Multivariate Gene Expression Analysis Reveals Functional Connectivity
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Genomic Variants Reveal Differential Evolutionary Constraints on Human Transglutaminases and Point Towards Unrecognized Significance of Transglutaminase 2
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Debrecen Electronic Archive RESEARCH ARTICLE Genomic variants reveal differential evolutionary constraints on human transglutaminases and point towards unrecognized significance of transglutaminase 2 Kiruphagaran Thangaraju1, RoÂbert KiraÂly1, MaÂte A. DemeÂny1, JaÂnos AndraÂs MoÂtyaÂn1, a1111111111 Mo nika Fuxreiter1,2, LaÂszlo FeÂsuÈs1,3* a1111111111 a1111111111 1 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, a1111111111 Debrecen, Hungary, 2 MTA-DE Momentum Laboratory of Protein Dynamics, Faculty of Medicine, University a1111111111 of Debrecen, Debrecen, Hungary, 3 MTA-DE Stem cell, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary * [email protected] OPEN ACCESS Abstract Citation: Thangaraju K, KiraÂly R, DemeÂny MA, AndraÂs MoÂtyaÂn J, Fuxreiter M, FeÂsuÈs L (2017) Transglutaminases (TGMs) catalyze Ca2+-dependent transamidation of proteins with speci- Genomic variants reveal differential evolutionary constraints on human transglutaminases and point fied roles in blood clotting (F13a) and in cornification (TGM1, TGM3). The ubiquitous TGM2 towards unrecognized significance of has well described enzymatic and non-enzymatic functions but in-spite of numerous studies transglutaminase 2. PLoS ONE 12(3): e0172189. its physiological function in humans has not been defined. We compared data on non-syn- doi:10.1371/journal.pone.0172189 onymous single nucleotide variations (nsSNVs) and loss-of-function variants on TGM1-7 Editor: Richard L. Eckert, University of Maryland and F13a from the Exome aggregation consortium dataset, and used computational and School of Medicine, UNITED STATES biochemical analysis to reveal the roles of damaging nsSNVs of TGM2. -
Genes in Eyecare Geneseyedoc 3 W.M
Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease. -
Differential Stromal Reprogramming in Benign and Malignant Naturally Occurring Canine Mammary Tumours Identifies Disease-Promoting Stromal Components
bioRxiv preprint doi: https://doi.org/10.1101/783621; this version posted September 26, 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. Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-promoting stromal components Parisa Amini 1,a, Sina Nassiri 2,a, Alexandra Malbon 3,4 and Enni Markkanen 1,* 1 Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland 2 Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland 3 Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland 4 current address: The Royal (Dick) School of Veterinary Studies and The Roslin Institute Easter Bush Campus, Midlothian, EH25 9RG a these authors contributed equally to the manuscript * Correspondence: [email protected]; ORCID: 0000-0001-7780-8233 Keywords Laser-capture microdissection, canine mammary carcinoma, canine mammary adenoma, breast cancer, tumour stroma, tumour microenvironment Summary statement: RNasequencing-based analysis of stromal reprogramming between benign and malignant naturally occurring canine mammary tumours identifies potential molecular drivers in cancer-associated stroma that support tumour growth and malignancy. Abstract The importance of cancer-associated stroma (CaS) for initiation and progression of cancer is well accepted. However, as stromal changes in benign forms of naturally occurring tumours are poorly understood, it remains unclear how CaS from benign and malignant tumours compare. Spontaneous canine mammary tumours are viewed as excellent models of human mammary carcinomas (mCa). -
A Unique and Specific Interaction Between Αt-Catenin and Plakophilin
2126 Research Article A unique and specific interaction between ␣T-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs Steven Goossens1,2,*, Barbara Janssens1,2,*,‡, Stefan Bonné1,2,§, Riet De Rycke1,2, Filip Braet1,2,¶, Jolanda van Hengel1,2 and Frans van Roy1,2,** 1Department for Molecular Biomedical Research, VIB and 2Department of Molecular Biology, Ghent University, B-9052 Ghent, Belgium *These authors contributed equally to this work ‡Present address: Wiley-VCH, Boschstrasse 12, D-69469 Weinheim, Germany §Present address: Diabetes Research Center, Brussels Free University (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium ¶Present address: Australian Key Centre for Microscopy and Microanalysis, The University of Sydney, NSW 2006, Australia **Author for correspondence (e-mail: [email protected]) Accepted 24 April 2007 Journal of Cell Science 120, 2126-2136 Published by The Company of Biologists 2007 doi:10.1242/jcs.004713 Summary Alpha-catenins play key functional roles in cadherin- desmosomal proteins in the heart localize not only to the catenin cell-cell adhesion complexes. We previously desmosomes in the intercalated discs but also at adhering reported on ␣T-catenin, a novel member of the ␣-catenin junctions with hybrid composition. We found that in the protein family. ␣T-catenin is expressed predominantly in latter junctions, endogenous plakophilin-2 colocalizes with cardiomyocytes, where it colocalizes with ␣E-catenin at the ␣T-catenin. By providing an extra link between the intercalated discs. Whether ␣T- and ␣E-catenin have cadherin-catenin complex and intermediate filaments, the specific or synergistic functions remains unknown. In this binding of ␣T-catenin to plakophilin-2 is proposed to be a study we used the yeast two-hybrid approach to identify means of modulating and strengthening cell-cell adhesion specific functions of ␣T-catenin. -
Appendix 2. Significantly Differentially Regulated Genes in Term Compared with Second Trimester Amniotic Fluid Supernatant
Appendix 2. Significantly Differentially Regulated Genes in Term Compared With Second Trimester Amniotic Fluid Supernatant Fold Change in term vs second trimester Amniotic Affymetrix Duplicate Fluid Probe ID probes Symbol Entrez Gene Name 1019.9 217059_at D MUC7 mucin 7, secreted 424.5 211735_x_at D SFTPC surfactant protein C 416.2 206835_at STATH statherin 363.4 214387_x_at D SFTPC surfactant protein C 295.5 205982_x_at D SFTPC surfactant protein C 288.7 1553454_at RPTN repetin solute carrier family 34 (sodium 251.3 204124_at SLC34A2 phosphate), member 2 238.9 206786_at HTN3 histatin 3 161.5 220191_at GKN1 gastrokine 1 152.7 223678_s_at D SFTPA2 surfactant protein A2 130.9 207430_s_at D MSMB microseminoprotein, beta- 99.0 214199_at SFTPD surfactant protein D major histocompatibility complex, class II, 96.5 210982_s_at D HLA-DRA DR alpha 96.5 221133_s_at D CLDN18 claudin 18 94.4 238222_at GKN2 gastrokine 2 93.7 1557961_s_at D LOC100127983 uncharacterized LOC100127983 93.1 229584_at LRRK2 leucine-rich repeat kinase 2 HOXD cluster antisense RNA 1 (non- 88.6 242042_s_at D HOXD-AS1 protein coding) 86.0 205569_at LAMP3 lysosomal-associated membrane protein 3 85.4 232698_at BPIFB2 BPI fold containing family B, member 2 84.4 205979_at SCGB2A1 secretoglobin, family 2A, member 1 84.3 230469_at RTKN2 rhotekin 2 82.2 204130_at HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2 81.9 222242_s_at KLK5 kallikrein-related peptidase 5 77.0 237281_at AKAP14 A kinase (PRKA) anchor protein 14 76.7 1553602_at MUCL1 mucin-like 1 76.3 216359_at D MUC7 mucin 7, -
Improved Memory and Reduced Anxiety in Δ-Catenin Transgenic Mice T Taeyong Ryua,1, Hyung Joon Parkb,1, Hangun Kimc, Young-Chang Choa, Byeong C
Experimental Neurology 318 (2019) 22–31 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr Research Paper Improved memory and reduced anxiety in δ-catenin transgenic mice T Taeyong Ryua,1, Hyung Joon Parkb,1, Hangun Kimc, Young-Chang Choa, Byeong C. Kimd, ⁎ ⁎⁎ Jihoon Jod, Young-Woo Seoe, Won-Seok Choib, , Kwonseop Kima, a College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea b School of Biological Sciences and Technology, College of Natural Sciences, College of Medicine, Chonnam National University, Gwangju 61186, Republic of Korea c College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon 57922, Republic of Korea d Department of Neurology, Chonnam National University Medical School, Gwnagju 61469, Republic of Korea e Korea Basic Science Institute, Gwangju Center, Gwangju 61186, Republic of Korea ARTICLE INFO ABSTRACT Keywords: δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to δ-Catenin the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about N-cadherin δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not Glutamate receptor been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a Memory transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was Sociability microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N- Anxiety cadherin, β-catenin, and p120-catenin than did wild type mice. -
New Tools for Early Diagnosis of Breast and Genitourinary Cancers
International Journal of Molecular Sciences Review Extracellular Vesicles: New Tools for Early Diagnosis of Breast and Genitourinary Cancers Anna Testa †, Emilio Venturelli † and Maria Felice Brizzi * Department of Medical Sciences, University of Turin, 10126 Turin, Italy; [email protected] (A.T.); [email protected] (E.V.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor. Keywords: oncology; extracellular vesicles; liquid biopsy Citation: Testa, A.; Venturelli, E.; Brizzi, M.F. Extracellular Vesicles: New Tools for Early Diagnosis of 1. Introduction Breast and Genitourinary Cancers. Cancer is a major public health problem representing the second cause of death world- Int. J. Mol. Sci. 22 2021, , 8430. wide after cardiovascular diseases. -
Viewed in Poste and Fidler, 1980) (See Fig
UNIVERSITY OF CINCINNATI _____________December 6 , 20 _____ 00 I,________________________________Randall Glenn Marsh ______________, hereby submit this as part of the requirements for the degree of: ________________________Doctorate of Philosophy (Ph.D.) ________________________ in: ________________________Cell and Molecular Biology ________________________ It is entitled: ________________________Characterization of a new role for plakoglobin________________________ in ________________________suppressing epithelial cell translocation________________________ ________________________________________________ ________________________________________________ Approved by: ________________________Dr. Robert Brackenbury, Ph.D. (Chair) ________________________Dr. Wallace Ip, Ph.D. ________________________Dr. Randal Morris, Ph.D. ________________________Dr. James Greenberg, M.D. ________________________ CHARACTERIZATION OF A NEW ROLE FOR PLAKOGLOBIN IN SUPPRESSING EPITHELIAL CELL TRANSLOCATION A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) in the Department of Cell Biology, Neurobiology, and Anatomy of the College of Medicine 2000 by Randall Glenn Marsh B.Sc., University of Alberta, 1989 M.Sc., University of Alberta, 1992 Committee Chair: Dr. Robert Brackenbury, Ph.D. ii ABSTRACT Despite advances in the treatment of cancer patients, spread, or metastasis, of tumor cells remains a major cause of -
Regulation of the Intermediate Filament Protein Nestin at Rodent Neuromuscular Junctions by Innervation and Activity
5948 • The Journal of Neuroscience, May 30, 2007 • 27(22):5948–5957 Development/Plasticity/Repair Regulation of the Intermediate Filament Protein Nestin at Rodent Neuromuscular Junctions by Innervation and Activity Hyuno Kang,1 Le Tian,1 Young-Jin Son,1 Yi Zuo,1 Diane Procaccino,1 Flora Love,1 Christopher Hayworth,1 Joshua Trachtenberg,1 Michelle Mikesh,1 Lee Sutton,1 Olga Ponomareva,1 John Mignone,2 Grigori Enikolopov,2 Mendell Rimer,1 and Wesley Thompson1 1Section of Neurobiology, Institute of Neuroscience, and Institute for Cell and Molecular Biology, University of Texas, Austin, Texas 78712, and 2Cold Spring Harbor Laboratories, Cold Spring Harbor, New York 11724 The intermediate filament nestin is localized postsynaptically at rodent neuromuscular junctions. The protein forms a filamentous network beneath and between the synaptic gutters, surrounds myofiber nuclei, and is associated with Z-discs adjacent to the junction. In situ hybridization shows that nestin mRNA is synthesized selectively by synaptic myonuclei. Although weak immunoreactivity is present in myelinating Schwann cells that wrap the preterminal axon, nestin is not detected in the terminal Schwann cells (tSCs) that cover the nerve terminal branches. However, after denervation of muscle, nestin is upregulated in tSCs and in SCs within the nerve distal to the lesion site. In contrast, immunoreactivity is strongly downregulated in the muscle fiber. Transgenic mice in which the nestin neural enhancer drives expression of a green fluorescent protein (GFP) reporter show that the regulation in SCs is transcriptional. However, the postsynaptic expression occurs through enhancer elements distinct from those responsible for regulation in SCs. Application of botuli- num toxin shows that the upregulation in tSCs and the loss of immunoreactivity in muscle fibers occurs with blockade of transmitter release. -
Proteomic Profiling of Two Distinct Populations of Extracellular
International Journal of Molecular Sciences Article Proteomic Profiling of Two Distinct Populations of Extracellular Vesicles Isolated from Human Seminal Plasma Xiaogang Zhang 1, Harmjan R. Vos 2 , Weiyang Tao 3 and Willem Stoorvogel 1,* 1 Department of Biomolecular Health Sciences, Faculty of Veterinary Science, Utrecht University, 3584 CM Utrecht, The Netherlands; [email protected] 2 Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center, 3584 CX Utrecht, The Netherlands; [email protected] 3 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, Netherlands; [email protected] * Correspondence: [email protected] Received: 1 September 2020; Accepted: 22 October 2020; Published: 26 October 2020 Abstract: Body fluids contain many populations of extracellular vesicles (EV) that differ in size, cellular origin, molecular composition, and biological activities. EV in seminal plasma are in majority originating from prostate epithelial cells, and hence are also referred to as prostasomes. Nevertheless, EV are also contributed by other accessory sex glands, as well as by the testis and epididymis. In a previous study, we isolated EV from seminal plasma of vasectomized men, thereby excluding contributions from the testis and epididymis, and identified two distinct EV populations with diameters of 50 and 100 nm, respectively. In the current study, we comprehensively analyzed the protein composition of these two EV populations using quantitative Liquid Chromatography-Mass Spectrometry (LC-MS/MS). In total 1558 proteins were identified. Of these, 45% was found only in ≈ the isolated 100 nm EV, 1% only in the isolated 50 nm EV, and 54% in both 100 nm and 50 nm EV. -
Supplementary Information – Postema Et Al., the Genetics of Situs Inversus Totalis Without Primary Ciliary Dyskinesia
1 Supplementary information – Postema et al., The genetics of situs inversus totalis without primary ciliary dyskinesia Table of Contents: Supplementary Methods 2 Supplementary Results 5 Supplementary References 6 Supplementary Tables and Figures Table S1. Subject characteristics 9 Table S2. Inbreeding coefficients per subject 10 Figure S1. Multidimensional scaling to capture overall genomic diversity 11 among the 30 study samples Table S3. Significantly enriched gene-sets under a recessive mutation model 12 Table S4. Broader list of candidate genes, and the sources that led to their 13 inclusion Table S5. Potential recessive and X-linked mutations in the unsolved cases 15 Table S6. Potential mutations in the unsolved cases, dominant model 22 2 1.0 Supplementary Methods 1.1 Participants Fifteen people with radiologically documented SIT, including nine without PCD and six with Kartagener syndrome, and 15 healthy controls matched for age, sex, education and handedness, were recruited from Ghent University Hospital and Middelheim Hospital Antwerp. Details about the recruitment and selection procedure have been described elsewhere (1). Briefly, among the 15 people with radiologically documented SIT, those who had symptoms reminiscent of PCD, or who were formally diagnosed with PCD according to their medical record, were categorized as having Kartagener syndrome. Those who had no reported symptoms or formal diagnosis of PCD were assigned to the non-PCD SIT group. Handedness was assessed using the Edinburgh Handedness Inventory (EHI) (2). Tables 1 and S1 give overviews of the participants and their characteristics. Note that one non-PCD SIT subject reported being forced to switch from left- to right-handedness in childhood, in which case five out of nine of the non-PCD SIT cases are naturally left-handed (Table 1, Table S1). -
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The Role of DHHC5-Mediated Palmitoylation of δ-Catenin in Cadherin Stability and Synapse Plasticity by Gian Stefano Brigidi B.Sc., McGill University, 2007 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Neuroscience) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2014 © Gian Stefano Brigidi, 2014 Abstract Synapses of the Central Nervous System are specialized junctions of cell-cell contact that transmit signals from one neuron to another in a rapid and efficient manner. Synapses are highly plastic structures that can be continually modified in response to fluctuations in neuronal activity. Changes in the number, size, and protein composition of synapses have been observed following alterations in neuronal activity in vitro and following the learning of specific tasks in vivo. Thus, elucidating the molecular mechanisms underlying activity-mediated trafficking of proteins to and from synaptic compartments is essential for our understanding of brain function. Previous work has demonstrated a requirement for the cadherin-adhesion complex in activity-induced enhancements in synapse strength, however the molecular mechanisms that translate synaptic activation into enhanced cadherin-based adhesion and synapse strengthening remain unknown. This dissertation discusses work that unravels how synaptic activity coordinates the enhancement of cadherin surface stabilization, enlargement of dendritic spines, and increased surface insertion of AMPA receptors. This work demonstrates that increased synaptic activity enhances the palmitoylation of a brain-specific component of the cadherin-adhesion complex, δ-catenin, which in turn causes δ-catenin to traffic toward the synaptic membrane in spines where it associates with and stabilizes surface N-cadherin.