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  • Articles  (769)
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  • 1
    Publication Date: 2002-03-23
    Description: Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beattie, Eric C -- Stellwagen, David -- Morishita, Wade -- Bresnahan, Jacqueline C -- Ha, Byeong Keun -- Von Zastrow, Mark -- Beattie, Michael S -- Malenka, Robert C -- DA00439/DA/NIDA NIH HHS/ -- MH063394/MH/NIMH NIH HHS/ -- NS 31193/NS/NINDS NIH HHS/ -- NS38079/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 22;295(5563):2282-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA. beattie.2@osu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11910117" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/pharmacology ; Astrocytes/*metabolism ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Gene Expression Regulation/drug effects ; Hippocampus/cytology/metabolism ; Neuronal Plasticity/drug effects ; Neurons/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I ; Synapses/drug effects/*metabolism ; Synaptic Transmission/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2002-10-05
    Description: The detection of single-nucleotide polymorphisms in pathogenic microorganisms has normally been carried out by trial and error. Here we show that DNA hybridization with high-density oligonucleotide arrays provides rapid and convenient detection of single-nucleotide polymorphisms in Plasmodium falciparum, despite its exceptionally high adenine-thymine (AT) content (82%). A disproportionate number of polymorphisms are found in genes encoding proteins associated with the cell membrane. These genes are targets for only 22% of the oligonucleotide probes but account for 69% of the polymorphisms. Genetic variation is also enriched in subtelomeric regions, which account for 22% of the chromosome but 76% of the polymorphisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkman, Sarah K -- Hartl, Daniel L -- Wirth, Dyann F -- Nielsen, Kaare M -- Choi, Mehee -- Batalov, Serge -- Zhou, Yingyao -- Plouffe, David -- Le Roch, Karine G -- Abagyan, Ruben -- Winzeler, Elizabeth A -- GM61351/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):216-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes/genetics ; DNA, Protozoan/genetics ; *Genes, Protozoan ; Genetic Variation ; Genome, Protozoan ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Oligonucleotide Probes ; Plasmodium falciparum/*genetics ; *Polymorphism, Single Nucleotide ; Protozoan Proteins/*genetics ; Sequence Analysis, DNA
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" 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/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2002-06-22
    Description: Positive-strand RNA viruses such as poliovirus replicate their genomes on intracellular membranes of their eukaryotic hosts. Electron microscopy has revealed that purified poliovirus RNA-dependent RNA polymerase forms planar and tubular oligomeric arrays. The structural integrity of these arrays correlates with cooperative RNA binding and RNA elongation and is sensitive to mutations that disrupt intermolecular contacts predicted by the polymerase structure. Membranous vesicles isolated from poliovirus-infected cells contain structures consistent with the presence of two-dimensional polymerase arrays on their surfaces during infection. Therefore, host cytoplasmic membranes may function as physical foundations for two-dimensional polymerase arrays, conferring the advantages of surface catalysis to viral RNA replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyle, John M -- Bullitt, Esther -- Bienz, Kurt -- Kirkegaard, Karla -- AI-42119/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2218-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077417" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Inclusion Bodies, Viral/metabolism/ultrastructure ; Microscopy, Electron ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Poliovirus/*enzymology/physiology ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; RNA Replicase/*chemistry/isolation & purification/*metabolism/ultrastructure ; RNA, Viral/biosynthesis/*metabolism ; Viral Core Proteins/metabolism ; Virus Replication
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  • 5
    Publication Date: 2002-01-05
    Description: The recently released human genome sequences provide us with reference data to conduct comparative genomic research on primates, which will be important to understand what genetic information makes us human. Here we present a first-generation human-chimpanzee comparative genome map and its initial analysis. The map was constructed through paired alignment of 77,461 chimpanzee bacterial artificial chromosome end sequences with publicly available human genome sequences. We detected candidate positions, including two clusters on human chromosome 21 that suggest large, nonrandom regions of difference between the two genomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fujiyama, Asao -- Watanabe, Hidemi -- Toyoda, Atsushi -- Taylor, Todd D -- Itoh, Takehiko -- Tsai, Shih-Feng -- Park, Hong-Seog -- Yaspo, Marie-Laure -- Lehrach, Hans -- Chen, Zhu -- Fu, Gang -- Saitou, Naruya -- Osoegawa, Kazutoyo -- de Jong, Pieter J -- Suto, Yumiko -- Hattori, Masahira -- Sakaki, Yoshiyuki -- New York, N.Y. -- Science. 2002 Jan 4;295(5552):131-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. afujiyam@gsc.riken.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11778049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes, Artificial, Bacterial ; Chromosomes, Human, Pair 21/genetics ; Cloning, Molecular ; Contig Mapping ; Female ; Gene Library ; *Genome ; *Genome, Human ; Humans ; Male ; Pan troglodytes/*genetics ; *Physical Chromosome Mapping ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Tagged Sites ; X Chromosome/genetics ; Y Chromosome/genetics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-08-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ingolia, Nicholas T -- Murray, Andrew W -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):948-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology and Bauer Center for Genomics Research, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169717" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Biological Evolution ; *Cell Cycle Proteins ; Cells, Cultured ; Dual Specificity Phosphatase 1 ; *Feedback, Physiological ; Immediate-Early Proteins/*metabolism ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; *Phosphoprotein Phosphatases ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Protein Phosphatase 1 ; Protein Tyrosine Phosphatases/*metabolism
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  • 7
    Publication Date: 2003-08-09
    Description: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaspar, Brian K -- Llado, Jeronia -- Sherkat, Nushin -- Rothstein, Jeffrey D -- Gage, Fred H -- AG12992/AG/NIA NIH HHS/ -- AG21876/AG/NIA NIH HHS/ -- NS33958/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907804" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/pathology/physiopathology/*therapy ; Animals ; Apoptosis ; Base Sequence ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Dependovirus/*genetics ; Disease Models, Animal ; Disease Progression ; Gene Transfer Techniques ; *Genetic Therapy ; *Genetic Vectors/administration & dosage ; Glial Cell Line-Derived Neurotrophic Factor ; Green Fluorescent Proteins ; Insulin-Like Growth Factor I/*genetics ; Luminescent Proteins/genetics ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Motor Neurons/pathology/virology ; Muscle, Skeletal/virology ; Nerve Growth Factors/genetics ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Random Allocation ; Spinal Cord/chemistry/pathology/virology ; Superoxide Dismutase/genetics/metabolism ; Ubiquitin/analysis
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  • 8
    Publication Date: 2003-10-04
    Description: Analysis of the human and mouse genomes identified an abundance of conserved non-genic sequences (CNGs). The significance and evolutionary depth of their conservation remain unanswered. We have quantified levels and patterns of conservation of 191 CNGs of human chromosome 21 in 14 mammalian species. We found that CNGs are significantly more conserved than protein-coding genes and noncoding RNAS (ncRNAs) within the mammalian class from primates to monotremes to marsupials. The pattern of substitutions in CNGs differed from that seen in protein-coding and ncRNA genes and resembled that of protein-binding regions. About 0.3% to 1% of the human genome corresponds to a previously unknown class of extremely constrained CNGs shared among mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dermitzakis, Emmanouil T -- Reymond, Alexandre -- Scamuffa, Nathalie -- Ucla, Catherine -- Kirkness, Ewen -- Rossier, Colette -- Antonarakis, Stylianos E -- New York, N.Y. -- Science. 2003 Nov 7;302(5647):1033-5. Epub 2003 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Medical Genetics and National Center of Competence in Research (NCCR) Frontiers in Genetics, University of Geneva Medical School and University Hospitals, 1211 Geneva, Switzerland. Emmanouil.Dermitzakis@medecine.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes, Human, Pair 21/*genetics ; Chromosomes, Mammalian/*genetics ; *Conserved Sequence ; DNA, Intergenic/*genetics ; Discriminant Analysis ; *Evolution, Molecular ; Female ; Genetic Code ; Genome ; Humans ; Male ; Mammals/*genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Proteins/genetics ; RNA, Untranslated/genetics ; Selection, Genetic ; Sequence Alignment ; Species Specificity ; Time ; Transcription, Genetic
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  • 9
    Publication Date: 2002-08-10
    Description: Primate-specific segmental duplications are considered important in human disease and evolution. The inability to distinguish between allelic and duplication sequence overlap has hampered their characterization as well as assembly and annotation of our genome. We developed a method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence. This test has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity. We mapped 169 large regions flanked by highly similar duplications. Twenty-four of these hot spots of genomic instability have been associated with genetic disease. Our analysis indicates a highly nonrandom chromosomal and genic distribution of recent segmental duplications, with a likely role in expanding protein diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, Jeffrey A -- Gu, Zhiping -- Clark, Royden A -- Reinert, Knut -- Samonte, Rhea V -- Schwartz, Stuart -- Adams, Mark D -- Myers, Eugene W -- Li, Peter W -- Eichler, Evan E -- CA094816/CA/NCI NIH HHS/ -- GM58815/GM/NIGMS NIH HHS/ -- HG002318/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1003-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Center for Computational Genomics, and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169732" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Base Sequence ; Biological Evolution ; Chromosomes, Human/genetics ; Computational Biology ; Databases, Nucleic Acid ; Exons ; Expressed Sequence Tags ; *Gene Duplication ; Gene Rearrangement ; *Genes, Duplicate ; Genetic Diseases, Inborn/genetics ; *Genome, Human ; Humans ; Models, Genetic ; Polymorphism, Single Nucleotide ; Proteome ; Recombination, Genetic ; Sequence Alignment
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  • 10
    Publication Date: 2002-04-27
    Description: Little is known of how plant disease resistance (R) proteins recognize pathogens and activate plant defenses. Rcr3 is specifically required for the function of Cf-2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain-like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L. pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these two species encode proteins that differ by only seven amino acids. Possible roles of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruger, Julia -- Thomas, Colwyn M -- Golstein, Catherine -- Dixon, Mark S -- Smoker, Matthew -- Tang, Saijun -- Mulder, Lonneke -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2002 Apr 26;296(5568):744-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976458" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Cladosporium/*physiology ; Cloning, Molecular ; Cysteine Endopeptidases/chemistry/*genetics/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Gene Expression Regulation, Plant ; *Genes, Plant ; Immunity, Innate ; Leucine/analogs & derivatives/pharmacology ; Lycopersicon esculentum/*enzymology/genetics/*microbiology/physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; *Plant Diseases ; Plant Leaves/enzymology ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/chemistry/metabolism ; Tobacco/genetics ; Transgenes
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallo, Robert C -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1728-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459576" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Serodiagnosis/history ; Acquired Immunodeficiency Syndrome/diagnosis/*history/immunology/virology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cells, Cultured ; France ; *HIV/classification/isolation & purification/physiology ; History, 20th Century ; Human T-lymphotropic virus 1/isolation & purification/physiology ; Human T-lymphotropic virus 2/isolation & purification/physiology ; Humans ; Interleukin-2/history/isolation & purification/physiology ; Patents as Topic/history ; RNA-Directed DNA Polymerase/history/isolation & purification/metabolism ; United States ; Virus Cultivation
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  • 12
    Publication Date: 2003-04-12
    Description: Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300-CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grossman, Steven R -- Deato, Maria E -- Brignone, Chrystelle -- Chan, Ho Man -- Kung, Andrew L -- Tagami, Hideaki -- Nakatani, Yoshihiro -- Livingston, David M -- CA15751/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):342-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690203" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/metabolism ; Animals ; Catalysis ; Cells, Cultured ; E1A-Associated p300 Protein ; Embryo, Mammalian ; Fibroblasts/metabolism ; Humans ; Ligases/antagonists & inhibitors/metabolism ; Mice ; Nuclear Proteins/antagonists & inhibitors/*metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Trans-Activators/antagonists & inhibitors/*metabolism ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-07-26
    Description: It is well known that hunting dramatically reduced all baleen whale populations, yet reliable estimates of former whale abundances are elusive. Based on coalescent models for mitochondrial DNA sequence variation, the genetic diversity of North Atlantic whales suggests population sizes of approximately 240,000 humpback, 360,000 fin, and 265,000 minke whales. Estimates for fin and humpback whales are far greater than those previously calculated for prewhaling populations and 6 to 20 times higher than present-day population estimates. Such discrepancies suggest the need for a quantitative reevaluation of historical whale populations and a fundamental revision in our conception of the natural state of the oceans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roman, Joe -- Palumbi, Stephen R -- New York, N.Y. -- Science. 2003 Jul 25;301(5632):508-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12881568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Base Sequence ; Conservation of Natural Resources ; DNA, Mitochondrial/genetics ; *Ecosystem ; Female ; Genetic Variation ; Genetics, Population ; Male ; Molecular Sequence Data ; Population Density ; Population Dynamics ; Time Factors ; *Whales/classification/genetics
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-01
    Description: Although curvature of biological surfaces has been considered from mathematical and biophysical perspectives, its molecular and developmental basis is unclear. We have studied the cin mutant of Antirrhinum, which has crinkly rather than flat leaves. Leaves of cin display excess growth in marginal regions, resulting in a gradual introduction of negative curvature during development. This reflects a change in the shape and the progression of a cell-cycle arrest front moving from the leaf tip toward the base. CIN encodes a TCP protein and is expressed downstream of the arrest front. We propose that CIN promotes zero curvature (flatness) by making cells more sensitive to an arrest signal, particularly in marginal regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Utpal -- Crawford, Brian C W -- Carpenter, Rosemary -- Coen, Enrico -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610308" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antirrhinum/cytology/*genetics/*growth & development/metabolism ; Base Sequence ; Cell Cycle ; Cell Differentiation ; Cell Division ; Cell Size ; Cyclin D3 ; Cyclins/genetics/metabolism ; Gene Deletion ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Histones/genetics/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Plant Leaves/anatomy & histology/cytology/*growth & development/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Surface Properties ; Transcription Factors/chemistry/genetics/*metabolism
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  • 15
    Publication Date: 2003-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nickle, David C -- Jensen, Mark A -- Gottlieb, Geoffrey S -- Shriner, Daniel -- Learn, Gerald H -- Rodrigo, Allen G -- Mullins, James I -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1515-8; author reply 1515-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624248" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines/immunology ; Base Sequence ; Consensus Sequence ; Evolution, Molecular ; Genes, env ; Genes, gag ; Genetic Variation ; HIV Antigens/genetics/immunology ; HIV-1/classification/*genetics/*immunology ; Humans ; *Phylogeny
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  • 16
    Publication Date: 2003-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nobrega, Marcelo A -- Ovcharenko, Ivan -- Afzal, Veena -- Rubin, Edward M -- HL66728/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 17;302(5644):413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14563999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/genetics ; Base Sequence ; Conserved Sequence ; *DNA, Intergenic ; *Drosophila Proteins ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Regulation ; Genes, Reporter ; Humans ; Introns ; Mice ; Mice, Transgenic ; Nuclear Proteins/*genetics ; Synteny ; Takifugu/genetics ; Tetraodontiformes/genetics ; Xenopus/genetics ; Zebrafish/genetics
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  • 17
    Publication Date: 2003-07-05
    Description: Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alavi, Alireza -- Hood, John D -- Frausto, Ricardo -- Stupack, Dwayne G -- Cheresh, David A -- CA45726/CA/NCI NIH HHS/ -- CA50286/CA/NCI NIH HHS/ -- CA75924/CA/NCI NIH HHS/ -- P01 CA78045/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):94-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12843393" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Survival ; Cells, Cultured ; Chick Embryo ; Endothelial Growth Factors/pharmacology ; Endothelium, Vascular/*cytology/drug effects ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Flavonoids/pharmacology ; Humans ; Intercellular Signaling Peptides and Proteins/pharmacology ; Lymphokines/pharmacology ; MAP Kinase Kinase 1 ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Neovascularization, Pathologic ; *Neovascularization, Physiologic/drug effects ; Phosphorylation ; Point Mutation ; Protein Transport ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins B-raf ; Proto-Oncogene Proteins c-raf/chemistry/genetics/*metabolism ; Signal Transduction ; Umbilical Veins ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; p21-Activated Kinases ; src-Family Kinases/antagonists & inhibitors/metabolism
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  • 18
    Publication Date: 2003-11-01
    Description: Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*genetics ; Calcium/*metabolism ; Cell Membrane/physiology ; Cells, Cultured ; *Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Electrophoretic Mobility Shift Assay ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Methyl-CpG-Binding Protein 2 ; Methylation ; Mice ; Mice, Knockout ; Neurons/metabolism/physiology ; Phosphorylation ; Potassium Chloride/pharmacology ; Precipitin Tests ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; *Transcription, Genetic
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  • 19
    Publication Date: 2000-01-05
    Description: High-precision genetic mapping was used to define the regions that contain centromere functions on each natural chromosome in Arabidopsis thaliana. These regions exhibited dramatic recombinational repression and contained complex DNA surrounding large arrays of 180-base pair repeats. Unexpectedly, the DNA within the centromeres was not merely structural but also encoded several expressed genes. The regions flanking the centromeres were densely populated by repetitive elements yet experienced normal levels of recombination. The genetically defined centromeres were well conserved among Arabidopsis ecotypes but displayed limited sequence homology between different chromosomes, excluding repetitive DNA. This investigation provides a platform for dissecting the role of individual sequences in centromeres in higher eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copenhaver, G P -- Nickel, K -- Kuromori, T -- Benito, M I -- Kaul, S -- Lin, X -- Bevan, M -- Murphy, G -- Harris, B -- Parnell, L D -- McCombie, W R -- Martienssen, R A -- Marra, M -- Preuss, D -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2468-74.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Chicago, Department of Molecular Genetics and Cell Biology, 1103 East 57 Street, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617454" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/chemistry/*genetics ; Base Composition ; Base Sequence ; Centromere/*genetics/physiology ; Conserved Sequence ; Contig Mapping ; Crosses, Genetic ; Crossing Over, Genetic ; DNA, Plant/chemistry/*genetics ; Gene Expression ; *Genes, Plant ; Meiosis ; Models, Genetic ; *Recombination, Genetic ; *Repetitive Sequences, Nucleic Acid ; Retroelements ; Sequence Analysis, DNA
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Mutation at the mouse progressive ankylosis (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. Here, we show that the ank locus encodes a multipass transmembrane protein (ANK) that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. A highly conserved gene is present in humans and other vertebrates. These results identify ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, A M -- Johnson, M D -- Kingsley, D M -- 5T32GM07365/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):265-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine, Stanford, CA 94305-5327, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*genetics/metabolism/pathology ; Base Sequence ; Biological Transport ; COS Cells ; Calcinosis/*genetics ; Chromosome Mapping ; Cloning, Molecular ; Dna ; Diphosphates/*metabolism ; Durapatite/metabolism ; Gene Expression ; Genetic Complementation Test ; Humans ; Membrane Proteins/*genetics/metabolism/*physiology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; Phenotype ; Phosphate Transport Proteins ; Physical Chromosome Mapping ; Sequence Homology, Nucleic Acid ; Tissue Distribution
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-06
    Description: A human cytomegalovirus gene array was used to identify a previously unidentified class of viral transcripts. These transcripts, termed virion RNAs, were packaged within infectious virions and were delivered to the host cell on infection. This mechanism of herpesvirus gene expression allows for viral genes to be expressed within an infected cell immediately after virus entry and in the absence of transcription from the viral genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bresnahan, W A -- Shenk, T -- CA85786/CA/NCI NIH HHS/ -- F32 AI010448/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2373-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875924" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Nucleus/metabolism ; Cells, Cultured ; Cytomegalovirus/*genetics/*physiology ; Dactinomycin/pharmacology ; Gene Expression ; Genes, Viral ; Genome, Viral ; Golgi Apparatus/metabolism ; Humans ; Nucleic Acid Hybridization ; Nucleic Acid Synthesis Inhibitors/pharmacology ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/*genetics/isolation & purification/metabolism ; RNA, Viral/*genetics/isolation & purification/metabolism ; Recombinant Fusion Proteins/metabolism ; Transcription, Genetic ; Viral Proteins/genetics/metabolism ; Virion/*genetics/physiology ; Virus Assembly
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  • 22
    Publication Date: 2000-09-01
    Description: Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉May, M J -- D'Acquisto, F -- Madge, L A -- Glockner, J -- Pober, J S -- Ghosh, S -- AI 33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1550-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968790" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; COS Cells ; Cells, Cultured ; E-Selectin/biosynthesis/genetics ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; I-kappa B Kinase ; Inflammation/drug therapy ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; NF-kappa B/*metabolism ; Peptides/chemistry/*pharmacology ; Point Mutation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
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  • 23
    Publication Date: 2000-05-29
    Description: Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis, resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramakrishnan, L -- Federspiel, N A -- Falkow, S -- AI 32396/AI/NIAID NIH HHS/ -- K08 AI 01400/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 May 26;288(5470):1436-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. lalitar@cmgm.stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10827956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/*genetics ; Cells, Cultured ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Glycine/analysis ; Granuloma/*microbiology/pathology ; Humans ; Macrophages/*microbiology ; Mutation ; Mycobacterium Infections, Nontuberculous/*microbiology/pathology ; Mycobacterium marinum/*genetics/growth & development/*pathogenicity ; Mycobacterium tuberculosis/genetics/pathogenicity ; Promoter Regions, Genetic ; Rana pipiens ; Tuberculosis/microbiology ; Virulence
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-06
    Description: Many evolutionary studies use comparisons across species to detect evidence of natural selection and to examine the rate of character evolution. Statistical analyses in these studies are usually performed by means of a species phylogeny to accommodate the effects of shared evolutionary history. The phylogeny is usually treated as known without error; this assumption is problematic because inferred phylogenies are subject to both stochastic and systematic errors. We describe methods for accommodating phylogenetic uncertainty in evolutionary studies by means of Bayesian inference. The methods are computationally intensive but general enough to be applied in most comparative evolutionary studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huelsenbeck, J P -- Rannala, B -- Masly, J P -- R01-HG01988/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2349-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Rochester, Rochester, NY 14627, USA. johnh@brahms.biology.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aphids/genetics ; Base Sequence ; Bayes Theorem ; *Biological Evolution ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Markov Chains ; Monte Carlo Method ; *Phylogeny ; Probability ; Stochastic Processes
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  • 25
    Publication Date: 2000-07-15
    Description: Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Coviella, I -- Berse, B -- Krauss, R -- Thies, R S -- Blusztajn, J K -- P01 AG09525/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):313-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894782" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/biosynthesis ; Animals ; Bone Morphogenetic Proteins/*physiology ; Carrier Proteins/genetics ; Cells, Cultured ; Central Nervous System ; Choline O-Acetyltransferase/genetics ; Embryo, Mammalian/metabolism ; Fibroblast Growth Factor 2/physiology ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Growth Differentiation Factor 2 ; *Membrane Transport Proteins ; Mice ; Neurons/metabolism ; Phenotype ; RNA, Messenger/metabolism ; Septum of Brain/embryology/metabolism ; Spinal Cord/embryology/metabolism ; Up-Regulation ; Vesicular Acetylcholine Transport Proteins ; *Vesicular Transport Proteins
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, K -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2319.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10917828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Consensus Sequence ; Conserved Sequence ; DNA-Binding Proteins/*metabolism ; *Databases, Factual ; GATA3 Transcription Factor ; Gene Expression Regulation ; Humans ; Interleukins/*genetics ; NFATC Transcription Factors ; *Nuclear Proteins ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism
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  • 27
    Publication Date: 2000-08-11
    Description: Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nissen, P -- Hansen, J -- Ban, N -- Moore, P B -- Steitz, T A -- GM22778/GM/NIGMS NIH HHS/ -- GM54216/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 11;289(5481):920-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry and Department of Chemistry, Yale University, and Howard Hughes Medical Institute, New Haven, CT 06520-8114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10937990" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeal Proteins/chemistry/metabolism ; Base Pairing ; Base Sequence ; Binding Sites ; Catalysis ; Crystallization ; Evolution, Molecular ; Haloarcula marismortui/chemistry/metabolism/ultrastructure ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligonucleotides/metabolism ; *Peptide Biosynthesis ; Peptides/metabolism ; Peptidyl Transferases/antagonists & inhibitors/chemistry/*metabolism ; Phosphates/chemistry/metabolism ; Protein Conformation ; Puromycin/metabolism ; RNA, Archaeal/chemistry/metabolism ; RNA, Catalytic/*chemistry/*metabolism ; RNA, Ribosomal, 23S/*chemistry/*metabolism ; RNA, Transfer/metabolism ; RNA, Transfer, Amino Acyl/metabolism ; Ribosomal Proteins/chemistry/metabolism ; Ribosomes/chemistry/*metabolism
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, M -- New York, N.Y. -- Science. 2000 Jun 23;288(5474):2115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10896574" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Bioethics ; DNA/genetics ; European Union ; France ; *Genes ; Humans ; Patents as Topic/*legislation & jurisprudence
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  • 29
    Publication Date: 2000-02-11
    Description: The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell-mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasec, P -- Braud, V M -- Rickards, C -- Powell, M B -- McSharry, B P -- Gadola, S -- Cerundolo, V -- Borysiewicz, L K -- McMichael, A J -- Wilkinson, G W -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669413" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; *Antigens, CD ; Cell Line ; Cell Membrane/immunology ; Cells, Cultured ; Conserved Sequence ; Cytomegalovirus/genetics/immunology/*metabolism ; Cytotoxicity, Immunologic ; Down-Regulation ; HLA Antigens/immunology/*metabolism ; Histocompatibility Antigens Class I/immunology/*metabolism ; Humans ; Killer Cells, Natural/*immunology ; Molecular Sequence Data ; Open Reading Frames ; Protein Sorting Signals/chemistry/*metabolism ; Receptors, Immunologic/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Transfection ; Up-Regulation ; Viral Proteins/chemistry/genetics/*metabolism
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  • 30
    Publication Date: 2000-05-08
    Description: The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tournier, C -- Hess, P -- Yang, D D -- Xu, J -- Turner, T K -- Nimnual, A -- Bar-Sagi, D -- Jones, S N -- Flavell, R A -- Davis, R J -- New York, N.Y. -- Science. 2000 May 5;288(5467):870-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry & Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptotic Protease-Activating Factor 1 ; Caspase 3 ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Cell Division ; Cells, Cultured ; Cytochrome c Group/*metabolism ; DNA Fragmentation ; Enzyme Activation ; Fibroblasts ; Gene Targeting ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Methyl Methanesulfonate/pharmacology ; Mice ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinases/genetics/*metabolism ; NF-kappa B/metabolism ; *Protein-Serine-Threonine Kinases ; Proteins/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Ultraviolet Rays
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  • 31
    Publication Date: 2000-04-25
    Description: Major histocompatibility complex class II (MHC II) molecules capture peptides within the endocytic pathway to generate T cell receptor (TCR) ligands. Immature dendritic cells (DCs) sequester intact antigens in lysosomes, processing and converting antigens into peptide-MHC II complexes upon induction of DC maturation. The complexes then accumulate in distinctive, nonlysosomal MHC II+ vesicles that appear to migrate to the cell surface. Although the vesicles exclude soluble lysosomal contents and antigen-processing machinery, many contain MHC I and B7 costimulatory molecules. After arrival at the cell surface, the MHC and costimulatory molecules remain clustered. Thus, transport of peptide-MHC II complexes by DCs not only accomplishes transfer from late endocytic compartments to the plasma membrane, but does so in a manner that selectively concentrates TCR ligands and costimulatory molecules for T cell contact.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turley, S J -- Inaba, K -- Garrett, W S -- Ebersold, M -- Unternaehrer, J -- Steinman, R M -- Mellman, I -- AI-13013/AI/NIAID NIH HHS/ -- AI-34098/AI/NIAID NIH HHS/ -- AI-39672/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):522-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520-8002, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10775112" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; *Antigen Presentation ; Antigens, CD/immunology/metabolism ; Antigens, CD86 ; B-Lymphocytes/immunology/metabolism ; Bicyclo Compounds, Heterocyclic/pharmacology ; Biological Transport ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism ; Endocytosis ; Endosomes/immunology/metabolism ; Histocompatibility Antigens Class I/immunology/metabolism ; Histocompatibility Antigens Class II/immunology/*metabolism ; Kinetics ; Ligands ; Lipopolysaccharides/immunology ; Lysosomes/immunology/metabolism ; Membrane Glycoproteins/immunology/metabolism ; Mice ; Mice, Inbred C3H ; Muramidase/immunology/*metabolism ; Peptide Fragments/immunology/*metabolism ; Receptors, Antigen, T-Cell/metabolism ; Thiazoles/pharmacology ; Thiazolidines
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2133-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chemoreceptor Cells/*physiology ; Humans ; Mice ; Multigene Family ; Receptors, Cell Surface/genetics/*physiology ; *Taste ; Taste Buds/*physiology ; Transducin/biosynthesis
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-05-08
    Description: The telomerase ribonucleoprotein has a phylogenetically divergent RNA subunit, which contains a short template for telomeric DNA synthesis. To understand how telomerase RNA participates in mechanistic aspects of telomere synthesis, we studied a conserved secondary structure adjacent to the template. Disruption of this structure caused DNA synthesis to proceed beyond the normal template boundary, resulting in altered telomere sequences, telomere shortening, and cellular growth defects. Compensatory mutations restored normal telomerase function. Thus, the RNA structure, rather than its sequence, specifies the template boundary. This study reveals a specific function for an RNA structure in the enzymatic action of telomerase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tzfati, Y -- Fulton, T B -- Roy, J -- Blackburn, E H -- GM26259/GM/NIGMS NIH HHS/ -- T32CA09270/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 May 5;288(5467):863-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0414, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797010" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Cloning, Molecular ; DNA, Fungal/biosynthesis ; Genes, Fungal ; Kluyveromyces/*enzymology/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; RNA, Fungal/*chemistry/genetics/*metabolism ; Telomerase/*chemistry/genetics/*metabolism ; Telomere/genetics/metabolism ; Templates, Genetic
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-21
    Description: We describe a single RNA sequence that can assume either of two ribozyme folds and catalyze the two respective reactions. The two ribozyme folds share no evolutionary history and are completely different, with no base pairs (and probably no hydrogen bonds) in common. Minor variants of this sequence are highly active for one or the other reaction, and can be accessed from prototype ribozymes through a series of neutral mutations. Thus, in the course of evolution, new RNA folds could arise from preexisting folds, without the need to carry inactive intermediate sequences. This raises the possibility that biological RNAs having no structural or functional similarity might share a common ancestry. Furthermore, functional and structural divergence might, in some cases, precede rather than follow gene duplication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schultes, E A -- Bartel, D P -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):448-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10903205" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Catalysis ; Evolution, Molecular ; Gene Duplication ; Hepatitis Delta Virus/enzymology/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Point Mutation ; RNA/metabolism ; RNA, Catalytic/*chemistry/genetics/*metabolism
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  • 35
    Publication Date: 2000-11-10
    Description: Reciprocal gene activation and restriction during cell type differentiation from a common lineage is a hallmark of mammalian organogenesis. A key question, then, is whether a critical transcriptional activator of cell type-specific gene targets can also restrict expression of the same genes in other cell types. Here, we show that whereas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one cell type, the somatotrope, it restricts its expression from a second cell type, the lactotrope. This distinction depends on a two-base pair spacing in accommodation of the bipartite POU domains on a conserved growth hormone promoter site. The allosteric effect on Pit-1, in combination with other DNA binding factors, results in the recruitment of a corepressor complex, including nuclear receptor corepressor N-CoR, which, unexpectedly, is required for active long-term repression of the growth hormone gene in lactotropes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scully, K M -- Jacobson, E M -- Jepsen, K -- Lunyak, V -- Viadiu, H -- Carriere, C -- Rose, D W -- Hooshmand, F -- Aggarwal, A K -- Rosenfeld, M G -- R01 DK18477/DK/NIDDK NIH HHS/ -- R01 DK54802/DK/NIDDK NIH HHS/ -- R01 GM49327/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 10;290(5494):1127-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11073444" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Conserved Sequence ; Crystallization ; DNA/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Female ; *Gene Expression Regulation ; Genes, Reporter ; Growth Hormone/*genetics ; Male ; Mice ; Mice, Transgenic ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Nuclear Receptor Co-Repressor 1 ; Pituitary Gland/cytology/*metabolism ; Prolactin/*genetics ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Tertiary ; Rats ; Repressor Proteins/chemistry/genetics/*metabolism ; Transcription Factor Pit-1 ; Transcription Factors/chemistry/genetics/*metabolism ; Transcriptional Activation
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  • 36
    Publication Date: 2000-08-19
    Description: Pig cloning will have a marked impact on the optimization of meat production and xenotransplantation. To clone pigs from differentiated cells, we microinjected the nuclei of porcine (Sus scrofa) fetal fibroblasts into enucleated oocytes, and development was induced by electroactivation. The transfer of 110 cloned embryos to four surrogate mothers produced an apparently normal female piglet. The clonal provenance of the piglet was indicated by her coat color and confirmed by DNA microsatellite analysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onishi, A -- Iwamoto, M -- Akita, T -- Mikawa, S -- Takeda, K -- Awata, T -- Hanada, H -- Perry, A C -- New York, N.Y. -- Science. 2000 Aug 18;289(5482):1188-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Breeding and Genetics, National Institute of Animal Industry, Tsukuba Norin Danchi, Ibaraki-ken 305-0901, Japan. onishi@niai.affrc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10947985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cloning, Organism/*methods ; Electric Stimulation ; Embryo Transfer ; Embryonic and Fetal Development ; Female ; Fetus/cytology ; Fibroblasts/ultrastructure ; Microinjections ; Microsatellite Repeats ; *Nuclear Transfer Techniques ; Oocytes ; Pregnancy ; *Swine/embryology/genetics
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-25
    Description: In eukaryotes, dozens of posttranscriptional modifications are directed to specific nucleotides in ribosomal RNAs (rRNAs) by small nucleolar RNAs (snoRNAs). We identified homologs of snoRNA genes in both branches of the Archaea. Eighteen small sno-like RNAs (sRNAs) were cloned from the archaeon Sulfolobus acidocaldarius by coimmunoprecipitation with archaeal fibrillarin and NOP56, the homologs of eukaryotic snoRNA-associated proteins. We trained a probabilistic model on these sRNAs to search for more sRNAs in archaeal genomic sequences. Over 200 additional sRNAs were identified in seven archaeal genomes representing both the Crenarchaeota and the Euryarchaeota. snoRNA-based rRNA processing was therefore probably present in the last common ancestor of Archaea and Eukarya, predating the evolution of a morphologically distinct nucleolus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Omer, A D -- Lowe, T M -- Russell, A G -- Ebhardt, H -- Eddy, S R -- Dennis, P P -- HG01363/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):517-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10775111" target="_blank"〉PubMed〈/a〉
    Keywords: Archaea/*genetics ; Archaeal Proteins/genetics ; Base Sequence ; Chromosomal Proteins, Non-Histone/genetics ; Cloning, Molecular ; Genome, Archaeal ; Methylation ; Models, Statistical ; Molecular Sequence Data ; Nuclear Proteins/genetics ; RNA Processing, Post-Transcriptional ; RNA, Archaeal/chemistry/*genetics/metabolism ; RNA, Guide/chemistry/genetics ; RNA, Ribosomal/chemistry/genetics/metabolism ; RNA, Small Nucleolar/chemistry/*genetics/metabolism ; Sulfolobus acidocaldarius/*genetics
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, C Y -- Lewis, R V -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1477-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Wyoming, Laramie, WY 82071-3944, USA. hayashi@uwyo.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688794" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Crossing Over, Genetic ; DNA/genetics ; DNA Replication ; *Evolution, Molecular ; *Exons ; Gene Conversion ; *Genes ; *Introns ; Molecular Sequence Data ; Mutation ; Proteins/chemistry/*genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Species Specificity ; Spiders/*genetics
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  • 39
    Publication Date: 2001-01-06
    Description: All aspects of cellular RNA metabolism and the replication of many viruses require DExH/D proteins that manipulate RNA in a manner that requires nucleoside triphosphates. Although DExH/D proteins have been shown to unwind purified RNA duplexes, most RNA molecules in the cellular environment are complexed with proteins. It has therefore been speculated that DExH/D proteins may also affect RNA-protein interactions. We demonstrate that the DExH protein NPH-II from vaccinia virus can displace the protein U1A from RNA in an active adenosine triphosphate-dependent fashion. NPH-II increases the rate of U1A dissociation by more than three orders of magnitude while retaining helicase processivity. This indicates that DExH/D proteins can effectively catalyze protein displacement from RNA and thereby participate in the structural reorganization of ribonucleoprotein assemblies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jankowsky, E -- Gross, C H -- Shuman, S -- Pyle, A M -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):121-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141562" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Acid Anhydride Hydrolases/chemistry/*metabolism ; Adenosine Triphosphate/metabolism ; Base Sequence ; Binding Sites ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleoside-Triphosphatase ; Protein Binding ; Protein Conformation ; RNA/chemistry/*metabolism ; RNA Helicases/chemistry/*metabolism ; *RNA-Binding Proteins ; Ribonucleoprotein, U1 Small Nuclear/*metabolism
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barres, B A -- Smith, S J -- New York, N.Y. -- Science. 2001 Nov 9;294(5545):1296-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Stanford University School of Medicine, Fairchild Science Building, Stanford, CA 94305-5125, USA. barres@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11701918" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoproteins E/metabolism/pharmacology ; Astrocytes/*metabolism ; Brain/metabolism ; Cells, Cultured ; Cholesterol/*metabolism/pharmacology ; Coculture Techniques ; Mice ; Neuroglia/metabolism ; Neuronal Plasticity ; Neurons/metabolism/*physiology ; Recombinant Proteins/pharmacology ; Signal Transduction ; Synapses/*physiology
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  • 41
    Publication Date: 2001-10-06
    Description: The definition of centromeres of human chromosomes requires a complete genomic understanding of these regions. Toward this end, we report integration of physical mapping, genetic, and functional approaches, together with sequencing of selected regions, to define the centromere of the human X chromosome and to explore the evolution of sequences responsible for chromosome segregation. The transitional region between expressed sequences on the short arm of the X and the chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is satellite-rich. At the junction between this satellite region and canonical DXZ1 repeats, diverged repeat units provide direct evidence of unequal crossover as the homogenizing force of these arrays. Results from deletion analysis of mitotically stable chromosome rearrangements and from a human artificial chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function. Evolutionary studies indicate that, while alpha satellite DNA present throughout the pericentromeric region of the X chromosome appears to be a descendant of an ancestral primate centromere, the current functional centromere based on DXZ1 sequences is the product of the much more recent concerted evolution of this satellite DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schueler, M G -- Higgins, A W -- Rudd, M K -- Gustashaw, K -- Willard, H F -- HD07518/HD/NICHD NIH HHS/ -- HD32111/HD/NICHD NIH HHS/ -- HG00107/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):109-15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, and, Research Institute, University Hospitals of Cleveland, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588252" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Centromere/chemistry/genetics/*physiology ; Chromosome Segregation ; Chromosomes, Artificial, Bacterial ; Chromosomes, Artificial, Human ; Computer Simulation ; Contig Mapping ; Crossing Over, Genetic ; *DNA, Satellite/chemistry/genetics/physiology ; Evolution, Molecular ; Humans ; Interspersed Repetitive Sequences ; Models, Genetic ; Phylogeny ; Repetitive Sequences, Nucleic Acid ; Restriction Mapping ; Sequence Analysis, DNA ; Sequence Deletion ; Sequence Tagged Sites ; Transfection ; Turner Syndrome/genetics ; X Chromosome/genetics/*physiology/ultrastructure
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  • 42
    Publication Date: 2001-11-03
    Description: SNAREs (soluble NSF-attachment protein receptors) are generally acknowledged as central components of membrane fusion reactions, but their precise function has remained enigmatic. Competing hypotheses suggest roles for SNAREs in mediating the specificity of fusion, catalyzing fusion, or actually executing fusion. We generated knockout mice lacking synaptobrevin/VAMP 2, the vesicular SNARE protein responsible for synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion. In the absence of synaptobrevin 2, spontaneous synaptic vesicle fusion and fusion induced by hypertonic sucrose were decreased approximately 10-fold, but fast Ca2+-triggered fusion was decreased more than 100-fold. Thus, synaptobrevin 2 may function in catalyzing fusion reactions and stabilizing fusion intermediates but is not absolutely required for synaptic fusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schoch, S -- Deak, F -- Konigstorfer, A -- Mozhayeva, M -- Sara, Y -- Sudhof, T C -- Kavalali, E T -- New York, N.Y. -- Science. 2001 Nov 2;294(5544):1117-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11691998" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Calcium/metabolism/pharmacology ; Cells, Cultured ; Hypertonic Solutions ; *Membrane Fusion ; Membrane Proteins/genetics/*physiology ; Mice ; Mice, Knockout ; Mutation ; Patch-Clamp Techniques ; Potassium/pharmacology ; Presynaptic Terminals/physiology ; Prosencephalon/physiology ; R-SNARE Proteins ; SNARE Proteins ; Sucrose/pharmacology ; Synapses/*physiology ; Synaptic Transmission ; Synaptic Vesicles/*physiology ; *Vesicular Transport Proteins
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  • 43
    Publication Date: 2001-11-27
    Description: Adhesions between fibroblastic cells and extracellular matrix have been studied extensively in vitro, but little is known about their in vivo counterparts. Here, we characterized the composition and function of adhesions in three-dimensional (3D) matrices derived from tissues or cell culture. "3D-matrix adhesions" differ from focal and fibrillar adhesions characterized on 2D substrates in their content of alpha5beta1 and alphavbeta3 integrins, paxillin, other cytoskeletal components, and tyrosine phosphorylation of focal adhesion kinase (FAK). Relative to 2D substrates, 3D-matrix interactions also display enhanced cell biological activities and narrowed integrin usage. These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesions, and as such they may be more biologically relevant to living organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cukierman, E -- Pankov, R -- Stevens, D R -- Yamada, K M -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1708-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721053" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; *Cell Adhesion/drug effects ; Cell Culture Techniques/methods ; Cell Division ; Cell Movement ; Cell Size ; Cells, Cultured ; Culture Techniques/methods ; Cycloheximide/pharmacology ; Cytoskeletal Proteins/metabolism ; Extracellular Matrix/chemistry/metabolism ; Fibroblasts/chemistry/*cytology/*metabolism ; Fibronectins/metabolism ; Fluorescent Antibody Technique, Indirect ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Focal Adhesions/chemistry/metabolism ; Glutaral/metabolism ; Humans ; Imaging, Three-Dimensional/*methods ; Integrins/metabolism ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Conformation ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; Time Factors
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pellman, D -- New York, N.Y. -- Science. 2001 Mar 30;291(5513):2555-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Pediatric Hematology/Oncology, Children's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. david_pellman@dfci.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11286276" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein ; Aneuploidy ; Animals ; Cell Transformation, Neoplastic ; Cells, Cultured ; Chromosome Aberrations ; Chromosome Segregation ; Chromosomes/*physiology ; Colonic Neoplasms/*genetics/metabolism/pathology ; Cytoskeletal Proteins/chemistry/*metabolism ; *Genes, APC ; Humans ; Kinetochores/*metabolism ; Mice ; Microtubule-Associated Proteins/metabolism ; Microtubules/*metabolism ; Mitosis ; Mutation ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases ; Spindle Apparatus/metabolism ; Stem Cells/cytology/metabolism ; *Trans-Activators ; beta Catenin
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  • 45
    Publication Date: 2001-05-12
    Description: Telomere proteins from ciliated protozoa bind to the single-stranded G-rich DNA extensions at the ends of macronuclear chromosomes. We have now identified homologous proteins in fission yeast and in humans. These Pot1 (protection of telomeres) proteins each bind the G-rich strand of their own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends. Deletion of the fission yeast pot1+ gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization. It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baumann, P -- Cech, T R -- New York, N.Y. -- Science. 2001 May 11;292(5519):1171-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349150" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chromosome Segregation/genetics ; Chromosomes, Fungal/genetics/metabolism ; Cloning, Molecular ; DNA/genetics/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Electrophoresis, Gel, Pulsed-Field ; Female ; Gene Deletion ; Gene Expression Profiling ; Heterozygote ; Humans ; Molecular Sequence Data ; Ovary/metabolism ; Phenotype ; RNA, Messenger/analysis/genetics ; Schizosaccharomyces/*genetics ; Schizosaccharomyces pombe Proteins ; Sequence Alignment ; Substrate Specificity ; Telomere/genetics/*metabolism ; *Telomere-Binding Proteins
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  • 46
    Publication Date: 2001-06-02
    Description: Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamaguchi, Y -- Filipovska, J -- Yano, K -- Furuya, A -- Inukai, N -- Narita, T -- Wada, T -- Sugimoto, S -- Konarska, M M -- Handa, H -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):124-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Frontier Collaborative Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8503, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387440" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Consensus Sequence/genetics ; Enzyme Activation ; HeLa Cells ; Hepatitis Antigens/chemistry/*metabolism ; *Hepatitis Delta Virus/chemistry/genetics/metabolism ; Hepatitis delta Antigens ; Humans ; Molecular Sequence Data ; Protein Binding ; Protein Subunits ; RNA Polymerase II/*metabolism ; RNA, Viral/biosynthesis/genetics ; Sequence Alignment ; Templates, Genetic ; Transcription Factors/antagonists & inhibitors/chemistry/metabolism ; *Transcription, Genetic ; Virus Replication
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  • 47
    Publication Date: 2001-03-10
    Description: Filopodia that extend from neuronal growth cones sample the environment for extracellular guidance cues, but the signals they transmit to growth cones are unknown. Filopodia were observed generating localized transient elevations of intracellular calcium ([Ca2+]i) that propagate back to the growth cone and stimulate global Ca2+ elevations. The frequency of filopodial Ca2+ transients was substrate-dependent and may be due in part to influx of Ca2+ through channels activated by integrin receptors. These transients slowed neurite outgrowth by reducing filopodial motility and promoted turning when stimulated differentially within filopodia on one side of the growth cone. These rapid signals appear to serve both as autonomous regulators of filopodial movement and as frequency-coded signals integrated within the growth cone and could be a common signaling process for many motile cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gomez, T M -- Robles, E -- Poo , M -- Spitzer, N C -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1983-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA. tmgomez@facstaff.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239161" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD29/metabolism ; Calcium/*metabolism ; *Calcium Signaling ; Cell Movement ; Cells, Cultured ; Culture Techniques ; Embryo, Nonmammalian/cytology ; Growth Cones/metabolism/*physiology ; Integrins/metabolism ; Laminin/pharmacology ; Microscopy, Confocal ; Neurites/metabolism/*physiology ; Neurons/physiology ; Oligopeptides/pharmacology ; Pseudopodia/*metabolism ; Tenascin/pharmacology ; Xenopus/embryology
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  • 48
    Publication Date: 2001-03-17
    Description: The role of NF-kappaB-inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK-/- mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK-/- cells manifested normal NF-kappaB DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-beta (LTbeta). However, NIK was selectively required for gene transcription induced through ligation of LTbeta receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-kappaB in a receptor-restricted manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, L -- Wu, L -- Wesche, H -- Arthur, C D -- White, J M -- Goeddel, D V -- Schreiber, R D -- New York, N.Y. -- Science. 2001 Mar 16;291(5511):2162-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11251123" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; B-Lymphocytes/metabolism ; Cells, Cultured ; DNA/metabolism ; Fibroblasts/metabolism ; Gene Targeting ; Genes, Reporter ; Interleukin-1/metabolism/pharmacology ; Ligands ; Lymphoid Tissue/abnormalities ; Lymphotoxin beta Receptor ; Mice ; Mice, Inbred C57BL ; NF-kappa B/genetics/*metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, Tumor Necrosis Factor/immunology/*metabolism ; Signal Transduction ; *Transcription, Genetic ; Tumor Necrosis Factor-alpha/metabolism/pharmacology
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  • 49
    Publication Date: 2001-08-18
    Description: The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor (VEGF) expression, including a marked increase in the amount of VEGF messenger RNA. Moreover, VEGF production in cultured Lkb1(-/-) fibroblasts was elevated in both normoxic and hypoxic conditions. These findings place Lkb1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb1 loss are mediated at least in part by VEGF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ylikorkala, A -- Rossi, D J -- Korsisaari, N -- Luukko, K -- Alitalo, K -- Henkemeyer, M -- Makela, T P -- New York, N.Y. -- Science. 2001 Aug 17;293(5533):1323-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cancer Biology Program, Haartman Institute and Biomedicum Helsinki, Post Office Box 63, University of Helsinki, Helsinki 00014, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/*abnormalities/embryology ; Cell Death ; Cell Hypoxia ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Embryo, Mammalian/*metabolism ; Embryonic and Fetal Development ; Endothelial Growth Factors/*genetics/*metabolism ; Endothelium, Vascular/abnormalities/cytology/embryology ; *Gene Expression Regulation, Developmental ; Gene Targeting ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; In Situ Hybridization ; Lymphokines/*genetics/*metabolism ; Mesoderm/cytology ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular/abnormalities/cytology/embryology ; Neural Tube Defects/embryology ; Nuclear Proteins/metabolism ; Phenotype ; Placenta/blood supply/embryology/metabolism ; Protein-Serine-Threonine Kinases/deficiency/genetics/*physiology ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; *Transcription Factors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
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  • 50
    Publication Date: 2001-06-26
    Description: Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gorre, M E -- Mohammed, M -- Ellwood, K -- Hsu, N -- Paquette, R -- Rao, P N -- Sawyers, C L -- GM07185/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):876-80. Epub 2001 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423618" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Antineoplastic Agents/metabolism/pharmacology/therapeutic use ; Base Sequence ; Benzamides ; Blast Crisis/genetics ; Cell Line ; Drug Resistance, Neoplasm/genetics ; Fusion Proteins, bcr-abl/*metabolism ; Gene Amplification ; *Genes, abl ; Humans ; Hydrogen Bonding ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/*genetics ; Molecular Sequence Data ; Philadelphia Chromosome ; Phosphorylation ; Piperazines/metabolism/*pharmacology/therapeutic use ; Point Mutation ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-abl/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Proto-Oncogene Proteins c-crk ; Pyrimidines/metabolism/*pharmacology/therapeutic use ; Recurrence ; Signal Transduction
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J -- New York, N.Y. -- Science. 2001 Sep 21;293(5538):2192-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11567120" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/metabolism/pathology/*physiopathology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Animals ; *Apoptosis ; Brain/*metabolism/pathology ; Carrier Proteins/metabolism ; Caspases/*metabolism ; Cells, Cultured ; DNA Fragmentation ; Enzyme Activation ; Humans ; In Situ Nick-End Labeling ; JNK Mitogen-Activated Protein Kinases ; Mice ; Microfilament Proteins/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Nerve Degeneration ; Neurons/metabolism/pathology/*physiology ; Synapses/enzymology
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  • 52
    Publication Date: 2001-06-09
    Description: The p53 protein is present in low amounts in normally growing cells and is activated in response to physiological insults. MDM2 regulates p53 either through inhibiting p53's transactivating function in the nucleus or by targeting p53 degradation in the cytoplasm. We identified a previously unknown nuclear export signal (NES) in the amino terminus of p53, spanning residues 11 to 27 and containing two serine residues phosphorylated after DNA damage, which was required for p53 nuclear export in colloboration with the carboxyl-terminal NES. Serine-15-phosphorylated p53 induced by ultraviolet irradiation was not exported. Thus, DNA damage-induced phosphorylation may achieve optimal p53 activation by inhibiting both MDM2 binding to, and the nuclear export of, p53.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Y -- Xiong, Y -- CA65572/CA/NCI NIH HHS/ -- K01 CA087580/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1910-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397945" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Animals ; Cell Fusion ; Cell Line ; Cell Nucleus/*metabolism ; Cells, Cultured ; Cytoplasm/metabolism ; *DNA Damage ; Mice ; Molecular Sequence Data ; Mutation ; *Nuclear Proteins ; Phosphorylation ; Phosphoserine/metabolism ; *Protein Sorting Signals ; Protein Structure, Tertiary ; Proteins/genetics/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Transfection ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53/*chemistry/genetics/*metabolism ; Ubiquitins/metabolism ; Ultraviolet Rays
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  • 53
    Publication Date: 2001-11-03
    Description: The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten-/- central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Groszer, M -- Erickson, R -- Scripture-Adams, D D -- Lesche, R -- Trumpp, A -- Zack, J A -- Kornblum, H I -- Liu, X -- Wu, H -- MH062800-01/MH/NIMH NIH HHS/ -- NS38489/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2186-9. Epub 2001 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11691952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Astrocytes/cytology ; Brain/abnormalities/*cytology/embryology ; Cell Count ; Cell Differentiation ; *Cell Division ; Cell Lineage ; Cell Size ; Cells, Cultured ; Female ; Flow Cytometry ; Fluoresceins/metabolism ; Gene Deletion ; Intermediate Filament Proteins/metabolism ; Male ; Mice ; Mice, Knockout ; *Nerve Tissue Proteins ; Nestin ; Neurons/*cytology ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases/*genetics/*physiology ; Stem Cells/*cytology ; Succinimides/metabolism ; Tumor Suppressor Proteins/*genetics/*physiology
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  • 54
    Publication Date: 2001-10-06
    Description: Toxoplasma gondii is a common human pathogen causing serious, even fatal, disease in the developing fetus and in immunocompromised patients. Despite its ability to reproduce sexually and its broad geographic and host range, Toxoplasma has a clonal population structure comprised principally of three lines. We have analyzed 15 polymorphic loci in the archetypal type I, II, and III strains and found that polymorphism was limited to, at most, two rather than three allelic classes and no polymorphism was detected between alleles in strains of a given type. Multilocus analysis of 10 nonarchetypal isolates likewise clustered the vast majority of alleles into the same two distinct ancestries. These data strongly suggest that the currently predominant genotypes exist as a pandemic outbreak from a genetic mixing of two discrete ancestral lines. To determine if such mixing could lead to the extreme virulence observed for some strains, we examined the F(1) progeny of a cross between a type II and III strain, both of which are relatively avirulent in mice. Among the progeny were recombinants that were at least 3 logs more virulent than either parent. Thus, sexual recombination, by combining polymorphisms in two distinct and competing clonal lines, can be a powerful force driving the natural evolution of virulence in this highly successful pathogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grigg, M E -- Bonnefoy, S -- Hehl, A B -- Suzuki, Y -- Boothroyd, J C -- AI04717/AI/NIAID NIH HHS/ -- AI21423/AI/NIAID NIH HHS/ -- AI41014/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):161-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588262" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Crosses, Genetic ; Genes, Protozoan ; Genetic Variation ; Genotype ; Humans ; Introns ; Lethal Dose 50 ; Mice ; Mice, Inbred CBA ; Molecular Sequence Data ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; *Recombination, Genetic ; Toxoplasma/classification/*genetics/isolation & purification/*pathogenicity ; Toxoplasmosis/*parasitology ; Toxoplasmosis, Animal/*parasitology ; Virulence/genetics
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  • 55
    Publication Date: 2001-04-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berkhout, B -- Das, A T -- Beerens, N -- New York, N.Y. -- Science. 2001 Apr 6;292(5514):7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11292864" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Genes, vpr ; Genome, Viral ; HIV-1/*genetics ; Humans ; *Mutation ; Proviruses/genetics ; *RNA Editing ; *Transcription, Genetic
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  • 56
    Publication Date: 2001-03-27
    Description: Many intracellular pathogens infect a broad range of host tissues, but the importance of T cells for immunity in these sites is unclear because most of our understanding of antimicrobial T cell responses comes from analyses of lymphoid tissue. Here, we show that in response to viral or bacterial infection, antigen-specific CD8 T cells migrated to nonlymphoid tissues and were present as long-lived memory cells. Strikingly, CD8 memory T cells isolated from nonlymphoid tissues exhibited effector levels of lytic activity directly ex vivo, in contrast to their splenic counterparts. These results point to the existence of a population of extralymphoid effector memory T cells poised for immediate response to infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masopust, D -- Vezys, V -- Marzo, A L -- Lefrancois, L -- AI41576/AI/NIAID NIH HHS/ -- DK45260/DK/NIDDK NIH HHS/ -- T32-AI07080/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 23;291(5512):2413-7. Epub 2001 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11264538" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Cell Movement ; Cells, Cultured ; Flow Cytometry ; H-2 Antigens/immunology ; *Immunologic Memory ; Intestine, Small/immunology ; Listeria monocytogenes/genetics/immunology ; Listeriosis/*immunology ; Liver/immunology ; Lung/immunology ; Lymphocyte Activation ; Lymphoid Tissue/immunology ; Mice ; Mice, Inbred C57BL ; Ovalbumin/immunology ; Phenotype ; Rhabdoviridae Infections/*immunology ; T-Lymphocyte Subsets/*immunology ; Vesicular stomatitis Indiana virus/immunology
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  • 57
    Publication Date: 2001-06-16
    Description: Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuccato, C -- Ciammola, A -- Rigamonti, D -- Leavitt, B R -- Goffredo, D -- Conti, L -- MacDonald, M E -- Friedlander, R M -- Silani, V -- Hayden, M R -- Timmusk, T -- Sipione, S -- Cattaneo, E -- E.0840/Telethon/Italy -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):493-8. Epub 2001 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408619" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Apoptosis ; Brain-Derived Neurotrophic Factor/biosynthesis/*genetics/metabolism ; Cell Survival ; Cells, Cultured ; Cerebral Cortex/cytology/*metabolism ; Corpus Striatum/cytology/*metabolism/pathology ; Exons ; Hippocampus/cytology/metabolism/pathology ; Humans ; Huntington Disease/*genetics/metabolism/pathology ; Mice ; Mice, Transgenic ; Mutation ; Nerve Degeneration ; Nerve Growth Factors/genetics/metabolism ; Nerve Tissue Proteins/genetics/*physiology ; Neurons/*metabolism/pathology ; Nuclear Proteins/genetics/*physiology ; Promoter Regions, Genetic ; Transcription, Genetic ; Transfection
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  • 58
    Publication Date: 2001-09-05
    Description: The developmental signaling functions of cell surface heparan sulfate proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report the identification of QSulf1, the avian ortholog of an evolutionarily conserved protein family related to heparan-specific N-acetyl glucosamine sulfatases. QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in quail embryos and is required for the activation of MyoD, a Wnt-induced regulator of muscle specification. QSulf1 is localized on the cell surface and regulates heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a mechanism that requires its catalytic activity, providing evidence that QSulf1 regulates Wnt signaling through desulfation of cell surface HSPGs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dhoot, G K -- Gustafsson, M K -- Ai, X -- Sun, W -- Standiford, D M -- Emerson , C P Jr -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Veterinary Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 OTU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533491" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Body Patterning ; CHO Cells ; Cell Membrane/metabolism ; Cells, Cultured ; Cloning, Molecular ; Coculture Techniques ; Cricetinae ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Hedgehog Proteins ; Heparan Sulfate Proteoglycans/*metabolism ; Heparin/metabolism/pharmacology ; Heparitin Sulfate/metabolism ; Molecular Sequence Data ; Muscles/cytology/*embryology/metabolism ; Mutation ; MyoD Protein/genetics/metabolism ; Oligonucleotides, Antisense ; Proto-Oncogene Proteins/*metabolism ; Quail/*embryology ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; *Signal Transduction ; Somites/metabolism ; Stem Cells/*metabolism ; Sulfatases/chemistry/genetics/*metabolism ; Trans-Activators/genetics/metabolism ; Transfection ; Wnt Proteins ; *Zebrafish Proteins
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  • 59
    Publication Date: 2001-02-07
    Description: Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are functionally immature. Astrocytes increase the number of mature, functional synapses on central nervous system (CNS) neurons by sevenfold and are required for synaptic maintenance in vitro. We also show that most synapses are generated concurrently with the development of glia in vivo. These data demonstrate a previously unknown function for glia in inducing and stabilizing CNS synapses, show that CNS synapse number can be profoundly regulated by nonneuronal signals, and raise the possibility that glia may actively participate in synaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ullian, E M -- Sapperstein, S K -- Christopherson, K S -- Barres, B A -- NS10784/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jan 26;291(5504):657-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University School of Medicine, Department of Neurobiology, Fairchild Science Building, Stanford, CA 94305-5125, USA. emu@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11158678" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/*physiology ; Calcium/metabolism ; *Calcium-Binding Proteins ; Cell Communication ; Cells, Cultured ; Coculture Techniques ; Excitatory Postsynaptic Potentials ; Fluorescent Dyes/metabolism ; Glutamic Acid/pharmacology ; Ionomycin/pharmacology ; Membrane Glycoproteins/metabolism ; Microscopy, Electron ; Nerve Tissue Proteins/metabolism ; Neuronal Plasticity ; Patch-Clamp Techniques ; Pyridinium Compounds/metabolism ; Quaternary Ammonium Compounds/metabolism ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/*physiology/ultrastructure ; Superior Colliculi/embryology/growth & development/ultrastructure ; Synapses/*physiology/ultrastructure ; Synaptic Transmission ; Synaptic Vesicles/metabolism ; Synaptophysin/metabolism ; Synaptotagmins
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enserink, M -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):24-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11191991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Artifacts ; Cell Membrane/parasitology/ultrastructure ; Cell Movement ; Cells, Cultured ; Hepatocytes/*parasitology/ultrastructure ; Humans ; Malaria/parasitology ; Mice ; Motion Pictures as Topic ; Plasmodium yoelii/growth & development/*physiology ; Vacuoles/physiology/ultrastructure
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  • 61
    Publication Date: 2001-05-12
    Description: Epigenetic silenced alleles of the Arabidopsis SUPERMAN locus (the clark kent alleles) are associated with dense hypermethylation at noncanonical cytosines (CpXpG and asymmetric sites, where X = A, T, C, or G). A genetic screen for suppressors of a hypermethylated clark kent mutant identified nine loss-of-function alleles of CHROMOMETHYLASE3 (CMT3), a novel cytosine methyltransferase homolog. These cmt3 mutants display a wild-type morphology but exhibit decreased CpXpG methylation of the SUP gene and of other sequences throughout the genome. They also show reactivated expression of endogenous retrotransposon sequences. These results show that a non-CpG DNA methyltransferase is responsible for maintaining epigenetic gene silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindroth, A M -- Cao, X -- Jackson, J P -- Zilberman, D -- McCallum, C M -- Henikoff, S -- Jacobsen, S E -- GM07104/GM/NIGMS NIH HHS/ -- GM07185/GM/NIGMS NIH HHS/ -- GM29009/GM/NIGMS NIH HHS/ -- GM60398/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2077-80. Epub 2001 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349138" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Arabidopsis/*genetics/metabolism ; *Arabidopsis Proteins ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; CpG Islands ; Crosses, Genetic ; Cytosine/metabolism ; *DNA Methylation ; DNA-Cytosine Methylases/chemistry/*genetics/*metabolism ; Dinucleoside Phosphates/metabolism ; Gene Expression Regulation, Plant ; *Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; Mutagenesis ; Oligonucleotides/*metabolism ; Phenotype ; Protein Structure, Tertiary ; Retroelements ; Transcription Factors/*genetics
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  • 62
    Publication Date: 2001-02-24
    Description: Human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. Although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. With the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropism. This gene, M45, shares sequence homology to ribonucleotide reductase genes. Endothelial cells infected with M45-mutant viruses rapidly undergo apoptosis, suggesting that a viral strategy to evade destruction by cellular apoptosis is indispensable for viral growth in endothelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brune, W -- Menard, C -- Heesemann, J -- Koszinowski, U H -- New York, N.Y. -- Science. 2001 Jan 12;291(5502):303-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. wbrune@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11209080" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Apoptosis ; Base Sequence ; Cell Line ; Cytopathogenic Effect, Viral ; DNA Transposable Elements ; Endothelium, Vascular/*cytology/*virology ; Fibroblasts/virology ; Frameshift Mutation ; Gene Library ; *Genes, Viral ; Mice ; Molecular Sequence Data ; Muromegalovirus/*genetics/growth & development/*physiology ; Mutagenesis, Insertional ; Open Reading Frames ; Phenotype ; Ribonucleotide Reductases/*genetics/physiology ; *Viral Proteins ; Virus Replication
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richter, J D -- Theurkauf, W E -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):60-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA. joel.richter@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441171" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Body Patterning/genetics ; Cell Division ; Cyclin B/*biosynthesis/genetics ; DNA-Binding Proteins/*biosynthesis/genetics ; *Drosophila Proteins ; Drosophila melanogaster/cytology/*embryology/genetics/*metabolism ; Gene Expression Regulation, Developmental ; Insect Proteins/genetics/metabolism ; Oocytes/metabolism ; Protein Binding ; *Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; *RNA-Binding Proteins ; Response Elements/genetics ; Transcription Factors/*biosynthesis/genetics ; Xenopus laevis/embryology/metabolism
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-12-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sohn, E -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1809.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729277" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Drosophila melanogaster/genetics/metabolism ; Fragile X Mental Retardation Protein ; Fragile X Syndrome/*etiology/genetics/*metabolism ; *Gene Expression Regulation ; Gene Library ; Humans ; Mice ; Microtubule-Associated Proteins/genetics/*metabolism ; Mutation/genetics ; Nerve Tissue Proteins/*metabolism ; Phenotype ; RNA, Messenger/chemistry/genetics/metabolism ; RNA-Binding Proteins/*metabolism ; Up-Regulation
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  • 65
    Publication Date: 2001-03-10
    Description: Initiation of protein synthesis in eukaryotes requires recruitment of the 40S ribosomal subunit to the messenger RNA (mRNA). In most cases, this depends on recognition of a modified nucleotide cap on the 5' end of the mRNA. However, an alternate pathway uses a structured RNA element in the 5' untranslated region of the messenger or viral RNA called an internal ribosomal entry site (IRES). Here, we present a cryo-electron microscopy map of the hepatitis C virus (HCV) IRES bound to the 40S ribosomal subunit at about 20 A resolution. IRES binding induces a pronounced conformational change in the 40S subunit and closes the mRNA binding cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the ribosomal decoding center.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spahn, C M -- Kieft, J S -- Grassucci, R A -- Penczek, P A -- Zhou, K -- Doudna, J A -- Frank, J -- GM60635/GM/NIGMS NIH HHS/ -- R37 GM29169/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1959-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Health Research Inc. at the, Wadsworth Center, Empire State Plaza, Albany, New York 12201-0509, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239155" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/chemistry/*metabolism ; Animals ; Base Sequence ; Cryoelectron Microscopy ; Hepacivirus/genetics/*metabolism/ultrastructure ; Image Processing, Computer-Assisted ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Messenger/metabolism ; RNA, Ribosomal, 18S/chemistry/metabolism ; RNA, Viral/chemistry/*metabolism ; Rabbits ; Ribosomes/*chemistry/*metabolism/ultrastructure
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finkel, E -- New York, N.Y. -- Science. 2001 Apr 27;292(5517):624-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11330312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*physiology ; Caenorhabditis elegans/physiology ; Caspase Inhibitors ; Caspases/*metabolism ; Cell Nucleus/metabolism ; Cells, Cultured ; Cysteine Proteinase Inhibitors/pharmacology ; Cytochrome c Group/metabolism ; Enzyme Activation ; Humans ; Intracellular Membranes/physiology ; Mice ; Mice, Knockout ; Mitochondria/*physiology ; Nuclear Proteins/metabolism ; Permeability ; Proteins/metabolism
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉States, D J -- New York, N.Y. -- Science. 2001 May 11;292(5519):1066-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11352052" target="_blank"〉PubMed〈/a〉
    Keywords: Authorship ; Base Sequence ; Databases as Topic ; *Human Genome Project/economics ; Humans ; National Institutes of Health (U.S.) ; *Public Sector/economics ; *Publishing ; Time Factors ; United States
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-11-03
    Description: Highly orchestrated molecular rearrangements are required for two membranes to fuse, as happens, for example, during neurotransmitter release into the synapse. In an elegant Perspective, Scales et al. discuss two studies (Schoch et al., Wang et al.) that shed new light on the protein interactions involved in membrane fusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scales, S J -- Finley, M F -- Scheller, R H -- New York, N.Y. -- Science. 2001 Nov 2;294(5544):1015-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech Inc., South San Francisco, CA 94080, USA. sscales@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11691976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Calcium Signaling ; *Calcium-Binding Proteins ; Catecholamines/metabolism ; Cell Membrane/metabolism ; Cells, Cultured ; Electrophysiology ; *Membrane Fusion ; Membrane Glycoproteins/*physiology ; Membrane Proteins/*physiology ; Mice ; Nerve Tissue Proteins/*physiology ; Neurotransmitter Agents/metabolism ; PC12 Cells ; Phospholipids/metabolism ; Protein Isoforms ; R-SNARE Proteins ; Rats ; SNARE Proteins ; Secretory Vesicles/*metabolism ; Synapses/physiology ; Synaptic Transmission ; Synaptic Vesicles/*metabolism ; Synaptotagmins ; *Vesicular Transport Proteins
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  • 69
    Publication Date: 2002-05-25
    Description: The sulfated peptide phytosulfokine (PSK) is an intercellular signal that plays a key role in cellular dedifferentiation and proliferation in plants. Using ligand-based affinity chromatography, we purified a 120-kilodalton membrane protein, specifically interacting with PSK, from carrot microsomal fractions. The corresponding complementary DNA encodes a 1021-amino acid receptor kinase that contains extracellular leucine-rich repeats, a single transmembrane domain, and a cytoplasmic kinase domain. Overexpression of this receptor kinase in carrot cells caused enhanced callus growth in response to PSK and a substantial increase in the number of tritium-labeled PSK binding sites, suggesting that PSK and this receptor kinase act as a ligand-receptor pair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsubayashi, Yoshikatsu -- Ogawa, Mari -- Morita, Akiko -- Sakagami, Youji -- New York, N.Y. -- Science. 2002 May 24;296(5572):1470-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. matsu@agr.nagoya-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12029134" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding, Competitive ; Cell Line ; Chromatography, Affinity ; DNA, Complementary ; Daucus carota/cytology/*enzymology/genetics/growth & development ; Genes, Plant ; Glycosylation ; Leucine ; Ligands ; Microsomes/enzymology ; Molecular Sequence Data ; Molecular Weight ; Peptide Hormones ; *Plant Growth Regulators ; Plant Proteins/*chemistry/genetics/isolation & purification/*metabolism ; Plants, Genetically Modified ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/isolation & purification/*metabolism ; Repetitive Sequences, Amino Acid
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  • 70
    Publication Date: 2002-03-02
    Description: The second messenger cyclic adenosine monophosphate (cAMP) is the most important modulator of sympathetic control over cardiac contractility. In cardiac myocytes and many other cell types, however, cAMP transduces the signal generated upon stimulation of various receptors and activates different cellular functions, raising the issue of how specificity can be achieved. In the general field of signal transduction, the view is emerging that specificity is guaranteed by tight localization of signaling events. Here, we show that in neonatal rat cardiac myocytes, beta-adrenergic stimulation generates multiple microdomains with increased concentration of cAMP in correspondence with the region of the transverse tubule/junctional sarcoplasmic reticulum membrane. The restricted pools of cAMP show a range of action as small as approximately 1 micrometer, and free diffusion of the second messenger is limited by the activity of phosphodiesterases. Furthermore, we demonstrate that such gradients of cAMP specifically activate a subset of protein kinase A molecules anchored in proximity to the T tubule.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zaccolo, Manuela -- Pozzan, Tullio -- TCP00089/Telethon/Italy -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1711-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Sciences and Venetian Institute for Molecular Medicine, University of Padua, Via Orus 2, 35129 Padua, Italy. manuela.zaccolo@unipd.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872839" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Methyl-3-isobutylxanthine/pharmacology ; A Kinase Anchor Proteins ; Adaptor Proteins, Signal Transducing ; Animals ; Animals, Newborn ; Cells, Cultured ; Colforsin/pharmacology ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Fluorescence ; Green Fluorescent Proteins ; Intracellular Membranes/metabolism ; Kinetics ; Luminescent Proteins ; Myocardium/*cytology/*metabolism/ultrastructure ; Norepinephrine/pharmacology ; Phosphodiesterase Inhibitors/pharmacology ; Proto-Oncogene Proteins/pharmacology ; Rats ; Receptors, Adrenergic, beta/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sarcoplasmic Reticulum/*metabolism ; Second Messenger Systems ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 71
    Publication Date: 2002-09-28
    Description: It has been known since 1986 that CD8 T lymphocytes from certain HIV-1-infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as alpha-defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human alpha-defensins. Synthetic and purified preparations of alpha-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that alpha-defensin 1, 2, and 3 collectively account for much of the anti-HIV-1 activity of CAF that is not attributable to beta-chemokines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Linqi -- Yu, Wenjie -- He, Tian -- Yu, Jian -- Caffrey, Rebecca E -- Dalmasso, Enrique A -- Fu, Siyu -- Pham, Thang -- Mei, Jianfeng -- Ho, Jaclyn J -- Zhang, Wenyong -- Lopez, Peter -- Ho, David D -- AI-42848/AI/NIAID NIH HHS/ -- M01-RR00102/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):995-1000. Epub 2002 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. lzhang@adarc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351674" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Monoclonal ; Antiviral Agents/chemistry/isolation & purification/*pharmacology ; CD8-Positive T-Lymphocytes/chemistry/*immunology ; Cells, Cultured ; Chemokines, CC/immunology/physiology ; HIV Infections/*immunology/virology ; HIV Long-Term Survivors ; HIV-1/drug effects/*physiology ; Humans ; Mass Spectrometry ; Molecular Sequence Data ; Neutrophils/chemistry/immunology ; Protein Array Analysis ; Virus Replication ; alpha-Defensins/chemistry/isolation & purification/pharmacology/*physiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 72
    Publication Date: 2002-05-23
    Description: Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peier, Andrea M -- Reeve, Alison J -- Andersson, David A -- Moqrich, Aziz -- Earley, Taryn J -- Hergarden, Anne C -- Story, Gina M -- Colley, Sian -- Hogenesch, John B -- McIntyre, Peter -- Bevan, Stuart -- Patapoutian, Ardem -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2046-9. Epub 2002 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016205" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Newborn ; Blotting, Northern ; CHO Cells ; Capsaicin/*analogs & derivatives/pharmacology ; *Cation Transport Proteins ; Cell Line ; Cells, Cultured ; Cloning, Molecular ; Cricetinae ; Epidermis/cytology/innervation/metabolism ; Ganglia, Spinal/metabolism ; *Hot Temperature ; Humans ; In Situ Hybridization ; Ion Channels/chemistry/genetics/*metabolism ; Keratinocytes/*metabolism ; Membrane Potentials ; Mice ; Molecular Sequence Data ; Nerve Endings/physiology ; Neurons/physiology ; Patch-Clamp Techniques ; RNA, Messenger/genetics/metabolism ; Ruthenium Red/pharmacology ; Signal Transduction ; Spinal Cord/metabolism ; TRPV Cation Channels ; Temperature
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 73
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKerracher, Lisa -- Ellezam, Benjamin -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1819-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Pathologie et Biologie Cellulaire, Universite de Montreal, 2900 Edouard-Montpetit, Montreal, Quebec, H3T 1J4 Canada. mckerral@patho.umontreal.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12052945" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/*physiology ; Animals ; Axonal Transport ; Axons/*physiology ; *Cell Communication ; Cell Differentiation ; Cell Polarity ; Cells, Cultured ; Coculture Techniques ; Dendrites/*physiology ; Embryo, Mammalian ; Nerve Crush ; *Nerve Regeneration ; Optic Nerve/cytology/physiology ; Peripheral Nerves/transplantation ; Rats ; Retinal Ganglion Cells/*physiology ; Signal Transduction ; Spinal Cord/cytology/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 74
    Publication Date: 2002-01-19
    Description: Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERbeta-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERbeta-deficient mice. Vascular smooth muscle cells isolated from ERbeta-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERbeta-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERbeta in the regulation of vascular function and blood pressure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Yan -- Bian, Zhao -- Lu, Ping -- Karas, Richard H -- Bao, Lin -- Cox, Daniel -- Hodgin, Jeffrey -- Shaul, Philip W -- Thoren, Peter -- Smithies, Oliver -- Gustafsson, Jan-Ake -- Mendelsohn, Michael E -- GM20069/GM/NIGMS NIH HHS/ -- HD30276/HD/NICHD NIH HHS/ -- HL53546/HL/NHLBI NIH HHS/ -- HL56235/HL/NHLBI NIH HHS/ -- P50 HL63494/HL/NHLBI NIH HHS/ -- R01 HL55309/HL/NHLBI NIH HHS/ -- R01 HL56069/HL/NHLBI NIH HHS/ -- R01 HL61298/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 18;295(5554):505-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology Research Institute, New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11799247" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-Agonists/pharmacology ; Animals ; Aorta ; Blood Pressure ; Cells, Cultured ; Estradiol/*analogs & derivatives/pharmacology ; Estrogen Antagonists/pharmacology ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Guanidines/pharmacology ; Humans ; Hypertension/*physiopathology ; In Vitro Techniques ; Male ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular/*physiology ; Nitric Oxide Synthase/genetics/metabolism ; Nitric Oxide Synthase Type II ; Nitroarginine/pharmacology ; Patch-Clamp Techniques ; Phenylephrine/pharmacology ; Potassium Channels/metabolism ; Receptors, Estrogen/genetics/*physiology ; *Vasoconstriction/drug effects
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  • 75
    Publication Date: 2002-05-04
    Description: Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024710/" 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/PMC3024710/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Yuan -- Ghosh, Pritam -- Charnay, Patrick -- Burns, Dennis K -- Parada, Luis F -- R01 NS034296/NS/NINDS NIH HHS/ -- R01 NS034296-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):920-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Developmental Biology, Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988578" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Axons/ultrastructure ; Cell Lineage ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cranial Nerves/pathology ; Culture Techniques ; Female ; *Genes, Neurofibromatosis 1 ; Genotype ; Heterozygote ; Hyperplasia ; Loss of Heterozygosity ; Male ; Mast Cells/chemistry/pathology ; Mice ; Mice, Transgenic ; Neurofibroma/genetics/*pathology ; Neurofibromatosis 1/genetics/*pathology ; Peripheral Nerves/pathology ; Schwann Cells/chemistry/*pathology ; Spinal Nerves/pathology
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  • 76
    Publication Date: 2002-09-21
    Description: Persons with the autosomal recessive disorder Bloom syndrome are predisposed to cancers of many types due to loss-of-function mutations in the BLM gene, which encodes a recQ-like helicase. Here we show that mice heterozygous for a targeted null mutation of Blm, the murine homolog of BLM, develop lymphoma earlier than wild-type littermates in response to challenge with murine leukemia virus and develop twice the number of intestinal tumors when crossed with mice carrying a mutation in the Apc tumor suppressor. These observations indicate that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition, a finding with important implications for cancer risk in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goss, Kathleen Heppner -- Risinger, Mary A -- Kordich, Jennifer J -- Sanz, Maureen M -- Straughen, Joel E -- Slovek, Lisa E -- Capobianco, Anthony J -- German, James -- Boivin, Gregory P -- Groden, Joanna -- CA63507/CA/NCI NIH HHS/ -- CA84291/CA/NCI NIH HHS/ -- CA88460/CA/NCI NIH HHS/ -- ES06096/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2051-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Department of Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242442" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoma/genetics/pathology ; Adenosine Triphosphatases/*genetics ; Alleles ; Animals ; Bloom Syndrome/*genetics ; Cells, Cultured ; Crosses, Genetic ; DNA Helicases/*genetics ; Female ; Gene Targeting ; Genes, APC ; *Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Intestinal Neoplasms/*genetics/pathology ; Leukemia Virus, Murine ; Loss of Heterozygosity ; Lymphoma, T-Cell/*genetics/virology ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; RecQ Helicases ; Sister Chromatid Exchange
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  • 77
    Publication Date: 2002-01-05
    Description: Many human cancers originate from defects in the DNA damage response (DDR). Although much is known about this process, it is likely that additional DDR genes remain to be discovered. To identify such genes, we used a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis in Caenorhabditis elegans. Together, these approaches identified 12 worm DDR orthologs and 11 novel DDR genes. One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia. Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boulton, Simon J -- Gartner, Anton -- Reboul, Jerome -- Vaglio, Philippe -- Dyson, Nick -- Hill, David E -- Vidal, Marc -- 5R01HG01715-02/HG/NHGRI NIH HHS/ -- 7 R33 CA81658-02/CA/NCI NIH HHS/ -- P01CA80111-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 4;295(5552):127-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11778048" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Base Sequence ; Caenorhabditis elegans/*genetics/metabolism/physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; *Chromosome Mapping ; Computational Biology ; DNA Damage/*genetics ; DNA Repair/*genetics ; DNA Replication ; Gamma Rays ; Gene Silencing ; *Genes, Helminth ; Genome ; Humans ; Open Reading Frames ; Phenotype ; Proteome ; Proto-Oncogene Proteins/genetics ; Recombination, Genetic ; Transcription Factors ; Two-Hybrid System Techniques
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  • 78
    Publication Date: 2002-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meegaskumbura, M -- Bossuyt, F -- Pethiyagoda, R -- Manamendra-Arachchi, K -- Bahir, M -- Milinkovitch, M C -- Schneider, C J -- New York, N.Y. -- Science. 2002 Oct 11;298(5592):379.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Boston University, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12376694" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/anatomy & histology/*classification/genetics/physiology ; Base Sequence ; Biological Evolution ; DNA, Mitochondrial/genetics ; *Ecosystem ; Embryonic Development ; Female ; Male ; Molecular Sequence Data ; Oviposition ; Ovum/physiology ; *Phylogeny ; Sri Lanka ; Trees
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  • 79
    Publication Date: 2002-08-24
    Description: The mammalian ovarian follicle consists of a multilayered complex of somatic cells that surround the oocyte. A signal from the follicle cells keeps the oocyte cell cycle arrested at prophase of meiosis I until luteinizing hormone from the pituitary acts on the follicle cells to release the arrest, causing meiosis to continue. Here we show that meiotic arrest can be released in mice by microinjecting the oocyte within the follicle with an antibody that inhibits the stimulatory heterotrimeric GTP-binding protein Gs. This indicates that Gs activity in the oocyte is required to maintain meiotic arrest within the ovarian follicle and suggests that the follicle may keep the cell cycle arrested by activating Gs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mehlmann, Lisa M -- Jones, Teresa L Z -- Jaffe, Laurinda A -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1343-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Connecticut Health Center, Farmington, CT 06032, USA. lmehlman@neuron.uchc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193786" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Cells, Cultured ; Cyclic AMP/metabolism ; Female ; GTP-Binding Protein alpha Subunits, Gi-Go/immunology/physiology ; GTP-Binding Protein alpha Subunits, Gs/antagonists & ; inhibitors/immunology/*physiology ; Hypoxanthine/pharmacology ; *Meiosis ; Mice ; Oocytes/drug effects/metabolism/*physiology ; Ovarian Follicle/*physiology ; Signal Transduction
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-22
    Description: The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brinster, Ralph L -- 36504/PHS HHS/ -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2174-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3850 Baltimore Avenue, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077400" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Separation ; Cells, Cultured ; Cryopreservation ; Humans ; Male ; Seminiferous Tubules/cytology ; Sertoli Cells/physiology ; *Spermatogenesis ; Spermatogonia/*cytology/physiology ; *Stem Cell Transplantation ; Stem Cells/physiology ; Testis/*cytology ; Transduction, Genetic ; *Transgenes ; Transplantation, Heterologous
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  • 81
    Publication Date: 2002-03-02
    Description: When bound by extracellular ligands, receptor tyrosine kinases (RTKs) on the cell surface transmit critical signals to the cell interior. Although signal termination is less well understood, protein tyrosine phosphatase-1B (PTP1B) is implicated in the dephosphorylation and inactivation of several RTKs. However, PTP1B resides on the cytoplasmic surface of the endoplasmic reticulum (ER), so how and when it accesses RTKs has been unclear. Using fluorescence resonance energy transfer (FRET) methods, we monitored interactions between the epidermal- and platelet-derived growth factor receptors and PTP1B. PTP1B-catalyzed dephosphorylation required endocytosis of the receptors and occurred at specific sites on the surface of the ER. Most of the RTKs activated at the cell surface showed interaction with PTP1B after internalization, establishing that RTK activation and inactivation are spatially and temporally partitioned within cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haj, Fawaz G -- Verveer, Peter J -- Squire, Anthony -- Neel, Benjamin G -- Bastiaens, Philippe I H -- R01 CA49152/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1708-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel-Deaconess Medical Center, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872838" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Catalytic Domain ; Cell Membrane/enzymology ; Cells, Cultured ; *Endocytosis ; Endoplasmic Reticulum/*enzymology ; Energy Transfer ; Epidermal Growth Factor/metabolism/pharmacology ; Fluorescence ; Mice ; Microscopy, Confocal ; Microscopy, Fluorescence ; Phosphorylation ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Protein Transport ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; Protein Tyrosine Phosphatases/chemistry/genetics/*metabolism ; Receptor, Epidermal Growth Factor/*metabolism ; Receptors, Platelet-Derived Growth Factor/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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  • 82
    Publication Date: 2002-12-14
    Description: The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dehal, Paramvir -- Satou, Yutaka -- Campbell, Robert K -- Chapman, Jarrod -- Degnan, Bernard -- De Tomaso, Anthony -- Davidson, Brad -- Di Gregorio, Anna -- Gelpke, Maarten -- Goodstein, David M -- Harafuji, Naoe -- Hastings, Kenneth E M -- Ho, Isaac -- Hotta, Kohji -- Huang, Wayne -- Kawashima, Takeshi -- Lemaire, Patrick -- Martinez, Diego -- Meinertzhagen, Ian A -- Necula, Simona -- Nonaka, Masaru -- Putnam, Nik -- Rash, Sam -- Saiga, Hidetoshi -- Satake, Masanobu -- Terry, Astrid -- Yamada, Lixy -- Wang, Hong-Gang -- Awazu, Satoko -- Azumi, Kaoru -- Boore, Jeffrey -- Branno, Margherita -- Chin-Bow, Stephen -- DeSantis, Rosaria -- Doyle, Sharon -- Francino, Pilar -- Keys, David N -- Haga, Shinobu -- Hayashi, Hiroko -- Hino, Kyosuke -- Imai, Kaoru S -- Inaba, Kazuo -- Kano, Shungo -- Kobayashi, Kenji -- Kobayashi, Mari -- Lee, Byung-In -- Makabe, Kazuhiro W -- Manohar, Chitra -- Matassi, Giorgio -- Medina, Monica -- Mochizuki, Yasuaki -- Mount, Steve -- Morishita, Tomomi -- Miura, Sachiko -- Nakayama, Akie -- Nishizaka, Satoko -- Nomoto, Hisayo -- Ohta, Fumiko -- Oishi, Kazuko -- Rigoutsos, Isidore -- Sano, Masako -- Sasaki, Akane -- Sasakura, Yasunori -- Shoguchi, Eiichi -- Shin-i, Tadasu -- Spagnuolo, Antoinetta -- Stainier, Didier -- Suzuki, Miho M -- Tassy, Olivier -- Takatori, Naohito -- Tokuoka, Miki -- Yagi, Kasumi -- Yoshizaki, Fumiko -- Wada, Shuichi -- Zhang, Cindy -- Hyatt, P Douglas -- Larimer, Frank -- Detter, Chris -- Doggett, Norman -- Glavina, Tijana -- Hawkins, Trevor -- Richardson, Paul -- Lucas, Susan -- Kohara, Yuji -- Levine, Michael -- Satoh, Nori -- Rokhsar, Daniel S -- HD-37105/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2157-67.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481130" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Apoptosis ; Base Sequence ; Cellulose/metabolism ; Central Nervous System/physiology ; Ciona intestinalis/anatomy & histology/classification/*genetics/physiology ; Computational Biology ; Endocrine System/physiology ; Gene Dosage ; Gene Duplication ; Genes ; Genes, Homeobox ; *Genome ; Heart/embryology/physiology ; Immunity/genetics ; Molecular Sequence Data ; Multigene Family ; Muscle Proteins/genetics ; Organizers, Embryonic/physiology ; Phylogeny ; Polymorphism, Genetic ; Proteins/genetics/physiology ; *Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Species Specificity ; Thyroid Gland/physiology ; Urochordata/genetics ; Vertebrates/anatomy & histology/classification/genetics/physiology
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  • 83
    Publication Date: 2002-03-30
    Description: Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlseder, Jan -- Smogorzewska, Agata -- de Lange, Titia -- AG16643/AG/NIA NIH HHS/ -- CA76027/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2446-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11923537" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Polyomavirus Transforming/genetics/metabolism ; *Cell Aging ; *Cell Division ; Cell Line ; Cells, Cultured ; DNA/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Humans ; Oncogene Proteins, Viral/genetics/metabolism ; Papillomavirus E7 Proteins ; *Repressor Proteins ; Retinoblastoma Protein/metabolism ; Retroviridae/genetics ; Telomere/metabolism/*physiology ; Telomeric Repeat Binding Protein 2 ; Transformation, Genetic ; Tumor Suppressor Protein p53/metabolism
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  • 84
    Publication Date: 2002-03-16
    Description: A 20-variable instance of the NP-complete three-satisfiability (3-SAT) problem was solved on a simple DNA computer. The unique answer was found after an exhaustive search of more than 1 million (2(20)) possibilities. This computational problem may be the largest yet solved by nonelectronic means. Problems of this size appear to be beyond the normal range of unaided human computation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Braich, Ravinderjit S -- Chelyapov, Nickolas -- Johnson, Cliff -- Rothemund, Paul W K -- Adleman, Leonard -- New York, N.Y. -- Science. 2002 Apr 19;296(5567):499-502. Epub 2002 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Southern California, Laboratory for Molecular Science, Los Angeles, CA 90089-1340, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896237" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; *Computers ; *Computing Methodologies ; *Dna ; DNA, Single-Stranded ; Electrophoresis, Polyacrylamide Gel ; Gene Library ; Nucleic Acid Hybridization ; Oligonucleotide Probes ; Polymerase Chain Reaction
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  • 85
    Publication Date: 2002-09-21
    Description: Micro-RNAs (miRNAs) are regulatory molecules that mediate effects by interacting with messenger RNA (mRNA) targets. Here we show that Arabidopsis thaliana miRNA 39 (also known as miR171), a 21-ribonucleotide species that accumulates predominantly in inflorescence tissues, is produced from an intergenic region in chromosome III and functionally interacts with mRNA targets encoding several members of the Scarecrow-like (SCL) family of putative transcription factors. miRNA 39 is complementary to an internal region of three SCL mRNAs. The interaction results in specific cleavage of target mRNA within the region of complementarity, indicating that this class of miRNA functions like small interfering RNA associated with RNA silencing to guide sequence-specific cleavage in a developmentally controlled manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Llave, Cesar -- Xie, Zhixin -- Kasschau, Kristin D -- Carrington, James C -- AI27832/AI/NIAID NIH HHS/ -- AI43288/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2053-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Gene Research and Biotechnology, and Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242443" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Base Pair Mismatch ; Base Sequence ; DNA, Intergenic ; Gene Silencing ; MicroRNAs ; Plant Leaves/genetics/metabolism ; Plant Stems/genetics/metabolism ; Plant Structures/genetics/metabolism ; RNA, Antisense/genetics/*metabolism ; RNA, Messenger/genetics/*metabolism ; RNA, Plant/genetics/metabolism ; RNA, Small Interfering ; RNA, Untranslated/genetics/*metabolism ; Transcription Factors/*genetics/metabolism
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-07-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2002 Jul 19;297(5580):328.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Cell Count ; Cell Division ; Cells, Cultured ; Cerebral Cortex/cytology/*embryology ; Cytoskeletal Proteins/*genetics/physiology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/*genetics/physiology ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Neurons/cytology/physiology ; Pituitary Gland/*cytology/growth & development ; Retina/*cytology/growth & development ; Stem Cells/cytology/*physiology ; Trans-Activators/*genetics/physiology ; beta Catenin
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  • 87
    Publication Date: 2002-12-21
    Description: The immunoglobulin G (IgG)-containing B lymphocyte antigen receptor (IgG-BCR) transmits a signal distinct from that of IgM-BCR or IgD-BCR, although all three use the same signal-transducing component, Igalpha/Igbeta. Here we demonstrate that the inhibitory coreceptor CD22 down-modulates signaling through IgM-BCR and IgD-BCR, but not that through IgG-BCR, because of the IgG cytoplasmic tail, which prevents CD22 phosphorylation. These results suggest that the cytoplasmic tail of IgG specifically enhances IgG-BCR signaling by preventing CD22-mediated signal inhibition. Enhanced signaling through IgG-BCR may be involved in efficient IgG production, which is crucial for immunity to pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakabayashi, Chisato -- Adachi, Takahiro -- Wienands, Jurgen -- Tsubata, Takeshi -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2392-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12493916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, B-Lymphocyte/metabolism ; B-Lymphocytes/immunology/metabolism ; Calcium/metabolism ; Calcium Signaling ; *Cell Adhesion Molecules ; Cells, Cultured ; Immunoglobulin D/immunology/metabolism ; Immunoglobulin G/chemistry/immunology/*metabolism ; Intracellular Signaling Peptides and Proteins ; Lectins/metabolism ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/metabolism ; Receptors, Antigen, B-Cell/chemistry/immunology/*metabolism ; Sialic Acid Binding Ig-like Lectin 2 ; *Signal Transduction ; Transfection ; Tumor Cells, Cultured
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  • 88
    Publication Date: 2002-09-14
    Description: Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in fully mature as well as immature CD123+ DCs. IDO+ DCs could also be readily detected in vivo, which suggests that these cells may represent a regulatory subset of APCs in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Munn, David H -- Sharma, Madhav D -- Lee, Jeffrey R -- Jhaver, Kanchan G -- Johnson, Theodore S -- Keskin, Derin B -- Marshall, Brendan -- Chandler, Phillip -- Antonia, Scott J -- Burgess, Russell -- Slingluff, Craig L Jr -- Mellor, Andrew L -- AI44219/AI/NIAID NIH HHS/ -- AI44759/AI/NIAID NIH HHS/ -- HL60137/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1867-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA. dmunn@mail.mcg.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228717" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen-Presenting Cells/enzymology/immunology ; Antigens, CD/analysis ; Cell Adhesion ; Cell Lineage ; Cells, Cultured ; Dendritic Cells/*enzymology/*immunology ; Down-Regulation ; Enzyme Inhibitors/pharmacology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma/pharmacology ; Interleukin-10/pharmacology ; Interleukin-3 Receptor alpha Subunit ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Lymphoid Tissue/cytology/enzymology ; Macrophages/enzymology ; Receptors, CCR6 ; Receptors, Chemokine/analysis ; Receptors, Interleukin-3/analysis ; T-Lymphocytes/*immunology ; Tryptophan/*analogs & derivatives/pharmacology ; Tryptophan Oxygenase/antagonists & inhibitors/*metabolism
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  • 89
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-03-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2002 Mar 15;295(5562):1989-91.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; *Cell Differentiation ; *Cell Fusion ; Cell Lineage ; Cells, Cultured ; Chromosome Aberrations ; Embryo, Mammalian/cytology ; Hybrid Cells/*physiology ; Mice ; Polyploidy ; Stem Cells/cytology/*physiology
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  • 90
    Publication Date: 2000-01-05
    Description: Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Estevez, A G -- Crow, J P -- Sampson, J B -- Reiter, C -- Zhuang, Y -- Richardson, G J -- Tarpey, M M -- Barbeito, L -- Beckman, J S -- R01 HL58209/HL/NHLBI NIH HHS/ -- R01 NS33291/NS/NINDS NIH HHS/ -- R01 NS36761/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2498-500.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617463" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/*enzymology/genetics/pathology ; Animals ; *Apoptosis ; Brain-Derived Neurotrophic Factor/pharmacology ; Cells, Cultured ; Chelating Agents/pharmacology ; Copper/metabolism ; Fluoresceins/metabolism ; Liposomes ; Motor Neurons/*cytology/metabolism ; Mutation ; Nitrates/metabolism ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Nitric Oxide Synthase Type I ; Oxidation-Reduction ; Rats ; Superoxide Dismutase/chemistry/genetics/*metabolism/toxicity ; Superoxides/metabolism ; Zinc/*metabolism
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plotkin, S A -- Koprowski, H -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2450.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636806" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Democratic Republic of the Congo ; History, 20th Century ; Humans ; Immunization Programs/history ; Pan troglodytes ; Poliovirus/growth & development ; Poliovirus Vaccine, Oral/*history ; Virus Cultivation
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  • 92
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):586-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10798984" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics ; Animals ; Bioethics ; Cattle/*genetics ; *Cell Aging/genetics ; Cell Division ; Cells, Cultured ; *Cloning, Organism ; Female ; Nuclear Transfer Techniques ; Oocytes/physiology ; Stem Cells ; Telomere/*ultrastructure
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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1418-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10722390" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animal Experimentation ; Animals ; Bioethics ; *Biomedical Research ; Bone Marrow Cells/cytology/physiology ; Cell Differentiation ; Cell Separation ; Cell Transplantation ; Cells, Cultured ; Child ; *Embryo Research ; Embryo, Mammalian/*cytology ; Federal Government ; Humans ; Mice ; Middle Aged ; Stem Cells/*cytology/physiology
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  • 94
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2136-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744530" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biochemistry/methods ; *Biotechnology/economics ; *Computational Biology ; Computers ; Databases, Factual ; Drug Industry ; Humans ; Investments ; Mass Spectrometry ; Peptide Mapping ; Proteins/chemistry/genetics/isolation & purification/physiology ; *Proteome
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  • 95
    Publication Date: 2000-04-28
    Description: The potential of cloning depends in part on whether the procedure can reverse cellular aging and restore somatic cells to a phenotypically youthful state. Here, we report the birth of six healthy cloned calves derived from populations of senescent donor somatic cells. Nuclear transfer extended the replicative life-span of senescent cells (zero to four population doublings remaining) to greater than 90 population doublings. Early population doubling level complementary DNA-1 (EPC-1, an age-dependent gene) expression in cells from the cloned animals was 3.5- to 5-fold higher than that in cells from age-matched (5 to 10 months old) controls. Southern blot and flow cytometric analyses indicated that the telomeres were also extended beyond those of newborn (〈2 weeks old) and age-matched control animals. The ability to regenerate animals and cells may have important implications for medicine and the study of mammalian aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanza, R P -- Cibelli, J B -- Blackwell, C -- Cristofalo, V J -- Francis, M K -- Baerlocher, G M -- Mak, J -- Schertzer, M -- Chavez, E A -- Sawyer, N -- Lansdorp, P M -- West, M D -- AG00378/AG/NIA NIH HHS/ -- AI29524/AI/NIAID NIH HHS/ -- GM56162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):665-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Advanced Cell Technology, One Innovation Drive, Worcester, MA 01605, USA. rlanza@advancedcell.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10784448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blotting, Southern ; Cattle/*genetics ; *Cell Aging ; Cell Division ; Cells, Cultured ; Clone Cells ; *Cloning, Organism ; DNA, Complementary ; Embryo Transfer ; *Eye Proteins ; Female ; Fibroblasts ; Flow Cytometry ; In Situ Hybridization, Fluorescence ; Longevity ; Matched-Pair Analysis ; *Nerve Growth Factors ; *Nuclear Transfer Techniques ; Proteins/genetics ; RNA, Messenger/genetics/metabolism ; Serpins/genetics ; Telomere/*ultrastructure
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  • 96
    Publication Date: 2000-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williamson, T L -- Corson, L B -- Huang, L -- Burlingame, A -- Liu, J -- Bruijn, L I -- Cleveland, D W -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):399.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10798964" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*enzymology/genetics/pathology ; Animals ; Apoptosis ; Cells, Cultured ; Copper/metabolism ; Humans ; Mice ; Motor Neurons/metabolism/*pathology ; Mutation ; Neurofilament Proteins/metabolism ; Nitrates/metabolism ; Superoxide Dismutase/*genetics/*metabolism ; Yeasts/cytology/metabolism ; Zinc/*metabolism/toxicity
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-24
    Description: Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes. We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca2+, Ca2+/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3',5'-monophosphate response element binding protein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stevens, B -- Fields, R D -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2267-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Developmental Neurobiology, National Institutes of Health, National Institute of Child Health and Human Development, Building 49, Room 5A38, 49 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10731149" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Adenosine Triphosphate/metabolism ; Animals ; Axons/*physiology ; Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Differentiation ; Cell Division ; Cells, Cultured ; Coculture Techniques ; Cyclic AMP Response Element-Binding Protein/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Early Growth Response Protein 1 ; Electric Stimulation ; Ganglia, Spinal/physiology ; Gene Expression Regulation, Developmental ; Genes, fos ; *Immediate-Early Proteins ; Mice ; Microscopy, Confocal ; Myelin Sheath/metabolism ; Neurons, Afferent/*physiology ; Phosphorylation ; Proto-Oncogene Proteins c-fos/metabolism ; Receptors, Purinergic P2/metabolism ; Schwann Cells/*cytology/*physiology ; Signal Transduction ; Transcription Factors/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-24
    Description: Exactly how signaling proteins know where they need to be in the cell is one of the intriguing mysteries of signal transduction biology. In a Perspective, Pouyssegur reviews new results that identify b-arrestin 2 as a scaffolding protein that holds together the different components of a MAPK signaling pathway that activates the transcription factor kinase, JNK3.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pouyssegur, J -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1515-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Nice 06189, France. pouysseg@unice.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11185509" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*metabolism ; Cell Nucleus/metabolism ; Cells, Cultured ; Cytosol/metabolism ; Endosomes/metabolism ; Enzyme Activation ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 7 ; MAP Kinase Kinase Kinase 5 ; MAP Kinase Kinase Kinases/metabolism ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 10 ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Receptor, Angiotensin, Type 1 ; Receptor, PAR-2 ; Receptors, Angiotensin/metabolism ; Receptors, Thrombin/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2000-08-19
    Description: To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉St Croix, B -- Rago, C -- Velculescu, V -- Traverso, G -- Romans, K E -- Montgomery, E -- Lal, A -- Riggins, G J -- Lengauer, C -- Vogelstein, B -- Kinzler, K W -- CA57345/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- CGAP S98-146A/PHS HHS/ -- New York, N.Y. -- Science. 2000 Aug 18;289(5482):1197-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins Oncology Center, Howard Hughes Medical Institute, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10947988" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers, Tumor ; Cell Separation ; Cells, Cultured ; Colon/*blood supply/metabolism ; Colorectal Neoplasms/*blood supply/genetics/metabolism/pathology ; Corpus Luteum/blood supply/metabolism ; Endothelium, Vascular/cytology/*metabolism/pathology ; Extracellular Matrix Proteins/genetics ; Female ; Gene Expression ; *Gene Expression Profiling ; Humans ; Intestinal Mucosa/blood supply/cytology/pathology ; Neoplasms/blood supply/genetics/metabolism ; Neovascularization, Pathologic/*genetics ; Neovascularization, Physiologic/genetics ; RNA, Messenger/genetics/metabolism ; Rectum/*blood supply/metabolism ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2000-04-15
    Description: The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (〉43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caterina, M J -- Leffler, A -- Malmberg, A B -- Martin, W J -- Trafton, J -- Petersen-Zeitz, K R -- Koltzenburg, M -- Basbaum, A I -- Julius, D -- NS07265/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 14;288(5464):306-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143-0450, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10764638" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Temperature/drug effects ; Calcium/metabolism ; Capsaicin/metabolism/*pharmacology ; Cells, Cultured ; Diterpenes/pharmacology ; Ganglia, Spinal/cytology ; Gene Targeting ; Hot Temperature ; Hydrogen-Ion Concentration ; Inflammation/physiopathology ; Mice ; Mice, Knockout ; Nerve Fibers/physiology ; Neurons/physiology ; Neurons, Afferent/*physiology ; Nociceptors/*physiology ; Pain/*physiopathology ; Pain Threshold ; Receptors, Drug/*physiology ; Spinal Cord/cytology/physiology ; TRPV Cation Channels
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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