Protein Phosphatase 2A, Complement Component 4, and APOE Genotype Linked To
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Deregulated Gene Expression Pathways in Myelodysplastic Syndrome Hematopoietic Stem Cells
Leukemia (2010) 24, 756–764 & 2010 Macmillan Publishers Limited All rights reserved 0887-6924/10 $32.00 www.nature.com/leu ORIGINAL ARTICLE Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells A Pellagatti1, M Cazzola2, A Giagounidis3, J Perry1, L Malcovati2, MG Della Porta2,MJa¨dersten4, S Killick5, A Verma6, CJ Norbury7, E Hellstro¨m-Lindberg4, JS Wainscoat1 and J Boultwood1 1LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK; 2Department of Hematology Oncology, University of Pavia Medical School, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Medizinische Klinik II, St Johannes Hospital, Duisburg, Germany; 4Division of Hematology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK; 6Albert Einstein College of Medicine, Bronx, NY, USA and 7Sir William Dunn School of Pathology, University of Oxford, Oxford, UK To gain insight into the molecular pathogenesis of the the World Health Organization.6,7 Patients with refractory myelodysplastic syndromes (MDS), we performed global gene anemia (RA) with or without ringed sideroblasts, according to expression profiling and pathway analysis on the hemato- poietic stem cells (HSC) of 183 MDS patients as compared with the the French–American–British classification, were subdivided HSC of 17 healthy controls. The most significantly deregulated based on the presence or absence of multilineage dysplasia. In pathways in MDS include interferon signaling, thrombopoietin addition, patients with RA with excess blasts (RAEB) were signaling and the Wnt pathways. Among the most signifi- subdivided into two categories, RAEB1 and RAEB2, based on the cantly deregulated gene pathways in early MDS are immuno- percentage of bone marrow blasts. -
Psychostimulant-Regulated Plasticity in Interneurons of the Nucleus Accumbens
Psychostimulant-Regulated Plasticity in Interneurons of the Nucleus Accumbens by David A. Gallegos Department of Neurobiology Duke University Date:_______________________ Approved: ___________________________ Anne E. West, Supervisor ___________________________ Jorg Grandl ___________________________ Debra Silver ___________________________ Gregory Crawford ___________________________ Hiro Matsunami Psychostimulant-Regulated Epigenetic Plasticity in Interneurons of the Nucleus Accumbens submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Neurobiology in the Graduate School of Duke University 2019 ABSTRACT Psychostimulant-Regulated Epigenetic Plasticity in Interneurons of the Nucleus Accumbens by David A. Gallegos Department of Neurobiology Duke University Date:_______________________ Approved: ___________________________ Anne E. West, Supervisor ___________________________ Jorg Grandl ___________________________ Debra Silver ___________________________ Gregory Crawford ___________________________ Hiro Matsunami An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Neurobiology in the Graduate School of Duke University 2019 Copyright by David Andres Gallegos 2019 Abstract Exposure to psychostimulant drugs of abuse exerts lasting influences on brain function via the regulation of immediate and persistent gene transcription. These changes in gene transcription drive the development of addictive-like -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Molecular Effects of Isoflavone Supplementation Human Intervention Studies and Quantitative Models for Risk Assessment
Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis committee Promotors Prof. Dr Pieter van ‘t Veer Professor of Nutritional Epidemiology Wageningen University Prof. Dr Evert G. Schouten Emeritus Professor of Epidemiology and Prevention Wageningen University Co-promotors Dr Anouk Geelen Assistant professor, Division of Human Nutrition Wageningen University Dr Lydia A. Afman Assistant professor, Division of Human Nutrition Wageningen University Other members Prof. Dr Jaap Keijer, Wageningen University Dr Hubert P.J.M. Noteborn, Netherlands Food en Consumer Product Safety Authority Prof. Dr Yvonne T. van der Schouw, UMC Utrecht Dr Wendy L. Hall, King’s College London This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. Dr M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Friday 20 June 2014 at 13.30 p.m. in the Aula. Vera van der Velpen Molecular effects of isoflavone supplementation: Human intervention studies and quantitative models for risk assessment 154 pages PhD thesis, Wageningen University, Wageningen, NL (2014) With references, with summaries in Dutch and English ISBN: 978-94-6173-952-0 ABSTRact Background: Risk assessment can potentially be improved by closely linked experiments in the disciplines of epidemiology and toxicology. -
CSE642 Final Version
Eindhoven University of Technology MASTER Dimensionality reduction of gene expression data Arts, S. Award date: 2018 Link to publication Disclaimer This document contains a student thesis (bachelor's or master's), as authored by a student at Eindhoven University of Technology. Student theses are made available in the TU/e repository upon obtaining the required degree. The grade received is not published on the document as presented in the repository. The required complexity or quality of research of student theses may vary by program, and the required minimum study period may vary in duration. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain Eindhoven University of Technology MASTER THESIS Dimensionality Reduction of Gene Expression Data Author: S. (Sako) Arts Daily Supervisor: dr. V. (Vlado) Menkovski Graduation Committee: dr. V. (Vlado) Menkovski dr. D.C. (Decebal) Mocanu dr. N. (Nikolay) Yakovets May 16, 2018 v1.0 Abstract The focus of this thesis is dimensionality reduction of gene expression data. I propose and test a framework that deploys linear prediction algorithms resulting in a reduced set of selected genes relevant to a specified case. Abstract In cancer research there is a large need to automate parts of the process of diagnosis, this is mainly to reduce cost, make it faster and more accurate. -
Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen
CLINICAL RESEARCH www.jasn.org Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen Rany M. Salem ,1 Jennifer N. Todd,2,3,4 Niina Sandholm ,5,6,7 Joanne B. Cole ,2,3,4 Wei-Min Chen,8 Darrell Andrews,9 Marcus G. Pezzolesi,10 Paul M. McKeigue,11 Linda T. Hiraki,12 Chengxiang Qiu,13 Viji Nair,14 Chen Di Liao,12 Jing Jing Cao,12 Erkka Valo ,5,6,7 Suna Onengut-Gumuscu,8 Adam M. Smiles,15 Stuart J. McGurnaghan,16 Jani K. Haukka,5,6,7 Valma Harjutsalo,5,6,7,17 Eoin P. Brennan,9 Natalie van Zuydam,18,19 Emma Ahlqvist,20 Ross Doyle,9 Tarunveer S. Ahluwalia ,21 Maria Lajer,21 Maria F. Hughes,9 Jihwan Park,13 Jan Skupien,15 Athina Spiliopoulou,11 Andrew Liu,22 Rajasree Menon,14,23 Carine M. Boustany-Kari,24 Hyun M. Kang,23,25 Robert G. Nelson,26 Ronald Klein,27 Barbara E. Klein,27 Kristine E. Lee ,27 Xiaoyu Gao,28 Michael Mauer,29 Silvia Maestroni,30 Maria Luiza Caramori,29 Ian H. de Boer ,31 Rachel G. Miller,32 Jingchuan Guo ,32 Andrew P. Boright,12 David Tregouet,33,34 Beata Gyorgy,33,34 Janet K. Snell-Bergeon,35 David M. Maahs,36 Shelley B. Bull ,37 Angelo J. Canty,38 Colin N.A. Palmer,39 Lars Stechemesser,40 Bernhard Paulweber,40 Raimund Weitgasser,40,41 Jelizaveta Sokolovska,42 Vita Rovıte,43 Valdis Pırags, 42,44 Edita Prakapiene,45 Lina Radzeviciene,46 Rasa Verkauskiene,46 Nicolae Mircea Panduru,6,47 Leif C. -
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. -
GWAS for Meat and Carcass Traits
G3: Genes|Genomes|Genetics Early Online, published on July 11, 2019 as doi:10.1534/g3.119.400452 GWAS for meat and carcass traits using imputed sequence level genotypes in pooled F2- designs in pigs Clemens Falker-Gieske,*,1,2 Iulia Blaj,†,2 Siegfried Preuß,‡ Jörn Bennewitz,‡ Georg Thaller,† Jens Tetens*,§ *Department of Animal Sciences, Georg-August-University, 37077 Göttingen, Germany. †Institute of Animal Breeding and Husbandry, Kiel University, 24118 Kiel, Germany. ‡Institute of Animal Husbandry and Breeding, University of Hohenheim, 70599 Stuttgart, Germany. §Center for Integrated Breeding Research, Georg-August-University, 37077 Göttingen, Germany. 1 © The Author(s) 2013. Published by the Genetics Society of America. Running title: Sequence level GWAS in pooled F2 pigs Keywords Genome wide association study Whole genome sequencing Imputation Meat, carcass, and production traits Variant calling 1Corresponding author: Clemens Falker-Gieske, Georg-August-University Goettingen, Department of Animal Sciences, Division Functional Breeding, Burckhardtweg 2, 37077 Goettingen, (+49) 551-39-23669 2contributed equally. 2 ABSTRACT In order to gain insight into the genetic architecture of economically important traits in pigs and to derive suitable genetic markers to improve these traits in breeding programs, many studies have been conducted to map quantitative trait loci. Shortcomings of these studies were low mapping resolution, large confidence intervals for quantitative trait loci-positions and large linkage disequilibrium blocks. Here, we overcome these shortcomings by pooling four large F2 designs to produce smaller linkage disequilibrium blocks and by resequencing the founder generation at high coverage and the F1 generation at low coverage for subsequent imputation of the F2 generation to whole genome sequencing marker density. -
SUPPLEMENTARY METHODS DNA Sequencing and Variant
Supplementary material J Med Genet SUPPLEMENTARY METHODS DNA sequencing and variant identification Genomic DNA was isolated from peripheral blood lymphocytes following standard procedures. Subsequently, exome enrichment was performed using the Agilent SureSelect Human All Exome V5 kit according to the manufacturer’s protocols. Exome sequencing was performed on an Illumina HiSeq system by BGI Europe (Copenhagen, Denmark). Read mapping along the hg19 reference genome (GRCh37/hg19) and variant calling were performed using BWA V.0.78(1) and GATK HaplotypeCaller V.3.3(2). A coverage of >20 reads was reached for 85.1% to 97.8% of the enriched regions. For variant annotation an in-house developed annotation and variant evaluation pipeline was used. For sequencing data of family W97-056, CNV detection was performed using CoNIFER V.0.2.2.(3) Genome sequencing was performed by BGI (Hong Kong, China) on a BGISeq500 using a 2x 100 bp paired end module, with a minimal median coverage of 30-fold per genome. Structural variants were called using Manta V.1.1.0(4) and CNVs using Control-FREEC.(5) Variants were validated and visualized using the IGV Software (V.2.4).(6) In the index case of family W08-1421, targeted DNA sequencing was performed using MIP sequencing.(7) MIPs were designed covering exons and exon-intron boundaries of a panel of 89 HL genes (Supplementary Table 6). Sequencing and data analysis were performed as previously described.(8) For each targeted region, an average coverage of 420 reads was obtained. A coverage of >20 reads was reached for 85.4% of the MIPs. -
Genome-Wide Association and Trans-Ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)
RESEARCH ARTICLE Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND) Sudha K. Iyengar1☯*, John R. Sedor2,3☯*, Barry I. Freedman4☯*, W. H. Linda Kao5†, Matthias Kretzler6, Benjamin J. Keller6, Hanna E. Abboud7†, Sharon G. Adler8, Lyle G. Best9, Donald W. Bowden10, Allison Burlock6, Yii-Der Ida Chen11, Shelley A. Cole12, Mary E. Comeau13, Jeffrey M. Curtis14, Jasmin Divers13, Christiane Drechsler15, Ravi Duggirala12, Robert C. Elston1, Xiuqing Guo11, Huateng Huang16, Michael Marcus Hoffmann17, Barbara V. Howard18, Eli Ipp19, Paul L. Kimmel20, Michael J. Klag21, William C. Knowler14, Orly F. Kohn22, Tennille S. Leak6, David J. Leehey23, Man Li24, Alka Malhotra14, Winfried März25, Viji Nair6, Robert G. Nelson14, Susanne B. Nicholas26, Stephen J. O’Brien27, Madeleine V. Pahl28, Rulan S. Parekh29, Marcus G. Pezzolesi30, Rebekah S. Rasooly31, Charles N. Rotimi32, Jerome I. Rotter11, Jeffrey R. Schelling2, Michael F. Seldin33, Vallabh O. Shah34, Adam M. Smiles35, Michael W. Smith36, Kent D. Taylor11, Farook Thameem37¤, Denyse P. Thornley-Brown38, Barbara J. Truitt1, OPEN ACCESS Christoph Wanner39, E. Jennifer Weil14, Cheryl A. Winkler40, Philip G. Zager41, Robert P. Igo, Jr1‡, Robert L. Hanson14‡, Carl D. Langefeld11‡, Family Investigation of Citation: Iyengar SK, Sedor JR, Freedman BI, Kao Nephropathy and Diabetes (FIND)¶ WHL, Kretzler M, Keller BJ, et al. (2015) Genome- Wide Association and Trans-ethnic Meta-Analysis for 1 Department of Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio, Advanced Diabetic Kidney Disease: Family United States of America, 2 Departments of Medicine, Case Western Reserve University, Cleveland, Ohio, Investigation of Nephropathy and Diabetes (FIND). -
Meta-Analysis of Gene Signatures and Key Pathways Indicates
www.nature.com/scientificreports OPEN Meta‑analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo‑resistance in AML Parastoo Modarres1, Farzaneh Mohamadi Farsani1,3, Amir Abas Nekouie2 & Sadeq Vallian1* The pathways and robust deregulated gene signatures involved in AML chemo‑resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo‑resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify signifcantly diferentially expressed genes between chemo‑resistance and chemo‑sensitive groups. Functional and pathway enrichment analysis of diferentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be diferentially expressed in the chemo‑ resistance compared to the chemo‑sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll‑like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro‑apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug‑resistance development in AML. Acute myeloid leukemia (AML) is one of the most aggressive, life-threatening hematological malignancies char- acterized by uncontrolled proliferation of abnormal diferentiated and nonfunctional myeloid precursor cells1. -
Temporal Proteomic Analysis of HIV Infection Reveals Remodelling of The
1 1 Temporal proteomic analysis of HIV infection reveals 2 remodelling of the host phosphoproteome 3 by lentiviral Vif variants 4 5 Edward JD Greenwood 1,2,*, Nicholas J Matheson1,2,*, Kim Wals1, Dick JH van den Boomen1, 6 Robin Antrobus1, James C Williamson1, Paul J Lehner1,* 7 1. Cambridge Institute for Medical Research, Department of Medicine, University of 8 Cambridge, Cambridge, CB2 0XY, UK. 9 2. These authors contributed equally to this work. 10 *Correspondence: [email protected]; [email protected]; [email protected] 11 12 Abstract 13 Viruses manipulate host factors to enhance their replication and evade cellular restriction. 14 We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a 15 comprehensive time course analysis of >6,500 viral and cellular proteins during HIV 16 infection. To enable specific functional predictions, we categorized cellular proteins regulated 17 by HIV according to their patterns of temporal expression. We focussed on proteins depleted 18 with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be 19 necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the 20 B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). 21 Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent 22 hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. 23 The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral 2 24 lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and 25 conserved Vif function.