Inter-Species Differences in Response to Hypoxia in Ipsc-Derived Cardiomyocytes from Humans and Chimpanzees
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Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
1847.Full-Text.Pdf
Published OnlineFirst January 29, 2016; DOI: 10.1158/0008-5472.CAN-15-1752 Cancer Molecular and Cellular Pathobiology Research RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1-Mediated Destruction Complex to Suppress Tumorigenesis Min-Goo Lee, Seong-In Jeong, Kyung-Phil Ko, Soon-Ki Park, Byung-Kyu Ryu, Ick-Young Kim, Jeong-Kook Kim, and Sung-Gil Chi Abstract RASSF1A is a tumor suppressor implicated in many tumorigenic as Rhotekin. As predicted on this basis, RASSF1A competed with processes; however, the basis for its tumor suppressor functions are Rhotekin to bind RhoA and to block its activation. RASSF1A not fully understood. Here we show that RASSF1A is a novel mutants unable to bind RhoA or Smurf1 failed to suppress antagonist of protumorigenic RhoA activity. Direct interaction RhoA-induced tumor cell proliferation, drug resistance, epitheli- between the C-terminal amino acids (256–277) of RASSF1A and al–mesenchymal transition, migration, invasion, and metastasis. active GTP-RhoA was critical for this antagonism. In addition, Clinically, expression levels of RASSF1A and RhoA were inversely interaction between the N-terminal amino acids (69-82) of correlated in many types of primary and metastatic tumors and RASSF1A and the ubiquitin E3 ligase Smad ubiquitination regu- tumor cell lines. Collectively, our findings showed how RASSF1A latory factor 1 (Smurf1) disrupted GTPase activity by facilitating may suppress tumorigenesis by intrinsically inhibiting the tumor- Smurf1-mediated ubiquitination of GTP-RhoA. We noted that the promoting activity of RhoA, thereby illuminating the potential RhoA-binding domain of RASSF1A displayed high sequence mechanistic consequences of RASSF1A inactivation in many can- homology with Rho-binding motifs in other RhoA effectors, such cers. -
The Landscape of Human Mutually Exclusive Splicing
bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. 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-ND 4.0 International license. The landscape of human mutually exclusive splicing Klas Hatje1,2,#,*, Ramon O. Vidal2,*, Raza-Ur Rahman2, Dominic Simm1,3, Björn Hammesfahr1,$, Orr Shomroni2, Stefan Bonn2§ & Martin Kollmar1§ 1 Group of Systems Biology of Motor Proteins, Department of NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany 2 Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany 3 Theoretical Computer Science and Algorithmic Methods, Institute of Computer Science, Georg-August-University Göttingen, Germany § Corresponding authors # Current address: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland $ Current address: Research and Development - Data Management (RD-DM), KWS SAAT SE, Einbeck, Germany * These authors contributed equally E-mail addresses: KH: [email protected], RV: [email protected], RR: [email protected], DS: [email protected], BH: [email protected], OS: [email protected], SB: [email protected], MK: [email protected] - 1 - bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. 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. -
MAP1S Antibody Rabbit Polyclonal Antibody Catalog # ALS16470
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 MAP1S Antibody Rabbit Polyclonal Antibody Catalog # ALS16470 Specification MAP1S Antibody - Product Information Application IHC Primary Accession Q66K74 Reactivity Human Host Rabbit Clonality Polyclonal Calculated MW 112kDa KDa MAP1S Antibody - Additional Information Gene ID 55201 Human Kidney: Formalin-Fixed, Paraffin-Embedded (FFPE) Other Names Microtubule-associated protein 1S, MAP-1S, BPY2-interacting protein 1, Microtubule-associated protein 8, Variable charge Y chromosome 2-interacting protein 1, VCY2-interacting protein 1, VCY2IP-1, MAP1S heavy chain, MAP1S light chain, MAP1S, BPY2IP1, C19orf5, MAP8, VCY2IP1 Target/Specificity Human MAP1S Reconstitution & Storage Human Testis: Formalin-Fixed, Aliquot and store at -20°C or -80°C. Avoid Paraffin-Embedded (FFPE) freeze-thaw cycles. Precautions MAP1S Antibody - Background MAP1S Antibody is for research use only and not for use in diagnostic or therapeutic Microtubule-associated protein that mediates procedures. aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing MAP1S Antibody - Protein Information center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity). Name MAP1S Synonyms BPY2IP1, C19orf5, MAP8, MAP1S Antibody - References VCY2IP1 Wong E.Y.,et al.Biol. Reprod. Function 70:775-784(2004). Microtubule-associated protein that Ding J.,et al.Biochem. Biophys. Res. Commun. mediates aggregation of mitochondria 339:172-179(2006). resulting in cell death and genomic Ota T.,et al.Nat. Genet. 36:40-45(2004). Page 1/2 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 destruction (MAGD). -
Microtubule-Associated Protein 1B, a Growth-Associated and Phosphorylated Scaffold Protein Beat M
Brain Research Bulletin 71 (2007) 541–558 Review Microtubule-associated protein 1B, a growth-associated and phosphorylated scaffold protein Beat M. Riederer a,b,∗ a D´epartement de Biologie Cellulaire et de Morphologie (DBCM), Universit´e de Lausanne, 9 rue du Bugnon, CH-1005 Lausanne, Switzerland b Centre des Neurosciences Psychiatriques (CNP), Hˆopital Psychiatrique, 1008 Prilly, Switzerland Received 20 October 2006; accepted 28 November 2006 Available online 27 December 2006 Abstract Microtubule-associated protein 1B, MAP1B, is one of the major growth associated and cytoskeletal proteins in neuronal and glial cells. It is present as a full length protein or may be fragmented into a heavy chain and a light chain. It is essential to stabilize microtubules during the elongation of dendrites and neurites and is involved in the dynamics of morphological structures such as microtubules, microfilaments and growth cones. MAP1B function is modulated by phosphorylation and influences microtubule stability, microfilaments and growth cone motility. Considering its large size, several interactions with a variety of other proteins have been reported and there is increasing evidence that MAP1B plays a crucial role in the stability of the cytoskeleton and may have other cellular functions. Here we review molecular and functional aspects of this protein, evoke its role as a scaffold protein and have a look at several pathologies where the protein may be involved. © 2006 Elsevier Inc. All rights reserved. Keywords: Microtubules; Actin; Cytoskeleton; Scaffold; -
Development of Novel Analysis and Data Integration Systems to Understand Human Gene Regulation
Development of novel analysis and data integration systems to understand human gene regulation Dissertation zur Erlangung des Doktorgrades Dr. rer. nat. der Fakult¨atf¨urMathematik und Informatik der Georg-August-Universit¨atG¨ottingen im PhD Programme in Computer Science (PCS) der Georg-August University School of Science (GAUSS) vorgelegt von Raza-Ur Rahman aus Pakistan G¨ottingen,April 2018 Prof. Dr. Stefan Bonn, Zentrum f¨urMolekulare Neurobiologie (ZMNH), Betreuungsausschuss: Institut f¨urMedizinische Systembiologie, Hamburg Prof. Dr. Tim Beißbarth, Institut f¨urMedizinische Statistik, Universit¨atsmedizin, Georg-August Universit¨at,G¨ottingen Prof. Dr. Burkhard Morgenstern, Institut f¨urMikrobiologie und Genetik Abtl. Bioinformatik, Georg-August Universit¨at,G¨ottingen Pr¨ufungskommission: Prof. Dr. Stefan Bonn, Zentrum f¨urMolekulare Neurobiologie (ZMNH), Referent: Institut f¨urMedizinische Systembiologie, Hamburg Prof. Dr. Tim Beißbarth, Institut f¨urMedizinische Statistik, Universit¨atsmedizin, Korreferent: Georg-August Universit¨at,G¨ottingen Prof. Dr. Burkhard Morgenstern, Weitere Mitglieder Institut f¨urMikrobiologie und Genetik Abtl. Bioinformatik, der Pr¨ufungskommission: Georg-August Universit¨at,G¨ottingen Prof. Dr. Carsten Damm, Institut f¨urInformatik, Georg-August Universit¨at,G¨ottingen Prof. Dr. Florentin W¨org¨otter, Physikalisches Institut Biophysik, Georg-August-Universit¨at,G¨ottingen Prof. Dr. Stephan Waack, Institut f¨urInformatik, Georg-August Universit¨at,G¨ottingen Tag der m¨undlichen Pr¨ufung: der 30. M¨arz2018 -
A Network Medicine Approach for Drug Repurposing in Duchenne Muscular Dystrophy
G C A T T A C G G C A T genes Article A Network Medicine Approach for Drug Repurposing in Duchenne Muscular Dystrophy Salvo Danilo Lombardo 1 , Maria Sofia Basile 2 , Rosella Ciurleo 2, Alessia Bramanti 2, Antonio Arcidiacono 3, Katia Mangano 3 , Placido Bramanti 2, Ferdinando Nicoletti 3,* and Paolo Fagone 3 1 Department of Structural & Computational Biology at the Max Perutz Labs, University of Vienna, 1010 Vienna, Austria; [email protected] 2 IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; sofi[email protected] (M.S.B.); [email protected] (R.C.); [email protected] (A.B.); [email protected] (P.B.) 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy; [email protected] (A.A.); [email protected] (K.M.); [email protected] (P.F.) * Correspondence: [email protected] Abstract: Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease caused by a lack of dystrophin, leading to membrane instability, cell damage, and inflammatory response. However, gene-editing alone is not enough to restore the healthy phenotype and additional treat- ments are required. In the present study, we have first conducted a meta-analysis of three microarray datasets, GSE38417, GSE3307, and GSE6011, to identify the differentially expressed genes (DEGs) be- tween healthy donors and DMD patients. We have then integrated this analysis with the knowledge Citation: Lombardo, S.D.; Basile, obtained from DisGeNET and DIAMOnD, a well-known algorithm for drug–gene association discov- M.S.; Ciurleo, R.; Bramanti, A.; eries in the human interactome. -
RASSF6; the Putative Tumor Suppressor of the RASSF Family
Review RASSF6; the Putative Tumor Suppressor of the RASSF Family Hiroaki Iwasa 1, Xinliang Jiang 2 and Yutaka Hata 1,2,* Received: 2 November 2015; Accepted: 1 December 2015; Published: 9 December 2015 Academic Editor: Reinhard Dammann 1 Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; [email protected] 2 Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-3-5803-5164; Fax: +81-3-5803-0121 Abstract: Humans have 10 genes that belong to the Ras association (RA) domain family (RASSF). Among them, RASSF7 to RASSF10 have the RA domain in the N-terminal region and are called the N-RASSF proteins. In contradistinction to them, RASSF1 to RASSF6 are referred to as the C-RASSF proteins. The C-RASSF proteins have the RA domain in the middle region and the Salvador/RASSF/Hippo domain in the C-terminal region. RASSF6 additionally harbors the PSD-95/Discs large/ZO-1 (PDZ)-binding motif. Expression of RASSF6 is epigenetically suppressed in human cancers and is generally regarded as a tumor suppressor. RASSF6 induces caspase-dependent and -independent apoptosis. RASSF6 interacts with mammalian Ste20-like kinases (homologs of Drosophila Hippo) and cross-talks with the Hippo pathway. RASSF6 binds MDM2 and regulates p53 expression. The interactions with Ras and Modulator of apoptosis 1 (MOAP1) are also suggested by heterologous protein-protein interaction experiments. RASSF6 regulates apoptosis and cell cycle through these protein-protein interactions, and is implicated in the NF-κB and JNK signaling pathways. -
The Cpg Island of the Novel Tumor Suppressor Gene RASSF1A Is Intensely Methylated in Primary Small Cell Lung Carcinomas
Oncogene (2001) 20, 3563 ± 3567 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc SHORT REPORTS The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas Reinhard Dammann1, Takashi Takahashi2 and Gerd P Pfeifer*,1 1Department of Biology, Beckman Research Institute, City of Hope Cancer Center, Duarte, California 91010, USA; 2Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan Loss of heterozygosity at 3p21.3 occurs in more than genes include the RB gene (13q), the p53 gene (17p), 90% of small cell lung carcinomas (SCLCs). The Ras and the p16 CDK inhibitor gene (9p). association domain family 1 (RASSF1) gene cloned from Allelic loss at 3p21 is an early event in lung tumor the lung tumor suppressor locus 3p21.3 consists of two pathogenesis, occurs at the stage of hyperplasia/ major alternative transcripts, RASSF1A and RASSF1C. metaplasia (Sundaresan et al., 1992; Hung et al., Epigenetic inactivation of isoform A (RASSF1A) was 1995; Thiberville et al., 1995; Wistuba et al., 1999), observed in 40% of primary non-small cell lung and as such may be critically involved in tumor carcinomas and in several tumor cell lines. Transfection initiation. Cross-sectional examination of individual of RASSF1A suppressed the growth of lung cancer cells NSCLC tumors showed that all portions of the tumor in vitro and in nude mice. Here we have analysed the shared concordant LOH at 3p despite morphological methylation status of the CpG island promoters of diversity (Yatabe et al., 2000). -
University of Groningen on the Elucidation of a Tumour Suppressor
University of Groningen On the elucidation of a tumour suppressor role of 3p in lung cancer Elst, Arja ter IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Elst, A. T. (2006). On the elucidation of a tumour suppressor role of 3p in lung cancer. s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 27-09-2021 Chapter 1 Candidate lung tumour suppressor regions at the short arm of chromosome 3. What evidence is there? Arja ter Elst Charles H.C.M. Buys Department of Medical Genetics, University Medical Center Groningen, Groningen, The Netherlands LUNG CANCER AND THE SHORT ARM OF CHROMOSOME 3 Lung cancer is the leading cause of cancer death among both men and women in the western world. -
RASSF1A-LATS1 Signalling Stabilises Replication Forks by Restricting CDK2
RASSF1A-LATS1 signalling stabilises replication forks by restricting CDK2-mediated phosphorylation of BRCA2 Dafni-Eleftheria Pefani1, Robert Latusek1, Isabel Pires1, Anna M. Grawenda1, Karen S. Yee1, Garth Hamilton1, Louise van der Weyden2, Fumiko Esashi3, Ester M. Hammond1 and Eric O’Neill1* 1CRUK/MRC Oxford Institute, Dept. of Oncology, University of Oxford, Oxford, OX3 7DQ, UK. 2The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK. 3Dunn School of Pathology, South Parks Road, University of Oxford, Oxford, OX1 3RE, UK. Email: [email protected] Tel. 0044 (0) 1865 617321 *corresponding author Word Count: 3,470 Figures 7: comprising 23 panels Supplementary Figures 7: comprising 22 panels Supplementary Figure with uncropped blots 1 Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. BRCA2 has a fundamental role in error-free DNA repair but additionally sustains genome integrity by promoting RAD51 nucleofilament formation at stalled replication forks. CDK2 phosphorylates BRCA2 (pS3291-BRCA2) to limit stabilising contacts with polymerised RAD51, however, how replication stress modulates CDK2 activity and whether loss of pS3291-BRCA2 regulation results in genomic instability of tumours is not known. Here we demonstrate that the hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that LATS1 forms part of an ATR mediated response to replication stress that requires the tumour suppressor RASSF1A. Importantly, perturbation of the ATR-RASSF1A-LATS1 signalling axis leads to genomic defects associated with loss of BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers. -
Changes in the Gene Expression Profile During Spontaneous Migraine Attacks
www.nature.com/scientificreports OPEN Changes in the gene expression profle during spontaneous migraine attacks Lisette J. A. Kogelman1,7*, Katrine Falkenberg1,7, Alfonso Buil2, Pau Erola3, Julie Courraud4, Susan Svane Laursen4, Tom Michoel5, Jes Olesen1 & Thomas F. Hansen1,2,6* Migraine attacks are delimited, allowing investigation of changes during and outside attack. Gene expression fuctuates according to environmental and endogenous events and therefore, we hypothesized that changes in RNA expression during and outside a spontaneous migraine attack exist which are specifc to migraine. Twenty-seven migraine patients were assessed during a spontaneous migraine attack, including headache characteristics and treatment efect. Blood samples were taken during attack, two hours after treatment, on a headache-free day and after a cold pressor test. RNA- Sequencing, genotyping, and steroid profling were performed. RNA-Sequences were analyzed at gene level (diferential expression analysis) and at network level, and genomic and transcriptomic data were integrated. We found 29 diferentially expressed genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specifc genes, that were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed mechanisms afected by changes in gene interactions, e.g. ‘ion transmembrane transport’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’. In conclusion, we uniquely investigated intra-individual changes in gene expression during a migraine attack. We revealed both genes and pathways potentially involved in the pathophysiology of migraine and/or migraine treatment. With a world-wide prevalence of 14.4% and global estimates of 5.6 years lost to disability, migraine is placed as the 2nd most disabling disease by the World Health Organization 1.