The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, 2013 Virginia Commonwealth University
The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, Aditi R. Chiplunkar, Benjamin C. Curtis, Gabriel L. Eades, Megan S. Kane, Sean J. Fox, Jack L. Haar, Joyce A. Lloyd
Human and Molecular Genetics Publications
Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.
Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single …
Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, 2013 Arizona Cancer Center
Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson
Dartmouth Scholarship
Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …
Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, 2013 University of Nebraska Medical Center
Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, Xiaosheng Wang, Richard Simon
Journal Articles: Genetics, Cell Biology & Anatomy
BACKGROUND:
Identification of genes that are synthetic lethal to p53 is an important strategy for anticancer therapy as p53 mutations have been reported to occur in more than half of all human cancer cases. Although genome-wide RNAi screening is an effective approach to finding synthetic lethal genes, it is costly and labor-intensive.
METHODS:
To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines, one next-generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA) project, and one gene expression data from the Cancer …
Nucleic Acid Oxidation In Human Health And Disease, 2013 Old Dominion University
Nucleic Acid Oxidation In Human Health And Disease, Mu-Rong Chao, Pavel Rossner Jr., Siamak Haghdoost, Hueiwang Anna Jeng, Chiung-Wen Hu
Community & Environmental Health Faculty Publications
No abstract provided.
A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., 2013 Georgia Health Sciences University
A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder
Department of Medicine Faculty Papers
OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.
METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …
The Characterisation Of Pax3 Expressant Cells In Adult Peripheral Nerve [Journal Article], 2013 Edith Cowan University
The Characterisation Of Pax3 Expressant Cells In Adult Peripheral Nerve [Journal Article], Judith Blake, Melanie Ziman
Research outputs 2013
Pax3 has numerous integral functions in embryonic tissue morphogenesis and knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue’s resident stem/progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of the role of Pax3 in other adult tissue stem and progenitor cells, it was hypothesised that the cells in adult peripheral nerve that express Pax3 …
Delivering Genetic Education And Genetic Counseling For Rare Diseases In Rural Brazil, 2013 Edith Cowan University
Delivering Genetic Education And Genetic Counseling For Rare Diseases In Rural Brazil, A.X. Acosta, K Abe-Sandes, R Giugliani, Alan H. Bittles
Research outputs 2013
Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million. Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services is limited in rural and remote regions of the country. Since there is no formally recognized Genetic Counseling profession, genetic counseling is provided by physicians, trained either in medical genetics or a related clinical discipline. A comprehensive medical genetics program has been established in Monte Santo, an inland …
Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, 2013 Edith Cowan University
Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett
Theses: Doctorates and Masters
PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.
PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …
Structured Genome-Scale Variant And Clinical Data Reporting For Meta-Analysis In An Era Of Genomic Medicine, 2013 Children's Mercy Hospital
Structured Genome-Scale Variant And Clinical Data Reporting For Meta-Analysis In An Era Of Genomic Medicine, Darrell L. Dinwiddie, Carol J. Saunders, Emily G. Farrow, Sarah E. Soden, Neil A. Miller, Stephen F. Kingsmore
Manuscripts, Articles, Book Chapters and Other Papers
The Journal of Genomes and Exomes is a new, peer-reviewed, open-access, online publication whose scope comprises reporting of high quality genome, exome, and gene panel sequences with attendant, detailed phenotypes. The intent of this journal is to facilitate comparisons between genome, exome and gene panel sequencing studies in order to assist significance testing of the genotypephenotype associations, particularly those in uncommon genetic diseases. While there is yet to be a consensus regarding these classifications, the definition of an empiric set is helpful in understanding error models. Herein we have suggested structured templates for submissions and the rationale for the data …
Exome Sequencing Reveals De Novo Germline Mutation Of The Mammalian Target Of Rapamycin (Mtor) In A Patient With Megalencephaly And Intractable Seizures, 2013 Children's Mercy Hospital
Exome Sequencing Reveals De Novo Germline Mutation Of The Mammalian Target Of Rapamycin (Mtor) In A Patient With Megalencephaly And Intractable Seizures, Laurie D. Smith, Carol J. Saunders, Darrell L. Dinwiddie, Andrea M. Atherton, Neil A. Miller, Sarah E. Soden, Emily G. Farrow, Ahmed T G Abdelmoity, Stephen F. Kingsmore
Manuscripts, Articles, Book Chapters and Other Papers
A de novo somatic mutation in the mammalian target of rapamycin (MTOR) has previously been described in one patient with hemimegalencephaly and epilepsy. Here, we present a case of a young girl with megalencephaly and intractable seizures who was found to have an MTOR mutation in multiple cell lineages (p.Cys1483Phe) and, therefore, presumed to be of germline origin. The mutation was detected in peripheral blood DNA by exome sequencing of the patient and her parents, substantiating the utility of this approach for detection of clinically relevant de novo variations.
Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, 2012 Virginia Commonwealth University
Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem
Theses and Dissertations
Krüppel-like factors KLF1 and KLF2 are closely related transcription factors with three zinc finger domains in their carboxy-termini. KLF1 (erythroid Krüppel-like factor, or EKLF) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic β- globin genes. KLF1 and KLF2 have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double knockout (KO) mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, and double KO embryos are more anemic and die sooner than either single KO. We have shown that KLF1 and KLF2 positively regulate the human …
Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, 2012 Norwegian Veterinary Institute
Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.
Dr. Torstein Tengs
Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …
From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, 2012 Virginia Commonwealth University
From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins
Theses and Dissertations
Family, twin and adoption studies consistently suggest that genetic factors strongly influence the risk for alcohol dependence (AD). Although the literature supports the role of genetics in AD, identification of specific genes contributing to the etiology of AD has proven difficult. These difficulties are due in part to the complex set of risk factors contributing to the development of AD. These risk factors include comorbidities with other clinical diagnoses and behavioral phenotypes (e.g., major depression), physiological differences that contribute to the differences between people in their level of response to ethanol (e.g., initial sensitivity) and finally the large number of …
Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, 2012 University of Tennessee Health Science Center
Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle
Theses and Dissertations (ETD)
MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …
New Fusion Transcripts Identified In Normal Karyotype Acute Myeloid Leukemia, 2012 University of Nebraska Medical Center
New Fusion Transcripts Identified In Normal Karyotype Acute Myeloid Leukemia, Hongxiu Wen, Yongjin Li, Sami N. Malek, Yeong C. Kim, Jia Xu, Pei Xian Chen, Fengxia Xiao, Xin Huang, Xianzheng Zhou, Zhenyu Xuan, Shiva Mankala, Guihua Hou, Janet D. Rowley, Michael Q. Zhang, San Ming Wang
Journal Articles: Genetics, Cell Biology & Anatomy
Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of …
Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, 2012 University of Nevada, Las Vegas
Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala
UNLV Theses, Dissertations, Professional Papers, and Capstones
Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO4 stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO4 is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …
Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, 2012 Marshall University
Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu
Biochemistry and Microbiology
Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing derivative of strain PAO381.
Post-Transcriptional Regulation Of Mammalian Gene Expression In Non-Coding Region Of Target Rna, 2012 The University of Texas Graduate School of Biomedical Sciences at Houston
Post-Transcriptional Regulation Of Mammalian Gene Expression In Non-Coding Region Of Target Rna, Jing Lin
Dissertations & Theses (Open Access)
Tumor Suppressor Candidate 2 (TUSC2) is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. TUSC2 mRNA transcripts could be detected on Northern blots in both normal lung and some lung cancer cell lines, but no endogenous TUSC2 protein could be detected in a majority of lung cancer cell lines. Mechanisms regulating TUSC2 protein expression and its inactivation in primary lung cancer cells are largely unknown. We investigated the role of the 5’- and 3’-untranslated regions (UTRs) of the TUSC2 gene in the regulation of TUSC2 protein expression. We found that two small upstream open-reading frames (uORFs) …
The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, 2012 Virginia Commonwealth University
The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, Tamer Hadi
Theses and Dissertations
Paget’s disease (PDB) is the second most common metabolic bone disease after osteoporosis, affecting up to 3% of adults over age 55. It is characterized by focal lesions of bone resorbed by hyperactive osteoclasts coupled with rapid formation of highly disorganized, low quality bone formed by osteoblasts. Such lesions cause skeletal deformity, fractures, and other symptoms that significantly decrease quality of life. In 2001, mutations in the SQSTM1/p62 gene were found in a subset of Paget’s patients. The work summarized in this dissertation sought to answer two broad questions: what is the function of p62 in normal bone homeostasis and …
On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., 2012 Virginia Commonwealth University
On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson
Theses and Dissertations
Obesity is a serious public health crisis and recent estimates of its incidence are the highest in United States history, with 35% and 17% of American adults and children affected, respectively. The clinical definition of adult obesity is operationalized as a body mass index (BMI) greater than 30 kg/m2. Although the prevalence of common obesity has increased dramatically over the past 30 years–largely thought to be due to changes in the environment, such as high calorie diets and sedentary lifestyles—twin and family studies have shown consistently that relative body weight is under considerable genetic influence in both children and adults, …