Identification of Prognostic and Metastasis-Related Alternative
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Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Genome‐Wide Association Studies of the Self‐Rating of Effects of Ethanol (SRE)
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by eScholarship - University of California UC San Diego UC San Diego Previously Published Works Title Genome-wide association studies of the self-rating of effects of ethanol (SRE). Permalink https://escholarship.org/uc/item/94p1n78c Journal Addiction biology, 25(2) ISSN 1355-6215 Authors Lai, Dongbing Wetherill, Leah Kapoor, Manav et al. Publication Date 2020-03-01 DOI 10.1111/adb.12800 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Received: 18 December 2018 Revised: 6 May 2019 Accepted: 27 May 2019 DOI: 10.1111/adb.12800 ORIGINAL ARTICLE Genome‐wide association studies of the self‐rating of effects of ethanol (SRE) Dongbing Lai1 | Leah Wetherill1 | Manav Kapoor2 | Emma C. Johnson3 | Melanie Schwandt4 | Vijay A. Ramchandani5 | David Goldman4 | Geoff Joslyn6 | Xi Rao1 | Yunlong Liu1 | Sean Farris7 | R. Dayne Mayfield7 | Danielle Dick8 | Victor Hesselbrock9 | John Kramer10 | Vivia V. McCutcheon3 | John Nurnberger1,11 | Jay Tischfield12 | Alison Goate2 | Howard J. Edenberg1,13 | Bernice Porjesz14 | Arpana Agrawal3 | Tatiana Foroud1 | Marc Schuckit15 1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 2 Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, New York 3 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 4 Office of the Clinical Director, National Institute on Alcohol Abuse -
Supplemental Data
Supplementary Materials 1. Supplementary Methods 2. Supplementary Figures • Figure S1. RNA-seq measurement of kidney gene expression for known markers of acute kidney injury (Kim-1, Fgβ) and kidney fibrosis (Col1a1, Fn1). • Figure S2. Histological, biochemical and molecular characteristics of mouse models of kidney fibrosis and acute kidney injury. • Figure S3. RNA-seq vs. qRT-PCR correlation of gene expression measurement for the 11 selected candidates. • Figure S4. Histological characteristics of a normal vs. fibrotic human kidney. 3. Supplementary Tables • Table S1. List of genes identified by RNA-seq as significantly different from normal at least at one time-point in the FA nephropathy progression. • Table S2. List of peptides used for selected reaction monitoring (SRM) assays. • Table S3. List of primers used for mouse qRT-PCR. • Table S4. List of primers used for human qRT-PCR. Page 1 of 31 1. Supplementary Methods Animal studies Biospecimen collection: At the moment of sacrifice, blood was collected from the inferior vena cava under isoflurane anesthesia, and, following opening of the thoracic cavity to ensure that the animal is deceased, the kidneys were retrieved and sectioned in samples dedicated for histology and immunfluorescence (fixed in 10% neutral buffered formalin), protein and RNA analysis (flash-frozen in liquid nitrogen). Similarly, liver tissue sections from the left lateral lobe of the ANIT fed mice were fixed in neutral buffered formalin for histopathological processing, while other liver sections were flash-frozen in liquid nitrogen. Blood was collected from mice in heparinized tubes and plasma was separated following centrifugation at 7500 g for 5 minutes. Blood urea nitrogen (BUN) was measured using an InfinityUrea kit (Thermo Fisher Scientific, Wilmington, DE) and serum creatinine (SCr) was measured using a Creatinine Analyzer II (Beckman Coulter). -
Bioinformatics Approach to Probe Protein-Protein Interactions
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2013 Bioinformatics Approach to Probe Protein-Protein Interactions: Understanding the Role of Interfacial Solvent in the Binding Sites of Protein-Protein Complexes;Network Based Predictions and Analysis of Human Proteins that Play Critical Roles in HIV Pathogenesis. Mesay Habtemariam Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Bioinformatics Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2997 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. ©Mesay A. Habtemariam 2013 All Rights Reserved Bioinformatics Approach to Probe Protein-Protein Interactions: Understanding the Role of Interfacial Solvent in the Binding Sites of Protein-Protein Complexes; Network Based Predictions and Analysis of Human Proteins that Play Critical Roles in HIV Pathogenesis. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. By Mesay Habtemariam B.Sc. Arbaminch University, Arbaminch, Ethiopia 2005 Advisors: Glen Eugene Kellogg, Ph.D. Associate Professor, Department of Medicinal Chemistry & Institute For Structural Biology And Drug Discovery Danail Bonchev, Ph.D., D.SC. Professor, Department of Mathematics and Applied Mathematics, Director of Research in Bioinformatics, Networks and Pathways at the School of Life Sciences Center for the Study of Biological Complexity. Virginia Commonwealth University Richmond, Virginia May 2013 ኃይልን በሚሰጠኝ በክርስቶስ ሁሉን እችላለሁ:: ፊልጵስዩስ 4:13 I can do all this through God who gives me strength. -
9Faaa2444c3ffa7b739bc49e981
Original Article Comparison of Protamine 1 to Protamine 2 mRNA Ratio and YBX2 gene mRNA Content in Testicular Tissue of Fertile and Azoospermic Men Sahar Moghbelinejad, Ph.D.1, 2, Reza Najafipour, Ph.D.1, 2*, Amir Samimi Hashjin, M.Sc.1 1. Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran 2. Department of Medical Genetics, Qazvin University of Medical Sciences, Qazvin, Iran Abstract Background: Although aberrant protamine (PRM) ratios have been observed in infertile men, the mechanisms that implicit the uncoupling of PRM1 and PRM2 expression remain unclear. To uncover these mechanisms, in this observational study we have compared the PRM1/PRM2 mRNA ratio and mRNA contents of two regulatory factors of these genes. Materials and Methods: In this experimental study, sampling was performed by a mul- ti-step method from 50 non-obstructive azoospermic and 12 normal men. After RNA extraction and cDNA synthesis, real-time quantitative polymerase chain reaction (RT- QPCR) was used to analyze the PRM1, PRM2, Y box binding protein 2 (YBX2) and JmjC-containing histone demethylase 2a (JHDM2A) genes in testicular biopsies of the studied samples. Results: The PRM1/PRM2 mRNA ratio differed significantly among studied groups, namely 0.21 ± 0.13 in azoospermic samples and -0.8 ± 0.22 in fertile samples. The amount of PRM2 mRNA, significantly reduced in azoospermic patients. Azoospermic men exhib- ited significant under expression of YBX2 gene compared to controls (P<0.001). mRNA content of this gene showed a positive correlation with PRM mRNA ratio (R=0.6, P=0.007). JHDM2A gene expression ratio did not show any significant difference between the studied groups (P=0.3). -
Proteomic Characterization of Transcription and Splicing Factors Associated with a Metastatic Phenotype in Colorectal Cancer
Proteomic characterization of transcription and splicing factors associated with a metastatic phenotype in colorectal cancer Sofía Torres1+, Irene García-Palmero1+, Consuelo Marín-Vicente1,2, Rubén A. Bartolomé1, Eva Calviño1, María Jesús Fernández-Aceñero3 and J. Ignacio Casal1* +. Equal authorship 1. Functional proteomics. Centro de Investigaciones Biológicas (CIB-CSIC). Ramiro de Maeztu 9. Madrid. Spain. 2. Proteomic facilities. CIB-CSIC. Madrid. Spain 3. Department of Pathology. Hospital Clínico. Madrid. Spain Running title: Transcription factors in metastatic colorectal cancer Keywords: SRSF3, transcription factors, splicing factors, metastasis, colorectal cancer *. Corresponding author J. Ignacio Casal Department of Cellular and Molecular Medicine Centro de Investigaciones Biológicas (CIB-CSIC) Ramiro de Maeztu, 9 28040 Madrid, Spain Phone: +34 918373112 Fax: +34 91 5360432 Email: [email protected] 1 ABSTRACT We investigated new transcription and splicing factors associated with the metastatic phenotype in colorectal cancer. A concatenated tandem array of consensus transcription factors (TFs)-response elements was used to pull down nuclear extracts in two different pairs of colorectal cancer cells, KM12SM/KM12C and SW620/480, genetically-related but differing in metastatic ability. Proteins were analyzed by label-free LC-MS and quantified with MaxLFQ. We found 240 proteins showing a significant dysregulation in highly- metastatic KM12SM cells relative to non-metastatic KM12C cells and 257 proteins in metastatic SW620 versus SW480. In both cell lines there were similar alterations in genuine TFs and components of the splicing machinery like UPF1, TCF7L2/TCF-4, YBX1 or SRSF3. However, a significant number of alterations were cell-line specific. Functional silencing of MAFG, TFE3, TCF7L2/TCF-4 and SRSF3 in KM12 cells caused alterations in adhesion, survival, proliferation, migration and liver homing, supporting their role in metastasis. -
RNA Binding Protein, Ybx2, Regulates RNA Stability During Cold-Induced
Page 1 of 51 Diabetes RNA binding protein, Ybx2, regulates RNA stability during cold-induced brown fat activation Dan Xu1,2*, Shaohai Xu3, Aung Maung Maung Kyaw2, Yen Ching Lim1, Sook Yoong Chia2, Diana Teh Chee Siang2, Juan R. Alvarez-Dominguez5, Peng Chen3, Melvin Khee-Shing Leow6,7,8, Lei Sun2,4* 1School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China 2Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore 3Division of Bioengineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457, Singapore 4Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore 5Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA 6Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore. 7Department of Endocrinology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore 8Office of Clinical Sciences, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore *Correspondence: [email protected] (D.X.); [email protected] (L.S.) Diabetes Publish Ahead of Print, published online September 29, 2017 Diabetes Page 2 of 51 Abstract Recent years have seen an upsurge of interest on brown adipose tissue (BAT) to combat the epidemic of obesity and diabetes. How its development and activation are regulated at the post-transcriptional level, however, has yet to be fully understood. RNA binding proteins (RBPs) lie in the center of post-transcriptional regulation. To systemically study the role of RBPs in BAT, we profiled >400 RBPs in different adipose depots and identified Y-box binding protein 2 (Ybx2) as a novel regulator in BAT activation. -
Twelve-Year Changes in Protein Profiles in Patients with and Without Gastric Bypass Surgery
medRxiv preprint doi: https://doi.org/10.1101/2020.08.13.20173666; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Twelve-year changes in protein profiles in patients with and without gastric bypass surgery. Noha A. Yousri1,2,*, Rudolf Engelke3, Hina Sarwath3, Rodrick D. McKinlay4, Steven C. Simper4, Ted D. Adams5,6, Frank Schmidt3,7, Karsten Suhre8, Steven C. Hunt1,6 1 Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar 2 Computer and Systems Engineering, Alexandria University, Egypt 3 Proteomics core, Weill Cornell Medicine, Doha, Qatar 4 Rocky Mountain Associated Physicians, Salt Lake City, Utah 5 Intermountain Live Well Center, Intermountain Healthcare, Salt Lake City, Utah 6 Department of Internal Medicine, University of Utah, Salt Lake City, Utah 7 Department of Biochemistry, Weill Cornell Medicine, Doha, Qatar 8 Department of Physiology and Biophysics, Weill Cornell Medicine, Doha, Qatar Short title: Proteomic changes after gastric bypass surgery Key words: obesity, bariatric surgery, longitudinal study, proteomics *Corresponding author: Noha A. Yousri, PhD, Department of Genetic Medicine, Weill Cornell Medicine, PO Box 24144, Education City, Doha, Qatar Email: [email protected] Phone: +974 4492 8425 Funding: Supported by a grant (DK-55006) from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, a U.S. Public Health Service research grant (MO1-RR00064) from the National Center for Research Resources, Biomedical Research Program funds from Intermountain Healthcare, and from Qatar Foundation to Weill Cornell Medicine. -
Genetics of Atrioventricular Canal Defects Flaminia Pugnaloni1, Maria Cristina Digilio2, Carolina Putotto1, Enrica De Luca1, Bruno Marino1 and Paolo Versacci1*
Pugnaloni et al. Italian Journal of Pediatrics (2020) 46:61 https://doi.org/10.1186/s13052-020-00825-4 REVIEW Open Access Genetics of atrioventricular canal defects Flaminia Pugnaloni1, Maria Cristina Digilio2, Carolina Putotto1, Enrica De Luca1, Bruno Marino1 and Paolo Versacci1* Abstract Atrioventricular canal defect (AVCD) represents a quite common congenital heart defect (CHD) accounting for 7.4% of all cardiac malformations. AVCD is a very heterogeneous malformation that can occur as a phenotypical cardiac aspect in the context of different genetic syndromes but also as an isolated, non-syndromic cardiac defect. AVCD has also been described in several pedigrees suggesting a pattern of familiar recurrence. Targeted Next Generation Sequencing (NGS) techniques are proved to be a powerful tool to establish the molecular heterogeneity of AVCD. Given the complexity of cardiac embryology, it is not surprising that multiple genes deeply implicated in cardiogenesis have been described mutated in patients with AVCD. This review attempts to examine the recent advances in understanding the molecular basis of this complex CHD in the setting of genetic syndromes or in non- syndromic patients. Keywords: Congenital heart disease, Atrioventricular canal defect, Genetics Introduction extracellular matrix, leading to absent or incomplete fu- The atrioventricular canal defect (AVCD), also called sion of ventral (antero-superior) and dorsal (postero-in- atrioventricular septal defect, is a quite common con- ferior) atrioventricular cushions [2–4]. Nevertheless, the genital heart defect (CHD), accounting for 7.4% of all hypothesis that extracardiac progenitor cells contribute cardiac malformations. It can be anatomically classified also to the growth of the inlet part of the heart has been in complete, partial and intermediate types. -
Contribution of Copy-Number Variation to Down Syndrome–Associated Atrioventricular Septal Defects
Original Research Article © American College of Medical Genetics and Genomics © American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE Contribution of copy-number variation to Down syndrome–associated atrioventricular septal defects Dhanya Ramachandran, PhD1, Jennifer G. Mulle, MPH, PhD1,2, Adam E. Locke, PhD3,9, Lora J.H. Bean, PhD1, Tracie C. Rosser, PhD1, Promita Bose, MS1, Kenneth J. Dooley, MD4, Clifford L. Cua, MD5, George T. Capone, MD6, Roger H. Reeves, PhD7, Cheryl L. Maslen, PhD8, David J. Cutler, PhD1, Stephanie L. Sherman, PhD1 and Michael E. Zwick, PhD1 Purpose: The goal of this study was to identify the contribution of contrast, cases had a greater burden of large, rare deletions (P < 0.01) large copy-number variants to Down syndrome–associated atrioven- and intersected more genes (P < 0.007) as compared with controls. tricular septal defects, the risk for which in the trisomic population is We also observed a suggestive enrichment of deletions intersecting 2,000-fold more as compared with that of the general disomic popu- ciliome genes in cases as compared with controls. lation. Conclusion: Our data provide strong evidence that large, rare dele- Methods: Genome-wide copy-number variant analysis was per- tions increase the risk of Down syndrome–associated atrioventricu- formed on 452 individuals with Down syndrome (210 cases with lar septal defects, whereas large, common copy-number variants do complete atrioventricular septal defects; 242 controls with structur- not appear to increase the risk of Down syndrome–associated atrio- ally normal hearts) using Affymetrix SNP 6.0 arrays, making this the ventricular septal defects. -
Rodent Models in Down Syndrome Research: Impact and Future Opportunities Yann Herault1,2,3,4,5,*, Jean M
© 2017. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2017) 10, 1165-1186 doi:10.1242/dmm.029728 REVIEW Rodent models in Down syndrome research: impact and future opportunities Yann Herault1,2,3,4,5,*, Jean M. Delabar5,6,7,8, Elizabeth M. C. Fisher5,9,10, Victor L. J. Tybulewicz5,10,11,12, Eugene Yu5,13,14 and Veronique Brault1,2,3,4 ABSTRACT significantly impairs health and autonomy of affected individuals Down syndrome is caused by trisomy of chromosome 21. To date, a (Khoshnood et al., 2011; Parker et al., 2010). Despite the wide multiplicity of mouse models with Down-syndrome-related features availability of prenatal diagnosis since the mid-1960s (Summers has been developed to understand this complex human et al., 2007) and the introduction of maternal serum screening in chromosomal disorder. These mouse models have been important 1984 (Inglis et al., 2012), the incidence of DS has not necessarily for determining genotype-phenotype relationships and identification decreased (Natoli et al., 2012; Loane et al., 2013; de Graaf et al., of dosage-sensitive genes involved in the pathophysiology of the 2016); in fact, prevalence is going up, largely because of increased condition, and in exploring the impact of the additional chromosome lifespan and maternal age (which is the single biggest risk factor) on the whole genome. Mouse models of Down syndrome have (Sherman et al., 2007; Loane et al., 2013). also been used to test therapeutic strategies. Here, we provide an A core set of features characterises most cases of DS, including overview of research in the last 15 years dedicated to the specific cognitive disabilities, hypotonia (Box 1) at birth and development and application of rodent models for Down syndrome.