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(12) Patent Application Publication (10) Pub. No.: US 2012/0070450 A1 Ishikawa Et Al
US 20120070450A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0070450 A1 Ishikawa et al. (43) Pub. Date: Mar. 22, 2012 (54) LEUKEMA STEM CELLMARKERS Publication Classification (51) Int. Cl. A 6LX 39/395 (2006.01) (75) Inventors: Fumihiko Ishikawa, Kanagawa CI2O I/68 (2006.01) (JP): Osamu Ohara, Kanagawa GOIN 2L/64 (2006.01) (JP); Yoriko Saito, Kanagawa (JP); A6IP35/02 (2006.01) Hiroshi Kitamura, Kanagawa (JP); C40B 30/04 (2006.01) Atsushi Hijikata, Kanagawa (JP); A63L/7088 (2006.01) Hidetoshi Ozawa, Kanagawa (JP); C07K 6/8 (2006.01) Leonard D. Shultz, Bar Harbor, C7H 2L/00 (2006.01) A6II 35/12 (2006.01) ME (US) CI2N 5/078 (2010.01) (52) U.S. Cl. .................. 424/173.1; 424/178.1; 424/93.7: (73) Assignee: RIKEN, Wako-shi (JP) 435/6.14; 435/723; 435/375; 506/9: 514/44 A: 530/389.6; 530/391.7:536/24.5 (57) ABSTRACT (21) Appl. No.: 13/258,993 The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) com PCT Fled: prising (1) measuring the expression level of human leukemic (22) Mar. 24, 2010 stem cell (LSC) marker genes in a biological sample collected from a Subject for a transcription product or translation prod uct of the gene as an analyte and (2) comparing the expression (86) PCT NO.: PCT/UP2010/0551.31 level with a reference value; an LSC-targeting therapeutic agent for AML capable of Suppressing the expression of a S371 (c)(1), gene selected from among LSC marker genes or a Substance (2), (4) Date: Dec. -
Type I Interferons and the Development of Impaired Vascular Function and Repair in Human and Murine Lupus
Type I Interferons and the Development of Impaired Vascular Function and Repair in Human and Murine Lupus by Seth G Thacker A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Immunology) in The University of Michigan 2011 Doctoral Committee: Associate Professor Mariana J. Kaplan, Chair Professor David A. Fox Professor Alisa E. Koch Professor Matthias Kretzler Professor Nicholas W. Lukacs Associate Professor Daniel T. Eitzman © Seth G Thacker 2011 Sharon, this work is dedicated to you. This achievement is as much yours as it is mine. Your support through all six years of this Ph.D. process has been incredible. You put up with my countless miscalculations on when I would finish experiments, and still managed to make me and our kids feel loved and special. Without you this would have no meaning. Sharon, you are the safe harbor in my life. ii Acknowledgments I have been exceptionally fortunate in my time here at the University of Michigan. I have been able to interact with so many supportive people over the years. I would like to express my thanks and admiration for my mentor. Mariana has taught me so much about writing, experimental design and being a successful scientist in general. I could never have made it here without her help. I would also like to thank Mike Denny. He had a hand in the beginning of all of my projects in one way or another, and was always quick and eager to help in whatever way he could. He really made my first year in the lab successful. -
List of Genes Used in Cell Type Enrichment Analysis
List of genes used in cell type enrichment analysis Metagene Cell type Immunity ADAM28 Activated B cell Adaptive CD180 Activated B cell Adaptive CD79B Activated B cell Adaptive BLK Activated B cell Adaptive CD19 Activated B cell Adaptive MS4A1 Activated B cell Adaptive TNFRSF17 Activated B cell Adaptive IGHM Activated B cell Adaptive GNG7 Activated B cell Adaptive MICAL3 Activated B cell Adaptive SPIB Activated B cell Adaptive HLA-DOB Activated B cell Adaptive IGKC Activated B cell Adaptive PNOC Activated B cell Adaptive FCRL2 Activated B cell Adaptive BACH2 Activated B cell Adaptive CR2 Activated B cell Adaptive TCL1A Activated B cell Adaptive AKNA Activated B cell Adaptive ARHGAP25 Activated B cell Adaptive CCL21 Activated B cell Adaptive CD27 Activated B cell Adaptive CD38 Activated B cell Adaptive CLEC17A Activated B cell Adaptive CLEC9A Activated B cell Adaptive CLECL1 Activated B cell Adaptive AIM2 Activated CD4 T cell Adaptive BIRC3 Activated CD4 T cell Adaptive BRIP1 Activated CD4 T cell Adaptive CCL20 Activated CD4 T cell Adaptive CCL4 Activated CD4 T cell Adaptive CCL5 Activated CD4 T cell Adaptive CCNB1 Activated CD4 T cell Adaptive CCR7 Activated CD4 T cell Adaptive DUSP2 Activated CD4 T cell Adaptive ESCO2 Activated CD4 T cell Adaptive ETS1 Activated CD4 T cell Adaptive EXO1 Activated CD4 T cell Adaptive EXOC6 Activated CD4 T cell Adaptive IARS Activated CD4 T cell Adaptive ITK Activated CD4 T cell Adaptive KIF11 Activated CD4 T cell Adaptive KNTC1 Activated CD4 T cell Adaptive NUF2 Activated CD4 T cell Adaptive PRC1 Activated -
Cytokine Nomenclature
RayBiotech, Inc. The protein array pioneer company Cytokine Nomenclature Cytokine Name Official Full Name Genbank Related Names Symbol 4-1BB TNFRSF Tumor necrosis factor NP_001552 CD137, ILA, 4-1BB ligand receptor 9 receptor superfamily .2. member 9 6Ckine CCL21 6-Cysteine Chemokine NM_002989 Small-inducible cytokine A21, Beta chemokine exodus-2, Secondary lymphoid-tissue chemokine, SLC, SCYA21 ACE ACE Angiotensin-converting NP_000780 CD143, DCP, DCP1 enzyme .1. NP_690043 .1. ACE-2 ACE2 Angiotensin-converting NP_068576 ACE-related carboxypeptidase, enzyme 2 .1 Angiotensin-converting enzyme homolog ACTH ACTH Adrenocorticotropic NP_000930 POMC, Pro-opiomelanocortin, hormone .1. Corticotropin-lipotropin, NPP, NP_001030 Melanotropin gamma, Gamma- 333.1 MSH, Potential peptide, Corticotropin, Melanotropin alpha, Alpha-MSH, Corticotropin-like intermediary peptide, CLIP, Lipotropin beta, Beta-LPH, Lipotropin gamma, Gamma-LPH, Melanotropin beta, Beta-MSH, Beta-endorphin, Met-enkephalin ACTHR ACTHR Adrenocorticotropic NP_000520 Melanocortin receptor 2, MC2-R hormone receptor .1 Activin A INHBA Activin A NM_002192 Activin beta-A chain, Erythroid differentiation protein, EDF, INHBA Activin B INHBB Activin B NM_002193 Inhibin beta B chain, Activin beta-B chain Activin C INHBC Activin C NM005538 Inhibin, beta C Activin RIA ACVR1 Activin receptor type-1 NM_001105 Activin receptor type I, ACTR-I, Serine/threonine-protein kinase receptor R1, SKR1, Activin receptor-like kinase 2, ALK-2, TGF-B superfamily receptor type I, TSR-I, ACVRLK2 Activin RIB ACVR1B -
CD4 T-Cell Cytokines Synergize to Induce Proliferation of Malignant and Nonmalignant Innate Intraepithelial Lymphocytes
CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes Yvonne M. C. Kooy-Winkelaara, Dagmar Bouwera, George M. C. Janssenb, Allan Thompsona, Martijn H. Brugmana, Frederike Schmitza, Arnoud H. de Rub, Tom van Gilsc, Gerd Boumac, Jon J. van Rooda,1, Peter A. van Veelenb, M. Luisa Mearind, Chris J. Mulderc, Frits Koninga, and Jeroen van Bergena,1 aDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands; bCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands; cDepartment of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam 1081 HZ, The Netherlands; and dDepartment of Pediatrics, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands Contributed by Jon J. van Rood, December 7, 2016 (sent for review January 6, 2016; reviewed by Georg Gasteiger and Bana Jabri) − Refractory celiac disease type II (RCDII) is a severe complication of lymphoma, because the Lin IELs expanded in RCDII often give celiac disease (CD) characterized by the presence of an enlarged rise to type I enteropathy-associated T-cell lymphoma (EATL). − clonal population of innate intraepithelial lymphocytes (IELs) lacking The main treatment goal in RCDII is to eliminate the Lin IEL − classical B-, T-, and natural killer (NK)-cell lineage markers (Lin IELs) population before its transformation into a high-grade lymphoma. in the duodenum. In ∼50% of patients with RCDII, these Lin−IELs Cladribine (2-CDA) is thought to be especially active against low- develop into a lymphoma for which no effective treatment is avail- grade malignancies with limited proliferative capacity, and reduces − able. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Primate Specific Retrotransposons, Svas, in the Evolution of Networks That Alter Brain Function
Title: Primate specific retrotransposons, SVAs, in the evolution of networks that alter brain function. Olga Vasieva1*, Sultan Cetiner1, Abigail Savage2, Gerald G. Schumann3, Vivien J Bubb2, John P Quinn2*, 1 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K 2 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK 3 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, D-63225 Germany *. Corresponding author Olga Vasieva: Institute of Integrative Biology, Department of Comparative genomics, University of Liverpool, Liverpool, L69 7ZB, [email protected] ; Tel: (+44) 151 795 4456; FAX:(+44) 151 795 4406 John Quinn: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK, [email protected]; Tel: (+44) 151 794 5498. Key words: SVA, trans-mobilisation, behaviour, brain, evolution, psychiatric disorders 1 Abstract The hominid-specific non-LTR retrotransposon termed SINE–VNTR–Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about 13.5 Myrs ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human. -
(CS-ⅣA-Be), a Novel IL-6R Antagonist, Inhibits IL-6/STAT3
Author Manuscript Published OnlineFirst on February 29, 2016; DOI: 10.1158/1535-7163.MCT-15-0551 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Chikusetsusaponin Ⅳa butyl ester (CS-Ⅳa-Be), a novel IL-6R antagonist, inhibits IL-6/STAT3 signaling pathway and induces cancer cell apoptosis Jie Yang 1, 2, Shihui Qian 2, Xueting Cai 1, 2, Wuguang Lu 1, 2, Chunping Hu 1, 2, * Xiaoyan Sun1, 2, Yang Yang1, 2, Qiang Yu 3, S. Paul Gao 4, Peng Cao 1, 2 1. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China 2. Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China 3. Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, 201203, China 4. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY10065, USA Running title: CS-Ⅳa-Be, a novel IL-6R antagonist, inhibits IL-6/STAT3 Keywords: Chikusetsusaponin Ⅳ a butyl ester (CS- Ⅳ a-Be), STAT3, IL-6R, antagonist, cancer Grant support: P. Cao received Jiangsu Province Funds for Distinguished Young Scientists (BK20140049) grant, J. Yang received National Natural Science Foundation of China (No. 81403151) grant, and X.Y. Sun received National Natural Science Foundation of China (No. 81202576) grant. Corresponding author: Peng Cao Institute: Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu, China Mailing address: 100#, Shizi Street, Hongshan Road, Nanjing, Jiangsu, China Tel: +86-25-85608666 Fax: +86-25-85608666 Email address: [email protected] The first co-authors: Jie Yang and Shihui Qian The authors disclose no potential conflicts of interest. -
IL-21R, Human, Recombinant (Sf9) Recombinant Human Interleukin 21 Receptor (Sf9 Cell-Derived)
IL-21R, human, recombinant (Sf9) Recombinant Human Interleukin 21 Receptor (Sf9 cell-derived) Instruction Manual Catalog Number C-62924 Synonyms Interleukin 21 Receptor, Novel Interleukin Receptor, IL-21 Receptor, NILR, Interleukin-21 Receptor, CD360 Antigen, IL-21R, CD360 Description Interleukin-21 receptor, also known as IL-21R is a member of the type I cytokine receptors family. IL-21R forms a heterodimeric receptor complex with the common gamma-chain, a receptor subunit which is also shared by the receptors for Interleukin 2, 4, 7, 9, and 15. Furthermore, IL-21 receptor transduces the growth promoting signal of IL-21, and is significant for the proliferation as well as differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of IL-21 receptor leads to the activation of numerous downstream signaling molecules, including JAK1, JAK3, STAT1, as well as STAT3. IL21R produced in Sf9 cells is a single, glycosylated polypeptide chain (20-232 a.a.) fused to an 8 aa His-tag at the C-terminus. It contains a total of 221 amino acids and has a molecular mass of 25.6 kDa. IL-21R shows multiple bands between 28-40 kDa on SDS-PAGE under reducing conditions and has been purified using proprietary chromatographic techniques. Quantity 10 µg Molecular Mass 25.6 kDa Source Sf9 cells Biological-Activity NA Specific Activity NA Formulation Sterile-filtered colorless protein solution (1 mg/ml) containing phosphate buffered saline (pH 7.4) and 10% glycerol. Reconstitution Please Note: Always centrifuge product briefly before opening vial. The dissolved protein can be diluted into other aqueous buffers and stored at -20°C for future use. -
IFN-Ε Protects Primary Macrophages Against HIV Infection
RESEARCH ARTICLE IFN-ε protects primary macrophages against HIV infection Carley Tasker,1 Selvakumar Subbian,2 Pan Gao,3 Jennifer Couret,1 Carly Levine,2 Saleena Ghanny,1 Patricia Soteropoulos,1 Xilin Zhao,1,2 Nathaniel Landau,4 Wuyuan Lu,3 and Theresa L. Chang1,2 1Department of Microbiology, Biochemistry and Molecular Genetics and 2Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.3Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.4Department of Microbiology, New York University School of Medicine, New York, New York, USA. IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. -
Structure-Based Tuning of Interleukin Receptor Complexes to Promote Anti- Tumor Immunity
Science Highlight – July 2021 Structure-based Tuning of Interleukin Receptor Complexes to Promote Anti- tumor Immunity Cells of the immune system communicate messages between them via small secreted complexes called cytokines. Cytokines are recognized by other cells through membrane receptors. These cell signaling pathways convey information about pathogens, cancers, or other problems that concern the immune system. Two of these cytokines, interleukin 12 (IL- 12) and Interleukin 23 (IL-23) are made by antigen-presenting cells and help to activate lymphocytes, including both T and NK cells. IL-12 and IL-23 have similar structures, which include a four-helix bundle α-subunit and a β- subunit called p40. Despite intense basic research and clinical interest in IL-12 and IL-23, a structural basis for receptor assembly has remained elusive. In work led by the Garcia group at Stanford University, researchers determined the crystal structure of the complete IL-23 receptor complex using x-ray crystallography data collected on SSRL beam line 12-2. Figure 1. Structural mechanism of IL-12 and IL-23 receptor assembly enables graded control of downstream signaling. (A) The 3.4 Å resolution crystal structure of the IL-23 receptor complex. P40 (orange) bridges IL-23 and IL-12. (B-C) CryoEM maps of the IL-23 (8 Å) and IL-12 (10 Å) receptor complexes, respectively. (D-E) Graded control of IL-12 and IL-23 signaling. STAT phosphorylation was analyzed by flow cytometry. The structure revealed that IL-23 uses the four-helix bundle and p40 subunits to engage its’ receptors in a modular fashion (Fig. -
Oas1b-Dependent Immune Transcriptional Profiles of West Nile
MULTIPARENTAL POPULATIONS Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross Richard Green,*,† Courtney Wilkins,*,† Sunil Thomas,*,† Aimee Sekine,*,† Duncan M. Hendrick,*,† Kathleen Voss,*,† Renee C. Ireton,*,† Michael Mooney,‡,§ Jennifer T. Go,*,† Gabrielle Choonoo,‡,§ Sophia Jeng,** Fernando Pardo-Manuel de Villena,††,‡‡ Martin T. Ferris,†† Shannon McWeeney,‡,§,** and Michael Gale Jr.*,†,1 *Department of Immunology and †Center for Innate Immunity and Immune Disease (CIIID), University of Washington, § Seattle, Washington 98109, ‡OHSU Knight Cancer Institute, Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, and **Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon 97239, ††Department of Genetics and ‡‡Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514 ABSTRACT The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus KEYWORDS infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. Oas However, the impact of Oas variation on overall innate immune programming and global gene expression flavivirus among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts viral infection in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of innate immunity genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, multiparental 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three populations wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B pro- Multi-parent tein.