DOCSLIB.ORG

Download Special Issue

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Download Special Issue BioMed Research International Network Proteomics: From Protein Structure to Protein-Protein Interaction Guest Editors: Guang Hu, Luisa Di Paola, Filippo Pullara, Zhongjie Liang, and Intawat Nookaew Network Proteomics: From Protein Structure to Protein-Protein Interaction BioMed Research International Network Proteomics: From Protein Structure to Protein-Protein Interaction Guest Editors: Guang Hu, Luisa Di Paola, Filippo Pullara, Zhongjie Liang, and Intawat Nookaew Copyright © 2017 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Network Proteomics: From Protein Structure to Protein-Protein Interaction Guang Hu, Luisa Di Paola, Filippo Pullara, Zhongjie Liang, and Intawat Nookaew Volume 2017, Article ID 8929613, 1 page Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists Yuwei Wang, Rui Han, Huimin Zhang, Hongli Liu, Jiazhong Li, Huanxiang Liu, and Paola Gramatica Volume 2017, Article ID 3572394, 18 pages Comparative Study of Elastic Network Model and Protein Contact Network for Protein Complexes: The Hemoglobin Case Guang Hu, Luisa Di Paola, Zhongjie Liang, and Alessandro Giuliani Volume 2017, Article ID 2483264, 15 pages Biomolecular Network-Based Synergistic Drug Combination Discovery Xiangyi Li, Guangrong Qin, Qingmin Yang, Lanming Chen, and Lu Xie Volume 2016, Article ID 8518945, 11 pages Identification of Hot Spots in Protein Structures Using Gaussian Network Model and Gaussian Naive Bayes Hua Zhang, Tao Jiang, and Guogen Shan Volume 2016, Article ID 4354901, 9 pages Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based onVirtualScreeningandBiologicalAssays Fei Ye, Weiyao Zhang, Wenchao Lu, Yiqian Xie, Hao Jiang, Jia Jin, and Cheng Luo Volume 2016, Article ID 7086390, 8 pages Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study Hua Wan, Shan Chang, Jian-ping Hu, Xu-hong Tian, and Mei-hua Wang Volume 2016, Article ID 8036450, 11 pages Networks Models of Actin Dynamics during Spermatozoa Postejaculatory Life: A Comparison among Human-Made and Text Mining-Based Models Nicola Bernabò, Alessandra Ordinelli, Marina Ramal Sanchez, Mauro Mattioli, and Barbara Barboni Volume 2016, Article ID 9795409, 8 pages Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks JingyuXu,PanpanWang,HongYang,JinZhou,YinghongLi,XiaoxuLi,WeiweiXue,ChunyanYu,Yubin Tian, and Feng Zhu Volume 2016, Article ID 2509385,9 pages Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study Nachon Raethong, Jirasak Wong-ekkabut, Kobkul Laoteng, and Wanwipa Vongsangnak Volume 2016, Article ID 8124636, 13 pages Hindawi Publishing Corporation BioMed Research International Volume 2017, Article ID 8929613, 1 page http://dx.doi.org/10.1155/2017/8929613 Editorial Network Proteomics: From Protein Structure to Protein-Protein Interaction Guang Hu,1 Luisa Di Paola,2 Filippo Pullara,3 Zhongjie Liang,1 and Intawat Nookaew4 1 Center for Systems Biology, School of Electronic and Information Engineering, Soochow University, Suzhou 215006, China 2Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Engineering, Universita` Campus Bio-Medico, Rome, Italy 3Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA 4Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA Correspondence should be addressed to Guang Hu; [email protected] Received 3 January 2017; Accepted 4 January 2017; Published 16 February 2017 Copyright © 2017 Guang Hu et al. This 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. With the emergence of high-throughput “omics” data, net- Protein-protein interactions not only are limited to work theory is being increasingly used to analyze biomolec- binary associations but also employ special topological struc- ular systems. In particular, proteins rarely act alone, which tures to perform their biological functions. N. Bernaboet` prompted the arrival of proteomics. “Network proteomics” al. approached the comparison of two networks models is just defined as the research area that introduces network obtained from two different text mining tools to suggest that theory to investigate biological networks ranging from pro- actin dynamics affect spermatozoa postejaculatory life. J. Xu tein structure networks to protein-protein interaction net- et al. also compared the topologies of network modes of drug- works. In addition, the application of network proteomics in kinase interactions between established targets and those of biomedical fields has increased significantly. This special issue clinical trial ones. has collected contributions, not only focusing on the state of Both protein structures and protein-protein interactions the art of methodology in “network proteomics” itself but also areinvolvedinthesubjectofagrowingnumberofphar- focusing on the current status and future direction of their macological studies. F. Ye et al. identified that compounds applications in translational medical informatics. DC C11 and DC C66 are two small inhibitors against protein- protein interactions between CARM1 and its substrates, while This issue starts with discussing the role of protein struc- Y. Wang et al. identified that CID 70128824, CID 70127147, ture that participates in interactions. N. Raethong et al. devel- and CID 70126881 are three potential inhibitors for targeting oped a strategy to annotate Aspergillus oryzae,whichwould theandrogenreceptortotreatprostatecancer.Finally,a enhance its metabolic network reconstruction. By using the review paper completes the issue. X. Li et al. introduced molecular dynamics simulation and principle component recent advances in the development of network models of analysis, H. Wan et al. investigated the interaction between identifying synergistic drug combinations. the last half repeat in TAL effectors and its binding DNA. This Altogether, we wish this issue has given a wider devel- work would give a deeper understanding of the recognition opment of structural biology and systems biology with the mechanism of protein-DNA interactions. advantage of biological network analysis as well as prospect- Protein complexes offer detailed structural characteristics ing the future of this area towards translational bioinforma- of protein-protein interactions. H. Zhang et al. proposed a tics and systems pharmacology. method by combining the high frequency modes of Gaussian network model and Gaussian Naive Bayes to identify hot Guang Hu spots, which are residues that contribute largely to protein- Luisa Di Paola protein interaction energy. G. Hu et al. performed a com- Filippo Pullara parative study of elastic network model and protein contact Zhongjie Liang network for protein complexes in case of hemoglobin. Intawat Nookaew Hindawi Publishing Corporation BioMed Research International Volume 2017, Article ID 3572394, 18 pages http://dx.doi.org/10.1155/2017/3572394 Research Article Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists Yuwei Wang,1 Rui Han,1 Huimin Zhang,1 Hongli Liu,1 Jiazhong Li,1 Huanxiang Liu,1 and Paola Gramatica2 1 School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou 730000, China 2Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100 Varese, Italy Correspondence should be addressed to Jiazhong Li; [email protected] Received 24 August 2016; Revised 11 October 2016; Accepted 16 November 2016; Published 15 February 2017 Academic Editor: Zhongjie Liang Copyright © 2017 Yuwei Wang et al. This 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. The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability. The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID 70128824, CID 70127147, and CID 70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide. In addition, molecular docking, molecular dynamics (MD) simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and
Load more

Recommended publications
  • Gpr161 Anchoring of PKA Consolidates GPCR and Camp Signaling
    Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling Verena A. Bachmanna,1, Johanna E. Mayrhofera,1, Ronit Ilouzb, Philipp Tschaiknerc, Philipp Raffeinera, Ruth Röcka, Mathieu Courcellesd,e, Federico Apeltf, Tsan-Wen Lub,g, George S. Baillieh, Pierre Thibaultd,i, Pia Aanstadc, Ulrich Stelzlf,j, Susan S. Taylorb,g,2, and Eduard Stefana,2 aInstitute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria; bDepartment of Chemistry and Biochemistry, University of California, San Diego, CA 92093; cInstitute of Molecular Biology, University of Innsbruck, 6020 Innsbruck, Austria; dInstitute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada H3C 3J7; eDépartement de Biochimie, Université de Montréal, Montreal, QC, Canada H3C 3J7; fOtto-Warburg Laboratory, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; gDepartment of Pharmacology, University of California, San Diego, CA 92093; hInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom; iDepartment of Chemistry, Université de Montréal, Montreal, QC, Canada H3C 3J7; and jInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, 8010 Graz, Austria Contributed by Susan S. Taylor, May 24, 2016 (sent for review February 18, 2016; reviewed by John J. G. Tesmer and Mark von Zastrow) Scaffolding proteins organize the information flow from activated G accounts for nanomolar binding affinities to PKA R subunit dimers protein-coupled receptors (GPCRs) to intracellular effector cascades (12, 13). Moreover, additional components of the cAMP signaling both spatially and temporally. By this means, signaling scaffolds, such machinery, such as GPCRs, adenylyl cyclases, and phosphodiester- as A-kinase anchoring proteins (AKAPs), compartmentalize kinase ases, physically interact with AKAPs (1, 5, 11, 14).
    [Show full text]
  • Identification and Characterization of RHOA-Interacting Proteins in Bovine Spermatozoa1
    BIOLOGY OF REPRODUCTION 78, 184–192 (2008) Published online before print 10 October 2007. DOI 10.1095/biolreprod.107.062943 Identification and Characterization of RHOA-Interacting Proteins in Bovine Spermatozoa1 Sarah E. Fiedler, Malini Bajpai, and Daniel W. Carr2 Department of Medicine, Oregon Health & Sciences University and Veterans Affairs Medical Center, Portland, Oregon 97239 ABSTRACT Guanine nucleotide exchange factors (GEFs) catalyze the GDP for GTP exchange [2]. Activation is negatively regulated by In somatic cells, RHOA mediates actin dynamics through a both guanine nucleotide dissociation inhibitors (RHO GDIs) GNA13-mediated signaling cascade involving RHO kinase and GTPase-activating proteins (GAPs) [1, 2]. Endogenous (ROCK), LIM kinase (LIMK), and cofilin. RHOA can be RHO can be inactivated via C3 exoenzyme ADP-ribosylation, negatively regulated by protein kinase A (PRKA), and it and studies have demonstrated RHO involvement in actin-based interacts with members of the A-kinase anchoring (AKAP) cytoskeletal response to extracellular signals, including lyso- family via intermediary proteins. In spermatozoa, actin poly- merization precedes the acrosome reaction, which is necessary phosphatidic acid (LPA) [2–4]. LPA is known to signal through for normal fertility. The present study was undertaken to G-protein-coupled receptors (GPCRs) [4, 5]; specifically, LPA- determine whether the GNA13-mediated RHOA signaling activated GNA13 (formerly Ga13) promotes RHO activation pathway may be involved in acrosome reaction in bovine through GEFs [4, 6]. Activated RHO-GTP then signals RHO caudal sperm, and whether AKAPs may be involved in its kinase (ROCK), resulting in the phosphorylation and activation targeting and regulation. GNA13, RHOA, ROCK2, LIMK2, and of LIM-kinase (LIMK), which in turn phosphorylates and cofilin were all detected by Western blot in bovine caudal inactivates cofilin, an actin depolymerizer, the end result being sperm.
    [Show full text]
  • Dissociation Between AKAP3 and PKARII Promotes AKAP3 Degradation in Sperm Capacitation
    Dissociation between AKAP3 and PKARII Promotes AKAP3 Degradation in Sperm Capacitation Pnina Hillman, Debby Ickowicz, Ruth Vizel, Haim Breitbart* The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel Abstract Ejaculated spermatozoa must undergo a series of biochemical modifications called capacitation, prior to fertilization. Protein-kinase A (PKA) mediates sperm capacitation, although its regulation is not fully understood. Sperm contain several A-kinase anchoring proteins (AKAPs), which are scaffold proteins that anchor PKA. In this study, we show that AKAP3 is degraded in bovine sperm incubated under capacitation conditions. The degradation rate is variable in sperm from different bulls and is correlated with the capacitation ability. The degradation of AKAP3 was significantly inhibited by MG-132, a proteasome inhibitor, indicating that AKAP3 degradation occurs via the proteasomal machinery. Treatment with Ca2+-ionophore induced further degradation of AKAP3; however, this effect was found to be enhanced in the absence of Ca2+ in the medium or when intracellular Ca2+ was chelated the degradation rate of AKAP3 was significantly enhanced when intracellular space was alkalized using NH4Cl, or when sperm were treated with Ht31, a peptide that contains the PKA-binding domain of AKAPs. Moreover, inhibition of PKA activity by H89, or its activation using 8Br-cAMP, increased AKAP3 degradation rate. This apparent contradiction could be explained by assuming that binding of PKA to AKAP3 protects AKAP3 from degradation. We conclude that AKAP3 degradation is regulated by intracellular alkalization and PKARII anchoring during sperm capacitation. Citation: Hillman P, Ickowicz D, Vizel R, Breitbart H (2013) Dissociation between AKAP3 and PKARII Promotes AKAP3 Degradation in Sperm Capacitation.
    [Show full text]
  • © Copyright 2021 Heather Raquel Dahlin
    © Copyright 2021 Heather Raquel Dahlin The Structure of Sperm Autoantigenic Protein (SPA17): An R2D2 Protein Critical to Cilia and Implicated in Oncogenesis Heather Raquel Dahlin A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2021 Reading Committee: John D. Scott, Chair Ning Zheng Linda Wordeman Program Authorized to Offer Degree: Pharmacology University of Washington Abstract Structure of SPA17: An R2D2 Protein Critical to Cilia and Implicated in Oncogenesis Heather Raquel Dahlin Chair of the Supervisory Committee: John D. Scott, Ph.D., Edwin G. Krebs- Speights Professor of Cell Signaling and Cancer Biology Pharmacology A-Kinase Anchoring proteins (AKAPs) localize the activity of cyclic AMP (cAMP)-Dependent Protein Kinase (PKA) through interaction of an amphipathic helix that binds to a conserved RIIα docking and dimerization (R2D2) domain on the N-terminus of PKA. Genome analysis indicates that at least thirteen other RIIα superfamily proteins exist in humans, which are not coupled to cyclic nucleotide binding domains and are largely localized to cilia and flagella. The newly reported R2D2 proteins exist in two lineages differing by their similarity to Type I or Type II PKA. Moreover, R2D2 domains bind to AKAPs and can contain extra regulatory sequences conferring novel functions and binding specificity. Here we detail the structure of one such domain comprising the N-terminus of Sperm Autoantigenic Protein 17 (SPA17) resolved to 1.72 Å. The structure of core hydrophobic sites for dimerization and AKAP binding are highly conserved between PKA and SPA17. Additional flanking sequences outside of the core R2D2 domain occlude the AKAP binding site and reduce the affinity for AKAP helices in the absence of heterodimerization with another R2D2 protein, ROPN1L.
    [Show full text]
  • TCTE1 Is a Conserved Component of the Dynein Regulatory Complex and Is Required for Motility and Metabolism in Mouse Spermatozoa
    TCTE1 is a conserved component of the dynein PNAS PLUS regulatory complex and is required for motility and metabolism in mouse spermatozoa Julio M. Castanedaa,b,1, Rong Huac,d,1, Haruhiko Miyatab, Asami Ojib,e, Yueshuai Guoc,d, Yiwei Chengc,d, Tao Zhouc,d, Xuejiang Guoc,d, Yiqiang Cuic,d, Bin Shenc, Zibin Wangc, Zhibin Huc,f, Zuomin Zhouc,d, Jiahao Shac,d, Renata Prunskaite-Hyyrylainena,g,h, Zhifeng Yua,i, Ramiro Ramirez-Solisj, Masahito Ikawab,e,k,2, Martin M. Matzuka,g,i,l,m,n,2, and Mingxi Liuc,d,2 aDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; bResearch Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan; cState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People’s Republic of China; dDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210029, People’s Republic of China; eGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan; fAnimal Core Facility of Nanjing Medical University, Nanjing 210029, People’s Republic of China; gCenter for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030; hFaculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland; iCenter for Drug Discovery, Baylor College of Medicine, Houston, TX 77030; jWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; kThe Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan; lDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; mDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and nDepartment of Pharmacology, Baylor College of Medicine, Houston, TX 77030 Contributed by Martin M.
    [Show full text]
  • Novel Targets of Apparently Idiopathic Male Infertility
    International Journal of Molecular Sciences Review Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility Rossella Cannarella * , Rosita A. Condorelli , Laura M. Mongioì, Sandro La Vignera * and Aldo E. Calogero Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [email protected] (R.A.C.); [email protected] (L.M.M.); [email protected] (A.E.C.) * Correspondence: [email protected] (R.C.); [email protected] (S.L.V.) Received: 8 February 2020; Accepted: 2 March 2020; Published: 3 March 2020 Abstract: Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility. Keywords: spermatogenetic failure; embryo growth; male infertility; spermatogenesis; recurrent pregnancy loss; sperm proteome; DNA fragmentation; sperm transcriptome 1. Introduction Infertility is a widespread condition in industrialized countries, affecting up to 15% of couples of childbearing age [1]. It is defined as the inability to achieve conception after 1–2 years of unprotected sexual intercourse [2].
    [Show full text]
  • View a Copy of This Licence, Visit
    Robertson et al. BMC Biology (2020) 18:103 https://doi.org/10.1186/s12915-020-00826-z RESEARCH ARTICLE Open Access Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets Matthew J. Robertson1,2, Katarzyna Kent3,4,5, Nathan Tharp3,4,5, Kaori Nozawa3,5, Laura Dean3,4,5, Michelle Mathew3,4,5, Sandra L. Grimm2,6, Zhifeng Yu3,5, Christine Légaré7,8, Yoshitaka Fujihara3,5,9,10, Masahito Ikawa9, Robert Sullivan7,8, Cristian Coarfa1,2,6*, Martin M. Matzuk1,3,5,6 and Thomas X. Garcia3,4,5* Abstract Background: The development of a safe, effective, reversible, non-hormonal contraceptive method for men has been an ongoing effort for the past few decades. However, despite significant progress on elucidating the function of key proteins involved in reproduction, understanding male reproductive physiology is limited by incomplete information on the genes expressed in reproductive tissues, and no contraceptive targets have so far reached clinical trials. To advance product development, further identification of novel reproductive tract-specific genes leading to potentially druggable protein targets is imperative. Results: In this study, we expand on previous single tissue, single species studies by integrating analysis of publicly available human and mouse RNA-seq datasets whose initial published purpose was not focused on identifying male reproductive tract-specific targets. We also incorporate analysis of additional newly acquired human and mouse testis and epididymis samples to increase the number of targets identified. We detected a combined total of 1178 genes for which no previous evidence of male reproductive tract-specific expression was annotated, many of which are potentially druggable targets.
    [Show full text]
  • Research Article Complex and Multidimensional Lipid Raft Alterations in a Murine Model of Alzheimer’S Disease
    SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2010, Article ID 604792, 56 pages doi:10.4061/2010/604792 Research Article Complex and Multidimensional Lipid Raft Alterations in a Murine Model of Alzheimer’s Disease Wayne Chadwick, 1 Randall Brenneman,1, 2 Bronwen Martin,3 and Stuart Maudsley1 1 Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA 2 Miller School of Medicine, University of Miami, Miami, FL 33124, USA 3 Metabolism Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA Correspondence should be addressed to Stuart Maudsley, [email protected] Received 17 May 2010; Accepted 27 July 2010 Academic Editor: Gemma Casadesus Copyright © 2010 Wayne Chadwick et al. This 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. Various animal models of Alzheimer’s disease (AD) have been created to assist our appreciation of AD pathophysiology, as well as aid development of novel therapeutic strategies. Despite the discovery of mutated proteins that predict the development of AD, there are likely to be many other proteins also involved in this disorder. Complex physiological processes are mediated by coherent interactions of clusters of functionally related proteins. Synaptic dysfunction is one of the hallmarks of AD. Synaptic proteins are organized into multiprotein complexes in high-density membrane structures, known as lipid rafts. These microdomains enable coherent clustering of synergistic signaling proteins.
    [Show full text]
  • Targeted Disruption of the Akap4 Gene Causes Defects in Sperm
    DevelopmentalBiology248,331–342(2002) doi:10.1006/dbio.2002.0728 View metadata, citation and similar papers at core.ac.uk brought to you by CORE TargetedDisruptionoftheAkap4GeneCauses provided by Elsevier - Publisher Connector DefectsinSpermFlagellumandMotility KiyoshiMiki,*,1 WilliamD.Willis,*PaulaR.Brown,* EugeniaH.Goulding,*KerryD.Fulcher,†andEdwardM.Eddy*,2 *GameteBiologySection,LaboratoryofReproductiveandDevelopmentalToxicology, NationalInstituteofEnvironmentalHealthSciences,NationalInstitutesofHealth, ResearchTrianglePark,NorthCarolina27709;and†PointLomaNazareneUniversity, SanDiego,California92106 A-kinaseanchoringproteins(AKAPs)tethercyclicAMP-dependentproteinkinasesandtherebylocalizephosphorylationof targetproteinsandinitiationofsignal-transductionprocessestriggeredbycyclicAMP.AKAPscanalsobescaffoldsfor kinasesandphosphatasesandformmacromolecularcomplexeswithotherproteinsinvolvedinsignaltransduction.Akap4 istranscribedonlyinthepostmeioticphaseofspermatogenesisandencodesthemostabundantproteininthefibrous sheath,anovelcytoskeletalstructurepresentintheprincipalpieceofthespermflagellum.Previousstudiesindicatedthat cyclicAMP-dependentsignalingprocessesareimportantintheregulationofspermmotility,andgenetargetingwasused heretotestthehypothesisthatAKAP4isascaffoldforproteincomplexesinvolvedinregulatingflagellarfunction.Sperm numberswerenotreducedinmalemicelackingAKAP4,butspermfailedtoshowprogressivemotilityandmalemicewere infertile.Thefibroussheathanlagenformed,butthedefinitivefibroussheathdidnotdevelop,theflagellumwasshortened, andproteinsusuallyassociatedwiththefibroussheathwereabsentorsubstantiallyreducedinamount.However,theother
    [Show full text]
  • Dissecting the Genetics of Human Communication
    DISSECTING THE GENETICS OF HUMAN COMMUNICATION: INSIGHTS INTO SPEECH, LANGUAGE, AND READING by HEATHER ASHLEY VOSS-HOYNES Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Epidemiology and Biostatistics CASE WESTERN RESERVE UNIVERSITY January 2017 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We herby approve the dissertation of Heather Ashely Voss-Hoynes Candidate for the degree of Doctor of Philosophy*. Committee Chair Sudha K. Iyengar Committee Member William Bush Committee Member Barbara Lewis Committee Member Catherine Stein Date of Defense July 13, 2016 *We also certify that written approval has been obtained for any proprietary material contained therein Table of Contents List of Tables 3 List of Figures 5 Acknowledgements 7 List of Abbreviations 9 Abstract 10 CHAPTER 1: Introduction and Specific Aims 12 CHAPTER 2: Review of speech sound disorders: epidemiology, quantitative components, and genetics 15 1. Basic Epidemiology 15 2. Endophenotypes of Speech Sound Disorders 17 3. Evidence for Genetic Basis Of Speech Sound Disorders 22 4. Genetic Studies of Speech Sound Disorders 23 5. Limitations of Previous Studies 32 CHAPTER 3: Methods 33 1. Phenotype Data 33 2. Tests For Quantitative Traits 36 4. Analytical Methods 42 CHAPTER 4: Aim I- Genome Wide Association Study 49 1. Introduction 49 2. Methods 49 3. Sample 50 5. Statistical Procedures 53 6. Results 53 8. Discussion 71 CHAPTER 5: Accounting for comorbid conditions 84 1. Introduction 84 2. Methods 86 3. Results 87 4. Discussion 105 CHAPTER 6: Hypothesis driven pathway analysis 111 1. Introduction 111 2. Methods 112 3. Results 116 4.
    [Show full text]
  • Rare Deletions at 16P13.11 Predispose to a Diverse Spectrum of Sporadic Epilepsy Syndromes
    ARTICLE Rare Deletions at 16p13.11 Predispose to a Diverse Spectrum of Sporadic Epilepsy Syndromes Erin L. Heinzen,1,23 Rodney A. Radtke,2,23 Thomas J. Urban,1,23 Gianpiero L. Cavalleri,5 Chantal Depondt,8 Anna C. Need,1 Nicole M. Walley,1 Paola Nicoletti,1 Dongliang Ge,1 Claudia B. Catarino,9,11 John S. Duncan,9,11 Dalia Kasperaviciute ˙ ,9 Sarah K. Tate,9 Luis O. Caboclo,9 Josemir W. Sander,9,11,12 Lisa Clayton,9 Kristen N. Linney,1 Kevin V. Shianna,1 Curtis E. Gumbs,1 Jason Smith,1 Kenneth D. Cronin,1 Jessica M. Maia,1 Colin P. Doherty,6 Massimo Pandolfo,8 David Leppert,13,15 Lefkos T. Middleton,16 Rachel A. Gibson,13 Michael R. Johnson,13,17 Paul M. Matthews,13,17 David Hosford,2 Reetta Ka¨lvia¨inen,18 Kai Eriksson,19 Anne-Mari Kantanen,18 Thomas Dorn,20 Jo¨rg Hansen,20 Gu¨nter Kra¨mer,20 Bernhard J. Steinhoff,21 Heinz-Gregor Wieser,22 Dominik Zumsteg,22 Marcos Ortega,22 Nicholas W. Wood,10 Julie Huxley-Jones,14 Mohamad Mikati,3 William B. Gallentine,3 Aatif M. Husain,2 Patrick G. Buckley,7 Ray L. Stallings,7 Mihai V. Podgoreanu,4 Norman Delanty,5 Sanjay M. Sisodiya,9,11,* and David B. Goldstein1,* Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls.
    [Show full text]
  • A-Kinase Anchoring Proteins AKAP1, -4, -10 and -11 with Different Subcellular Localizations in Sertoli Cells and Their Roles in Male Fertility
    A-kinase anchoring proteins AKAP1, -4, -10 and -11 with different subcellular localizations in Sertoli cells and their roles in male fertility Inaugural Dissertation submitted to the Faculty of Medicine in partial fulfillment of the requirements for the PhD-Degree of the Faculties of Veterinary Medicine and Medicine of the Justus Liebig University Giessen by M. Sc. Wang, Wenwen of Qingdao, China Gießen (2016) From the Institute for Anatomy and Cell Biology, Medical Cell Biology Director: Prof. Dr. med. Eveline Baumgart-Vogt of the Faculty of Medicine of the Justus Liebig University Giessen First Supervisor: Prof. Dr. med. Eveline Baumgart-Vogt Second Supervisor: Prof. Dr. habil. Christiane Herden Committee Members: Prof. Dr. Klaus-Dieter Schlüter, Prof. Dr. med. Eveline Baumgart-Vogt, Prof. Dr. habil. Christiane Herden Date of Doctoral Defense: 18th May 2016 II Declaration “I declare that I have completed this dissertation single-handedly without the unauthorized help of a second party and only with the assistance acknowledged therein. I have appropriately acknowledged and referenced all text passages that are derived literally from or are based on the content of published or unpublished work of others, and all information that relates to verbal communications. I have abided by the principles of good scientific conduct laid down in the charter of the Justus Liebig University of Giessen in carrying out the investigations described in the dissertation.” Wenwen Wang th Date: 18 May 2016 Place: Gießen, Germany III Contents 1 INTRODUCTION
    [Show full text]