Genes Involved and Proteins
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Dissertation Philip Böhler
Three Tales of Death: New Pathways in the Induction, Inhibition and Execution of Apoptosis Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf vorgelegt von Philip Böhler aus Bonn Düsseldorf, Juni 2019 aus dem Institut für Molekulare Medizin I der Heinrich-Heine-Universität Düsseldorf Gedruckt mit der Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf Berichterstatter: 1. Prof. Dr. Sebastian Wesselborg 2. Prof. Dr. Henrike Heise Tag der mündlichen Prüfung: 29. Oktober 2019 “Where the first primal cell was, there was I also. Where man is, there am I. When the last life crawls under freezing stars, there will I be.” — DEATH, in: Mort, by Terry Pratchett “Right away I found out something about biology: it was very easy to find a question that was very interesting, and that nobody knew the answer to.” — Richard Feynman, in: Surely You're Joking, Mr. Feynman! Acknowledgements (Danksagung) Acknowledgements (Danksagung) Viele Menschen haben zum Gelingen meiner Forschungsarbeit und dieser Dissertation beigetragen, und nicht alle können hier namentlich erwähnt werden. Dennoch möchte ich einige besonders hervorheben. An erster Stelle möchte ich Professor Sebastian Wesselborg danken, der diese Dissertation als Erstgutachter betreut hat und der mir die Möglichkeit gab, die dazugehörigen experimentellen Arbeiten am Institut für Molekulare Medizin durchzuführen. Er und Professor Björn Stork, dem ich für die herzliche Aufnahme in seine Arbeitsgruppe danke, legten durch die richtige Mischung aus aktiver Förderung und dem Freiraum zur Umsetzung eigener wissenschaftlicher Ideen die ideale Grundlage für die Forschungsprojekte, aus denen diese Dissertation entstand. Professorin Henrike Heise, die sich freundlicherweise zur Betreuung dieser Dissertation als Zweitgutachterin bereiterklärt hat, gilt ebenfalls mein herzlicher Dank. -
Identification of Key Candidate Genes for Colorectal Cancer by Bioinformatics Analysis
ONCOLOGY LETTERS 18: 6583-6593, 2019 Identification of key candidate genes for colorectal cancer by bioinformatics analysis ZHIHUA CHEN1*, YILIN LIN1*, JI GAO2*, SUYONG LIN1, YAN ZHENG1, YISU LIU1 and SHAO QIN CHEN1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University; 2School of Nursing, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China Received December 27, 2018; Accepted August 16, 2019 DOI: 10.3892/ol.2019.10996 Abstract. Colorectal cancer (CRC) is one of the most Introduction common cancers of the digestive tract. Although numerous studies have been conducted to elucidate the cause of CRC, Colorectal cancer (CRC) ranks third (13.5%) and second the exact mechanism of CRC development remains to be (9.5%) among the incidence of malignancies worldwide determined. To identify candidate genes that may be involved in male and female patients, respectively, and is a serious in CRC development and progression, the microarray datasets hazard to human health (1). Previous studies have demon- GSE41657, GSE77953 and GSE113513 were downloaded from strated that the molecular pathogenesis of CRC is mostly the Gene Expression Omnibus database. Gene Ontology and caused by genetic mutations (2,3). Numerous studies over Kyoto Encyclopedia of Genes and Genomes were used for the past two decades have reported that genetic mutations functional enrichment analysis of differentially expressed are associated with the prognosis and treatment of CRC, and genes (DEGs). A protein-protein interaction network was targeted therapies have been developed (4-7). The progres- constructed, and the hub genes were subjected to module sion of CRC is usually accompanied by the activation of the analysis and identification using Search Tool for the Retrieval KRAS and BRAF genes and the inhibition of the p53 tumour of Interacting Genes/Proteins and Cytoscape. -
Supplementary A
Genomic Analysis of the Immune Gene Repertoire of Amphioxus Reveals Extraordinary Innate Complexity and Diversity Supplementary A Content 1 TLR system....................................................................................................................................2 2 NLR system ...................................................................................................................................4 3 LRRIG genes .................................................................................................................................5 4 Other LRR-containing models.......................................................................................................6 5 Domain combinations in amphioxus C-type lectins ......................................................................8 References.........................................................................................................................................9 Table S1. Cross-species comparison of the immune-related protein domains................................10 Table S2. Information of 927 amphioxus CTL gene models containing single CTLD domain. ....11 Table S3. Grouping of the amphioxus DFD gene models based on their architectures..................12 Figure S1. Two structural types of TLR. ........................................................................................13 Figure S2. Phylogenetic analysis of amphioxus P-TLRs and all vertebrate TLR families.............14 Figure S3. Phylogenetic analysis of amphioxus TLRs -
Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in Partial Satisfaction
Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Sciences in the Copyright 2013 by Jonathan Foster Russell ii I dedicate this dissertation to Mom and Dad, for their adamantine love and support iii No man has earned the right to intellectual ambition until he has learned to lay his course by a star which he has never seen—to dig by the divining rod for springs which he may never reach. In saying this, I point to that which will make your study heroic. For I say to you in all sadness of conviction, that to think great thoughts you must be heroes as well as idealists. Only when you have worked alone – when you have felt around you a black gulf of solitude more isolating than that which surrounds the dying man, and in hope and in despair have trusted to your own unshaken will – then only will you have achieved. Thus only can you gain the secret isolated joy of the thinker, who knows that, a hundred years after he is dead and forgotten, men who never heard of him will be moving to the measure of his thought—the subtile rapture of a postponed power, which the world knows not because it has no external trappings, but which to his prophetic vision is more real than that which commands an army. -Oliver Wendell Holmes, Jr. iv ACKNOWLEDGMENTS I am humbled by the efforts of many, many others who were essential for this work. -
NLRP3) Inflammasome Activity Is Regulated by and Potentially Targetable Through Bruton Tyrosine Kinase
Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase Thesis submitted as requirement to fulfill the degree „Doctor of Philosophy“ (Ph.D.) at the Faculty of Medicine Eberhard Karls University Tübingen by Xiao Liu (刘晓) from Shandong, China 2018 1 Dean: Professor Dr. I. B. Autenrieth 1. Reviewer: Professor A. Weber 2. Reviewer: Professor S. Beer-Hammer 2 Content Content Figures ..................................................................................................................................................... iv Tables ....................................................................................................................................................... vi Abbreviations ........................................................................................................................................ vii 1 Introduction ....................................................................................................................................... 1 1.1 The human immune system .................................................................................................... 1 1.1.1 Innate immune response ................................................................................................................... 1 1.1.2 Adaptive immune response ............................................................................................................. 2 1.2 Inflammasomes are a group of -
The Conservation and Uniqueness of the Caspase Family in the Basal
Xu et al. BMC Biology 2011, 9:60 http://www.biomedcentral.com/1741-7007/9/60 RESEARCHARTICLE Open Access The conservation and uniqueness of the caspase family in the basal chordate, amphioxus Liqun Xu†, Shaochun Yuan†, Jun Li, Jie Ruan, Shengfeng Huang, Manyi Yang, Huiqing Huang, Shangwu Chen, Zhenghua Ren and Anlong Xu* Abstract Background: The caspase family, which plays a central role in apoptosis in metazoans, has undergone an expansion in amphioxus, increasing to 45 members through domain recombination and shuffling. Results: In order to shed light on the conservation and uniqueness of this family in amphioxus, we cloned three representative caspase genes, designated as bbtCaspase-8, bbtCaspase-1/2 and bbtCaspase3-like, from the amphioxus Branchiostoma belcheri tsingtauense. We found that bbtCaspase-8 with conserved protein architecture is involved in the Fas-associated death domain-Caspase-8 mediated pro-apoptotic extrinsic pathway, while bbtCaspase3-like may mediate a nuclear apoptotic pathway in amphioxus. Also, bbtCaspase-1/2 can co-localize with bbtFADD2 in the nucleus, and be recruited to the cytoplasm by amphioxus apoptosis associated speck-like proteins containing a caspase recruitment domain, indicating that bbtCaspase-1/2 may serve as a switch between apoptosis and caspase-dependent innate immune response in invertebrates. Finally, amphioxus extrinsic apoptotic pathway related caspases played important roles in early embryogenesis. Conclusions: Our study not only demonstrates the conservation of bbtCaspase-8 in apoptosis, but also reveals the unique features of several amphioxus caspases with novel domain architectures arose some 500 million years ago. Background intrinsic pathway is triggered by death stimuli generated Programmed cell death is a gene-guided process for the within the cell, such as DNA damage, leading to the elimination of unnecessary or harmful cells in which the release of mitochondrial cytochrome c, which associates cysteine proteases caspases are core elements [1-3]. -
Linkage and Association Studies in African
中国科技论文在线 http://www.paper.edu.cn Molecular Psychiatry (2006),1–12 & 2006 Nature Publishing Group All rights reserved 1359-4184/06 $30.00 www.nature.com/mp ORIGINAL ARTICLE Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence MD Li1, D Sun1,2, X-Y Lou1, J Beuten1, TJ Payne3 and JZ Ma4 1Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA; 2Department of Animal Genetics and Breeding and Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, China Agricultural University, Beijing, PR China; 3ACT Center for Tobacco Treatment, Education and Research, University of Mississippi Medical Center, Jackson, MS, USA and 4Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA Our previous linkage study demonstrated that the 9q22–q23 chromosome region showed a ‘suggestive’ linkage to nicotine dependence (ND) in the Framingham Heart Study population. In this study, we provide further evidence for the linkage of this region to ND in an independent sample. Within this region, the gene encoding Src homology 2 domain-containing transform- ing protein C3 (SHC3) represents a plausible candidate for association with ND, assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstro¨ m Test for ND (FTND). We utilized 11 single-nucleotide polymorphisms within SHC3 to examine the association with ND in 602 nuclear families of either African-American (AA) or European- American (EA) origin. Individual SNP-based analysis indicated three SNPs for AAs and one for EAs were significantly associated with at least one ND measure. -
Anglemetry of Neural Axis Cell Differentiation Genes by Structural Pressurotopy of DNA Loop Strand Segment Tropy in Reference to Tissue Macro-Compliance Hemant Sarin
Sarin Translational Medicine Communications (2019) 4:13 Translational Medicine https://doi.org/10.1186/s41231-019-0045-4 Communications RESEARCH Open Access Anglemetry of neural axis cell differentiation genes by structural pressurotopy of DNA loop strand segment tropy in reference to tissue macro-compliance Hemant Sarin Abstract Background: Even as the eukaryotic stranded DNA is known to heterochromatinize at the nuclear envelope in response to mechanical strain, the precise mechanistic basis for alterations in chromatin gene transcription in differentiating cell lineages has been difficult to determine due to limited spatial resolution for detection of shifts in reference to a specific gene in vitro. In this study, heterochromatin shift during euchromatin gene transcription has been studied by parallel determinations of DNA strand loop segmentation tropy nano-compliance (esebssiwaagoTQ units, linear nl), gene positioning angulation in linear normal two- 0 dimensional (2-D) z, y-vertical plane (anglemetry, ), horizontal alignment to the z, x-plane (vectormetry; mA, mM,a.u.),andby pressuromodulation mapping of differentiated neuron cell sub-class operating range for neuroaxis gene expression in reference to tissue macro-compliance (Peff). Methods: The esebssiwaagoTQ effectivepressureunit(Peff) maxima and minima for horizontal gene intergene base segment tropy loop alignment were determined (n = 224); the Peff esebssiwaagoTQ quotient were determined (n =28)foranalysisof gene intergene base loop segment tropy structure nano-compliance (n = 28; n = 188); and gene positioning anglemetry and vectormetry was performed (n = 42). The sebs intercept-to-sebssiwa intercept quotient for linear normalization was determined (bsebs/bsebssiwa) by exponential plotting of sub-episode block sum (sebs) (x1, y1; x2, y2) and sub-episode block sum split integrated weighted average (sebssiwa) functions was performed, and the sebs – sebssiwa function residuals were determined. -
A Genome-Wide Resource and Visualization Tool to Design CRISPR/Cas9 Screens for Editing Protein-RNA Interaction Sites in the Human Genome
bioRxiv preprint doi: https://doi.org/10.1101/654640; this version posted September 3, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. SliceIt: A genome-wide resource and visualization tool to design CRISPR/Cas9 screens for editing protein-RNA interaction sites in the human genome Sasank Vemuri1Ψ, Rajneesh Srivastava1Ψ, Quoseena Mir1, Seyedsasan Hashemikhabir1, X. Charlie Dong2, 1, 3, 4* Sarath Chandra Janga 1Department of BioHealth Informatics, School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, Indiana 46202 2Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 635 Barnhill Drive, Indianapolis, Indiana, 46202 3Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, Indiana, 46202 4Centre for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, Indiana, 46202 ΨBoth the authors contributed equally to this study and should be considered as joint first authors Keywords: RNA binding proteins, In silico library, CRISPR/Cas9, Guide RNA, Pooled CRISPR screens, Protein-RNA interactions, Post-transcriptional control *Correspondence should be addressed to: Sarath Chandra Janga ([email protected]) 719 Indiana Avenue Ste 319, Walker Plaza Building Indianapolis, Indiana – 46202 Tel: +1-317-278-4147, Fax: +1-317-278-9201 bioRxiv preprint doi: https://doi.org/10.1101/654640; this version posted September 3, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
Pharmacological Mechanisms Underlying the Therapeutic Effects of Danhong Injection on Cerebral Ischemia
Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 5584809, 10 pages https://doi.org/10.1155/2021/5584809 Research Article Pharmacological Mechanisms Underlying the Therapeutic Effects of Danhong Injection on Cerebral Ischemia Yifei Qi ,1,2 Yihuai Zou ,1 Lin Chen ,2 Jun Liu ,2 Yingying Zhang ,1 and Zhong Wang 2 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China 2Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China Correspondence should be addressed to Zhong Wang; [email protected] Received 1 February 2021; Revised 16 April 2021; Accepted 10 May 2021; Published 21 May 2021 Academic Editor: Baotong Zhang Copyright © 2021 Yifei Qi et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Although Danhong injection (DHI) has been proved to be curative, the mechanism of its action against ischemia stroke (IS) is not clear. Here, we explored the therapeutic basis of DHI by network pharmacology. Methods. Putative targets and activity scores for each compound in DHI were obtained from the Traditional Chinese Medicine System Pharmacology Database, Encyclopedia of Traditional Chinese Medicine, and Quantitative Structure Activity Relationships. Next, target proteins of IS were identified on GeneCards and CTD. Overlapping targets of DHI associated with IS were acquired via Venn diagram. GO and KEGG pathway analyses were done using WebGestalt. Cytoscape software was used for PPI network construction and hub nodes screening. Several validation studies were carried out by using AutoDock-Vina, label-free mass spectrometry, and transcriptome RNA-sequencing. -
Assembly and Regulation of the Death Effector Domain Complexes
Citation: Cell Death and Disease (2015) 6, e1866; doi:10.1038/cddis.2015.213 OPEN & 2015 Macmillan Publishers Limited All rights reserved 2041-4889/15 www.nature.com/cddis Review DED or alive: assembly and regulation of the death effector domain complexes JS Riley1, A Malik1, C Holohan1 and DB Longley*,1 Death effector domains (DEDs) are protein–protein interaction domains initially identified in proteins such as FADD, FLIP and caspase-8 involved in regulating apoptosis. Subsequently, these proteins have been shown to have important roles in regulating other forms of cell death, including necroptosis, and in regulating other important cellular processes, including autophagy and inflammation. Moreover, these proteins also have prominent roles in innate and adaptive immunity and during embryonic development. In this article, we review the various roles of DED-containing proteins and discuss recent developments in our understanding of DED complex formation and regulation. We also briefly discuss opportunities to therapeutically target DED complex formation in diseases such as cancer. Cell Death and Disease (2015) 6, e1866; doi:10.1038/cddis.2015.213; published online 27 August 2015 Facts Are DED-containing proteins potential therapeutic targets for inflammatory diseases? FADD, FLIP, procaspase-8 and procaspase-10 all contain death effector domains (DEDs). Cell death is critical for maintaining homeostasis in multi- The DED is a conserved protein sub-domain that mediates cellular organisms; too much can result in pathologies such as important protein–protein interactions. neurodegeneration, whereas too little can lead to the DED-containing proteins form a variety of complexes that accumulation of malignant cancerous cells. -
The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation
ANRV306-IY25-19 ARI 11 February 2007 12:51 The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation Hyun Ho Park,1 Yu-Chih Lo,1 Su-Chang Lin,1 Liwei Wang,1 Jin Kuk Yang,1,2 and Hao Wu1 1Department of Biochemistry, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021; email: [email protected] 2Department of Chemistry, Soongsil University, Seoul 156-743, Korea Annu. Rev. Immunol. 2007. 25:561–86 Key Words First published online as a Review in Advance on death domain (DD), death effector domain (DED), tandem DED, January 2, 2007 caspase recruitment domain (CARD), pyrin domain (PYD), crystal The Annual Review of Immunology is online at structure, NMR structure immunol.annualreviews.org This article’s doi: Abstract 10.1146/annurev.immunol.25.022106.141656 The death domain (DD) superfamily comprising the death domain Copyright c 2007 by Annual Reviews. (DD) subfamily, the death effector domain (DED) subfamily, the Annu. Rev. Immunol. 2007.25:561-586. Downloaded from arjournals.annualreviews.org by CORNELL UNIVERSITY MEDICAL COLLEGE on 03/29/07. For personal use only. All rights reserved caspase recruitment domain (CARD) subfamily, and the pyrin do- 0732-0582/07/0423-0561$20.00 main (PYD) subfamily is one of the largest domain superfamilies. By mediating homotypic interactions within each domain subfam- ily, these proteins play important roles in the assembly and activation of apoptotic and inflammatory complexes. In this chapter, we review the molecular complexes assembled by these proteins, the structural and biochemical features of these domains, and the molecular in- teractions mediated by them.