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  • Mutation  (590)
  • American Association for the Advancement of Science (AAAS)  (590)
  • 2005-2009  (538)
  • 1980-1984  (52)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2006-11-04
    Description: One hundred years ago a small group of psychiatrists described the abnormal protein deposits in the brain that define the most common neurodegenerative diseases. Over the past 25 years, it has become clear that the proteins forming the deposits are central to the disease process. Amyloid-beta and tau make up the plaques and tangles of Alzheimer's disease, where these normally soluble proteins assemble into amyloid-like filaments. Tau inclusions are also found in a number of related disorders. Genetic studies have shown that dysfunction of amyloid-beta or tau is sufficient to cause dementia. The ongoing molecular dissection of the neurodegenerative pathways is expected to lead to a true understanding of disease pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goedert, Michel -- Spillantini, Maria Grazia -- G0301152/Medical Research Council/United Kingdom -- MC_U105184291/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2006 Nov 3;314(5800):777-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, UK. mg@mrc-lmb.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17082447" target="_blank"〉PubMed〈/a〉
    Keywords: *Alzheimer Disease/genetics/history/metabolism/pathology ; Amyloid beta-Peptides/chemistry/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Animals ; Apolipoproteins E/genetics ; Brain/pathology ; Brain Chemistry ; History, 20th Century ; Humans ; Mutation ; Neurofibrillary Tangles/chemistry/pathology ; Plaque, Amyloid/chemistry/pathology ; Presenilin-1/genetics/metabolism ; tau Proteins/chemistry/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2006-04-22
    Description: Given the considerable challenges to the rapid development of an effective vaccine against influenza, antiviral agents will play an important role as a first-line defense if a new pandemic occurs. The large-scale use of drugs for chemoprophylaxis and treatment will impose strong selection for the evolution of drug-resistant strains. The ensuing transmission of those strains could substantially limit the effectiveness of the drugs as a first-line defense. Summarizing recent data on the rate at which the treatment of influenza infection generates resistance de novo and on the transmission fitness of resistant virus, we discuss possible implications for the epidemiological spread of drug resistance in the context of an established population dynamic model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Regoes, Roland R -- Bonhoeffer, Sebastian -- New York, N.Y. -- Science. 2006 Apr 21;312(5772):389-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Integrative Biology, ETH Zurich, ETH Zentrum CHN K12.1, Universitatsstrasse 16, CH 8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16627735" target="_blank"〉PubMed〈/a〉
    Keywords: Acetamides/pharmacology/therapeutic use ; Amantadine/pharmacology/therapeutic use ; Antiviral Agents/*pharmacology/*therapeutic use ; Computer Simulation ; Disease Outbreaks ; *Drug Resistance, Viral/genetics ; Humans ; Influenza A virus/*drug effects/genetics/pathogenicity ; Influenza, Human/*drug therapy/epidemiology/*prevention & control/virology ; Mathematics ; Models, Biological ; Mutation ; Neuraminidase/antagonists & inhibitors ; Orthomyxoviridae/*drug effects/genetics/pathogenicity ; Oseltamivir ; Population Dynamics
    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2006-05-27
    Description: The allure of the emerging genomic technologies in cancer is their ability to generate new biomarkers that predict how individual cancer patients will respond to various treatments. However, productive implementation of cancer biomarkers into patient care will require fundamental changes in how we consider approvals for cancer indications and how we track patient responses. Here we briefly describe ongoing efforts to identify and to validate cancer biomarkers, discuss the technological hurdles that lie ahead, and then focus on the more pressing political and cultural issues that, if left unheeded, could derail many of the anticipated benefits of biomarker research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, William S -- Friend, Stephen H -- New York, N.Y. -- Science. 2006 May 26;312(5777):1165-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33613, USA. dalton@moffitt.usf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16728629" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes ; *Biomarkers, Tumor ; Biotechnology ; Clinical Trials as Topic ; Databases, Factual ; Drug Industry ; Gene Expression Regulation, Neoplastic ; Genomics ; Humans ; Intellectual Property ; Interprofessional Relations ; Mutation ; Neoplasms/genetics/*therapy ; *Patient Care Management ; Private Sector ; Proteomics ; Public Sector
    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
    Publication Date: 2006-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2006 Mar 31;311(5769):1847.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16574828" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics ; DNA Mutational Analysis ; False Negative Reactions ; Female ; *Genes, BRCA1 ; *Genes, BRCA2 ; *Genetic Testing ; Humans ; Mutation ; Nucleic Acid Amplification Techniques ; Ovarian Neoplasms/*genetics ; Sensitivity and Specificity
    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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  • 5
    Publication Date: 2006-04-08
    Description: According to Darwinian theory, complexity evolves by a stepwise process of elaboration and optimization under natural selection. Biological systems composed of tightly integrated parts seem to challenge this view, because it is not obvious how any element's function can be selected for unless the partners with which it interacts are already present. Here we demonstrate how an integrated molecular system-the specific functional interaction between the steroid hormone aldosterone and its partner the mineralocorticoid receptor-evolved by a stepwise Darwinian process. Using ancestral gene resurrection, we show that, long before the hormone evolved, the receptor's affinity for aldosterone was present as a structural by-product of its partnership with chemically similar, more ancient ligands. Introducing two amino acid changes into the ancestral sequence recapitulates the evolution of present-day receptor specificity. Our results indicate that tight interactions can evolve by molecular exploitation-recruitment of an older molecule, previously constrained for a different role, into a new functional complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bridgham, Jamie T -- Carroll, Sean M -- Thornton, Joseph W -- F32-GM074398/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 7;312(5770):97-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16601189" target="_blank"〉PubMed〈/a〉
    Keywords: Aldosterone/chemistry/*metabolism ; Amino Acid Substitution ; Animals ; Bayes Theorem ; Binding Sites ; Desoxycorticosterone/metabolism ; *Evolution, Molecular ; Gene Duplication ; Hagfishes ; Hydrocortisone/metabolism ; Lampreys ; Ligands ; Mutation ; Perciformes ; Phylogeny ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/metabolism ; Receptors, Mineralocorticoid/chemistry/*genetics/*metabolism ; Receptors, Steroid/chemistry/*genetics/*metabolism ; Skates (Fish)
    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2006-03-11
    Description: Crop domestication frequently began with the selection of plants that did not naturally shed ripe fruits or seeds. The reduction in grain shattering that led to cereal domestication involved genetic loci of large effect. The molecular basis of this key domestication transition, however, remains unknown. Here we show that human selection of an amino acid substitution in the predicted DNA binding domain encoded by a gene of previously unknown function was primarily responsible for the reduction of grain shattering in rice domestication. The substitution undermined the gene function necessary for the normal development of an abscission layer that controls the separation of a grain from the pedicel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Changbao -- Zhou, Ailing -- Sang, Tao -- New York, N.Y. -- Science. 2006 Mar 31;311(5769):1936-9. Epub 2006 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Michigan State University, East Lansing, MI 48824, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16527928" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Amino Acid Substitution ; Biological Evolution ; Chromosome Mapping ; Computational Biology ; Crops, Agricultural/*genetics/growth & development ; Flowers/growth & development ; Gene Expression ; Genes, Plant ; Genotype ; Molecular Sequence Data ; Mutation ; Oryza/cytology/*genetics/growth & development ; Phenotype ; Plant Proteins/chemistry/*genetics ; Plants, Genetically Modified ; Quantitative Trait Loci ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Transcription Factors/chemistry/*genetics ; Transformation, 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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  • 7
    Publication Date: 2006-07-01
    Description: The formation of glutaminyl transfer RNA (Gln-tRNA(Gln)) differs among the three domains of life. Most bacteria employ an indirect pathway to produce Gln-tRNA(Gln) by a heterotrimeric glutamine amidotransferase CAB (GatCAB) that acts on the misacylated Glu-tRNA(Gln). Here, we describe a series of crystal structures of intact GatCAB from Staphylococcus aureus in the apo form and in the complexes with glutamine, asparagine, Mn2+, and adenosine triphosphate analog. Two identified catalytic centers for the glutaminase and transamidase reactions are markedly distant but connected by a hydrophilic ammonia channel 30 A in length. Further, we show that the first U-A base pair in the acceptor stem and the D loop of tRNA(Gln) serve as identity elements essential for discrimination by GatCAB and propose a complete model for the overall concerted reactions to synthesize Gln-tRNA(Gln).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakamura, Akiyoshi -- Yao, Min -- Chimnaronk, Sarin -- Sakai, Naoki -- Tanaka, Isao -- New York, N.Y. -- Science. 2006 Jun 30;312(5782):1954-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Advanced Life Sciences, Hokkaido University, Sapporo 060-0810, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16809541" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Amino Acid Sequence ; Aminoacyltransferases/metabolism ; Ammonia/*metabolism ; Apoenzymes/chemistry/metabolism ; Asparagine/metabolism ; Base Pairing ; Catalytic Domain ; Crystallography, X-Ray ; Glutaminase/metabolism ; Glutamine/*chemistry/metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Magnesium/metabolism ; Manganese/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits ; RNA, Bacterial/chemistry/metabolism ; RNA, Transfer, Amino Acyl/chemistry/*metabolism ; RNA, Transfer, Gln/*chemistry/metabolism ; Staphylococcus aureus/*enzymology/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2006-06-10
    Description: Horizontal gene transfer plays a major role in microbial evolution. However, newly acquired sequences can decrease fitness unless integrated into preexisting regulatory networks. We found that the histone-like nucleoid structuring protein (H-NS) selectively silences horizontally acquired genes by targeting sequences with GC content lower than the resident genome. Mutations in hns are lethal in Salmonella unless accompanied by compensatory mutations in other regulatory loci. Thus, H-NS provides a previously unrecognized mechanism of bacterial defense against foreign DNA, enabling the acquisition of DNA from exogenous sources while avoiding detrimental consequences from unregulated expression of newly acquired genes. Characteristic GC/AT ratios of bacterial genomes may facilitate discrimination between a cell's own DNA and foreign DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Navarre, William Wiley -- Porwollik, Steffen -- Wang, Yipeng -- McClelland, Michael -- Rosen, Henry -- Libby, Stephen J -- Fang, Ferric C -- AI034829/AI/NIAID NIH HHS/ -- AI049417/AI/NIAID NIH HHS/ -- AI052237/AI/NIAID NIH HHS/ -- AI057733/AI/NIAID NIH HHS/ -- AI39557/AI/NIAID NIH HHS/ -- AI48622/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 14;313(5784):236-8. Epub 2006 Jun 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16763111" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics/*metabolism ; Base Composition ; Binding Sites ; Chromatin Immunoprecipitation ; DNA, Bacterial/*chemistry/*genetics ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; *Gene Silencing ; *Gene Transfer, Horizontal ; Genome, Bacterial ; Helicobacter pylori/genetics ; Models, Genetic ; Mutation ; Oligonucleotide Array Sequence Analysis ; Repressor Proteins/genetics/*metabolism ; Salmonella typhimurium/*genetics/physiology
    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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  • 9
    Publication Date: 2006-03-18
    Description: During development, cells monitor and adjust their rates of accumulation to produce organs of predetermined size. We show here that central nervous system-specific deletion of the essential adherens junction gene, alphaE-catenin, causes abnormal activation of the hedgehog pathway, resulting in shortening of the cell cycle, decreased apoptosis, and cortical hyperplasia. We propose that alphaE-catenin connects cell-density-dependent adherens junctions with the developmental hedgehog pathway and that this connection may provide a negative feedback loop controlling the size of developing cerebral cortex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556178/" 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/PMC2556178/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lien, Wen-Hui -- Klezovitch, Olga -- Fernandez, Tania E -- Delrow, Jeff -- Vasioukhin, Valeri -- P41 RR011823/RR/NCRR NIH HHS/ -- P41 RR011823-128171/RR/NCRR NIH HHS/ -- R01 CA098161/CA/NCI NIH HHS/ -- R01 CA098161-01A1/CA/NCI NIH HHS/ -- R01 CA098161-02/CA/NCI NIH HHS/ -- R01 CA098161-03/CA/NCI NIH HHS/ -- R01 CA098161-04/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2006 Mar 17;311(5767):1609-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16543460" target="_blank"〉PubMed〈/a〉
    Keywords: Adherens Junctions/*physiology/ultrastructure ; Animals ; Apoptosis ; Cell Adhesion ; Cell Count ; Cell Cycle ; Cell Differentiation ; Cell Polarity ; Central Nervous System/embryology ; Cerebral Cortex/cytology/*embryology/pathology/physiology ; Hedgehog Proteins ; Hyperplasia ; Mice ; Mitosis ; Models, Biological ; Mutation ; Neurons/cytology/*physiology/ultrastructure ; Oligonucleotide Array Sequence Analysis ; *Signal Transduction ; Stem Cells/cytology/ultrastructure ; Trans-Activators/*metabolism ; Up-Regulation ; alpha Catenin/genetics/*physiology
    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
    Publication Date: 2006-07-15
    Description: Plants have evolved a powerful immune system to defend against infection by most microbial organisms. However, successful pathogens, such as Pseudomonas syringae, have developed countermeasures and inject virulence proteins into the host plant cell to suppress immunity and cause devastating diseases. Despite intensive research efforts, the molecular targets of bacterial virulence proteins that are important for plant disease development have remained obscure. Here, we show that a conserved P. syringae virulence protein, HopM1, targets an immunity-associated protein, AtMIN7, in Arabidopsis thaliana. HopM1 mediates the destruction of AtMIN7 via the host proteasome. Our results illustrate a strategy by which a bacterial pathogen exploits the host proteasome to subvert host immunity and causes infection in plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nomura, Kinya -- Debroy, Sruti -- Lee, Yong Hoon -- Pumplin, Nathan -- Jones, Jonathan -- He, Sheng Yang -- New York, N.Y. -- Science. 2006 Jul 14;313(5784):220-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16840699" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/metabolism ; Arabidopsis/*immunology/metabolism/*microbiology ; Arabidopsis Proteins/*metabolism ; Bacterial Proteins/genetics/metabolism ; Brefeldin A/pharmacology ; Glucans/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Immunity, Innate ; Mutation ; Plant Diseases/*microbiology ; Plant Leaves/metabolism/microbiology ; Plants, Genetically Modified ; Proteasome Endopeptidase Complex/metabolism ; Protein Transport ; Pseudomonas syringae/genetics/growth & development/*pathogenicity ; Tobacco/metabolism ; Two-Hybrid System Techniques ; Ubiquitins/metabolism ; Virulence Factors/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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