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  • Articles  (220)
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  • 2000-2004  (206)
  • 1940-1944  (14)
  • 2004  (206)
  • 1942  (14)
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  • 2000-2004  (206)
  • 1940-1944  (14)
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  • 1
    Publication Date: 2004-01-06
    Description: To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698949/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698949/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Siming -- Armstrong, Christopher M -- Bertin, Nicolas -- Ge, Hui -- Milstein, Stuart -- Boxem, Mike -- Vidalain, Pierre-Olivier -- Han, Jing-Dong J -- Chesneau, Alban -- Hao, Tong -- Goldberg, Debra S -- Li, Ning -- Martinez, Monica -- Rual, Jean-Francois -- Lamesch, Philippe -- Xu, Lai -- Tewari, Muneesh -- Wong, Sharyl L -- Zhang, Lan V -- Berriz, Gabriel F -- Jacotot, Laurent -- Vaglio, Philippe -- Reboul, Jerome -- Hirozane-Kishikawa, Tomoko -- Li, Qianru -- Gabel, Harrison W -- Elewa, Ahmed -- Baumgartner, Bridget -- Rose, Debra J -- Yu, Haiyuan -- Bosak, Stephanie -- Sequerra, Reynaldo -- Fraser, Andrew -- Mango, Susan E -- Saxton, William M -- Strome, Susan -- Van Den Heuvel, Sander -- Piano, Fabio -- Vandenhaute, Jean -- Sardet, Claude -- Gerstein, Mark -- Doucette-Stamm, Lynn -- Gunsalus, Kristin C -- Harper, J Wade -- Cusick, Michael E -- Roth, Frederick P -- Hill, David E -- Vidal, Marc -- R01 AG011085/AG/NIA NIH HHS/ -- R01 GM034059/GM/NIGMS NIH HHS/ -- R01 GM034059-18/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):540-3. Epub 2004 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704431" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Computational Biology ; Evolution, Molecular ; Genes, Helminth ; Genomics ; Open Reading Frames ; Phenotype ; Protein Binding ; Proteome/*metabolism ; Transcription, Genetic ; Two-Hybrid System Techniques
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  • 2
    Publication Date: 2004-07-13
    Description: We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hazuda, Daria J -- Young, Steven D -- Guare, James P -- Anthony, Neville J -- Gomez, Robert P -- Wai, John S -- Vacca, Joseph P -- Handt, Larry -- Motzel, Sherri L -- Klein, Hilton J -- Dornadula, Geethanjali -- Danovich, Robert M -- Witmer, Marc V -- Wilson, Keith A A -- Tussey, Lynda -- Schleif, William A -- Gabryelski, Lori S -- Jin, Lixia -- Miller, Michael D -- Casimiro, Danilo R -- Emini, Emilio A -- Shiver, John W -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):528-32. Epub 2004 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA. daria_hazuda@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247437" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology ; Animals ; Anti-HIV Agents/administration & dosage/blood/pharmacology/therapeutic use ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Drug Resistance, Viral ; HIV Integrase/genetics/metabolism ; HIV Integrase Inhibitors/administration & dosage/blood/pharmacology/therapeutic ; use ; HIV-1/drug effects/enzymology/genetics/*physiology ; Immunity, Cellular ; Integrase Inhibitors/administration & dosage/blood/pharmacology/*therapeutic use ; Integrases/genetics/metabolism ; Leukocytes, Mononuclear/virology ; Macaca mulatta ; Mutation ; Naphthyridines/administration & dosage/blood/pharmacology/*therapeutic use ; Simian Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology ; Simian Immunodeficiency Virus/drug effects/enzymology/genetics/*physiology ; Viral Load ; Viremia/drug therapy ; Virus Replication/drug effects
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  • 3
    Publication Date: 2004-07-27
    Description: Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verez-Bencomo, V -- Fernandez-Santana, V -- Hardy, Eugenio -- Toledo, Maria E -- Rodriguez, Maria C -- Heynngnezz, Lazaro -- Rodriguez, Arlene -- Baly, Alberto -- Herrera, Luis -- Izquierdo, Mabel -- Villar, Annette -- Valdes, Yury -- Cosme, Karelia -- Deler, Mercedes L -- Montane, Manuel -- Garcia, Ernesto -- Ramos, Alexis -- Aguilar, Aristides -- Medina, Ernesto -- Torano, Gilda -- Sosa, Ivan -- Hernandez, Ibis -- Martinez, Raydel -- Muzachio, Alexis -- Carmenates, Ania -- Costa, Lourdes -- Cardoso, Felix -- Campa, Concepcion -- Diaz, Manuel -- Roy, Rene -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):522-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Synthetic Antigens, Facultad de Quimica, Universidad de la Habana, Ciudad Habana, Cuba, 10400. vicente@fq.uh.cu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15273395" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antibodies, Bacterial/biosynthesis/blood ; Child, Preschool ; Double-Blind Method ; Glycoconjugates/immunology ; Haemophilus Vaccines/administration & dosage/*chemical synthesis/*immunology ; Haemophilus influenzae type b/*immunology ; Humans ; Immunization Schedule ; Immunoglobulin G/blood ; Infant ; Polysaccharides/*chemical synthesis/*immunology/isolation & purification ; Polysaccharides, Bacterial/*immunology/isolation & purification ; Tetanus Toxoid/immunology ; Vaccines, Conjugate/administration & dosage/immunology
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  • 4
    Publication Date: 2004-04-24
    Description: The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618874/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618874/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jen, Joanna C -- Chan, Wai-Man -- Bosley, Thomas M -- Wan, Jijun -- Carr, Janai R -- Rub, Udo -- Shattuck, David -- Salamon, Georges -- Kudo, Lili C -- Ou, Jing -- Lin, Doris D M -- Salih, Mustafa A M -- Kansu, Tulay -- Al Dhalaan, Hesham -- Al Zayed, Zayed -- MacDonald, David B -- Stigsby, Bent -- Plaitakis, Andreas -- Dretakis, Emmanuel K -- Gottlob, Irene -- Pieh, Christina -- Traboulsi, Elias I -- Wang, Qing -- Wang, Lejin -- Andrews, Caroline -- Yamada, Koki -- Demer, Joseph L -- Karim, Shaheen -- Alger, Jeffry R -- Geschwind, Daniel H -- Deller, Thomas -- Sicotte, Nancy L -- Nelson, Stanley F -- Baloh, Robert W -- Engle, Elizabeth C -- DC00162/DC/NIDCD NIH HHS/ -- DC05524/DC/NIDCD NIH HHS/ -- EY12498/EY/NEI NIH HHS/ -- EY13583/EY/NEI NIH HHS/ -- EY15298/EY/NEI NIH HHS/ -- EY15311/EY/NEI NIH HHS/ -- MH60233/MH/NIMH NIH HHS/ -- P30 HD 18655/HD/NICHD NIH HHS/ -- R01 EY008313/EY/NEI NIH HHS/ -- R01 EY008313-14/EY/NEI NIH HHS/ -- R01 HL066251/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1509-13. Epub 2004 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15105459" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Motifs ; Amino Acid Sequence ; Axons/*physiology ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Female ; Functional Laterality ; Genetic Linkage ; Humans ; In Situ Hybridization ; Magnetic Resonance Imaging ; Male ; Medulla Oblongata/growth & development/pathology ; Microsatellite Repeats ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Neural Pathways ; Ophthalmoplegia/*genetics/pathology/physiopathology ; Pedigree ; Protein Structure, Tertiary ; Receptors, Immunologic/chemistry/*genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rhombencephalon/*growth & development/pathology ; Scoliosis/*genetics/pathology/physiopathology ; Sequence Analysis, DNA ; Syndrome
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  • 5
    Publication Date: 2004-02-21
    Description: The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunet, Anne -- Sweeney, Lora B -- Sturgill, J Fitzhugh -- Chua, Katrin F -- Greer, Paul L -- Lin, Yingxi -- Tran, Hien -- Ross, Sarah E -- Mostoslavsky, Raul -- Cohen, Haim Y -- Hu, Linda S -- Cheng, Hwei-Ling -- Jedrychowski, Mark P -- Gygi, Steven P -- Sinclair, David A -- Alt, Frederick W -- Greenberg, Michael E -- NIHP30-HD18655/HD/NICHD NIH HHS/ -- P01 NS35138-17/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 26;303(5666):2011-5. Epub 2004 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Center for Blood Research (CBR) Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976264" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Apoptosis ; Cell Cycle ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; Cerebellum/cytology ; Forkhead Transcription Factors ; Gene Expression Profiling ; Gene Expression Regulation ; Histone Deacetylases/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Knockout ; Neurons/cytology ; *Oxidative Stress ; Phosphorylation ; Proteins/genetics ; Recombinant Proteins/metabolism ; Sirtuin 1 ; Sirtuins/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
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  • 6
    Publication Date: 2004-02-07
    Description: A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Amy Hin Yan -- Lesage, Guillaume -- Bader, Gary D -- Ding, Huiming -- Xu, Hong -- Xin, Xiaofeng -- Young, James -- Berriz, Gabriel F -- Brost, Renee L -- Chang, Michael -- Chen, YiQun -- Cheng, Xin -- Chua, Gordon -- Friesen, Helena -- Goldberg, Debra S -- Haynes, Jennifer -- Humphries, Christine -- He, Grace -- Hussein, Shamiza -- Ke, Lizhu -- Krogan, Nevan -- Li, Zhijian -- Levinson, Joshua N -- Lu, Hong -- Menard, Patrice -- Munyana, Christella -- Parsons, Ainslie B -- Ryan, Owen -- Tonikian, Raffi -- Roberts, Tania -- Sdicu, Anne-Marie -- Shapiro, Jesse -- Sheikh, Bilal -- Suter, Bernhard -- Wong, Sharyl L -- Zhang, Lan V -- Zhu, Hongwei -- Burd, Christopher G -- Munro, Sean -- Sander, Chris -- Rine, Jasper -- Greenblatt, Jack -- Peter, Matthias -- Bretscher, Anthony -- Bell, Graham -- Roth, Frederick P -- Brown, Grant W -- Andrews, Brenda -- Bussey, Howard -- Boone, Charles -- GM39066/GM/NIGMS NIH HHS/ -- GM61221/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):808-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764870" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Computational Biology ; Cystic Fibrosis/genetics ; Gene Deletion ; Genes, Essential ; *Genes, Fungal ; Genetic Diseases, Inborn/genetics ; Genotype ; Humans ; Molecular Sequence Data ; Multifactorial Inheritance ; Mutation ; Phenotype ; Polymorphism, Genetic ; Retinitis Pigmentosa/genetics ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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  • 7
    Publication Date: 2004-11-06
    Description: Phosphorylation of the human histone variant H2A.X and H2Av, its homolog in Drosophila melanogaster, occurs rapidly at sites of DNA double-strand breaks. Little is known about the function of this phosphorylation or its removal during DNA repair. Here, we demonstrate that the Drosophila Tip60 (dTip60) chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av. Both the histone acetyltransferase dTip60 as well as the adenosine triphosphatase Domino/p400 catalyze the exchange of phospho-H2Av. Thus, these data reveal a previously unknown mechanism for selective histone exchange that uses the concerted action of two distinct chromatin-remodeling enzymes within the same multiprotein complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kusch, Thomas -- Florens, Laurence -- Macdonald, W Hayes -- Swanson, Selene K -- Glaser, Robert L -- Yates, John R 3rd -- Abmayr, Susan M -- Washburn, Michael P -- Workman, Jerry L -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2084-7. Epub 2004 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tnk@stowers-institute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528408" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyl Coenzyme A/metabolism ; Acetylation ; Acetyltransferases/genetics/*metabolism ; Adenosine Triphosphatases/metabolism ; Animals ; Cell Line ; *DNA Damage ; DNA Repair ; Dimerization ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/genetics/*metabolism ; Embryo, Nonmammalian/metabolism ; Histone Acetyltransferases ; Histones/*metabolism ; Multiprotein Complexes/*metabolism ; Nucleosomes/*metabolism ; Phosphorylation ; RNA Interference ; Recombinant Proteins/metabolism ; Transcription Factors/metabolism
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  • 8
    Publication Date: 2004-12-14
    Description: Mammalian oocytes are held in prophase arrest by an unknown signal from the surrounding somatic cells. Here we show that the orphan Gs-linked receptor GPR3, which is localized in the oocyte, maintains this arrest. Oocytes from Gpr3 knockout mice resume meiosis within antral follicles, independently of an increase in luteinizing hormone, and this phenotype can be reversed by injection of Gpr3 RNA into the oocytes. Thus, the GPR3 receptor is a link in communication between the somatic cells and oocyte of the ovarian follicle and is crucial for the regulation of meiosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mehlmann, Lisa M -- Saeki, Yoshinaga -- Tanaka, Shigeru -- Brennan, Thomas J -- Evsikov, Alexei V -- Pendola, Frank L -- Knowles, Barbara B -- Eppig, John J -- Jaffe, Laurinda A -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1947-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Connecticut Health Center (UCHC), Farmington, CT 06032, USA. lmehlmann@neuron.uchc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591206" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Animals ; Chondroitin Sulfate Proteoglycans/genetics/metabolism ; Expressed Sequence Tags ; Female ; Granulosa Cells/physiology ; Heterotrimeric GTP-Binding Proteins/*metabolism ; In Situ Hybridization ; Lectins, C-Type ; Ligands ; Luteinizing Hormone/metabolism ; *Meiosis ; Metaphase ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitosis ; Oocytes/*physiology ; Ovarian Follicle/*physiology ; RNA/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/*physiology ; Versicans
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  • 9
    Publication Date: 2004-01-13
    Description: A family of unusual proteins is deposited in flat, structural platelets in reflective tissues of the squid Euprymna scolopes. These proteins, which we have named reflectins, are encoded by at least six genes in three subfamilies and have no reported homologs outside of squids. Reflectins possess five repeating domains, which are highly conserved among members of the family. The proteins have a very unusual composition, with four relatively rare residues (tyrosine, methionine, arginine, and tryptophan) comprising approximately 57% of a reflectin, and several common residues (alanine, isoleucine, leucine, and lysine) occurring in none of the family members. These protein-based reflectors in squids provide a marked example of nanofabrication in animal systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crookes, Wendy J -- Ding, Lin-Lin -- Huang, Qing Ling -- Kimbell, Jennifer R -- Horwitz, Joseph -- McFall-Ngai, Margaret J -- NEI R01 EY3897/EY/NEI NIH HHS/ -- R01 A150661/PHS HHS/ -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):235-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kewalo Marine Laboratory, Pacific Biomedical Research Center, University of Hawaii-Manoa, 41 Ahui Street, Honolulu, HI 96813, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716016" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/analysis ; Animals ; DNA, Complementary ; Decapodiformes/anatomy & histology/*chemistry/genetics ; Electrophoresis, Polyacrylamide Gel ; Immunoblotting ; Immunohistochemistry ; *Light ; Microscopy, Immunoelectron ; Molecular Sequence Data ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Proteins/*analysis/*chemistry/genetics/isolation & purification ; Sequence Alignment ; Solubility
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  • 10
    Publication Date: 2004-07-13
    Description: Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leist, Marcel -- Ghezzi, Pietro -- Grasso, Giovanni -- Bianchi, Roberto -- Villa, Pia -- Fratelli, Maddalena -- Savino, Costanza -- Bianchi, Marina -- Nielsen, Jacob -- Gerwien, Jens -- Kallunki, Pekka -- Larsen, Anna Kirstine -- Helboe, Lone -- Christensen, Soren -- Pedersen, Lars O -- Nielsen, Mette -- Torup, Lars -- Sager, Thomas -- Sfacteria, Alessandra -- Erbayraktar, Serhat -- Erbayraktar, Zubeyde -- Gokmen, Necati -- Yilmaz, Osman -- Cerami-Hand, Carla -- Xie, Qiao-Wen -- Coleman, Thomas -- Cerami, Anthony -- Brines, Michael -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):239-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉H. Lundbeck A/S, 2500 Valby, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Binding Sites ; Cells, Cultured ; Diabetic Neuropathies/drug therapy ; Drug Design ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Erythropoiesis ; Erythropoietin/*analogs & ; derivatives/chemistry/genetics/metabolism/pharmacology/*therapeutic use ; Female ; Hematocrit ; Humans ; Ligands ; Mice ; Mice, Inbred C3H ; Mutagenesis ; Nervous System Diseases/*drug therapy ; Neurons/metabolism ; Neuroprotective Agents/chemistry/metabolism/pharmacology/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptors, Erythropoietin/metabolism ; Recombinant Proteins ; Signal Transduction ; Spinal Cord Compression/drug therapy ; Stroke/drug therapy ; Structure-Activity Relationship
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