HOOK3 Is a Scaffold for the Opposite-Polarity Microtubule-Based
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PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
Product Datasheet KIF1C Antibody NB100-57510
Product Datasheet KIF1C Antibody NB100-57510 Unit Size: 0.1 ml Store at 4C. Do not freeze. Reviews: 1 Publications: 1 Protocols, Publications, Related Products, Reviews, Research Tools and Images at: www.novusbio.com/NB100-57510 Updated 3/16/2021 v.20.1 Earn rewards for product reviews and publications. Submit a publication at www.novusbio.com/publications Submit a review at www.novusbio.com/reviews/destination/NB100-57510 Page 1 of 3 v.20.1 Updated 3/16/2021 NB100-57510 KIF1C Antibody Product Information Unit Size 0.1 ml Concentration 0.2 mg/ml Storage Store at 4C. Do not freeze. Clonality Polyclonal Preservative 0.09% Sodium Azide Isotype IgG Purity Immunogen affinity purified Buffer TBS and 0.1% BSA Product Description Host Rabbit Gene ID 10749 Gene Symbol KIF1C Species Human, Mouse Immunogen The immunogen recognized by this antibody maps to a region between residue 1053 and the C-terminus (residue 1103) of human kinesin family member 1C (lethal toxin sensitivity 1) using the numbering given in entry NP_006603.2 (GeneID 10749). Product Application Details Applications Western Blot, Immunoprecipitation Recommended Dilutions Western Blot 1:2000-1:10000, Immunoprecipitation 2 - 5 ug/mg lysate Page 2 of 3 v.20.1 Updated 3/16/2021 Images Western Blot: KIF1C Antibody [NB100-57510] - KIF1C is a novel HOOK3 -interacting protein.sfGFP-3xFLAG and full length (FL) HOOK3, HOOK3 (1-552), and HOOK3 (553-718) all tagged with sfGFP and 3xFLAG were immunoprecipitated with alpha-FLAG antibodies from transiently transfected HEK-293T cells. Western blots with alpha-HC, alpha- FAM160A2, alpha-KIF1C, and alpha-FLAG antibodies were used to determine which proteins co-immunoprecipitated with each HOOK3 construct.DOI:http://dx.doi.org/10.7554/eLife.28257.015 Image collected and cropped by CiteAb from the following publication (https://elifesciences.org/articles/28257), licensed under a CC-BY licence. -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
047605V1.Full.Pdf
bioRxiv preprint doi: https://doi.org/10.1101/047605; this version posted April 8, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Assembly and Activation of Dynein-Dynactin by the Cargo Adaptor Protein Hook3 Courtney M. Schroeder1,2 and Ronald D. Vale1,2 1The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA 2Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA. Corresponding Author: Ronald D. Vale Dept. of Cellular and Molecular Pharmacology University of California, San Francisco Genentech Hall, MC 2200, Room N312A 600-16th Street San Francisco, CA 94158-2517 E-mail: [email protected] Phone: 415-476-6380 Fax: 415-514-4412 bioRxiv preprint doi: https://doi.org/10.1101/047605; this version posted April 8, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 2 Abstract Metazoan cytoplasmic dynein moves processively along microtubules with the aid of dynactin and an adaptor protein that joins dynein and dynactin into a stable ternary complex. Here, we have examined how Hook3, a cargo adaptor involved in Golgi and endosome transport, forms a motile dynein-dynactin complex. We show that the conserved Hook domain interacts directly with the dynein light intermediate chain 1 (LIC1). -
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. -
Evidence for Differential Alternative Splicing in Blood of Young Boys With
Stamova et al. Molecular Autism 2013, 4:30 http://www.molecularautism.com/content/4/1/30 RESEARCH Open Access Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders Boryana S Stamova1,2,5*, Yingfang Tian1,2,4, Christine W Nordahl1,3, Mark D Shen1,3, Sally Rogers1,3, David G Amaral1,3 and Frank R Sharp1,2 Abstract Background: Since RNA expression differences have been reported in autism spectrum disorder (ASD) for blood and brain, and differential alternative splicing (DAS) has been reported in ASD brains, we determined if there was DAS in blood mRNA of ASD subjects compared to typically developing (TD) controls, as well as in ASD subgroups related to cerebral volume. Methods: RNA from blood was processed on whole genome exon arrays for 2-4–year-old ASD and TD boys. An ANCOVA with age and batch as covariates was used to predict DAS for ALL ASD (n=30), ASD with normal total cerebral volumes (NTCV), and ASD with large total cerebral volumes (LTCV) compared to TD controls (n=20). Results: A total of 53 genes were predicted to have DAS for ALL ASD versus TD, 169 genes for ASD_NTCV versus TD, 1 gene for ASD_LTCV versus TD, and 27 genes for ASD_LTCV versus ASD_NTCV. These differences were significant at P <0.05 after false discovery rate corrections for multiple comparisons (FDR <5% false positives). A number of the genes predicted to have DAS in ASD are known to regulate DAS (SFPQ, SRPK1, SRSF11, SRSF2IP, FUS, LSM14A). In addition, a number of genes with predicted DAS are involved in pathways implicated in previous ASD studies, such as ROS monocyte/macrophage, Natural Killer Cell, mTOR, and NGF signaling. -
Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer
Supplementary Materials: Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer Marcos Díaz-Gay, Sebastià Franch-Expósito, Coral Arnau-Collell, Solip Park, Fran Supek, Jenifer Muñoz, Laia Bonjoch, Anna Gratacós-Mulleras, Paula A. Sánchez-Rojas, Clara Esteban-Jurado, Teresa Ocaña, Miriam Cuatrecasas, Maria Vila-Casadesús, Juan José Lozano, Genis Parra, Steve Laurie, Sergi Beltran, EPICOLON Consortium, Antoni Castells, Luis Bujanda, Joaquín Cubiella, Francesc Balaguer and Sergi Castellví-Bel 100 80 10x ≥ age r 60 egions with cove r 40 ed r % of sha 20 0 I140 H458 H460 H461 H466 H468 H469 H470 FAM1 FAM3 FAM4 FAM19 FAM20 FAM22 FAM23 FAMN1 FAMN3 FAMN4 Families Figure S1. Histogram representing the percentage of genomic regions with a high-quality value of coverage (≥10×) with respect to all shared sequenced regions for each of the germline-tumor paired samples. Horizontal red line indicates sample filtering threshold (≥70% of shared regions with coverage above 10×). Figure S2. Pedigrees of the 18 families included in the study. Sample selected for germline and tumor whole-exome sequencing is indicated with an arrow. Filled symbols indicate affected for colorectal cancer (upper right quarter), adenoma/s (lower right quarter), gynecological cancer (ovary, uterine or breast cancer) (upper left quarter) and liver, stomach or pancreatic cancer (lower left quarter). Other cancer types are indicated in text with no symbol. IDs from samples undergoing germline whole-exome sequencing are also shown. AA/on-AA, advanced adenoma/non-advanced adenoma. Table S1. Description of germline copy number variants detected after calling with CoNIFER and ExomeDepth. -
S41467-020-18249-3.Pdf
ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible. -
RNA Editing at Baseline and Following Endoplasmic Reticulum Stress
RNA Editing at Baseline and Following Endoplasmic Reticulum Stress By Allison Leigh Richards A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Human Genetics) in The University of Michigan 2015 Doctoral Committee: Professor Vivian G. Cheung, Chair Assistant Professor Santhi K. Ganesh Professor David Ginsburg Professor Daniel J. Klionsky Dedication To my father, mother, and Matt without whom I would never have made it ii Acknowledgements Thank you first and foremost to my dissertation mentor, Dr. Vivian Cheung. I have learned so much from you over the past several years including presentation skills such as never sighing and never saying “as you can see…” You have taught me how to think outside the box and how to create and explain my story to others. I would not be where I am today without your help and guidance. Thank you to the members of my dissertation committee (Drs. Santhi Ganesh, David Ginsburg and Daniel Klionsky) for all of your advice and support. I would also like to thank the entire Human Genetics Program, and especially JoAnn Sekiguchi and Karen Grahl, for welcoming me to the University of Michigan and making my transition so much easier. Thank you to Michael Boehnke and the Genome Science Training Program for supporting my work. A very special thank you to all of the members of the Cheung lab, past and present. Thank you to Xiaorong Wang for all of your help from the bench to advice on my career. Thank you to Zhengwei Zhu who has helped me immensely throughout my thesis even through my panic. -
Variation in Protein Coding Genes Identifies Information
bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number. -
Maternal Diabetes and Obesity Influence the Fetal Epigenome in a Largely Hispanic Population Heather E
Rizzo et al. Clinical Epigenetics (2020) 12:34 https://doi.org/10.1186/s13148-020-0824-9 RESEARCH Open Access Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population Heather E. Rizzo1, Elia N. Escaname2,3, Nicholas B. Alana1,3, Elizabeth Lavender2,3, Jonathan Gelfond3 , Roman Fernandez3, Matthew A. Hibbs1, Jonathan M. King1*, Nicholas R. Carr4 and Cynthia L. Blanco2,3 Abstract Background: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. Methods: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. Results: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. -
Breakpoint Characterization of the Der(19)T(11;19)(Q13;P13) in the Ovarian Cancer Cell Line SKOV-3
GENES, CHROMOSOMES & CANCER 52:512–522 (2013) Breakpoint Characterization of the der(19)t(11;19)(q13;p13) in the Ovarian Cancer Cell Line SKOV-3 Wiebke Onkes,1 Regina Fredrik,1 Francesca Micci,2,3 Benjamin J Scho¨nbeck,4 Jose I Martin-Subero,5 Reinhard Ullmann,6 Felix Hilpert,1 Karen Bra¨utigam,7 Ottmar Janssen,4 Nicolai Maass,7 Reiner Siebert,8 Sverre Heim,2,3 Norbert Arnold,1 and Jo¨rg Weimer1* 1Department of Obstetrics and Gynaecology,University Medical Center Schleswig-Holstein, Christian-Albrechts University,Kiel, Germany 2Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 3Centre for Cancer Biomedicine, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway 4Molecular Immunology,Institute of Immunology,University Medical Center Schleswig-Holstein, Kiel,Germany 5Department of Anatomic Pathology,Pharmacology and Microbiology,University of Barcelona, Barcelona, Spain 6Department Human Molecular Genetics, Max Planck Institute for Molecular Genetics,14195 Berlin, Germany 7Department of Gynecology and Obstetrics, University Medical Center RWTH, Aachen, Germany 8Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel/ University Kiel,Germany About 20% of ovarian carcinomas show alterations of 19p13 and/or 19q13 in the form of added extra material whose ori- gin often is from chromosome 11. Based on earlier spectral karyotype analysis of the ovarian cancer cell line SKOV-3, which shows an unbalanced translocation der(19)t(11;19), the aim of this study was to determine the precise breakpoints of that derivative chromosome. After rough delimitation of the breakpoints of microdissected derivative chromosomes by array analysis, we designed a matrix of primers spanning 11q13.2 and 19p13.2 detecting multiple amplicons on genomic and cDNA.