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Hereditary Spastic Paraplegias
Hereditary Spastic Paraplegias Authors: Doctors Enza Maria Valente1 and Marco Seri2 Creation date: January 2003 Update: April 2004 Scientific Editor: Doctor Franco Taroni 1Neurogenetics Istituto CSS Mendel, Viale Regina Margherita 261, 00198 Roma, Italy. e.valente@css- mendel.it 2Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università degli studi di Bologna, Laboratorio di Genetica Medica, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.mailto:[email protected] Abstract Keywords Disease name and synonyms Definition Classification Differential diagnosis Prevalence Clinical description Management including treatment Diagnostic methods Etiology Genetic counseling Antenatal diagnosis References Abstract Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. Clinically, HSPs can be divided into two main groups: pure and complex forms. Pure HSPs are characterized by slowly progressive lower extremity spasticity and weakness, often associated with hypertonic urinary disturbances, mild reduction of lower extremity vibration sense, and, occasionally, of joint position sensation. Complex HSP forms are characterized by the presence of additional neurological or non-neurological features. Pure HSP is estimated to affect 9.6 individuals in 100.000. HSP may be inherited as an autosomal dominant, autosomal recessive or X-linked recessive trait, and multiple recessive and dominant forms exist. The majority of reported families (70-80%) displays autosomal dominant inheritance, while the remaining cases follow a recessive mode of transmission. To date, 24 different loci responsible for pure and complex HSP have been mapped. Despite the large and increasing number of HSP loci mapped, only 9 autosomal and 2 X-linked genes have been so far identified, and a clear genetic basis for most forms of HSP remains to be elucidated. -
H00010618-M02 規格 : [ 100 Ug ] List All
TGOLN2 monoclonal antibody (M02), clone 2F11 Catalog # : H00010618-M02 規格 : [ 100 ug ] List All Specification Application Image Product Mouse monoclonal antibody raised against a partial recombinant Western Blot (Recombinant protein) Description: TGOLN2. Immunohistochemistry Immunogen: TGOLN2 (NP_006455, 229 a.a. ~ 327 a.a) partial recombinant protein (Formalin/PFA-fixed paraffin- with GST tag. MW of the GST tag alone is 26 KDa. embedded sections) Sequence: QGPIDGPSKSGAEEQTSKDSPNKVVPEQPSRKDHSKPISNPSDNKELPK ADTNQLADKGKLSPHAFKTESGEETDLISPPQEEVKSSEPTEDVEPKEAE Host: Mouse Reactivity: Human enlarge Isotype: IgG2a Kappa Immunofluorescence Quality Control Antibody Reactive Against Recombinant Protein. Testing: enlarge Sandwich ELISA (Recombinant protein) Western Blot detection against Immunogen (36.63 KDa) . enlarge Storage Buffer: In 1x PBS, pH 7.4 ELISA Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Publication Reference 1. Phenylalanine Residues at the Carboxyl-terminus of the Herpes Simplex Virus Type-1 UL20 Membrane Protein Regulate Cytoplasmic Virion Envelopment and Infectious Virus Production. Charles AS, Chouljenko VN, Jambunathan N, Subramanian R, Mottram P, Kousoulas KGJ Virol. 2014 Apr 23. 2. Distinctive features of degenerating Purkinje cells in spinocerebellar ataxia type 31. Yoshida K, Asakawa M, Suzuki-Kouyama E, Tabata K, Shintaku M, Ikeda S, Oyanagi KNeuropathology. 2014 Jun;34(3):261-7. doi: 10.1111/neup.12090. Epub 2013 Dec 17. 3. Abnormal localization of leucine-rich repeat kinase 2 to the endosomal-lysosomal compartment in lewy body disease. Page 1 of 3 2016/5/22 Higashi S, Moore DJ, Yamamoto R, Minegishi M, Sato K, Togo T, Katsuse O, Uchikado H, Furukawa Y, Hino H, Kosaka K, Emson PC, Wada K, Dawson VL, Dawson TM, Arai H, Iseki E.J Neuropathol Exp Neurol. -
Chromosome Mis-Segregation and Cytokinesis Failure in Trisomic
RESEARCH ARTICLE elifesciences.org Chromosome mis-segregation and cytokinesis failure in trisomic human cells Joshua M Nicholson1,2, Joana C Macedo3,4,5, Aaron J Mattingly1†, Darawalee Wangsa6, Jordi Camps6‡, Vera Lima7, Ana M Gomes3, Sofia Doria´ 7, Thomas Ried6, Elsa Logarinho3,4,5*, Daniela Cimini1,2* 1Department of Biological Sciences, Virginia Tech, Blacksburg, United States; 2Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, United States; 3Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; 4Instituto de Investigac¸a˜ o e Inovac¸a˜ oemSaude-i3S,´ Universidade do Porto, Porto, Portugal; 5Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; 6Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States; 7Department of Genetics, Faculdade de Medicina, *For correspondence: elsa. [email protected] (EL); Universidade do Porto, Porto, Portugal [email protected] (DC) Present address: †Cell and Tissue Biology, School of Dentistry, Abstract Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at University of California, San high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of Francisco, San Francisco, United aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer States; ‡Gastrointestinal and cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as Pancreatic Oncology Group, euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher Hospital Clınic,´ Centro de Investigacion´ Biomedica´ en Red rates of chromosome mis-segregation compared to their euploid counterparts. -
Hereditary Spastic Paraplegia: from Genes, Cells and Networks to Novel Pathways for Drug Discovery
brain sciences Review Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery Alan Mackay-Sim Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia; a.mackay-sim@griffith.edu.au Abstract: Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affect- ing the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across geno- types despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms. This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes. Keywords: neurodegeneration; motor neuron disease; spastic paraplegia; endoplasmic reticulum; Citation: Mackay-Sim, A. Hereditary protein-protein interaction network Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery. Brain Sci. 2021, 11, 403. -
Drosophila and Human Transcriptomic Data Mining Provides Evidence for Therapeutic
Drosophila and human transcriptomic data mining provides evidence for therapeutic mechanism of pentylenetetrazole in Down syndrome Author Abhay Sharma Institute of Genomics and Integrative Biology Council of Scientific and Industrial Research Delhi University Campus, Mall Road Delhi 110007, India Tel: +91-11-27666156, Fax: +91-11-27662407 Email: [email protected] Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 Running head: Pentylenetetrazole mechanism in Down syndrome 1 Abstract Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ’s therapeutic effect is however not clear. Microarray profiling has previously reported differential expression of genes in DS. No mammalian transcriptomic data on PTZ treatment however exists. Nevertheless, a Drosophila model inspired by rodent models of PTZ induced kindling plasticity has recently been described. Microarray profiling has shown PTZ’s downregulatory effect on gene expression in fly heads. In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential mechanism of PTZ action in DS. I find that transcriptomic correlates of chronic PTZ in Drosophila and DS counteract each other. A significant enrichment is observed between PTZ downregulated and DS upregulated genes, and a significant depletion between PTZ downregulated and DS dowwnregulated genes. Further, the common genes in PTZ Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 downregulated and DS upregulated sets show enrichment for MAP kinase pathway. My analysis suggests that downregulation of MAP kinase pathway may mediate therapeutic effect of PTZ in DS. Existing evidence implicating MAP kinase pathway in DS supports this observation. -
The Effects of Chromosome Number on Mitotic Fidelity and Karyotype Stability
The Effects of Chromosome Number on Mitotic Fidelity and Karyotype Stability Joshua M. Nicholson Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biological Sciences Daniela Cimini, Chair John Robertson Roderick Jensen Richard Walker May 4th, 2015 Blacksburg, Virginia Keywords: aneuploidy, cancer, chromosome mis-segregation, tetraploidy, cytokinesis failure The Effects of Chromosome Number on Mitotic Fidelity and Karyotype Stability Joshua M. Nicholson Abstract The correct number of chromosomes is important for the maintenance of healthy cells and organisms. Maintenance of a correct chromosome number depends on the accurate distribution of chromosomes to the daughter cells during cell division, and errors in chromosome segregation result in abnormal chromosome numbers, or aneuploidy. Aneuploidy is typically associated with deleterious effects on organismal and cellular fitness; however, aneuploidy has also been associated with enhanced cellular growth in certain contexts, such as cancer. Another type of deviation from the normal chromosome number can occur when entire sets of chromosomes are added to the normal (diploid) chromosome number, resulting in polyploidy. Whereas polyploidy is found in certain normal tissues and organisms, tetraploidy (four sets of chromosomes) is associated with a number of precancerous lesions and is believed to promote aneuploidy and tumorigenesis. While it is clear that chromosome mis-segregation causes aneuploidy, the effect of aneuploidy on chromosome segregation is less clear. Similarly, it is unclear whether and how tetraploidy may affect chromosome segregation. The work described here shows that aneuploidy can cause chromosome mis- segregation and induces chromosome-specific phenotypic effects. -
Datasheet: MCA4333Z Product Details
Datasheet: MCA4333Z Description: MOUSE ANTI HUMAN TGN46:Preservative Free Specificity: TGN46 Other names: TGOLN2 Format: Preservative Free Product Type: Monoclonal Antibody Clone: 2F11 Isotype: IgG2a Quantity: 0.1 mg Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Flow Cytometry Immunohistology - Frozen Immunohistology - Paraffin (1) 0.1 - 10 ug/ml ELISA Immunoprecipitation Western Blotting Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Suggested working dilutions are given as a guide only. It is recommended that the user titrates the product for use in their own system using appropriate negative/positive controls. (1)This product requires antigen retrieval using heat treatment prior to staining of paraffin sections.Sodium citrate buffer pH 6.0 is recommended for this purpose. Target Species Human Product Form Purified IgG - liquid Preparation Purified IgG prepared by affinity chromatography on Protein A Buffer Solution Phosphate buffered saline Preservative None present Stabilisers Approx. Protein Ig concentration 0.5 mg/ml Concentrations Immunogen Recombinant protein with a GST tag corresponding to amino acids 229-328 of human TGN46 Page 1 of 3 External Database Links UniProt: O43493 Related reagents Entrez Gene: 10618 TGOLN2 Related reagents Synonyms TGN46, TGN51 Fusion Partners Spleen cells from BALB/c mice were fused with cells from the Sp2/0 myeloma cell line. -
The Parkinson's-Disease-Associated Receptor GPR37 Undergoes
© 2016. Published by The Company of Biologists Ltd | Journal of Cell Science (2016) 129, 1366-1377 doi:10.1242/jcs.176115 RESEARCH ARTICLE The Parkinson’s-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding S. Orvokki Mattila, Jussi T. Tuusa* and Ulla E. Petäjä-Repo‡ ABSTRACT like receptor [Pael receptor (Imai et al., 2001)]. Mutations in the PARK2 The G-protein-coupled receptor 37 ( GPR37) has been implicated in gene leading to the loss of the ubiquitin ligase activity of the juvenile form of Parkinson’s disease, in dopamine signalling and parkin are the most common causes of AR-JP (Kitada et al., 1998). in the survival of dopaminergic cells in animal models. The structure An insoluble form of GPR37 has been reported to accumulate in the and function of the receptor, however, have remained enigmatic. brains of AR-JP patients (Imai et al., 2001) and also in the core of ’ Here, we demonstrate that although GPR37 matures and is exported Lewy bodies of Parkinson s disease patients in general (Murakami from the endoplasmic reticulum in a normal manner upon et al., 2004). Thus, the intracellular aggregation and impaired heterologous expression in HEK293 and SH-SY5Y cells, its long ubiquitylation of unfolded GPR37 by parkin have been proposed to extracellular N-terminus is subject to metalloproteinase-mediated be linked with the death of dopaminergic neurons characteristic of ’ limited proteolysis between E167 and Q168. The proteolytic Parkinson s disease (Imai et al., 2001; Kitao et al., 2007). Based on processing is a rapid and efficient process that occurs constitutively. -
Overview of Research on Fusion Genes in Prostate Cancer
2011 Review Article Overview of research on fusion genes in prostate cancer Chunjiao Song1,2, Huan Chen3 1Medical Research Center, Shaoxing People’s Hospital, Shaoxing University School of Medicine, Shaoxing 312000, China; 2Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, China; 3Key Laboratory of Microorganism Technology and Bioinformatics Research of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310000, China Contributions: (I) Conception and design: C Song; (II) Administrative support: Shaoxing Municipal Health and Family Planning Science and Technology Innovation Project (2017CX004) and Shaoxing Public Welfare Applied Research Project (2018C30058); (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: C Song; (V) Data analysis and interpretation: H Chen; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Chunjiao Song. No. 568 Zhongxing Bei Road, Shaoxing 312000, China. Email: [email protected]. Abstract: Fusion genes are known to drive and promote carcinogenesis and cancer progression. In recent years, the rapid development of biotechnologies has led to the discovery of a large number of fusion genes in prostate cancer specimens. To further investigate them, we summarized the fusion genes. We searched related articles in PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases, and the data of 92 literatures were summarized after preliminary screening. In this review, we summarized approximated 400 fusion genes since the first specific fusion TMPRSS2-ERG was discovered in prostate cancer in 2005. Some of these are prostate cancer specific, some are high-frequency in the prostate cancer of a certain ethnic group. This is a summary of scientific research in related fields and suggests that some fusion genes may become biomarkers or the targets for individualized therapies. -
Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you. -
1 Novel Expression Signatures Identified by Transcriptional Analysis
ARD Online First, published on October 7, 2009 as 10.1136/ard.2009.108043 Ann Rheum Dis: first published as 10.1136/ard.2009.108043 on 7 October 2009. Downloaded from Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis 1Paul A Lyons, 1Eoin F McKinney, 1Tim F Rayner, 1Alexander Hatton, 1Hayley B Woffendin, 1Maria Koukoulaki, 2Thomas C Freeman, 1David RW Jayne, 1Afzal N Chaudhry, and 1Kenneth GC Smith. 1Cambridge Institute for Medical Research and Department of Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK 2Roslin Institute, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK Correspondence should be addressed to Dr Paul Lyons or Prof Kenneth Smith, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK. Telephone: +44 1223 762642, Fax: +44 1223 762640, E-mail: [email protected] or [email protected] Key words: Gene expression, autoimmune disease, SLE, vasculitis Word count: 2,906 The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Annals of the Rheumatic Diseases and any other BMJPGL products to exploit all subsidiary rights, as set out in their licence (http://ard.bmj.com/ifora/licence.pdf). http://ard.bmj.com/ on September 29, 2021 by guest. Protected copyright. 1 Copyright Article author (or their employer) 2009. -
Transcriptomic Causal Networks Identified Patterns of Differential Gene Regulation in Human Brain from Schizophrenia Cases Versus Controls
Transcriptomic Causal Networks identified patterns of differential gene regulation in human brain from Schizophrenia cases versus controls Akram Yazdani1, Raul Mendez-Giraldez2, Michael R Kosorok3, Panos Roussos1,4,5 1Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA 2Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, NC, USA 3Department of Biostatistics, University of North Carolina at Chapel Hill, NC, USA 4Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA 5Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, 10468, USA Abstract Common and complex traits are the consequence of the interaction and regulation of multiple genes simultaneously, which work in a coordinated way. However, the vast majority of studies focus on the differential expression of one individual gene at a time. Here, we aim to provide insight into the underlying relationships of the genes expressed in the human brain in cases with schizophrenia (SCZ) and controls. We introduced a novel approach to identify differential gene regulatory patterns and identify a set of essential genes in the brain tissue. Our method integrates genetic, transcriptomic, and Hi-C data and generates a transcriptomic-causal network. Employing this approach for analysis of RNA-seq data from CommonMind Consortium, we identified differential regulatory patterns for SCZ cases and control groups to unveil the mechanisms that control the transcription of the genes in the human brain. Our analysis identified modules with a high number of SCZ-associated genes as well as assessing the relationship of the hubs with their down-stream genes in both, cases and controls.