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  • Mice  (1,444)
  • Female  (1,333)
  • Models, Molecular  (460)
  • Kinetics
  • American Association for the Advancement of Science (AAAS)  (3,225)
  • 2005-2009  (1,835)
  • 1990-1994  (1,390)
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  • 1
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    American Chemical Society fall meeting, 16-20 August, Washington, D.C. Sugary Achilles' heel raises hope for broad-acting antiviral drugs (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1200. doi: 10.1126/science.325_1200a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729635" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*metabolism/*pharmacology ; Animals ; Anti-HIV Agents/metabolism/pharmacology ; Antiviral Agents/*metabolism/*pharmacology ; Ebolavirus/drug effects ; HIV/drug effects ; Humans ; Lectins/*metabolism/*pharmacology ; Mannose/*metabolism ; Mice ; Microbial Sensitivity Tests ; Plant Lectins ; SARS Virus/drug effects ; Virus Diseases/drug therapy ; Viruses/*drug effects
    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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    Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: Genetic exchange has not been shown to be a mechanism underlying the extensive diversity of Leishmania parasites. We report here evidence that the invertebrate stages of Leishmania are capable of having a sexual cycle consistent with a meiotic process like that described for African trypanosomes. Hybrid progeny were generated that bore full genomic complements from both parents, but kinetoplast DNA maxicircles from one parent. Mating occurred only in the sand fly vector, and hybrids were transmitted to the mammalian host by sand fly bite. Genetic exchange likely contributes to phenotypic diversity in natural populations, and analysis of hybrid progeny will be useful for positional cloning of the genes controlling traits such as virulence, tissue tropism, and drug resistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729066/" 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/PMC2729066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akopyants, Natalia S -- Kimblin, Nicola -- Secundino, Nagila -- Patrick, Rachel -- Peters, Nathan -- Lawyer, Phillip -- Dobson, Deborah E -- Beverley, Stephen M -- Sacks, David L -- A1020941/PHS HHS/ -- A1029646/PHS HHS/ -- R01 AI029646/AI/NIAID NIH HHS/ -- R01 AI029646-20/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):265-8. doi: 10.1126/science.1169464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiprotozoal Agents/pharmacology ; DNA, Kinetoplast/genetics ; DNA, Protozoan/analysis/genetics ; Drug Resistance ; Female ; Genes, Protozoan ; *Hybridization, Genetic ; Insect Vectors/*parasitology ; Leishmania major/drug effects/*genetics/*growth & development/pathogenicity ; Leishmaniasis, Cutaneous/parasitology ; Meiosis ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Phenotype ; Phlebotomus/*parasitology ; Polymorphism, Single Nucleotide
    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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    The transcriptional repressor DEC2 regulates sleep length in mammals (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-15
    Description: Sleep deprivation can impair human health and performance. Habitual total sleep time and homeostatic sleep response to sleep deprivation are quantitative traits in humans. Genetic loci for these traits have been identified in model organisms, but none of these potential animal models have a corresponding human genotype and phenotype. We have identified a mutation in a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner. These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884988/" 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/PMC2884988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Ying -- Jones, Christopher R -- Fujiki, Nobuhiro -- Xu, Ying -- Guo, Bin -- Holder, Jimmy L Jr -- Rossner, Moritz J -- Nishino, Seiji -- Fu, Ying-Hui -- HL059596/HL/NHLBI NIH HHS/ -- MH074924/MH/NIMH NIH HHS/ -- R01 HL059596/HL/NHLBI NIH HHS/ -- R01 HL059596-09/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):866-70. doi: 10.1126/science.1174443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California at San Francisco, Mission Bay, 1550 Fourth Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679812" target="_blank"〉PubMed〈/a〉
    Keywords: Activity Cycles/genetics ; Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Animals, Genetically Modified ; Basic Helix-Loop-Helix Transcription Factors/chemistry/*genetics/physiology ; Child ; Circadian Rhythm/genetics ; Drosophila/genetics ; Electroencephalography ; Electromyography ; Female ; Homeostasis ; Humans ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Sleep/*genetics/physiology ; Sleep Deprivation ; Sleep, REM/genetics/physiology ; Transcription Factors/chemistry/genetics/physiology ; Wakefulness
    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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    An analytical solution to the kinetics of breakable filament assembly (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-17
    Description: We present an analytical treatment of a set of coupled kinetic equations that governs the self-assembly of filamentous molecular structures. Application to the case of protein aggregation demonstrates that the kinetics of amyloid growth can often be dominated by secondary rather than by primary nucleation events. Our results further reveal a range of general features of the growth kinetics of fragmenting filamentous structures, including the existence of generic scaling laws that provide mechanistic information in contexts ranging from in vitro amyloid growth to the in vivo development of mammalian prion diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowles, Tuomas P J -- Waudby, Christopher A -- Devlin, Glyn L -- Cohen, Samuel I A -- Aguzzi, Adriano -- Vendruscolo, Michele -- Terentjev, Eugene M -- Welland, Mark E -- Dobson, Christopher M -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1533-7. doi: 10.1126/science.1178250.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007899" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*chemistry ; Biochemical Processes ; Glutathione Peroxidase/chemistry ; Insulin/chemistry ; Kinetics ; Lactoglobulins/chemistry ; Mathematical Concepts ; Multiprotein Complexes/*chemistry ; Peptide Termination Factors/chemistry ; Peptides/chemistry ; Prions/chemistry ; *Protein Multimerization ; Saccharomyces cerevisiae Proteins/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 5
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    Polymorphic butterfly reveals the missing link in ecological speciation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-07
    Description: Ecological speciation occurs when ecologically based, divergent selection causes the evolution of reproductive isolation. There are many empirical examples of this process; however, there exists a poorly characterized stage during which the traits that distinguish species ecologically and reproductively segregate in a single population. By using a combination of genetic mapping, mate-choice experiments, field observations, and population genetics, we studied a butterfly population with a mimetic wing color polymorphism and found that the butterflies exhibited partial, color-based, assortative mate preference. These traits represent the divergent, ecologically based signal and preference components of sexual isolation that usually distinguish incipient and sibling species. The association between behavior and recognition trait in a single population may enhance the probability of speciation and provides an example of the missing link between an interbreeding population and isolated species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875868/" 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/PMC2875868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chamberlain, Nicola L -- Hill, Ryan I -- Kapan, Durrell D -- Gilbert, Lawrence E -- Kronforst, Marcus R -- GM068763/GM/NIGMS NIH HHS/ -- P50 GM068763/GM/NIGMS NIH HHS/ -- P50 GM068763-06/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):847-50. doi: 10.1126/science.1179141.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892982" target="_blank"〉PubMed〈/a〉
    Keywords: Amplified Fragment Length Polymorphism Analysis ; Animals ; Butterflies/anatomy & histology/*genetics/*physiology ; Color ; Ecosystem ; Female ; Genes, Insect ; Genetic Linkage ; *Genetic Speciation ; Linkage Disequilibrium ; Male ; *Mating Preference, Animal ; Molecular Sequence Data ; Phenotype ; *Pigmentation/genetics ; *Polymorphism, Genetic ; Reproduction ; Selection, Genetic ; Wings, Animal/*anatomy & histology
    Print ISSN: 0036-8075
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  • 6
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    Flexible learning of multiple speech structures in bilingual infants (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-11
    Description: Children acquire their native language according to a well-defined time frame. Surprisingly, although children raised in bilingual environments have to learn roughly twice as much about language as their monolingual peers, the speed of acquisition is comparable in monolinguals and bilinguals. Here, we show that preverbal 12-month-old bilingual infants have become more flexible at learning speech structures than monolinguals. When given the opportunity to simultaneously learn two different regularities, bilingual infants learned both, whereas monolinguals learned only one of them. Hence, bilinguals may acquire two languages in the time in which monolinguals acquire one because they quickly become more flexible learners.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kovacs, Agnes Melinda -- Mehler, Jacques -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):611-2. doi: 10.1126/science.1173947. Epub 2009 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scuola Internazionale Superiore di Studi Avanzati-SISSA, Via Beirut 4, 34014 Trieste, Italy. agneskovacs@mtapi.hu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589962" target="_blank"〉PubMed〈/a〉
    Keywords: *Child Language ; Female ; Humans ; Infant ; *Language Development ; *Learning ; Male ; *Multilingualism ; *Speech Perception
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Orc1 controls centriole and centrosome copy number in human cells (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: Centrosomes, each containing a pair of centrioles, organize microtubules in animal cells, particularly during mitosis. DNA and centrosomes are normally duplicated once before cell division to maintain optimal genome integrity. We report a new role for the Orc1 protein, a subunit of the origin recognition complex (ORC) that is a key component of the DNA replication licensing machinery, in controlling centriole and centrosome copy number in human cells, independent of its role in DNA replication. Cyclin A promotes Orc1 localization to centrosomes where Orc1 prevents Cyclin E-dependent reduplication of both centrioles and centrosomes in a single cell division cycle. The data suggest that Orc1 is a regulator of centriole and centrosome reduplication as well as the initiation of DNA replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653626/" 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/PMC2653626/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemerly, Adriana S -- Prasanth, Supriya G -- Siddiqui, Khalid -- Stillman, Bruce -- CA13106/CA/NCI NIH HHS/ -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-310025/CA/NCI NIH HHS/ -- P01 CA013106-36/CA/NCI NIH HHS/ -- P01 CA013106-370025/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):789-93. doi: 10.1126/science.1166745.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor 11724, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197067" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle ; Cell Line, Tumor ; Centrioles/*physiology ; Centrosome/*physiology ; Cyclin A/metabolism ; Cyclin E/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; DNA Replication ; HeLa Cells ; Humans ; Kinetics ; Mutant Proteins/metabolism ; Origin Recognition Complex/genetics/*metabolism ; RNA Interference ; RNA, Small Interfering ; Transfection
    Print ISSN: 0036-8075
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  • 8
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    Recruitment of an area involved in eye movements during mental arithmetic (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-09
    Description: Throughout the history of mathematics, concepts of number and space have been tightly intertwined. We tested the hypothesis that cortical circuits for spatial attention contribute to mental arithmetic in humans. We trained a multivariate classifier algorithm to infer the direction of an eye movement, left or right, from the brain activation measured in the posterior parietal cortex. Without further training, the classifier then generalized to an arithmetic task. Its left versus right classification could be used to sort out subtraction versus addition trials, whether performed with symbols or with sets of dots. These findings are consistent with the suggestion that mental arithmetic co-opts parietal circuitry associated with spatial coding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knops, Andre -- Thirion, Bertrand -- Hubbard, Edward M -- Michel, Vincent -- Dehaene, Stanislas -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1583-5. doi: 10.1126/science.1171599. Epub 2009 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Cognitive Neuroimaging Unit, F-91191 Gif-sur-Yvette, France. knops.andre@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423779" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Eye Movements/*physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; *Mathematics ; Mental Processes/*physiology ; Parietal Lobe/*physiology ; Recruitment, Neurophysiological
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  • 9
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    Platelets kill intraerythrocytic malarial parasites and mediate survival to infection (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMorran, Brendan J -- Marshall, Vikki M -- de Graaf, Carolyn -- Drysdale, Karen E -- Shabbar, Meriam -- Smyth, Gordon K -- Corbin, Jason E -- Alexander, Warren S -- Foote, Simon J -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):797-800. doi: 10.1126/science.1166296.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Menzies Research Institute, University of Tasmania, Private Bag 23, Hobart, Tasmania 7000, Australia. brendan.mcmorran@utas.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197068" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Animals ; Aspirin/pharmacology ; Blood Platelets/metabolism/*physiology ; Erythrocytes/*parasitology ; Female ; Humans ; In Situ Nick-End Labeling ; Malaria/*blood/immunology/*parasitology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plasmodium chabaudi/*growth & development ; Plasmodium falciparum/*growth & development ; Platelet Activation ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Count ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2Y1 ; Receptors, Thrombopoietin/genetics
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  • 10
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    Basin-scale coherence in phenology of shrimps and phytoplankton in the North Atlantic Ocean (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-09
    Description: Climate change could lead to mismatches between the reproductive cycles of marine organisms and their planktonic food. We tested this hypothesis by comparing shrimp (Pandalus borealis) egg hatching times and satellite-derived phytoplankton bloom dynamics throughout the North Atlantic. At large spatial and long temporal (10 years or longer) scales, hatching was correlated with the timing of the spring phytoplankton bloom. Annual egg development and hatching times were determined locally by bottom water temperature. We conclude that different populations of P. borealis have adapted to local temperatures and bloom timing, matching egg hatching to food availability under average conditions. This strategy is vulnerable to interannual oceanographic variability and long-term climatic changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koeller, P -- Fuentes-Yaco, C -- Platt, T -- Sathyendranath, S -- Richards, A -- Ouellet, P -- Orr, D -- Skuladottir, U -- Wieland, K -- Savard, L -- Aschan, M -- New York, N.Y. -- Science. 2009 May 8;324(5928):791-3. doi: 10.1126/science.1170987.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Fisheries and Oceans, Bedford Institute of Oceanography, Post Office Box 1006, Dartmouth, B2Y 4A2 Nova Scotia, Canada. koellerp@mar.dfo-mpo.gc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423827" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Climate ; *Cold Temperature ; *Ecosystem ; Female ; Ovum/growth & development/physiology ; Pandalidae/*physiology ; Phytoplankton/*physiology ; Population Dynamics ; Reproduction ; Seasons ; *Seawater
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  • 11
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    A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Edwards, Marcus J -- Flatman, Ruth H -- Mitchenall, Lesley A -- Stevenson, Clare E M -- Le, Tung B K -- Clarke, Thomas A -- McKay, Adam R -- Fiedler, Hans-Peter -- Buttner, Mark J -- Lawson, David M -- Maxwell, Anthony -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1415-8. doi: 10.1126/science.1179123.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965760" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/metabolism/pharmacology ; Binding Sites ; Coumarins/chemistry/metabolism/pharmacology ; Crystallography, X-Ray ; DNA Gyrase/*chemistry/genetics/*metabolism ; DNA, Bacterial/metabolism ; Drug Resistance, Bacterial ; Escherichia coli/drug effects/*enzymology/genetics ; Glycosides/chemistry/metabolism/pharmacology ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Molecular Weight ; Mutagenesis, Site-Directed ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Topoisomerase II Inhibitors
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  • 12
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    Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-11
    Description: Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784927/" 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/PMC2784927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hensley, Scott E -- Das, Suman R -- Bailey, Adam L -- Schmidt, Loren M -- Hickman, Heather D -- Jayaraman, Akila -- Viswanathan, Karthik -- Raman, Rahul -- Sasisekharan, Ram -- Bennink, Jack R -- Yewdell, Jonathan W -- GM 57073/GM/NIGMS NIH HHS/ -- U54 GM62116/GM/NIGMS NIH HHS/ -- Z01 AI001014-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 30;326(5953):734-6. doi: 10.1126/science.1178258.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900932" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antigenic Variation/genetics/*immunology ; Cell Line ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology/*metabolism ; Influenza A Virus, H1N1 Subtype/genetics/*immunology ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Immunological ; Mutation ; Receptors, Virus/*metabolism ; Serial Passage
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  • 13
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    Scientific publishing. Paper retracted following genome data breach (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1486-7. doi: 10.1126/science.325_1486a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762616" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; *Databases, Genetic ; Female ; Homeodomain Proteins/genetics ; Humans ; *National Institutes of Health (U.S.) ; Publishing/*standards ; *Retraction of Publication as Topic ; Substance-Related Disorders/genetics ; Transcription Factors/genetics ; United States
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  • 14
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    The taste of carbonation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-17
    Description: Carbonated beverages are commonly available and immensely popular, but little is known about the cellular and molecular mechanisms underlying the perception of carbonation in the mouth. In mammals, carbonation elicits both somatosensory and chemosensory responses, including activation of taste neurons. We have identified the cellular and molecular substrates for the taste of carbonation. By targeted genetic ablation and the silencing of synapses in defined populations of taste receptor cells, we demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO2 taste sensor. Together, these studies reveal the basis of the taste of carbonation as well as the contribution of taste cells in the orosensory response to CO2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654389/" 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/PMC3654389/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chandrashekar, Jayaram -- Yarmolinsky, David -- von Buchholtz, Lars -- Oka, Yuki -- Sly, William -- Ryba, Nicholas J P -- Zuker, Charles S -- Z01 DE000561-15/Intramural NIH HHS/ -- Z01 DE000561-16/Intramural NIH HHS/ -- ZIA DE000561-17/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):443-5. doi: 10.1126/science.1174601.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, 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/19833970" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Benzolamide/pharmacology ; Bicarbonates/metabolism ; Calcium Channels/metabolism ; Carbon Dioxide/*metabolism ; *Carbonated Beverages ; Carbonic Anhydrase IV/antagonists & inhibitors/genetics/*metabolism ; Carbonic Anhydrase Inhibitors/pharmacology ; Carbonic Anhydrases/metabolism ; Chorda Tympani Nerve/physiology ; Gene Expression Profiling ; Mice ; Mice, Transgenic ; Protons ; Receptors, Cell Surface/metabolism ; Taste/*physiology ; Taste Buds/enzymology/*physiology ; *Taste Perception
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  • 15
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    A single peptide-MHC complex positively selects a diverse and specific CD8 T cell repertoire (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-07
    Description: Pathogen recognition by T cells is dependent on their exquisite specificity for self-major histocompatibility complex (MHC) molecules presenting a bound peptide. Although this specificity results from positive and negative selection of developing T cells in the thymus, the relative contribution of these two processes remains controversial. To address the relation between the selecting peptide-MHC complex and the specificity of mature T cells, we generated transgenic mice that express a single peptide-MHC class I complex. We demonstrate that positive selection of CD8 T cells in these mice results in an MHC-specific repertoire. Although selection on a single complex is peptide promiscuous, mature T cells are highly peptide specific. Thus, positive selection imparts MHC and peptide specificity on the peripheral CD8 T cell repertoire.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828816/" 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/PMC2828816/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Baomei -- Primeau, Tina M -- Myers, Nancy -- Rohrs, Henry W -- Gross, Michael L -- Lybarger, Lonnie -- Hansen, Ted H -- Connolly, Janet M -- 2P41RR000954/RR/NCRR NIH HHS/ -- AI 027568/AI/NIAID NIH HHS/ -- AI 055849/AI/NIAID NIH HHS/ -- P41 GM103422/GM/NIGMS NIH HHS/ -- P41 RR000954/RR/NCRR NIH HHS/ -- P41 RR000954-32S1/RR/NCRR NIH HHS/ -- R01 AI027568/AI/NIAID NIH HHS/ -- R01 AI027568-17/AI/NIAID NIH HHS/ -- R01 AI055849/AI/NIAID NIH HHS/ -- R01 AI055849-05/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):871-4. doi: 10.1126/science.1177627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892989" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Cross Reactions ; Cytotoxicity, Immunologic ; H-2 Antigens/genetics/*immunology ; Lymphocyte Activation ; Major Histocompatibility Complex/*immunology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Ovalbumin/immunology ; Peptides/*immunology ; Protein Multimerization ; Spleen/cytology/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Thymus Gland/cytology/immunology ; Vesiculovirus/immunology
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  • 16
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    Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-07
    Description: X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patients for whom there were no matched donors. Autologous CD34+ cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1, and then re-infused into the patients after they had received myeloablative treatment. Over a span of 24 to 30 months of follow-up, we detected polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein. These results strongly suggest that hematopoietic stem cells were transduced in the patients. Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cartier, Nathalie -- Hacein-Bey-Abina, Salima -- Bartholomae, Cynthia C -- Veres, Gabor -- Schmidt, Manfred -- Kutschera, Ina -- Vidaud, Michel -- Abel, Ulrich -- Dal-Cortivo, Liliane -- Caccavelli, Laure -- Mahlaoui, Nizar -- Kiermer, Veronique -- Mittelstaedt, Denice -- Bellesme, Celine -- Lahlou, Najiba -- Lefrere, Francois -- Blanche, Stephane -- Audit, Muriel -- Payen, Emmanuel -- Leboulch, Philippe -- l'Homme, Bruno -- Bougneres, Pierre -- Von Kalle, Christof -- Fischer, Alain -- Cavazzana-Calvo, Marina -- Aubourg, Patrick -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):818-23. doi: 10.1126/science.1171242.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM UMR745, University Paris-Descartes, 75279 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892975" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/*genetics ; Adrenoleukodystrophy/genetics/pathology/*therapy ; Animals ; Brain/pathology ; Cell Differentiation ; Cell Lineage ; Child ; Disease Progression ; Fatty Acids/blood ; Female ; Gene Expression ; *Genetic Therapy ; *Genetic Vectors ; HIV-1/*genetics ; Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology/virology ; Humans ; Leukocytes, Mononuclear/metabolism ; Male ; Mice ; Microglia/cytology/metabolism ; Myeloablative Agonists/therapeutic use ; Transduction, Genetic ; Transplantation Conditioning ; Transplantation, Autologous ; Virus Integration
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  • 17
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    Structure and mechanism of a Na+-independent amino acid transporter (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-18
    Description: Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity amino acid transporter, at 2.35 angstrom resolution. The structure contains 12 transmembrane helices, with the first 10 consisting of an inverted structural repeat of 5 transmembrane helices like the leucine transporter LeuT. The ApcT structure reveals an inward-facing, apo state and an amine moiety of lysine-158 located in a position equivalent to the sodium ion site Na2 of LeuT. We propose that lysine-158 is central to proton-coupled transport and that the amine group serves the same functional role as the Na2 ion in LeuT, thus demonstrating common principles among proton- and sodium-coupled transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851542/" 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/PMC2851542/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaffer, Paul L -- Goehring, April -- Shankaranarayanan, Aruna -- Gouaux, Eric -- R01 MH070039/MH/NIMH NIH HHS/ -- R01 MH070039-05/MH/NIMH NIH HHS/ -- T32 GM008281/GM/NIGMS NIH HHS/ -- T32 GM008281-17/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-040002/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1010-4. doi: 10.1126/science.1176088. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608859" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/*metabolism ; Amino Acids/metabolism ; Antiporters/chemistry ; Apoproteins/chemistry/metabolism ; Archaeal Proteins/*chemistry/*metabolism ; Crystallization ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry ; Methanococcus/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protons ; Sodium/metabolism ; Substrate Specificity
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  • 18
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    Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-30
    Description: Transcribing RNA polymerases oscillate between three stable states, two of which, pre- and posttranslocated, were previously subjected to x-ray crystal structure determination. We report here the crystal structure of RNA polymerase II in the third state, the reverse translocated, or "backtracked" state. The defining feature of the backtracked structure is a binding site for the first backtracked nucleotide. This binding site is occupied in case of nucleotide misincorporation in the RNA or damage to the DNA, and is termed the "P" site because it supports proofreading. The predominant mechanism of proofreading is the excision of a dinucleotide in the presence of the elongation factor SII (TFIIS). Structure determination of a cocrystal with TFIIS reveals a rearrangement whereby cleavage of the RNA may take place.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718261/" 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/PMC2718261/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Dong -- Bushnell, David A -- Huang, Xuhui -- Westover, Kenneth D -- Levitt, Michael -- Kornberg, Roger D -- GM036559/GM/NIGMS NIH HHS/ -- GM041455/GM/NIGMS NIH HHS/ -- GM049985/GM/NIGMS NIH HHS/ -- K99 GM085136/GM/NIGMS NIH HHS/ -- K99 GM085136-01/GM/NIGMS NIH HHS/ -- R00 GM085136/GM/NIGMS NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM041455/GM/NIGMS NIH HHS/ -- R01 GM049985/GM/NIGMS NIH HHS/ -- R01 GM049985-16/GM/NIGMS NIH HHS/ -- R37 GM036659/GM/NIGMS NIH HHS/ -- R37 GM036659-22/GM/NIGMS NIH HHS/ -- R37 GM041455/GM/NIGMS NIH HHS/ -- R37 GM041455-20/GM/NIGMS NIH HHS/ -- U54 GM072970/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1203-6. doi: 10.1126/science.1168729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478184" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pair Mismatch ; Crystallography, X-Ray ; Guanosine Monophosphate/chemistry/metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Oligoribonucleotides/chemistry/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/chemistry/*metabolism ; RNA Polymerase II/*chemistry/*metabolism ; Saccharomyces cerevisiae/*enzymology ; *Transcription, Genetic ; Transcriptional Elongation Factors/chemistry/*metabolism
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  • 19
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    Education. Science needs kids with vision (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1190-1. doi: 10.1126/science.325_1190b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729624" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Aptitude Tests ; Child ; *Child, Gifted ; *Cognition ; Female ; Humans ; Male ; Sex Characteristics ; *Space Perception
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  • 20
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    Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-03-17
    Description: Once all chromosomes are connected to the mitotic spindle (bioriented), anaphase is initiated by the protein ubiquitylation activity of the anaphase-promoting complex/cyclosome (APC/C) and its coactivator Cdc20 (APC/C(Cdc20)). Before chromosome biorientation, anaphase is delayed by a mitotic checkpoint complex (MCC) that inhibits APC/C(Cdc20). We used single-particle electron microscopy to obtain three-dimensional models of human APC/C in various functional states: bound to MCC, to Cdc20, or to neither (apo-APC/C). These experiments revealed that MCC associates with the Cdc20 binding site on APC/C, locks the otherwise flexible APC/C in a "closed" state, and prevents binding and ubiquitylation of a wide range of different APC/C substrates. These observations clarify the structural basis for the inhibition of APC/C by spindle checkpoint proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989460/" 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/PMC2989460/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herzog, Franz -- Primorac, Ivana -- Dube, Prakash -- Lenart, Peter -- Sander, Bjorn -- Mechtler, Karl -- Stark, Holger -- Peters, Jan-Michael -- F 3407/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1477-81. doi: 10.1126/science.1163300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286556" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Cdc20 Proteins ; Cell Cycle Proteins/chemistry/metabolism ; HeLa Cells ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Microscopy, Electron ; *Mitosis ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Spindle Apparatus/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligase Complexes/*chemistry/*metabolism ; Ubiquitination
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  • 21
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    Function of mitochondrial Stat3 in cellular respiration (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-10
    Description: Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3(-/-) cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758306/" 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/PMC2758306/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegrzyn, Joanna -- Potla, Ramesh -- Chwae, Yong-Joon -- Sepuri, Naresh B V -- Zhang, Qifang -- Koeck, Thomas -- Derecka, Marta -- Szczepanek, Karol -- Szelag, Magdalena -- Gornicka, Agnieszka -- Moh, Akira -- Moghaddas, Shadi -- Chen, Qun -- Bobbili, Santha -- Cichy, Joanna -- Dulak, Jozef -- Baker, Darren P -- Wolfman, Alan -- Stuehr, Dennis -- Hassan, Medhat O -- Fu, Xin-Yuan -- Avadhani, Narayan -- Drake, Jennifer I -- Fawcett, Paul -- Lesnefsky, Edward J -- Larner, Andrew C -- CA098924/CA/NCI NIH HHS/ -- P01AG15885/AG/NIA NIH HHS/ -- R01 AI059710/AI/NIAID NIH HHS/ -- R01 AI059710-03/AI/NIAID NIH HHS/ -- R01 AI059710-04/AI/NIAID NIH HHS/ -- R01 CA098924/CA/NCI NIH HHS/ -- R01 CA098924-03/CA/NCI NIH HHS/ -- R01 CA098924-04/CA/NCI NIH HHS/ -- R01 CA098924-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):793-7. doi: 10.1126/science.1164551. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131594" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Respiration ; Cells, Cultured ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Homeostasis ; Mice ; Mitochondria/*metabolism ; Mitochondria, Heart/metabolism ; Mitochondria, Liver/metabolism ; Mitochondrial Membranes/metabolism ; NADH, NADPH Oxidoreductases/metabolism ; Oxidative Phosphorylation ; Phosphorylation ; Precursor Cells, B-Lymphoid/metabolism ; STAT3 Transcription Factor/chemistry/*metabolism ; Serine/metabolism ; Signal Transduction
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    High-throughput sequencing of the zebrafish antibody repertoire (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-09
    Description: Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" 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/PMC3086368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, Joshua A -- Jiang, Ning -- White, Richard A 3rd -- Fisher, Daniel S -- Quake, Stephen R -- DP1 OD000251/OD/NIH HHS/ -- DP1 OD000251-04/OD/NIH HHS/ -- DP1 OD000251-05/OD/NIH HHS/ -- DP1 OD000251-06/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):807-10. doi: 10.1126/science.1170020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Program, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423829" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/genetics ; Antibody Diversity ; Base Sequence ; Complementarity Determining Regions/*genetics ; Computational Biology ; Female ; Gene Library ; *Genes, Immunoglobulin Heavy Chain ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Joining Region/genetics ; Immunoglobulin M/*genetics ; Male ; Molecular Sequence Data ; Recombination, Genetic ; Sequence Analysis, DNA ; VDJ Exons ; Zebrafish/genetics/*immunology
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    Predicting elections: child's play! (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-03
    Description: In two experiments, children and adults rated pairs of faces from election races. Naive adults judged a pair on competence; after playing a game, children chose who they would prefer to be captain of their boat. Children's (as well as adults') preferences accurately predicted actual election outcomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Antonakis, John -- Dalgas, Olaf -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1183. doi: 10.1126/science.1167748.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Business and Economics, University of Lausanne, 1015 Lausanne, Switzerland. john.antonakis@unil.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251621" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; *Choice Behavior ; *Face ; Female ; Forecasting ; Games, Experimental ; Humans ; Male ; Middle Aged ; Physiognomy ; *Politics ; Probability ; Regression Analysis ; Young Adult
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The subtle transmission of race bias via televised nonverbal behavior (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: Compared with more explicit racial slurs and statements, biased facial expressions and body language may resist conscious identification and thus produce a hidden social influence. In four studies, we show that race biases can be subtly transmitted via televised nonverbal behavior. Characters on 11 popular television shows exhibited more negative nonverbal behavior toward black than toward status-matched white characters. Critically, exposure to prowhite (versus problack) nonverbal bias increased viewers' bias even though patterns of nonverbal behavior could not be consciously reported. These findings suggest that hidden patterns of televised nonverbal behavior influence bias among viewers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764987/" 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/PMC3764987/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisbuch, Max -- Pauker, Kristin -- Ambady, Nalini -- F32 MH078350/MH/NIMH NIH HHS/ -- F32MH078350/MH/NIMH NIH HHS/ -- R01 MH070833/MH/NIMH NIH HHS/ -- R01 MH070833-02/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1711-4. doi: 10.1126/science.1178358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Tufts University, 490 Boston Avenue, Medford, MA 02155, USA. max.weisbuch@tufts.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019288" target="_blank"〉PubMed〈/a〉
    Keywords: *African Continental Ancestry Group ; Cues ; *European Continental Ancestry Group ; Facial Expression ; Female ; Humans ; Kinesics ; Male ; *Nonverbal Communication ; *Prejudice ; *Television ; United States
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    Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-13
    Description: Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca2+) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca2+ sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995306/" 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/PMC2995306/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aoki, Scott T -- Settembre, Ethan C -- Trask, Shane D -- Greenberg, Harry B -- Harrison, Stephen C -- Dormitzer, Philip R -- AI-21362/AI/NIAID NIH HHS/ -- CA-13202/CA/NCI NIH HHS/ -- DK-56339/DK/NIDDK NIH HHS/ -- R37 CA013202/CA/NCI NIH HHS/ -- R37 CA013202-38/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jun 12;324(5933):1444-7. doi: 10.1126/science.1170481.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19520960" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/immunology/metabolism ; Antibodies, Viral/chemistry/*immunology/metabolism ; Antigens, Viral/*chemistry/genetics/*immunology/metabolism ; Binding Sites ; Binding Sites, Antibody ; Calcium/metabolism ; Capsid Proteins/*chemistry/genetics/*immunology/metabolism ; Crystallography, X-Ray ; Epitopes/immunology ; Immunoglobulin Fab Fragments/chemistry/*immunology/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Neutralization Tests ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Protein Subunits ; Recombinant Proteins/chemistry ; Rotavirus/*chemistry/immunology ; Serotyping
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    Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-28
    Description: P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052/" 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/PMC2720052/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aller, Stephen G -- Yu, Jodie -- Ward, Andrew -- Weng, Yue -- Chittaboina, Srinivas -- Zhuo, Rupeng -- Harrell, Patina M -- Trinh, Yenphuong T -- Zhang, Qinghai -- Urbatsch, Ina L -- Chang, Geoffrey -- F32 GM078914/GM/NIGMS NIH HHS/ -- F32 GM078914-03/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM078914/GM/NIGMS NIH HHS/ -- GM61905/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-050002/GM/NIGMS NIH HHS/ -- R01 GM061905/GM/NIGMS NIH HHS/ -- R01 GM061905-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1718-22. doi: 10.1126/science.1168750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325113" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/chemistry ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry ; Mice ; Models, Molecular ; Molecular Sequence Data ; P-Glycoprotein/antagonists & inhibitors/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Stereoisomerism ; Verapamil/metabolism/pharmacology
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    DICER1 mutations in familial pleuropulmonary blastoma (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-27
    Description: Pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that is often part of an inherited cancer syndrome. PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation. Here, we show that 11 multiplex PPB families harbor heterozygous germline mutations in DICER1, a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs. Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma). We hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098036/" 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/PMC3098036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, D Ashley -- Ivanovich, Jennifer -- Priest, John R -- Gurnett, Christina A -- Dehner, Louis P -- Desruisseau, David -- Jarzembowski, Jason A -- Wikenheiser-Brokamp, Kathryn A -- Suarez, Brian K -- Whelan, Alison J -- Williams, Gretchen -- Bracamontes, Dawn -- Messinger, Yoav -- Goodfellow, Paul J -- P30 CA091842/CA/NCI NIH HHS/ -- P30 CA091842-07/CA/NCI NIH HHS/ -- P30 CA091842-08/CA/NCI NIH HHS/ -- R01 CA143167/CA/NCI NIH HHS/ -- R01 HL109265/HL/NHLBI NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Washington University Medical Center, St. Louis, MO 63110, USA. dashill@cnmc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556464" target="_blank"〉PubMed〈/a〉
    Keywords: DEAD-box RNA Helicases/chemistry/*genetics ; Epithelium/metabolism ; Female ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Heterozygote ; Humans ; Lung Neoplasms/enzymology/*genetics/pathology ; Male ; Pedigree ; Pulmonary Blastoma/enzymology/*genetics/pathology ; Ribonuclease III/chemistry/*genetics
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    Blue or red? Exploring the effect of color on cognitive task performances (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-02-07
    Description: Existing research reports inconsistent findings with regard to the effect of color on cognitive task performances. Some research suggests that blue or green leads to better performances than red; other studies record the opposite. Current work reconciles this discrepancy. We demonstrate that red (versus blue) color induces primarily an avoidance (versus approach) motivation (study 1, n = 69) and that red enhances performance on a detail-oriented task, whereas blue enhances performance on a creative task (studies 2 and 3, n = 208 and 118). Further, we replicate these results in the domains of product design (study 4, n = 42) and persuasive message evaluation (study 5, n = 161) and show that these effects occur outside of individuals' consciousness (study 6, n = 68). We also provide process evidence suggesting that the activation of alternative motivations mediates the effect of color on cognitive task performances.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mehta, Ravi -- Zhu, Rui Juliet -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1226-9. doi: 10.1126/science.1169144. Epub 2009 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sauder School of Business, University of British Columbia, 2053 Main Mall, Vancouver, BC V6T 1Z2, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197022" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; *Cognition ; *Color ; Creativity ; Female ; Humans ; Male ; *Mental Processes ; Mental Recall ; Motivation ; *Task Performance and Analysis ; Young Adult
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    Population structure mediates sexual conflict in water striders (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-11-07
    Description: Sexual conflict occurs when males and females act against each others' interest, typically resulting in selection favoring harmful males. We performed laboratory experiments on sexual conflict that both confined individuals in isolated groups, which prevents selection acting counter to this conflict, and provided more naturalistic multigroup population structures. We show that in water striders, aggressive male mating behavior was strongly favored within groups but not favored in a multigroup population when individuals can freely disperse among groups. These observations explain the persistence of less-aggressive males within natural populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eldakar, Omar Tonsi -- Dlugos, Michael J -- Pepper, John W -- Wilson, David Sloan -- 5 K12 GM000708/GM/NIGMS NIH HHS/ -- K12 GM000708/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):816. doi: 10.1126/science.1180183.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Insect Science, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892974" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression ; Animals ; Female ; Heteroptera/*physiology ; Male ; Mating Preference, Animal ; Population Dynamics ; *Sexual Behavior, Animal
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    Harmonic convergence in the love songs of the dengue vector mosquito (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-10
    Description: The familiar buzz of flying mosquitoes is an important mating signal, with the fundamental frequency of the female's flight tone signaling her presence. In the yellow fever and dengue vector Aedes aegypti, both sexes interact acoustically by shifting their flight tones to match, resulting in a courtship duet. Matching is made not at the fundamental frequency of 400 hertz (female) or 600 hertz (male) but at a shared harmonic of 1200 hertz, which exceeds the previously known upper limit of hearing in mosquitoes. Physiological recordings from Johnston's organ (the mosquito's "ear") reveal sensitivity up to 2000 hertz, consistent with our observed courtship behavior. These findings revise widely accepted limits of acoustic behavior in mosquitoes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847473/" 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/PMC2847473/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cator, Lauren J -- Arthur, Ben J -- Harrington, Laura C -- Hoy, Ronald R -- R01 DC000103/DC/NIDCD NIH HHS/ -- R01 DC000103-34/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1077-9. doi: 10.1126/science.1166541. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131593" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*physiology ; *Animal Communication ; Animals ; Auditory Perception ; Dengue/transmission ; Evoked Potentials ; Female ; Flight, Animal ; Hearing ; Insect Vectors/*physiology ; Male ; Pitch Perception ; Sense Organs/physiology ; *Sexual Behavior, Animal ; Wings, Animal/physiology
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    Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785900/" 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/PMC2785900/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ashall, Louise -- Horton, Caroline A -- Nelson, David E -- Paszek, Pawel -- Harper, Claire V -- Sillitoe, Kate -- Ryan, Sheila -- Spiller, David G -- Unitt, John F -- Broomhead, David S -- Kell, Douglas B -- Rand, David A -- See, Violaine -- White, Michael R H -- BB/C007158/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C008219/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C520471/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/D010748/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E004210/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E012965/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F005938/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0071581/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0082191/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC5204711/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBD0107481/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBF0059381/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500346/Medical Research Council/United Kingdom -- G0500346(73596)/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):242-6. doi: 10.1126/science.1164860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359585" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Feedback, Physiological ; *Gene Expression ; Humans ; I-kappa B Proteins/metabolism ; Mice ; Models, Biological ; Models, Statistical ; NF-kappa B/*metabolism ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; Stochastic Processes ; Transcription Factor RelA/*metabolism ; *Transcription, Genetic ; Transfection ; Tumor Necrosis Factor-alpha/*metabolism
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    Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-03
    Description: Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884172/" 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/PMC2884172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuchibhotla, Kishore V -- Lattarulo, Carli R -- Hyman, Bradley T -- Bacskai, Brian J -- EB000768/EB/NIBIB NIH HHS/ -- F31 NS058075-02/NS/NINDS NIH HHS/ -- NS580752/NS/NINDS NIH HHS/ -- R01 AG008487/AG/NIA NIH HHS/ -- R01 AG008487-19/AG/NIA NIH HHS/ -- R01 EB000768/EB/NIBIB NIH HHS/ -- R01 EB000768-08/EB/NIBIB NIH HHS/ -- S10 RR025645/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1211-5. doi: 10.1126/science.1169096.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251629" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/pathology/*physiopathology ; Amyloid beta-Peptides/analysis ; Animals ; Astrocytes/metabolism/pathology/*physiology ; Calcium/*metabolism ; *Calcium Signaling ; Disease Models, Animal ; Homeostasis ; Humans ; Mice ; Mice, Transgenic ; Microscopy, Fluorescence, Multiphoton ; Neurons/pathology/physiology ; Plaque, Amyloid/pathology
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    Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-01
    Description: Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730530/" 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/PMC3730530/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slack, Emma -- Hapfelmeier, Siegfried -- Stecher, Barbel -- Velykoredko, Yuliya -- Stoel, Maaike -- Lawson, Melissa A E -- Geuking, Markus B -- Beutler, Bruce -- Tedder, Thomas F -- Hardt, Wolf-Dietrich -- Bercik, Premysl -- Verdu, Elena F -- McCoy, Kathy D -- Macpherson, Andrew J -- AI56363/AI/NIAID NIH HHS/ -- CA105001/CA/NCI NIH HHS/ -- R01 CA105001/CA/NCI NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):617-20. doi: 10.1126/science.1172747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada. andrew.macpherson@insel.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/biosynthesis/blood/*immunology ; Bacteremia/immunology/microbiology ; Bacteria/growth & development/*immunology/isolation & purification ; Bacterial Infections/immunology/microbiology ; CD4-Positive T-Lymphocytes/immunology ; Colony Count, Microbial ; Enterococcus faecalis/growth & development/immunology/isolation & purification ; Escherichia coli K12/growth & development/immunology/isolation & purification ; Germ-Free Life ; Immunity ; *Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Intestines/immunology/*microbiology ; Lymphoid Tissue/microbiology ; Mice ; Mice, Inbred C57BL ; Permeability ; Respiratory Burst ; Signal Transduction ; Specific Pathogen-Free Organisms ; Spleen/microbiology ; Toll-Like Receptors/genetics/*metabolism
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    DNA binding site sequence directs glucocorticoid receptor structure and activity (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-18
    Description: Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" 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/PMC2777810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijsing, Sebastiaan H -- Pufall, Miles A -- So, Alex Y -- Bates, Darren L -- Chen, Lin -- Yamamoto, Keith R -- GM08537/GM/NIGMS NIH HHS/ -- R01 CA020535/CA/NCI NIH HHS/ -- R01 CA020535-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):407-10. doi: 10.1126/science.1164265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA/*chemistry/*metabolism ; Humans ; Ligands ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Isoforms/chemistry/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/*metabolism ; Transcriptional Activation
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    Crystal structure of the catalytic core of an RNA-polymerase ribozyme (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.0 angstrom crystal structure of this ligase. The architecture resembles a tripod, its three legs converging near the ligation junction. Interacting with this tripod scaffold through a series of 10 minor-groove interactions (including two A-minor triads) is the unpaired segment that contributes to and organizes the active site. A cytosine nucleobase and two backbone phosphates abut the ligation junction; their location suggests a model for catalysis resembling that of proteinaceous polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978776/" 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/PMC3978776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shechner, David M -- Grant, Robert A -- Bagby, Sarah C -- Koldobskaya, Yelena -- Piccirilli, Joseph A -- Bartel, David P -- GM61835/GM/NIGMS NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1271-5. doi: 10.1126/science.1174676.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965478" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Magnesium/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Polynucleotide Ligases/chemistry/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Ribonucleotides/chemistry/metabolism
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    Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1 (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-21
    Description: Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA-binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the regulation of life span and establish a role for SIRT1 in protein homeostasis and the HSR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429349/" 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/PMC3429349/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westerheide, Sandy D -- Anckar, Julius -- Stevens, Stanley M Jr -- Sistonen, Lea -- Morimoto, Richard I -- R01 AG026647/AG/NIA NIH HHS/ -- R01 AG026647-01/AG/NIA NIH HHS/ -- R01 AG026647-02/AG/NIA NIH HHS/ -- R01 AG026647-03/AG/NIA NIH HHS/ -- R01 AG026647-04/AG/NIA NIH HHS/ -- R01 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109-19/GM/NIGMS NIH HHS/ -- R37 GM038109-20/GM/NIGMS NIH HHS/ -- R37 GM038109-21/GM/NIGMS NIH HHS/ -- R37 GM038109-22/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1063-6. doi: 10.1126/science.1165946.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL, 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229036" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Cell Aging/*physiology ; Chromatin Immunoprecipitation ; DNA/metabolism ; DNA-Binding Proteins/*metabolism ; Down-Regulation ; HSP70 Heat-Shock Proteins/*genetics ; HeLa Cells ; *Heat-Shock Response ; Homeostasis ; Humans ; Mice ; Molecular Sequence Data ; *Promoter Regions, Genetic ; RNA, Small Interfering ; Sirtuin 1 ; Sirtuins/genetics/*metabolism ; *Stress, Psychological ; Transcription Factors/*metabolism ; Transfection
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    Neural mechanisms of a genome-wide supported psychosis variant (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-02
    Description: Schizophrenia is a devastating, highly heritable brain disorder of unknown etiology. Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706). We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage-dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. Our findings establish disturbed connectivity as a neurogenetic risk mechanism for psychosis supported by genome-wide association, show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Esslinger, Christine -- Walter, Henrik -- Kirsch, Peter -- Erk, Susanne -- Schnell, Knut -- Arnold, Claudia -- Haddad, Leila -- Mier, Daniela -- Opitz von Boberfeld, Carola -- Raab, Kyeon -- Witt, Stephanie H -- Rietschel, Marcella -- Cichon, Sven -- Meyer-Lindenberg, Andreas -- New York, N.Y. -- Science. 2009 May 1;324(5927):605. doi: 10.1126/science.1167768.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, J5, 68159 Mannheim, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407193" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Affective Symptoms/genetics/physiopathology ; Bipolar Disorder/genetics/physiopathology ; Brain Mapping ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Hippocampus/*physiology ; Humans ; Kruppel-Like Transcription Factors/*genetics ; Magnetic Resonance Imaging ; Male ; Mental Processes ; Phenotype ; *Polymorphism, Single Nucleotide ; Prefrontal Cortex/*physiology ; Schizophrenia/*genetics/physiopathology
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    Demography. Chinese men: a rising tide of troublemakers? (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1166. doi: 10.1126/science.323.5918.1166.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251607" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Crime ; Female ; Humans ; Male ; *Marriage ; *Sex Ratio ; *Social Problems
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    A gene necessary for reproductive suppression in termites (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-05-09
    Description: A major transition in evolution is the origin of a division between reproduction and work among individuals. Nowhere is this divide more striking than in social insects, where workers rarely produce offspring even though they are often capable of reproduction should the queen or king die. The molecular mechanisms that control worker reproduction remain largely unknown. We used a combination of behavioral assays and RNA interference (RNAi) to identify a gene required for the reproductive division of labor between the queen and the workers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korb, Judith -- Weil, Tobias -- Hoffmann, Katharina -- Foster, Kevin R -- Rehli, Michael -- New York, N.Y. -- Science. 2009 May 8;324(5928):758. doi: 10.1126/science.1170660.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Behavioral Biology, University of Osnabrueck, Barbarastrasse 11, D-49076 Osnabrueck, Germany. judith.korb@biologie.uni-osnabrueck.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423819" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Evolution, Molecular ; Female ; *Genes ; Glycoside Hydrolases/*genetics/*metabolism ; Isoptera/enzymology/*genetics/*physiology ; RNA Interference ; Reproduction/genetics ; Social Behavior
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    Structural plasticity in actin and tubulin polymer dynamics (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-22
    Description: Actin filaments and microtubules polymerize and depolymerize by adding and removing subunits at polymer ends, and these dynamics drive cytoplasmic organization, cell division, and cell motility. Since Wegner proposed the treadmilling theory for actin in 1976, it has largely been assumed that the chemical state of the bound nucleotide determines the rates of subunit addition and removal. This chemical kinetics view is difficult to reconcile with observations revealing multiple structural states of the polymer that influence polymerization dynamics but that are not strictly coupled to the bound nucleotide state. We refer to these phenomena as "structural plasticity" and discuss emerging evidence that they play a central role in polymer dynamics and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864651/" 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/PMC2864651/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kueh, Hao Yuan -- Mitchison, Timothy J -- GM 23928/GM/NIGMS NIH HHS/ -- R01 GM023928/GM/NIGMS NIH HHS/ -- R01 GM023928-31/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):960-3. doi: 10.1126/science.1168823.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19696342" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry/metabolism/ultrastructure ; Actin Depolymerizing Factors/metabolism ; Actins/*chemistry/metabolism ; Adenosine Triphosphate/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Kinetics ; Microfilament Proteins/metabolism ; Microtubules/*chemistry/metabolism/ultrastructure ; Models, Biological ; Tubulin/*chemistry/metabolism
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    Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-18
    Description: Genomic expansions of simple tandem repeats can give rise to toxic RNAs that contain expanded repeats. In myotonic dystrophy, the expression of expanded CUG repeats (CUGexp) causes abnormal regulation of alternative splicing and neuromuscular dysfunction. We used a transgenic mouse model to show that derangements of myotonic dystrophy are reversed by a morpholino antisense oligonucleotide, CAG25, that binds to CUGexp RNA and blocks its interaction with muscleblind-like 1 (MBNL1), a CUGexp-binding protein. CAG25 disperses nuclear foci of CUGexp RNA and reduces the overall burden of this toxic RNA. As MBNL1 is released from sequestration, the defect of alternative splicing regulation is corrected, thereby restoring ion channel function. These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109973/" 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/PMC4109973/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wheeler, Thurman M -- Sobczak, Krzysztof -- Lueck, John D -- Osborne, Robert J -- Lin, Xiaoyan -- Dirksen, Robert T -- Thornton, Charles A -- AR/NS48143/AR/NIAMS NIH HHS/ -- AR046806/AR/NIAMS NIH HHS/ -- K08 NS064293/NS/NINDS NIH HHS/ -- K24 AR048143/AR/NIAMS NIH HHS/ -- NIDCR-T32DE07202/DE/NIDCR NIH HHS/ -- R01 AR046806/AR/NIAMS NIH HHS/ -- R01 AR049077/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):336-9. doi: 10.1126/science.1173110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608921" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/*metabolism ; Actins/genetics ; Alternative Splicing ; Animals ; Cell Line ; Cell Nucleus/metabolism ; Chloride Channels/metabolism ; DNA-Binding Proteins/*metabolism ; Humans ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myotonic Dystrophy/*drug therapy/*genetics/metabolism ; Myotonin-Protein Kinase ; Oligodeoxyribonucleotides, Antisense/*pharmacology/therapeutic use ; Protein-Serine-Threonine Kinases/genetics ; RNA, Messenger/genetics ; RNA-Binding Proteins/*metabolism ; Transcription, Genetic ; *Trinucleotide Repeat Expansion
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    Diversity and complexity in DNA recognition by transcription factors (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-16
    Description: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" 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/PMC2905877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badis, Gwenael -- Berger, Michael F -- Philippakis, Anthony A -- Talukder, Shaheynoor -- Gehrke, Andrew R -- Jaeger, Savina A -- Chan, Esther T -- Metzler, Genita -- Vedenko, Anastasia -- Chen, Xiaoyu -- Kuznetsov, Hanna -- Wang, Chi-Fong -- Coburn, David -- Newburger, Daniel E -- Morris, Quaid -- Hughes, Timothy R -- Bulyk, Martha L -- R01 HG003985/HG/NHGRI NIH HHS/ -- R01 HG003985-01/HG/NHGRI NIH HHS/ -- R01 HG003985-02/HG/NHGRI NIH HHS/ -- R01 HG003985-03/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Mice ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/*metabolism
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    Proteome organization in a genome-reduced bacterium (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: The genome of Mycoplasma pneumoniae is among the smallest found in self-replicating organisms. To study the basic principles of bacterial proteome organization, we used tandem affinity purification-mass spectrometry (TAP-MS) in a proteome-wide screen. The analysis revealed 62 homomultimeric and 116 heteromultimeric soluble protein complexes, of which the majority are novel. About a third of the heteromultimeric complexes show higher levels of proteome organization, including assembly into larger, multiprotein complex entities, suggesting sequential steps in biological processes, and extensive sharing of components, implying protein multifunctionality. Incorporation of structural models for 484 proteins, single-particle electron microscopy, and cellular electron tomograms provided supporting structural details for this proteome organization. The data set provides a blueprint of the minimal cellular machinery required for life.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuhner, Sebastian -- van Noort, Vera -- Betts, Matthew J -- Leo-Macias, Alejandra -- Batisse, Claire -- Rode, Michaela -- Yamada, Takuji -- Maier, Tobias -- Bader, Samuel -- Beltran-Alvarez, Pedro -- Castano-Diez, Daniel -- Chen, Wei-Hua -- Devos, Damien -- Guell, Marc -- Norambuena, Tomas -- Racke, Ines -- Rybin, Vladimir -- Schmidt, Alexander -- Yus, Eva -- Aebersold, Ruedi -- Herrmann, Richard -- Bottcher, Bettina -- Frangakis, Achilleas S -- Russell, Robert B -- Serrano, Luis -- Bork, Peer -- Gavin, Anne-Claude -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1235-40. doi: 10.1126/science.1176343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965468" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*analysis/isolation & purification/metabolism ; Computational Biology ; *Genome, Bacterial ; Mass Spectrometry/methods ; Metabolic Networks and Pathways ; Microscopy, Electron ; Models, Biological ; Models, Molecular ; Multiprotein Complexes/*analysis/metabolism ; Mycoplasma pneumoniae/*chemistry/*genetics/metabolism/ultrastructure ; Pattern Recognition, Automated ; Protein Interaction Mapping ; *Proteome ; Systems Biology
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    IL-21R on T cells is critical for sustained functionality and control of chronic viral infection (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-05-30
    Description: Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and functionality of CD8+ T cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. Cell-autonomous IL-21 receptor (IL-21R)-dependent signaling by CD8+ T cells was required for sustained cell proliferation and cytokine production during chronic infection. Il21r-/- mice showed normal CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute and after resolved infection with several other nonpersistent viruses. These data suggest that IL-21R signaling is required for the maintenance of polyfunctional T cells during chronic viral infections and have implications for understanding the immune response to other persisting antigens, such as tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frohlich, Anja -- Kisielow, Jan -- Schmitz, Iwana -- Freigang, Stefan -- Shamshiev, Abdijapar T -- Weber, Jacqueline -- Marsland, Benjamin J -- Oxenius, Annette -- Kopf, Manfred -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1576-80. doi: 10.1126/science.1172815. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Humans ; Immunologic Memory ; Interferon-gamma/biosynthesis ; Lymphocytic Choriomeningitis/*immunology ; Mice ; Mice, Inbred C57BL ; Peptide Fragments/biosynthesis ; Receptors, Interleukin-21/*immunology ; Signal Transduction
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    Altered heterochromatin binding by a hybrid sterility protein in Drosophila sibling species (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-11-26
    Description: Hybrid sterility of the heterogametic sex is one of the first postzygotic reproductive barriers to evolve during speciation, yet the molecular basis of hybrid sterility is poorly understood. We show that the hybrid male sterility gene Odysseus-site homeobox (OdsH) encodes a protein that localizes to evolutionarily dynamic loci within heterochromatin and leads to their decondensation. In Drosophila mauritiana x Drosophila simulans male hybrids, OdsH from D. mauritiana (OdsHmau) acts as a sterilizing factor by associating with the heterochromatic Y chromosome of D. simulans, whereas D. simulans OdsH (OdsHsim) does not. Characterization of sterile hybrid testes revealed that OdsH abundance and localization in the premeiotic phases of spermatogenesis differ between species. These results reveal that rapid heterochromatin evolution affects the onset of hybrid sterility.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987944/" 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/PMC2987944/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bayes, Joshua J -- Malik, Harmit S -- R01 GM074108/GM/NIGMS NIH HHS/ -- R01 GM074108-05/GM/NIGMS NIH HHS/ -- R01-GM74108/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1538-41. doi: 10.1126/science.1181756. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98185, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933102" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Chromosomes/metabolism/physiology ; Crosses, Genetic ; DNA, Satellite/*metabolism ; Drosophila/genetics/*physiology ; Drosophila Proteins/genetics/*metabolism ; Female ; Fertility ; G2 Phase ; Genetic Speciation ; Heterochromatin/*metabolism ; Homeodomain Proteins/genetics/*metabolism ; Hybridization, Genetic ; Male ; Meiosis ; Recombinant Fusion Proteins/metabolism ; Spermatocytes/cytology/metabolism ; Spermatogenesis ; Testis/metabolism ; X Chromosome/metabolism ; Y Chromosome/*metabolism/physiology
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    HDAC4 regulates neuronal survival in normal and diseased retinas (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-10
    Description: Histone deacetylase 4 (HDAC4) shuttles between the nucleus and cytoplasm and serves as a nuclear co-repressor that regulates bone and muscle development. We report that HDAC4 regulates the survival of retinal neurons in the mouse in normal and pathological conditions. Reduction in HDAC4 expression during normal retinal development led to apoptosis of rod photoreceptors and bipolar (BP) interneurons, whereas overexpression reduced naturally occurring cell death of the BP cells. HDAC4 overexpression in a mouse model of retinal degeneration prolonged photoreceptor survival. The survival effect was due to the activity of HDAC4 in the cytoplasm and relied at least partly on the activity of hypoxia-inducible factor 1alpha (HIF1alpha). These data provide evidence that HDAC4 plays an important role in promoting the survival of retinal neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339762/" 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/PMC3339762/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Bo -- Cepko, Constance L -- EYO 14466/PHS HHS/ -- R01 EY014466/EY/NEI NIH HHS/ -- R01 EY014466-05/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):256-9. doi: 10.1126/science.1166226.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. bochen@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131628" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Apoptosis ; Cell Nucleus/enzymology ; Cell Survival ; Cytoplasm/enzymology ; Electroporation ; Histone Deacetylases/genetics/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mice ; Mutation ; Retina/cytology/*enzymology ; Retinal Degeneration/*enzymology/pathology ; Retinal Neurons/enzymology/*physiology ; Retinal Rod Photoreceptor Cells/enzymology/*physiology ; Rhodopsin/genetics/metabolism ; Transfection
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    Structure of a type IV secretion system core complex (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-01-10
    Description: Type IV secretion systems (T4SSs) are important virulence factors used by Gram-negative bacterial pathogens to inject effectors into host cells or to spread plasmids harboring antibiotic resistance genes. We report the 15 angstrom resolution cryo-electron microscopy structure of the core complex of a T4SS. The core complex is composed of three proteins, each present in 14 copies and forming a approximately 1.1-megadalton two-chambered, double membrane-spanning channel. The structure is double-walled, with each component apparently spanning a large part of the channel. The complex is open on the cytoplasmic side and constricted on the extracellular side. Overall, the T4SS core complex structure is different in both architecture and composition from the other known double membrane-spanning secretion system that has been structurally characterized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fronzes, Remi -- Schafer, Eva -- Wang, Luchun -- Saibil, Helen R -- Orlova, Elena V -- Waksman, Gabriel -- 070776/Wellcome Trust/United Kingdom -- BB/C516144/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C516179/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F010281/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):266-8. doi: 10.1126/science.1166101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck College, Malet Street, London, WC1E 7HX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131631" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry/genetics/ultrastructure ; Bacterial Proteins/*chemistry/genetics/*ultrastructure ; Cloning, Molecular ; Cryoelectron Microscopy ; Gram-Negative Bacteria/*chemistry/genetics/pathogenicity ; Imaging, Three-Dimensional ; Models, Molecular ; Multiprotein Complexes/chemistry/ultrastructure ; *Plasmids ; Protein Conformation ; Protein Structure, Quaternary ; Virulence Factors/*chemistry/genetics
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    S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-04-04
    Description: Mitochondria continuously undergo two opposing processes, fission and fusion. The disruption of this dynamic equilibrium may herald cell injury or death and may contribute to developmental and neurodegenerative disorders. Nitric oxide functions as a signaling molecule, but in excess it mediates neuronal injury, in part via mitochondrial fission or fragmentation. However, the underlying mechanism for nitric oxide-induced pathological fission remains unclear. We found that nitric oxide produced in response to beta-amyloid protein, thought to be a key mediator of Alzheimer's disease, triggered mitochondrial fission, synaptic loss, and neuronal damage, in part via S-nitrosylation of dynamin-related protein 1 (forming SNO-Drp1). Preventing nitrosylation of Drp1 by cysteine mutation abrogated these neurotoxic events. SNO-Drp1 is increased in brains of human Alzheimer's disease patients and may thus contribute to the pathogenesis of neurodegeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823371/" 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/PMC2823371/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Dong-Hyung -- Nakamura, Tomohiro -- Fang, Jianguo -- Cieplak, Piotr -- Godzik, Adam -- Gu, Zezong -- Lipton, Stuart A -- P01 ES016738/ES/NIEHS NIH HHS/ -- P01 ES016738-01/ES/NIEHS NIH HHS/ -- P01 ES016738-010003/ES/NIEHS NIH HHS/ -- P01 ES016738-02/ES/NIEHS NIH HHS/ -- P01 ES016738-020003/ES/NIEHS NIH HHS/ -- P01 HD029587/HD/NICHD NIH HHS/ -- P01 HD029587-16/HD/NICHD NIH HHS/ -- P01 HD29587/HD/NICHD NIH HHS/ -- P30 NS057096/NS/NINDS NIH HHS/ -- P30 NS057096-04/NS/NINDS NIH HHS/ -- R01 EY005477/EY/NEI NIH HHS/ -- R01 EY005477-25/EY/NEI NIH HHS/ -- R01 EY05477/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):102-5. doi: 10.1126/science.1171091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 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/19342591" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/metabolism/pathology ; Amino Acid Motifs ; Amyloid beta-Peptides/*metabolism/pharmacology ; Animals ; Cell Line ; Cell Line, Tumor ; Cerebral Cortex/cytology ; Cysteine/analogs & derivatives/genetics/metabolism/pharmacology ; Female ; GTP Phosphohydrolases/chemistry/*metabolism ; Humans ; Male ; Mice ; Mice, Transgenic ; Microtubule-Associated Proteins/chemistry/*metabolism ; Mitochondria/drug effects/physiology/*ultrastructure ; Mitochondrial Proteins/chemistry/*metabolism ; Models, Molecular ; Mutation ; Neurons/drug effects/*ultrastructure ; Nitric Oxide/*metabolism ; Peptide Fragments/metabolism/pharmacology ; Protein Multimerization ; Protein Structure, Tertiary ; S-Nitrosothiols/pharmacology
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    Neuroscience. Enzyme lets you enjoy the bubbly (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):349. doi: 10.1126/science.326_349a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833928" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Dioxide/*metabolism ; *Carbonated Beverages ; Carbonic Anhydrase IV/antagonists & inhibitors/genetics/*metabolism ; Carbonic Anhydrase Inhibitors/pharmacology ; Humans ; Mechanoreceptors/physiology ; Mice ; Protons ; Taste Buds/cytology/*enzymology/physiology ; *Taste Perception
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    Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-03
    Description: Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666000/" 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/PMC2666000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Qian -- She, Hua -- Gearing, Marla -- Colla, Emanuela -- Lee, Michael -- Shacka, John J -- Mao, Zixu -- AG023695/AG/NIA NIH HHS/ -- NS038065/NS/NINDS NIH HHS/ -- NS048254/NS/NINDS NIH HHS/ -- NS055077/NS/NINDS NIH HHS/ -- NS47466/NS/NINDS NIH HHS/ -- NS57098/NS/NINDS NIH HHS/ -- P30 NS055077/NS/NINDS NIH HHS/ -- P30 NS055077-01A2/NS/NINDS NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- P50 AG025688-03/AG/NIA NIH HHS/ -- R01 AG023695/AG/NIA NIH HHS/ -- R01 AG023695-02/AG/NIA NIH HHS/ -- R01 AG023695-03/AG/NIA NIH HHS/ -- R01 AG023695-04/AG/NIA NIH HHS/ -- R01 AG023695-05/AG/NIA NIH HHS/ -- R01 NS048254/NS/NINDS NIH HHS/ -- R01 NS048254-02/NS/NINDS NIH HHS/ -- R01 NS048254-03/NS/NINDS NIH HHS/ -- R01 NS048254-04/NS/NINDS NIH HHS/ -- R01 NS048254-05/NS/NINDS NIH HHS/ -- R01 NS048254-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):124-7. doi: 10.1126/science.1166088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Ammonium Chloride/pharmacology ; Animals ; *Autophagy ; Brain/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cytoplasm/metabolism ; DNA/metabolism ; HSC70 Heat-Shock Proteins/metabolism ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomes/metabolism ; MADS Domain Proteins/*metabolism ; MEF2 Transcription Factors ; Mice ; Mice, Transgenic ; Molecular Chaperones/*metabolism ; Myogenic Regulatory Factors/chemistry/*metabolism ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Protein Binding ; Protein Transport ; Rats ; Rats, Long-Evans ; alpha-Synuclein/genetics/metabolism
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    U.S. higher education. Report finds no gender bias in faculty hiring, resources (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1250-1. doi: 10.1126/science.324_1250a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498138" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Mobility ; Faculty/*statistics & numerical data ; Female ; Humans ; Male ; Personnel Selection ; *Prejudice ; *Research ; Universities/manpower/statistics & numerical data
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    Circadian rhythms. A circadian loop asSIRTs itself (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wijnen, Herman -- R01 GM078339/GM/NIGMS NIH HHS/ -- R01 GM078339-03/GM/NIGMS NIH HHS/ -- R01 GM78839/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):598-9. doi: 10.1126/science.1174132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Virginia, Charlottesville, VA 22904, USA. hw9u@virginai.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407188" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Acetylation ; Acrylamides/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; *Biological Clocks ; CLOCK Proteins ; *Circadian Rhythm ; Cytokines/antagonists & inhibitors/genetics/*metabolism ; *Feedback, Physiological ; Gene Expression Regulation ; Mice ; Mutation ; NAD/*metabolism ; Nicotinamide Phosphoribosyltransferase/antagonists & ; inhibitors/genetics/*metabolism ; Piperidines/pharmacology ; Sirtuin 1 ; Sirtuins/*metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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    A spindle assembly checkpoint protein functions in prophase I arrest and prometaphase progression (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: Two critical stages of mammalian oocyte regulation are prophase I arrest, which is important for sustaining the oocyte pool, and the progression through meiosis I (MI) to produce fertilizable eggs. We have found that the spindle assembly checkpoint protein BubR1 regulates both stages in mouse oocytes. We show that oocytes depleted of BubR1 cannot sustain prophase I arrest and readily undergo germinal vesicle breakdown, a marker for reentry into MI. BubR1-depleted oocytes then arrest before completing MI, marked by failure of polar body extrusion. Both meiotic defects in BubR1-depleted oocytes are due to reduced activity of the master regulator known as the anaphase-promoting complex (APC), brought about through diminished levels of the APC coactivator Cdh1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428834/" 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/PMC3428834/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Homer, Hayden -- Gui, Liming -- Carroll, John -- 082587/Wellcome Trust/United Kingdom -- 082587/Z/07/Z/Wellcome Trust/United Kingdom -- G0400530/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):991-4. doi: 10.1126/science.1175326.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oocyte and Embryo Research Laboratory, Department of Cell and Developmental Biology, Division of Biosciences and Institute for Women's Health, University College London, London, UK. h.homer@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965510" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase-Promoting Complex-Cyclosome ; Animals ; Carrier Proteins/metabolism ; Cdc20 Proteins ; Cdh1 Proteins ; Cell Cycle Proteins/metabolism ; Cyclin B1/metabolism ; Female ; Gene Silencing ; Meiosis/*physiology ; Meiotic Prophase I/*physiology ; Mice ; Oocytes/*physiology ; Prometaphase/*physiology/*radiation effects ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Securin ; Ubiquitin-Protein Ligase Complexes/metabolism
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    CD24 and Siglec-10 selectively repress tissue damage-induced immune responses (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-07
    Description: Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor kappaB (NF-kappaB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765686/" 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/PMC2765686/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Guo-Yun -- Tang, Jie -- Zheng, Pan -- Liu, Yang -- AI064350/AI/NIAID NIH HHS/ -- CA112001/CA/NCI NIH HHS/ -- CA58033/CA/NCI NIH HHS/ -- R01 AI064350/AI/NIAID NIH HHS/ -- R01 AI064350-04/AI/NIAID NIH HHS/ -- R01 CA058033/CA/NCI NIH HHS/ -- R01 CA058033-16A2/CA/NCI NIH HHS/ -- R01 CA112001/CA/NCI NIH HHS/ -- R01 CA112001-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19264983" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/toxicity ; Animals ; Antigens, CD24/genetics/*metabolism ; Cytokines/metabolism ; Dendritic Cells/immunology ; HMGB1 Protein/chemistry/immunology/*metabolism ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; *Immunity, Innate ; Immunoprecipitation ; Inflammation/*immunology ; Lectins/*metabolism ; Lipopolysaccharides/toxicity ; Liver/immunology/pathology ; Mice ; Mutant Proteins/chemistry/metabolism ; Necrosis/chemically induced/immunology ; Protein Structure, Tertiary ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Receptors, Antigen, B-Cell/*metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Pattern Recognition/immunology/metabolism ; Signal Transduction ; Transcription Factor RelA/metabolism
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    Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-03
    Description: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwiatkowski, T J Jr -- Bosco, D A -- Leclerc, A L -- Tamrazian, E -- Vanderburg, C R -- Russ, C -- Davis, A -- Gilchrist, J -- Kasarskis, E J -- Munsat, T -- Valdmanis, P -- Rouleau, G A -- Hosler, B A -- Cortelli, P -- de Jong, P J -- Yoshinaga, Y -- Haines, J L -- Pericak-Vance, M A -- Yan, J -- Ticozzi, N -- Siddique, T -- McKenna-Yasek, D -- Sapp, P C -- Horvitz, H R -- Landers, J E -- Brown, R H Jr -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1205-8. doi: 10.1126/science.1166066.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. tkwiatkowski@partners.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251627" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Amino Acid Substitution ; Amyotrophic Lateral Sclerosis/*genetics/metabolism/pathology ; Animals ; Brain/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Chromosomes, Human, Pair 16/*genetics ; Cytoplasm/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Exons ; Female ; Humans ; Male ; Mice ; Motor Neurons/chemistry/metabolism/ultrastructure ; Mutant Proteins/chemistry/genetics/metabolism ; *Mutation, Missense ; Neurons/metabolism/ultrastructure ; RNA/metabolism ; RNA-Binding Protein FUS/chemistry/*genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Analysis, DNA ; Spinal Cord/pathology
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    Mutations in two independent pathways are sufficient to create hermaphroditic nematodes (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-12-08
    Description: Although the nematode Caenorhabditis elegans produces self-fertile hermaphrodites, it descended from a male/female species, so hermaphroditism provides a model for the origin of novel traits. In the related species C. remanei, which has only male and female sexes, lowering the activity of tra-2 by RNA interference created XX animals that made spermatids as well as oocytes, but their spermatids could not activate without the addition of male seminal fluid. However, by lowering the expression of both tra-2 and swm-1, a gene that regulates sperm activation in C. elegans, we produced XX animals with active sperm that were self-fertile. Thus, the evolution of hermaphroditism in Caenorhabditis probably required two steps: a mutation in the sex-determination pathway that caused XX spermatogenesis and a mutation that allowed these spermatids to self-activate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldi, Chris -- Cho, Soochin -- Ellis, Ronald E -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1002-5. doi: 10.1126/science.1176013.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Caenorhabditis/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Crosses, Genetic ; Disorders of Sex Development/genetics ; Female ; Genes, Helminth ; Germ Cells/physiology ; Male ; Membrane Proteins/genetics/physiology ; Molecular Sequence Data ; *Mutation ; Oogenesis ; Ovulation ; Phylogeny ; Reproduction ; Selection, Genetic ; Sex Determination Processes ; Spermatids/physiology ; Spermatogenesis
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    A cytidine deaminase edits C to U in transfer RNAs in Archaea (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-05-02
    Description: All canonical transfer RNAs (tRNAs) have a uridine at position 8, involved in maintaining tRNA tertiary structure. However, the hyperthermophilic archaeon Methanopyrus kandleri harbors 30 (out of 34) tRNA genes with cytidine at position 8. Here, we demonstrate C-to-U editing at this location in the tRNA's tertiary core, and present the crystal structure of a tRNA-specific cytidine deaminase, CDAT8, which has the cytidine deaminase domain linked to a tRNA-binding THUMP domain. CDAT8 is specific for C deamination at position 8, requires only the acceptor stem hairpin for activity, and belongs to a unique family within the "cytidine deaminase-like" superfamily. The presence of this C-to-U editing enzyme guarantees the proper folding and functionality of all M. kandleri tRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857566/" 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/PMC2857566/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Randau, Lennart -- Stanley, Bradford J -- Kohlway, Andrew -- Mechta, Sarah -- Xiong, Yong -- Soll, Dieter -- AI078831/AI/NIAID NIH HHS/ -- GM22854/GM/NIGMS NIH HHS/ -- R01 GM022854/GM/NIGMS NIH HHS/ -- R01 GM022854-33/GM/NIGMS NIH HHS/ -- R33 AI078831/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):657-9. doi: 10.1126/science.1170123.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. lennart.randau@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407206" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Catalytic Domain ; Crystallography, X-Ray ; Cytidine Deaminase/*chemistry/*metabolism ; Deamination ; Euryarchaeota/enzymology/genetics/*metabolism ; Genes, Archaeal ; Models, Chemical ; Models, Molecular ; Nucleic Acid Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; *RNA Editing ; RNA, Archaeal/chemistry/genetics/*metabolism ; RNA, Transfer/chemistry/genetics/*metabolism
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    Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-09-04
    Description: The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Dijkgraaf, Gerrit J P -- Alicke, Bruno -- Januario, Thomas -- Ahn, Christina P -- Holcomb, Thomas -- Pujara, Kanan -- Stinson, Jeremy -- Callahan, Christopher A -- Tang, Tracy -- Bazan, J Fernando -- Kan, Zhengyan -- Seshagiri, Somasekar -- Hann, Christine L -- Gould, Stephen E -- Low, Jennifer A -- Rudin, Charles M -- de Sauvage, Frederic J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19726788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Anilides/metabolism/pharmacology/*therapeutic use ; Animals ; Antineoplastic Agents/metabolism/pharmacology/*therapeutic use ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cinnamates/pharmacology ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/genetics/*metabolism ; Humans ; Medulloblastoma/*drug therapy/*genetics/pathology ; Mice ; Molecular Sequence Data ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Mutation, Missense ; Neoplasm Metastasis ; Protein Conformation ; Pyridines/metabolism/pharmacology/*therapeutic use ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Signal Transduction ; Veratrum Alkaloids/pharmacology
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    A vital role for interleukin-21 in the control of a chronic viral infection (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-05-16
    Description: Understanding the factors that regulate the induction, quality, and longevity of antiviral T cell responses is essential for devising rational strategies to prevent or combat infections. In this study, we show that interleukin-21 (IL-21), likely produced by CD4+ T cells, directly influences the generation of polyfunctional CD8+ T cells and that the number of CD4+ T cells that produce IL-21 differs markedly between acute and chronic infections. IL-21 regulates the development of CD8+ T cell exhaustion and the ability to contain chronic lymphocytic choriomeningitis virus infection. Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736049/" 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/PMC2736049/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, John S -- Du, Ming -- Zajac, Allan J -- AI049360/AI/NIAID NIH HHS/ -- AI067993/AI/NIAID NIH HHS/ -- R01 AI049360/AI/NIAID NIH HHS/ -- R01 AI049360-08/AI/NIAID NIH HHS/ -- R01 AI067993/AI/NIAID NIH HHS/ -- R01 AI067993-03/AI/NIAID NIH HHS/ -- T32 AI007051/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1572-6. doi: 10.1126/science.1175194. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Interleukins/*immunology ; Lymphocytic Choriomeningitis/*immunology ; Lymphocytic choriomeningitis virus ; Mice ; Mice, Inbred C57BL ; Viral Load
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    Mechanistic analysis of a dynamin effector (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-15
    Description: Dynamin-related proteins (DRPs) can generate forces to remodel membranes. In cells, DRPs require additional proteins [DRP-associated proteins (DAPs)] to conduct their functions. To dissect the mechanistic role of a DAP, we used the yeast mitochondrial division machine as a model, which requires the DRP Dnm1, and two other proteins, Mdv1 and Fis1. Mdv1 played a postmitochondrial targeting role in division by specifically interacting and coassembling with the guanosine triphosphate-bound form of Dnm1. This regulated interaction nucleated and promoted the self-assembly of Dnm1 into helical structures, which drive membrane scission. The nucleation of DRP assembly probably represents a general regulatory strategy for this family of filament-forming proteins, similar to F-actin regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lackner, Laura L -- Horner, Jennifer S -- Nunnari, Jodi -- 1F32GM078749/GM/NIGMS NIH HHS/ -- R01 GM062942/GM/NIGMS NIH HHS/ -- R01GM062942/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):874-7. doi: 10.1126/science.1176921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679814" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; GTP Phosphohydrolases/chemistry/genetics/*metabolism ; Guanosine Triphosphate/analogs & derivatives/metabolism ; Intracellular Membranes/physiology ; Kinetics ; Liposomes/metabolism ; Mitochondria/*physiology ; Mitochondrial Proteins/chemistry/genetics/*metabolism ; Models, Biological ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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    Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-25
    Description: Polyphosphate (polyP) occurs ubiquitously in cells, but its functions are poorly understood and its synthesis has only been characterized in bacteria. Using x-ray crystallography, we identified a eukaryotic polyphosphate polymerase within the membrane-integral vacuolar transporter chaperone (VTC) complex. A 2.6 angstrom crystal structure of the catalytic domain grown in the presence of adenosine triphosphate (ATP) reveals polyP winding through a tunnel-shaped pocket. Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. Mutational analysis of the transmembrane domain indicates that VTC may integrate cytoplasmic polymer synthesis with polyP membrane translocation. Identification of the polyP-synthesizing enzyme opens the way to determine the functions of polyP in lower eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hothorn, Michael -- Neumann, Heinz -- Lenherr, Esther D -- Wehner, Mark -- Rybin, Vladimir -- Hassa, Paul O -- Uttenweiler, Andreas -- Reinhardt, Monique -- Schmidt, Andrea -- Seiler, Jeanette -- Ladurner, Andreas G -- Herrmann, Christian -- Scheffzek, Klaus -- Mayer, Andreas -- G0500367/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):513-6. doi: 10.1126/science.1168120.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390046" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Catalysis ; Catalytic Domain ; Crystallography, X-Ray ; Membrane Proteins/*chemistry/metabolism ; Models, Molecular ; Phosphotransferases/*chemistry/metabolism ; Polyphosphates/*chemistry/metabolism ; Protein Conformation ; Saccharomyces cerevisiae/enzymology/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism
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    Paleoanthropology. Bringing hominins back to life (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, Michael -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):136-9. doi: 10.1126/science.325_136.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589975" target="_blank"〉PubMed〈/a〉
    Keywords: *Anatomy, Artistic ; Animals ; Biological Evolution ; Facial Expression ; Female ; Fossils ; Hominidae/*anatomy & histology ; Humans ; Male ; *Models, Anatomic ; Museums ; Skin Pigmentation
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    Microbiology. Mosquitoes cut short (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Read, Andrew F -- Thomas, Matthew B -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):51-2. doi: 10.1126/science.1168659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA. a.read@psu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119208" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics/*microbiology/physiology/virology ; Animals ; Dengue/prevention & control/transmission ; Dengue Virus/*growth & development ; Female ; Humans ; Insect Vectors/genetics/*microbiology/physiology/virology ; Longevity ; Malaria/prevention & control/transmission ; Male ; Pest Control, Biological ; Selection, Genetic ; Virulence ; Wolbachia/genetics/pathogenicity/*physiology
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    Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-08
    Description: Tumor progression is driven by genetic mutations, but little is known about the environmental conditions that select for these mutations. Studying the transcriptomes of paired colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently up-regulated in cells with KRAS or BRAF mutations. The mutant cells exhibited enhanced glucose uptake and glycolysis and survived in low-glucose conditions, phenotypes that all required GLUT1 expression. In contrast, when cells with wild-type KRAS alleles were subjected to a low-glucose environment, very few cells survived. Most surviving cells expressed high levels of GLUT1, and 4% of these survivors had acquired KRAS mutations not present in their parents. The glycolysis inhibitor 3-bromopyruvate preferentially suppressed the growth of cells with KRAS or BRAF mutations. Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820374/" 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/PMC2820374/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Jihye -- Rago, Carlo -- Cheong, Ian -- Pagliarini, Ray -- Angenendt, Philipp -- Rajagopalan, Harith -- Schmidt, Kerstin -- Willson, James K V -- Markowitz, Sandy -- Zhou, Shibin -- Diaz, Luis A Jr -- Velculescu, Victor E -- Lengauer, Christoph -- Kinzler, Kenneth W -- Vogelstein, Bert -- Papadopoulos, Nickolas -- CA43460/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-27/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1555-9. doi: 10.1126/science.1174229. Epub 2009 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661383" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Gene Targeting ; *Genes, ras ; Glucose/*metabolism ; Glucose Transporter Type 1/genetics/metabolism ; Glycolysis/drug effects ; Humans ; Lactic Acid/metabolism ; Mice ; Mice, Nude ; *Mutation ; Neoplasm Transplantation ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins B-raf/*genetics ; Pyruvates/pharmacology ; Transplantation, Heterologous
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    Science in society. China reins in wilder impulses in treatment of 'Internet addiction' (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1630-1. doi: 10.1126/science.324_1630.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556477" target="_blank"〉PubMed〈/a〉
    Keywords: *Behavior, Addictive/diagnosis/therapy ; China ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; *Internet ; Male
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    The structure of the ribosome with elongation factor G trapped in the posttranslocational state (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-17
    Description: Elongation factor G (EF-G) is a guanosine triphosphatase (GTPase) that plays a crucial role in the translocation of transfer RNAs (tRNAs) and messenger RNA (mRNA) during translation by the ribosome. We report a crystal structure refined to 3.6 angstrom resolution of the ribosome trapped with EF-G in the posttranslocational state using the antibiotic fusidic acid. Fusidic acid traps EF-G in a conformation intermediate between the guanosine triphosphate and guanosine diphosphate forms. The interaction of EF-G with ribosomal elements implicated in stimulating catalysis, such as the L10-L12 stalk and the L11 region, and of domain IV of EF-G with the tRNA at the peptidyl-tRNA binding site (P site) and with mRNA shed light on the role of these elements in EF-G function. The stabilization of the mobile stalks of the ribosome also results in a more complete description of its structure.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763468/" 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/PMC3763468/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Yong-Gui -- Selmer, Maria -- Dunham, Christine M -- Weixlbaumer, Albert -- Kelley, Ann C -- Ramakrishnan, V -- 082086/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 30;326(5953):694-9. doi: 10.1126/science.1179709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833919" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry ; Catalysis ; Crystallography, X-Ray ; Fusidic Acid/chemistry/pharmacology ; Models, Molecular ; Peptide Elongation Factor G/*chemistry ; Protein Biosynthesis ; Protein Conformation ; Protein Structure, Tertiary ; Protein Synthesis Inhibitors/chemistry/pharmacology ; RNA, Bacterial/chemistry ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosomes/*chemistry ; Thermus thermophilus
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    Immunology. A chronic need for IL-21 (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Lisa D S -- Jameson, Stephen C -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1525-6. doi: 10.1126/science.1176487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19541985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Interleukins/*immunology ; Mice ; Virus Diseases/*immunology
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    Structure and mechanism of an amino acid antiporter (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-30
    Description: Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid-resistance (AR) systems to survive the acidic environment in the stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 A resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Xiang -- Lu, Feiran -- Zhou, Lijun -- Dang, Shangyu -- Sun, Linfeng -- Li, Xiaochun -- Wang, Jiawei -- Shi, Yigong -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1565-8. doi: 10.1126/science.1173654. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478139" target="_blank"〉PubMed〈/a〉
    Keywords: Agmatine/metabolism ; Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/genetics/metabolism/physiology ; Antiporters/*chemistry/genetics/metabolism/physiology ; Arginine/metabolism ; Conserved Sequence ; Crystallography, X-Ray ; Escherichia coli O157/*chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism/physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation
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    Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-03-03
    Description: beta-lactam antibiotics are ineffective against Mycobacterium tuberculosis, being rapidly hydrolyzed by the chromosomally encoded blaC gene product. The carbapenem class of beta-lactams are very poor substrates for BlaC, allowing us to determine the three-dimensional structure of the covalent BlaC-meropenem covalent complex at 1.8 angstrom resolution. When meropenem was combined with the beta-lactamase inhibitor clavulanate, potent activity against laboratory strains of M. tuberculosis was observed [minimum inhibitory concentration (MIC(meropenem)) less than 1 microgram per milliliter], and sterilization of aerobically grown cultures was observed within 14 days. In addition, this combination exhibited inhibitory activity against anaerobically grown cultures that mimic the "persistent" state and inhibited the growth of 13 extensively drug-resistant strains of M. tuberculosis at the same levels seen for drug-susceptible strains. Meropenem and clavulanate are Food and Drug Administration-approved drugs and could potentially be used to treat patients with currently untreatable disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679150/" 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/PMC2679150/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hugonnet, Jean-Emmanuel -- Tremblay, Lee W -- Boshoff, Helena I -- Barry, Clifton E 3rd -- Blanchard, John S -- AI33696/AI/NIAID NIH HHS/ -- Z01 AI000693-15/Intramural NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1215-8. doi: 10.1126/science.1167498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251630" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Antibiotics, Antitubercular/*pharmacology ; Catalytic Domain ; Clavulanic Acid/*pharmacology ; Crystallography, X-Ray ; Drug Combinations ; *Drug Resistance, Multiple, Bacterial ; Enzyme Inhibitors/pharmacology ; Extensively Drug-Resistant Tuberculosis/*microbiology ; Humans ; Kinetics ; Mass Spectrometry ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis/*drug effects/enzymology/growth & development ; Thienamycins/metabolism/*pharmacology ; beta-Lactamase Inhibitors ; beta-Lactamases/*chemistry/metabolism
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    Human substantia nigra neurons encode unexpected financial rewards (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-17
    Description: The brain's sensitivity to unexpected outcomes plays a fundamental role in an organism's ability to adapt and learn new behaviors. Emerging research suggests that midbrain dopaminergic neurons encode these unexpected outcomes. We used microelectrode recordings during deep brain stimulation surgery to study neuronal activity in the human substantia nigra (SN) while patients with Parkinson's disease engaged in a probabilistic learning task motivated by virtual financial rewards. Based on a model of the participants' expected reward, we divided trial outcomes into expected and unexpected gains and losses. SN neurons exhibited significantly higher firing rates after unexpected gains than unexpected losses. No such differences were observed after expected gains and losses. This result provides critical support for the hypothesized role of the SN in human reinforcement learning.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839450/" 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/PMC2839450/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zaghloul, Kareem A -- Blanco, Justin A -- Weidemann, Christoph T -- McGill, Kathryn -- Jaggi, Jurg L -- Baltuch, Gordon H -- Kahana, Michael J -- MH062196/MH/NIMH NIH HHS/ -- MH61975/MH/NIMH NIH HHS/ -- P50 MH062196/MH/NIMH NIH HHS/ -- P50 MH062196-090008/MH/NIMH NIH HHS/ -- R01 MH061975/MH/NIMH NIH HHS/ -- R01 MH061975-08/MH/NIMH NIH HHS/ -- R01 NS048598/NS/NINDS NIH HHS/ -- R01 NS048598-04/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1496-9. doi: 10.1126/science.1167342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA. zaghlouk@uphs.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286561" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Deep Brain Stimulation ; Dopamine/physiology ; Economics ; *Feedback, Psychological ; Female ; Humans ; *Learning ; Male ; Microelectrodes ; Middle Aged ; Models, Psychological ; Neurons/*physiology ; Parkinson Disease/physiopathology/therapy ; Probability ; Reinforcement (Psychology) ; *Reward ; Substantia Nigra/cytology/*physiology
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    Small-molecule activators of a proenzyme (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-07
    Description: Virtually all of the 560 human proteases are stored as inactive proenyzmes and are strictly regulated. We report the identification and characterization of the first small molecules that directly activate proenzymes, the apoptotic procaspases-3 and -6. It is surprising that these compounds induce autoproteolytic activation by stabilizing a conformation that is both more active and more susceptible to intermolecular proteolysis. These procaspase activators bypass the normal upstream proapoptotic signaling cascades and induce rapid apoptosis in a variety of cell lines. Systematic biochemical and biophysical analyses identified a cluster of mutations in procaspase-3 that resist small-molecule activation both in vitro and in cells. Compounds that induce gain of function are rare, and the activators reported here will enable direct control of the executioner caspases in apoptosis and in cellular differentiation. More generally, these studies presage the discovery of other proenzyme activators to explore fundamental processes of proenzyme activation and their fate-determining roles in biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886848/" 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/PMC2886848/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolan, Dennis W -- Zorn, Julie A -- Gray, Daniel C -- Wells, James A -- F32 CA119641/CA/NCI NIH HHS/ -- F32 CA119641-03/CA/NCI NIH HHS/ -- R01 CA136779/CA/NCI NIH HHS/ -- R21 N5057022/PHS HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):853-8. doi: 10.1126/science.1177585.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California, San Francisco, Byers Hall, 1700 4th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzopyrans/chemistry/*metabolism/pharmacology ; Biocatalysis ; Caspase 3/chemistry/genetics/*metabolism ; Caspase 6/chemistry/genetics/*metabolism ; Caspase Inhibitors ; Catalytic Domain ; Cell Line, Transformed ; Cell Line, Tumor ; Cells, Cultured ; Enzyme Activation ; Enzyme Activators/chemistry/*metabolism/pharmacology ; Enzyme Inhibitors/metabolism/pharmacology ; Enzyme Precursors/antagonists & inhibitors/chemistry/genetics/*metabolism ; Granzymes/metabolism ; Humans ; Imidazoles/chemistry/*metabolism/pharmacology ; Kinetics ; Mice ; Molecular Structure ; Mutagenesis ; Pyridines/chemistry/*metabolism/pharmacology ; Signal Transduction ; Small Molecule Libraries/chemistry/metabolism
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    Promoting interest and performance in high school science classes (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: We tested whether classroom activities that encourage students to connect course materials to their lives will increase student motivation and learning. We hypothesized that this effect will be stronger for students who have low expectations of success. In a randomized field experiment with high school students, we found that a relevance intervention, which encouraged students to make connections between their lives and what they were learning in their science courses, increased interest in science and course grades for students with low success expectations. The results have implications for the development of science curricula and theories of motivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hulleman, Chris S -- Harackiewicz, Judith M -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1410-2. doi: 10.1126/science.1177067.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Graduate Psychology, James Madison University, Harrisonburg, VA 22807, USA. hullemcs@jmu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965759" target="_blank"〉PubMed〈/a〉
    Keywords: *Achievement ; Adolescent ; Biology/*education ; Curriculum ; Educational Measurement ; Female ; Humans ; *Learning ; Male ; *Motivation ; Natural Science Disciplines/*education ; Regression Analysis ; Science/*education
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    Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-18
    Description: Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766560/" 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/PMC2766560/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Robert J -- Poholek, Amanda C -- DiToro, Daniel -- Yusuf, Isharat -- Eto, Danelle -- Barnett, Burton -- Dent, Alexander L -- Craft, Joe -- Crotty, Shane -- AR40072/AR/NIAMS NIH HHS/ -- AR44076/AR/NIAMS NIH HHS/ -- P30 AR053495/AR/NIAMS NIH HHS/ -- R01 063107/PHS HHS/ -- R01 072543/PHS HHS/ -- R01 AI063107/AI/NIAID NIH HHS/ -- R01 AI063107-01A1/AI/NIAID NIH HHS/ -- R01 AI072543/AI/NIAID NIH HHS/ -- R01 AI072543-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1006-10. doi: 10.1126/science.1175870. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Formation ; Arenaviridae Infections/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology/immunology ; Cell Differentiation ; Cell Lineage ; Cytokines/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation ; Germinal Center/cytology/immunology ; Lymphocyte Activation ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/cytology/*immunology ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; Transcription Factors/genetics/*metabolism
    Print ISSN: 0036-8075
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    A functional role for adult hippocampal neurogenesis in spatial pattern separation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-11
    Description: The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate pattern separation-the formation of distinct and orthogonal representations of mnemonic information-and also undergoes neurogenesis throughout life. How neurogenesis contributes to hippocampal function is largely unknown. Using adult mice in which hippocampal neurogenesis was ablated, we found specific impairments in spatial discrimination with two behavioral assays: (i) a spatial navigation radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse touch screen. Mice with ablated neurogenesis were impaired when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space. Thus, newborn neurons may be necessary for normal pattern separation function in the DG of adult mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997634/" 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/PMC2997634/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clelland, C D -- Choi, M -- Romberg, C -- Clemenson, G D Jr -- Fragniere, A -- Tyers, P -- Jessberger, S -- Saksida, L M -- Barker, R A -- Gage, F H -- Bussey, T J -- NS-050217/NS/NINDS NIH HHS/ -- R01 NS050217/NS/NINDS NIH HHS/ -- R01 NS050217-05/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):210-3. doi: 10.1126/science.1173215.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19590004" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Dentate Gyrus/cytology/*physiology ; Discrimination Learning/*physiology ; Female ; Hippocampus/cytology/*physiology ; Maze Learning ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; *Neurogenesis ; Neurons/*physiology ; Psychomotor Performance ; *Space Perception
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    The vital role of ORWH (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hultgren, Scott -- Goldstein, Jill M -- Delancey, John O L -- Bandstra, Emmalee S -- Brady, Kathleen T -- Brown, Jeanette S -- Deng, Hong-Wen -- Dunaif, Andrea -- Ehrmann, David A -- Mayer, Emeran A -- Sinha, Rajita -- Tobet, Stuart -- Levine, Jon E -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1009-10. doi: 10.1126/science.323.5917.1009c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229019" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research ; Clinical Trials as Topic ; Female ; Humans ; National Institutes of Health (U.S.)/*organization & administration ; Occupations ; Research Support as Topic ; United States ; *Women's Health
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    The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-14
    Description: The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/" 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/PMC2947205/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fontanilla, Dominique -- Johannessen, Molly -- Hajipour, Abdol R -- Cozzi, Nicholas V -- Jackson, Meyer B -- Ruoho, Arnold E -- F31 DA022932/DA/NIDA NIH HHS/ -- NS30016/NS/NINDS NIH HHS/ -- R01 MH065503/MH/NIMH NIH HHS/ -- R01 MH065503-01A1/MH/NIMH NIH HHS/ -- R01 NS030016/NS/NINDS NIH HHS/ -- R01 NS030016-08/NS/NINDS NIH HHS/ -- R01 NS030016-09/NS/NINDS NIH HHS/ -- T32 GM08688/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):934-7. doi: 10.1126/science.1166127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COS Cells ; Cell Line ; Cells, Cultured ; Cercopithecus aethiops ; Guinea Pigs ; Hallucinogens/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/metabolism ; N,N-Dimethyltryptamine/*metabolism ; Rats ; Receptors, sigma/agonists/antagonists & inhibitors/*metabolism ; Tryptamines/metabolism
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    Secondary replicative function of CD8+ T cells that had developed an effector phenotype (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-24
    Description: Models of the differentiation of memory CD8+ T cells that replicate during secondary infections differ over whether such cells had acquired effector function during primary infections. We created a transgenic mouse line that permits mapping of the fate of granzyme B (gzmB)-expressing CD8+ T cells and their progeny by indelibly marking them with enhanced yellow fluorescent protein (EYFP). Virus-specific CD8+ T cells express gzmB within the first 2 days of a primary response to infection with influenza, without impairment of continued primary clonal expansion. On secondary infection, virus-specific CD8+ T cells that became EYFP+ during a primary infection clonally expand as well as all virus-specific CD8+ T cells. Thus, CD8+ T cells that have acquired an effector phenotype during primary infection may function as memory cells with replicative function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653633/" 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/PMC2653633/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bannard, Oliver -- Kraman, Matthew -- Fearon, Douglas T -- 075289/Wellcome Trust/United Kingdom -- 082259/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):505-9. doi: 10.1126/science.1166831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164749" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation ; Cell Division ; Granzymes/genetics/metabolism ; *Immunologic Memory ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/immunology ; Luminescent Proteins/genetics/metabolism ; Lung/immunology ; Mice ; Mice, Transgenic ; Orthomyxoviridae Infections/*immunology ; Phenotype ; Spleen/immunology ; T-Lymphocyte Subsets/cytology/immunology
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    Sequential sympatric speciation across trophic levels (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: A major cause for biodiversity may be biodiversity itself. As new species form, they may create new niches for others to exploit, potentially catalyzing a chain reaction of speciation events across trophic levels. We tested for such sequential radiation in the Rhagoletis pomonella (Diptera: Tephritidae) complex, a model for sympatric speciation via host plant shifting. We report that the parasitic wasp Diachasma alloeum (Hymenoptera: Braconidae) has formed new incipient species as a result of specializing on diversifying fly hosts, including the recently derived apple-infesting race of R. pomonella. Furthermore, we show that traits that differentially adapt R. pomonella flies to their host plants have also quickly evolved and serve as ecological barriers to reproduction, isolating the wasps. Speciation therefore cascades as the effects of new niche construction move across trophic levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forbes, Andrew A -- Powell, Thomas H Q -- Stelinski, Lukasz L -- Smith, James J -- Feder, Jeffrey L -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):776-9. doi: 10.1126/science.1166981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Notre Dame, Galvin Life Sciences Building, Notre Dame, IN 46556, USA. aaforbes@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197063" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biodiversity ; Cues ; DNA, Mitochondrial/genetics ; Female ; Fruit ; Gene Flow ; Gene Frequency ; Genes, Insect ; *Genetic Speciation ; Genetic Variation ; Haplotypes ; Host-Parasite Interactions ; Male ; Microsatellite Repeats ; Molecular Sequence Data ; Odors ; Sexual Behavior, Animal ; Tephritidae/*genetics/growth & development/*parasitology/physiology ; Wasps/*genetics/growth & development/physiology
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    Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-07
    Description: The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADalpha and the scaffolding protein MO25alpha through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADalpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADalpha and MO25alpha promote the active conformation of LKB1, which is stabilized by MO25alpha interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518268/" 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/PMC3518268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeqiraj, Elton -- Filippi, Beatrice Maria -- Deak, Maria -- Alessi, Dario R -- van Aalten, Daan M F -- 087590/Wellcome Trust/United Kingdom -- C33794/A10969/Cancer Research UK/United Kingdom -- G0900138/Medical Research Council/United Kingdom -- MC_U127070193/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1707-11. doi: 10.1126/science.1178377. Epub 2009 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892943" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adaptor Proteins, Vesicular Transport/*chemistry/metabolism ; Allosteric Regulation ; Amino Acid Sequence ; Binding Sites ; Calcium-Binding Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Mutant Proteins/chemistry/metabolism ; Mutation ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*chemistry/metabolism
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    The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-01
    Description: Epac2, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rap1, is activated by adenosine 3',5'-monophosphate. Fluorescence resonance energy transfer and binding experiments revealed that sulfonylureas, widely used antidiabetic drugs, interact directly with Epac2. Sulfonylureas activated Rap1 specifically through Epac2. Sulfonylurea-stimulated insulin secretion was reduced both in vitro and in vivo in mice lacking Epac2, and the glucose-lowering effect of the sulfonylurea tolbutamide was decreased in these mice. Epac2 thus contributes to the effect of sulfonylureas to promote insulin secretion. Because Epac2 is also required for the action of incretins, gut hormones crucial for potentiating insulin secretion, it may be a promising target for antidiabetic drug development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Chang-Liang -- Katoh, Megumi -- Shibasaki, Tadao -- Minami, Kohtaro -- Sunaga, Yasuhiro -- Takahashi, Harumi -- Yokoi, Norihide -- Iwasaki, Masahiro -- Miki, Takashi -- Seino, Susumu -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):607-10. doi: 10.1126/science.1172256.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644119" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Blood Glucose/analysis ; COS Cells ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Cercopithecus aethiops ; Cyclic AMP/*metabolism ; Fluorescence Resonance Energy Transfer ; Glucose/administration & dosage ; Glyburide/metabolism/pharmacology ; Guanine Nucleotide Exchange Factors/genetics/*metabolism ; Hypoglycemic Agents/chemistry/*metabolism/pharmacology ; Insulin/blood/secretion ; Islets of Langerhans/secretion ; Mice ; Mice, Inbred C57BL ; Sulfonylurea Compounds/chemistry/*metabolism/pharmacology ; Tolbutamide/metabolism/pharmacology ; rap1 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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    RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-06-06
    Description: Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase receptor-interacting protein 3 (RIP3) as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulates TNF-induced reactive oxygen species production, which partially accounts for RIP3's ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Duan-Wu -- Shao, Jing -- Lin, Juan -- Zhang, Na -- Lu, Bao-Ju -- Lin, Sheng-Cai -- Dong, Meng-Qiu -- Han, Jiahuai -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):332-6. doi: 10.1126/science.1172308. Epub 2009 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498109" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; *Apoptosis ; Cell Line ; Energy Metabolism ; Glutamate Dehydrogenase/metabolism ; Glutamate-Ammonia Ligase/metabolism ; Glycogen Phosphorylase/metabolism ; Mice ; NIH 3T3 Cells ; *Necrosis ; RNA Interference ; Reactive Oxygen Species/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/*metabolism ; Tumor Necrosis Factor-alpha/*pharmacology
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    Pre-target axon sorting establishes the neural map topography (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-07-11
    Description: Sensory information detected by the peripheral nervous system is represented as a topographic map in the brain. It has long been thought that the topography of the map is determined by graded positional cues that are expressed by the target. Here, we analyzed the pre-target axon sorting for olfactory map formation in mice. In olfactory sensory neurons, an axon guidance receptor, Neuropilin-1, and its repulsive ligand, Semaphorin-3A, are expressed in a complementary manner. We found that expression levels of Neuropilin-1 determined both pre-target sorting and projection sites of axons. Olfactory sensory neuron-specific knockout of Semaphorin-3A perturbed axon sorting and altered the olfactory map topography. Thus, pre-target axon sorting plays an important role in establishing the topographic order based on the relative levels of guidance molecules expressed by axons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imai, Takeshi -- Yamazaki, Takahiro -- Kobayakawa, Reiko -- Kobayakawa, Ko -- Abe, Takaya -- Suzuki, Misao -- Sakano, Hitoshi -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):585-90. doi: 10.1126/science.1173596. Epub 2009 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Brain Mapping ; Cell Communication ; Cues ; Cyclic AMP/metabolism ; Ligands ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neuroglia/physiology ; Neuropilin-1/*metabolism ; Olfactory Bulb/cytology/*physiology ; Olfactory Mucosa/cytology/physiology ; Olfactory Pathways/cytology/*physiology ; Olfactory Receptor Neurons/cytology/*physiology ; Receptors, Odorant/metabolism ; Semaphorin-3A/metabolism ; Signal Transduction
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    Complete resequencing of 40 genomes reveals domestication events and genes in silkworm (Bombyx) (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-08-29
    Description: A single-base pair resolution silkworm genetic variation map was constructed from 40 domesticated and wild silkworms, each sequenced to approximately threefold coverage, representing 99.88% of the genome. We identified ~16 million single-nucleotide polymorphisms, many indels, and structural variations. We find that the domesticated silkworms are clearly genetically differentiated from the wild ones, but they have maintained large levels of genetic variability, suggesting a short domestication event involving a large number of individuals. We also identified signals of selection at 354 candidate genes that may have been important during domestication, some of which have enriched expression in the silk gland, midgut, and testis. These data add to our understanding of the domestication processes and may have applications in devising pest control strategies and advancing the use of silkworms as efficient bioreactors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951477/" 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/PMC3951477/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xia, Qingyou -- Guo, Yiran -- Zhang, Ze -- Li, Dong -- Xuan, Zhaoling -- Li, Zhuo -- Dai, Fangyin -- Li, Yingrui -- Cheng, Daojun -- Li, Ruiqiang -- Cheng, Tingcai -- Jiang, Tao -- Becquet, Celine -- Xu, Xun -- Liu, Chun -- Zha, Xingfu -- Fan, Wei -- Lin, Ying -- Shen, Yihong -- Jiang, Lan -- Jensen, Jeffrey -- Hellmann, Ines -- Tang, Si -- Zhao, Ping -- Xu, Hanfu -- Yu, Chang -- Zhang, Guojie -- Li, Jun -- Cao, Jianjun -- Liu, Shiping -- He, Ningjia -- Zhou, Yan -- Liu, Hui -- Zhao, Jing -- Ye, Chen -- Du, Zhouhe -- Pan, Guoqing -- Zhao, Aichun -- Shao, Haojing -- Zeng, Wei -- Wu, Ping -- Li, Chunfeng -- Pan, Minhui -- Li, Jingjing -- Yin, Xuyang -- Li, Dawei -- Wang, Juan -- Zheng, Huisong -- Wang, Wen -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Lu, Cheng -- Nielsen, Rasmus -- Zhou, Zeyang -- Wang, Jian -- Xiang, Zhonghuai -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):433-6. doi: 10.1126/science.1176620. Epub 2009 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Sericultural Laboratory of Agricultural Ministry, College of Biotechnology, Southwest University, Chongqing 400715, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bombyx/classification/*genetics ; Digestive System/metabolism ; Exocrine Glands/metabolism ; Female ; Gene Expression ; *Genes, Insect ; *Genetic Variation ; *Genome, Insect ; INDEL Mutation ; Linkage Disequilibrium ; Male ; Phylogeny ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Selection, Genetic ; *Sequence Analysis, DNA ; Testis/metabolism
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    Rab35 controls actin bundling by recruiting fascin as an effector protein (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-09-05
    Description: Actin filaments are key components of the eukaryotic cytoskeleton that provide mechanical structure and generate forces during cell shape changes, growth, and migration. Actin filaments are dynamically assembled into higher-order structures at specified locations to regulate diverse functions. The Rab family of small guanosine triphosphatases is evolutionarily conserved and mediates intracellular vesicle trafficking. We found that Rab35 regulates the assembly of actin filaments during bristle development in Drosophila and filopodia formation in cultured cells. These effects were mediated by the actin-bundling protein fascin, which directly associated with active Rab35. Targeting Rab35 to the outer mitochondrial membrane triggered actin recruitment, demonstrating a role for an intracellular trafficking protein in localized actin assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jun -- Fonovic, Marko -- Suyama, Kaye -- Bogyo, Matthew -- Scott, Matthew P -- U54 RR020843/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1250-4. doi: 10.1126/science.1174921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729655" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism/ultrastructure ; Actins/*metabolism ; Animals ; Carrier Proteins/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Drosophila/anatomy & histology/growth & development/metabolism ; Drosophila Proteins/genetics/*metabolism ; HeLa Cells ; Humans ; Mice ; Microfilament Proteins/*metabolism ; Mitochondrial Membranes/metabolism ; NIH 3T3 Cells ; Pseudopodia/metabolism/ultrastructure ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; rab GTP-Binding Proteins/genetics/*metabolism
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    Polydnaviruses of braconid wasps derive from an ancestral nudivirus (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-02-14
    Description: Many species of parasitoid wasps inject polydnavirus particles in order to manipulate host defenses and development. Because the DNA packaged in these particles encodes almost no viral structural proteins, their relation to viruses has been debated. Characterization of complementary DNAs derived from braconid wasp ovaries identified genes encoding subunits of a viral RNA polymerase and structural components of polydnavirus particles related most closely to those of nudiviruses--a sister group of baculoviruses. The conservation of this viral machinery in different braconid wasp lineages sharing polydnaviruses suggests that parasitoid wasps incorporated a nudivirus-related genome into their own genetic material. We found that the nudiviral genes themselves are no longer packaged but are actively transcribed and produce particles used to deliver genes essential for successful parasitism in lepidopteran hosts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bezier, Annie -- Annaheim, Marc -- Herbiniere, Juline -- Wetterwald, Christoph -- Gyapay, Gabor -- Bernard-Samain, Sylvie -- Wincker, Patrick -- Roditi, Isabel -- Heller, Manfred -- Belghazi, Maya -- Pfister-Wilhem, Rita -- Periquet, Georges -- Dupuy, Catherine -- Huguet, Elisabeth -- Volkoff, Anne-Nathalie -- Lanzrein, Beatrice -- Drezen, Jean-Michel -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):926-30. doi: 10.1126/science.1166788.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherche sur la Biologie de l'Insecte, CNRS UMR 6035, Universite Francois Rabelais, Parc de Grandmont, 37200 Tours, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213916" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Baculoviridae/genetics ; Biological Evolution ; *DNA, Viral/analysis ; Expressed Sequence Tags ; Female ; Genome, Insect ; Molecular Sequence Data ; Ovary/virology ; Polydnaviridae/*genetics/physiology ; Viral Structural Proteins/genetics ; Virion/genetics ; Virus Integration ; Wasps/*virology
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    Cell signaling. Aging is RSKy business (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaeberlein, Matt -- Kapahi, Pankaj -- R01 AG031108/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 2;326(5949):55-6. doi: 10.1126/science.1181034.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA. kaeber@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797648" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/genetics/metabolism ; Aging/*physiology ; Animals ; Caloric Restriction ; Enzyme Activation ; Female ; Gene Expression ; Longevity/*physiology ; Male ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Protein Biosynthesis ; Protein Kinases/metabolism ; Protein Subunits ; Ribosomal Protein S6/*metabolism ; Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism ; *Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases
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    Epicontinental seas versus open-ocean settings: the kinetics of mass extinction and origination (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-12-08
    Description: Environmental perturbations during mass extinctions were likely manifested differently in epicontinental seas than in open-ocean-facing habitats of comparable depth. Here, we present a dissection of origination and extinction in epicontinental seas versus open-ocean-facing coastal regions in the Permian through Cretaceous periods, an interval through which both settings are well represented in the fossil record. Results demonstrate that extinction rates were significantly higher in open-ocean settings than in epicontinental seas during major mass extinctions but not at other times and that origination rates were significantly higher in open-ocean settings for a protracted interval from the Late Jurassic through the Late Cretaceous. These patterns are manifested even when other paleogeographic and environmental variables are held fixed, indicating that epicontinental seas and open-ocean-facing coastlines carry distinct macroevolutionary signatures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Arnold I -- Foote, Michael -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1106-9. doi: 10.1126/science.1180061.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, University of Cincinnati, Post Office Box 210013, Cincinnati, OH 45221, USA. arnold.miller@uc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965428" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Bivalvia ; *Ecosystem ; Environment ; *Extinction, Biological ; Geologic Sediments ; Geological Phenomena ; Kinetics ; Oceans and Seas
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    Draxin, a repulsive guidance protein for spinal cord and forebrain commissures (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-01-20
    Description: Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Islam, Shahidul M -- Shinmyo, Yohei -- Okafuji, Tatsuya -- Su, Yuhong -- Naser, Iftekhar Bin -- Ahmed, Giasuddin -- Zhang, Sanbing -- Chen, Sandy -- Ohta, Kunimasa -- Kiyonari, Hiroshi -- Abe, Takaya -- Tanaka, Satomi -- Nishinakamura, Ryuichi -- Terashima, Toshio -- Kitamura, Toshio -- Tanaka, Hideaki -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):388-93. doi: 10.1126/science.1165187.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150847" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Axons/*physiology ; COS Cells ; Cercopithecus aethiops ; Chick Embryo ; Coculture Techniques ; Corpus Callosum/embryology/metabolism ; Electroporation ; Growth Cones/metabolism/physiology ; Intercellular Signaling Peptides and ; Proteins/chemistry/genetics/metabolism/*physiology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Neurites/metabolism/*physiology ; Neurogenesis ; Neuroglia/metabolism ; Prosencephalon/abnormalities/*embryology/metabolism ; Recombinant Proteins/metabolism ; Spinal Cord/*embryology/metabolism ; Tissue Culture Techniques
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    Mechanically activated integrin switch controls alpha5beta1 function (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-01-31
    Description: The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that alpha(5)beta(1) integrin switches between relaxed and tensioned states in response to myosin II-generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the alpha(5)beta(1)-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedland, Julie C -- Lee, Mark H -- Boettiger, David -- GM57388/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):642-4. doi: 10.1126/science.1168441.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179533" target="_blank"〉PubMed〈/a〉
    Keywords: Actins ; Biophysical Phenomena ; Cell Adhesion ; Cell Line, Tumor ; Cytoskeleton/*physiology ; Fibronectins/chemistry/*metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Integrin alpha5beta1/*chemistry/*metabolism ; Ligands ; Models, Molecular ; Myosin Type II/antagonists & inhibitors/metabolism ; Phosphorylation ; Protein Binding ; Protein Conformation ; Signal Transduction
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    KLF family members regulate intrinsic axon regeneration ability (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-10
    Description: Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Kruppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882032/" 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/PMC2882032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, Darcie L -- Blackmore, Murray G -- Hu, Ying -- Kaestner, Klaus H -- Bixby, John L -- Lemmon, Vance P -- Goldberg, Jeffrey L -- P30 EY014801/EY/NEI NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- R01 NS059866-01A2/NS/NINDS NIH HHS/ -- R01 NS061348/NS/NINDS NIH HHS/ -- R01 NS061348-01A2/NS/NINDS NIH HHS/ -- R01 NS061348-02/NS/NINDS NIH HHS/ -- R01 NS061348-03/NS/NINDS NIH HHS/ -- R01 NS061348-04/NS/NINDS NIH HHS/ -- R03 EY016790/EY/NEI NIH HHS/ -- R03 EY016790-01/EY/NEI NIH HHS/ -- R03 EY016790-02/EY/NEI NIH HHS/ -- R03 EY016790-03/EY/NEI NIH HHS/ -- T32 NS007459/NS/NINDS NIH HHS/ -- T32 NS07492/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):298-301. doi: 10.1126/science.1175737.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815778" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology/ultrastructure ; Cell Count ; Cell Survival ; Cells, Cultured ; Down-Regulation ; Gene Knockout Techniques ; Growth Cones/physiology ; Hippocampus/cytology/physiology ; Kruppel-Like Transcription Factors/genetics/*physiology ; Mice ; Nerve Crush ; Nerve Regeneration ; Neurites/physiology ; Neurons/*physiology ; Optic Nerve Injuries/physiopathology ; Rats ; Retinal Ganglion Cells/cytology/*physiology ; Transcription, Genetic ; Transfection ; Up-Regulation
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    Three-dimensional structural view of the central metabolic network of Thermotoga maritima (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-19
    Description: Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (approximately 30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833182/" 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/PMC2833182/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ying -- Thiele, Ines -- Weekes, Dana -- Li, Zhanwen -- Jaroszewski, Lukasz -- Ginalski, Krzysztof -- Deacon, Ashley M -- Wooley, John -- Lesley, Scott A -- Wilson, Ian A -- Palsson, Bernhard -- Osterman, Andrei -- Godzik, Adam -- P20 GM076221/GM/NIGMS NIH HHS/ -- P20 GM076221-03/GM/NIGMS NIH HHS/ -- U54 GM074898/GM/NIGMS NIH HHS/ -- U54 GM074898-05/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1544-9. doi: 10.1126/science.1174671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Center for Molecular Modeling (JCMM), Burnham Institute for Medical Research, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762644" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Computational Biology ; Computer Simulation ; Enzymes/*chemistry/*metabolism ; Evolution, Molecular ; Genes, Bacterial ; Genome, Bacterial ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Systems Biology ; Thermotoga maritima/chemistry/genetics/*metabolism
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  • 92
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    Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-03
    Description: Mammals have single-rowed dentitions, whereas many nonmammalian vertebrates have teeth in multiple rows. Neither the molecular mechanism regulating iterative tooth initiation nor that restricting mammalian tooth development in one row is known. We found that mice lacking the transcription factor odd-skipped related-2 (Osr2) develop supernumerary teeth lingual to their molars because of expansion of the odontogenic field. Osr2 was expressed in a lingual-to-buccal gradient and restricted expression of bone morphogenetic protein 4 (Bmp4), an essential odontogenic signal, in the developing tooth mesenchyme. Expansion of odontogenic field in Osr2-deficient mice required Msx1, a feedback activator of Bmp4 expression. These findings suggest that the Bmp4-Msx1 pathway propagates mesenchymal activation for sequential tooth induction and that spatial modulation of this pathway provides a mechanism for patterning vertebrate dentition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650836/" 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/PMC2650836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Zunyi -- Lan, Yu -- Chai, Yang -- Jiang, Rulang -- R01 DE013681/DE/NIDCR NIH HHS/ -- R01 DE013681-06/DE/NIDCR NIH HHS/ -- R01 DE013681-07/DE/NIDCR NIH HHS/ -- R01 DE013681-08/DE/NIDCR NIH HHS/ -- R01 DE013681-09/DE/NIDCR NIH HHS/ -- R01DE013681/DE/NIDCR NIH HHS/ -- T32DE007202/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1232-4. doi: 10.1126/science.1167418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Oral Biology and Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251632" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Protein 4/metabolism ; Dentition ; Epithelium/embryology/metabolism ; Gene Expression ; Gene Expression Profiling ; MSX1 Transcription Factor/genetics/*metabolism ; Mesoderm/embryology/metabolism ; Mice ; Molar/embryology ; Morphogenesis ; Mutation ; *Odontogenesis ; Tooth Germ/embryology/metabolism ; Tooth, Supernumerary/*embryology ; Transcription Factors/genetics/*metabolism
    Print ISSN: 0036-8075
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  • 93
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    Cellular basis of itch sensation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-08
    Description: Itch and pain are two distinct sensations. Although our previous study suggested that gastrin-releasing peptide receptor (GRPR) is an itch-specific gene in the spinal cord, a long-standing question of whether there are separate neuronal pathways for itch and pain remains unsettled. We selectively ablated lamina I neurons expressing GRPR in the spinal cord of mice. These mice showed profound scratching deficits in response to all of the itching (pruritogenic) stimuli tested, irrespective of their histamine dependence. In contrast, pain behaviors were unaffected. Our data also suggest that GRPR+ neurons are different from the spinothalamic tract neurons that have been the focus of the debate. Together, the present study suggests that GRPR+ neurons constitute a long-sought labeled line for itch sensation in the spinal cord.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786498/" 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/PMC2786498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Yan-Gang -- Zhao, Zhong-Qiu -- Meng, Xiu-Li -- Yin, Jun -- Liu, Xian-Yu -- Chen, Zhou-Feng -- P01 NS049048-23/NS/NINDS NIH HHS/ -- P30 NS057105/NS/NINDS NIH HHS/ -- P30 NS057105-04/NS/NINDS NIH HHS/ -- R01 AR056318/AR/NIAMS NIH HHS/ -- R01 AR056318-01A1/AR/NIAMS NIH HHS/ -- R01 NS046036/NS/NINDS NIH HHS/ -- R01 NS046036-05/NS/NINDS NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1531-4. doi: 10.1126/science.1174868. Epub 2009 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Anesthesiology, Psychiatry, and Developmental Biology, Washington University School of Medicine Pain Center, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661382" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/physiology ; Animals ; Behavior, Animal ; Bombesin/pharmacology ; Chronic Disease ; Histamine ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Pain/physiopathology ; Pruritus/*physiopathology ; Receptors, Bombesin/genetics/*metabolism ; Ribosome Inactivating Proteins, Type 1/pharmacology ; Sensation/physiology ; Spinal Cord/*cytology ; Spinothalamic Tracts/cytology/physiology
    Print ISSN: 0036-8075
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    Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown. We have shown that tumor-derived IDH1 mutations impair the enzyme's affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, alpha-ketoglutarate (alpha-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by alpha-KG. The rise in HIF-1alpha levels was reversible by an alpha-KG derivative. HIF-1alpha levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251015/" 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/PMC3251015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Shimin -- Lin, Yan -- Xu, Wei -- Jiang, Wenqing -- Zha, Zhengyu -- Wang, Pu -- Yu, Wei -- Li, Zhiqiang -- Gong, Lingling -- Peng, Yingjie -- Ding, Jianping -- Lei, Qunying -- Guan, Kun-Liang -- Xiong, Yue -- R01 CA068377/CA/NCI NIH HHS/ -- R01 CA068377-14/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):261-5. doi: 10.1126/science.1170944.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, 130 Dong-An Road, Shanghai 200032, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359588" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Astrocytoma/genetics/metabolism ; Biocatalysis ; Brain Neoplasms/*genetics/metabolism ; Cell Line ; Child ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Glioblastoma/genetics/metabolism ; Glioma/*genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & ; inhibitors/genetics/*metabolism ; Isocitrate Dehydrogenase/chemistry/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Male ; Middle Aged ; Mutant Proteins/chemistry/metabolism ; Oligodendroglioma/genetics/metabolism ; Oxalates/pharmacology ; Protein Multimerization
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    Knockout rats via embryo microinjection of zinc-finger nucleases (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
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    Identification of splenic reservoir monocytes and their deployment to inflammatory sites (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-01
    Description: A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803111/" 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/PMC2803111/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swirski, Filip K -- Nahrendorf, Matthias -- Etzrodt, Martin -- Wildgruber, Moritz -- Cortez-Retamozo, Virna -- Panizzi, Peter -- Figueiredo, Jose-Luiz -- Kohler, Rainer H -- Chudnovskiy, Aleksey -- Waterman, Peter -- Aikawa, Elena -- Mempel, Thorsten R -- Libby, Peter -- Weissleder, Ralph -- Pittet, Mikael J -- 1R01HL095612/HL/NHLBI NIH HHS/ -- P01 A154904/PHS HHS/ -- P01 AI054904/AI/NIAID NIH HHS/ -- P01 AI054904-010001/AI/NIAID NIH HHS/ -- P50 CA086355/CA/NCI NIH HHS/ -- P50 CA086355-07/CA/NCI NIH HHS/ -- P50 CA86355/CA/NCI NIH HHS/ -- R00 HL094533/HL/NHLBI NIH HHS/ -- R01 HL095629/HL/NHLBI NIH HHS/ -- R01 HL096576/HL/NHLBI NIH HHS/ -- R24 CA69246/CA/NCI NIH HHS/ -- U01 HL080731/HL/NHLBI NIH HHS/ -- U01 HL080731-05/HL/NHLBI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):612-6. doi: 10.1126/science.1175202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. fswirski@mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644120" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/blood/pharmacology ; Animals ; Antigens, Ly/metabolism ; Bone Marrow Cells/physiology ; Cell Differentiation ; Cell Movement ; Cell Size ; Female ; Inflammation/*pathology ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology/*physiology ; Myocardial Infarction/immunology/*pathology/*physiopathology ; Myocardium/*immunology/*pathology ; Rats ; Rats, Wistar ; Receptors, Angiotensin/metabolism ; Spleen/cytology/*immunology ; Splenectomy
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    Self-sustained replication of an RNA enzyme (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-10
    Description: An RNA enzyme that catalyzes the RNA-templated joining of RNA was converted to a format whereby two enzymes catalyze each other's synthesis from a total of four oligonucleotide substrates. These cross-replicating RNA enzymes undergo self-sustained exponential amplification in the absence of proteins or other biological materials. Amplification occurs with a doubling time of about 1 hour and can be continued indefinitely. Populations of various cross-replicating enzymes were constructed and allowed to compete for a common pool of substrates, during which recombinant replicators arose and grew to dominate the population. These replicating RNA enzymes can serve as an experimental model of a genetic system. Many such model systems could be constructed, allowing different selective outcomes to be related to the underlying properties of the genetic system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652413/" 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/PMC2652413/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lincoln, Tracey A -- Joyce, Gerald F -- R01 GM065130/GM/NIGMS NIH HHS/ -- R01 GM065130-07/GM/NIGMS NIH HHS/ -- R01GM065130/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1229-32. doi: 10.1126/science.1167856. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131595" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Biocatalysis ; Directed Molecular Evolution ; Kinetics ; Nucleic Acid Conformation ; Oligonucleotides/*metabolism ; Polynucleotide Ligases/*chemistry/metabolism ; RNA, Catalytic/chemistry/*metabolism
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    Sexual conflict resolved by invasion of a novel sex determiner in Lake Malawi cichlid fishes (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-03
    Description: Sex determination mechanisms differ among animal species, but it is not clear how these differences evolve. New sex determiners may arise in response to sexual conflicts, which occur when traits benefit one sex but hinder the other. We identified the genetic basis for the orange-blotch (OB) color pattern, a trait under sexually antagonistic selection in the cichlid fish of Lake Malawi, East Africa. The OB phenotype is due to a cis-regulatory mutation in the Pax7 gene. OB provides benefits of camouflage to females but disrupts the species-specific male color patterns used for mate recognition. We suggest that the resulting sexual conflict over the OB allele has been resolved by selection for a novel female sex determination locus that has invaded populations with an ancestral male sex determination system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174268/" 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/PMC3174268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Reade B -- Ser, Jennifer R -- Kocher, Thomas D -- F32HD051383/HD/NICHD NIH HHS/ -- R01 HD058635/HD/NICHD NIH HHS/ -- R01 HD058635-04/HD/NICHD NIH HHS/ -- R01HD058635/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):998-1001. doi: 10.1126/science.1174705. Epub 2009 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Maryland, College Park, MD 20742, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797625" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Animals ; Biological Evolution ; Chromosome Mapping ; Cichlids/*genetics/*physiology ; Female ; Fresh Water ; Gene Expression Regulation ; Genetic Fitness ; Genetic Speciation ; Haplotypes ; Linkage Disequilibrium ; Male ; *Mating Preference, Animal ; Melanophores/cytology/metabolism ; Microsatellite Repeats ; Molecular Sequence Data ; PAX7 Transcription Factor/*genetics ; Phenotype ; Pigmentation/*genetics ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; Sex Characteristics ; *Sex Determination Processes ; Sexual Behavior, Animal
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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    Conservation biology. Research wolves of Yellowstone killed in hunt (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morell, Virginia -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):506-7. doi: 10.1126/science.326_506.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900867" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; *Conservation of Natural Resources ; Ecosystem ; Female ; Montana ; *Research ; *Wolves
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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    Breakthrough of the year. Ardipithecus ramidus (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1598-9. doi: 10.1126/science.326.5960.1598-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019252" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Bone and Bones/anatomy & histology ; Ethiopia ; Female ; *Fossils ; Geography ; *Hominidae/anatomy & histology/classification/physiology ; Humans ; Locomotion ; Posture ; Skeleton ; Walking
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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