A Comprehensive Mapping of the Structure and Gene Organisation in the Sheep MHC Class I Region N
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ABCG1 (ABC8), the Human Homolog of the Drosophila White Gene, Is a Regulator of Macrophage Cholesterol and Phospholipid Transport
ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport Jochen Klucken*, Christa Bu¨ chler*, Evelyn Orso´ *, Wolfgang E. Kaminski*, Mustafa Porsch-Ozcu¨ ¨ ru¨ mez*, Gerhard Liebisch*, Michael Kapinsky*, Wendy Diederich*, Wolfgang Drobnik*, Michael Dean†, Rando Allikmets‡, and Gerd Schmitz*§ *Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, 93042 Regensburg, Germany; †National Cancer Institute, Laboratory of Genomic Diversity, Frederick, MD 21702-1201; and ‡Departments of Ophthalmology and Pathology, Columbia University, Eye Research Addition, New York, NY 10032 Edited by Jan L. Breslow, The Rockefeller University, New York, NY, and approved November 3, 1999 (received for review June 14, 1999) Excessive uptake of atherogenic lipoproteins such as modified low- lesterol transport. Although several effector molecules have been density lipoprotein complexes by vascular macrophages leads to proposed to participate in macrophage cholesterol efflux (6, 9), foam cell formation, a critical step in atherogenesis. Cholesterol efflux including endogenous apolipoprotein E (10) and the cholesteryl mediated by high-density lipoproteins (HDL) constitutes a protective ester transfer protein (11), the detailed molecular mechanisms mechanism against macrophage lipid overloading. The molecular underlying cholesterol export in these cells have not yet been mechanisms underlying this reverse cholesterol transport process are characterized. currently not fully understood. To identify effector proteins that are Recently, mutations of the ATP-binding cassette (ABC) trans- involved in macrophage lipid uptake and release, we searched for porter ABCA1 gene have been causatively linked to familial HDL genes that are regulated during lipid influx and efflux in human deficiency and Tangier disease (12–14). -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Transcriptional and Post-Transcriptional Regulation of ATP-Binding Cassette Transporter Expression
Transcriptional and Post-transcriptional Regulation of ATP-binding Cassette Transporter Expression by Aparna Chhibber DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmaceutical Sciences and Pbarmacogenomies in the Copyright 2014 by Aparna Chhibber ii Acknowledgements First and foremost, I would like to thank my advisor, Dr. Deanna Kroetz. More than just a research advisor, Deanna has clearly made it a priority to guide her students to become better scientists, and I am grateful for the countless hours she has spent editing papers, developing presentations, discussing research, and so much more. I would not have made it this far without her support and guidance. My thesis committee has provided valuable advice through the years. Dr. Nadav Ahituv in particular has been a source of support from my first year in the graduate program as my academic advisor, qualifying exam committee chair, and finally thesis committee member. Dr. Kathy Giacomini graciously stepped in as a member of my thesis committee in my 3rd year, and Dr. Steven Brenner provided valuable input as thesis committee member in my 2nd year. My labmates over the past five years have been incredible colleagues and friends. Dr. Svetlana Markova first welcomed me into the lab and taught me numerous laboratory techniques, and has always been willing to act as a sounding board. Michael Martin has been my partner-in-crime in the lab from the beginning, and has made my days in lab fly by. Dr. Yingmei Lui has made the lab run smoothly, and has always been willing to jump in to help me at a moment’s notice. -
A Comprehensive Transcriptome Analysis of Skeletal Muscles in Two Polish Pig Breeds Differing in Fat and Meat Quality Traits
Genetics and Molecular Biology, 41, 1, 125-136 (2018) Copyright © 2018, Sociedade Brasileira de Genética. Printed in Brazil DOI: http://dx.doi.org/10.1590/1678-4685-GMB-2016-0101 Research Article A comprehensive transcriptome analysis of skeletal muscles in two Polish pig breeds differing in fat and meat quality traits Katarzyna Piórkowska1 , Kacper òukowski3, Katarzyna Ropka-Molik1, Miros»aw Tyra2 and Artur Gurgul1 1Department of Animal Molecular Biology, National Research Institute of Animal Production, Balice, Poland. 2Department of Pig Breeding, National Research Institute of Animal Production, Balice, Poland. 3Department of Cattle Breeding, National Research Institute of Animal Production, Balice, Poland. Abstract Pork is the most popular meat in the world. Unfortunately, the selection pressure focused on high meat content led to a reduction in pork quality. The present study used RNA-seq technology to identify metabolic process genes related to pork quality traits and fat deposition. Differentially expressed genes (DEGs) were identified between pigs of Pulawska and Polish Landrace breeds for two the most important muscles (semimembranosus and longissimus dorsi). A total of 71 significant DEGs were reported: 15 for longissimus dorsi and 56 for semimembranosus muscles. The genes overexpressed in Pulawska pigs were involved in lipid metabolism (APOD, LXRA, LIPE, AP2B1, ENSSSCG00000028753 and OAS2) and proteolysis (CST6, CTSD, ISG15 and UCHL1). In Polish Landrace pigs, genes playing a role in biological adhesion (KIT, VCAN, HES1, SFRP2, CDH11, SSX2IP and PCDH17), actin cytoskeletal organisation (FRMD6, LIMK1, KIF23 and CNN1) and calcium ion binding (PVALB, CIB2, PCDH17, VCAN and CDH11) were transcriptionally more active. The present study allows for better understanding of the physiological processes associated with lipid metabolism and muscle fiber organization. -
AB-PN532 PPP1R11-Py64 Antibody Phosphosite-Specific Polyclonal Antibody for Monitoring the Phosphorylation of Human PPP1R11 (HCG V)
AB-PN532 PPP1R11-pY64 Antibody Phosphosite-specific polyclonal antibody for monitoring the phosphorylation of human PPP1R11 (HCG V) Address: 8755 Ash Street, Suite 1 Vancouver, British Columbia, Email: [email protected] Canada V6P 6T3 Phone: 604-323-2547 Target Protein Name Long: Protein phosphatase 1 regulatory subunit 11 HCG V; HCG-V; HCGV; Hemochromatosis candidate gene V protein; inhibitor-3; IPP3; MGC125741; MGC125742; MGC125743; PP1RB; PPP1R11; Protein phosphatase 1 regulatory subunit 11; protein phosphatase 1, regulatory Alias: (inhibitor) subunit 11; protein phosphatase 1, regulatory (inhibitor) subunit 11, isoform 1; Protein phosphatase inhibitor 3; t-complex-associated-testis- expressed 5; TCTE5; TCTEX5 UniProt ID: O60927 Sequence Predicted Mass (KDa): 13953 126 AA; O60927) Observed SDS-PAGE Mass (KDa): 18-23 Immunogen Antibody Immunogen Source: Human PPP1R11 (HCG V) sequence peptide Cat. No.: PE-04ADI99 Antibody Immunogen Sequence: CCI(pY)EKP(bA)C (bA) = beta-alanine Corresponds to amino acid residues C61 to P67; In the PPI_Ypi1 domain. This is Location in Target: the major in vivo phosphorylation site in PPP1R11. Peptide Type: For phosphosite-specific recognition of target. Target Phosphosite: Tyr-64 Production Antibody Host Species: Rabbit Antibody Type: Polyclonal Antibody Ig Isotype Clone Lot: Immunoglobulin G The immunizing peptide was produced by solid phase synthesis on a multipep peptide synthesizer and purified by reverse-phase hplc chromatography. Purity was assessed by analytical hplc and the amino acid sequence confirmed by mass spectrometry analysis. This peptide was coupled to KLH prior to immunization into rabbits. New Zealand White rabbits were subcutaneously Production Method: injected with KLH-coupled immunizing peptide every 4 weeks for 4 months. -
Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you. -
Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response
International Journal of Molecular Sciences Article Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response Viktor Hlaváˇc 1,2 , Radka Václavíková 1,2, Veronika Brynychová 1,2, Renata Koževnikovová 3, Katerina Kopeˇcková 4, David Vrána 5 , Jiˇrí Gatˇek 6 and Pavel Souˇcek 1,2,* 1 Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic; [email protected] (V.H.); [email protected] (R.V.); [email protected] (V.B.) 2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic 3 Department of Oncosurgery, Medicon Services, 140 00 Prague, Czech Republic; [email protected] 4 Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic; [email protected] 5 Department of Oncology, Medical School and Teaching Hospital, Palacky University, 779 00 Olomouc, Czech Republic; [email protected] 6 Department of Surgery, EUC Hospital and University of Tomas Bata in Zlin, 760 01 Zlin, Czech Republic; [email protected] * Correspondence: [email protected]; Tel.: +420-267-082-711 Received: 19 November 2020; Accepted: 11 December 2020; Published: 15 December 2020 Abstract: Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). -
It Is Illeg Al to P O St Th Is Co P Yrig H Ted P D F O N an Y W Eb Site. It Is Illegal
Letters to the Editor It is Geneillegal Expression to Profiling post ofthis the xMHC copyrighted Region and HIST1H4C PDF encodeon histones.any Strong website. evidence of associations Reveals 9 Candidate Genes in Schizophrenia was observed within and around histone genes in schizophrenia.2 Abnormal expression of genes related to nucleosome and histone To the Editor: Strong association of the extended major structure and function has also been found in both schizophrenia 3 histocompatibility complex (xMHC) region on human patients and their siblings. MRPS18B encodes ribosomal protein chromosome 6 with schizophrenia has been supported by a that helps in mitochondrial protein synthesis. TUBB encodes number of genome-wide association studies.1 However, since tubulin that is the major constituent of microtubules. Altered the xMHC region is featured by numerous polymorphisms, expression of TUBB has been reported in a previous microarray 4 dense gene clusters, and strong linkage disequilibrium, it is study in schizophrenia patients. ABCF1 and BTN3A3 are difficult to attribute the association to specific genes. A targeted immune-related genes. BTN3A3 is involved in T-cell activity scrutinization of gene expression in the xMHC region can in adaptive immune response. ABCF1 enhances protein provide valuable candidate genes for future validation. Here synthesis and promotes inflammation. Decreased expression we utilize 2 real-time polymerase chain reaction (PCR)–based of ABCF1 had been found in the whole blood of patients with platforms and 2 sample sets to investigate protein-coding gene schizophrenia and identified as a hub gene in a gene expressional 5 expressions in the xMHC region in peripheral blood leukocytes subnetwork. -
Genomic Approaches to Dissect Innate Immune Pathways
Genomic Approaches to Dissect Innate Immune Pathways The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Lee, Mark N. 2012. Genomic Approaches to Dissect Innate Immune Pathways. Doctoral dissertation, Harvard University. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10403683 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA © 2012 – Mark N. Lee All rights reserved Dissertation Advisor: Dr. Nir Hacohen Mark N. Lee Genomic approaches to dissect innate immune pathways Abstract The innate immune system is of central importance to the early containment of infection. When receptors of innate immunity recognize molecular patterns on pathogens, they initiate an immediate immune response by inducing the expression of cytokines and other host defense genes. Altered expression or function of the receptors, the molecules that mediate the signal transduction cascade, or the cytokines themselves can predispose individuals to infectious or autoimmune diseases. Here we used genomic approaches to uncover novel components underlying the innate immune response to cytosolic DNA and to characterize variation in the innate immune responses of human dendritic cells to bacterial and viral ligands. In order to identify novel genes involved in the cytosolic DNA sensing pathway, we first identified candidate proteins that interact with known signaling molecules or with dsDNA in the cytoplasm. We then knocked down 809 proteomic, genomic, or domain-based candidates in a high-throughput siRNA screen and measured cytokine production after DNA stimulation. -
Identification and Functional Analysis of Five Genes That Encode Distinct Isoforms of Protein Phosphatase 1 in Nilaparvata Lugens
www.nature.com/scientificreports OPEN Identifcation and functional analysis of fve genes that encode distinct isoforms of protein phosphatase 1 in Nilaparvata lugens Weixia Wang1, Tingheng Zhu2*, Fengxiang Lai1, Pinjun Wan1, Qi Wei1 & Qiang Fu1* Ten distinct cDNAs encoding fve diferent protein phosphatases 1 (PPP1) were cloned from Nilaparvata lugens. NlPPP1α and NlPPP1β are highly conserved whereas NlPPP1-Y, NlPPP1-Y1 and NlPPP1-Y2 are lowly conserved among insects. NlPPP1α and NlPPP1β exhibited a ubiquitous expression, while NlPPP1-Y, NlPPP1-Y1, and NlPPP1-Y2 were obviously detected from the 4th instar nymph to imago developmental stages in males, especially detected in internal reproductive organ and fat bodies of the male. Injection nymphs with dsRNA of NlPPP1α or NlPPP1β was able to reduce the target gene expression in a range of 71.5–91.0%, inducing a maximum mortality rate of 95.2% or 97.2% at 10th day after injection and eclosion ratio down by 65.5–100.0%. Injection with dsNlPPP1Ys targeted to NlPPP1-Y, NlPPP1-Y1and NlPPP1-Y2 was able to induce a maximum mortality rate of 95.5% at 10th day after injection, eclosion ratio down by 86.4%. Knock-down one of the male-biased NlPPP1 genes has no efect on survival and eclosion ratio. Injection of 4th instar nymph with dsNlPPP1Ys led to reduced oviposition amount and hatchability, down by 44.7% and 19.6% respectively. Knock-down of NlPPP1-Y1 or NlPPP1-Y2 gene did not signifcantly afect oviposition amount but signifcantly afected hatchability. The results indicate that the male-biased NlPPP1 genes have overlapping functions in N. -
RNA-Seq Reveals Conservation of Function Among the Yolk Sacs Of
RNA-seq reveals conservation of function among the PNAS PLUS yolk sacs of human, mouse, and chicken Tereza Cindrova-Daviesa, Eric Jauniauxb, Michael G. Elliota,c, Sungsam Gongd,e, Graham J. Burtona,1, and D. Stephen Charnock-Jonesa,d,e,1,2 aCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, United Kingdom; bElizabeth Garret Anderson Institute for Women’s Health, Faculty of Population Health Sciences, University College London, London, WC1E 6BT, United Kingdom; cSt. John’s College, University of Cambridge, Cambridge, CB2 1TP, United Kingdom; dDepartment of Obstetrics and Gynaecology, University of Cambridge, Cambridge, CB2 0SW, United Kingdom; and eNational Institute for Health Research, Cambridge Comprehensive Biomedical Research Centre, Cambridge, CB2 0QQ, United Kingdom Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved May 5, 2017 (received for review February 14, 2017) The yolk sac is phylogenetically the oldest of the extraembryonic yolk sac plays a critical role during organogenesis (3–5, 8–10), membranes. The human embryo retains a yolk sac, which goes there are limited data to support this claim. Obtaining experi- through primary and secondary phases of development, but its mental data for the human is impossible for ethical reasons, and importance is controversial. Although it is known to synthesize thus we adopted an alternative strategy. Here, we report RNA proteins, its transport functions are widely considered vestigial. sequencing (RNA-seq) data derived from human and murine yolk Here, we report RNA-sequencing (RNA-seq) data for the human sacs and compare them with published data from the yolk sac of and murine yolk sacs and compare those data with data for the the chicken. -
Organization of the Class I Region of the Bovine Major
ORGANIZATION OF THE CLASS I REGION OF THE BOVINE MAJOR HISTOCOMPATIBILITY COMPLEX (BOLA) AND THE CHARACTERIZATION OF A CLASS I FRAMESHIFT DELETION (BOLA-Adel) PREVALENT IN FERAL BOVIDS A Dissertation by NICOLE RAMLACHAN Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY December 2004 Major Subject: Genetics ORGANIZATION OF THE CLASS I REGION OF THE BOVINE MAJOR HISTOCOMPATIBILITY COMPLEX (BOLA) AND THE CHARACTERIZATION OF A CLASS I FRAMESHIFT DELETION (BOLA-Adel) PREVALENT IN FERAL BOVIDS A Dissertation by NICOLE RAMLACHAN Submitted to Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved as to style and content by: _________________________ _________________________ Loren C. Skow Bhanu P. Chowdhary (Chair of Committee) (Member) _________________________ _________________________ James E. Womack Rajesh C. Miranda (Member) (Member) _________________________ _________________________ Geoffrey M. Kapler Evelyn Tiffany-Castiglioni (Chair of Genetics Faculty) (Head of Department) December 2004 Major Subject: Genetics iii ABSTRACT Organization of the Class I Region of the Bovine Major Histocompatibility Complex (BoLA) and the Characterization of a Class I Frameshift Deletion (BoLA-Adel) Prevalent in Feral Bovids. (December 2004) Nicole Ramlachan, B.Sc., University of Guelph, Ontario, Canada; M.Sc., University of Guelph, Ontario, Canada Chair of Advisory Committee: Dr. Loren Skow The major histocompatibility complex (MHC) is a genomic region containing genes of immunomodulatory importance. MHC class I genes encode cell-surface glycoproteins that present peptides to circulating T cells, playing a key role in recognition of self and non-self. Studies of MHC loci in vertebrates have examined levels of polymorphism and molecular evolutionary processes generating diversity.