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  • Articles  (387)
  • Latest Papers from Table of Contents or Articles in Press  (387)
  • Rats  (231)
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  • Articles  (387)
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  • 2020-2022
  • 2000-2004  (171)
  • 1980-1984  (216)
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  • 1
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    Genetic definition and sequence analysis of Arabidopsis centromeres (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 2
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    Role of the mouse ank gene in control of tissue calcification and arthritis (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 3
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    A structural model of transcription elongation (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-01
    Description: The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and transcript RNA or template DNA onto the x-ray crystal structure. In the resulting model, the downstream duplex DNA is nestled in a trough formed by the beta' subunit and enclosed on top by the beta subunit. In the RNAP channel, the RNA/DNA hybrid extends from the enzyme active site, along a region of the beta subunit harboring rifampicin resistance mutations, to the beta' subunit "rudder." The single-stranded RNA is then extruded through another channel formed by the beta-subunit flap domain. The model provides insight into the functional properties of the transcription complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korzheva, N -- Mustaev, A -- Kozlov, M -- Malhotra, A -- Nikiforov, V -- Goldfarb, A -- Darst, S A -- GM30717/GM/NIGMS NIH HHS/ -- GM49242/GM/NIGMS NIH HHS/ -- GM53759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):619-25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Public Health Research Institute, 455 First Avenue, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10915625" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cross-Linking Reagents ; Crystallography, X-Ray ; DNA/chemistry/genetics/*metabolism ; DNA Primers ; DNA-Directed RNA Polymerases/*chemistry/genetics/metabolism ; Models, Molecular ; Mutation ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry/metabolism ; Oligoribonucleotides/chemistry/metabolism ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Messenger/chemistry/genetics/*metabolism ; Templates, Genetic ; Thermus/enzymology ; *Transcription, Genetic
    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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  • 4
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    A subset of viral transcripts packaged within human cytomegalovirus particles (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 5
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    Neuroscience. Early insult rewires pain circuits (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-12
    Description: On page 628, neuroscientists report that painful stimuli delivered to rats shortly after birth permanently rewire the spinal cord circuits that respond to pain. Not only do the circuits contain more axons, but the axons extend to more areas of the spinal cord than they normally would. The results should help convince skeptics of the importance of managing pain in human infants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):521-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939955" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways ; Aging ; Animals ; Animals, Newborn ; Axons/*physiology ; Hindlimb/innervation ; Humans ; Infant, Newborn ; Inflammation/physiopathology ; *Pain ; Pain Threshold ; Rats ; Sciatic Nerve/*anatomy & histology/physiology ; Spinal Cord/*cytology
    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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  • 6
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    Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-05-20
    Description: A hippocampal pyramidal neuron receives more than 10(4) excitatory glutamatergic synapses. Many of these synapses contain the molecular machinery for messenger RNA translation, suggesting that the protein complement (and thus function) of each synapse can be regulated on the basis of activity. Here, local postsynaptic protein synthesis, triggered by synaptic activation of metabotropic glutamate receptors, was found to modify synaptic transmission within minutes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huber, K M -- Kayser, M S -- Bear, M F -- New York, N.Y. -- Science. 2000 May 19;288(5469):1254-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Neuroscience, Brown University, Providence, RI 02912, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10818003" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/pharmacology ; Animals ; Anisomycin/pharmacology ; Dendrites/drug effects/*metabolism ; Electric Stimulation ; Excitatory Amino Acid Antagonists/pharmacology ; Hippocampus/*metabolism/physiology ; Methoxyhydroxyphenylglycol/analogs & derivatives/pharmacology ; Nerve Tissue Proteins/antagonists & inhibitors/*biosynthesis/genetics ; Neural Inhibition/drug effects/*physiology ; Protein Biosynthesis/drug effects ; Protein Synthesis Inhibitors/pharmacology ; RNA, Messenger/metabolism ; Rats ; Receptors, Metabotropic Glutamate/*physiology ; Synaptic Transmission/drug effects/physiology ; Xanthenes/pharmacology
    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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  • 7
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    Accommodating phylogenetic uncertainty in evolutionary studies (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 8
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    Learning-induced LTP in neocortex (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-20
    Description: The hypothesis that learning occurs through long-term potentiation (LTP)- and long-term depression (LTD)-like mechanisms is widely held but unproven. This hypothesis makes three assumptions: Synapses are modifiable, they modify with learning, and they strengthen through an LTP-like mechanism. We previously established the ability for synaptic modification and a synaptic strengthening with motor skill learning in horizontal connections of the rat motor cortex (MI). Here we investigated whether learning strengthened these connections through LTP. We demonstrated that synapses in the trained MI were near the ceiling of their modification range, compared with the untrained MI, but the range of synaptic modification was not affected by learning. In the trained MI, LTP was markedly reduced and LTD was enhanced. These results are consistent with the use of LTP to strengthen synapses during learning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rioult-Pedotti, M S -- Friedman, D -- Donoghue, J P -- NS27164/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):533-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Brown University, Providence, RI 02912, USA. mengia_rioult@brown.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039938" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electric Stimulation ; Female ; Learning/*physiology ; Long-Term Potentiation/*physiology ; Models, Neurological ; Motor Cortex/*physiology ; Motor Skills ; Neuronal Plasticity ; Rats ; Rats, Sprague-Dawley ; Synapses/*physiology ; Synaptic Transmission
    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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  • 9
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    Neurobiology. Receptors as kissing cousins (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milligan, G -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):65-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10766637" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/metabolism ; Animals ; Cell Line ; Cerebral Cortex/metabolism ; Corpus Striatum/metabolism ; Dimerization ; Energy Transfer ; Fluorescence ; GTP-Binding Proteins/*metabolism ; Ligands ; Rats ; Receptor Cross-Talk ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/agonists/*metabolism ; Receptors, Dopamine D5 ; Receptors, GABA-A/metabolism ; Receptors, Somatostatin/agonists/*metabolism ; Signal Transduction ; Somatostatin/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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  • 10
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    Database searches for binding sites (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 11
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    Evolution. Parasites make scaredy-rats foolhardy (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmer, C -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):525-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Biological Evolution ; *Fear ; Female ; Humans ; Male ; *Personality ; Rats ; Toxoplasma/*physiology ; Toxoplasmosis, Animal/parasitology/*psychology ; Toxoplasmosis, Cerebral/parasitology/*psychology
    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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  • 12
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    The structural basis of ribosome activity in peptide bond synthesis (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    Print ISSN: 0036-8075
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  • 13
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    European science policy. France rebels against gene-patenting law (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 14
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    Structure of the RNA polymerase domain of E. coli primase (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-03-31
    Description: All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other DNA or RNA polymerase palm folds, but is instead related to the "toprim" fold. On the basis of the structure, it is likely that DnaG binds nucleic acid in a groove clustered with invariant residues and that DnaG is positioned within the replisome to accept single-stranded DNA directly from the replicative helicase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, J L -- Roche, D D -- Lynch, A S -- Berger, J M -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2482-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, no. 3206, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741967" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; DNA Helicases/chemistry/metabolism ; DNA Primase/*chemistry/*metabolism ; DNA Replication ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/*metabolism ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Escherichia coli/*enzymology/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/biosynthesis ; Recombinant Proteins/chemistry/metabolism ; Templates, Genetic
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  • 15
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    Neuroscience. A new look at how neurons compute (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2256-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11041785" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chloride Channels/metabolism ; Chlorides/metabolism ; Culture Techniques ; Dendrites/physiology ; Motion Perception/*physiology ; Neural Inhibition ; Patch-Clamp Techniques ; Rabbits ; Retinal Ganglion Cells/*physiology ; Signal Transduction ; Sodium Channels/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 16
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    Template boundary in a yeast telomerase specified by RNA structure (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Neurobiology. A new clue to how alcohol damages brains (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):947-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10691562" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzodiazepines/adverse effects/toxicity ; Brain/cytology/*drug effects/growth & development ; Ethanol/blood/*toxicity ; Female ; Humans ; Infant, Newborn ; Nerve Degeneration ; Neurons/cytology/*drug effects ; Pregnancy ; Rats ; Receptors, GABA/*drug effects/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*drug effects/metabolism
    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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    One sequence, two ribozymes: implications for the emergence of new ribozyme folds (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 19
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    Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 20
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    Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-11
    Description: DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, S K -- Fienberg, A A -- O'Callaghan, J P -- Snyder, G L -- Allen, P B -- Dash, P K -- Moore, A N -- Mitchell, A J -- Bibb, J -- Greengard, P -- O'Malley, B W -- MH49662/MH/NIMH NIH HHS/ -- MH57442/MH/NIMH NIH HHS/ -- NS 35457/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1053-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. smani@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669419" target="_blank"〉PubMed〈/a〉
    Keywords: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; Animals ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dopamine/pharmacology ; Dopamine Agonists/pharmacology ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Female ; Hypothalamus/metabolism ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Nerve Tissue Proteins ; Oligonucleotides, Antisense/pharmacology ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Posture ; Progesterone/*pharmacology ; Proteins/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Progesterone/metabolism ; Serotonin/pharmacology ; Sexual Behavior, Animal/*drug effects ; Signal Transduction
    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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  • 21
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    Homologs of small nucleolar RNAs in Archaea (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 22
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    An early taste of things to come (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marcus, M -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1878.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11012357" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn/physiology ; Embryonic and Fetal Development ; Female ; *Food Preferences/physiology ; Humans ; Rats ; *Taste
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  • 23
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    Molecular architecture and evolution of a modular spider silk protein gene (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 24
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    Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 25
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    Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-02-26
    Description: Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobayashi, N -- Fujiwara, T -- Westerman, K A -- Inoue, Y -- Sakaguchi, M -- Noguchi, H -- Miyazaki, M -- Cai, J -- Tanaka, N -- Fox, I J -- Leboulch, P -- DK48794/DK/NIDDK NIH HHS/ -- HL55435/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1258-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉First Department of Surgery and Department of Cell Biology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678831" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Antigens, Polyomavirus Transforming/genetics ; Cell Culture Techniques/*methods ; Cell Differentiation ; Cell Line ; *Cell Transplantation ; Gene Expression ; Genetic Vectors ; Hepatectomy ; Humans ; Integrases/metabolism ; Liver/*cytology/metabolism/pathology ; Liver Failure, Acute/metabolism/pathology/*prevention & control/therapy ; Liver Regeneration ; Mice ; Mice, SCID ; Rats ; Retroviridae/genetics ; Spleen/cytology ; Transfection ; *Viral Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 26
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    Proteomics. Can Celera do it again? (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 27
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    Techview: molecular biology. Bead-based fiber-optic arrays (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walt, D R -- New York, N.Y. -- Science. 2000 Jan 21;287(5452):451-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Tufts University, Medford, MA 02155, USA. david.walt@tufts.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10671175" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Probes ; *Fiber Optic Technology ; Fluorescent Dyes ; Gene Expression Profiling/*methods ; Image Processing, Computer-Assisted ; Microspheres ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis/*methods ; Optical Fibers
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  • 28
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    Perspectives: neurobiology. Diversity in inhibition (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miles, R -- New York, N.Y. -- Science. 2000 Jan 14;287(5451):244-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Neurobiologie Cellulaire, INSERM, Institut Pasteur, Paris, France. miles@pasteur.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10660424" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/physiology/ultrastructure ; Brain/cytology/*physiology ; Dendrites/physiology/ultrastructure ; Evoked Potentials ; Gap Junctions/physiology ; Interneurons/*cytology/*physiology ; *Neural Inhibition ; Neurotransmitter Agents/metabolism ; Pyramidal Cells/physiology ; Rats ; Sodium Channels/physiology ; Synapses/*physiology ; *Synaptic Transmission
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  • 29
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    Suppression of mutations in mitochondrial DNA by tRNAs imported from the cytoplasm (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-16
    Description: Mitochondrial import of a cytoplasmic transfer RNA (tRNA) in yeast requires the preprotein import machinery and cytosolic factors. We investigated whether the tRNA import pathway can be used to correct respiratory deficiencies due to mutations in the mitochondrial DNA and whether this system can be transferred into human cells. We show that cytoplasmic tRNAs with altered aminoacylation identity can be specifically targeted to the mitochondria and participate in mitochondrial translation. We also show that human mitochondria, which do not normally import tRNAs, are able to internalize yeast tRNA derivatives in vitro and that this import requires an essential yeast import factor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kolesnikova, O A -- Entelis, N S -- Mireau, H -- Fox, T D -- Martin, R P -- Tarassov, I A -- GM29362/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1931-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉FRE 2168 du CNRS, Mecanismes Moleculaires de la Division Cellulaire et du Developpement, 21 rue Rene Descartes, 67084 Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10988073" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Base Sequence ; Biological Transport ; Cytoplasm/metabolism ; DNA, Mitochondrial/genetics/*metabolism ; Genes, Fungal ; Humans ; In Vitro Techniques ; Mitochondria/*metabolism ; Molecular Sequence Data ; Saccharomyces cerevisiae/genetics/metabolism ; Suppression, Genetic
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    Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-08
    Description: During animal development, cells become progressively more restricted in the cell types to which they can give rise. In the central nervous system (CNS), for example, multipotential stem cells produce various kinds of specified precursors that divide a limited number of times before they terminally differentiate into either neurons or glial cells. We show here that certain extracellular signals can induce oligodendrocyte precursor cells to revert to multipotential neural stem cells, which can self-renew and give rise to neurons and astrocytes, as well as to oligodendrocytes. Thus, these precursor cells have greater developmental potential than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kondo, T -- Raff, M -- New York, N.Y. -- Science. 2000 Sep 8;289(5485):1754-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Developmental Neurobiology Programme, MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London, London WC1E 6BT, UK. t.kondo@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10976069" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Astrocytes/chemistry/*cytology ; Blood ; Bone Morphogenetic Proteins/pharmacology ; Cell Culture Techniques ; *Cell Differentiation ; Cells, Cultured ; Culture Media ; Culture Media, Serum-Free ; Fibroblast Growth Factor 2/pharmacology ; Galactosylceramides/analysis ; Glial Fibrillary Acidic Protein/analysis ; Glutamate Decarboxylase/biosynthesis/genetics ; Isoenzymes/biosynthesis/genetics ; Neurofilament Proteins/analysis/biosynthesis ; Neurons/chemistry/*cytology ; Oligodendroglia/chemistry/*cytology ; Optic Nerve/cytology ; Platelet-Derived Growth Factor/pharmacology ; Rats ; Stem Cells/chemistry/*cytology ; Thyroid Hormones/pharmacology
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    Regulation of STAT3 by direct binding to the Rac1 GTPase (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-06
    Description: The signal transducers and activators of transcription (STAT) transcription factors become phosphorylated on tyrosine and translocate to the nucleus after stimulation of cells with growth factors or cytokines. We show that the Rac1 guanosine triphosphatase can bind to and regulate STAT3 activity. Dominant negative Rac1 inhibited STAT3 activation by growth factors, whereas activated Rac1 stimulated STAT3 phosphorylation on both tyrosine and serine residues. Moreover, activated Rac1 formed a complex with STAT3 in mammalian cells. Yeast two-hybrid analysis indicated that STAT3 binds directly to active but not inactive Rac1 and that the interaction occurs via the effector domain. Rac1 may serve as an alternate mechanism for targeting STAT3 to tyrosine kinase signaling complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, A R -- Vikis, H G -- Stewart, S -- Fanburg, B L -- Cochran, B H -- Guan, K L -- GM-54304/GM/NIGMS NIH HHS/ -- K08-HL-03547/HL/NHLBI NIH HHS/ -- P30-DK34928/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Oct 6;290(5489):144-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pulmonary and Critical Care Division, Tupper Research Institute, New England Medical Center, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11021801" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; COS Cells ; Cell Line ; Cercopithecus aethiops ; DNA-Binding Proteins/genetics/*metabolism ; Enzyme Activation ; Epidermal Growth Factor/pharmacology ; Gene Expression Regulation ; Genes, Reporter ; Genetic Vectors ; Guanine Nucleotide Exchange Factors/genetics/metabolism ; Humans ; Janus Kinase 2 ; Mutation ; Neoplasm Proteins ; Phosphorylation ; Phosphoserine/metabolism ; Phosphotyrosine/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proteins/genetics/metabolism ; *Proto-Oncogene Proteins ; Rats ; STAT3 Transcription Factor ; Signal Transduction ; Trans-Activators/genetics/*metabolism ; Transfection ; Two-Hybrid System Techniques ; rac1 GTP-Binding Protein/genetics/*metabolism
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    Potent analgesic effects of GDNF in neuropathic pain states (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-06
    Description: Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucher, T J -- Okuse, K -- Bennett, D L -- Munson, J B -- Wood, J N -- McMahon, S B -- New York, N.Y. -- Science. 2000 Oct 6;290(5489):124-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Neuroscience Research, King's College London, London SE1 7EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11021795" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Analgesics, Non-Narcotic/pharmacology/*therapeutic use ; Animals ; Ganglia, Spinal/physiopathology ; Glial Cell Line-Derived Neurotrophic Factor ; Hot Temperature ; Hyperalgesia/*drug therapy ; Ligation ; Nerve Fibers/drug effects/physiology ; Nerve Fibers, Myelinated/drug effects/physiology ; *Nerve Growth Factors ; Nerve Tissue Proteins/pharmacology/*therapeutic use ; Neural Conduction/drug effects ; Neurons, Afferent/drug effects/physiology ; Pain/*drug therapy ; Pain Threshold/drug effects ; Peripheral Nervous System Diseases/*physiopathology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Sciatic Nerve ; Sodium Channels/genetics/metabolism ; Spinal Nerves ; Touch
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    Translating biomolecular recognition into nanomechanics (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-04-15
    Description: We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found to provide a true molecular recognition signal despite large nonspecific responses of individual cantilevers. Hybridization of complementary oligonucleotides shows that a single base mismatch between two 12-mer oligonucleotides is clearly detectable. Similar experiments on protein A-immunoglobulin interactions demonstrate the wide-ranging applicability of nanomechanical transduction to detect biomolecular recognition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fritz, J -- Baller, M K -- Lang, H P -- Rothuizen, H -- Vettiger, P -- Meyer, E -- Guntherodt, H -- Gerber, C -- Gimzewski, J K -- New York, N.Y. -- Science. 2000 Apr 14;288(5464):316-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IBM Research, Zurich Research Laboratory, Saumerstrasse 4, CH-8803 Ruschlikon, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10764640" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Specificity ; Base Pair Mismatch ; Base Pairing ; Chemistry, Physical ; Goats ; Gold/*chemistry ; Hydrogen Bonding ; Immunoglobulin Constant Regions/*chemistry ; Ligands ; *Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/*chemistry ; Physicochemical Phenomena ; Rabbits ; Silicon/*chemistry ; Staphylococcal Protein A/*chemistry ; Static Electricity ; Stress, Mechanical ; Thionucleotides/chemistry
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    RNA structure. Ribozyme evolution at the crossroads (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-12
    Description: Molecules that have similar sequences usually adopt the same structures and have the same functions. In his Perspective, Joyce explains that this is not always the case. In a remarkable study (Schultes and Bartel), an RNA sequence has been designed that can adopt two different structures, each with a different catalytic function. Joyce details how this study sheds light on the evolution of enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joyce, G F -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):401-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. gjoyce@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939951" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; *Evolution, Molecular ; Hepatitis Delta Virus/enzymology/genetics ; Mutation ; Nucleic Acid Conformation ; RNA, Catalytic/*chemistry/genetics/*metabolism
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    Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-03-04
    Description: The synergistic response of cells to the stimulation of multiple receptors has been ascribed to receptor cross talk; however, the specific molecules that mediate the resultant signal amplification have not been defined. Here a 24-kilodalton single transmembrane protein, designated calcyon, we functionally characterize that interacts with the D1 dopamine receptor. Calcyon localizes to dendritic spines of D1 receptor-expressing pyramidal cells in prefrontal cortex. These studies delineate a mechanism of Gq- and Gs-coupled heterotrimeric GTP-binding protein-coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca2+i) release as a result of interaction with calcyon. The role of calcyon in potentiating Ca2+-dependent signaling should provide insight into the D1 receptor-modulated cognitive functions of prefrontal cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lezcano, N -- Mrzljak, L -- Eubanks, S -- Levenson, R -- Goldman-Rakic, P -- Bergson, C -- MH56608/MH/NIMH NIH HHS/ -- P50 MH068789/MH/NIMH NIH HHS/ -- P50 MH44866/MH/NIMH NIH HHS/ -- R01 MH063271/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1660-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698743" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Benzazepines/pharmacology ; Brain/cytology/metabolism ; Calcium/metabolism ; Calcium Signaling ; Cell Line ; Cyclic AMP/metabolism ; Dendrites/chemistry/metabolism ; Dopamine Agonists/pharmacology ; Female ; Heterotrimeric GTP-Binding Proteins/metabolism ; Humans ; Macaca mulatta ; Membrane Proteins/analysis/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Prefrontal Cortex/cytology/*metabolism ; Pyramidal Cells/chemistry/*metabolism ; Rabbits ; *Receptor Cross-Talk ; Receptors, Dopamine D1/analysis/*metabolism ; Receptors, Neurotransmitter/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Two-Hybrid System Techniques
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    Creating a protein-based element of inheritance (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-01-29
    Description: Proteins capable of self-perpetuating changes in conformation and function (known as prions) can serve as genetic elements. To test whether novel prions could be created by recombinant methods, a yeast prion determinant was fused to the rat glucocorticoid receptor. The fusion protein existed in different heritable functional states, switched between states at a low spontaneous rate, and could be induced to switch by experimental manipulations. The complete change in phenotype achieved by transferring a prion determinant from one protein to another confirms the protein-only nature of prion inheritance and establishes a mechanism for engineering heritable changes in phenotype that should be broadly applicable.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Lindquist, S -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):661-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 South Maryland Avenue MC1028, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10650001" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fungal Proteins/*chemistry/genetics/*metabolism ; Genes, Reporter ; Guanidine/pharmacology ; Heat-Shock Proteins/pharmacology ; Peptide Termination Factors ; Phenotype ; Prions/*chemistry/genetics/*metabolism ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/genetics ; *Saccharomyces cerevisiae Proteins ; Transcription, Genetic ; Transformation, Genetic
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    Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-07-07
    Description: Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geller, D S -- Farhi, A -- Pinkerton, N -- Fradley, M -- Moritz, M -- Spitzer, A -- Meinke, G -- Tsai, F T -- Sigler, P B -- Lifton, R P -- New York, N.Y. -- Science. 2000 Jul 7;289(5476):119-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, Room 154, 295 Congress Avenue, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10884226" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Aldosterone/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Base Sequence ; Binding, Competitive ; Dimerization ; Female ; Heterozygote ; Humans ; Hypertension/etiology/*genetics/metabolism ; Male ; Models, Molecular ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Pregnancy ; *Pregnancy Complications, Cardiovascular/etiology/metabolism ; Progesterone/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Mineralocorticoid/chemistry/*genetics/*metabolism ; Receptors, Steroid/chemistry/metabolism ; Steroids/metabolism
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    The role of GTP-binding protein activity in fast central synaptic transmission (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-07-21
    Description: Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved in exocytosis, endocytosis, and recycling of vesicles in yeast and mammalian secretory cells. However, little is known about their contribution to fast synaptic transmission. We loaded guanine nucleotide analogs directly into a giant nerve terminal in rat brainstem slices. Inhibition of G-protein activity had no effect on basal synaptic transmission, but augmented synaptic depression and significantly slowed recovery from depression. A nonhydrolyzable GTP analog blocked recovery of transmission from activity-dependent depression. Neither effect was accompanied by a change in presynaptic calcium currents. Thus, G proteins contribute to fast synaptic transmission by refilling synaptic vesicles depleted after massive exocytosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, T -- Hori, T -- Kajikawa, Y -- Tsujimoto, T -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):460-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan. ttakahas-tky@umin.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10903208" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Stem/metabolism ; Calcium/metabolism ; Excitatory Postsynaptic Potentials ; Exocytosis ; GTP-Binding Proteins/*physiology ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Diphosphate/*analogs & derivatives/pharmacology ; Guanosine Triphosphate/metabolism ; In Vitro Techniques ; Patch-Clamp Techniques ; Presynaptic Terminals/metabolism ; Rats ; Rats, Wistar ; *Synaptic Transmission ; Synaptic Vesicles/*metabolism ; Thionucleotides/pharmacology
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    Scanometric DNA array detection with nanoparticle probes (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-09-08
    Description: A method for analyzing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional flatbed scanner is described here. Labeling oligonucleotide targets with nanoparticle rather than fluorophore probes substantially alters the melting profiles of the targets from an array substrate. This difference permits the discrimination of an oligonucleotide sequence from targets with single nucleotide mismatches with a selectivity that is over three times that observed for fluorophore-labeled targets. In addition, when coupled with a signal amplification method based on nanoparticle-promoted reduction of silver(I), the sensitivity of this scanometric array detection system exceeds that of the analogous fluorophore system by two orders of magnitude.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taton, T A -- Mirkin, C A -- Letsinger, R L -- GM 57356/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 8;289(5485):1757-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Center for Nanofabrication and Molecular Self-Assembly, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10976070" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pair Mismatch ; Base Pairing ; Carbocyanines ; Fluorescent Dyes ; Gold ; Microscopy, Confocal ; Microscopy, Fluorescence ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis/instrumentation/*methods ; *Oligonucleotide Probes ; Sensitivity and Specificity ; Temperature
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    HSV latency-associated transcript and neuronal apoptosis (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, R L -- Sawtell, N M -- New York, N.Y. -- Science. 2000 Sep 8;289(5485):1651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0524, USA. Richard.Thompson@UC.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11001720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Specificity ; *Apoptosis ; Blotting, Western ; Cell Nucleus/enzymology ; Cytoplasm/enzymology ; DNA Fragmentation ; Genes, Viral ; Herpesvirus 1, Human/genetics/*physiology ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Mice ; Neurons/*cytology/*virology ; Poly(ADP-ribose) Polymerases/analysis/immunology ; Rabbits ; Virus Latency/*genetics
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    Cell biology. A universal bicarbonate sensor (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-12
    Description: The life-span of sperm may be short but it is certainly busy. The three principal molecular events that prepare sperm for fertilization are all controlled by the intracellular nucleotide adenosine 3',5'-monophosphate (cAMP). One of these, capacitation, is also regulated by bicarbonate ions. The elusive connection between cAMP and bicarbonate ions now appears to be solved as Kaupp and Weyand explain in their Perspective. Bicarbonate ions enter sperm through the anion transporter in the sperm plasma membrane and activate the soluble form of adenylyl cyclase, the enzyme that synthesizes cAMP (Chen et al.)〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaupp, U B -- Weyand, I -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):559-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biologische Informationsverarbeitung, Forschungszentrum Jlich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939966" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/chemistry/*metabolism ; Animals ; Bicarbonates/*metabolism/pharmacology ; Calcium Channels/metabolism ; Catalytic Domain ; Cyclic AMP/*metabolism ; Cyclic Nucleotide-Gated Cation Channels ; Enzyme Activation ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Ion Channels/metabolism ; Male ; Molecular Weight ; *Muscle Proteins ; Potassium Channels ; Rats ; Signal Transduction ; Solubility ; *Sperm Capacitation ; Sperm Motility ; Sperm Tail/physiology ; Spermatozoa/metabolism/*physiology
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    Asef, a link between the tumor suppressor APC and G-protein signaling (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-19
    Description: The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawasaki, Y -- Senda, T -- Ishidate, T -- Koyama, R -- Morishita, T -- Iwayama, Y -- Higuchi, O -- Akiyama, T -- New York, N.Y. -- Science. 2000 Aug 18;289(5482):1194-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10947987" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein ; Amino Acid Sequence ; Animals ; Brain/metabolism ; Cell Line ; Cell Membrane/ultrastructure ; Cell Size ; Colon/cytology/metabolism ; Cytoplasm/metabolism ; Cytoskeletal Proteins/*metabolism ; Guanine Nucleotide Exchange Factors/chemistry/genetics/*metabolism ; Guanosine Diphosphate/metabolism ; Humans ; Immunoblotting ; Intestinal Mucosa/cytology/metabolism ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Precipitin Tests ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/metabolism ; Rho Guanine Nucleotide Exchange Factors ; Signal Transduction ; *Trans-Activators ; Transfection ; Two-Hybrid System Techniques ; beta Catenin ; rac GTP-Binding Proteins/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The complete atomic structure of the large ribosomal subunit at 2.4 A resolution (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-11
    Description: The large ribosomal subunit catalyzes peptide bond formation and binds initiation, termination, and elongation factors. We have determined the crystal structure of the large ribosomal subunit from Haloarcula marismortui at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to form a large, monolithic structure. Proteins are abundant everywhere on its surface except in the active site where peptide bond formation occurs and where it contacts the small subunit. Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ban, N -- Nissen, P -- Hansen, J -- 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):905-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics & Biochemistry 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/10937989" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeal Proteins/chemistry/metabolism ; Base Sequence ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; Haloarcula marismortui/*chemistry/ultrastructure ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Conformation ; Protein Folding ; RNA, Archaeal/chemistry/metabolism ; RNA, Ribosomal, 23S/*chemistry/metabolism ; RNA, Ribosomal, 5S/*chemistry/metabolism ; Ribosomal Proteins/*chemistry/metabolism ; Ribosomes/*chemistry/ultrastructure
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    Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-07-07
    Description: The structure of the cytoplasmic assembly of voltage-dependent K+ channels was solved by x-ray crystallography at 2.1 angstrom resolution. The assembly includes the cytoplasmic (T1) domain of the integral membrane alpha subunit together with the oxidoreductase beta subunit in a fourfold symmetric T1(4)beta4 complex. An electrophysiological assay showed that this complex is oriented with four T1 domains facing the transmembrane pore and four beta subunits facing the cytoplasm. The transmembrane pore communicates with the cytoplasm through lateral, negatively charged openings above the T1(4)beta4 complex. The inactivation peptides of voltage-dependent K(+) channels reach their site of action by entering these openings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gulbis, J M -- Zhou, M -- Mann, S -- MacKinnon, R -- GM47400/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 7;289(5476):123-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Neurobiology and Biophysics, 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/10884227" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallography, X-Ray ; Cytoplasm/chemistry ; Kv1.1 Potassium Channel ; Kv1.4 Potassium Channel ; Macromolecular Substances ; Models, Molecular ; Mutation ; Oocytes ; Oxidoreductases/chemistry/metabolism ; Patch-Clamp Techniques ; Peptides/metabolism ; Potassium Channels/*chemistry/genetics/*metabolism ; *Potassium Channels, Voltage-Gated ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Xenopus
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    Group II introns designed to insert into therapeutically relevant DNA target sites in human cells (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-07-21
    Description: Mobile group II intron RNAs insert directly into DNA target sites and are then reverse-transcribed into genomic DNA by the associated intron-encoded protein. Target site recognition involves modifiable base-pairing interactions between the intron RNA and a 〉14-nucleotide region of the DNA target site, as well as fixed interactions between the protein and flanking regions. Here, we developed a highly efficient Escherichia coli genetic assay to determine detailed target site recognition rules for the Lactococcus lactis group II intron Ll.LtrB and to select introns that insert into desired target sites. Using human immunodeficiency virus-type 1 (HIV-1) proviral DNA and the human CCR5 gene as examples, we show that group II introns can be retargeted to insert efficiently into virtually any target DNA and that the retargeted introns retain activity in human cells. This work provides the practical basis for potential applications of targeted group II introns in genetic engineering, functional genomics, and gene therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, H -- Karberg, M -- Long, M -- Jones, J P 3rd -- Sullenger, B -- Lambowitz, A M -- AI40981/AI/NIAID NIH HHS/ -- GM37949/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):452-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, and Section of Molecular Genetics and Microbiology, School of Biological Sciences, University of Texas, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10903206" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Cell Line ; DNA/*genetics ; DNA, Viral/genetics ; Escherichia coli/genetics ; *Gene Targeting ; Genes, pol ; Genetic Therapy ; HIV-1/genetics ; Humans ; *Introns ; Lactococcus lactis/genetics ; Molecular Sequence Data ; Proviruses/genetics ; RNA, Catalytic/*genetics ; Receptors, CCR5/genetics ; Recombination, Genetic ; Transfection
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    Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-15
    Description: A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gupta, A -- Wang, Y -- Markram, H -- New York, N.Y. -- Science. 2000 Jan 14;287(5451):273-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, The Weizmann Institute for Science, 76100 Rehovot, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10634775" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Dendrites/physiology/ultrastructure ; In Vitro Techniques ; Interneurons/cytology/*physiology ; Neocortex/*cytology/physiology ; *Neural Inhibition ; Patch-Clamp Techniques ; Potassium/metabolism ; Pyramidal Cells/cytology/physiology ; Rats ; Rats, Wistar ; Somatosensory Cortex/cytology/physiology ; Synapses/*physiology ; *Synaptic Transmission ; gamma-Aminobutyric Acid/*physiology
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    Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1 (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-29
    Description: Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urano, F -- Wang, X -- Bertolotti, A -- Zhang, Y -- Chung, P -- Harding, H P -- Ron, D -- DK47119/DK/NIDDK NIH HHS/ -- ES08681/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):664-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10650002" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Endoplasmic Reticulum/*metabolism ; Endoribonucleases/genetics/*metabolism ; Enzyme Activation ; Gene Targeting ; Humans ; JNK Mitogen-Activated Protein Kinases ; *Membrane Proteins ; Mitogen-Activated Protein Kinases/*metabolism ; Multienzyme Complexes/genetics/*metabolism ; Protein Kinases/genetics/*metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proteins/chemistry/genetics/*metabolism ; Rats ; Recombinant Fusion Proteins/metabolism ; TNF Receptor-Associated Factor 2 ; Thapsigargin/pharmacology ; Two-Hybrid System Techniques ; eIF-2 Kinase/metabolism
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    Evidence for the evolution of bdelloid rotifers without sexual reproduction or genetic exchange (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-05-20
    Description: The Class Bdelloidea of the Phylum Rotifera is the largest metazoan taxon in which males, hermaphrodites, and meiosis are unknown. We conducted a molecular genetic test of this indication that bdelloid rotifers may have evolved without sexual reproduction or genetic exchange. The test is based on the expectation that after millions of years without these processes, genomes will no longer contain pairs of closely similar haplotypes and instead will contain highly divergent descendants of formerly allelic nucleotide sequences. We find that genomes of individual bdelloid rotifers, representing four different species, appear to lack pairs of closely similar sequences and contain representatives of two ancient lineages that began to diverge before the bdelloid radiation many millions of years ago when sexual reproduction and genetic exchange may have ceased.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mark Welch, D -- Meselson, M -- New York, N.Y. -- Science. 2000 May 19;288(5469):1211-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10817991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacterial Proteins ; Base Sequence ; *Biological Evolution ; DNA-Binding Proteins/genetics ; Genes, Helminth ; HSP90 Heat-Shock Proteins ; Heat-Shock Proteins/genetics ; Molecular Sequence Data ; Phylogeny ; *Recombination, Genetic ; Reproduction, Asexual/*genetics ; Rotifera/*classification/*genetics/physiology ; Saccharomyces cerevisiae Proteins ; Sequence Analysis, DNA ; Sigma Factor/genetics ; Species Specificity ; TATA-Box Binding Protein ; Transcription Factors/genetics ; Triose-Phosphate Isomerase/genetics
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    Mechanism of ATP-dependent promoter melting by transcription factor IIH (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-05-29
    Description: We show that transcription factor IIH ERCC3 subunit, the DNA helicase responsible for adenosine triphosphate (ATP)-dependent promoter melting during transcription initiation, does not interact with the promoter region that undergoes melting but instead interacts with DNA downstream of this region. We show further that promoter melting does not change protein-DNA interactions upstream of the region that undergoes melting but does change interactions within and downstream of this region. Our results rule out the proposal that IIH functions in promoter melting through a conventional DNA-helicase mechanism. We propose that IIH functions as a molecular wrench: rotating downstream DNA relative to fixed upstream protein-DNA interactions, thereby generating torque on, and melting, the intervening DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, T K -- Ebright, R H -- Reinberg, D -- GM37120/GM/NIGMS NIH HHS/ -- GM53665/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 May 26;288(5470):1418-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10827951" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Base Sequence ; DNA/*chemistry/*metabolism ; DNA Helicases/metabolism ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/*metabolism ; Humans ; Models, Genetic ; Molecular Sequence Data ; Nucleic Acid Conformation ; *Promoter Regions, Genetic ; Protein Binding ; RNA Polymerase II/metabolism ; Transcription Factor TFIIH ; Transcription Factors/*metabolism ; *Transcription Factors, TFII ; Transcription, Genetic
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    Developmental biology. Brain cells turning over a new leaf (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2000 Sep 8;289(5485):1666.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11001723" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Blood ; Cell Culture Techniques ; *Cell Differentiation ; Cells, Cultured ; Culture Media ; Fibroblast Growth Factors/pharmacology ; Neurons/*cytology ; Oligodendroglia/*cytology ; Rats ; Stem Cells/*cytology
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    Down-regulation of the macrophage lineage through interaction with OX2 (CD200) (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-12-02
    Description: OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoek, R M -- Ruuls, S R -- Murphy, C A -- Wright, G J -- Goddard, R -- Zurawski, S M -- Blom, B -- Homola, M E -- Streit, W J -- Brown, M H -- Barclay, A N -- Sedgwick, J D -- New York, N.Y. -- Science. 2000 Dec 1;290(5497):1768-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11099416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD ; Antigens, Surface/*metabolism ; Arthritis, Experimental/immunology/pathology ; Cell Lineage ; Central Nervous System/immunology/pathology ; Denervation ; *Down-Regulation ; Encephalomyelitis, Autoimmune, Experimental/immunology/pathology ; Facial Nerve ; Gene Targeting ; Joints/immunology/pathology ; Lymph Nodes/cytology ; Macrophage Activation ; Macrophages/cytology/metabolism/*physiology ; Mice ; Mice, Inbred C57BL ; Microglia/physiology ; Neurons/physiology ; Rats ; Receptors, Immunologic/metabolism ; Spleen/cytology
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    Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-11
    Description: The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ikonomidou, C -- Bittigau, P -- Ishimaru, M J -- Wozniak, D F -- Koch, C -- Genz, K -- Price, M T -- Stefovska, V -- Horster, F -- Tenkova, T -- Dikranian, K -- Olney, J W -- AG 11355/AG/NIA NIH HHS/ -- DA 05072/DA/NIDA NIH HHS/ -- MH 38894/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1056-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Neurology, Charite, Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzodiazepines/pharmacology ; Dose-Response Relationship, Drug ; Ethanol/administration & dosage/blood/*toxicity ; Female ; Fetal Alcohol Spectrum Disorders/*pathology ; GABA Modulators/pharmacology ; Humans ; *Nerve Degeneration ; Neurons/cytology/pathology ; Organ Size/drug effects ; Pregnancy ; Prosencephalon/cytology/*drug effects/embryology/growth & development ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A/*drug effects/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*drug effects/metabolism ; Synapses/drug effects/physiology
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    Neuroscience. New stroke treatment strategy explored (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1379, 1381.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10722377" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood-Brain Barrier ; Brain/*pathology ; Cell Death ; Dependovirus/genetics ; Gene Transfer Techniques ; Humans ; Neurons/*pathology ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & ; inhibitors/*genetics/*immunology/physiology ; Status Epilepticus/pathology/*therapy ; Stroke/pathology/*therapy ; Vaccination ; Vaccines, DNA/*therapeutic use
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    Calcium sensitivity of glutamate release in a calyx-type terminal (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-11
    Description: Synaptic efficacy critically depends on the presynaptic intracellular calcium concentration ([Ca2+]i). We measured the calcium sensitivity of glutamate release in a rat auditory brainstem synapse by laser photolysis of caged calcium. A rise in [Ca2+]i to 1 micromolar readily evoked release. An increase to 〉30 micromolar depleted the releasable vesicle pool in 〈0.5 millisecond. A comparison with action potential-evoked release suggested that a brief increase of [Ca2+]i to approximately 10 micromolar would be sufficient to reproduce the physiological release pattern. Thus, the calcium sensitivity of release at this synapse is high, and the distinction between phasic and delayed release is less pronounced than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bollmann, J H -- Sakmann, B -- Borst, J G -- New York, N.Y. -- Science. 2000 Aug 11;289(5481):953-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institute for Medical Research, Department of Cell Physiology, Jahnstrasse 29, D-69120 Heidelberg, Germany. jbollman@mpimf-heidelberg.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10937999" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Stem/*metabolism ; Calcium/*metabolism ; Excitatory Postsynaptic Potentials ; Glutamic Acid/*metabolism ; Patch-Clamp Techniques ; Photolysis ; Presynaptic Terminals/metabolism ; Rats ; Rats, Wistar ; Synapses/*metabolism ; Synaptic Transmission ; Synaptic Vesicles/metabolism
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    Start sites of bidirectional DNA synthesis at the human lamin B2 origin (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-03-17
    Description: The initiation sites of bidirectional synthesis at the DNA replication origin located at the 3' end of the human lamin B2 gene were investigated. RNA-primed nascent DNA molecules were subjected to second-strand synthesis with appropriate primers, amplified by ligation-mediated polymerase chain reaction, and size fractionated. Evidence for precise start sites was obtained. Exploration of close to 1 kilobase, coupled to inhibition of Okazaki fragment synthesis, demonstrates that the leading strands initiate at precise nucleotides on either helix, overlapping by three base pairs, within the area bound to a protein complex possibly analogous to the prereplicative complex of yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abdurashidova, G -- Deganuto, M -- Klima, R -- Riva, S -- Biamonti, G -- Giacca, M -- Falaschi, A -- New York, N.Y. -- Science. 2000 Mar 17;287(5460):2023-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology and Molecular Medicine Units, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10720330" target="_blank"〉PubMed〈/a〉
    Keywords: AT Rich Sequence ; Base Sequence ; DNA/biosynthesis ; DNA Primers/metabolism ; *DNA Replication ; Emetine/pharmacology ; G1 Phase ; HeLa Cells ; Humans ; *Lamin Type B ; Lamins ; Molecular Sequence Data ; Nuclear Proteins/*genetics ; Protein Binding ; *Replication Origin ; S Phase
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    Resetting central and peripheral circadian oscillators in transgenic rats (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-04-28
    Description: In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamazaki, S -- Numano, R -- Abe, M -- Hida, A -- Takahashi, R -- Ueda, M -- Block, G D -- Sakaki, Y -- Menaker, M -- Tei, H -- MH56647/MH/NIMH NIH HHS/ -- R01 MH056647/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):682-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10784453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Biological Clocks/*physiology ; Cell Cycle Proteins ; Circadian Rhythm/*physiology ; Culture Techniques ; Darkness ; Genes, Reporter ; Light ; Liver/physiology ; Luciferases/genetics/metabolism ; Lung/physiology ; Male ; Mice ; Motor Activity ; Muscle, Skeletal/physiology ; Nuclear Proteins/genetics/physiology ; Period Circadian Proteins ; Promoter Regions, Genetic ; Rats ; Suprachiasmatic Nucleus/*physiology
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    Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-01
    Description: Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Y -- Cann, M J -- Litvin, T N -- Iourgenko, V -- Sinclair, M L -- Levin, L R -- Buck, J -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):625-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10915626" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/chemistry/genetics/isolation & purification/*metabolism ; Animals ; Bicarbonates/*metabolism/pharmacology ; Catalytic Domain ; Cell Line ; Cyanobacteria/enzymology ; Cyclic AMP/metabolism ; Enzyme Activation ; Evolution, Molecular ; Humans ; Hydrogen-Ion Concentration ; Male ; Phylogeny ; Rats ; Recombinant Proteins/isolation & purification/metabolism ; Second Messenger Systems ; Signal Transduction ; Solubility ; Sperm Capacitation ; Spermatozoa/enzymology/*metabolism/physiology ; Testis/metabolism
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    Function of an axonal chemoattractant modulated by metalloprotease activity (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-26
    Description: The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. We have also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galko, M J -- Tessier-Lavigne, M -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1365-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958786" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; CHO Cells ; Cell Adhesion Molecules/chemistry/*metabolism ; Cricetinae ; Culture Techniques ; Growth Cones/physiology ; Metalloendopeptidases/antagonists & inhibitors/*metabolism ; Nerve Growth Factors/*metabolism ; Phenanthrolines/pharmacology ; Protease Inhibitors/pharmacology ; Rats ; Spinal Cord/*cytology/*enzymology/metabolism ; *Tumor Suppressor Proteins
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    Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-07-21
    Description: The guanosine triphosphatase Rab1 regulates the transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus through interaction with effector molecules, but the molecular mechanisms by which this occurs are unknown. Here, the tethering factor p115 was shown to be a Rab1 effector that binds directly to activated Rab1. Rab1 recruited p115 to coat protein complex II (COPII) vesicles during budding from the endoplasmic reticulum, where it interacted with a select set of COPII vesicle-associated SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. We propose that Rab1-regulated assembly of functional effector-SNARE complexes defines a conserved molecular mechanism to coordinate recognition between subcellular compartments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allan, B B -- Moyer, B D -- Balch, W E -- CA58689/CA/NCI NIH HHS/ -- GM 33301/GM/NIGMS NIH HHS/ -- GM42336/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):444-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Cell and Molecular Biology, 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/10903204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; Carrier Proteins/*metabolism ; Endoplasmic Reticulum/*metabolism ; Golgi Apparatus/*metabolism ; Intracellular Membranes/metabolism ; Membrane Fusion ; *Membrane Glycoproteins ; Membrane Proteins/*metabolism ; Mutation ; Organelles/metabolism ; Phosphoproteins/*metabolism ; Rats ; Recombinant Fusion Proteins/metabolism ; SNARE Proteins ; *Saccharomyces cerevisiae Proteins ; *Vesicular Transport Proteins ; Viral Envelope Proteins/metabolism ; rab1 GTP-Binding Proteins/*metabolism
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    Altered nociceptive neuronal circuits after neonatal peripheral inflammation (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-01
    Description: Nociceptive neuronal circuits are formed during embryonic and postnatal times when painful stimuli are normally absent or limited. Today, medical procedures for neonates with health risks can involve tissue injury and pain for which the long-term effects are unknown. To investigate the impact of neonatal tissue injury and pain on development of nociceptive neuronal circuitry, we used an animal model of persistent hind paw peripheral inflammation. We found that, as adults, these animals exhibited spinal neuronal circuits with increased input and segmental changes in nociceptive primary afferent axons and altered responses to sensory stimulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruda, M A -- Ling, Q D -- Hohmann, A G -- Peng, Y B -- Tachibana, T -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):628-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular Neuroscience Section, Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA. maruda@dir.nidcr.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10915627" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways ; Animals ; Animals, Newborn ; Axons/physiology ; Cell Count ; Freund's Adjuvant ; Ganglia, Spinal/cytology/physiology ; Hindlimb/innervation ; Inflammation/physiopathology ; Male ; Neurons, Afferent/cytology/*physiology ; *Pain ; Pain Measurement ; Pain Threshold ; Posterior Horn Cells/cytology/*physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/cytology/physiology ; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
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    The evolutionary fate and consequences of duplicate genes (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-11-10
    Description: Gene duplication has generally been viewed as a necessary source of material for the origin of evolutionary novelties, but it is unclear how often gene duplicates arise and how frequently they evolve new functions. Observations from the genomic databases for several eukaryotic species suggest that duplicate genes arise at a very high rate, on average 0.01 per gene per million years. Most duplicated genes experience a brief period of relaxed selection early in their history, with a moderate fraction of them evolving in an effectively neutral manner during this period. However, the vast majority of gene duplicates are silenced within a few million years, with the few survivors subsequently experiencing strong purifying selection. Although duplicate genes may only rarely evolve new functions, the stochastic silencing of such genes may play a significant role in the passive origin of new species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lynch, M -- Conery, J S -- R01-GM36827/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 10;290(5494):1151-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Oregon, Eugene, OR 97403, USA. mlynch@oregon.uoregon.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11073452" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Arabidopsis/genetics ; Base Sequence ; Caenorhabditis elegans/genetics ; Chickens/genetics ; Databases, Factual ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Silencing ; *Genes, Duplicate ; *Genome ; Humans ; Mice ; Models, Genetic ; Mutation ; Oryza/genetics ; Probability ; Proteins/chemistry/genetics ; Saccharomyces cerevisiae/genetics ; Selection, Genetic ; Stochastic Processes ; Time Factors
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    Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-07-06
    Description: Efferent feedback onto sensory organs provides a means to modulate input to the central nervous system. In the developing mammalian cochlea, inner hair cells are transiently innervated by efferent fibers, even before sensory function begins. Here, we show that neonatal inner hair cells are inhibited by cholinergic synaptic input before the onset of hearing. The synaptic currents, as well as the inner hair cell's response to acetylcholine, are mediated by a nicotinic (alpha9-containing) receptor and result in the activation of small-conductance calcium-dependent potassium channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glowatzki, E -- Fuchs, P A -- DC 00276/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2366-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Center for Hearing Sciences, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. eglowatz@bme.jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875922" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/*pharmacology ; Action Potentials ; Animals ; Animals, Newborn ; Apamin/pharmacology ; Bungarotoxins/pharmacology ; Calcium/metabolism ; Cholinergic Antagonists/pharmacology ; Electric Conductivity ; Hair Cells, Auditory, Inner/drug effects/*physiology ; In Vitro Techniques ; *Neural Inhibition ; Neurons, Efferent/physiology ; Patch-Clamp Techniques ; Potassium/metabolism ; Potassium Channels/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic/*metabolism ; Strychnine/pharmacology ; Synapses/*physiology ; Synaptic Transmission/*drug effects
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    Dendritic computation of direction selectivity by retinal ganglion cells (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-29
    Description: Direction-selective ganglion cells (DSGCs) in the retina respond strongly when stimulated by image motion in a preferred direction but are only weakly excited by image motion in the opposite null direction. Such coding represents an early manifestation of complex information processing in the visual system, but the cellular locus and the synaptic mechanisms have yet to be elucidated. We recorded the synaptic activity of DSGCs using strategies to observe the asymmetric inhibitory inputs that underlie the generation of direction selectivity. The critical nonlinear interactions between the excitatory and inhibitory inputs took place postsynaptically within the dendrites of the DSGCs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, W R -- He, S -- Levick, W R -- Vaney, D I -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2347-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉John Curtin School of Medical Research, Centre for Visual Sciences, Department of Psychology, Australian National University, Canberra, ACT 2601, Australia. Rowland.Taylor@anu.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11009420" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Chloride Channels/metabolism ; Chlorides/metabolism ; Culture Techniques ; Dendrites/*physiology ; Excitatory Postsynaptic Potentials ; Interneurons/physiology ; Motion Perception/*physiology ; Neural Inhibition ; Patch-Clamp Techniques ; Rabbits ; Retinal Ganglion Cells/*physiology ; Sodium Channels/metabolism ; Synapses/physiology ; Synaptic Transmission ; gamma-Aminobutyric Acid/physiology
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    Identification of HE1 as the second gene of Niemann-Pick C disease (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-12-23
    Description: Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naureckiene, S -- Sleat, D E -- Lackland, H -- Fensom, A -- Vanier, M T -- Wattiaux, R -- Jadot, M -- Lobel, P -- DK45992/DK/NIDDK NIH HHS/ -- DK54317/DK/NIDDK NIH HHS/ -- NS37918/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 22;290(5500):2298-301.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11125141" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biological Transport ; CHO Cells ; *Carrier Proteins ; Cell Membrane/metabolism ; Cells, Cultured ; Cholesterol/*metabolism ; Cricetinae ; Culture Media, Conditioned ; Fibroblasts/metabolism ; Glycoproteins/chemistry/*genetics/*metabolism/pharmacology ; Humans ; Lysosomes/*metabolism ; Molecular Sequence Data ; Mutation ; Niemann-Pick Diseases/*genetics/metabolism ; Rats ; Receptor, IGF Type 2/metabolism ; Recombinant Proteins/metabolism/pharmacology ; Transfection
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    Specific mutations induced by triplex-forming oligonucleotides in mice (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-20
    Description: Triplex-forming oligonucleotides (TFOs) recognize and bind to specific duplex DNA sequences and have been used extensively to modify gene function in cells. Although germ line mutations can be incorporated by means of embryonic stem cell technology, little progress has been made toward introducing mutations in somatic cells of living organisms. Here we demonstrate that TFOs can induce mutations at specific genomic sites in somatic cells of adult mice. Mutation detection was facilitated by the use of transgenic mice bearing chromosomal copies of the supF and cII reporter genes. Mice treated with a supF-targeted TFO displayed about fivefold greater mutation frequencies in the supF gene compared with mice treated with a scrambled sequence control oligomer. No mutagenesis was detected in the control gene (cII) with either oligonucleotide. These results demonstrate that site-specific, TFO-directed genome modification can be accomplished in intact animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vasquez, K M -- Narayanan, L -- Glazer, P M -- CA64186/CA/NCI NIH HHS/ -- CA75723/CA/NCI NIH HHS/ -- F32 CA075723/CA/NCI NIH HHS/ -- GM54731/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):530-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Therapeutic Radiology and Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039937" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pair Mismatch ; Base Sequence ; DNA/chemistry/*genetics/metabolism ; *Gene Targeting ; Genes, Reporter ; Genes, Suppressor ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; *Mutagenesis, Site-Directed ; Mutation ; Oligodeoxyribonucleotides/chemistry/*genetics/metabolism ; RNA, Transfer/genetics
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    Questioning evidence for recombination in human mitochondrial DNA (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kivisild, T -- Villems, R -- New York, N.Y. -- Science. 2000 Jun 16;288(5473):1931.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Estonian Biocentre and Department of Evolutionary Biology, Tartu University, 23 Riia Street, 51010 Tartu, Estonia. tkivisil@ebc.ee〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10877700" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Haplotypes ; Hominidae/genetics ; Humans ; Phylogeny ; Polymorphism, Genetic ; *Recombination, Genetic
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    Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-03-24
    Description: To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, Y -- Shi, S H -- Esteban, J A -- Piccini, A -- Poncer, J C -- Malinow, R -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2262-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10731148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Catalytic Domain ; Cell Line ; Hippocampus/cytology/metabolism ; Humans ; *Long-Term Potentiation ; Membrane Potentials ; Mutation ; Organ Culture Techniques ; Patch-Clamp Techniques ; Phosphorylation ; Protein Structure, Tertiary ; Proteins/*metabolism ; Pyramidal Cells/metabolism/*physiology ; Rats ; Receptors, AMPA/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Synapses/*metabolism ; Synaptic Transmission
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    DNA cuts its teeth--as an enzyme (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finkel, E -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2441-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636800" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carotid Arteries ; Catalysis ; Catalytic Domain ; Cell Division ; *DNA, Catalytic ; DNA, Single-Stranded/chemistry/*metabolism/therapeutic use ; DNA-Binding Proteins/*genetics/physiology ; Directed Molecular Evolution ; Early Growth Response Protein 1 ; *Immediate-Early Proteins ; Muscle, Smooth, Vascular/cytology/injuries/metabolism ; RNA, Catalytic/metabolism ; RNA, Messenger/genetics/*metabolism ; Rats ; Transcription Factors/*genetics/physiology ; Wound Healing
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    A myosin I isoform in the nucleus (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-13
    Description: A nuclear isoform of myosin I beta that contains a unique 16-amino acid amino-terminal extension has been identified. An affinity-purified antibody to the 16-amino acid peptide demonstrated nuclear staining. Confocal and electron microscopy revealed that nuclear myosin I beta colocalized with RNA polymerase II in an alpha-amanitin- and actinomycin D-sensitive manner. The antibody coimmunoprecipitated RNA polymerase II and blocked in vitro RNA synthesis. This isoform of myosin I beta appears to be in a complex with RNA polymerase II and may affect transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pestic-Dragovich, L -- Stojiljkovic, L -- Philimonenko, A A -- Nowak, G -- Ke, Y -- Settlage, R E -- Shabanowitz, J -- Hunt, D F -- Hozak, P -- de Lanerolle, P -- GM 37537/GM/NIGMS NIH HHS/ -- GM 56489/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 13;290(5490):337-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11030652" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Actins/metabolism ; Amanitins/pharmacology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Nucleus/*metabolism ; Cloning, Molecular ; Dactinomycin/pharmacology ; Exons ; HeLa Cells ; Humans ; Mice ; Microscopy, Confocal ; Microscopy, Electron ; *Molecular Motor Proteins ; Molecular Sequence Data ; Myosins/chemistry/genetics/immunology/*metabolism ; Nucleic Acid Synthesis Inhibitors/pharmacology ; Precipitin Tests ; Protein Isoforms/chemistry/genetics/immunology/metabolism ; RNA/*biosynthesis ; RNA Polymerase II/*metabolism ; *Transcription, Genetic
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    Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-26
    Description: Latent infections with periodic reactivation are a common outcome after acute infection with many viruses. The latency-associated transcript (LAT) gene is required for wild-type reactivation of herpes simplex virus (HSV). However, the underlying mechanisms remain unclear. In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT(-) virus but not with LAT(+) viruses. In addition, a plasmid expressing LAT blocked apoptosis in cultured cells. Thus, LAT promotes neuronal survival after HSV-1 infection by reducing apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perng, G C -- Jones, C -- Ciacci-Zanella, J -- Stone, M -- Henderson, G -- Yukht, A -- Slanina, S M -- Hofman, F M -- Ghiasi, H -- Nesburn, A B -- Wechsler, S L -- EY07566/EY/NEI NIH HHS/ -- EY11629/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1500-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns & Allen Research Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688801" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Line ; Genes, Viral ; Herpesvirus 1, Human/genetics/*physiology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Keratitis, Herpetic/*pathology/*virology ; Mutation ; Neurons/*pathology/virology ; Poly(ADP-ribose) Polymerases/immunology/metabolism ; Rabbits ; Transcription, Genetic ; Trigeminal Ganglion/pathology/virology ; Virus Activation ; Virus Latency/*genetics
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    Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3 (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-11-25
    Description: beta-Arrestins, originally discovered in the context of heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) desensitization, also function in internalization and signaling of these receptors. We identified c-Jun amino-terminal kinase 3 (JNK3) as a binding partner of beta-arrestin 2 using a yeast two-hybrid screen and by coimmunoprecipitation from mouse brain extracts or cotransfected COS-7 cells. The upstream JNK activators apoptosis signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinase (MAPK) kinase 4 were also found in complex with beta-arrestin 2. Cellular transfection of beta-arrestin 2 caused cytosolic retention of JNK3 and enhanced JNK3 phosphorylation stimulated by ASK1. Moreover, stimulation of the angiotensin II type 1A receptor activated JNK3 and triggered the colocalization of beta-arrestin 2 and active JNK3 to intracellular vesicles. Thus, beta-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonald, P H -- Chow, C W -- Miller, W E -- Laporte, S A -- Field, M E -- Lin, F T -- Davis, R J -- Lefkowitz, R J -- CA65861/CA/NCI NIH HHS/ -- CA85422/CA/NCI NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090355" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/metabolism/pharmacology ; Animals ; Arrestins/genetics/*metabolism ; COS Cells ; Cell Line ; Cell Nucleus/metabolism ; Cytosol/enzymology/metabolism ; Endosomes/enzymology/metabolism ; Enzyme Activation ; Humans ; *MAP Kinase Kinase 4 ; MAP Kinase Kinase Kinase 5 ; MAP Kinase Kinase Kinases/*metabolism ; *MAP Kinase Signaling System ; Mice ; Mitogen-Activated Protein Kinase 10 ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Mutation ; Phosphorylation ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Rats ; Receptor, Angiotensin, Type 1 ; Receptors, Angiotensin/*metabolism ; Recombinant Fusion Proteins/metabolism ; Transfection ; Two-Hybrid System Techniques
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    An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-26
    Description: The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉During, M J -- Symes, C W -- Lawlor, P A -- Lin, J -- Dunning, J -- Fitzsimons, H L -- Poulsen, D -- Leone, P -- Xu, R -- Dicker, B L -- Lipski, J -- Young, D -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1453-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine and Department of Physiology, University of Auckland School of Medicine, Auckland, New Zealand. matthew.during@mail.tju.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688787" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Animals ; Antibody Affinity ; Autoantibodies/analysis/blood/cerebrospinal fluid/*immunology ; Blood-Brain Barrier ; Dependovirus/genetics ; Epilepsy, Temporal Lobe/pathology/*therapy ; Epitope Mapping ; Epitopes ; Genetic Vectors ; Hippocampus/pathology ; Intestinal Mucosa/immunology/metabolism ; Lymphocyte Activation ; Motor Activity ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & ; inhibitors/biosynthesis/*genetics/*immunology ; Status Epilepticus/prevention & control ; Stroke/*therapy ; Transgenes ; Vaccination ; Vaccines, DNA/*therapeutic use
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    PSD-95 involvement in maturation of excitatory synapses (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-11-18
    Description: PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉El-Husseini, A E -- Schnell, E -- Chetkovich, D M -- Nicoll, R A -- Bredt, D S -- New York, N.Y. -- Science. 2000 Nov 17;290(5495):1364-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11082065" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dendrites/ultrastructure ; Excitatory Postsynaptic Potentials ; Hippocampus/cytology ; Interneurons/cytology/metabolism/*physiology ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Nerve Tissue Proteins/chemistry/genetics/metabolism/*physiology ; Patch-Clamp Techniques ; Presynaptic Terminals/physiology ; Protein Structure, Tertiary ; Pyramidal Cells/cytology/metabolism/*physiology ; Rats ; Receptor Aggregation ; Receptors, AMPA/metabolism ; Receptors, Glutamate/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism/*physiology ; Synaptic Transmission ; Synaptic Vesicles/physiology ; Transfection
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    Distal initiation and active propagation of action potentials in interneuron dendrites (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-01-15
    Description: Fast and reliable activation of inhibitory interneurons is critical for the stability of cortical neuronal networks. Active conductances in dendrites may facilitate interneuron activation, but direct experimental evidence was unavailable. Patch-clamp recordings from dendrites of hippocampal oriens-alveus interneurons revealed high densities of voltage-gated sodium and potassium ion channels. Simultaneous recordings from dendrites and somata suggested that action potential initiation occurs preferentially in the axon with long threshold stimuli, but can be shifted to somatodendritic sites when brief stimuli are applied. After initiation, action potentials propagate over the somatodendritic domain with constant amplitude, high velocity, and reliability, even during high-frequency trains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martina, M -- Vida, I -- Jonas, P -- New York, N.Y. -- Science. 2000 Jan 14;287(5451):295-300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiologisches Institut der Universitat Freiburg, Anatomisches Institut der Universitat Freiburg, D-79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10634782" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/physiology/ultrastructure ; Dendrites/*physiology/ultrastructure ; Excitatory Postsynaptic Potentials ; Hippocampus/cytology/*physiology ; In Vitro Techniques ; Interneurons/chemistry/cytology/*physiology ; Ion Channel Gating ; Patch-Clamp Techniques ; Potassium/metabolism ; Potassium Channels/physiology ; Rats ; Rats, Wistar ; Sodium/metabolism ; Sodium Channels/*physiology ; Somatostatin/analysis ; Synapses/physiology/ultrastructure ; Tetrodotoxin/pharmacology
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    Resetting of circadian time in peripheral tissues by glucocorticoid signaling (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-09-29
    Description: In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balsalobre, A -- Brown, S A -- Marcacci, L -- Tronche, F -- Kellendonk, C -- Reichardt, H M -- Schutz, G -- Schibler, U -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2344-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Biologie Moleculaire, Sciences II, Universite de Geneve, 30 Quai Ernest Ansermet, CH-1211 Geneve, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11009419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; Cell Cycle Proteins ; Cell Line ; Circadian Rhythm/*physiology ; *DNA-Binding Proteins ; Dexamethasone/analogs & derivatives/*pharmacology ; Female ; *Gene Expression Regulation/drug effects ; Kidney/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred Strains ; Mutation ; Myocardium/metabolism ; Neurons/metabolism ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; Rats ; Receptors, Glucocorticoid/genetics/metabolism ; *Signal Transduction ; Suprachiasmatic Nucleus/metabolism ; Transcription Factors/genetics/metabolism
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    Selfish DNA in protein-coding genes of Rickettsia (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-13
    Description: Rickettsia conorii, the aetiological agent of Mediterranean spotted fever, is an intracellular bacterium transmitted by ticks. Preliminary analyses of the nearly complete genome sequence of R. conorii have revealed 44 occurrences of a previously undescribed palindromic repeat (150 base pairs long) throughout the genome. Unexpectedly, this repeat was found inserted in-frame within 19 different R. conorii open reading frames likely to encode functional proteins. We found the same repeat in proteins of other Rickettsia species. The finding of a mobile element inserted in many unrelated genes suggests the potential role of selfish DNA in the creation of new protein sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogata, H -- Audic, S -- Barbe, V -- Artiguenave, F -- Fournier, P E -- Raoult, D -- Claverie, J M -- New York, N.Y. -- Science. 2000 Oct 13;290(5490):347-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Information Genetique & Structurale, CNRS-AVENTIS UMR 1889, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11030655" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/*genetics ; Base Sequence ; Conserved Sequence ; DNA, Bacterial/*genetics ; Evolution, Molecular ; Genome, Bacterial ; *Interspersed Repetitive Sequences ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nucleic Acid Conformation ; Open Reading Frames/*genetics ; Protein Biosynthesis ; Protein Conformation ; Protein Structure, Secondary ; RNA, Bacterial/chemistry/genetics/metabolism ; RNA, Messenger/chemistry/*genetics/metabolism ; Rickettsia/*genetics ; Rickettsia conorii/*genetics
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    Voltage- and tension-dependent lipid mobility in the outer hair cell plasma membrane (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-29
    Description: The mechanism responsible for electromotility of outer hair cells in the ear is unknown but is thought to reside within the plasma membrane. Lipid lateral diffusion in the outer hair cell plasma membrane is a sigmoidal function of transmembrane potential and bathing media osmolality. Cell depolarization or hyposmotic challenge shorten the cell and reduce membrane fluidity by half. Changing the membrane tension with amphipathic drugs results in similar reductions. These dynamic changes in membrane fluidity represent the modulation of membrane tension by lipid-protein interactions. The voltage dependence may be associated with the force-generating motors that contribute to the exquisite sensitivity of mammalian hearing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976274/" 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/PMC1976274/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oghalai, J S -- Zhao, H B -- Kutz, J W -- Brownell, W E -- R01 DC000354/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):658-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology and Communicative Sciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10650000" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/drug effects/physiology ; Cells, Cultured ; Chlorpromazine/pharmacology ; Diffusion ; Erythrocyte Membrane/drug effects/physiology ; Fluorescent Dyes/metabolism ; Guinea Pigs ; Hair Cells, Auditory, Outer/drug effects/*physiology/ultrastructure ; Lipid Bilayers ; *Membrane Fluidity ; Membrane Potentials ; Osmolar Concentration ; Patch-Clamp Techniques ; Phospholipids/*physiology ; Pressure ; Pyridinium Compounds/metabolism ; Rats ; Salicylates/pharmacology
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    Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter (2000)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2000-08-11
    Description: Previous work has identified two families of proteins that transport classical neurotransmitters into synaptic vesicles, but the protein responsible for vesicular transport of the principal excitatory transmitter glutamate has remained unknown. We demonstrate that a protein that is unrelated to any known neurotransmitter transporters and that was previously suggested to mediate the Na(+)-dependent uptake of inorganic phosphate across the plasma membrane transports glutamate into synaptic vesicles. In addition, we show that this vesicular glutamate transporter, VGLUT1, exhibits a conductance for chloride that is blocked by glutamate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bellocchio, E E -- Reimer, R J -- Fremeau, R T Jr -- Edwards, R H -- New York, N.Y. -- Science. 2000 Aug 11;289(5481):957-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California at San Francisco School of Medicine, 513 Parnassus Avenue, San Francisco, CA 94143-0435, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10938000" target="_blank"〉PubMed〈/a〉
    Keywords: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology ; Adenosine Triphosphate/metabolism ; Animals ; Biological Transport, Active/drug effects ; Carrier Proteins/genetics/*metabolism ; Cell Membrane/metabolism ; Chlorides/metabolism ; Glutamic Acid/*metabolism ; Hydrogen-Ion Concentration ; PC12 Cells ; Phosphates/metabolism ; Potassium Chloride/metabolism ; Rats ; Sodium-Phosphate Cotransporter Proteins ; *Symporters ; Synaptic Vesicles/*metabolism ; Transfection
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    Ultraconserved elements in the human genome (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-05-08
    Description: There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bejerano, Gill -- Pheasant, Michael -- Makunin, Igor -- Stephen, Stuart -- Kent, W James -- Mattick, John S -- Haussler, David -- 1P41HG02371/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 May 28;304(5675):1321-5. Epub 2004 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. jill@soe.ucsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15131266" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Base Sequence ; Chickens/genetics ; Computational Biology ; *Conserved Sequence ; DNA, Intergenic ; Dogs/genetics ; Evolution, Molecular ; Exons ; Gene Expression Regulation ; Genes ; Genome ; *Genome, Human ; Humans ; Introns ; Mice/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; RNA/chemistry/genetics/metabolism ; Rats/genetics ; Takifugu/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The Biology of Genomes meeting. The case of the disappearing DNA hotspots (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2004 Jun 11;304(5677):1590.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15192195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Biological Evolution ; *Genome ; *Genome, Human ; Humans ; Pan troglodytes/*genetics ; *Polymorphism, Single Nucleotide ; *Recombination, Genetic
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    A link between mRNA turnover and RNA interference in Arabidopsis (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-11-06
    Description: In RNA interference (RNAi), double-stranded RNA (dsRNA) triggers degradation of homologous messenger RNA. In many organisms, RNA-dependent RNA polymerase (RdRp) is required to initiate or amplify RNAi, but the substrate for dsRNA synthesis in vivo is not known. Here, we show that RdRp-dependent transgene silencing in Arabidopsis was caused by mutation of XRN4, which is a ribonuclease (RNase) implicated in mRNA turnover by means of decapping and 5'-3' exonucleolysis. When both XRN4 and the RdRp were mutated, the plants accumulated decapped transgene mRNA. We propose that mRNAs lacking a cap structure become exposed to RdRp to initiate or maintain RNAi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gazzani, S -- Lawrenson, T -- Woodward, C -- Headon, D -- Sablowski, R -- BBS/E/J/00000594/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2004 Nov 5;306(5698):1046-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/*genetics ; Arabidopsis Proteins/genetics ; Exoribonucleases/genetics ; Gene Silencing ; Homeodomain Proteins/genetics ; Mutation ; Plant Proteins/genetics ; Plants, Genetically Modified ; RNA Caps ; *RNA Interference ; RNA Replicase/metabolism ; RNA, Messenger/*metabolism ; RNA, Plant/*metabolism ; Rats ; Recombinant Fusion Proteins/genetics
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    Protein kinase C overactivity impairs prefrontal cortical regulation of working memory (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-10-30
    Description: The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birnbaum, S G -- Yuan, P X -- Wang, M -- Vijayraghavan, S -- Bloom, A K -- Davis, D J -- Gobeske, K T -- Sweatt, J D -- Manji, H K -- Arnsten, A F T -- AG06036/AG/NIA NIH HHS/ -- P50 MH068789/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 29;306(5697):882-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Yale Medical School, 333 Cedar Street, New Haven, CT 06520-8001, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15514161" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-Agonists/pharmacology ; Alkaloids ; Animals ; Benzophenanthridines ; Carbolines/pharmacology ; Electrophysiology ; Enzyme Activation ; Female ; Imidazoles/pharmacology ; Lithium Carbonate/pharmacology ; Macaca mulatta ; Male ; Memory/drug effects/*physiology ; Neurons/drug effects/physiology ; Phenanthridines/pharmacology ; Prefrontal Cortex/enzymology/*physiology ; Protein Kinase C/antagonists & inhibitors/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1/physiology ; Signal Transduction ; Stress, Physiological/physiopathology ; Tetradecanoylphorbol Acetate/pharmacology ; Valproic Acid/pharmacology
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    Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-05-01
    Description: The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, Carl C H -- Brecht, Michael -- Hahn, Thomas T G -- Sakmann, Bert -- New York, N.Y. -- Science. 2004 Apr 30;304(5671):739-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology, Max-Planck-Institute for Medical Research, Jahnstrasse 29, Heidelberg D-69120, Germany. carl.petersen@epfl.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15118164" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Image Processing, Computer-Assisted ; In Vitro Techniques ; Nerve Net/physiology ; *Neuronal Plasticity ; Patch-Clamp Techniques ; Pyramidal Cells/*physiology/ultrastructure ; Rats ; Rats, Wistar ; Somatosensory Cortex/cytology/growth & development/*physiology ; Synapses/*physiology ; Synaptic Transmission ; Vibrissae/*physiology
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    Recruitment and spreading of the C. elegans dosage compensation complex along X chromosomes (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-21
    Description: To achieve X-chromosome dosage compensation, organisms must distinguish X chromosomes from autosomes. We identified multiple, cis-acting regions that recruit the Caenorhabditis elegans dosage compensation complex (DCC) through a search for regions of X that bind the complex when detached from X. The DCC normally assembles along the entire X chromosome, but not all detached regions recruit the complex, despite having genes known to be dosage compensated on the native X. Thus, the DCC binds first to recruitment sites, then spreads to neighboring X regions to accomplish chromosome-wide gene repression. From a large chromosomal domain, we defined a 793-base pair fragment that functions in vivo as an X-recognition element to recruit the DCC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Csankovszki, Gyorgyi -- McDonel, Patrick -- Meyer, Barbara J -- F32-GM065007/GM/NIGMS NIH HHS/ -- R37-GM30702/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1182-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/*genetics/metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Carrier Proteins/metabolism ; Chromosomes/metabolism ; Cosmids ; DNA-Binding Proteins/metabolism ; Disorders of Sex Development ; *Dosage Compensation, Genetic ; Female ; In Situ Hybridization, Fluorescence ; Male ; Models, Genetic ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; Repetitive Sequences, Nucleic Acid ; X Chromosome/*metabolism
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    Society for Neuroscience meeting. Brain cells may pay the price for a bad night's sleep (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2004 Nov 12;306(5699):1126.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15539581" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death ; *Cell Hypoxia ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Diet ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Exercise ; Hippocampus/*cytology/physiology ; Humans ; *Learning ; Long-Term Potentiation ; Memory ; Neurons/*physiology ; Rats ; Sleep Apnea Syndromes/*physiopathology
    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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    2004 Nobel Prizes. Axel, Buck share award for deciphering how the nose knows (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2004 Oct 8;306(5694):207.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15472044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; Olfactory Receptor Neurons/physiology ; Rats ; *Receptors, Odorant/genetics/physiology ; Smell/*physiology ; United States
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    Cellular distribution of nonionic micelles (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moghimi, S M -- Hunter, A C -- Murray, J C -- Szewczyk, A -- New York, N.Y. -- Science. 2004 Jan 30;303(5658):626-8; author reply 626-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14752144" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Azides/*chemistry ; Cations ; Drug Carriers/*metabolism ; Endocytosis ; Ethylene Oxide/chemistry/metabolism ; Hydrogen-Ion Concentration ; Lactones/chemistry/metabolism ; Lysosomes/metabolism ; *Micelles ; Nanotechnology ; Organelles/*metabolism ; PC12 Cells ; Polymers ; Rats ; Rhodamines/*chemistry ; Solubility ; Surface-Active Agents
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    Derivatives of erythropoietin that are tissue protective but not erythropoietic (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-13
    Description: Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leist, Marcel -- Ghezzi, Pietro -- Grasso, Giovanni -- Bianchi, Roberto -- Villa, Pia -- Fratelli, Maddalena -- Savino, Costanza -- Bianchi, Marina -- Nielsen, Jacob -- Gerwien, Jens -- Kallunki, Pekka -- Larsen, Anna Kirstine -- Helboe, Lone -- Christensen, Soren -- Pedersen, Lars O -- Nielsen, Mette -- Torup, Lars -- Sager, Thomas -- Sfacteria, Alessandra -- Erbayraktar, Serhat -- Erbayraktar, Zubeyde -- Gokmen, Necati -- Yilmaz, Osman -- Cerami-Hand, Carla -- Xie, Qiao-Wen -- Coleman, Thomas -- Cerami, Anthony -- Brines, Michael -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):239-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉H. Lundbeck A/S, 2500 Valby, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Binding Sites ; Cells, Cultured ; Diabetic Neuropathies/drug therapy ; Drug Design ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Erythropoiesis ; Erythropoietin/*analogs & ; derivatives/chemistry/genetics/metabolism/pharmacology/*therapeutic use ; Female ; Hematocrit ; Humans ; Ligands ; Mice ; Mice, Inbred C3H ; Mutagenesis ; Nervous System Diseases/*drug therapy ; Neurons/metabolism ; Neuroprotective Agents/chemistry/metabolism/pharmacology/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptors, Erythropoietin/metabolism ; Recombinant Proteins ; Signal Transduction ; Spinal Cord Compression/drug therapy ; Stroke/drug therapy ; Structure-Activity Relationship
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    Structural basis of transcription: separation of RNA from DNA by RNA polymerase II (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-14
    Description: The structure of an RNA polymerase II-transcribing complex has been determined in the posttranslocation state, with a vacancy at the growing end of the RNA-DNA hybrid helix. At the opposite end of the hybrid helix, the RNA separates from the template DNA. This separation of nucleic acid strands is brought about by interaction with a set of proteins loops in a strand/loop network. Formation of the network must occur in the transition from abortive initiation to promoter escape.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westover, Kenneth D -- Bushnell, David A -- Kornberg, Roger D -- GM49985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1014-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963331" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Crystallization ; Crystallography, X-Ray ; DNA, Single-Stranded/*chemistry/metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry/metabolism ; Oligoribonucleotides/chemistry/metabolism ; Promoter Regions, Genetic ; Protein Conformation ; RNA Polymerase II/*chemistry/*metabolism ; RNA, Complementary/*chemistry/metabolism ; Saccharomyces cerevisiae/enzymology ; Templates, Genetic ; Transcription Factor TFIIB/metabolism ; *Transcription, Genetic
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    Neuroscience. Epileptic neurons go wireless (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Staley, Kevin -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):482-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80262, USA. kevin.staley@uchsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15273382" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/physiology ; Dendrites/*physiology ; Epilepsy, Temporal Lobe/*physiopathology ; Feedback, Physiological ; Hippocampus/cytology/*physiopathology ; Humans ; Nerve Net/physiology ; Neural Inhibition ; Neurons/*physiology ; Pilocarpine/administration & dosage ; Potassium/*metabolism ; Potassium Channels/*physiology ; Rats ; Synapses/physiology ; Synaptic Transmission
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    SUMO modification of Huntingtin and Huntington's disease pathology (2004)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2004-04-06
    Description: Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)-1 or by ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes its capacity to repress transcription. In a Drosophila model of HD, SUMOylation of Httex1p exacerbates neurodegeneration, whereas ubiquitination of Httex1p abrogates neurodegeneration. Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steffan, Joan S -- Agrawal, Namita -- Pallos, Judit -- Rockabrand, Erica -- Trotman, Lloyd C -- Slepko, Natalia -- Illes, Katalin -- Lukacsovich, Tamas -- Zhu, Ya-Zhen -- Cattaneo, Elena -- Pandolfi, Pier Paolo -- Thompson, Leslie Michels -- Marsh, J Lawrence -- CA-62203/CA/NCI NIH HHS/ -- HD36049/HD/NICHD NIH HHS/ -- HD36081/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2004 Apr 2;304(5667):100-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15064418" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Cell Line ; Cell Nucleus/metabolism ; Corpus Striatum/cytology ; Cytoplasm/metabolism ; Drosophila ; Genes, MDR ; HeLa Cells ; Humans ; Huntington Disease/metabolism/*pathology ; Lysine/genetics/metabolism ; Mutation ; Nerve Degeneration ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Neurons/metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Proline/genetics/metabolism ; Promoter Regions, Genetic ; Rats ; Recombinant Fusion Proteins/metabolism ; SUMO-1 Protein/genetics/*metabolism ; Transcription, Genetic ; Transfection ; Ubiquitin/metabolism
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    Neutrophil extracellular traps kill bacteria (2004)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2004-03-06
    Description: Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brinkmann, Volker -- Reichard, Ulrike -- Goosmann, Christian -- Fauler, Beatrix -- Uhlemann, Yvonne -- Weiss, David S -- Weinrauch, Yvette -- Zychlinsky, Arturo -- AI037720/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 5;303(5663):1532-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21/22, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15001782" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appendicitis/immunology ; Bacterial Proteins/metabolism ; Blood Bactericidal Activity ; Cytochalasin D/pharmacology ; Cytoplasmic Granules/metabolism ; DNA/analysis/metabolism ; Dysentery, Bacillary/immunology ; Endopeptidases/metabolism ; Histones/analysis/metabolism ; Humans ; *Immunity, Innate ; Leukocyte Elastase/analysis/metabolism ; Microscopy, Electron ; *Neutrophil Activation ; Neutrophils/chemistry/*immunology/physiology/ultrastructure ; Phagocytosis ; Rabbits ; Salmonella typhimurium/immunology/*physiology ; Shigella flexneri/immunology/*physiology ; Staphylococcus aureus/immunology/*physiology ; Virulence Factors/metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 93
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    Multiple Ebola virus transmission events and rapid decline of central African wildlife (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-17
    Description: Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a result of Ebola infection. Recovered carcasses were infected by a variety of Ebola strains, suggesting that Ebola outbreaks in great apes result from multiple virus introductions from the natural host. Surveillance of animal mortality may help to predict and prevent human Ebola outbreaks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leroy, Eric M -- Rouquet, Pierre -- Formenty, Pierre -- Souquiere, Sandrine -- Kilbourne, Annelisa -- Froment, Jean-Marc -- Bermejo, Magdalena -- Smit, Sheilag -- Karesh, William -- Swanepoel, Robert -- Zaki, Sherif R -- Rollin, Pierre E -- New York, N.Y. -- Science. 2004 Jan 16;303(5656):387-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherche pour le Developpement, UR034, Centre International de Recherches Medicales de Franceville, BP 769 Franceville, Gabon. Eric.Leroy@ird.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14726594" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Central/epidemiology ; Animals ; Animals, Wild/*virology ; Ape Diseases/*epidemiology/virology ; Base Sequence ; *Disease Outbreaks/veterinary ; Disease Reservoirs ; Ebolavirus/classification/*genetics/isolation & purification ; Gabon/epidemiology ; Genes, Viral ; Gorilla gorilla/virology ; Hemorrhagic Fever, Ebola/*epidemiology/transmission/*veterinary/virology ; Humans ; Molecular Sequence Data ; Pan troglodytes/virology ; Population Density ; Population Surveillance ; Ruminants/virology ; Viral Envelope Proteins/genetics
    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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  • 94
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    Medicine. A wily recruiter in the battle against toxic beta amyloid aggregation (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, Ingrid -- New York, N.Y. -- Science. 2004 Oct 29;306(5697):791-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15514121" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid beta-Peptides/*chemistry/metabolism/toxicity ; Animals ; Cell Death/drug effects ; Cells, Cultured ; Congo Red/*analogs & derivatives/*chemical ; synthesis/chemistry/*metabolism/*pharmacology ; Ligands ; Neurons/cytology/*drug effects ; Piperidines/*chemical synthesis/chemistry/metabolism/*pharmacology ; Protein Conformation ; Rats ; Tacrolimus Binding Proteins/*metabolism/pharmacology
    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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  • 95
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    Distinct ensemble codes in hippocampal areas CA3 and CA1 (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-24
    Description: The hippocampus has differentiated into an extensively connected recurrent stage (CA3) followed by a feed-forward stage (CA1). We examined the function of this structural differentiation by determining how cell ensembles in rat CA3 and CA1 generate representations of rooms with common spatial elements. In CA3, distinct subsets of pyramidal cells were activated in each room, regardless of the similarity of the testing enclosure. In CA1, the activated populations overlapped, and the overlap increased in similar enclosures. After exposure to a novel room, ensemble activity developed slower in CA3 than CA1, suggesting that the representations emerged independently.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leutgeb, Stefan -- Leutgeb, Jill K -- Treves, Alessandro -- Moser, May-Britt -- Moser, Edvard I -- New York, N.Y. -- Science. 2004 Aug 27;305(5688):1295-8. Epub 2004 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for the Biology of Memory, Medical-Technical Research Centre, Norwegian University of Science and Technology, 7489 Trondheim, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15272123" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; Cues ; Electrodes, Implanted ; Entorhinal Cortex/physiology ; Hippocampus/cytology/*physiology ; Male ; *Memory ; Nerve Net/*physiology ; Neurons/*physiology ; Pyramidal Cells/*physiology ; Rats ; Rats, Long-Evans ; *Space Perception
    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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  • 96
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    The complete genome sequence of Propionibacterium acnes, a commensal of human skin (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-08-03
    Description: Propionibacterium acnes is a major inhabitant of adult human skin, where it resides within sebaceous follicles, usually as a harmless commensal although it has been implicated in acne vulgaris formation. The entire genome sequence of this Gram-positive bacterium encodes 2333 putative genes and revealed numerous gene products involved in degrading host molecules, including sialidases, neuraminidases, endoglycoceramidases, lipases, and pore-forming factors. Surface-associated and other immunogenic factors have been identified, which might be involved in triggering acne inflammation and other P. acnes-associated diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruggemann, Holger -- Henne, Anke -- Hoster, Frank -- Liesegang, Heiko -- Wiezer, Arnim -- Strittmatter, Axel -- Hujer, Sandra -- Durre, Peter -- Gottschalk, Gerhard -- New York, N.Y. -- Science. 2004 Jul 30;305(5684):671-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gottingen Genomics Laboratory, Institute of Microbiology and Genetics, Georg-August-University Gottingen, Grisebachstrasse 8, 37077 Gottingen, Germany. hbruegg@pasteur.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15286373" target="_blank"〉PubMed〈/a〉
    Keywords: Acne Vulgaris/immunology/microbiology ; Amino Acid Motifs ; Amino Acid Sequence ; Antigens, Bacterial/chemistry/genetics ; Bacterial Proteins/chemistry/genetics/immunology ; Base Sequence ; Chromosomes, Bacterial/genetics ; Computational Biology ; Energy Metabolism ; Esterases/genetics/metabolism ; Genes, Bacterial ; *Genome, Bacterial ; Heat-Shock Proteins/chemistry/genetics ; Humans ; Hydrolases/genetics/metabolism ; Lipase/genetics/metabolism ; Molecular Sequence Data ; Oxidative Phosphorylation ; Propionibacterium acnes/*genetics/immunology/physiology ; *Sequence Analysis, DNA ; Skin/*microbiology
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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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    RNA-mediated metal-metal bond formation in the synthesis of hexagonal palladium nanoparticles (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-04-17
    Description: RNA sequences have been discovered that mediate the growth of hexagonal palladium nanoparticles. In vitro selection techniques were used to evolve an initial library of approximately 10(14) unique RNA sequences through eight cycles of selection to yield several active sequence families. Of the five families, all representative members could form crystalline hexagonal palladium platelets. The palladium particle growth occurred in aqueous solution at ambient temperature, without any endogenous reducing agent, and at low concentrations of metal precursor (100 micromolar). Relative to metal precursor, the RNA concentration was significantly lower (1 micromolar), yet micrometer-size crystalline hexagonal palladium particles were formed rapidly (7.5 to 1 minutes).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gugliotti, Lina A -- Feldheim, Daniel L -- Eaton, Bruce E -- New York, N.Y. -- Science. 2004 May 7;304(5672):850-2. Epub 2004 Apr 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15087507" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chemistry, Physical ; Crystallization ; DNA, Complementary ; DNA-Directed RNA Polymerases/metabolism ; *Nanotubes ; Palladium/*chemistry ; Particle Size ; Physicochemical Phenomena ; Polymerase Chain Reaction ; RNA/*chemistry ; Temperature ; Transcription, Genetic ; Viral Proteins
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    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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    Obesity research. New data on appetite-suppressing peptide challenge critics (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gura, Trisha -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1453-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567820" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetite/*drug effects ; Appetite Depressants/administration & dosage/*pharmacology ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Gastric Emptying/drug effects ; Humans ; Macaca mulatta ; Peptide Fragments ; Peptide YY/administration & dosage/metabolism/*pharmacology ; Rats
    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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  • 99
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    Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-13
    Description: Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondrial iron-sulfur proteins including aconitase. We found that aconitase can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants. Frataxin interacted with aconitase in a citrate-dependent fashion, reduced the level of oxidant-induced inactivation, and converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the protein. Thus, frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bulteau, Anne-Laure -- O'Neill, Heather A -- Kennedy, Mary Claire -- Ikeda-Saito, Masao -- Isaya, Grazia -- Szweda, Luke I -- AG-15709/AG/NIA NIH HHS/ -- AG-16339/AG/NIA NIH HHS/ -- NRSA 44748/NR/NINR NIH HHS/ -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):242-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247478" target="_blank"〉PubMed〈/a〉
    Keywords: Aconitate Hydratase/antagonists & inhibitors/*metabolism ; Animals ; Citric Acid/metabolism/pharmacology ; Dithiothreitol/metabolism ; Electron Spin Resonance Spectroscopy ; Enzyme Activation ; Ferrous Compounds/metabolism ; Hydrogen Peroxide/pharmacology ; Iron/*metabolism ; Iron-Binding Proteins/*metabolism ; Male ; Mitochondria/*metabolism ; Mitochondria, Heart/*metabolism ; Molecular Chaperones/*metabolism ; Oxidation-Reduction ; Oxidative Stress ; Oxygen Consumption ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/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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  • 100
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    Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-31
    Description: Sixty-one SARS coronavirus genomic sequences derived from the early, middle, and late phases of the severe acute respiratory syndrome (SARS) epidemic were analyzed together with two viral sequences from palm civets. Genotypes characteristic of each phase were discovered, and the earliest genotypes were similar to the animal SARS-like coronaviruses. Major deletions were observed in the Orf8 region of the genome, both at the start and the end of the epidemic. The neutral mutation rate of the viral genome was constant but the amino acid substitution rate of the coding sequences slowed during the course of the epidemic. The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chinese SARS Molecular Epidemiology Consortium -- New York, N.Y. -- Science. 2004 Mar 12;303(5664):1666-9. Epub 2004 Jan 29.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14752165" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Amino Acid Substitution ; Animals ; Base Sequence ; Carnivora/virology ; China/epidemiology ; Cluster Analysis ; Coronavirus/genetics/isolation & purification ; *Disease Outbreaks ; *Evolution, Molecular ; *Genome, Viral ; Genotype ; Humans ; Membrane Glycoproteins/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Open Reading Frames ; Phylogeny ; Point Mutation ; RNA, Viral/genetics ; SARS Virus/*genetics/isolation & purification/physiology ; Selection, Genetic ; Sequence Deletion ; Severe Acute Respiratory Syndrome/*epidemiology/*virology ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins/genetics ; Viral Matrix Proteins/chemistry/genetics
    Print ISSN: 0036-8075
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