Genome-Wide Analysis of Genetic Predisposition to Alzheimer's
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AP2A2 Antibody Cat
AP2A2 Antibody Cat. No.: 63-513 AP2A2 Antibody Formalin-fixed and paraffin-embedded human Flow cytometric analysis of HepG2 cells using AP2A2 hepatocarcinoma with AP2A2 Antibody , which was Antibody (bottom histogram) compared to a negative peroxidase-conjugated to the secondary antibody, control cell (top histogram). FITC-conjugated goat-anti- followed by DAB staining. rabbit secondary antibodies were used for the analysis. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This AP2A2 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 610-637 amino acids from the Central region of human AP2A2. TESTED APPLICATIONS: Flow, IHC-P, WB For WB starting dilution is: 1:1000 APPLICATIONS: For IHC-P starting dilution is: 1:10~50 For FACS starting dilution is: 1:10~50 September 25, 2021 1 https://www.prosci-inc.com/ap2a2-antibody-63-513.html PREDICTED MOLECULAR 104 kDa WEIGHT: Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: AP2A2 AP-2 complex subunit alpha-2, 100 kDa coated vesicle -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
Análise Integrativa De Perfis Transcricionais De Pacientes Com
UNIVERSIDADE DE SÃO PAULO FACULDADE DE MEDICINA DE RIBEIRÃO PRETO PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Ribeirão Preto – 2012 ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Tese apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Genética Orientador: Prof. Dr. Eduardo Antonio Donadi Co-orientador: Prof. Dr. Geraldo A. S. Passos Ribeirão Preto – 2012 AUTORIZO A REPRODUÇÃO E DIVULGAÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE. FICHA CATALOGRÁFICA Evangelista, Adriane Feijó Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. Ribeirão Preto, 2012 192p. Tese de Doutorado apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Área de Concentração: Genética. Orientador: Donadi, Eduardo Antonio Co-orientador: Passos, Geraldo A. 1. Expressão gênica – microarrays 2. Análise bioinformática por module maps 3. Diabetes mellitus tipo 1 4. Diabetes mellitus tipo 2 5. Diabetes mellitus gestacional FOLHA DE APROVAÇÃO ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. -
Methylglyoxal Down-Regulates the Expression of Cell Cycle Associated
www.nature.com/scientificreports OPEN Methylglyoxal down-regulates the expression of cell cycle associated genes and activates the p53 Received: 8 May 2018 Accepted: 12 December 2018 pathway in human umbilical vein Published: xx xx xxxx endothelial cells Jana D. Braun1, Diego O. Pastene1, Annette Breedijk1, Angelica Rodriguez1, Björn B. Hofmann1, Carsten Sticht2, Elke von Ochsenstein3, Heike Allgayer3, Jacob van den Born4, Stephan Bakker4, Sibylle J. Hauske1, Bernhard K. Krämer1, Benito A. Yard1 & Thomas Albrecht1 Although methylglyoxal (MGO) has emerged as key mediator of diabetic microvascular complications, the infuence of MGO on the vascular transcriptome has not thoroughly been assessed. Since diabetes is associated with low grade infammation causing sustained nuclear factor-kappa B (NF-κB) activation, the current study addressed 1) to what extent MGO changes the transcriptome of human umbilical vein endothelial cells (HUVECs) exposed to an infammatory milieu, 2) what are the dominant pathways by which these changes occur and 3) to what extent is this afected by carnosine, a putative scavenger of MGO. Microarray analysis revealed that exposure of HUVECs to high MGO concentrations signifcantly changes gene expression, characterized by prominent down-regulation of cell cycle associated genes and up-regulation of heme oxygenase-1 (HO-1). KEGG-based pathway analysis identifed six signifcantly enriched pathways of which the p53 pathway was the most afected. No signifcant enrichment of infammatory pathways was found, yet, MGO did inhibit VCAM-1 expression in Western blot analysis. Carnosine signifcantly counteracted MGO-mediated changes in a subset of diferentially expressed genes. Collectively, our results suggest that MGO initiates distinct transcriptional changes in cell cycle/apoptosis genes, which may explain MGO toxicity at high concentrations. -
Ykt6 Membrane-To-Cytosol Cycling Regulates Exosomal Wnt Secretion
bioRxiv preprint doi: https://doi.org/10.1101/485565; this version posted December 3, 2018. 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. Ykt6 membrane-to-cytosol cycling regulates exosomal Wnt secretion Karen Linnemannstöns1,2, Pradhipa Karuna1,2, Leonie Witte1,2, Jeanette Kittel1,2, Adi Danieli1,2, Denise Müller1,2, Lena Nitsch1,2, Mona Honemann-Capito1,2, Ferdinand Grawe3,4, Andreas Wodarz3,4 and Julia Christina Gross1,2* Affiliations: 1Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany. 2Developmental Biochemistry, University Medical Center Goettingen, Goettingen, Germany. 3Molecular Cell Biology, Institute I for Anatomy, University of Cologne Medical School, Cologne, Germany 4Cluster of Excellence-Cellular Stress Response in Aging-Associated Diseases (CECAD), Cologne, Germany *Correspondence: Dr. Julia Christina Gross, Hematology and Oncology/Developmental Biochemistry, University Medical Center Goettingen, Justus-von-Liebig Weg 11, 37077 Goettingen Germany Abstract Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. -
Integrating Protein Copy Numbers with Interaction Networks to Quantify Stoichiometry in Mammalian Endocytosis
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 2020. 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. Integrating protein copy numbers with interaction networks to quantify stoichiometry in mammalian endocytosis Daisy Duan1, Meretta Hanson1, David O. Holland2, Margaret E Johnson1* 1TC Jenkins Department of Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218. 2NIH, Bethesda, MD, 20892. *Corresponding Author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 2020. 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. Abstract Proteins that drive processes like clathrin-mediated endocytosis (CME) are expressed at various copy numbers within a cell, from hundreds (e.g. auxilin) to millions (e.g. clathrin). Between cell types with identical genomes, copy numbers further vary significantly both in absolute and relative abundance. These variations contain essential information about each protein’s function, but how significant are these variations and how can they be quantified to infer useful functional behavior? Here, we address this by quantifying the stoichiometry of proteins involved in the CME network. We find robust trends across three cell types in proteins that are sub- vs super-stoichiometric in terms of protein function, network topology (e.g. -
Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR
Published OnlineFirst June 26, 2018; DOI: 10.1158/0008-5472.CAN-17-3858 Cancer Tumor Biology and Immunology Research Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR Dysregulation and Signaling in Lung Adenocarcinoma Shiao-Ya Hong1, Yu-Rung Kao1, Te-Chang Lee1, and Cheng-Wen Wu1,2,3,4 Abstract CBLC (CBL proto-oncogene c) belongs to the CBL protein ubiquitinated and positively regulated aEGFR stability family, which has E3 ubiquitin ligase activity toward activated through the conjugation of polyubiquitin by K6 and K11 receptor tyrosine kinases. CBLC is frequently upregulated in linkages. This CBLC-mediated polyubiquitination promoted non–small cell lung cancer (NSCLC), yet very little is known either preferential recycling of aEGFR back to the plasma about the functions of CBLC in tumorigenesis. Here we show membrane or trafficking to the cell nucleus. IHC analyses that CBLC is an epigenetically demethylated target and its revealed a positive correlation between phospho-EGFR and expression can be upregulated in NSCLC after treatment with CBLC in lung adenocarcinoma. In summary, we demonstrate a the DNA methylation inhibitor 50-azacytidine. Depletion novel mechanism by which aEGFR escapes lysosomal degra- of CBLC significantly inhibited cell viability and clonogenicity dation in a CBLC/ubiquitin-dependent manner to sustain its in vitro and reduced tumor growth in a xenograft model. CBLC activation. Our work identifies CBLC as a potential diagnostic silencing further sensitized EGFR-mutated NSCLC cells to biomarker and also points to its utilization as a novel thera- treatment with tyrosine kinase inhibitors. Conversely, ectopic peutic target for NSCLC therapy. expression of CBLC enhanced the activation of EGFR and downstream ERK1/2 signaling after ligand stimulation by Significance: This work demonstrates the role of CBLC expres- competing with CBL for EGFR binding. -
Identification and Validation of Genes Affecting Aortic Lesions in Mice
Identification and validation of genes affecting aortic lesions in mice Xia Yang, … , Aldons J. Lusis, Pek Yee Lum J Clin Invest. 2010;120(7):2414-2422. https://doi.org/10.1172/JCI42742. Research Article Cardiology Atherosclerosis represents the most significant risk factor for coronary artery disease (CAD), the leading cause of death in developed countries. To better understand the pathogenesis of atherosclerosis, we applied a likelih ood-based model selection method to infer gene-disease causality relationships for the aortic lesion trait in a segregating mouse population demonstrating a spectrum of susceptibility to developing atherosclerotic lesions. We identified 292 genes that tested causal for aortic lesions from liver and adipose tissues of these mice, and we experimentally validated one of these candidate causal genes, complement component 3a receptor 1 (C3ar1), using a knockout mouse model. We also found that genes identified by this method overlapped with genes progressively regulated in the aortic arches of 2 mouse models of atherosclerosis during atherosclerotic lesion development. By comparing our gene set with findings from public human genome-wide association studies (GWAS) of CAD and related traits, we found that 5 genes identified by our study overlapped with published studies in humans in which they were identified as risk factors for multiple atherosclerosis- related pathologies, including myocardial infarction, serum uric acid levels, mean platelet volume, aortic root size, and heart failure. Candidate causal genes were also found to be enriched with CAD risk polymorphisms identified by the Wellcome Trust Case Control Consortium (WTCCC). Our findings therefore validate the ability of causality testing procedures to […] Find the latest version: https://jci.me/42742/pdf Research article Identification and validation of genes affecting aortic lesions in mice Xia Yang,1,2 Larry Peterson,3 Rolf Thieringer,4 Joshua L. -
A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder
INVESTIGATION A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder Aparna Prasad,* Daniele Merico,* Bhooma Thiruvahindrapuram,* John Wei,* Anath C. Lionel,*,† Daisuke Sato,* Jessica Rickaby,* Chao Lu,* Peter Szatmari,‡ Wendy Roberts,§ Bridget A. Fernandez,** Christian R. Marshall,*,†† Eli Hatchwell,‡‡ Peggy S. Eis,‡‡ and Stephen W. Scherer*,†,††,1 *The Centre for Applied Genomics, Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto M5G 1L7, Canada, †Department of Molecular Genetics, University of Toronto, Toronto M5G 1L7, Canada, ‡Offord Centre for Child Studies, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton L8P 3B6, § Canada, Autism Research Unit, The Hospital for Sick Children, Toronto M5G 1X8, Canada, **Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada, ††McLaughlin Centre, University of Toronto, Toronto M5G 1L7, Canada, and ‡‡Population Diagnostics, Inc., Melville, New York 11747 ABSTRACT The identification of rare inherited and de novo copy number variations (CNVs) in human KEYWORDS subjects has proven a productive approach to highlight risk genes for autism spectrum disorder (ASD). A rare variants variety of microarrays are available to detect CNVs, including single-nucleotide polymorphism (SNP) arrays gene copy and comparative genomic hybridization (CGH) arrays. Here, we examine a cohort of 696 unrelated ASD number cases using a high-resolution one-million feature CGH microarray, the majority of which were previously chromosomal genotyped with SNP arrays. Our objective was to discover new CNVs in ASD cases that were not detected abnormalities by SNP microarray analysis and to delineate novel ASD risk loci via combined analysis of CGH and SNP array cytogenetics data sets on the ASD cohort and CGH data on an additional 1000 control samples. -
Mouse Atg10 Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Atg10 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Atg10 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Atg10 gene (NCBI Reference Sequence: NM_025770 ; Ensembl: ENSMUSG00000021619 ) is located on Mouse chromosome 13. 8 exons are identified, with the ATG start codon in exon 2 and the TGA stop codon in exon 7 (Transcript: ENSMUST00000022119). Exon 2 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Atg10 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-326J5 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 2 starts from about 100% of the coding region. The knockout of Exon 2 will result in frameshift of the gene. The size of intron 1 for 5'-loxP site insertion: 15505 bp, and the size of intron 2 for 3'-loxP site insertion: 54005 bp. The size of effective cKO region: ~605 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 2 8 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Atg10 Homology arm cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. -
Associated Fibroblasts in Non-Small Cell Lung Cancer
Prognostic gene-expression signature of carcinoma- associated fibroblasts in non-small cell lung cancer Roya Navaba,1, Dan Strumpfa,1, Bizhan Bandarchia,1, Chang-Qi Zhua,1, Melania Pintiliea, Varune Rohan Ramnarinea, Emin Ibrahimova, Nikolina Radulovicha, Lisa Leunga, Malgorzata Barczyka,b, Devang Panchala, Christine Toa, James J. Yuna, Sandy Dera, Frances A. Shepherda,c, Igor Jurisicaa,d,e, and Ming-Sound Tsaoa,e,f,2 aThe Campbell Family Institute for Cancer Research, Ontario Cancer Institute at Princess Margaret Hospital, University Health Network, Toronto, ON, Canada M5G 2M9; bDepartment of Biomedicine, Jonas Lies vei, N-5009 Bergen, Norway; Departments of cMedicine, dComputer Science, and eMedical Biophysics, and fLaboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5A 2N4 Edited* by Tak Wah Mak, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute at Princess Margaret Hospital, University Health Network, Toronto, ON, Canada, and approved March 10, 2011 (received for review September 28, 2010) The tumor microenvironment strongly influences cancer develop- Results ment, progression, and metastasis. The role of carcinoma-associated Cultured CAFs Display Features of Myofibroblasts. By using a study fibroblasts (CAFs) in these processes and their clinical impact has protocol approved by the Institutional Research Ethics Board, not been studied systematically in non-small cell lung carcinoma CAFs and NFs were cultured from 15 surgically resected primary (NSCLC). We established primary cultures of CAFs and matched nor- NSCLCs, and the histologically confirmed normal lung tissue was mal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that obtained from the same lobe (Table S1A). Both the primary CAFs have greater ability than NFs to enhance the tumorigenicity of cultured CAFs and tumor stromal fibroblasts expressed α-smooth lung cancer cell lines. -
Downloaded from the App Store and Nucleobase, Nucleotide and Nucleic Acid Metabolism 7 Google Play
Hoytema van Konijnenburg et al. Orphanet J Rare Dis (2021) 16:170 https://doi.org/10.1186/s13023-021-01727-2 REVIEW Open Access Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app Eva M. M. Hoytema van Konijnenburg1†, Saskia B. Wortmann2,3,4†, Marina J. Koelewijn2, Laura A. Tseng1,4, Roderick Houben6, Sylvia Stöckler‑Ipsiroglu5, Carlos R. Ferreira7 and Clara D. M. van Karnebeek1,2,4,8* Abstract Background: The Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disabil‑ ity (collectively ‘treatable IDs’). Our aim is to update the 2012 review on treatable IDs and App to capture the advances made in the identifcation of new IMDs along with increased pathophysiological insights catalyzing therapeutic development and implementation. Methods: Two independent reviewers queried PubMed, OMIM and Orphanet databases to reassess all previously included disorders and therapies and to identify all reports on Treatable IDs published between 2012 and 2021. These were included if listed in the International Classifcation of IMDs (ICIMD) and presenting with ID as a major feature, and if published evidence for a therapeutic intervention improving ID primary and/or secondary outcomes is avail‑ able. Data on clinical symptoms, diagnostic testing, treatment strategies, efects on outcomes, and evidence levels were extracted and evaluated by the reviewers and external experts. The generated knowledge was translated into a diagnostic algorithm and updated version of the App with novel features. Results: Our review identifed 116 treatable IDs (139 genes), of which 44 newly identifed, belonging to 17 ICIMD categories.