Endemic Chameleon Fauna, Philip Shirk
Theses and Dissertations
Chameleons are an understudied taxon facing many threats, including collection for the international pet trade and habitat loss and fragmentation. A recent field study reports a highly female-biased sex ratio in the Eastern Arc Endemic Usambara three horned chameleon, Trioceros deremensis, a large, sexually dimorphic species. This species is collected for the pet trade, and local collectors report males bring a higher price because only this sex has horns. Thus, sex ratios may vary due to differential rates of survival or harvesting. Alternatively, they may simply appear to be skewed if differences in habitat use biases detection of the sexes. …
Role Of Fyn And Lyn In Igg-Mediate Immune Responses, Yves Falanga
Role Of Fyn And Lyn In Igg-Mediate Immune Responses, Yves Falanga
Theses and Dissertations
Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage and neutrophil secretion of platelet activating factor subsequent to FcγR stimulation by IgG/Ag complexes. I have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). I found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38 and JNK phosphorylation. Additionally, IgG XL of …
The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy
The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy
Theses and Dissertations
Orofacial anomalies make up about a third of the 120,000 birth defects each year in the United States. Children born with these abnormalities must undergo immense physical and emotional strain in order to correct the defects. In fact, about $697 million is spent every year surgically treating children with cleft lip and/or cleft palate (2011). In countries where surgery is not an option, this abnormality causes immense difficulties in eating, hearing, speech, and psychosocial development. The causes of cleft lip/palate are extremely complex. Genetics play a role in the anomaly; however, 95% of cleft palate cases are non-syndromic and likely …
Mda-7/Il-24; A Promising Cancer Therapeutic Agent, Hossein Hamed
Mda-7/Il-24; A Promising Cancer Therapeutic Agent, Hossein Hamed
Theses and Dissertations
Glioblastoma multiforme (GBM) is an aggressive cancer that affects millions of patients per year. Conventional therapies combining chemotherapeutic agents with radiation can only extend survival by a few months; therefore, there is a dire need for an effective means of treating this deadly disease. Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), currently in the early stages of FDA pre-IND drug trials, has proven to be an effective cancer specific cytokine, able to trigger the onset of mitochondrial dysfunction and/or autophagy. GBM’s have mutations that often result in the activation of cytoprotective cell signaling pathways, preventing cancer therapeutics and even MDA-7/IL-24 treatments from being …
The Effect Of Various Chemical Factors On Angiogenesis In The Chick Chorio-Allantoic Membrane, Heather Hammond
The Effect Of Various Chemical Factors On Angiogenesis In The Chick Chorio-Allantoic Membrane, Heather Hammond
Theses and Dissertations
The chick chorio-allantoic membrane (CAM) contains a complex vascular network commonly used to study angiogenesis. The application of chemical factors and oxygen barrier films onto this tissue can easily influence the process of angiogenesis. In this study, oxygen barrier film patches (Krehalon, polyvinylidene chloride, 12 μm thick, O2 transmission rate = 2.19 cm3•ml/100 in2•day•atm) were applied to areas of the CAM. Holes were made in the film and alginate beads incubated in various chemical factors were placed in the holes. After 24 and 48 hours of exposure to the alginate beads, images were taken of the tissue using a stereomicroscope …
N-Terminal Processing Of Ribosomal Protein L27 In Staphylococcus Aureus, J. Harry Caufield
N-Terminal Processing Of Ribosomal Protein L27 In Staphylococcus Aureus, J. Harry Caufield
Theses and Dissertations
The bacterial ribosome is essential to cell growth yet little is known about how its proteins attain their mature structures. Recent studies indicate that certain Staphlyococcus aureus bacteriophage protein sequences contain specific sites that may be cleaved by a non-bacteriophage enzyme (Poliakov et al. 2008). The phage cleavage site was found to bear sequence similarity to the N-terminus of S. aureus ribosomal protein L27. Previous studies in E. coli (Wower et al.1998; Maguire et al. 2005) found that L27 is situated adjacent to the ribosomal peptidyl transferase site, where it likely aids in new peptide formation. The predicted S. aureus …
Impacts Of Rdx Soil Contamination Across An Age Gradient For The Native Shrub Morella Cerifera., Stephen Via
Impacts Of Rdx Soil Contamination Across An Age Gradient For The Native Shrub Morella Cerifera., Stephen Via
Theses and Dissertations
Understanding the impacts of explosive contamination on vegetation is key to understanding explosives behavior in the environment. I quantified shrub growth responses to 1,3,5-trinitroperhydro-1,35-triazine (RDX) soil contamination across three life stages and I hypothesized that RDX would have the greatest impact on seed germination. Morella cerifera seeds were germinated on soils amended with RDX up to 1500 mg RDX kg-1 dry soil. Juvenile and adult individuals were exposed for 6 weeks to soil amended with RDX up to 750 and 1500 mg RDX kg-1 dry soil, respectively. Morphological responses were quantified for juveniles while physiological measurements were quantified for adults. …
Expression Of Foreign Genes In The Pseudomonas Bacteriophage Pf3, Krystin Weathers
Expression Of Foreign Genes In The Pseudomonas Bacteriophage Pf3, Krystin Weathers
Theses and Dissertations
Filamentous bacteriophages were engineered to express foreign genes with the ultimate purpose of displaying transmission control anti-malarial peptides as in phage display. It was hypothesized that expression of foreign genes would be possible using the phage’s promoters. This hypothesis was tested by assuming that promoters for the phage major coat protein (MCP) gene would also promote the expression of any foreign gene inserted downstream of the MCP gene. As proof of principle, the bacteriophages Pf3, Pf1, and M13 were engineered in this way to successfully synthesize Enhanced Green Fluorescent Protein (EGFP). Type 88 phage display on the EGFP recombinant Pf3 …
Functional And Biochemical Consequences Of Single Nucleotide Polymorphisms In The Human Vesicular Monoamine Transporter 1 Gene (Slc18a1) By Sally Gamal Shukry, B.S., Sally Gamal Shukry
Functional And Biochemical Consequences Of Single Nucleotide Polymorphisms In The Human Vesicular Monoamine Transporter 1 Gene (Slc18a1) By Sally Gamal Shukry, B.S., Sally Gamal Shukry
Theses and Dissertations
Abstract FUNCTIONAL AND BIOCHEMICAL CONSEQUENCES OF SINGLE NUCLEOTIDE POLYMORPHISMS IN THE HUMAN VESICULAR MONOAMINE TRANSPORTER 1 GENE (SLC18A1) By Sally Gamal Shukry, B.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Biology at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Advisor: Jennifer K. Stewart Associate Professor and Graduate Director, Department of Biology Single nucleotide polymorphisms (SNP) in the human VMAT1 gene (SLC18A1) have been associated with schizophrenia in three different populations: Han Chinese, Western European and Japanese. Effects of these mutations on transport function of the hVMAT1 protein have not …
A Multifaceted Approach Identifies Erbb2 And Erbb3 Proteins And Microrna-125b As Key Contributors To Prostate Cancer Progression, Danielle Weaver
A Multifaceted Approach Identifies Erbb2 And Erbb3 Proteins And Microrna-125b As Key Contributors To Prostate Cancer Progression, Danielle Weaver
Theses and Dissertations
Prostate cancer is the most common cancer affecting men today. Therefore, there is a strong need for accurate biomarkers and successful therapeutic treatments. A novel approach combining a computationally built protein-protein interaction network of proven microRNA protein targets with high throughput proteomics identified ErbB2 and ErbB3 as key proteins in prostate cancer. These results coupled with microRNA array screening of an androgen-independent prostate cancer progression model, substantiated by single microRNA analysis, suggested miR125b as a key tumor suppressor contributing to prostate cancer progression. miR125b expression was shown to be substantially increased in the non-tumorigenic P69 cell line compared to its …
Assessing The Genotoxicity Of Triclosan In Tadpoles Of The American Bullfrog, Lithobates Catesbeianus., David Emery
Assessing The Genotoxicity Of Triclosan In Tadpoles Of The American Bullfrog, Lithobates Catesbeianus., David Emery
Theses and Dissertations
Amphibians are particularly sensitive to environmental degradation and, therefore, serve as effective environmental quality indicators. Research has suggested that amphibian declines are exacerbated by manmade environmental toxicants, especially those found in high concentrations in urban areas. The NIH has pinpointed genotoxicity as a major route of cancer causation, and has since developed stringent testing procedures for potentially hazardous chemicals. One such method, recognized for its simplicity and economy, is the micronucleus assay. A study was conducted assessing the genotoxicity of the widely used antimicrobial agent Triclosan to American Bullfrog tadpoles. Lithobates catesbeianus tadpoles were reared in glass aquaria containing ultra-high …
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Theses and Dissertations
There are gaps in the fundamental understanding of the expression of nitric oxide synthases (NOS) in the microvasculature. We examined co-localization of NOS1 (nNOS), NOS2 (iNOS) and NOS3 (eNOS) in the spinotrapezius muscle of young adult male Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats according to fiber type using immunohistochemistry and brightfield microscopy. Data regarding fiber distribution, population and morphology data were collected. Alkaline phosphatase staining was used to determine capillary density and average number of capillaries around a fiber. Gel electrophoresis and Western blot techniques were used to compare myosin heavy chain (MHC) protein expression with fiber type population …
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Theses and Dissertations
DNA methylation is the most recognizable epigenetic mechanism. In general, DNA hypomethylation is associated with increased gene expression whereas DNA hypermethylation is associated with decreased gene expression. To date, little is known about the role of DNA methylation in the pathophysiology of preeclampsia. In this study, we examined the differences in DNA methylation in omental arteries of normal pregnant and preeclamptic women using the high throughput Illumina HumanMethylation27 BeadChip assay. We found 1,685 genes with a significant difference in DNA methylation at a false discovery rate of < 10% with many inflammatory genes having reduced methylation. The thromboxane synthase gene was the most hypomethylated gene in preeclamptic women as compared to normal pregnant women. When we examined the expression of thromboxane synthase in omental arteries of normal pregnant and preeclamptic women we found it to be significantly increased in preeclamptic women. The increased expression was observed in vascular smooth muscle cells, endothelial cells and infiltrating neutrophils. Experimentally induced DNA hypomethylation increased the expression of thromboxane synthase in the neutrophil-like HL-60 cell line, whereas tumor necrosis factor α (TNFα), a neutrophil product, increased its expression in cultured human vascular smooth muscle cells (VSMC). These finding suggest that DNA methylation and release of TNFα by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in systemic blood vessels of preeclamptic women, contributing to the hypertension and coagulation abnormalities. We also explored the possible contribution of DNA methylation to the altered expression of genes involved in collagen metabolism in preeclampsia. Several matrix metalloproteinase (MMP) genes, including MMP1 and MMP8, were significantly less methylated in preeclamptic women, whereas TIMP and COL genes were either significantly more methylated or had no significant change in their DNA methylation status. Experimentally induced DNA hypomethylation increased the expression of MMP-1, but not TIMP-1 or COL1A1, in cultured VSMCs and increased the expression of MMP-1 and MMP-8 in HL-60 cells. These findings suggest that DNA methylation contributes to the imbalance in genes involved in collagen metabolism in blood vessels of preeclamptic women.
Optimizing Read Mapping To Reference Genomes To Determine Composition And Species Prevalence In Microbial Communities, John Martin, Sean Sykes, Sarah Young, Karthik Kota, Riva Sanka, Nihar U. Sheth, Joshua Orvis, Erica Sodergren, Zhengyuan Wang, George M. Weinstock, Makedonka Mitreva
Optimizing Read Mapping To Reference Genomes To Determine Composition And Species Prevalence In Microbial Communities, John Martin, Sean Sykes, Sarah Young, Karthik Kota, Riva Sanka, Nihar U. Sheth, Joshua Orvis, Erica Sodergren, Zhengyuan Wang, George M. Weinstock, Makedonka Mitreva
Study of Biological Complexity Publications
The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners …