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  • Transfection  (378)
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  • American Association for the Advancement of Science (AAAS)  (736)
  • EMBO Press
  • Essen : Verl. Glückauf
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Oxford University Press
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  • 1990-1994  (365)
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  • 1
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    Fossil plant relative abundances indicate sudden loss of Late Triassic biodiversity in East Greenland (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-23
    Description: The pace of Late Triassic (LT) biodiversity loss is uncertain, yet it could help to decipher causal mechanisms of mass extinction. We investigated relative abundance distributions (RADs) of six LT plant assemblages from the Kap Stewart Group, East Greenland, to determine the pace of collapse of LT primary productivity. RADs displayed not simply decreases in the number of taxa, but decreases in the number of common taxa. Likelihood tests rejected a hypothesis of continuously declining diversity. Instead, the RAD shift occurred over the upper two-to-four fossil plant assemblages and most likely over the last three (final 13 meters), coinciding with increased atmospheric carbon dioxide concentration and global warming. Thus, although the LT event did not induce mass extinction of plant families, it accompanied major and abrupt change in their ecology and diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McElwain, Jennifer C -- Wagner, Peter J -- Hesselbo, Stephen P -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1554-6. doi: 10.1126/science.1171706.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UCD School of Biology and Environmental Science, University College Dublin, National University of Ireland, Belfield, Dublin 4, Ireland. jennifer.mcelwain@ucd.ie〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19541995" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; Biological Evolution ; *Extinction, Biological ; *Fossils ; Greenland ; Likelihood Functions ; Models, Biological ; *Plants/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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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
    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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    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
    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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    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Biochemistry. Through a mirror, differently (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheps, Jonathan A -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1679-80. doi: 10.1126/science.1172428.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genetics and Developmental Biology, BC Cancer Research Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3 Canada. jsheps@bccrc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325102" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Drug Design ; Lipid Bilayers/chemistry ; Models, Biological ; Oligopeptides/chemistry/metabolism ; P-Glycoprotein/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Stereoisomerism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    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
    Print ISSN: 0036-8075
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  • 8
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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
    Print ISSN: 0036-8075
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  • 9
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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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Comment on "Energy uptake and allocation during ontogeny" (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-05
    Description: Hou et al. (Reports, 31 October 2008, p. 736) presented a model for energy uptake and allocation over an organism's growth and development. However, their model does not account for allocation to reproduction (essential to adults) and growth without assimilation (essential to embryos) and is therefore only applicable to organisms growing with abundant food in the juvenile stage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sousa, Tania -- Marques, Goncalo M -- Domingos, Tiago -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1206; author reply 1206. doi: 10.1126/science.1169523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Environment and Energy Section, DEM, and IN+ Center for Innovation Technology and Policy Research, Instituto Superior Tecnico, Lisboa, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729640" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Metabolism ; Biomass ; Birds/embryology/growth & development/*metabolism ; Embryo, Mammalian/metabolism ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Energy Intake ; *Energy Metabolism ; Food ; *Growth ; Mammals/embryology/growth & development/*metabolism ; Models, Biological ; Oxygen Consumption ; Reproduction
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  • 11
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    Details of insect wing design and deformation enhance aerodynamic function and flight efficiency (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-19
    Description: Insect wings are complex structures that deform dramatically in flight. We analyzed the aerodynamic consequences of wing deformation in locusts using a three-dimensional computational fluid dynamics simulation based on detailed wing kinematics. We validated the simulation against smoke visualizations and digital particle image velocimetry on real locusts. We then used the validated model to explore the effects of wing topography and deformation, first by removing camber while keeping the same time-varying twist distribution, and second by removing camber and spanwise twist. The full-fidelity model achieved greater power economy than the uncambered model, which performed better than the untwisted model, showing that the details of insect wing topography and deformation are important aerodynamically. Such details are likely to be important in engineering applications of flapping flight.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, John -- Walker, Simon M -- Bomphrey, Richard J -- Taylor, Graham K -- Thomas, Adrian L R -- 204513/European Research Council/International -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1549-52. doi: 10.1126/science.1175928.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Information Technology, University of New South Wales, Australian Defence Force Academy, Canberra, Australian Capital Territory 2600, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762645" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Computer Simulation ; Flight, Animal/*physiology ; Grasshoppers/*anatomy & histology/*physiology ; Models, Biological ; Movement ; Wings, Animal/*anatomy & histology/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
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    The Red Queen and the Court Jester: species diversity and the role of biotic and abiotic factors through time (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: Evolution may be dominated by biotic factors, as in the Red Queen model, or abiotic factors, as in the Court Jester model, or a mixture of both. The two models appear to operate predominantly over different geographic and temporal scales: Competition, predation, and other biotic factors shape ecosystems locally and over short time spans, but extrinsic factors such as climate and oceanographic and tectonic events shape larger-scale patterns regionally and globally, and through thousands and millions of years. Paleobiological studies suggest that species diversity is driven largely by abiotic factors such as climate, landscape, or food supply, and comparative phylogenetic approaches offer new insights into clade dynamics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benton, Michael J -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):728-32. doi: 10.1126/science.1157719.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Sciences, University of Bristol, Bristol BS8 1RJ, UK. mike.benton@bristol.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197051" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Biological Evolution ; Climate ; Fossils ; *Genetic Speciation ; Geography ; Geological Phenomena ; Logistic Models ; Models, Biological ; Phylogeny ; Time
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 13
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    Rebuilding global fisheries (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-08-01
    Description: After a long history of overexploitation, increasing efforts to restore marine ecosystems and rebuild fisheries are under way. Here, we analyze current trends from a fisheries and conservation perspective. In 5 of 10 well-studied ecosystems, the average exploitation rate has recently declined and is now at or below the rate predicted to achieve maximum sustainable yield for seven systems. Yet 63% of assessed fish stocks worldwide still require rebuilding, and even lower exploitation rates are needed to reverse the collapse of vulnerable species. Combined fisheries and conservation objectives can be achieved by merging diverse management actions, including catch restrictions, gear modification, and closed areas, depending on local context. Impacts of international fleets and the lack of alternatives to fishing complicate prospects for rebuilding fisheries in many poorer regions, highlighting the need for a global perspective on rebuilding marine resources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Worm, Boris -- Hilborn, Ray -- Baum, Julia K -- Branch, Trevor A -- Collie, Jeremy S -- Costello, Christopher -- Fogarty, Michael J -- Fulton, Elizabeth A -- Hutchings, Jeffrey A -- Jennings, Simon -- Jensen, Olaf P -- Lotze, Heike K -- Mace, Pamela M -- McClanahan, Tim R -- Minto, Coilin -- Palumbi, Stephen R -- Parma, Ana M -- Ricard, Daniel -- Rosenberg, Andrew A -- Watson, Reg -- Zeller, Dirk -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):578-85. doi: 10.1126/science.1173146.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Dalhousie University, Halifax, NS B3H 4J1, Canada. bworm@dal.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644114" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Biomass ; *Conservation of Natural Resources ; *Ecosystem ; *Fisheries/methods ; *Fishes/anatomy & histology ; Internationality ; Marine Biology ; Models, Biological ; Oceans and Seas ; Population Dynamics
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  • 14
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    Ecology. The key to Pandora's box (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stevenson, P A -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):594-5. doi: 10.1126/science.1169280.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology II, Faculty for Biosciences, Psychology and Pharmacology, Leipzig University, Talstrasse 33, 04103 Leipzig, Germany. stevenson@rz.unileipzig.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179520" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; *Behavior, Animal ; Crowding ; *Flight, Animal ; Grasshoppers/anatomy & histology/*physiology ; Models, Biological ; Nervous System Physiological Phenomena ; Population Density ; Serotonin/*physiology ; Social Behavior
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
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    Cell biology. Nuclear export of small RNAs (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, Murray -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1195-6. doi: 10.1126/science.1183273.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. ms@mrc-lmb.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965455" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Karyopherins/chemistry/metabolism ; MicroRNAs/chemistry/*metabolism ; Models, Biological ; Nuclear Pore/metabolism ; Nucleic Acid Conformation ; RNA Processing, Post-Transcriptional ; RNA, Small Nuclear/chemistry/*metabolism ; RNA, Transfer/chemistry/*metabolism ; Receptors, Cytoplasmic and Nuclear/chemistry/metabolism ; ran GTP-Binding Protein/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 16
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    Adaptive radiation: contrasting theory with data (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: Biologists have long been fascinated by the exceptionally high diversity displayed by some evolutionary groups. Adaptive radiation in such clades is not only spectacular, but is also an extremely complex process influenced by a variety of ecological, genetic, and developmental factors and strongly dependent on historical contingencies. Using modeling approaches, we identify 10 general patterns concerning the temporal, spatial, and genetic/morphological properties of adaptive radiation. Some of these are strongly supported by empirical work, whereas for others, empirical support is more tentative. In almost all cases, more data are needed. Future progress in our understanding of adaptive radiation will be most successful if theoretical and empirical approaches are integrated, as has happened in other areas of evolutionary biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gavrilets, Sergey -- Losos, Jonathan B -- GM56693/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):732-7. doi: 10.1126/science.1157966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, TN 37996, USA. sergey@tiem.utk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197052" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biodiversity ; *Biological Evolution ; Ecosystem ; Fossils ; *Genetic Speciation ; Genetic Variation ; Models, Biological ; Phylogeny ; Selection, Genetic
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  • 17
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    The extracellular matrix: not just pretty fibrils (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-12-08
    Description: The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536535/" 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/PMC3536535/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hynes, Richard O -- P01 HL066105/HL/NHLBI NIH HHS/ -- R01 CA017007/CA/NCI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1216-9. doi: 10.1126/science.1176009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rohynes@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965464" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; *Cell Physiological Processes ; Extracellular Matrix/*physiology ; Extracellular Matrix Proteins/chemistry/*metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Models, Biological ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Signal Transduction ; Transforming Growth Factor beta/metabolism
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  • 18
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    Tuning the activation threshold of a kinase network by nested feedback loops (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-25
    Description: Determining proper responsiveness to incoming signals is fundamental to all biological systems. We demonstrate that intracellular signaling nodes can tune a signaling network's response threshold away from the basal median effective concentration established by ligand-receptor interactions. Focusing on the bistable kinase network that governs progesterone-induced meiotic entry in Xenopus oocytes, we characterized glycogen synthase kinase-3beta (GSK-3beta) as a dampener of progesterone responsiveness. GSK-3beta engages the meiotic kinase network through a double-negative feedback loop; this specific feedback architecture raises the progesterone threshold in correspondence with the strength of double-negative signaling. We also identified a marker of nutritional status, l-leucine, which lowers the progesterone threshold, indicating that oocytes integrate additional signals into their cell-fate decisions by modulating progesterone responsiveness.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880456/" 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/PMC2880456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Justman, Quincey A -- Serber, Zach -- Ferrell, James E Jr -- El-Samad, Hana -- Shokat, Kevan M -- AI49006/AI/NIAID NIH HHS/ -- GM46383/GM/NIGMS NIH HHS/ -- R01 AI044009/AI/NIAID NIH HHS/ -- R01 AI044009-10/AI/NIAID NIH HHS/ -- R01 GM046383/GM/NIGMS NIH HHS/ -- R01 GM046383-19/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):509-12. doi: 10.1126/science.1169498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Group in Biophysics, 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/19390045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Activation ; Feedback, Physiological ; Glycogen Synthase Kinase 3/*metabolism ; Leucine/metabolism ; *MAP Kinase Signaling System/physiology ; Meiosis/physiology ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; Oocytes/*cytology/*metabolism ; Oogenesis/*physiology ; Phosphorylation ; Progesterone/*physiology ; Xenopus
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  • 19
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    KLF family members regulate intrinsic axon regeneration ability (2009)
    American Association for the Advancement of Science (AAAS)
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    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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  • 20
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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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  • 21
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    Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-18
    Description: DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715015/" 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/PMC2715015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tahiliani, Mamta -- Koh, Kian Peng -- Shen, Yinghua -- Pastor, William A -- Bandukwala, Hozefa -- Brudno, Yevgeny -- Agarwal, Suneet -- Iyer, Lakshminarayan M -- Liu, David R -- Aravind, L -- Rao, Anjana -- AI44432/AI/NIAID NIH HHS/ -- K08 HL089150/HL/NHLBI NIH HHS/ -- R01 GM065865/GM/NIGMS NIH HHS/ -- R01 GM065865-05A1/GM/NIGMS NIH HHS/ -- R01GM065865/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):930-5. doi: 10.1126/science.1170116. Epub 2009 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372391" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/analysis/metabolism ; DNA/chemistry/*metabolism ; DNA Methylation ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Dinucleoside Phosphates/metabolism ; Embryonic Stem Cells/chemistry/metabolism ; Humans ; Hydroxylation ; Mass Spectrometry ; Mice ; Molecular Sequence Data ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; RNA Interference ; Sequence Alignment ; Transfection
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  • 22
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    Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-20
    Description: Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer-based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713345/" 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/PMC2713345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Dan -- Vader, Gerben -- Vromans, Martijn J M -- Lampson, Michael A -- Lens, Susanne M A -- GM083988/GM/NIGMS NIH HHS/ -- R01 GM083988/GM/NIGMS NIH HHS/ -- R01 GM083988-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1350-3. doi: 10.1126/science.1167000. Epub 2009 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150808" target="_blank"〉PubMed〈/a〉
    Keywords: Aurora Kinase B ; Aurora Kinases ; Autoantigens/metabolism ; Biosensing Techniques ; Cell Line, Tumor ; Centromere/enzymology/*metabolism ; Chromatids/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomes, Human/*metabolism ; Fluorescence Resonance Energy Transfer ; HeLa Cells ; Humans ; Kinetochores/*metabolism ; Microtubules/*metabolism ; Mitosis ; Models, Biological ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Recombinant Fusion Proteins/metabolism ; Spindle Apparatus/*metabolism
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    The increasing complexity of the cancer stem cell paradigm (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-27
    Description: The investigation and study of cancer stem cells (CSCs) have received enormous attention over the past 5 to 10 years but remain topics of considerable controversy. Opinions about the validity of the CSC hypothesis, the biological properties of CSCs, and the relevance of CSCs to cancer therapy differ widely. In the following commentary, we discuss the nature of the debate, the parameters by which CSCs can or cannot be defined, and the identification of new potential therapeutic targets elucidated by considering cancer as a problem in stem cell biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873047/" 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/PMC2873047/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, Jeffrey M -- Jordan, Craig T -- R01 CA122206/CA/NCI NIH HHS/ -- R01 CA122206-02/CA/NCI NIH HHS/ -- R01-CA122206/CA/NCI NIH HHS/ -- R37 CA016303/CA/NCI NIH HHS/ -- R37 CA016303-36/CA/NCI NIH HHS/ -- R37-CA16303/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1670-3. doi: 10.1126/science.1171837.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Mice ; Models, Biological ; Neoplasm Transplantation ; Neoplasms/genetics/metabolism/*pathology/therapy ; Neoplastic Stem Cells/cytology/*physiology ; Transcription, Genetic
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  • 24
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    Input-specific spine entry of soma-derived Vesl-1S protein conforms to synaptic tagging (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-16
    Description: Late-phase synaptic plasticity depends on the synthesis of new proteins that must function only in the activated synapses. The synaptic tag hypothesis requires input-specific functioning of these proteins after undirected transport. Confirmation of this hypothesis requires specification of a biochemical tagging activity and an example protein that behaves as the hypothesis predicts. We found that in rat neurons, soma-derived Vesl-1S (Homer-1a) protein, a late-phase plasticity-related synaptic protein, prevailed in every dendrite and did not enter spines. N-methyl-d-aspartate receptor activation triggered input-specific spine entry of Vesl-1S proteins, which met many criteria for synaptic tagging. These results suggest that Vesl-1S supports the hypothesis and that the activity-dependent regulation of spine entry functions as a synaptic tag.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Daisuke -- Ozawa, Fumiko -- Inokuchi, Kaoru -- New York, N.Y. -- Science. 2009 May 15;324(5929):904-9. doi: 10.1126/science.1171498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan. dada@mitils.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443779" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Carrier Proteins/genetics/*metabolism ; Cells, Cultured ; Dendrites/*metabolism ; Dendritic Spines/*metabolism/ultrastructure ; Hippocampus/cytology/metabolism ; Mice ; *Neuronal Plasticity ; Plasmids ; Protein Transport ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Synapses/*metabolism ; Synaptic Transmission ; Transfection
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    Evolution. Symmetry in turns (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tobalske, Bret W -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):190-1. doi: 10.1126/science.1172839.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Field Research Station at Fort Missoula, Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA. bret.tobalske@mso.umt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359571" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Birds/anatomy & histology/*physiology ; Body Size ; Chiroptera/anatomy & histology/*physiology ; Flight, Animal/*physiology ; Insects/anatomy & histology/*physiology ; Models, Biological ; Motion ; Movement ; Nervous System Physiological Phenomena ; Rotation ; Torque ; Wings, Animal/anatomy & histology/*physiology
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  • 26
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    A periplasmic reducing system protects single cysteine residues from oxidation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: The thiol group of the amino acid cysteine can be modified to regulate protein activity. The Escherichia coli periplasm is an oxidizing environment in which most cysteine residues are involved in disulfide bonds. However, many periplasmic proteins contain single cysteine residues, which are vulnerable to oxidation to sulfenic acids and then irreversibly modified to sulfinic and sulfonic acids. We discovered that DsbG and DsbC, two thioredoxin-related proteins, control the global sulfenic acid content of the periplasm and protect single cysteine residues from oxidation. DsbG interacts with the YbiS protein and, along with DsbC, regulates oxidation of its catalytic cysteine residue. Thus, a potentially widespread mechanism controls sulfenic acid modification in the cellular environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Depuydt, Matthieu -- Leonard, Stephen E -- Vertommen, Didier -- Denoncin, Katleen -- Morsomme, Pierre -- Wahni, Khadija -- Messens, Joris -- Carroll, Kate S -- Collet, Jean-Francois -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1109-11. doi: 10.1126/science.1179557.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉de Duve Institute, Universite catholique de Louvain, B-1200 Brussels, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965429" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Cysteine/chemistry/*metabolism ; Disulfides/chemistry/metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Models, Biological ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidoreductases/chemistry/genetics/*metabolism ; Periplasm/*metabolism ; Periplasmic Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Protein Disulfide-Isomerases/chemistry/genetics/*metabolism ; Proteomics ; Substrate Specificity ; Sulfenic Acids/metabolism
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    Axon regeneration requires a conserved MAP kinase pathway (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-24
    Description: Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. The failure to regenerate in some cases is due to a lack of activation of cell-intrinsic regeneration pathways. These pathways might be targeted for the development of therapies that can restore neuron function after injury or disease. Here, we show that the DLK-1 mitogen-activated protein (MAP) kinase pathway is essential for regeneration in Caenorhabditis elegans motor neurons. Loss of this pathway eliminates regeneration, whereas activating it improves regeneration. Further, these proteins also regulate the later step of growth cone migration. We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729122/" 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/PMC2729122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammarlund, Marc -- Nix, Paola -- Hauth, Linda -- Jorgensen, Erik M -- Bastiani, Michael -- 1R21NS060275/NS/NINDS NIH HHS/ -- NS034307/NS/NINDS NIH HHS/ -- R21 NS060275-02/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):802-6. doi: 10.1126/science.1165527. Epub 2009 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112-0840, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164707" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Axons/*physiology/ultrastructure ; Axotomy ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Growth Cones/physiology ; MAP Kinase Kinase 4/genetics/metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Models, Biological ; Motor Neurons/*physiology ; Mutation ; Nerve Regeneration/physiology ; RNA Interference ; gamma-Aminobutyric Acid/metabolism
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    Structural insight into nascent polypeptide chain-mediated translational stalling (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-26
    Description: Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation of the upstream TnaC leader peptide, a process for which interactions between the TnaC nascent chain and the ribosomal exit tunnel are critical. We determined a 5.8 angstrom-resolution cryo-electron microscopy and single-particle reconstruction of a ribosome stalled during translation of the tnaC leader gene. The nascent chain was extended within the exit tunnel, making contacts with ribosomal components at distinct sites. Upon stalling, two conserved residues within the peptidyltransferase center adopted conformations that preclude binding of release factors. We propose a model whereby interactions within the tunnel are relayed to the peptidyltransferase center to inhibit translation. Moreover, we show that nascent chains adopt distinct conformations within the ribosomal exit tunnel.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920484/" 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/PMC2920484/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seidelt, Birgit -- Innis, C Axel -- Wilson, Daniel N -- Gartmann, Marco -- Armache, Jean-Paul -- Villa, Elizabeth -- Trabuco, Leonardo G -- Becker, Thomas -- Mielke, Thorsten -- Schulten, Klaus -- Steitz, Thomas A -- Beckmann, Roland -- GM022778/GM/NIGMS NIH HHS/ -- P41 RR005969/RR/NCRR NIH HHS/ -- P41 RR005969-19/RR/NCRR NIH HHS/ -- P41-RR05969/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1412-5. doi: 10.1126/science.1177662. Epub 2009 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center and Center for Integrated Protein Science Munich (CIPSM), Department for Chemistry and Biochemistry, University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933110" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Escherichia coli/*genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/*metabolism/ultrastructure ; Gene Expression Regulation, Bacterial ; Image Processing, Computer-Assisted ; Models, Biological ; Models, Molecular ; Operon ; Peptidyl Transferases/metabolism ; *Protein Biosynthesis ; Protein Conformation ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribosomal Proteins/chemistry/metabolism/ultrastructure ; Ribosomes/*metabolism/ultrastructure ; Tryptophanase/biosynthesis/*genetics
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    Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-03
    Description: Intraspecific chemical communication is mediated by signals called pheromones. Caenorhabditis elegans secretes a mixture of small molecules (collectively termed dauer pheromone) that regulates entry into the alternate dauer larval stage and also modulates adult behavior via as yet unknown receptors. Here, we identify two heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) that mediate dauer formation in response to a subset of dauer pheromone components. The SRBC-64 and SRBC-66 GPCRs are members of the large Caenorhabditis-specific SRBC subfamily and are expressed in the ASK chemosensory neurons, which are required for pheromone-induced dauer formation. Expression of both, but not each receptor alone, confers pheromone-mediated effects on heterologous cells. Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448937/" 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/PMC4448937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kyuhyung -- Sato, Koji -- Shibuya, Mayumi -- Zeiger, Danna M -- Butcher, Rebecca A -- Ragains, Justin R -- Clardy, Jon -- Touhara, Kazushige -- Sengupta, Piali -- F32 GM077943/GM/NIGMS NIH HHS/ -- P30 NS045713/NS/NINDS NIH HHS/ -- P30 NS45713/NS/NINDS NIH HHS/ -- R01 CA024487/CA/NCI NIH HHS/ -- R01 CA24487/CA/NCI NIH HHS/ -- R01 GM056223/GM/NIGMS NIH HHS/ -- R01 GM56223/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):994-8. doi: 10.1126/science.1176331. Epub 2009 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Calcium/metabolism ; Cell Line ; Chemoreceptor Cells/metabolism ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/physiology ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; Hexoses/chemistry/physiology ; Humans ; Mutation ; Pheromones/*physiology ; Receptors, G-Protein-Coupled ; Reproduction ; Signal Transduction ; Transfection
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    p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells affected by radiation to cause the GI syndrome are derived from the epithelium or endothelium and whether the target cells die by apoptosis or other mechanisms are controversial issues. Studying mouse models, we found that selective deletion of the proapoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after sub-total-body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not from endothelial cells, sensitized irradiated mice to the GI syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the GI syndrome after irradiation. These results suggest that the GI syndrome is caused by the death of GI epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897160/" 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/PMC2897160/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirsch, David G -- Santiago, Philip M -- di Tomaso, Emmanuelle -- Sullivan, Julie M -- Hou, Wu-Shiun -- Dayton, Talya -- Jeffords, Laura B -- Sodha, Pooja -- Mercer, Kim L -- Cohen, Rhianna -- Takeuchi, Osamu -- Korsmeyer, Stanley J -- Bronson, Roderick T -- Kim, Carla F -- Haigis, Kevin M -- Jain, Rakesh K -- Jacks, Tyler -- K08 CA 114176/CA/NCI NIH HHS/ -- K08 CA114176/CA/NCI NIH HHS/ -- K08 CA114176-05/CA/NCI NIH HHS/ -- P01 CA080124/CA/NCI NIH HHS/ -- P01 CA080124-01A1/CA/NCI NIH HHS/ -- P01 CA80124/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30 CA014051-38/CA/NCI NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- RC1 AI078521/AI/NIAID NIH HHS/ -- RC1 AI078521-01/AI/NIAID NIH HHS/ -- RC1-AI078521/AI/NIAID NIH HHS/ -- U19-AI06775/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 29;327(5965):593-6. doi: 10.1126/science.1166202. Epub 2009 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019247" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Death ; Epithelial Cells/cytology/physiology/radiation effects ; Gamma Rays/*adverse effects ; Gene Deletion ; Genes, p53 ; Intestinal Diseases/etiology/pathology/*physiopathology ; Intestinal Mucosa/pathology/physiopathology/*radiation effects ; Intestine, Small/pathology/physiopathology/*radiation effects ; Mesoderm/cytology ; Mice ; Mice, Transgenic ; Models, Biological ; Radiation Dosage ; Radiation Injuries/etiology/pathology/*physiopathology ; Tumor Suppressor Protein p53/*physiology ; bcl-2 Homologous Antagonist-Killer Protein/genetics/metabolism ; bcl-2-Associated X Protein/genetics/metabolism
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    Species response to environmental change: impacts of food web interactions and evolution (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-07
    Description: How environmental change affects species abundances depends on both the food web within which species interact and their potential to evolve. Using field experiments, we investigated both ecological and evolutionary responses of pea aphids (Acyrthosiphon pisum), a common agricultural pest, to increased frequency of episodic heat shocks. One predator species ameliorated the decrease in aphid population growth with increasing heat shocks, whereas a second predator did not, with this contrast caused by behavioral differences between predators. We also compared aphid strains with stably inherited differences in heat tolerance caused by bacterial endosymbionts and showed the potential for rapid evolution for heat-shock tolerance. Our results illustrate how ecological and evolutionary complexities should be incorporated into predictions of the consequences of environmental change for species' populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harmon, Jason P -- Moran, Nancy A -- Ives, Anthony R -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1347-50. doi: 10.1126/science.1167396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Wisconsin, Madison, WI 53706, USA. jharmon@wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19265021" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aphids/genetics/microbiology/*physiology ; Beetles/*physiology ; Biological Evolution ; Buchnera/genetics/physiology ; *Ecosystem ; *Food Chain ; *Hot Temperature ; Models, Biological ; Population Density ; Population Dynamics ; Population Growth ; Predatory Behavior ; Symbiosis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Wingbeat time and the scaling of passive rotational damping in flapping flight (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: Flying animals exhibit remarkable capabilities for both generating maneuvers and stabilizing their course and orientation after perturbation. Here we show that flapping fliers ranging in size from fruit flies to large birds benefit from substantial damping of angular velocity through a passive mechanism termed flapping counter-torque (FCT). Our FCT model predicts that isometrically scaled animals experience similar damping on a per-wingbeat time scale, resulting in similar turning dynamics in wingbeat time regardless of body size. The model also shows how animals may simultaneously specialize in both maneuverability and stability (at the cost of efficiency) and provides a framework for linking morphology, wing kinematics, maneuverability, and flight dynamics across a wide range of flying animals spanning insects, bats, and birds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hedrick, Tyson L -- Cheng, Bo -- Deng, Xinyan -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):252-5. doi: 10.1126/science.1168431.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. thedrick@bio.unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359586" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Birds/anatomy & histology/*physiology ; Body Size ; Chiroptera/anatomy & histology/*physiology ; Flight, Animal ; Insects/anatomy & histology/*physiology ; Mathematical Concepts ; Models, Biological ; Motion ; Movement ; Nervous System Physiological Phenomena ; Rotation ; Torque ; Wings, Animal/anatomy & histology/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-17
    Description: Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in the mammalian central nervous system (CNS). It is involved in multiple physiological functions and is a target for treatment of various CNS disorders, including schizophrenia. We report that Norbin, a neuron-specific protein, physically interacts with mGluR5 in vivo, increases the cell surface localization of the receptor, and positively regulates mGluR5 signaling. Genetic deletion of Norbin attenuates mGluR5-dependent stable changes in synaptic function measured as long-term depression or long-term potentiation of synaptic transmission in the hippocampus. As with mGluR5 knockout mice or mice treated with mGluR5-selective antagonists, Norbin knockout mice showed a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations both in sensorimotor gating and psychotomimetic-induced locomotor activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796550/" 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/PMC2796550/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Hong -- Westin, Linda -- Nong, Yi -- Birnbaum, Shari -- Bendor, Jacob -- Brismar, Hjalmar -- Nestler, Eric -- Aperia, Anita -- Flajolet, Marc -- Greengard, Paul -- DA 10044/DA/NIDA NIH HHS/ -- MH074866/MH/NIMH NIH HHS/ -- MH66172/MH/NIMH NIH HHS/ -- P01 DA010044/DA/NIDA NIH HHS/ -- P01 DA010044-020002/DA/NIDA NIH HHS/ -- P01 DA010044-030002/DA/NIDA NIH HHS/ -- P01 DA010044-04/DA/NIDA NIH HHS/ -- P01 DA010044-040002/DA/NIDA NIH HHS/ -- P01 DA010044-05/DA/NIDA NIH HHS/ -- P01 DA010044-050002/DA/NIDA NIH HHS/ -- P01 DA010044-06/DA/NIDA NIH HHS/ -- P01 DA010044-060002/DA/NIDA NIH HHS/ -- P01 DA010044-07/DA/NIDA NIH HHS/ -- P01 DA010044-070002/DA/NIDA NIH HHS/ -- P01 DA010044-08/DA/NIDA NIH HHS/ -- P01 DA010044-080002/DA/NIDA NIH HHS/ -- P01 DA010044-09/DA/NIDA NIH HHS/ -- P01 DA010044-090002/DA/NIDA NIH HHS/ -- P01 DA010044-10/DA/NIDA NIH HHS/ -- P01 DA010044-100002/DA/NIDA NIH HHS/ -- P01 DA010044-11/DA/NIDA NIH HHS/ -- P01 DA010044-110005/DA/NIDA NIH HHS/ -- P01 DA010044-12/DA/NIDA NIH HHS/ -- P01 DA010044-120005/DA/NIDA NIH HHS/ -- P01 DA010044-129002/DA/NIDA NIH HHS/ -- P01 DA010044-13/DA/NIDA NIH HHS/ -- P01 DA010044-130005/DA/NIDA NIH HHS/ -- P01 DA010044-139002/DA/NIDA NIH HHS/ -- P01 DA010044-14/DA/NIDA NIH HHS/ -- P01 DA010044-140005/DA/NIDA NIH HHS/ -- P01 DA010044-149002/DA/NIDA NIH HHS/ -- P01 DA010044-14S1/DA/NIDA NIH HHS/ -- P01 DA010044-14S10005/DA/NIDA NIH HHS/ -- P01 DA010044-14S19002/DA/NIDA NIH HHS/ -- P50 MH074866/MH/NIMH NIH HHS/ -- P50 MH074866-010001/MH/NIMH NIH HHS/ -- P50 MH074866-020001/MH/NIMH NIH HHS/ -- P50 MH074866-030001/MH/NIMH NIH HHS/ -- P50 MH074866-039001/MH/NIMH NIH HHS/ -- P50 MH074866-040001/MH/NIMH NIH HHS/ -- P50 MH074866-050001/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1554-7. doi: 10.1126/science.1178496.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007903" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism ; Calcium/metabolism ; Calcium Signaling ; Cell Line ; Cell Membrane/metabolism ; Humans ; Mice ; Mice, Knockout ; Motor Activity ; Nerve Tissue Proteins/genetics/*metabolism ; Neuronal Plasticity ; Protein Binding ; Rats ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/genetics/*metabolism ; Reflex, Startle ; Schizophrenia/physiopathology ; *Signal Transduction ; Synaptic Transmission ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Human induced pluripotent stem cells free of vector and transgene sequences (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-28
    Description: Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. We describe the derivation of human iPS cells with the use of nonintegrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. These results demonstrate that reprogramming human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors and removes one obstacle to the clinical application of human iPS cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758053/" 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/PMC2758053/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Junying -- Hu, Kejin -- Smuga-Otto, Kim -- Tian, Shulan -- Stewart, Ron -- Slukvin, Igor I -- Thomson, James A -- P01 GM081629/GM/NIGMS NIH HHS/ -- P01 GM081629-01A1/GM/NIGMS NIH HHS/ -- P51 RR000167/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):797-801. doi: 10.1126/science.1172482. Epub 2009 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Morgridge Institute for Research, Madison, WI 53707-7365, USA. jyyu2008@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325077" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cell Shape ; *Cellular Reprogramming ; Clone Cells ; Embryonic Stem Cells/cytology ; Epstein-Barr Virus Nuclear Antigens/genetics ; Fibroblasts ; Gene Expression Profiling ; *Genetic Vectors ; Humans ; *Plasmids ; Pluripotent Stem Cells/*cytology/metabolism/transplantation ; Transcription Factors/genetics ; Transfection ; *Transgenes
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-21
    Description: Embryogenesis depends on self-regulatory interactions between spatially separated signaling centers, but few of these are well understood. Limb development is regulated by epithelial-mesenchymal (e-m) feedback loops between sonic hedgehog (SHH) and fibroblast growth factor (FGF) signaling involving the bone morphogenetic protein (BMP) antagonist Gremlin1 (GREM1). By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates and SHH then propagates e-m feedback signaling through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/GREM1 module to the slower SHH/GREM1/FGF e-m feedback loop. This self-regulatory signaling network results in robust regulation of distal limb development that is able to compensate for variations by interconnectivity among the three signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benazet, Jean-Denis -- Bischofberger, Mirko -- Tiecke, Eva -- Goncalves, Alexandre -- Martin, James F -- Zuniga, Aimee -- Naef, Felix -- Zeller, Rolf -- 2R01DE12324-12/DE/NIDCR NIH HHS/ -- R01DE16329/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1050-3. doi: 10.1126/science.1168755.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229034" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; Bone Morphogenetic Protein 4/genetics/metabolism ; Epithelium/embryology/metabolism ; *Feedback, Physiological ; Fibroblast Growth Factors/genetics/metabolism ; Forelimb/*embryology ; Hedgehog Proteins/genetics/metabolism ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Limb Buds/embryology/metabolism ; Mesoderm/metabolism ; Mice ; Models, Biological ; *Signal Transduction ; Toes/embryology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Competitive interactions between cells: death, growth, and geography (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-27
    Description: Competitive interactions between cells are the basis of many homeostatic processes in biology. Some of the best-described cases of competition between cells occur in Drosophila: cell competition, whereby somatic cells within a growing epithelium compete with one another for contribution to the adult, and stem cell competition, in which germline or somatic stem cells vie for residency in the niche. Both types of competition are conserved physiological processes, with much to tell us about how cellular neighborhoods influence cell behavior, and have importance to stem cell biology, regeneration and transplantation, and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736143/" 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/PMC2736143/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Laura A -- GMO78464/PHS HHS/ -- HD42770/HD/NICHD NIH HHS/ -- R01 GM078464/GM/NIGMS NIH HHS/ -- R01 GM078464-01/GM/NIGMS NIH HHS/ -- R01 GM078464-02/GM/NIGMS NIH HHS/ -- R01 GM078464-03/GM/NIGMS NIH HHS/ -- R01 HD042770/HD/NICHD NIH HHS/ -- R01 HD042770-02/HD/NICHD NIH HHS/ -- R01 HD042770-03/HD/NICHD NIH HHS/ -- R01 HD042770-04/HD/NICHD NIH HHS/ -- R01 HD042770-05/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1679-82. doi: 10.1126/science.1163862.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. lj180@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556501" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; *Cell Communication ; *Cell Physiological Phenomena ; *Cell Proliferation ; Drosophila/cytology ; Homeostasis ; Models, Biological ; Signal Transduction ; Stem Cell Niche/physiology ; Stem Cells/cytology/*physiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-17
    Description: Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2- and ephrin-B1-expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling revealed that signaling between mixed EphB2- and ephrin-B1-expressing cells is asymmetric and that the distinct cell types use different tyrosine kinases and targets to process signals induced by cell-cell contact. We provide systems- and cell-specific network models of contact-initiated signaling between two distinct cell types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jorgensen, Claus -- Sherman, Andrew -- Chen, Ginny I -- Pasculescu, Adrian -- Poliakov, Alexei -- Hsiung, Marilyn -- Larsen, Brett -- Wilkinson, David G -- Linding, Rune -- Pawson, Tony -- MC_U117532048/Medical Research Council/United Kingdom -- MOP-6849/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1502-9. doi: 10.1126/science.1176615.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute (SLRI), Mount Sinai Hospital, Toronto M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007894" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Algorithms ; Cell Line ; Ephrin-B1/genetics/*metabolism ; Humans ; Ligands ; Mass Spectrometry ; Models, Biological ; PDZ Domains ; Phosphorylation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein-Tyrosine Kinases/metabolism ; Proteomics ; RNA, Small Interfering ; Receptor, EphB2/genetics/*metabolism ; *Signal Transduction ; Tyrosine/metabolism ; src Homology Domains
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The bacterial species challenge: making sense of genetic and ecological diversity (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-02-07
    Description: The Bacteria and Archaea are the most genetically diverse superkingdoms of life, and techniques for exploring that diversity are only just becoming widespread. Taxonomists classify these organisms into species in much the same way as they classify eukaryotes, but differences in their biology-including horizontal gene transfer between distantly related taxa and variable rates of homologous recombination-mean that we still do not understand what a bacterial species is. This is not merely a semantic question; evolutionary theory should be able to explain why species exist at all levels of the tree of life, and we need to be able to define species for practical applications in industry, agriculture, and medicine. Recent studies have emphasized the need to combine genetic diversity and distinct ecology in an attempt to define species in a coherent and convincing fashion. The resulting data may help to discriminate among the many theories of prokaryotic species that have been produced to date.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fraser, Christophe -- Alm, Eric J -- Polz, Martin F -- Spratt, Brian G -- Hanage, William P -- 089472/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):741-6. doi: 10.1126/science.1159388.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Disease Epidemiology, Imperial College London, London W2 1PG, UK. c.fraser@imperial.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197054" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*classification/*genetics ; *Biodiversity ; Biological Evolution ; *Ecosystem ; Extinction, Biological ; Genes, Bacterial ; *Genetic Speciation ; *Genetic Variation ; Models, Biological ; Models, Genetic ; Recombination, Genetic ; Selection, Genetic
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    Nuclear hormone receptor regulation of microRNAs controls developmental progression (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-04
    Description: In response to small-molecule signals such as retinoids or steroids, nuclear receptors activate gene expression to regulate development in different tissues. MicroRNAs turn off target gene expression within cells by binding complementary regions in messenger RNA transcripts, and they have been broadly implicated in development and disease. Here we show that the Caenorhabditis elegans nuclear receptor DAF-12 and its steroidal ligand directly activate promoters of let-7 microRNA family members to down-regulate the microRNA target hbl-1, which drives progression of epidermal stem cells from second to third larval stage patterns of cell division. Conversely, the receptor without the ligand represses microRNA expression during developmental arrest. These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757405/" 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/PMC2757405/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bethke, Axel -- Fielenbach, Nicole -- Wang, Zhu -- Mangelsdorf, David J -- Antebi, Adam -- GM077201/GM/NIGMS NIH HHS/ -- R01 GM077201/GM/NIGMS NIH HHS/ -- R01 GM077201-03/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):95-8. doi: 10.1126/science.1164899.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*growth & development/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Line ; Cholestenes/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Down-Regulation ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Humans ; Ligands ; MicroRNAs/*genetics ; Mutation ; RNA, Helminth/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism ; Response Elements ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transfection ; Up-Regulation
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    Recombination of retrotransposon and exogenous RNA virus results in nonretroviral cDNA integration (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-20
    Description: Retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex DNA viruses. In contrast, RNA viruses were believed not to integrate into the host's genome under any circumstances. We found that illegitimate recombination between an exogenous nonretroviral RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA. The resulting complementary DNA was integrated into the host's genome with an IAP element. Thus, RNA viruses should be closely scrutinized for any capacity to interact with endogenous retroviral elements before their approval for therapeutic use in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geuking, Markus B -- Weber, Jacqueline -- Dewannieux, Marie -- Gorelik, Elieser -- Heidmann, Thierry -- Hengartner, Hans -- Zinkernagel, Rolf M -- Hangartner, Lars -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):393-6. doi: 10.1126/science.1167375.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. geuking@mcmaster.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arenaviridae Infections/virology ; Base Sequence ; Cell Line ; DNA, Complementary/*genetics ; Genes, Intracisternal A-Particle/*genetics ; Glycoproteins/genetics ; Humans ; Lymphocytic choriomeningitis virus/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Viral/*genetics ; *Recombination, Genetic ; *Reverse Transcription ; Transfection ; Viral Proteins/genetics ; *Virus Integration
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    HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-10
    Description: The mammalian innate immune system is activated by foreign nucleic acids. Detection of double-stranded DNA (dsDNA) in the cytoplasm triggers characteristic antiviral responses and macrophage cell death. Cytoplasmic dsDNA rapidly activated caspase 3 and caspase 1 in bone marrow-derived macrophages. We identified the HIN-200 family member and candidate lupus susceptibility factor, p202, as a dsDNA binding protein that bound stably and rapidly to transfected DNA. Knockdown studies showed p202 to be an inhibitor of DNA-induced caspase activation. Conversely, the related pyrin domain-containing HIN-200 factor, AIM2 (p210), was required for caspase activation by cytoplasmic dsDNA. This work indicates that HIN-200 proteins can act as pattern recognition receptors mediating responses to cytoplasmic dsDNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Tara L -- Idris, Adi -- Dunn, Jasmyn A -- Kelly, Greg M -- Burnton, Carol M -- Hodgson, Samantha -- Hardy, Lani L -- Garceau, Valerie -- Sweet, Matthew J -- Ross, Ian L -- Hume, David A -- Stacey, Katryn J -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1057-60. doi: 10.1126/science.1169841. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Queensland, Institute for Molecular Bioscience, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131592" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspase 1/*metabolism ; Caspase 3/*metabolism ; Cell Line ; Cytoplasm/*metabolism ; DNA/immunology/*metabolism ; DNA-Binding Proteins/isolation & purification/metabolism ; Enzyme Activation ; Immunity, Innate ; Intracellular Signaling Peptides and Proteins/chemistry/genetics/isolation & ; purification/*metabolism ; Macrophages/immunology/*metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Inbred Strains ; RNA, Small Interfering ; Receptors, Pattern Recognition/*metabolism ; Symporters ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Origins. On the origin of sexual reproduction (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmer, Carl -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1254-6. doi: 10.1126/science.324_1254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498143" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Female ; Host-Parasite Interactions ; Humans ; Male ; Mating Preference, Animal ; *Meiosis ; Models, Biological ; Mutation ; Recombination, Genetic ; *Reproduction ; *Sex
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    Comment on "Energy uptake and allocation during ontogeny" (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-05
    Description: We demonstrate that the model of energy allocation during ontogeny of Hou et al. (Reports, 31 October 2008, p. 736) fails to account for the observed elevation of metabolic rate in growing organisms compared with similarly sized adults of different species. The basic model assumptions of the three-quarter power scaling for resting metabolism and constancy of the mass-specific maintenance metabolism need to be reassessed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Makarieva, Anastassia M -- Gorshkov, Victor G -- Li, Bai-Lian -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1206; author reply 1206. doi: 10.1126/science.1171303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Theoretical Physics Division, Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg, Russia. elba@peterlink.ru〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729641" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Metabolism ; Birds/growth & development/*metabolism ; Body Weight ; *Energy Metabolism ; *Growth ; Mammals/growth & development/*metabolism ; Models, Biological ; Species Specificity
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    Breaking the code of DNA binding specificity of TAL-type III effectors (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-11-26
    Description: The pathogenicity of many bacteria depends on the injection of effector proteins via type III secretion into eukaryotic cells in order to manipulate cellular processes. TAL (transcription activator-like) effectors from plant pathogenic Xanthomonas are important virulence factors that act as transcriptional activators in the plant cell nucleus, where they directly bind to DNA via a central domain of tandem repeats. Here, we show how target DNA specificity of TAL effectors is encoded. Two hypervariable amino acid residues in each repeat recognize one base pair in the target DNA. Recognition sequences of TAL effectors were predicted and experimentally confirmed. The modular protein architecture enabled the construction of artificial effectors with new specificities. Our study describes the functionality of a distinct type of DNA binding domain and allows the design of DNA binding domains for biotechnology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boch, Jens -- Scholze, Heidi -- Schornack, Sebastian -- Landgraf, Angelika -- Hahn, Simone -- Kay, Sabine -- Lahaye, Thomas -- Nickstadt, Anja -- Bonas, Ulla -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1509-12. doi: 10.1126/science.1178811. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Institute of Biology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 10, D-06099 Halle (Saale) Germany. jens.boch@genetik.uni-halle.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933107" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/genetics ; Bacterial Proteins/chemistry/metabolism ; Base Pairing ; Base Sequence ; Biotechnology ; Capsicum/genetics ; DNA, Plant/*chemistry/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Genes, Plant ; Models, Biological ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding ; Repetitive Sequences, Amino Acid ; Tobacco/genetics ; Transcription Factors/chemistry/metabolism ; *Transcriptional Activation ; Xanthomonas/*metabolism/pathogenicity
    Print ISSN: 0036-8075
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    Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6 (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-03
    Description: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516382/" 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/PMC4516382/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vance, Caroline -- Rogelj, Boris -- Hortobagyi, Tibor -- De Vos, Kurt J -- Nishimura, Agnes Lumi -- Sreedharan, Jemeen -- Hu, Xun -- Smith, Bradley -- Ruddy, Deborah -- Wright, Paul -- Ganesalingam, Jeban -- Williams, Kelly L -- Tripathi, Vineeta -- Al-Saraj, Safa -- Al-Chalabi, Ammar -- Leigh, P Nigel -- Blair, Ian P -- Nicholson, Garth -- de Belleroche, Jackie -- Gallo, Jean-Marc -- Miller, Christopher C -- Shaw, Christopher E -- 078662/Wellcome Trust/United Kingdom -- G0300329/Medical Research Council/United Kingdom -- G0500289/Medical Research Council/United Kingdom -- G0501573/Medical Research Council/United Kingdom -- G0600676/Medical Research Council/United Kingdom -- G0600974/Medical Research Council/United Kingdom -- G0900688/Medical Research Council/United Kingdom -- MC_G1000733/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1208-11. doi: 10.1126/science.1165942.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251628" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Amino Acid Sequence ; Amyotrophic Lateral Sclerosis/*genetics/metabolism/pathology ; Animals ; Brain/pathology ; Cell Line ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/analysis/genetics/metabolism ; Female ; Humans ; Inclusion Bodies/chemistry/ultrastructure ; Male ; Molecular Sequence Data ; Motor Neurons/metabolism ; *Mutation, Missense ; Pedigree ; RNA-Binding Protein FUS/analysis/*genetics/*metabolism ; Rats ; Spinal Cord/pathology ; Transfection
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    Cell signaling in space and time: where proteins come together and when they're apart (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: Signal transduction can be defined as the coordinated relay of messages derived from extracellular cues to intracellular effectors. More simply put, information received on the cell surface is processed across the plasma membrane and transmitted to intracellular targets. This requires that the activators, effectors, enzymes, and substrates that respond to cellular signals come together when they need to.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041271/" 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/PMC3041271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, John D -- Pawson, Tony -- 57793/Canadian Institutes of Health Research/Canada -- 6849/Canadian Institutes of Health Research/Canada -- GM48231/GM/NIGMS NIH HHS/ -- R37 GM048231/GM/NIGMS NIH HHS/ -- R37 GM048231-19/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1220-4. doi: 10.1126/science.1175668.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Howard Hughes Medical Institute, Box 357750, University of Washington School of Medicine, Seattle, WA 98195, USA. scottjdw@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965465" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Membrane/*metabolism ; Cell Nucleus/*metabolism ; Cytoplasm/*metabolism ; Enzymes/metabolism ; Humans ; MAP Kinase Signaling System ; Models, Biological ; Multiprotein Complexes/metabolism ; Protein Interaction Domains and Motifs ; Proteins/*metabolism ; *Signal Transduction ; Time Factors ; Transcription, Genetic
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    A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-17
    Description: beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673--〉valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728497/" 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/PMC2728497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Fede, Giuseppe -- Catania, Marcella -- Morbin, Michela -- Rossi, Giacomina -- Suardi, Silvia -- Mazzoleni, Giulia -- Merlin, Marco -- Giovagnoli, Anna Rita -- Prioni, Sara -- Erbetta, Alessandra -- Falcone, Chiara -- Gobbi, Marco -- Colombo, Laura -- Bastone, Antonio -- Beeg, Marten -- Manzoni, Claudia -- Francescucci, Bruna -- Spagnoli, Alberto -- Cantu, Laura -- Del Favero, Elena -- Levy, Efrat -- Salmona, Mario -- Tagliavini, Fabrizio -- NS42029/NS/NINDS NIH HHS/ -- R01 NS042029/NS/NINDS NIH HHS/ -- R01 NS042029-01A1/NS/NINDS NIH HHS/ -- R01 NS042029-02/NS/NINDS NIH HHS/ -- R01 NS042029-03/NS/NINDS NIH HHS/ -- R01 NS042029-04/NS/NINDS NIH HHS/ -- R01 NS042029-05/NS/NINDS NIH HHS/ -- R01 NS042029-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1473-7. doi: 10.1126/science.1168979.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurology and Neuropathology, "Carlo Besta" National Neurological Institute, 20133 Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286555" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alzheimer Disease/*genetics/metabolism ; Amino Acid Substitution ; Amyloid/*metabolism ; Amyloid beta-Peptides/chemistry/metabolism ; Amyloid beta-Protein Precursor/*genetics/metabolism ; Cell Line ; Dementia/*genetics/metabolism ; Female ; *Genes, Recessive ; Heterozygote ; Homozygote ; Humans ; Kinetics ; Male ; *Mutation ; Pedigree ; Peptide Fragments/chemistry/metabolism ; Protein Binding ; Transfection
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    Evidence for ecological speciation and its alternative (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-02-07
    Description: Natural selection commonly drives the origin of species, as Darwin initially claimed. Mechanisms of speciation by selection fall into two broad categories: ecological and mutation-order. Under ecological speciation, divergence is driven by divergent natural selection between environments, whereas under mutation-order speciation, divergence occurs when different mutations arise and are fixed in separate populations adapting to similar selection pressures. Tests of parallel evolution of reproductive isolation, trait-based assortative mating, and reproductive isolation by active selection have demonstrated that ecological speciation is a common means by which new species arise. Evidence for mutation-order speciation by natural selection is more limited and has been best documented by instances of reproductive isolation resulting from intragenomic conflict. However, we still have not identified all aspects of selection, and identifying the underlying genes for reproductive isolation remains challenging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schluter, Dolph -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):737-41. doi: 10.1126/science.1160006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biodiversity Research Centre and Zoology Department, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. schluter@zoology.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197053" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; Biological Evolution ; *Ecosystem ; Genes ; *Genetic Speciation ; Genetic Variation ; Models, Biological ; Models, Genetic ; *Mutation ; Phenotype ; Plants/genetics ; Quantitative Trait Loci ; Reproduction ; *Selection, Genetic
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    The dynamics of phenotypic change and the shrinking sheep of St. Kilda (2009)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2009-07-04
    Description: Environmental change, including climate change, can cause rapid phenotypic change via both ecological and evolutionary processes. Because ecological and evolutionary dynamics are intimately linked, a major challenge is to identify their relative roles. We exactly decomposed the change in mean body weight in a free-living population of Soay sheep into all the processes that contribute to change. Ecological processes contribute most, with selection--the underpinning of adaptive evolution--explaining little of the observed phenotypic trend. Our results enable us to explain why selection has so little effect even though weight is heritable, and why environmental change has caused a decline in the body size of Soay sheep.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ozgul, Arpat -- Tuljapurkar, Shripad -- Benton, Tim G -- Pemberton, Josephine M -- Clutton-Brock, Tim H -- Coulson, Tim -- P01 AG022500/AG/NIA NIH HHS/ -- P01/AG/22500/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):464-7. doi: 10.1126/science.1173668. Epub 2009 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berkshire SL5 7PY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19574350" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Biological ; Animals ; *Biological Evolution ; *Body Size ; Body Weight ; Ecosystem ; *Environment ; Female ; Male ; Models, Biological ; Phenotype ; Sheep, Domestic/*anatomy & histology/growth & development
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    Auxin-dependent patterning and gamete specification in the Arabidopsis female gametophyte (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-06
    Description: The female reproductive unit of flowering plants, the haploid female gametophyte, is highly reduced relative to other land plants. We show that patterning of the Arabidopsis female gametophyte depends on an asymmetric distribution of the hormone auxin during its syncitial development. Furthermore, this auxin gradient is correlated with location-specific auxin biosynthesis, rather than auxin efflux that directs patterning in the diploid sporophytic tissues comprising the rest of the plant. Manipulation of auxin responses or synthesis induces switching of gametic and nongametic cell identities and specialized nonreproductive cells to exhibit attributes presumptively lost during angiosperm evolution. These findings may account for the unique egg cell specification characteristic of angiosperms and the formation of seeds with single diploid embryos while containing endosperm that can have variable numbers of parental haploid genomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pagnussat, Gabriela C -- Alandete-Saez, Monica -- Bowman, John L -- Sundaresan, Venkatesan -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1684-9. doi: 10.1126/science.1167324. Epub 2009 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant 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/19498110" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*cytology/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Biological Evolution ; Down-Regulation ; Flowers/*cytology/growth & development/metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; Germ Cells/*cytology/growth & development/metabolism ; Indoleacetic Acids/*metabolism ; Membrane Transport Proteins/genetics/metabolism ; MicroRNAs ; Mitosis ; Models, Biological ; Oxygenases/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Seeds/cytology ; Signal Transduction
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    Evolution. Dynamics of body size evolution (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-09-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Kaustuv -- New York, N.Y. -- Science. 2008 Sep 12;321(5895):1451-2. doi: 10.1126/science.1163097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Ecology, Behavior and Evolution, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. kroy@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787156" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Body Size ; Climate ; Ecosystem ; Extinction, Biological ; Greenhouse Effect ; Models, Biological ; Population Dynamics ; Stochastic Processes ; Temperature
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    ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-07-26
    Description: Membrane and secretory proteins cotranslationally enter and are folded in the endoplasmic reticulum (ER). Misfolded or unassembled proteins are discarded by a process known as ER-associated degradation (ERAD), which involves their retrotranslocation into the cytosol. ERAD substrates frequently contain disulfide bonds that must be cleaved before their retrotranslocation. Here, we found that an ER-resident protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ERAD through its physical and functional associations with EDEM (ER degradation-enhancing alpha-mannosidase-like protein) and an ER-resident chaperone BiP. Thus, ERdj5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ushioda, Ryo -- Hoseki, Jun -- Araki, Kazutaka -- Jansen, Gregor -- Thomas, David Y -- Nagata, Kazuhiro -- New York, N.Y. -- Science. 2008 Jul 25;321(5888):569-72. doi: 10.1126/science.1159293.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18653895" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Substitution ; Animals ; Cell Line ; Endoplasmic Reticulum/*metabolism ; Glutathione/metabolism ; HSP40 Heat-Shock Proteins/chemistry/genetics/*metabolism ; Heat-Shock Proteins/metabolism ; Humans ; Immunoglobulin J-Chains/chemistry/metabolism ; Membrane Proteins/metabolism ; Mice ; Molecular Chaperones/chemistry/genetics/*metabolism ; Mutation ; Oxidation-Reduction ; Protein Disulfide Reductase (Glutathione)/metabolism ; Protein Disulfide-Isomerases/metabolism ; Protein Folding ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism ; Transfection ; Two-Hybrid System Techniques ; alpha 1-Antitrypsin/chemistry/metabolism
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    Feedback loops shape cellular signals in space and time (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-10-18
    Description: Positive and negative feedback loops are common regulatory elements in biological signaling systems. We discuss core feedback motifs that have distinct roles in shaping signaling responses in space and time. We also discuss approaches to experimentally investigate feedback loops in signaling systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680159/" 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/PMC2680159/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brandman, Onn -- Meyer, Tobias -- R01 GM030179/GM/NIGMS NIH HHS/ -- R01 GM030179-25/GM/NIGMS NIH HHS/ -- R01 GM063702/GM/NIGMS NIH HHS/ -- R01 GM063702-06/GM/NIGMS NIH HHS/ -- R01GM030179/GM/NIGMS NIH HHS/ -- R01GM063702/GM/NIGMS NIH HHS/ -- R01MH064801/MH/NIMH NIH HHS/ -- R33 CA120732/CA/NCI NIH HHS/ -- R33 CA120732-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):390-5. doi: 10.1126/science.1160617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California-San Francisco and Howard Hughes Medical Institute, San Francisco, CA 94158, USA. Onn.Brandman@ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18927383" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; *Calcium Signaling ; Cell Membrane/metabolism ; Chemotaxis, Leukocyte ; Computer Simulation ; Endoplasmic Reticulum/metabolism ; *Feedback, Physiological ; Models, Biological ; Neutrophils/*metabolism/physiology ; Phosphatidylinositol 3-Kinases/*metabolism ; *Signal Transduction
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    Experimental evidence for spatial self-organization and its emergent effects in mussel bed ecosystems (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-11-01
    Description: Spatial self-organization is the main theoretical explanation for the global occurrence of regular or otherwise coherent spatial patterns in ecosystems. Using mussel beds as a model ecosystem, we provide an experimental demonstration of spatial self-organization. Under homogeneous laboratory conditions, mussels developed regular patterns, similar to those in the field. An individual-based model derived from our experiments showed that interactions between individuals explained the observed patterns. Furthermore, a field study showed that pattern formation affected ecosystem-level processes in terms of improved growth and resistance to wave action. Our results imply that spatial self-organization is an important determinant of the structure and functioning of ecosystems, and it needs to be considered in their conservation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van de Koppel, Johan -- Gascoigne, Joanna C -- Theraulaz, Guy -- Rietkerk, Max -- Mooij, Wolf M -- Herman, Peter M J -- D18866/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):739-42. doi: 10.1126/science.1163952.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Spatial Ecology Department, the Netherlands Institute of Ecology (NIOO-KNAW), Post Office Box 140, 4400 AC Yerseke, Netherlands. J.vandeKoppel@nioo.knaw.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974353" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomass ; Bivalvia/*physiology ; *Ecosystem ; Models, Biological ; Movement ; Population Dynamics ; Spatial Behavior ; Wales
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    Robust, tunable biological oscillations from interlinked positive and negative feedback loops (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-07-05
    Description: A simple negative feedback loop of interacting genes or proteins has the potential to generate sustained oscillations. However, many biological oscillators also have a positive feedback loop, raising the question of what advantages the extra loop imparts. Through computational studies, we show that it is generally difficult to adjust a negative feedback oscillator's frequency without compromising its amplitude, whereas with positive-plus-negative feedback, one can achieve a widely tunable frequency and near-constant amplitude. This tunability makes the latter design suitable for biological rhythms like heartbeats and cell cycles that need to provide a constant output over a range of frequencies. Positive-plus-negative oscillators also appear to be more robust and easier to evolve, rationalizing why they are found in contexts where an adjustable frequency is unimportant.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728800/" 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/PMC2728800/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Tony Yu-Chen -- Choi, Yoon Sup -- Ma, Wenzhe -- Pomerening, Joseph R -- Tang, Chao -- Ferrell, James E Jr -- GM61726/GM/NIGMS NIH HHS/ -- GM77544/GM/NIGMS NIH HHS/ -- R01 GM061276/GM/NIGMS NIH HHS/ -- R01 GM061276-06/GM/NIGMS NIH HHS/ -- R01 GM061276-07/GM/NIGMS NIH HHS/ -- R01 GM061276-08/GM/NIGMS NIH HHS/ -- R01 GM077544/GM/NIGMS NIH HHS/ -- R01 GM077544-01/GM/NIGMS NIH HHS/ -- R01 GM077544-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jul 4;321(5885):126-9. doi: 10.1126/science.1156951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18599789" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Anaphase-Promoting Complex-Cyclosome ; Animals ; *Biological Clocks ; Biological Evolution ; CDC2 Protein Kinase/*metabolism ; *Cell Cycle ; Cell Division ; Circadian Rhythm ; Cyclin B/biosynthesis/metabolism ; Embryo, Nonmammalian/cytology/metabolism ; *Feedback, Physiological ; Interphase ; Models, Biological ; Monte Carlo Method ; Ubiquitin-Protein Ligase Complexes/metabolism ; Xenopus Proteins/metabolism ; Xenopus laevis
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    Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-04-12
    Description: Cytidine deaminases of the APOBEC3 family all have specificity for single-stranded DNA, which may become exposed during replication or transcription of double-stranded DNA. Three human APOBEC3A (hA3A), hA3B, and hA3H genes are expressed in keratinocytes and skin, leading us to determine whether genetic editing of human papillomavirus (HPV) DNA occurred. In a study of HPV1a plantar warts and HPV16 precancerous cervical biopsies, hyperedited HPV1a and HPV16 genomes were found. Strictly analogous results were obtained from transfection experiments with HPV plasmid DNA and the three nuclear localized enzymes: hA3A, hA3C, and hA3H. Thus, stochastic or transient overexpression of APOBEC3 genes may expose the genome to a broad spectrum of mutations that could influence the development of tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vartanian, Jean-Pierre -- Guetard, Denise -- Henry, Michel -- Wain-Hobson, Simon -- New York, N.Y. -- Science. 2008 Apr 11;320(5873):230-3. doi: 10.1126/science.1153201.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Retrovirology Unit, Institut Pasteur, 28 Rue de Docteur Roux, 75724 Paris cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18403710" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cervix Uteri/virology ; Cytidine/metabolism ; Cytosine Deaminase/*metabolism ; DNA Mismatch Repair ; DNA, Viral/genetics/*metabolism ; Female ; Genome, Viral ; Human papillomavirus 16/*genetics ; Humans ; Mupapillomavirus/*genetics ; Mutation ; Papillomavirus Infections/enzymology/virology ; Precancerous Conditions/enzymology/*virology ; Transfection ; Uterine Cervical Neoplasms/enzymology/*virology ; Warts/enzymology/*virology
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    Molecular architecture of the "stressosome," a signal integration and transduction hub (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-10-04
    Description: A commonly used strategy by microorganisms to survive multiple stresses involves a signal transduction cascade that increases the expression of stress-responsive genes. Stress signals can be integrated by a multiprotein signaling hub that responds to various signals to effect a single outcome. We obtained a medium-resolution cryo-electron microscopy reconstruction of the 1.8-megadalton "stressosome" from Bacillus subtilis. Fitting known crystal structures of components into this reconstruction gave a pseudoatomic structure, which had a virus capsid-like core with sensory extensions. We suggest that the different sensory extensions respond to different signals, whereas the conserved domains in the core integrate the varied signals. The architecture of the stressosome provides the potential for cooperativity, suggesting that the response could be tuned dependent on the magnitude of chemophysical insult.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marles-Wright, Jon -- Grant, Tim -- Delumeau, Olivier -- van Duinen, Gijs -- Firbank, Susan J -- Lewis, Peter J -- Murray, James W -- Newman, Joseph A -- Quin, Maureen B -- Race, Paul R -- Rohou, Alexis -- Tichelaar, Willem -- van Heel, Marin -- Lewis, Richard J -- BB/D000521/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F001533/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 3;322(5898):92-6. doi: 10.1126/science.1159572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18832644" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus subtilis/*chemistry/metabolism/ultrastructure ; Bacterial Proteins/*chemistry/metabolism/ultrastructure ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Image Processing, Computer-Assisted ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/*chemistry/metabolism/ultrastructure ; Phosphoproteins/*chemistry/metabolism/ultrastructure ; Phosphorylation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*chemistry/metabolism/ultrastructure ; Sigma Factor/metabolism ; *Signal Transduction
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    Pyogenic bacterial infections in humans with MyD88 deficiency (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-08-02
    Description: MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688396/" 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/PMC2688396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Bernuth, Horst -- Picard, Capucine -- Jin, Zhongbo -- Pankla, Rungnapa -- Xiao, Hui -- Ku, Cheng-Lung -- Chrabieh, Maya -- Mustapha, Imen Ben -- Ghandil, Pegah -- Camcioglu, Yildiz -- Vasconcelos, Julia -- Sirvent, Nicolas -- Guedes, Margarida -- Vitor, Artur Bonito -- Herrero-Mata, Maria Jose -- Arostegui, Juan Ignacio -- Rodrigo, Carlos -- Alsina, Laia -- Ruiz-Ortiz, Estibaliz -- Juan, Manel -- Fortuny, Claudia -- Yague, Jordi -- Anton, Jordi -- Pascal, Mariona -- Chang, Huey-Hsuan -- Janniere, Lucile -- Rose, Yoann -- Garty, Ben-Zion -- Chapel, Helen -- Issekutz, Andrew -- Marodi, Laszlo -- Rodriguez-Gallego, Carlos -- Banchereau, Jacques -- Abel, Laurent -- Li, Xiaoxia -- Chaussabel, Damien -- Puel, Anne -- Casanova, Jean-Laurent -- U19 AI057234/AI/NIAID NIH HHS/ -- U19 AI057234-02/AI/NIAID NIH HHS/ -- U19 AIO57234-02/PHS HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Aug 1;321(5889):691-6. doi: 10.1126/science.1158298.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genetics of Infectious Diseases, INSERM U550, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18669862" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Bacterial Infections/*genetics/*immunology ; Cell Line, Transformed ; Child ; Child, Preschool ; Cytokines/metabolism ; Disease Susceptibility ; Female ; Gene Deletion ; Humans ; Immunity, Innate ; Male ; Mice ; Mutation, Missense ; Myeloid Differentiation Factor 88/*deficiency/genetics/metabolism ; Pneumococcal Infections/genetics/immunology ; Pseudomonas Infections/genetics/immunology ; Receptors, Interleukin-1/immunology/metabolism ; Signal Transduction ; Staphylococcal Infections/genetics/immunology ; Toll-Like Receptors/immunology/metabolism ; Transfection
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    Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-09-06
    Description: The canonical Wnt-beta-catenin signaling pathway is initiated by inducing phosphorylation of one of the Wnt receptors, low-density lipoprotein receptor-related protein 6 (LRP6), at threonine residue 1479 (Thr1479) and serine residue 1490 (Ser1490). By screening a human kinase small interfering RNA library, we identified phosphatidylinositol 4-kinase type II alpha and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6 phosphorylation at Ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P2] through frizzled and dishevelled, the latter of which directly interacted with and activated PIP5KI. In turn, PtdIns (4,5)P2 regulated phosphorylation of LRP6 at Thr1479 and Ser1490. Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532521/" 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/PMC2532521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, Weijun -- Choi, Sun-Cheol -- Wang, He -- Qin, Yuanbo -- Volpicelli-Daley, Laura -- Swan, Laura -- Lucast, Louise -- Khoo, Cynthia -- Zhang, Xiaowu -- Li, Lin -- Abrams, Charles S -- Sokol, Sergei Y -- Wu, Dianqing -- AR051476/AR/NIAMS NIH HHS/ -- CA132317/CA/NCI NIH HHS/ -- DA018343/DA/NIDA NIH HHS/ -- HL080706/HL/NHLBI NIH HHS/ -- NS36251/NS/NINDS NIH HHS/ -- P30 DA018343/DA/NIDA NIH HHS/ -- R01 AR051476/AR/NIAMS NIH HHS/ -- R01 AR051476-01A1/AR/NIAMS NIH HHS/ -- R01 AR051476-02/AR/NIAMS NIH HHS/ -- R01 AR051476-03/AR/NIAMS NIH HHS/ -- R01 CA132317/CA/NCI NIH HHS/ -- R01 CA132317-01A2/CA/NCI NIH HHS/ -- R01 CA139395/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1350-3. doi: 10.1126/science.1160741.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772438" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Axin Protein ; Cell Line ; Frizzled Receptors/metabolism ; Humans ; LDL-Receptor Related Proteins/*metabolism ; Low Density Lipoprotein Receptor-Related Protein-6 ; Mice ; Models, Biological ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; RNA, Small Interfering ; Recombinant Proteins/metabolism ; Repressor Proteins/metabolism ; Serine/metabolism ; Signal Transduction ; Threonine/metabolism ; Wnt Proteins/*metabolism ; Wnt3 Protein ; Wnt3A Protein ; Xenopus/embryology ; Xenopus Proteins
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    Reversible compartmentalization of de novo purine biosynthetic complexes in living cells (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-04-05
    Description: Purines are synthesized de novo in 10 chemical steps that are catalyzed by six enzymes in eukaryotes. Studies in vitro have provided little evidence of anticipated protein-protein interactions that would enable substrate channeling and regulation of the metabolic flux. We applied fluorescence microscopy to HeLa cells and discovered that all six enzymes colocalize to form clusters in the cellular cytoplasm. The association and dissociation of these enzyme clusters can be regulated dynamically, by either changing the purine levels of or adding exogenous agents to the culture media. Collectively, the data provide strong evidence for the formation of a multi-enzyme complex, the "purinosome," to carry out de novo purine biosynthesis in cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉An, Songon -- Kumar, Ravindra -- Sheets, Erin D -- Benkovic, Stephen J -- R21 AG030949/AG/NIA NIH HHS/ -- R21 AG030949-01/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2008 Apr 4;320(5872):103-6. doi: 10.1126/science.1152241.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA. sua13@psu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388293" target="_blank"〉PubMed〈/a〉
    Keywords: Azaserine/pharmacology ; Binding Sites ; Carbon-Nitrogen Ligases/genetics/*metabolism ; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor/genetics/*metabolism ; Cell Compartmentation ; Cell Line ; Cell Line, Tumor ; Culture Media ; Cytoplasm/*enzymology ; Fluorescent Antibody Technique ; HeLa Cells ; Humans ; Hypoxanthine/pharmacology ; Microscopy, Fluorescence ; Multienzyme Complexes/genetics/*metabolism ; Phosphoribosylglycinamide Formyltransferase/genetics/*metabolism ; Purines/*biosynthesis ; Recombinant Fusion Proteins/metabolism ; Transfection
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    The serine protease TMPRSS6 is required to sense iron deficiency (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-03
    Description: Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430097/" 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/PMC2430097/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Du, Xin -- She, Ellen -- Gelbart, Terri -- Truksa, Jaroslav -- Lee, Pauline -- Xia, Yu -- Khovananth, Kevin -- Mudd, Suzanne -- Mann, Navjiwan -- Moresco, Eva Marie Y -- Beutler, Ernest -- Beutler, Bruce -- AI054523/AI/NIAID NIH HHS/ -- DK53505-09/DK/NIDDK NIH HHS/ -- R01 DK053505-09/DK/NIDDK NIH HHS/ -- U54 AI054523/AI/NIAID NIH HHS/ -- U54 AI054523-019005/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 May 23;320(5879):1088-92. doi: 10.1126/science.1157121. Epub 2008 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451267" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Macrocytic/genetics/metabolism ; Animals ; Antimicrobial Cationic Peptides/*genetics/metabolism ; Cell Line, Tumor ; Gene Expression Regulation ; Hepcidins ; Humans ; Iron/blood/*deficiency/metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Models, Biological ; Mutation ; Phenotype ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Serine Endopeptidases/chemistry/genetics/*metabolism ; Signal Transduction ; Transfection
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    Systems biology. The scale of prediction (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baliga, Nitin S -- New York, N.Y. -- Science. 2008 Jun 6;320(5881):1297-8. doi: 10.1126/science.1159485.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Systems Biology, 1441 N. 34th Street, Seattle, WA 98103, USA. nbaliga@systemsbiology.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18535232" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; *Bacterial Physiological Phenomena ; Computer Simulation ; Directed Molecular Evolution ; *Ecosystem ; Environment ; Escherichia coli/genetics/physiology ; *Gene Regulatory Networks ; *Metabolic Networks and Pathways ; Models, Biological ; Systems Biology
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    Generation of pluripotent stem cells from adult mouse liver and stomach cells (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-02-16
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aoi, Takashi -- Yae, Kojiro -- Nakagawa, Masato -- Ichisaka, Tomoko -- Okita, Keisuke -- Takahashi, Kazutoshi -- Chiba, Tsutomu -- Yamanaka, Shinya -- New York, N.Y. -- Science. 2008 Aug 1;321(5889):699-702. doi: 10.1126/science.1154884. Epub 2008 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology ; Cell Differentiation ; Cell Proliferation ; *Cellular Reprogramming ; Chimera ; Clone Cells ; Culture Media ; Embryonic Stem Cells/cytology/metabolism ; Epithelial Cells/*cytology ; Gastric Mucosa/*cytology ; Genetic Vectors ; Hepatocytes/*cytology ; Mice ; Mice, Nude ; Neoplasms/etiology ; Pluripotent Stem Cells/*cytology/metabolism ; Retroviridae/genetics ; Stem Cell Transplantation ; Transcription Factors/genetics ; Transfection ; Virus Integration
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    Traction dynamics of filopodia on compliant substrates (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-17
    Description: Cells sense the environment's mechanical stiffness to control their own shape, migration, and fate. To better understand stiffness sensing, we constructed a stochastic model of the "motor-clutch" force transmission system, where molecular clutches link F-actin to the substrate and mechanically resist myosin-driven F-actin retrograde flow. The model predicts two distinct regimes: (i) "frictional slippage," with fast retrograde flow and low traction forces on stiff substrates and (ii) oscillatory "load-and-fail" dynamics, with slower retrograde flow and higher traction forces on soft substrates. We experimentally confirmed these model predictions in embryonic chick forebrain neurons by measuring the nanoscale dynamics of single-growth-cone filopodia. Furthermore, we experimentally observed a model-predicted switch in F-actin dynamics around an elastic modulus of 1 kilopascal. Thus, a motor-clutch system inherently senses and responds to the mechanical stiffness of the local environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Clarence E -- Odde, David J -- R01-GM-76177/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 12;322(5908):1687-91. doi: 10.1126/science.1163595.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074349" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*physiology ; Actins/*physiology ; Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cells, Cultured ; Chick Embryo ; Compliance ; Computer Simulation ; Elastic Modulus ; Elasticity ; Growth Cones/*physiology/ultrastructure ; Models, Biological ; Myosin Type II/physiology ; Neurons/physiology ; Pseudopodia/*physiology ; Surface Tension
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    Biophysics. Clutch dynamics (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aratyn-Schaus, Yvonne -- Gardel, Margaret L -- DP1 OD003354/OD/NIH HHS/ -- DP1 OD003354-01/OD/NIH HHS/ -- DP1 OD003354-02/OD/NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 12;322(5908):1646-7. doi: 10.1126/science.1168102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074337" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*physiology ; Actins/*physiology ; Animals ; Biomechanical Phenomena ; *Cell Adhesion ; Extracellular Matrix/physiology ; Focal Adhesions/*physiology ; Growth Cones/*physiology ; Models, Biological ; Myosin Type II/physiology ; Pseudopodia/*physiology
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    Structural basis for specific substrate recognition by the chloroplast signal recognition particle protein cpSRP43 (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-07-16
    Description: Secretory and membrane proteins carry amino-terminal signal sequences that, in cotranslational targeting, are recognized by the signal recognition particle protein SRP54 without sequence specificity. The most abundant membrane proteins on Earth are the light-harvesting chlorophyll a/b binding proteins (LHCPs). They are synthesized in the cytoplasm, imported into the chloroplast, and posttranslationally targeted to the thylakoid membrane by cpSRP, a heterodimer formed by cpSRP54 and cpSRP43. We present the 1.5 angstrom crystal structure of cpSRP43 characterized by a unique arrangement of chromodomains and ankyrin repeats. The overall shape and charge distribution of cpSRP43 resembles the SRP RNA, which is absent in chloroplasts. The complex with the internal signal sequence of LHCPs reveals that cpSRP43 specifically recognizes a DPLG peptide motif. We describe how cpSPR43 adapts the universally conserved SRP system to posttranslational targeting and insertion of the LHCP family of membrane proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stengel, Katharina F -- Holdermann, Iris -- Cain, Peter -- Robinson, Colin -- Wild, Klemens -- Sinning, Irmgard -- New York, N.Y. -- Science. 2008 Jul 11;321(5886):253-6. doi: 10.1126/science.1158640.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemie-Zentrum der Universitat Heidelberg, INF328, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18621669" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Ankyrin Repeat ; Arabidopsis/chemistry/*metabolism ; Arabidopsis Proteins/*chemistry/metabolism ; Calorimetry ; Chloroplast Proteins ; Crystallography, X-Ray ; Dimerization ; Hydrophobic and Hydrophilic Interactions ; Light-Harvesting Protein Complexes/chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Tertiary ; Protein Subunits ; RNA, Plant/chemistry/metabolism ; Signal Recognition Particle/*chemistry/*metabolism ; Thylakoids/metabolism
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    Beta-arrestin-mediated localization of smoothened to the primary cilium (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-24
    Description: beta-Arrestins have important roles in the regulation of seven-transmembrane receptors (7TMRs). Smoothened (Smo) is a 7TMR that mediates effects of Hedgehog on developmental processes and whose dysregulation may cause tumorigenesis. beta-Arrestins are required for endocytosis of Smo and signaling to Gli transcription factors. In mammalian cells, Smo-dependent signaling requires translocation to primary cilia. We demonstrated that beta-arrestins mediate the activity-dependent interaction of Smo and the kinesin motor protein Kif3A. This multimeric complex localized to primary cilia and was disrupted in cells transfected with beta-arrestin small interfering RNA. beta-Arrestin 1 or beta-arrestin 2 depletion prevented the localization of Smo to primary cilia and the Smo-dependent activation of Gli. These results suggest roles for beta-arrestins in mediating the intracellular transport of a 7TMR to its obligate subcellular location for signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587210/" 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/PMC2587210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kovacs, Jeffrey J -- Whalen, Erin J -- Liu, Renshui -- Xiao, Kunhong -- Kim, Jihee -- Chen, Minyong -- Wang, Jiangbo -- Chen, Wei -- Lefkowitz, Robert J -- 5R01 CA113656-02/CA/NCI NIH HHS/ -- 5T32 AI007217-25/AI/NIAID NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- R01 CA113656/CA/NCI NIH HHS/ -- R01 CA113656-02/CA/NCI NIH HHS/ -- R01 CA113656-03/CA/NCI NIH HHS/ -- R01 HL016037/HL/NHLBI NIH HHS/ -- R01 HL016037-35/HL/NHLBI NIH HHS/ -- R01 HL070631/HL/NHLBI NIH HHS/ -- R01 HL070631-04/HL/NHLBI NIH HHS/ -- T32 AI007217/AI/NIAID NIH HHS/ -- T32 AI007217-25/AI/NIAID NIH HHS/ -- T32 AI007217-26/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jun 27;320(5884):1777-81. doi: 10.1126/science.1157983. Epub 2008 May 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/genetics/*metabolism ; Cilia/*metabolism ; Hedgehog Proteins/metabolism ; Kinesin/*metabolism ; Mice ; Microscopy, Confocal ; Molecular Motor Proteins/*metabolism ; NIH 3T3 Cells ; Protein Transport ; RNA Interference ; Receptors, G-Protein-Coupled/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Transfection
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    Auxin gradients are associated with polarity changes in trees (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-06-21
    Description: Models of plant growth and development propose that changes in cell polarity are mediated by gradients of the plant hormone auxin. With use of gas chromatography-mass spectrometry, we measured the redistribution of endogenous auxin in stems of quaking aspen trees (Populus tremuloides) after wounding. Persistent (lasting at least 24 hours) auxin gradients were observed in the region of the cambium where cell polarity was changing. A computer model of the auxin redistribution shows agreement with measured concentrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kramer, Eric M -- Lewandowski, Michael -- Beri, Satvik -- Bernard, Jessica -- Borkowski, Matthew -- Borkowski, Michael H -- Burchfield, Laura Ann -- Mathisen, Brenda -- Normanly, Jennifer -- New York, N.Y. -- Science. 2008 Jun 20;320(5883):1610. doi: 10.1126/science.1156130.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physics Department, Bard College at Simon'sRock, Great Barrington, MA 01230, USA and Centre for Plant Integrative Biology at the University of Nottingham, UK. ekramer@simons-rock.edu [corrected]〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18566279" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Polarity ; Computer Simulation ; Indoleacetic Acids/*metabolism ; Meristem/cytology/*metabolism ; Models, Biological ; Populus/*cytology/growth & development/*metabolism ; Wood/*cytology
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    Regulation of microtubule dynamics by reaction cascades around chromosomes (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-10-25
    Description: During spindle assembly, chromosomes generate gradients of microtubule stabilization through a reaction-diffusion process, but how this is achieved is not well understood. We measured the spatial distribution of microtubule aster asymmetry around chromosomes by incubating centrosomes and micropatterned chromatin patches in frog egg extracts. We then screened for microtubule stabilization gradient shapes that would generate such spatial distributions with the use of computer simulations. Only a long-range, sharply decaying microtubule stabilization gradient could generate aster asymmetries fitting the experimental data. We propose a reaction-diffusion model that combines the chromosome generated Ran-guanosine triphosphate-Importin reaction network to a secondary phosphorylation network as a potential mechanism for the generation of such gradients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Athale, Chaitanya A -- Dinarina, Ana -- Mora-Coral, Maria -- Pugieux, Celine -- Nedelec, Francois -- Karsenti, Eric -- New York, N.Y. -- Science. 2008 Nov 21;322(5905):1243-7. doi: 10.1126/science.1161820. Epub 2008 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948504" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/physiology ; Centrosome/physiology ; Chromatin/physiology ; Chromosomes, Human/physiology ; Computer Simulation ; Diffusion ; Humans ; Microtubule-Associated Proteins/physiology ; Microtubules/*physiology ; Models, Biological ; Nuclear Proteins/physiology ; Ovum/cytology ; Phosphoproteins/physiology ; Spindle Apparatus/*physiology ; Xenopus ; Xenopus Proteins/physiology ; ran GTP-Binding Protein/metabolism
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    Physiology. Burn fat, live longer (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-11-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Ting -- New York, N.Y. -- Science. 2008 Nov 7;322(5903):865-6. doi: 10.1126/science.1166150.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tgx@stowersinstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18988829" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/metabolism ; Cell Proliferation ; Forkhead Transcription Factors ; Genes, Helminth ; Germ Cells/cytology/*metabolism ; Intestines/cytology/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Lipase/genetics/metabolism ; *Lipid Metabolism ; *Longevity ; Models, Animal ; Models, Biological ; Reproduction ; Signal Transduction ; Stem Cells/cytology/*metabolism ; Transcription Factors/metabolism
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    The evolution and distribution of species body size (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-07-19
    Description: The distribution of species body size within taxonomic groups exhibits a heavy right tail extending over many orders of magnitude, where most species are much larger than the smallest species. We provide a simple model of cladogenetic diffusion over evolutionary time that omits explicit mechanisms for interspecific competition and other microevolutionary processes, yet fully explains the shape of this distribution. We estimate the model's parameters from fossil data and find that it robustly reproduces the distribution of 4002 mammal species from the late Quaternary. The observed fit suggests that the asymmetric distribution arises from a fundamental trade-off between the short-term selective advantages (Cope's rule) and long-term selective risks of increased species body size in the presence of a taxon-specific lower limit on body size.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clauset, Aaron -- Erwin, Douglas H -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):399-401. doi: 10.1126/science.1157534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA. aaronc@santafe.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635801" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Body Size ; Computer Simulation ; Extinction, Biological ; Fossils ; Genetic Speciation ; Mammals/*anatomy & histology/classification/physiology ; Models, Biological ; Selection, Genetic
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    Resource partitioning and sympatric differentiation among closely related bacterioplankton (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-24
    Description: Identifying ecologically differentiated populations within complex microbial communities remains challenging, yet is critical for interpreting the evolution and ecology of microbes in the wild. Here we describe spatial and temporal resource partitioning among Vibrionaceae strains coexisting in coastal bacterioplankton. A quantitative model (AdaptML) establishes the evolutionary history of ecological differentiation, thus revealing populations specific for seasons and life-styles (combinations of free-living, particle, or zooplankton associations). These ecological population boundaries frequently occur at deep phylogenetic levels (consistent with named species); however, recent and perhaps ongoing adaptive radiation is evident in Vibrio splendidus, which comprises numerous ecologically distinct populations at different levels of phylogenetic differentiation. Thus, environmental specialization may be an important correlate or even trigger of speciation among sympatric microbes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunt, Dana E -- David, Lawrence A -- Gevers, Dirk -- Preheim, Sarah P -- Alm, Eric J -- Polz, Martin F -- New York, N.Y. -- Science. 2008 May 23;320(5879):1081-5. doi: 10.1126/science.1157890.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497299" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Atlantic Ocean ; Biological Evolution ; *Ecosystem ; *Genetic Speciation ; Markov Chains ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Plankton/*physiology ; Seasons ; Seawater/*microbiology ; Vibrio/classification/genetics/physiology ; Vibrionaceae/classification/genetics/*physiology ; Zooplankton/physiology
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    Myosin I can act as a molecular force sensor (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-07-05
    Description: The ability to sense molecular tension is crucial for a wide array of cellular processes, including the detection of auditory stimuli, control of cell shape, and internalization and transport of membranes. We show that myosin I, a motor protein that has been implicated in powering key steps in these processes, dramatically alters its motile properties in response to tension. We measured the displacement generated by single myosin I molecules, and we determined the actin-attachment kinetics with varying tensions using an optical trap. The rate of myosin I detachment from actin decreases 〉75-fold under tension of 2 piconewtons or less, resulting in myosin I transitioning from a low (〈0.2) to a high (〉0.9) duty-ratio motor. This impressive tension sensitivity supports a role for myosin I as a molecular force sensor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493443/" 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/PMC2493443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laakso, Joseph M -- Lewis, John H -- Shuman, Henry -- Ostap, E Michael -- AR051174/AR/NIAMS NIH HHS/ -- GM057247/GM/NIGMS NIH HHS/ -- P01 AR051174/AR/NIAMS NIH HHS/ -- P01 AR051174-050003/AR/NIAMS NIH HHS/ -- R01 GM057247-10/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jul 4;321(5885):133-6. doi: 10.1126/science.1159419.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pennsylvania Muscle Institute and Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18599791" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Actomyosin/physiology ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Animals ; Biophysical Phenomena ; Biophysics ; Kinetics ; Likelihood Functions ; Models, Biological ; Molecular Motor Proteins/metabolism/*physiology ; Monte Carlo Method ; Myosin Type I/chemistry/metabolism/*physiology ; Optical Tweezers ; Protein Structure, Tertiary ; Rabbits ; Stress, Mechanical
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    Morphogenetic cell movements: diversity from modular mechanical properties (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-06
    Description: Animal tissue and organ development requires the orchestration of cell movements, including those of interconnected cell groups, termed collective cell movements. Such movements are incredibly diverse. Recent work suggests that two core cellular properties, cell-cell adhesion and contractility, can largely determine geometry, packing, sorting, and rearrangement of epithelial cell layers. Two additional force-generating properties, the ability to generate cell protrusions and cell adhesion to the extracellular matrix, contribute to active motility. These mechanical properties can be regulated independently in cells, suggesting that they can be employed in a combinatorial manner. A small number of properties used in combination could, in principle, generate a diverse array of cell shapes and arrangements and thus orchestrate the varied morphogenetic events observed during metazoan organ development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Montell, Denise J -- R01GM73164/GM/NIGMS NIH HHS/ -- U54 GM064346/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1502-5. doi: 10.1126/science.1164073.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Center for Cell Dynamics, Rangos Building, Suite 450, 855 North Wolfe Street, Baltimore, MD 21205, USA. dmontell@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; *Cell Movement ; Cell Physiological Processes ; Cell Polarity ; Cell Shape ; Cell Surface Extensions/physiology/ultrastructure ; *Embryonic Development ; Extracellular Matrix/physiology ; Models, Biological ; *Morphogenesis ; Organogenesis
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    Midbody targeting of the ESCRT machinery by a noncanonical coiled coil in CEP55 (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-10-25
    Description: The ESCRT (endosomal sorting complex required for transport) machinery is required for the scission of membrane necks in processes including the budding of HIV-1 and cytokinesis. An essential step in cytokinesis is recruitment of the ESCRT-I complex and the ESCRT-associated protein ALIX to the midbody (the structure that tethers two daughter cells) by the protein CEP55. Biochemical experiments show that peptides from ALIX and the ESCRT-I subunit TSG101 compete for binding to the ESCRT and ALIX-binding region (EABR) of CEP55. We solved the crystal structure of EABR bound to an ALIX peptide at a resolution of 2.0 angstroms. The structure shows that EABR forms an aberrant dimeric parallel coiled coil. Bulky and charged residues at the interface of the two central heptad repeats create asymmetry and a single binding site for an ALIX or TSG101 peptide. Both ALIX and ESCRT-I are required for cytokinesis, which suggests that multiple CEP55 dimers are required for function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720046/" 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/PMC2720046/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hyung Ho -- Elia, Natalie -- Ghirlando, Rodolfo -- Lippincott-Schwartz, Jennifer -- Hurley, James H -- Z01 DK036125-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Oct 24;322(5901):576-80. doi: 10.1126/science.1162042.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948538" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Calcium-Binding Proteins/*chemistry/*metabolism ; Cell Cycle Proteins/*chemistry/*metabolism ; Cellular Structures/metabolism ; Crystallography, X-Ray ; *Cytokinesis ; DNA-Binding Proteins/chemistry/metabolism ; Dimerization ; Endosomal Sorting Complexes Required for Transport ; Endosomes/metabolism ; HeLa Cells ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Models, Molecular ; Nuclear Proteins/*chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Transcription Factors/chemistry/metabolism ; Transfection
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    Developmental biology. On growth and force (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulder, Bela -- New York, N.Y. -- Science. 2008 Dec 12;322(5908):1643-4. doi: 10.1126/science.1168512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Systems, FOM Institute for Atomic and Molecular Physics, Kruislaan 407, 1098 SJ Amsterdam, Netherlands. mulder@amolf.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074335" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/anatomy & histology/*cytology/*growth & development ; Cell Physiological Phenomena ; Cell Shape ; Cell Wall/physiology/ultrastructure ; Cellulose ; Dinitrobenzenes/pharmacology ; Meristem/cytology/growth & development ; Microfibrils/physiology ; Microtubules/*physiology ; Models, Biological ; Morphogenesis ; Plant Cells ; Plant Development ; Plant Shoots/anatomy & histology/cytology/*growth & development ; Stress, Mechanical ; Sulfanilamides/pharmacology ; Tubulin Modulators/pharmacology
    Print ISSN: 0036-8075
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    From signals to patterns: space, time, and mathematics in developmental biology (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-10-18
    Description: We now have a wealth of information about the molecular signals that act on cells in embryos, but how do the control systems based on these signals generate pattern and govern the timing of developmental events? Here, I discuss four examples to show how mathematical modeling and quantitative experimentation can give some useful answers. The examples concern the Bicoid gradient in the early Drosophila embryo, the dorsoventral patterning of a frog embryo by bone morphogenetic protein signals, the auxin-mediated patterning of plant meristems, and the Notch-dependent somite segmentation clock.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Julian -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):399-403. doi: 10.1126/science.1166154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vertebrate Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18927385" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning ; Bone Morphogenetic Proteins/metabolism ; Drosophila/embryology/metabolism ; Embryo, Nonmammalian/*metabolism ; *Embryonic Development ; Feedback, Physiological ; Homeodomain Proteins/metabolism ; Indoleacetic Acids/metabolism ; Mathematics ; Meristem/*growth & development/metabolism ; Models, Biological ; Receptors, Notch/metabolism ; *Signal Transduction ; Somites/embryology ; Trans-Activators/metabolism ; Xenopus/embryology/metabolism ; Zebrafish/embryology/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Reconstitution of pilus assembly reveals a bacterial outer membrane catalyst (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-03-29
    Description: Type 1 pili from uropathogenic Escherichia coli are a prototype of adhesive surface organelles assembled and secreted by the conserved chaperone/usher pathway. We reconstituted type 1 pilus biogenesis from purified pilus proteins. The usher FimD acted as a catalyst to accelerate the ordered assembly of protein subunits independently of cellular energy. Its activity was highly dependent on the adhesin subunit FimH, which triggered the conversion of FimD into a high-efficiency assembly catalyst. Furthermore, a simple kinetic model adequately rationalized usher-catalyzed pilus assembly in vivo. Our results contribute to a mechanistic understanding of protein-catalyzed biogenesis of supramolecular protein complexes at the bacterial outer cell membrane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishiyama, Mireille -- Ishikawa, Takashi -- Rechsteiner, Helene -- Glockshuber, Rudi -- New York, N.Y. -- Science. 2008 Apr 18;320(5874):376-9. doi: 10.1126/science.1154994. Epub 2008 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18369105" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Escherichia coli/metabolism ; Bacterial Outer Membrane Proteins/*metabolism ; Catalysis ; Escherichia coli/*metabolism/ultrastructure ; Escherichia coli Proteins/genetics/*metabolism ; Fimbriae Proteins/genetics/*metabolism ; Fimbriae, Bacterial/*metabolism/ultrastructure ; Kinetics ; Models, Biological ; Temperature
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    Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-10-11
    Description: A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in vivo imaging at 1.5 billion voxels per minute provides "digital embryos," that is, comprehensive databases of cell positions, divisions, and migratory tracks. Our analysis of global cell division patterns reveals a maternally defined initial morphodynamic symmetry break, which identifies the embryonic body axis. We further derive a model of germ layer formation and show that the mesendoderm forms from one-third of the embryo's cells in a single event. Our digital embryos, with 55 million nucleus entries, are provided as a resource.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keller, Philipp J -- Schmidt, Annette D -- Wittbrodt, Joachim -- Stelzer, Ernst H K -- New York, N.Y. -- Science. 2008 Nov 14;322(5904):1065-9. doi: 10.1126/science.1162493. Epub 2008 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany. keller@embl.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845710" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Body Patterning ; *Cell Division ; Cell Nucleus/physiology ; Databases, Factual ; Embryo, Nonmammalian/*cytology ; *Embryonic Development ; Endoderm/embryology ; Germ Layers/cytology/*embryology/physiology ; Image Processing, Computer-Assisted ; Mesoderm/embryology ; Microscopy, Fluorescence/methods ; Models, Biological ; Motion Pictures as Topic ; Mutation ; Software ; Zebrafish/*embryology/genetics ; beta Catenin/analysis
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    Spatial regulators for bacterial cell division self-organize into surface waves in vitro (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-10
    Description: In the bacterium Escherichia coli, the Min proteins oscillate between the cell poles to select the cell center as division site. This dynamic pattern has been proposed to arise by self-organization of these proteins, and several models have suggested a reaction-diffusion type mechanism. Here, we found that the Min proteins spontaneously formed planar surface waves on a flat membrane in vitro. The formation and maintenance of these patterns, which extended for hundreds of micrometers, required adenosine 5'-triphosphate (ATP), and they persisted for hours. We present a reaction-diffusion model of the MinD and MinE dynamics that accounts for our experimental observations and also captures the in vivo oscillations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loose, Martin -- Fischer-Friedrich, Elisabeth -- Ries, Jonas -- Kruse, Karsten -- Schwille, Petra -- New York, N.Y. -- Science. 2008 May 9;320(5877):789-92. doi: 10.1126/science.1154413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnologisches Zentrum der Technischen Universitat Dresden, Tatzberg 47-51, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18467587" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*physiology ; Adenosine Triphosphate/physiology ; Bacterial Proteins ; Cell Cycle Proteins/*physiology ; Cell Division/*physiology ; Cell-Free System ; Cytoskeletal Proteins ; Diffusion ; Escherichia coli/*physiology ; Escherichia coli Proteins/*physiology ; Models, Biological ; Oscillometry
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  • 81
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    An oncogene-induced DNA damage model for cancer development (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-03-08
    Description: Of all types of DNA damage, DNA double-strand breaks (DSBs) pose the greatest challenge to cells. One might have, therefore, anticipated that a sizable number of DNA DSBs would be incompatible with cell proliferation. Yet recent experimental findings suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs. This continuous formation of DNA DSBs may contribute to the genomic instability that characterizes the vast majority of human cancers. In addition, in precancerous lesions, these DNA DSBs activate p53, which, by inducing apoptosis or senescence, raises a barrier to tumor progression. Breach of this barrier by various mechanisms, most notably by p53 mutations, that impair the DNA damage response pathway allows cancers to develop. Thus, oncogene-induced DNA damage may explain two key features of cancer: genomic instability and the high frequency of p53 mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halazonetis, Thanos D -- Gorgoulis, Vassilis G -- Bartek, Jiri -- New York, N.Y. -- Science. 2008 Mar 7;319(5868):1352-5. doi: 10.1126/science.1140735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland. Thanos.Halazonetis@molbio.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18323444" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Proliferation ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Replication ; Disease Progression ; Genes, p53 ; Genomic Instability ; Humans ; Models, Biological ; Mutation ; Neoplasms/*genetics/pathology/physiopathology ; *Oncogenes ; Precancerous Conditions/*genetics/pathology/physiopathology ; Tumor Suppressor Protein p53/metabolism
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    TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-09-06
    Description: Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear. Treatment of bronchial epithelial cells with interleukin-4 (IL-4) causes increased calcium-dependent chloride channel activity, presumably by regulating expression of the corresponding genes. We performed a global gene expression analysis to identify membrane proteins that are regulated by IL-4. Transfection of epithelial cells with specific small interfering RNA against each of these proteins shows that TMEM16A, a member of a family of putative plasma membrane proteins with unknown function, is associated with calcium-dependent chloride current, as measured with halide-sensitive fluorescent proteins, short-circuit current, and patch-clamp techniques. Our results indicate that TMEM16A is an intrinsic constituent of the calcium-dependent chloride channel. Identification of a previously unknown family of membrane proteins associated with chloride channel function will improve our understanding of chloride transport physiopathology and allow for the development of pharmacological tools useful for basic research and drug development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caputo, Antonella -- Caci, Emanuela -- Ferrera, Loretta -- Pedemonte, Nicoletta -- Barsanti, Cristina -- Sondo, Elvira -- Pfeffer, Ulrich -- Ravazzolo, Roberto -- Zegarra-Moran, Olga -- Galietta, Luis J V -- GGP05103/Telethon/Italy -- New York, N.Y. -- Science. 2008 Oct 24;322(5901):590-4. doi: 10.1126/science.1163518. Epub 2008 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772398" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Animals ; Bronchi/cytology/*metabolism ; Calcium/*metabolism ; Cell Line ; Cell Membrane/*metabolism ; Cells, Cultured ; Chloride Channels/*metabolism ; Chlorides/*metabolism ; Epithelial Cells/metabolism ; Humans ; Interleukin-4/metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Neoplasm Proteins/chemistry/genetics/*metabolism ; Oligonucleotide Array Sequence Analysis ; Patch-Clamp Techniques ; RNA, Small Interfering ; Respiratory Mucosa/cytology/metabolism ; Transfection
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    Developmental patterning by mechanical signals in Arabidopsis (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-12-17
    Description: A central question in developmental biology is whether and how mechanical forces serve as cues for cellular behavior and thereby regulate morphogenesis. We found that morphogenesis at the Arabidopsis shoot apex depends on the microtubule cytoskeleton, which in turn is regulated by mechanical stress. A combination of experiments and modeling shows that a feedback loop encompassing tissue morphology, stress patterns, and microtubule-mediated cellular properties is sufficient to account for the coordinated patterns of microtubule arrays observed in epidermal cells, as well as for patterns of apical morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamant, Olivier -- Heisler, Marcus G -- Jonsson, Henrik -- Krupinski, Pawel -- Uyttewaal, Magalie -- Bokov, Plamen -- Corson, Francis -- Sahlin, Patrik -- Boudaoud, Arezki -- Meyerowitz, Elliot M -- Couder, Yves -- Traas, Jan -- New York, N.Y. -- Science. 2008 Dec 12;322(5908):1650-5. doi: 10.1126/science.1165594.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INRA, Laboratoire de Reproduction et Developpement des Plantes, 46 Allee d'Italie, 69364 Lyon Cedex 07, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074340" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/anatomy & histology/cytology/*growth & development ; Cell Shape ; Cell Wall/physiology/ultrastructure ; Cellulose ; Dinitrobenzenes/pharmacology ; Meristem/cytology/*growth & development ; Microfibrils/physiology ; Microtubules/*physiology/ultrastructure ; Models, Biological ; Morphogenesis ; Plant Epidermis/physiology ; Plant Shoots/anatomy & histology/cytology/*growth & development ; Plant Stems/cytology/growth & development ; Pressure ; Stress, Mechanical ; Sulfanilamides/pharmacology ; Tubulin Modulators/pharmacology
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    Selective blockade of microRNA processing by Lin28 (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-02-23
    Description: MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked posttranscriptionally in embryonic stem cells, embryonal carcinoma cells, and primary tumors. Here we show that Lin28, a developmentally regulated RNA binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we found that Lin28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368499/" 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/PMC3368499/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viswanathan, Srinivas R -- Daley, George Q -- Gregory, Richard I -- DK70055/DK/NIDDK NIH HHS/ -- DP1 OD000256/OD/NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Apr 4;320(5872):97-100. doi: 10.1126/science.1154040. Epub 2008 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Program, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18292307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Embryonal ; Cell Differentiation ; Cell Line, Transformed ; Cell Line, Tumor ; Cellular Reprogramming ; DNA-Binding Proteins/metabolism ; Down-Regulation ; Embryonic Stem Cells/cytology/*metabolism ; Humans ; Mice ; MicroRNAs/*metabolism ; Pluripotent Stem Cells/cytology/metabolism ; Protein Binding ; RNA Interference ; *RNA Processing, Post-Transcriptional ; RNA-Binding Proteins/genetics/*metabolism ; Ribonuclease III/metabolism ; Transfection ; Up-Regulation
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    The spread of Ras activity triggered by activation of a single dendritic spine (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-06-17
    Description: In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745709/" 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/PMC2745709/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harvey, Christopher D -- Yasuda, Ryohei -- Zhong, Haining -- Svoboda, Karel -- AS1398/Autism Speaks/ -- R01 MH080047/MH/NIMH NIH HHS/ -- R01 MH080047-01/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jul 4;321(5885):136-40. doi: 10.1126/science.1159675. Epub 2008 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18556515" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cell Membrane/metabolism ; Dendritic Spines/*physiology ; Diffusion ; Fluorescence Resonance Energy Transfer ; GTPase-Activating Proteins/metabolism ; Glutamic Acid/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Hippocampus/cytology/physiology ; *Long-Term Potentiation ; Pyramidal Cells/*physiology ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Synapses/*physiology ; Transfection ; ras Proteins/*metabolism
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    Detection of GTP-tubulin conformation in vivo reveals a role for GTP remnants in microtubule rescues (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-10-18
    Description: Microtubules display dynamic instability, with alternating phases of growth and shrinkage separated by catastrophe and rescue events. The guanosine triphosphate (GTP) cap at the growing end of microtubules, whose presence is essential to prevent microtubule catastrophes in vitro, has been difficult to observe in vivo. We selected a recombinant antibody that specifically recognizes GTP-bound tubulin in microtubules and found that GTP-tubulin was indeed present at the plus end of growing microtubules. Unexpectedly, GTP-tubulin remnants were also present in older parts of microtubules, which suggests that GTP hydrolysis is sometimes incomplete during polymerization. Observations in living cells suggested that these GTP remnants may be responsible for the rescue events in which microtubules recover from catastrophe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dimitrov, Ariane -- Quesnoit, Melanie -- Moutel, Sandrine -- Cantaloube, Isabelle -- Pous, Christian -- Perez, Franck -- New York, N.Y. -- Science. 2008 Nov 28;322(5906):1353-6. doi: 10.1126/science.1165401. Epub 2008 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR144, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18927356" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Cell Line ; Computer Simulation ; Dimerization ; Fluorescent Antibody Technique ; Guanosine Triphosphate/*analysis/metabolism ; HeLa Cells ; Humans ; Microtubules/*chemistry/metabolism/ultrastructure ; Models, Biological ; Monte Carlo Method ; Protein Conformation ; Recombinant Fusion Proteins/metabolism ; Tubulin/analysis/*chemistry/immunology/metabolism
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    Molecular biology. The paradox of silent heterochromatin (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Djupedal, Ingela -- Ekwall, Karl -- New York, N.Y. -- Science. 2008 May 2;320(5876):624-5. doi: 10.1126/science.1158923.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biosciences and Medical Nutrition, Karolinska Institutet, Sweden/School of Life Sciences, University College Sodertorn, NOVUM, 141 57 Huddinge, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451292" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle/genetics ; Heterochromatin/*physiology ; Models, Biological ; RNA Interference ; RNA Polymerase II/metabolism ; RNA, Fungal/physiology ; Schizosaccharomyces/genetics/physiology ; Transcription, Genetic
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  • 88
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    FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-09-13
    Description: The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849753/" 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/PMC2849753/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mao, Jian-Hua -- Kim, Il-Jin -- Wu, Di -- Climent, Joan -- Kang, Hio Chung -- DelRosario, Reyno -- Balmain, Allan -- R01 CA116481/CA/NCI NIH HHS/ -- U01 CA084244/CA/NCI NIH HHS/ -- U01 CA084244-08/CA/NCI NIH HHS/ -- U01 CA084244-09/CA/NCI NIH HHS/ -- U01 CA084244-10/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 12;321(5895):1499-502. doi: 10.1126/science.1162981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787170" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/drug therapy/genetics/*metabolism/pathology ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; F-Box Proteins/genetics/*metabolism ; Gene Deletion ; Gene Dosage ; Gene Silencing ; Genes, Tumor Suppressor ; Humans ; Mice ; Mice, Nude ; Mutation ; Neoplasm Transplantation ; PTEN Phosphohydrolase/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Sirolimus/pharmacology/therapeutic use ; TOR Serine-Threonine Kinases ; Transfection ; Tumor Suppressor Proteins/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination
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  • 89
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    Surface mobility of postsynaptic AMPARs tunes synaptic transmission (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-04-12
    Description: AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral diffusion, observed in both intact hippocampi and cultured neurons, allows fast exchange of desensitized receptors with naive functional ones within or near the postsynaptic density. Recovery from depression in the tens of millisecond time range can be explained in part by this fast receptor exchange. Preventing AMPAR surface movements through cross-linking, endogenous clustering, or calcium rise all slow recovery from depression. Physiological regulation of postsynaptic receptor mobility affects the fidelity of synaptic transmission by shaping the frequency dependence of synaptic responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715948/" 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/PMC2715948/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heine, Martin -- Groc, Laurent -- Frischknecht, Renato -- Beique, Jean-Claude -- Lounis, Brahim -- Rumbaugh, Gavin -- Huganir, Richard L -- Cognet, Laurent -- Choquet, Daniel -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Apr 11;320(5873):201-5. doi: 10.1126/science.1152089.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, UMR 5091, Universite Bordeaux, Bordeaux, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18403705" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Calcium/metabolism ; Cells, Cultured ; Diffusion ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials ; Fluorescence Recovery After Photobleaching ; Glutamic Acid/metabolism ; Hippocampus/cytology/*physiology ; Kynurenic Acid/pharmacology ; Neuronal Plasticity ; Neurons/physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/*metabolism ; Recombinant Fusion Proteins/metabolism ; Synapses/drug effects/*physiology ; *Synaptic Transmission/drug effects ; Transfection
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  • 90
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    Cancer. Aneuploidy advantages? (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-11-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hernando, Eva -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):692-3. doi: 10.1126/science.1166151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. eva.hernando@med.nyu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974340" target="_blank"〉PubMed〈/a〉
    Keywords: *Aneuploidy ; Animals ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Survival ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Gene Amplification ; Genomic Instability ; Humans ; Mice ; Models, Biological ; Mutation ; Neoplasms/*genetics ; *Trisomy
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  • 91
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    A competitive inhibitor traps LeuT in an open-to-out conformation (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-12-17
    Description: Secondary transporters are workhorses of cellular membranes, catalyzing the movement of small molecules and ions across the bilayer and coupling substrate passage to ion gradients. However, the conformational changes that accompany substrate transport, the mechanism by which a substrate moves through the transporter, and principles of competitive inhibition remain unclear. We used crystallographic and functional studies on the leucine transporter (LeuT), a model for neurotransmitter sodium symporters, to show that various amino acid substrates induce the same occluded conformational state and that a competitive inhibitor, tryptophan (Trp), traps LeuT in an open-to-out conformation. In the Trp complex, the extracellular gate residues arginine 30 and aspartic acid 404 define a second weak binding site for substrates or inhibitors as they permeate from the extracellular solution to the primary substrate site, which demonstrates how residues that participate in gating also mediate permeation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832577/" 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/PMC2832577/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Satinder K -- Piscitelli, Chayne L -- Yamashita, Atsuko -- Gouaux, Eric -- K99 MH083050-02/MH/NIMH NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 MH070039/MH/NIMH NIH HHS/ -- R01 MH070039-05/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Dec 12;322(5908):1655-61. doi: 10.1126/science.1166777.〈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/19074341" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Transport Systems/antagonists & inhibitors/*chemistry/*metabolism ; Amino Acids/metabolism/pharmacology ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Binding, Competitive ; Biological Transport ; Crystallization ; Crystallography, X-Ray ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Leucine/*metabolism ; Ligands ; Models, Biological ; Models, Molecular ; Protein Conformation ; Protein Structure, Tertiary ; Sodium/metabolism ; Symporters/antagonists & inhibitors/*chemistry/*metabolism ; Tryptophan/metabolism/*pharmacology
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    Origin of stem cells in organogenesis (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-12-06
    Description: The development of individual organs in animal embryos involves the formation of tissue-specific stem cells that sustain cell renewal of their own tissue for the lifetime of the organism. Although details of their origin are not always known, tissue-specific stem cells usually share the expression of key transcription factors with cells of the embryonic rudiment from which they arise, and are probably in a similar developmental state. On the other hand, the isolation of pluripotent stem cells from the postnatal organism has encouraged the formulation of models of embryonic and postnatal development that are at variance with the conventional ones. Possible explanations for the existence of such cells, and the issue of whether they also exist in vivo, are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slack, J M W -- G0300415/Medical Research Council/United Kingdom -- G0500220/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1498-501. doi: 10.1126/science.1162782.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Institute, University of Minnesota, McGuire Translational Research Facility, 2001 6th Street SE, Minneapolis, MN 55455, USA. slack017@umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056975" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/cytology/physiology ; Animals ; Cell Differentiation ; Cell Lineage ; Cell Separation ; Cell Transdifferentiation ; Cells, Cultured ; Embryonic Stem Cells/cytology/physiology ; Humans ; Models, Biological ; Neural Crest/cytology ; *Organogenesis ; Pluripotent Stem Cells/cytology/physiology ; Stem Cell Niche ; Stem Cells/cytology/*physiology ; Transcription Factors/metabolism
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  • 93
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    Energy uptake and allocation during ontogeny (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-11-01
    Description: All organisms face the problem of how to fuel ontogenetic growth. We present a model, empirically grounded in data from birds and mammals, that correctly predicts how growing animals allocate food energy between synthesis of new biomass and maintenance of existing biomass. Previous energy budget models have typically had their bases in rates of either food consumption or metabolic energy expenditure. Our model provides a framework that reconciles these two approaches and highlights the fundamental principles that determine rates of food assimilation and rates of energy allocation to maintenance, biosynthesis, activity, and storage. The model predicts that growth and assimilation rates for all animals should cluster closely around two universal curves. Data for mammals and birds of diverse body sizes and taxa support these predictions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891030/" 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/PMC2891030/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hou, Chen -- Zuo, Wenyun -- Moses, Melanie E -- Woodruff, William H -- Brown, James H -- West, Geoffrey B -- DK36263/DK/NIDDK NIH HHS/ -- P20 RR-018754/RR/NCRR NIH HHS/ -- P20 RR018754/RR/NCRR NIH HHS/ -- P20 RR018754-06A1/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):736-9. doi: 10.1126/science.1162302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA. houc@santafe.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974352" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Metabolism ; Biomass ; Birds/embryology/growth & development/*metabolism ; Body Size ; *Energy Intake ; *Energy Metabolism ; Female ; Food ; *Growth ; Male ; Mammals/embryology/growth & development/*metabolism ; Mathematics ; Models, Biological
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    RNA exosome depletion reveals transcription upstream of active human promoters (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-12-06
    Description: Studies have shown that the bulk of eukaryotic genomes is transcribed. Transcriptome maps are frequently updated, but low-abundant transcripts have probably gone unnoticed. To eliminate RNA degradation, we depleted the exonucleolytic RNA exosome from human cells and then subjected the RNA to tiling microarray analysis. This revealed a class of short, polyadenylated and highly unstable RNAs. These promoter upstream transcripts (PROMPTs) are produced approximately 0.5 to 2.5 kilobases upstream of active transcription start sites. PROMPT transcription occurs in both sense and antisense directions with respect to the downstream gene. In addition, it requires the presence of the gene promoter and is positively correlated with gene activity. We propose that PROMPT transcription is a common characteristic of RNA polymerase II (RNAPII) transcribed genes with a possible regulatory potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Preker, Pascal -- Nielsen, Jesper -- Kammler, Susanne -- Lykke-Andersen, Soren -- Christensen, Marianne S -- Mapendano, Christophe K -- Schierup, Mikkel H -- Jensen, Torben Heick -- New York, N.Y. -- Science. 2008 Dec 19;322(5909):1851-4. doi: 10.1126/science.1164096. Epub 2008 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, C. F. Mollers Alle, Building 1130, Aarhus University, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056938" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Methylation ; Exosomes/*metabolism ; HeLa Cells ; Humans ; Oligonucleotide Array Sequence Analysis ; *Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA Stability ; RNA, Antisense/*genetics/*metabolism ; RNA, Messenger/*genetics/*metabolism ; Transcription Factors/metabolism ; Transcription Initiation Site ; *Transcription, Genetic ; Transfection
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  • 95
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    Membrane proteins of the endoplasmic reticulum induce high-curvature tubules (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-03-01
    Description: The tubular structure of the endoplasmic reticulum (ER) appears to be generated by integral membrane proteins, the reticulons and a protein family consisting of DP1 in mammals and Yop1p in yeast. Here, individual members of these families were found to be sufficient to generate membrane tubules. When we purified yeast Yop1p and incorporated it into proteoliposomes, narrow tubules (approximately 15 to 17 nanometers in diameter) were generated. Tubule formation occurred with different lipids; required essentially only the central portion of the protein, including its two long hydrophobic segments; and was prevented by mutations that affected tubule formation in vivo. Tubules were also formed by reconstituted purified yeast Rtn1p. Tubules made in vitro were narrower than normal ER tubules, due to a higher concentration of tubule-inducing proteins. The shape and oligomerization of the "morphogenic" proteins could explain the formation of the tubular ER.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Junjie -- Shibata, Yoko -- Voss, Christiane -- Shemesh, Tom -- Li, Zongli -- Coughlin, Margaret -- Kozlov, Michael M -- Rapoport, Tom A -- Prinz, William A -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1247-50. doi: 10.1126/science.1153634.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18309084" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biopolymers/chemistry/metabolism ; COS Cells ; Cercopithecus aethiops ; Endoplasmic Reticulum/*chemistry/metabolism/*ultrastructure ; Hydrophobic and Hydrophilic Interactions ; Intracellular Membranes/chemistry/ultrastructure ; Lipid Bilayers ; Membrane Lipids/chemistry ; Membrane Proteins/*chemistry/*metabolism ; Membrane Transport Proteins/*chemistry/*metabolism ; Microscopy, Electron ; Models, Biological ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Proteolipids/chemistry ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism
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    The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-01-26
    Description: The propagation of information through signaling cascades spans a wide range of time scales, including the rapid ligand-receptor interaction and the much slower response of downstream gene expression. To determine which dynamic range dominates a response, we used periodic stimuli to measure the frequency dependence of signal transduction in the osmo-adaptation pathway of Saccharomyces cerevisiae. We applied system identification methods to infer a concise predictive model. We found that the dynamics of the osmo-adaptation response are dominated by a fast-acting negative feedback through the kinase Hog1 that does not require protein synthesis. After large osmotic shocks, an additional, much slower, negative feedback through gene expression allows cells to respond faster to future stimuli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916730/" 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/PMC2916730/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mettetal, Jerome T -- Muzzey, Dale -- Gomez-Uribe, Carlos -- van Oudenaarden, Alexander -- 5 R90 DK071511-01/DK/NIDDK NIH HHS/ -- R01 GM068957/GM/NIGMS NIH HHS/ -- R01 GM068957-05/GM/NIGMS NIH HHS/ -- R01 GM068957-06/GM/NIGMS NIH HHS/ -- R01-GM068957/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 25;319(5862):482-4. doi: 10.1126/science.1151582.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18218902" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Cell Nucleus/metabolism ; *Feedback, Physiological ; Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Glycerol/*metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Osmolar Concentration ; Osmotic Pressure ; Phosphorylation ; Saccharomyces cerevisiae/genetics/metabolism/*physiology ; Saccharomyces cerevisiae Proteins/*metabolism ; Signal Transduction ; Systems Biology
    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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    Cell signaling. Getting your loops straight. Introduction (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, L Bryan -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):389. doi: 10.1126/science.322.5900.389.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18927382" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Feedback, Physiological ; Models, Biological ; *Signal Transduction ; Yeasts/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    Predictive behavior within microbial genetic networks (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-05-10
    Description: The homeostatic framework has dominated our understanding of cellular physiology. We question whether homeostasis alone adequately explains microbial responses to environmental stimuli, and explore the capacity of intracellular networks for predictive behavior in a fashion similar to metazoan nervous systems. We show that in silico biochemical networks, evolving randomly under precisely defined complex habitats, capture the dynamical, multidimensional structure of diverse environments by forming internal representations that allow prediction of environmental change. We provide evidence for such anticipatory behavior by revealing striking correlations of Escherichia coli transcriptional responses to temperature and oxygen perturbations-precisely mirroring the covariation of these parameters upon transitions between the outside world and the mammalian gastrointestinal tract. We further show that these internal correlations reflect a true associative learning paradigm, because they show rapid decoupling upon exposure to novel environments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931280/" 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/PMC2931280/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tagkopoulos, Ilias -- Liu, Yir-Chung -- Tavazoie, Saeed -- DP1 OD003787/OD/NIH HHS/ -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-01/GM/NIGMS NIH HHS/ -- P50 GM071508-06/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jun 6;320(5881):1313-7. doi: 10.1126/science.1154456. Epub 2008 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18467556" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Aerobiosis ; Anaerobiosis ; Computer Simulation ; Directed Molecular Evolution ; Ecosystem ; Escherichia coli/*genetics/growth & development/*physiology ; *Gene Regulatory Networks ; Homeostasis ; Kinetics ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Statistical ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oxygen/analysis ; Temperature ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    Positive regulation of Itk PH domain function by soluble IP4 (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-07
    Description: Pleckstrin homology (PH) domain-mediated protein recruitment to cellular membranes is of paramount importance for signal transduction. The recruitment of many PH domains is controlled through production and turnover of their membrane ligand, phosphatidylinositol 3,4,5-trisphosphate (PIP3). We show that phosphorylation of the second messenger inositol 1,4,5-trisphosphate (IP3) into inositol 1,3,4,5-tetrakisphosphate (IP4) establishes another mode of PH domain regulation through a soluble ligand. At physiological concentrations, IP4 promoted PH domain binding to PIP3. In primary mouse CD4+CD8+ thymocytes, this was required for full activation of the protein tyrosine kinase Itk after T cell receptor engagement. Our data suggest that IP4 establishes a feedback loop of phospholipase C-gamma1 activation through Itk that is essential for T cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yina H -- Grasis, Juris A -- Miller, Andrew T -- Xu, Ruo -- Soonthornvacharin, Stephen -- Andreotti, Amy H -- Tsoukas, Constantine D -- Cooke, Michael P -- Sauer, Karsten -- AR048848/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):886-9. Epub 2007 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, 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/17412921" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; *Amino Acid Motifs ; Animals ; Diglycerides/metabolism ; Feedback, Physiological ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol Phosphates/*metabolism/pharmacology ; Lymphopoiesis ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Organ Culture Techniques ; Phosphatidylinositol Phosphates/metabolism ; Phospholipase C gamma/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/*metabolism ; Receptors, Antigen, T-Cell/immunology ; Second Messenger Systems ; Signal Transduction ; Solubility ; T-Lymphocytes/cytology/immunology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    Plant science. Reproductive dialog (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCormick, Sheila -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):606-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Gene Expression Center, USDA Agricultural Research Service-UC Berkeley, 800 Buchanan Street, Albany, CA 94710, USA. sheilamc@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673644" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/enzymology/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/enzymology ; Crosses, Genetic ; Evolution, Molecular ; Flowers/cytology/enzymology/*physiology ; Genes, Plant ; Ligands ; Models, Biological ; Mutation ; Phosphotransferases/*genetics/*metabolism ; Pollen Tube/growth & development/*physiology ; Reproduction ; Signal Transduction ; Species Specificity
    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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