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  • Mice  (169)
  • 2005-2009  (169)
  • 1980-1984
  • 2007  (169)
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  • 2005-2009  (169)
  • 1980-1984
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  • 1
    Publication Date: 2007
    Description: Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425380/" 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/PMC3425380/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huber, Daniel -- Petreanu, Leopoldo -- Ghitani, Nima -- Ranade, Sachin -- Hromadka, Tomas -- Mainen, Zach -- Svoboda, Karel -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jan 3;451(7174):61-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18094685" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology/radiation effects ; Algal Proteins/genetics/metabolism ; Animals ; Behavior, Animal/*physiology/*radiation effects ; Cerebral Cortex/cytology/*physiology/*radiation effects ; Electric Stimulation ; Learning/*physiology/radiation effects ; Mice ; Movement/*physiology ; Optics and Photonics ; Photic Stimulation ; Pyramidal Cells/metabolism/radiation effects ; Rhodopsins, Microbial/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2007
    Description: Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, In-Hyun -- Zhao, Rui -- West, Jason A -- Yabuuchi, Akiko -- Huo, Hongguang -- Ince, Tan A -- Lerou, Paul H -- Lensch, M William -- Daley, George Q -- England -- Nature. 2008 Jan 10;451(7175):141-6. Epub 2007 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18157115" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Differentiation ; Cell Shape ; Cells, Cultured ; DNA Methylation ; DNA-Binding Proteins/genetics ; Embryonic Stem Cells/cytology/metabolism ; Fetus/cytology ; Fibroblasts/cytology ; Gene Expression Profiling ; HMGB Proteins/genetics/*metabolism ; Homeodomain Proteins/genetics ; Humans ; Infant, Newborn ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Mice ; Octamer Transcription Factor-3/genetics/*metabolism ; Pluripotent Stem Cells/*cytology/*metabolism/transplantation ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; SOXB1 Transcription Factors ; Teratoma/pathology ; Transcription Factors/genetics/*metabolism ; Transplantation, Heterologous
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    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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  • 4
    Publication Date: 2007-04-14
    Description: The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bankovich, Alexander J -- Raunser, Stefan -- Juo, Z Sean -- Walz, Thomas -- Davis, Mark M -- Garcia, K Christopher -- T32 AI007290/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):291-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Complementarity Determining Regions/chemistry/physiology ; Crystallography, X-Ray ; Humans ; Immunoglobulin Heavy Chains/chemistry/physiology ; Immunoglobulin Light Chains/chemistry/physiology ; Immunoglobulin Light Chains, Surrogate ; Membrane Glycoproteins/*chemistry/physiology/ultrastructure ; Mice ; Models, Molecular ; Pre-B Cell Receptors ; Protein Conformation ; Receptors, Antigen, B-Cell/*chemistry/physiology/ultrastructure ; Recombinant Proteins ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2007-03-31
    Description: Differentiation of hepatic stellate cells (HSCs) to extracellular matrix- and growth factor-producing cells supports liver regeneration through promotion of hepatocyte proliferation. We show that the neurotrophin receptor p75NTR, a tumor necrosis factor receptor superfamily member expressed in HSCs after fibrotic and cirrhotic liver injury in humans, is a regulator of liver repair. In mice, depletion of p75NTR exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75NTR-/- HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75NTR signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75NTR to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Passino, Melissa A -- Adams, Ryan A -- Sikorski, Shoana L -- Akassoglou, Katerina -- 5T32-GM07752/GM/NIGMS NIH HHS/ -- NS051470/NS/NINDS NIH HHS/ -- P30-NS047101/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 30;315(5820):1853-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California, San Diego (UCSD), La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17395831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Disease Progression ; Extracellular Matrix/metabolism ; Fibroblasts/*cytology ; Hepatocyte Growth Factor/metabolism ; Hepatocytes/*cytology ; Liver/*cytology/metabolism/pathology/physiology ; Liver Diseases/metabolism/*pathology ; *Liver Regeneration ; Mice ; Nerve Growth Factor/pharmacology ; Receptors, Nerve Growth Factor/genetics/*metabolism ; Signal Transduction ; rho GTP-Binding Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Irvine, Robin -- New York, N.Y. -- Science. 2007 May 11;316(5826):845-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. rfi20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol Phosphates/*metabolism ; Lymphocytes/physiology ; Mice ; Phosphatidylinositol Diacylglycerol-Lyase/genetics/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Phosphorylation ; Phosphotransferases (Phosphate Group Acceptor)/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/*metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Repressor Proteins/metabolism ; Saccharomyces cerevisiae/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Schizosaccharomyces/genetics/metabolism ; Second Messenger Systems ; *Signal Transduction ; Solubility
    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christensen, Soren Tvorup -- Ott, Carolyn Marie -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):330-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Copenhagen, Copenhagen DK-2100, Denmark. stchristensen@aki.ku.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism ; Cilia/*physiology ; Hedgehog Proteins/*metabolism ; Kruppel-Like Transcription Factors/metabolism ; Mice ; Receptors, Cell Surface/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; *Signal Transduction ; Sterols/metabolism ; 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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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chun, Jerold -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):208-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jchun@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endothelium, Vascular/physiology ; Fingolimod Hydrochloride ; Humans ; Immunosuppressive Agents/pharmacology ; Lymphocytes/*physiology ; Lysophospholipids/isolation & purification/*physiology ; Mice ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Propylene Glycols/pharmacology ; Receptors, Lysosphingolipid/metabolism ; Sphingosine/*analogs & derivatives/isolation & ; purification/pharmacology/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Firestein, Gary S -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):952-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Allergy and Immunology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC 0656, La Jolla, CA 92093-0656, USA. gfirestein@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17303744" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis, Rheumatoid/immunology/pathology/*therapy ; Cadherins/*antagonists & inhibitors/genetics/physiology ; Disease Models, Animal ; Humans ; Mice ; Synovial Membrane/*cytology/pathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2007-03-24
    Description: Changes in the genes encoding sensory receptor proteins are an essential step in the evolution of new sensory capacities. In primates, trichromatic color vision evolved after changes in X chromosome-linked photopigment genes. To model this process, we studied knock-in mice that expressed a human long-wavelength-sensitive (L) cone photopigment in the form of an X-linked polymorphism. Behavioral tests demonstrated that heterozygous females, whose retinas contained both native mouse pigments and human L pigment, showed enhanced long-wavelength sensitivity and acquired a new capacity for chromatic discrimination. An inherent plasticity in the mammalian visual system thus permits the emergence of a new dimension of sensory experience based solely on gene-driven changes in receptor organization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobs, Gerald H -- Williams, Gary A -- Cahill, Hugh -- Nathans, Jeremy -- EY002052/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 23;315(5819):1723-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Research Institute and Department of Psychology, University of California, Santa Barbara, CA 93106, USA. jacobs@psych.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17379811" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Color Perception/*genetics ; Discrimination (Psychology) ; Electroretinography ; Female ; Genetic Engineering ; Heterozygote ; Humans ; Light ; Male ; Mice ; Neuronal Plasticity ; Primates/genetics/physiology ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Pigments/*genetics/*physiology ; X Chromosome/genetics ; X Chromosome Inactivation
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fitzgerald, Katherine A -- Golenbock, Douglas T -- New York, N.Y. -- Science. 2007 Jun 15;316(5831):1574-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA. kate.fitzgerald@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17569850" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Vesicular Transport/metabolism ; *Adjuvants, Immunologic ; Animals ; Crystallography, X-Ray ; Glycolipids/chemistry/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lipid A/*analogs & derivatives/chemistry/immunology/metabolism ; Lymphocyte Activation ; Lymphocyte Antigen 96/*chemistry/metabolism ; Mice ; Phosphates/metabolism ; Protein Conformation ; Receptors, Interleukin/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; Toll-Like Receptor 4/chemistry/*immunology/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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  • 12
    Publication Date: 2007-07-07
    Description: The in vivo potential of neural stem cells in the postnatal mouse brain is not known, but because they produce many different types of neurons, they must be either very versatile or very diverse. By specifically targeting stem cells and following their progeny in vivo, we showed that postnatal stem cells in different regions produce different types of neurons, even when heterotopically grafted or grown in culture. This suggests that rather than being plastic and homogeneous, neural stem cells are a restricted and diverse population of progenitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merkle, Florian T -- Mirzadeh, Zaman -- Alvarez-Buylla, Arturo -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):381-4. Epub 2007 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California, San Francisco, San Francisco, CA 94143-0525, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615304" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Animals, Newborn ; Astrocytes/cytology ; Brain/*cytology ; Cell Differentiation ; Cells, Cultured ; Interneurons/cytology ; Lateral Ventricles/cytology ; Mice ; Neuroglia/cytology ; Neurons/*cytology ; Olfactory Bulb/cytology ; Stem Cell Transplantation ; Transplantation, Heterotopic
    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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  • 13
    Publication Date: 2007-11-03
    Description: The limb blastemal cells of an adult salamander regenerate the structures distal to the level of amputation, and the surface protein Prod 1 is a critical determinant of their proximodistal identity. The anterior gradient protein family member nAG is a secreted ligand for Prod 1 and a growth factor for cultured newt blastemal cells. nAG is sequentially expressed after amputation in the regenerating nerve and the wound epidermis-the key tissues of the stem cell niche-and its expression in both locations is abrogated by denervation. The local expression of nAG after electroporation is sufficient to rescue a denervated blastema and regenerate the distal structures. Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696928/" 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/PMC2696928/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Anoop -- Godwin, James W -- Gates, Phillip B -- Garza-Garcia, A Acely -- Brockes, Jeremy P -- G0600229/Medical Research Council/United Kingdom -- G0600229(77696)/Medical Research Council/United Kingdom -- G9537983/Medical Research Council/United Kingdom -- G9537983(56733)/Medical Research Council/United Kingdom -- MC_U117574559/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):772-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD59/*physiology ; COS Cells ; Cells, Cultured ; Cercopithecus aethiops ; Denervation ; Extremities/innervation ; Glycosylphosphatidylinositols/physiology ; Growth Substances ; Intercellular Signaling Peptides and Proteins/isolation & ; purification/*physiology/secretion ; Ligands ; Mice ; Notophthalmus viridescens ; Peripheral Nerves/*physiology ; Regeneration/*physiology ; Stem Cells/*cytology ; Two-Hybrid System Techniques
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 14
    Publication Date: 2007-02-03
    Description: The 66-kilodalton isoform of the growth factor adapter Shc (p66Shc) translates oxidative damage into cell death by acting as reactive oxygen species (ROS) producer within mitochondria. However, the signaling link between cellular stress and mitochondrial proapoptotic activity of p66Shc was not known. We demonstrate that protein kinase C beta, activated by oxidative conditions in the cell, induces phosphorylation of p66Shc and triggers mitochondrial accumulation of the protein after it is recognized by the prolyl isomerase Pin1. Once imported, p66Shc causes alterations of mitochondrial Ca2+ responses and three-dimensional structure, thus inducing apoptosis. These data identify a signaling route that activates an apoptotic inducer shortening the life span and could be a potential target of pharmacological approaches to inhibit aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinton, Paolo -- Rimessi, Alessandro -- Marchi, Saverio -- Orsini, Francesca -- Migliaccio, Enrica -- Giorgio, Marco -- Contursi, Cristina -- Minucci, Saverio -- Mantovani, Fiamma -- Wieckowski, Mariusz R -- Del Sal, Giannino -- Pelicci, Pier Giuseppe -- Rizzuto, Rosario -- GGP05284/Telethon/Italy -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):659-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrera, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272725" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adenosine Triphosphate/metabolism/pharmacology ; Animals ; *Apoptosis ; Calcium/metabolism ; Calcium Signaling ; *Cell Aging ; Cell Survival ; Cells, Cultured ; Cyclosporine/pharmacology ; Hydrogen Peroxide/metabolism/pharmacology ; Mice ; Mitochondria/*metabolism/ultrastructure ; Mutation ; Oxidative Stress ; Peptidylprolyl Isomerase/*metabolism ; Permeability ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors/genetics/*metabolism ; Protein Kinase C beta ; Reactive Oxygen Species/metabolism ; Recombinant Fusion Proteins/metabolism ; Shc Signaling Adaptor Proteins ; *Signal Transduction
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  • 15
    Publication Date: 2007-02-10
    Description: A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willis, Simon N -- Fletcher, Jamie I -- Kaufmann, Thomas -- van Delft, Mark F -- Chen, Lin -- Czabotar, Peter E -- Ierino, Helen -- Lee, Erinna F -- Fairlie, W Douglas -- Bouillet, Philippe -- Strasser, Andreas -- Kluck, Ruth M -- Adams, Jerry M -- Huang, David C S -- CA43540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):856-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism ; BH3 Interacting Domain Death Agonist Protein/chemistry/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Humans ; Ligands ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Knockout ; Models, Biological ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/metabolism ; Protein Structure, Tertiary ; Proteins/metabolism ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/chemistry/*metabolism ; bcl-Associated Death Protein/metabolism ; bcl-X Protein/metabolism
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  • 16
    Publication Date: 2007-05-26
    Description: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berghuis, Paul -- Rajnicek, Ann M -- Morozov, Yury M -- Ross, Ruth A -- Mulder, Jan -- Urban, Gabriella M -- Monory, Krisztina -- Marsicano, Giovanni -- Matteoli, Michela -- Canty, Alison -- Irving, Andrew J -- Katona, Istvan -- Yanagawa, Yuchio -- Rakic, Pasko -- Lutz, Beat -- Mackie, Ken -- Harkany, Tibor -- DA00286/DA/NIDA NIH HHS/ -- DA015916/DA/NIDA NIH HHS/ -- DA11322/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1212-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525344" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cannabinoid Receptor Modulators/metabolism/*physiology ; Cell Movement ; Cells, Cultured ; Cerebral Cortex/cytology/embryology/ultrastructure ; *Endocannabinoids ; Growth Cones/physiology/ultrasonography ; In Situ Hybridization ; Interneurons/metabolism/*physiology/ultrasonography ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/agonists/*physiology ; Signal Transduction ; Stem Cells/metabolism ; Synapses/physiology/ultrasonography ; Xenopus Proteins/physiology ; Xenopus laevis ; gamma-Aminobutyric Acid/metabolism
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  • 17
    Publication Date: 2007-04-21
    Description: The mechanisms controlling the establishment of the embryonic-abembryonic (E-Ab) axis of the mammalian blastocyst are controversial. We used in vitro time-lapse imaging and in vivo lineage labeling to provide evidence that the E-Ab axis of the mouse blastocyst is generated independently of early cell lineage. Rather, both the boundary between two-cell blastomeres and the E-Ab axis of the blastocyst align relative to the ellipsoidal shape of the zona pellucida (ZP), an extraembryonic structure. Lack of correlation between cell lineage and the E-Ab axis can be explained by the rotation of the embryo within the ZP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurotaki, Yoko -- Hatta, Kohei -- Nakao, Kazuki -- Nabeshima, Yo-Ichi -- Fujimori, Toshihiko -- New York, N.Y. -- Science. 2007 May 4;316(5825):719-23. Epub 2007 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446354" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology/physiology ; Blastocyst Inner Cell Mass ; Blastomeres/*physiology ; Body Patterning ; Cell Lineage ; Cell Movement ; Cell Nucleus/physiology ; *Embryonic Development ; Green Fluorescent Proteins ; Image Processing, Computer-Assisted ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Motion Pictures as Topic ; Rotation ; Zona Pellucida/physiology/*ultrastructure
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  • 18
    Publication Date: 2007-01-20
    Description: The Staphylococcus aureus Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by strains epidemiologically associated with the current outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and with the often-lethal necrotizing pneumonia. To investigate the role of PVL in pulmonary disease, we tested the pathogenicity of clinical isolates, isogenic PVL-negative and PVL-positive S. aureus strains, as well as purified PVL, in a mouse acute pneumonia model. Here we show that PVL is sufficient to cause pneumonia and that the expression of this leukotoxin induces global changes in transcriptional levels of genes encoding secreted and cell wall-anchored staphylococcal proteins, including the lung inflammatory factor staphylococcal protein A (Spa).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Labandeira-Rey, Maria -- Couzon, Florence -- Boisset, Sandrine -- Brown, Eric L -- Bes, Michele -- Benito, Yvonne -- Barbu, Elena M -- Vazquez, Vanessa -- Hook, Magnus -- Etienne, Jerome -- Vandenesch, Francois -- Bowden, M Gabriela -- AI020624/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1130-3. Epub 2007 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17234914" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics ; Calcium-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; Exotoxins/genetics/*physiology ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Hemorrhage ; Leukocidins/genetics/*physiology ; Lung/microbiology/*pathology ; Methicillin Resistance ; Mice ; Mice, Inbred BALB C ; Necrosis ; Oligonucleotide Array Sequence Analysis ; Pneumonia, Staphylococcal/*microbiology/*pathology ; Staphylococcal Protein A/genetics/*metabolism ; Staphylococcus aureus/genetics/growth & development/metabolism/*pathogenicity ; Transcription, Genetic ; Virulence ; Virulence Factors/genetics/*physiology
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  • 19
    Publication Date: 2007-05-26
    Description: Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706583/" 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/PMC2706583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sobhian, Bijan -- Shao, Genze -- Lilli, Dana R -- Culhane, Aedin C -- Moreau, Lisa A -- Xia, Bing -- Livingston, David M -- Greenberg, Roger A -- K08 CA106597/CA/NCI NIH HHS/ -- K08 CA106597-01A2/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1198-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Genetics and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525341" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; BRCA1 Protein/*metabolism ; Binding Sites ; Carrier Proteins/*metabolism ; Cell Line ; DNA/*metabolism ; *DNA Breaks, Double-Stranded ; DNA Repair/physiology ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; Tumor Suppressor Proteins/metabolism ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/metabolism
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  • 20
    Publication Date: 2007-10-13
    Description: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Laura D -- Parsons, D Williams -- Jones, Sian -- Lin, Jimmy -- Sjoblom, Tobias -- Leary, Rebecca J -- Shen, Dong -- Boca, Simina M -- Barber, Thomas -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Dezso, Zoltan -- Ustyanksky, Vadim -- Nikolskaya, Tatiana -- Nikolsky, Yuri -- Karchin, Rachel -- Wilson, Paul A -- Kaminker, Joshua S -- Zhang, Zemin -- Croshaw, Randal -- Willis, Joseph -- Dawson, Dawn -- Shipitsin, Michail -- Willson, James K V -- Sukumar, Saraswati -- Polyak, Kornelia -- Park, Ben Ho -- Pethiyagoda, Charit L -- Pant, P V Krishna -- Ballinger, Dennis G -- Sparks, Andrew B -- Hartigan, James -- Smith, Douglas R -- Suh, Erick -- Papadopoulos, Nickolas -- Buckhaults, Phillip -- Markowitz, Sanford D -- Parmigiani, Giovanni -- Kinzler, Kenneth W -- Velculescu, Victor E -- Vogelstein, Bert -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- CA112828/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- GM070219/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1108-13. Epub 2007 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/metabolism ; Cell Line ; Chromosome Mapping ; Colorectal Neoplasms/*genetics/metabolism ; Computational Biology ; DNA, Neoplasm ; Databases, Genetic ; Genes, Neoplasm ; Genome, Human ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neoplasm Proteins/genetics/metabolism ; Sequence Analysis, DNA
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2007 Sep 7;317(5843):1305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17823319" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*therapeutic use ; Clinical Trials as Topic ; HIV Protease Inhibitors/*therapeutic use ; Humans ; Mice ; Nelfinavir/therapeutic use
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  • 22
    Publication Date: 2007-02-17
    Description: Migrating cells extend protrusions, probing the surrounding matrix in search of permissive sites to form adhesions. We found that actin fibers polymerizing along the leading edge directed local protrusions and drove synchronous sideways movement of beta1 integrin adhesion receptors. These movements lead to the clustering and positioning of conformationally activated, but unligated, beta1 integrins along the leading edge of fibroblast lamellae and growth cone filopodia. Thus, rapid actin-based movement of primed integrins along the leading edge suggests a "sticky fingers" mechanism to probe for new adhesion sites and to direct migration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galbraith, Catherine G -- Yamada, Kenneth M -- Galbraith, James A -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):992-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17303755" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*physiology ; Animals ; Antigens, CD29/*physiology ; Cell Adhesion/*physiology ; Cell Adhesion Molecules/metabolism ; Cell Line ; Cell Movement/*physiology ; Extracellular Matrix/metabolism ; Fibroblasts/physiology ; Fibronectins/metabolism ; Green Fluorescent Proteins/metabolism ; Mice ; Microfilament Proteins/metabolism ; NIH 3T3 Cells ; Phosphoproteins/metabolism ; Protein Binding ; Pseudopodia/metabolism
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  • 23
    Publication Date: 2007-09-22
    Description: Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Junt, Tobias -- Schulze, Harald -- Chen, Zhao -- Massberg, Steffen -- Goerge, Tobias -- Krueger, Andreas -- Wagner, Denisa D -- Graf, Thomas -- Italiano, Joseph E Jr -- Shivdasani, Ramesh A -- von Andrian, Ulrich H -- HL068130/HL/NHLBI NIH HHS/ -- HL56949/HL/NHLBI NIH HHS/ -- HL63143/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1767-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885137" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins ; Blood Platelets/*cytology ; Bone Marrow/*physiology ; Cells, Cultured ; Luminescent Proteins ; Megakaryocytes/*cytology ; Mice ; Microscopy, Fluorescence, Multiphoton ; Platelet Membrane Glycoprotein IIb ; Shear Strength ; Thrombopoiesis/*physiology
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):612-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673648" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD34/analysis ; CD4-Positive T-Lymphocytes/immunology/virology ; Clinical Trials as Topic ; *Genetic Therapy ; Genetic Vectors ; HIV/genetics/immunology ; HIV Antibodies/genetics/immunology ; HIV Infections/*immunology/*therapy ; Hematopoietic Stem Cells/immunology ; Humans ; *Immunotherapy ; Mice ; Transduction, Genetic
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahl, Barbara C -- Peters, Georg -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1082-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medical Microbiology, University of Munster, Domagkstrasse 10, D-49149 Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17322047" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Bacterial/genetics/metabolism ; Animals ; Bacterial Toxins/analysis ; Exotoxins/analysis/*physiology ; Gene Expression Regulation, Bacterial ; Hemorrhage ; Leukocidins/analysis/*physiology ; Lung/chemistry/microbiology/*pathology ; Methicillin Resistance ; Mice ; Models, Biological ; Necrosis ; Phagocytosis ; Pneumonia, Staphylococcal/*microbiology/*pathology ; Respiratory Mucosa/microbiology ; Staphylococcal Protein A/genetics/*metabolism ; Staphylococcus aureus/genetics/growth & development/metabolism/*pathogenicity ; Virulence Factors/analysis/*physiology
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  • 26
    Publication Date: 2007-10-13
    Description: The catalytic (C) subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is inhibited by two classes of regulatory subunits, RI and RII. The RII subunits are substrates as well as inhibitors and do not require adenosine triphosphate (ATP) to form holoenzyme, which distinguishes them from RI subunits. To understand the molecular basis for isoform diversity, we solved the crystal structure of an RIIalpha holoenzyme and compared it to the RIalpha holoenzyme. Unphosphorylated RIIalpha(90-400), a deletion mutant, undergoes major conformational changes as both of the cAMP-binding domains wrap around the C subunit's large lobe. The hallmark of this conformational reorganization is the helix switch in domain A. The C subunit is in an open conformation, and its carboxyl-terminal tail is disordered. This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036697/" 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/PMC4036697/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jian -- Brown, Simon H J -- von Daake, Sventja -- Taylor, Susan S -- GM34921/GM/NIGMS NIH HHS/ -- R01 GM034921/GM/NIGMS NIH HHS/ -- R01 GM034921-23/GM/NIGMS NIH HHS/ -- T32-CA009524/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):274-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932298" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Animals ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ; Cyclic AMP-Dependent Protein Kinases/*chemistry/genetics/metabolism ; Holoenzymes/chemistry ; Hydrophobic and Hydrophilic Interactions ; Isoenzymes/chemistry ; Mice ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 27
    Publication Date: 2007-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jiang I -- Crabtree, Gerald R -- New York, N.Y. -- Science. 2007 Jun 22;316(5832):1710-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howared Hughes Medical Institute and Stanford University School of Medicine, Stanford, CA 94305-5323, USA. crabtree@cmgm.stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17588921" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*physiology ; Animals ; Cell Nucleus/*physiology ; Cell Shape/physiology ; Gene Expression Regulation ; Mice ; Protein Transport ; Serum Response Factor/physiology ; Signal Transduction/*physiology ; Trans-Activators/*physiology ; Transcription, Genetic/physiology
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  • 28
    Publication Date: 2007-01-27
    Description: Primary pneumonic plague is transmitted easily, progresses rapidly, and causes high mortality, but the mechanisms by which Yersinia pestis overwhelms the lungs are largely unknown. We show that the plasminogen activator Pla is essential for Y. pestis to cause primary pneumonic plague but is less important for dissemination during pneumonic plague than during bubonic plague. Experiments manipulating its temporal expression showed that Pla allows Y. pestis to replicate rapidly in the airways, causing a lethal fulminant pneumonia; if unexpressed, inflammation is aborted, and lung repair is activated. Inhibition of Pla expression prolonged the survival of animals with the disease, offering a therapeutic option to extend the period during which antibiotics are effective.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lathem, Wyndham W -- Price, Paul A -- Miller, Virginia L -- Goldman, William E -- AI53298/AI/NIAID NIH HHS/ -- DK52574/DK/NIDDK NIH HHS/ -- F32 AI069688-01/AI/NIAID NIH HHS/ -- NRSA T32 GM07067/GM/NIGMS NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 26;315(5811):509-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17255510" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Colony Count, Microbial ; Cytokines/genetics/metabolism ; Female ; Fibrinogen/metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Bacterial ; Lung/immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mutation ; Plague/immunology/*microbiology/pathology ; Plasminogen/metabolism ; Plasminogen Activators/genetics/*metabolism ; Pneumonia, Bacterial/immunology/*microbiology/pathology ; Spleen/microbiology ; Tetracyclines/pharmacology ; Virulence Factors/genetics/metabolism ; Yersinia pestis/enzymology/genetics/growth & development/*pathogenicity
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gatfield, David -- Schibler, Ueli -- New York, N.Y. -- Science. 2007 May 25;316(5828):1135-6. Epub 2007 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and NCCR Frontiers in Genetics, Sciences III, University of Geneva, CH-1211 Geneva-4, Switzerland. david.gatfield@molbio.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495136" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/physiology ; Circadian Rhythm/genetics/*physiology ; Cryptochromes ; F-Box Proteins/physiology ; Flavoproteins/physiology ; Mice ; Nuclear Proteins/physiology ; Period Circadian Proteins ; Phenotype ; Proteasome Endopeptidase Complex/*physiology ; Transcription Factors/physiology
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geddis, Amy E -- Kaushansky, Kenneth -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1689-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pediatrics and Medicine, University of California, San Diego, CA 92103-8811, USA. kkaushansky@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885117" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Blood Platelets/*cytology ; Humans ; Megakaryocytes/*cytology ; Mice ; Thrombopoiesis/*physiology
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  • 31
    Publication Date: 2007-08-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):884-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702917" target="_blank"〉PubMed〈/a〉
    Keywords: *Advisory Committees ; Animals ; Benzhydryl Compounds ; Child ; Endocrine Disruptors/administration & dosage/*toxicity ; Female ; Humans ; Male ; Mice ; Phenols/administration & dosage/*toxicity ; Pregnancy ; United States
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  • 32
    Publication Date: 2007-11-03
    Description: During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karnik, Satyajit K -- Chen, Hainan -- McLean, Graeme W -- Heit, Jeremy J -- Gu, Xueying -- Zhang, Andrew Y -- Fontaine, Magali -- Yen, Michael H -- Kim, Seung K -- T32DK007217-32/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975067" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Diabetes, Gestational/*etiology/metabolism ; Female ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/metabolism ; Pregnancy ; Prolactin/metabolism ; Proto-Oncogene Proteins/*physiology ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):729.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes, Gestational/*metabolism ; Female ; Humans ; Insulin-Secreting Cells/cytology ; Mice ; Pregnancy ; Prolactin/physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Tumor Suppressor Proteins/*physiology
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-10-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Richard -- New York, N.Y. -- Science. 2007 Oct 19;318(5849):390; author reply 390.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17947563" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Animals ; Glucuronidase/deficiency/*genetics ; Humans ; Mice ; *Models, Animal ; Signal Transduction ; Vitamin D/*administration & dosage/metabolism ; Wnt Proteins/metabolism
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  • 35
    Publication Date: 2007-11-17
    Description: Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, David Yu -- Turberfield, Andrew J -- Yurke, Bernard -- Winfree, Erik -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1121-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computation and Neural Systems, California Institute of Technology, MC 136-93, 1200 East California Boulevard, Pasadena, CA91125, USA. dzhang@dna.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalysis ; Chemical Engineering ; *Computers, Molecular ; DNA/*chemistry ; Entropy ; Equipment Design ; Feedback, Physiological ; Mice ; Nanotechnology ; Nucleic Acid Hybridization ; Rabbits
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  • 36
    Publication Date: 2007-01-27
    Description: The normal synovium forms a membrane at the edges of joints and provides lubrication and nutrients for the cartilage. In rheumatoid arthritis, the synovium is the site of inflammation, and it participates in an organized tissue response that damages cartilage and bone. We identified cadherin-11 as essential for the development of the synovium. Cadherin-11-deficient mice have a hypoplastic synovial lining, display a disorganized synovial reaction to inflammation, and are resistant to inflammatory arthritis. Cadherin-11 therapeutics prevent and reduce arthritis in mouse models. Thus, synovial cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, David M -- Kiener, Hans P -- Agarwal, Sandeep K -- Noss, Erika H -- Watts, Gerald F M -- Chisaka, Osamu -- Takeichi, Masatoshi -- Brenner, Michael B -- K08 AR2214/AR/NIAMS NIH HHS/ -- R01 AR48114/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):1006-10. Epub 2007 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17255475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/therapeutic use ; Arthritis, Experimental ; Arthritis, Rheumatoid/metabolism/*pathology/therapy ; Cadherins/*antagonists & inhibitors/biosynthesis/deficiency/*physiology ; Cell Adhesion/physiology ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Fibroblasts/metabolism ; L Cells (Cell Line) ; Male ; Mice ; Mice, Inbred C57BL ; Organ Culture Techniques ; Synovial Membrane/*cytology/*pathology
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2007 Nov 9;318(5852):899-900.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17991833" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Adult Stem Cells/chemistry/*cytology ; Animals ; Biomarkers/*analysis ; Brain/cytology/embryology ; Brain Chemistry ; Child ; Fatty Acids/analysis ; Hippocampus/chemistry/*cytology ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Mice ; Rats ; Stem Cells/chemistry/*cytology
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  • 38
    Publication Date: 2007-07-21
    Description: PDZ domains have long been thought to cluster into discrete functional classes defined by their peptide-binding preferences. We used protein microarrays and quantitative fluorescence polarization to characterize the binding selectivity of 157 mouse PDZ domains with respect to 217 genome-encoded peptides. We then trained a multidomain selectivity model to predict PDZ domain-peptide interactions across the mouse proteome with an accuracy that exceeds many large-scale, experimental investigations of protein-protein interactions. Contrary to the current paradigm, PDZ domains do not fall into discrete classes; instead, they are evenly distributed throughout selectivity space, which suggests that they have been optimized across the proteome to minimize cross-reactivity. We predict that focusing on families of interaction domains, which facilitates the integration of experimentation and modeling, will play an increasingly important role in future investigations of protein function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674608/" 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/PMC2674608/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stiffler, Michael A -- Chen, Jiunn R -- Grantcharova, Viara P -- Lei, Ying -- Fuchs, Daniel -- Allen, John E -- Zaslavskaia, Lioudmila A -- MacBeath, Gavin -- 1 RO1 GM072872-01/GM/NIGMS NIH HHS/ -- 5 T32 GM07598-25/GM/NIGMS NIH HHS/ -- R01 GM072872/GM/NIGMS NIH HHS/ -- R01 GM072872-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):364-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641200" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Animals ; Computational Biology ; Computer Simulation ; Fluorescence Polarization ; Mice ; Peptides/*metabolism ; Protein Array Analysis ; Protein Binding ; *Protein Structure, Tertiary ; Proteome/chemistry/*metabolism
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  • 39
    Publication Date: 2007-02-03
    Description: Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Heung Kyu -- Lund, Jennifer M -- Ramanathan, Balaji -- Mizushima, Noboru -- Iwasaki, Akiko -- AI054359/AI/NIAID NIH HHS/ -- AI064705/AI/NIAID NIH HHS/ -- AI07019/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 9;315(5817):1398-401. Epub 2007 Feb 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Dendritic Cells/*immunology/physiology/*virology ; Endosomes/immunology/virology ; Female ; Immunity, Innate ; Interferon-alpha/metabolism ; Interleukin-12/metabolism ; Lysosomes/virology ; Male ; Membrane Glycoproteins/*immunology ; Mice ; Mice, Transgenic ; Phagosomes/physiology/ultrastructure ; RNA, Viral/*immunology/metabolism ; Rhabdoviridae Infections/*immunology ; Toll-Like Receptor 7/*immunology ; Vesicular stomatitis Indiana virus/*immunology/physiology ; Virus Replication
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  • 40
    Publication Date: 2007-07-07
    Description: Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms and pathways involved are not well understood. Tumor development is regulated by products of several modifier genes, but instructions for their tumor-specific expression are currently unknown. We show that the signaling through the adaptor protein MyD88 has a critical role in spontaneous tumor development in mice with heterozygous mutation in the adenomatous polyposis coli (APC) gene. We found that MyD88-dependent signaling controls the expression of several key modifier genes of intestinal tumorigenesis and has a critical role in both spontaneous and carcinogen-induced tumor development. This study thus reveals the important role of an innate immune signaling pathway in intestinal tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rakoff-Nahoum, Seth -- Medzhitov, Ruslan -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):124-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Immunobiology, 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/17615359" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Proliferation ; Colonic Neoplasms/genetics/immunology/pathology/physiopathology ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Genes, APC ; Immunity, Innate ; Intestinal Neoplasms/genetics/immunology/pathology/*physiopathology ; Intestine, Large/pathology ; Intestine, Small/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/genetics/*physiology ; *Signal Transduction
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reis e Sousa, Caetano -- New York, N.Y. -- Science. 2007 Mar 9;315(5817):1376-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. caetano@cancer.org.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17347432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Cytokines/metabolism ; Dendritic Cells/*immunology/physiology/*virology ; Endosomes/immunology/virology ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/immunology ; Membrane Glycoproteins/immunology/physiology ; Mice ; Mice, Transgenic ; RNA, Viral/*immunology/metabolism ; Rhabdoviridae Infections/*immunology ; Signal Transduction ; Toll-Like Receptor 7/immunology/physiology ; Toll-Like Receptor 9/immunology/physiology ; Toll-Like Receptors/immunology/*physiology ; Vesicular stomatitis Indiana virus/*immunology/physiology ; Virus Replication
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  • 42
    Publication Date: 2007-05-19
    Description: Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kapranov, Philipp -- Cheng, Jill -- Dike, Sujit -- Nix, David A -- Duttagupta, Radharani -- Willingham, Aarron T -- Stadler, Peter F -- Hertel, Jana -- Hackermuller, Jorg -- Hofacker, Ivo L -- Bell, Ian -- Cheung, Evelyn -- Drenkow, Jorg -- Dumais, Erica -- Patel, Sandeep -- Helt, Gregg -- Ganesh, Madhavan -- Ghosh, Srinka -- Piccolboni, Antonio -- Sementchenko, Victor -- Tammana, Hari -- Gingeras, Thomas R -- N01-CO-12400/CO/NCI NIH HHS/ -- U01HG003147/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1484-8. Epub 2007 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Affymetrix Laboratory, Affymetrix, Inc., 3420 Central Expressway, Santa Clara, CA, 95051, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17510325" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytosol/metabolism ; Exons ; Gene Expression ; Genome ; *Genome, Human ; HeLa Cells ; Humans ; Mice ; Promoter Regions, Genetic ; RNA/*genetics/metabolism ; RNA Precursors/*genetics/metabolism ; RNA, Messenger/*genetics/*metabolism ; Synteny ; Terminator Regions, Genetic ; *Transcription, Genetic
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  • 43
    Publication Date: 2007-05-05
    Description: We found that, in the mouse visual cortex, action potentials generated in a single layer-2/3 pyramidal (excitatory) neuron can reliably evoke large, constant-latency inhibitory postsynaptic currents in other nearby pyramidal cells. This effect is mediated by axo-axonic ionotropic glutamate receptor-mediated excitation of the nerve terminals of inhibitory interneurons, which connect to the target pyramidal cells. Therefore, individual cortical excitatory neurons can generate inhibition independently from the somatic firing of inhibitory interneurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Ming -- Yoshimura, Yumiko -- Takada, Naoki -- Horibe, Shoko -- Komatsu, Yukio -- New York, N.Y. -- Science. 2007 May 4;316(5825):758-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478724" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/metabolism ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Glutamic Acid/metabolism/pharmacology ; *Inhibitory Postsynaptic Potentials ; Interneurons/physiology ; Mice ; Mice, Inbred C57BL ; Neural Inhibition ; Patch-Clamp Techniques ; Presynaptic Terminals/physiology ; Pyramidal Cells/*physiology ; Receptors, AMPA/physiology ; Receptors, Kainic Acid/physiology ; Synapses/*physiology ; Synaptic Transmission ; Visual Cortex/cytology/*physiology ; gamma-Aminobutyric Acid/metabolism
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  • 44
    Publication Date: 2007-04-28
    Description: By screening N-ethyl-N-nitrosourea-mutagenized animals for alterations in rhythms of wheel-running activity, we identified a mouse mutation, after hours (Afh). The mutation, a Cys(358)Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours in homozygotes. Circadian transcriptional and translational oscillations are attenuated in Afh mice. The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2::Luciferase tissue slices. Our in vivo and in vitro studies reveal a central role for Fbxl3 in mammalian circadian timekeeping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Godinho, Sofia I H -- Maywood, Elizabeth S -- Shaw, Linda -- Tucci, Valter -- Barnard, Alun R -- Busino, Luca -- Pagano, Michele -- Kendall, Rachel -- Quwailid, Mohamed M -- Romero, M Rosario -- O'neill, John -- Chesham, Johanna E -- Brooker, Debra -- Lalanne, Zuzanna -- Hastings, Michael H -- Nolan, Patrick M -- MC_U105170643/Medical Research Council/United Kingdom -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 May 11;316(5826):897-900. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463252" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; CLOCK Proteins ; COS Cells ; Cell Cycle Proteins/genetics/metabolism ; Cercopithecus aethiops ; *Circadian Rhythm/genetics ; Crosses, Genetic ; Cryptochromes ; F-Box Proteins/*genetics/*physiology ; Female ; Flavoproteins/genetics/metabolism ; Gene Expression Regulation ; Liver/metabolism ; Lung/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; *Point Mutation ; Suprachiasmatic Nucleus/metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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  • 45
    Publication Date: 2007-02-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):587.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272695" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Genetic Engineering ; Homeodomain Proteins/genetics/physiology ; Liver/cytology/*embryology ; Mice ; Organ Size ; Pancreas/cytology/*embryology ; Stem Cells/*physiology ; Trans-Activators/genetics/physiology
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  • 46
    Publication Date: 2007-04-21
    Description: Competition between neurons is necessary for refining neural circuits during development and may be important for selecting the neurons that participate in encoding memories in the adult brain. To examine neuronal competition during memory formation, we conducted experiments with mice in which we manipulated the function of CREB (adenosine 3',5'-monophosphate response element-binding protein) in subsets of neurons. Changes in CREB function influenced the probability that individual lateral amygdala neurons were recruited into a fear memory trace. Our results suggest a competitive model underlying memory formation, in which eligible neurons are selected to participate in amemorytrace as a function of their relative CREB activity at the time of learning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Jin-Hee -- Kushner, Steven A -- Yiu, Adelaide P -- Cole, Christy J -- Matynia, Anna -- Brown, Robert A -- Neve, Rachael L -- Guzowski, John F -- Silva, Alcino J -- Josselyn, Sheena A -- AG13622/AG/NIA NIH HHS/ -- P01HD33098/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):457-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446403" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiology ; Animals ; Conditioning (Psychology) ; Cyclic AMP Response Element-Binding Protein/genetics/*metabolism ; Cytoskeletal Proteins/genetics/metabolism ; Fear ; Genetic Vectors ; Memory/*physiology ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neuronal Plasticity ; Neurons/metabolism/*physiology ; Transcription, Genetic
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  • 47
    Publication Date: 2007-03-03
    Description: IKKepsilon is an IKK (inhibitor of nuclear factor kappaBkinase)-related kinase implicated in virus induction of interferon-beta (IFNbeta). We report that, although mice lacking IKKepsilon produce normal amounts of IFNbeta, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKKepsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKepsilon is activated by IFNbeta and that IKKepsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKepsilon plays a critical role in the IFN-inducible antiviral transcriptional response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tenoever, Benjamin R -- Ng, Sze-Ling -- Chua, Mark A -- McWhirter, Sarah M -- Garcia-Sastre, Adolfo -- Maniatis, Tom -- F31 AI056678/AI/NIAID NIH HHS/ -- P01AI058113/AI/NIAID NIH HHS/ -- R01AI46954/AI/NIAID NIH HHS/ -- U19AI62623/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1274-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332413" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/genetics/metabolism ; Animals ; Cells, Cultured ; Dimerization ; *Gene Expression Regulation ; I-kappa B Kinase/genetics/*metabolism ; *Influenza A Virus, H1N1 Subtype/immunology/physiology ; Interferon-Stimulated Gene Factor 3/metabolism ; Interferon-beta/*immunology/metabolism ; Lung/pathology/virology ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/*immunology/metabolism/pathology/virology ; Phosphorylation ; Promoter Regions, Genetic ; RNA-Binding Proteins ; STAT1 Transcription Factor/metabolism ; STAT2 Transcription Factor/metabolism ; Signal Transduction ; Transcription, Genetic ; Viral Load ; Virus Replication
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  • 48
    Publication Date: 2007-12-08
    Description: It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor-induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Jacob -- Wernig, Marius -- Markoulaki, Styliani -- Sun, Chiao-Wang -- Meissner, Alexander -- Cassady, John P -- Beard, Caroline -- Brambrink, Tobias -- Wu, Li-Chen -- Townes, Tim M -- Jaenisch, Rudolf -- 2-R01-HL057619/HL/NHLBI NIH HHS/ -- 5-R37-CA084198/CA/NCI NIH HHS/ -- 5-RO1-CA087869/CA/NCI NIH HHS/ -- 5-RO1-HDO45022/PHS HHS/ -- New York, N.Y. -- Science. 2007 Dec 21;318(5858):1920-3. Epub 2007 Dec 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18063756" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sickle Cell/blood/physiopathology/*therapy ; Animals ; Cell Differentiation ; Cells, Cultured ; *Cellular Reprogramming ; DNA-Binding Proteins/genetics ; Disease Models, Animal ; Embryonic Stem Cells/cytology ; Erythrocyte Count ; Fibroblasts/*cytology ; Genes, myc ; Globins/genetics ; Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology ; Hemoglobin A/analysis ; Hemoglobin, Sickle/analysis ; Humans ; Kidney Concentrating Ability ; Kruppel-Like Transcription Factors/genetics ; Male ; Mice ; Octamer Transcription Factor-3/genetics ; Pluripotent Stem Cells/*cytology ; SOXB1 Transcription Factors ; Trans-Activators/genetics ; Transduction, Genetic
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiNardo, Steve -- Braun, Robert E -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1696-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104-6058, USA. sdinardo@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885122" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Male ; Mice ; Pluripotent Stem Cells/cytology ; Spermatogonia/*cytology ; Testis/*cytology
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansson, Goran K -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):206-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Center for Molecular Medicine, Karolinska Institute, Stockholm, SE-17176, Sweden. goran.hansson@ki.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431157" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendritic Cells/physiology ; Humans ; Lipase/metabolism ; Lipids/*blood ; Liver/enzymology/*physiology ; Lymphotoxin beta Receptor/metabolism ; Lymphotoxin-alpha/*physiology ; Mice ; T-Lymphocytes/physiology ; Tumor Necrosis Factor Ligand Superfamily Member 14/*physiology
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  • 51
    Publication Date: 2007-07-14
    Description: The temporal and spatial regulation of gene expression in mammalian development is linked to the establishment of functional chromatin domains. Here, we report that tissue-specific transcription of a retrotransposon repeat in the murine growth hormone locus is required for gene activation. This repeat serves as a boundary to block the influence of repressive chromatin modifications. The repeat element is able to generate short, overlapping Pol II-and Pol III-driven transcripts, both of which are necessary and sufficient to enable a restructuring of the regulated locus into nuclear compartments. These data suggest that transcription of interspersed repetitive sequences may represent a developmental strategy for the establishment of functionally distinct domains within the mammalian genome to control gene activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lunyak, Victoria V -- Prefontaine, Gratien G -- Nunez, Esperanza -- Cramer, Thorsten -- Ju, Bong-Gun -- Ohgi, Kenneth A -- Hutt, Kasey -- Roy, Rosa -- Garcia-Diaz, Angel -- Zhu, Xiaoyan -- Yung, Yun -- Montoliu, Lluis -- Glass, Christopher K -- Rosenfeld, Michael G -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):248-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA. vlunyak@uscd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626886" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromatin Immunoprecipitation ; DNA Polymerase II/metabolism ; DNA Polymerase III/metabolism ; *Gene Expression Regulation, Developmental ; Growth Hormone/*genetics ; Histones/metabolism ; *Insulator Elements ; Methylation ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; *Organogenesis ; Pituitary Gland/*embryology/metabolism ; *Short Interspersed Nucleotide Elements ; *Transcription, Genetic ; Transcriptional Activation
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  • 52
    Publication Date: 2007-07-07
    Description: Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naugler, Willscott E -- Sakurai, Toshiharu -- Kim, Sunhwa -- Maeda, Shin -- Kim, Kyounghyun -- Elsharkawy, Ahmed M -- Karin, Michael -- CA118165/CA/NCI NIH HHS/ -- DK007202/DK/NIDDK NIH HHS/ -- ES004151/ES/NIEHS NIH HHS/ -- ES006376/ES/NIEHS NIH HHS/ -- R01 CA118165/CA/NCI NIH HHS/ -- R01 ES006376/ES/NIEHS NIH HHS/ -- T32 CA121938/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):121-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Tetrachloride/administration & dosage ; Diethylnitrosamine/administration & dosage/metabolism ; Estradiol/pharmacology ; Female ; Hepatocytes ; Interleukin-6/blood/genetics/*metabolism ; Kupffer Cells/*metabolism ; Liver/metabolism/pathology ; Liver Neoplasms, Experimental/chemically induced/immunology/*physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/*physiology ; Necrosis ; Ovariectomy ; RNA, Messenger/genetics/metabolism ; *Sex Characteristics
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  • 53
    Publication Date: 2007-02-10
    Description: Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guy, Jacky -- Gan, Jian -- Selfridge, Jim -- Cobb, Stuart -- Bird, Adrian -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1143-7. Epub 2007 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology, Edinburgh University, King's Buildings, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/metabolism ; Chimera ; Disease Models, Animal ; Female ; *Gene Expression Regulation ; Gene Targeting ; Long-Term Potentiation ; Male ; Methyl-CpG-Binding Protein 2/*genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Phenotype ; Rett Syndrome/*genetics/physiopathology/*therapy ; Synaptic Transmission ; Tamoxifen/pharmacology ; Transgenes
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  • 54
    Publication Date: 2007-04-28
    Description: MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell-dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thai, To-Ha -- Calado, Dinis Pedro -- Casola, Stefano -- Ansel, K Mark -- Xiao, Changchun -- Xue, Yingzi -- Murphy, Andrew -- Frendewey, David -- Valenzuela, David -- Kutok, Jeffery L -- Schmidt-Supprian, Marc -- Rajewsky, Nikolaus -- Yancopoulos, George -- Rao, Anjana -- Rajewsky, Klaus -- AI064345/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 27;316(5824):604-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463289" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Cytokines/biosynthesis ; Germinal Center/*immunology ; Immunoglobulin G/analysis ; Lymphocyte Activation ; Lymphotoxin-alpha/biosynthesis ; Lymphotoxin-beta/biosynthesis ; Mice ; Mice, Knockout ; Mice, Transgenic ; MicroRNAs/genetics/*physiology ; Nitrophenols/immunology ; Peyer's Patches/immunology ; Phenylacetates ; Somatic Hypermutation, Immunoglobulin ; Spleen/immunology ; T-Lymphocytes/cytology/*immunology/metabolism ; Th1 Cells/cytology/immunology ; Th2 Cells/cytology/immunology ; Tumor Necrosis Factor-alpha/biosynthesis
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hajnoczky, Gyorgy -- Hoek, Jan B -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):607-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. gyorgy.hajnoczky@jefferson.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272709" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; *Apoptosis ; Autophagy ; Calcium Signaling ; *Cell Aging ; Cytoplasm/metabolism ; Hydrogen Peroxide/metabolism/pharmacology ; Intracellular Membranes/metabolism ; Mice ; Mitochondria/*metabolism ; Models, Biological ; Peptidylprolyl Isomerase/metabolism ; Permeability ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Kinase C beta ; Protein Transport ; Reactive Oxygen Species/metabolism ; Shc Signaling Adaptor Proteins ; *Signal Transduction
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  • 56
    Publication Date: 2007-07-14
    Description: Changes in protein-protein interactions may allow polypeptides to perform unexpected regulatory functions. Mammalian ShcA docking proteins have amino-terminal phosphotyrosine (pTyr) binding (PTB) and carboxyl-terminal Src homology 2 (SH2) domains, which recognize specific pTyr sites on activated receptors, and a central region with two phosphorylated tyrosine-X-asparagine (pYXN) motifs (where X represents any amino acid) that each bind the growth factor receptor-bound protein 2 (Grb2) adaptor. Phylogenetic analysis indicates that ShcA may signal through both pYXN-dependent and -independent pathways. We show that, in mice, cardiomyocyte-expressed ShcA directs mid-gestational heart development by a PTB-dependent mechanism that does not require the pYXN motifs. In contrast, the pYXN motifs are required with PTB and SH2 domains in the same ShcA molecule for the formation of muscle spindles, skeletal muscle sensory organs that regulate motor behavior. Thus, combinatorial differences in ShcA docking interactions may yield multiple signaling mechanisms to support diversity in tissue morphogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575375/" 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/PMC2575375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hardy, W Rod -- Li, Lingying -- Wang, Zhi -- Sedy, Jiri -- Fawcett, James -- Frank, Eric -- Kucera, Jan -- Pawson, Tony -- R01 NS024373/NS/NINDS NIH HHS/ -- R01 NS024373-18/NS/NINDS NIH HHS/ -- R01 NS024373-19/NS/NINDS NIH HHS/ -- R01 NS024373-20/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):251-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626887" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Ataxia ; Excitatory Postsynaptic Potentials ; Genetic Complementation Test ; Heart/*embryology ; Mice ; Mice, Knockout ; *Morphogenesis ; Motor Activity ; Muscle Spindles/*embryology ; Muscle, Skeletal/*embryology/metabolism ; Mutation ; Myocytes, Cardiac/*metabolism ; Neurons, Afferent/physiology ; Phosphorylation ; Protein Structure, Tertiary ; Shc Signaling Adaptor Proteins ; Signal Transduction ; src Homology Domains
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: Much progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakaguchi, Shimon -- Powrie, Fiona -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):627-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Pathology, 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/17673654" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens/immunology ; Autoimmune Diseases/immunology ; Forkhead Transcription Factors/metabolism ; Homeostasis ; Humans ; Immune Tolerance ; Infection/immunology ; Inflammation/immunology ; Lymphocyte Activation ; Mice ; Self Tolerance ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/*immunology/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 58
    Publication Date: 2007-04-28
    Description: One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Busino, Luca -- Bassermann, Florian -- Maiolica, Alessio -- Lee, Choogon -- Nolan, Patrick M -- Godinho, Sofia I H -- Draetta, Giulio F -- Pagano, Michele -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- R01-GM57587/GM/NIGMS NIH HHS/ -- R21-CA125173/CA/NCI NIH HHS/ -- R37-CA76584/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):900-4. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463251" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; CLOCK Proteins ; Cell Cycle Proteins/genetics/metabolism ; Cells, Cultured ; *Circadian Rhythm/genetics ; Cryptochromes ; F-Box Proteins/genetics/*metabolism ; Flavoproteins/genetics/*metabolism ; HeLa Cells ; Humans ; Mice ; NIH 3T3 Cells ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; Promoter Regions, Genetic ; RNA Interference ; SKP Cullin F-Box Protein Ligases/*metabolism ; Trans-Activators/metabolism ; Transcription Factors/genetics/metabolism ; Transfection ; Ubiquitin/metabolism
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  • 59
    Publication Date: 2007-04-21
    Description: Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are depleted of repeat sequences, which raises questions about a role for mammalian Piwi's in transposon control. A search for murine small RNAs that might program Piwi proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which MILI catalyzes the formation of piRNA 5' ends. Mili mutants derepress LINE-1 (L1) and intracisternal A particle and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aravin, Alexei A -- Sachidanandam, Ravi -- Girard, Angelique -- Fejes-Toth, Katalin -- Hannon, Gregory J -- New York, N.Y. -- Science. 2007 May 4;316(5825):744-7. Epub 2007 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Howard Hughes Medical Institute (HHMI), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446352" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Argonaute Proteins ; Cluster Analysis ; Computational Biology ; DNA Methylation ; Genes, Intracisternal A-Particle ; Long Interspersed Nucleotide Elements ; Male ; Meiosis ; Mice ; Mutation ; Proteins/*metabolism ; RNA, Antisense/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; *Retroelements ; Reverse Transcriptase Polymerase Chain Reaction ; Short Interspersed Nucleotide Elements ; Spermatocytes/cytology/*metabolism ; Spermatogenesis ; *Suppression, Genetic
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  • 60
    Publication Date: 2007-10-06
    Description: Mounting a protective immune response is critically dependent on the orchestrated movement of cells within lymphoid organs. We report here the visualization, using major histocompatability complex class I tetramers, of the CD8-positive (CD8) T cell response in the spleens of mice to Listeria monocytogenes infection. A multistage pathway was revealed that included initial activation at the borders of the B and T cell zones followed by cluster formation with antigenpresenting cells leading to CD8 T cell exit to the red pulp via bridging channels. Strikingly, many memory CD8 T cells localized to the B cell zones and, when challenged, underwent rapid migration to the T cell zones where proliferation occurred, followed by egress via bridging channels in parallel with the primary response. Thus, the ability to track endogenous immune responses has uncovered both distinct and overlapping mechanisms and anatomical locations driving primary and secondary immune responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846662/" 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/PMC2846662/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khanna, Kamal M -- McNamara, Jeffery T -- Lefrancois, Leo -- AI41576/AI/NIAID NIH HHS/ -- AI56172/AI/NIAID NIH HHS/ -- DRG-1886-05/PHS HHS/ -- P01 AI056172/AI/NIAID NIH HHS/ -- P01 AI056172-05/AI/NIAID NIH HHS/ -- R01 AI041576/AI/NIAID NIH HHS/ -- R01 AI041576-06/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Oct 5;318(5847):116-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University of Connecticut, Farmington, CT 06030, U.S.A.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916739" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD/analysis ; Antigens, CD8/analysis ; B-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology/physiology ; Cell Movement ; Dendritic Cells/immunology/physiology ; Fluorescent Dyes ; Histocompatibility Antigens Class I ; *Immunologic Memory ; Kinetics ; Listeria monocytogenes/*immunology ; Listeriosis/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Receptors, Antigen, T-Cell/analysis ; Spleen/cytology/*immunology ; Staining and Labeling ; T-Lymphocyte Subsets/cytology/immunology/physiology
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  • 61
    Publication Date: 2007-03-03
    Description: A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, John T -- Palanivel, Vikram R -- Kinjyo, Ichiko -- Schambach, Felix -- Intlekofer, Andrew M -- Banerjee, Arnob -- Longworth, Sarah A -- Vinup, Kristine E -- Mrass, Paul -- Oliaro, Jane -- Killeen, Nigel -- Orange, Jordan S -- Russell, Sarah M -- Weninger, Wolfgang -- Reiner, Steven L -- AI007532/AI/NIAID NIH HHS/ -- AI042370/AI/NIAID NIH HHS/ -- AI053827/AI/NIAID NIH HHS/ -- AI055428/AI/NIAID NIH HHS/ -- AI061699/AI/NIAID NIH HHS/ -- AI069380/AI/NIAID NIH HHS/ -- CA114114/CA/NCI NIH HHS/ -- CA87812/CA/NCI NIH HHS/ -- DK007066/DK/NIDDK NIH HHS/ -- GM007170/GM/NIGMS NIH HHS/ -- R01 AI061699/AI/NIAID NIH HHS/ -- T32 AI055428/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 23;315(5819):1687-91. Epub 2007 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332376" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen Presentation ; Antigens, CD/analysis ; Antigens, CD8/analysis ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation ; *Cell Division ; Cell Lineage ; Cell Polarity ; Dendritic Cells/immunology ; *Immunologic Memory ; Intracellular Signaling Peptides and Proteins/metabolism ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Lymphocyte Activation ; Membrane Proteins/analysis ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitosis ; Nerve Tissue Proteins/analysis ; Protein Kinase C/metabolism ; Receptors, Antigen, T-Cell/immunology ; Receptors, Interferon/analysis ; Signal Transduction ; T-Lymphocyte Subsets/*cytology/*immunology ; T-Lymphocytes, Helper-Inducer/immunology
    Print ISSN: 0036-8075
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  • 62
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sapienza, Carmen -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):46-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fels Institute for Cancer Research and Department of Pathology, Temple University Medical School, 3307 North Broad Street, Philadelphia, PA 19140, USA. sapienza@temple.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axonemal Dyneins ; Body Patterning ; Cell Line ; Cells, Cultured ; Chromatids/*physiology ; *Chromosome Segregation ; DNA Replication ; Dyneins/*genetics/*physiology ; Ectoderm/*cytology ; Embryonic Stem Cells/*cytology ; Endoderm/*cytology ; Interphase ; Mice ; Mitosis ; Recombination, Genetic ; Spindle Apparatus/physiology/ultrastructure
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  • 63
    Publication Date: 2007-05-15
    Description: Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell-instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978506/" 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/PMC2978506/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeda, Takahiro -- Merghoub, Taha -- Hobbs, Robin M -- Dong, Lin -- Maeda, Manami -- Zakrzewski, Johannes -- van den Brink, Marcel R M -- Zelent, Arthur -- Shigematsu, Hirokazu -- Akashi, Koichi -- Teruya-Feldstein, Julie -- Cattoretti, Giorgio -- Pandolfi, Pier Paolo -- CA-102142/CA/NCI NIH HHS/ -- R01 CA102142/CA/NCI NIH HHS/ -- R01 CA102142-06A1/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):860-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495164" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*cytology/physiology ; Bone Marrow Cells/cytology ; Cell Lineage ; Cells, Cultured ; DNA-Binding Proteins/*genetics/physiology ; Gene Deletion ; Hematopoietic Stem Cells/*cytology/physiology ; *Lymphopoiesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Biological ; *Proto-Oncogenes ; Receptors, Notch/*metabolism ; Signal Transduction ; T-Lymphocytes/*cytology/physiology ; Thymus Gland/cytology ; Transcription Factors/*genetics/physiology
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  • 64
    Publication Date: 2007-09-01
    Description: MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide, non-protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons (DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs and is deficient in midbrain tissue from patients with Parkinson's disease. miR-133b regulates the maturation and function of midbrain DNs within a negative feedback circuit that includes the paired-like homeodomain transcription factor Pitx3. We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782470/" 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/PMC2782470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jongpil -- Inoue, Keiichi -- Ishii, Jennifer -- Vanti, William B -- Voronov, Sergey V -- Murchison, Elizabeth -- Hannon, Gregory -- Abeliovich, Asa -- R01 NS064433/NS/NINDS NIH HHS/ -- R01 NS064433-01/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1220-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pathology and Neurology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons 15-403, 630 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761882" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Aged ; Aged, 80 and over ; Animals ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Dopamine/*metabolism ; Embryonic Stem Cells ; *Feedback, Physiological ; Female ; Gene Expression Regulation ; Homeodomain Proteins/*metabolism ; Humans ; Locomotion ; Male ; Mesencephalon/cytology/*metabolism ; Mice ; MicroRNAs/*metabolism ; Middle Aged ; Models, Biological ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Rats ; Ribonuclease III/genetics/metabolism ; Transcription Factors/*metabolism ; Transcription, Genetic
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  • 65
    Publication Date: 2007-06-09
    Description: We describe a sensitive mRNA profiling technology, PMAGE (for "polony multiplex analysis of gene expression"), which detects messenger RNAs (mRNAs) as rare as one transcript per three cells. PMAGE incorporates an improved ligation-based method to sequence 14-nucleotide tags derived from individual mRNA molecules. One sequence tag from each mRNA molecule is amplified onto a separate 1-micrometer bead, denoted as a polymerase colony or polony, and about 5 million polonies are arrayed in a flow cell for parallel sequencing. Using PMAGE, we identified early transcriptional changes that preceded pathological manifestations of hypertrophic cardiomyopathy in mice carrying a disease-causing mutation. PMAGE provided a comprehensive profile of cardiac mRNAs, including low-abundance mRNAs encoding signaling molecules and transcription factors that are likely to participate in disease pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jae Bum -- Porreca, Gregory J -- Song, Lei -- Greenway, Steven C -- Gorham, Joshua M -- Church, George M -- Seidman, Christine E -- Seidman, J G -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1481-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17556586" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiomyopathy, Hypertrophic/*genetics/pathology/physiopathology ; DNA, Complementary ; Fibrosis/genetics/pathology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Gene Library ; Heart Ventricles/metabolism ; Mice ; Mutation ; Myocardial Contraction ; Myocardium/*metabolism ; Myosin Heavy Chains/genetics ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Templates, Genetic ; Transcription Factors/genetics ; *Transcription, Genetic ; Ventricular Myosins/genetics
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hebert, Sebastien S -- De Strooper, Bart -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1179-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetics, VIB and KULeuven, Herestraat 49, Leuven, Belgium. bart.destrooper@med.kuleuven.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761871" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Animals ; Brain/physiology/*physiopathology ; Cell Death ; Cell Differentiation ; Cells, Cultured ; Dopamine/*metabolism ; Feedback, Physiological ; Humans ; Mice ; MicroRNAs/genetics/*metabolism ; Neurodegenerative Diseases/genetics/*physiopathology ; Neurons/cytology/metabolism/*physiology ; Parkinson Disease/genetics/*physiopathology ; RNA, Messenger/genetics/metabolism ; Ribonuclease III/metabolism ; Transcription Factors/metabolism
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  • 67
    Publication Date: 2007-08-04
    Description: Toll-like receptors (TLRs) trigger the production of inflammatory cytokines and shape adaptive and innate immunity to pathogens. We report the identification of B cell leukemia (Bcl)-3 as an essential negative regulator of TLR signaling. By blocking ubiquitination of p50, a member of the nuclear factor (NF)-kappaB family, Bcl-3 stabilizes a p50 complex that inhibits gene transcription. As a consequence, Bcl-3-deficient mice and cells were found to be hypersensitive to TLR activation and unable to control responses to lipopolysaccharides. Thus, p50 ubiquitination blockade by Bcl-3 limits the strength of TLR responses and maintains innate immune homeostasis. These findings indicate that the p50 ubiquitination pathway can be selectively targeted to control deleterious inflammatory diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carmody, Ruaidhri J -- Ruan, Qingguo -- Palmer, Scott -- Hilliard, Brendan -- Chen, Youhai H -- AI069289/AI/NIAID NIH HHS/ -- AI50059/AI/NIAID NIH HHS/ -- DK070691/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):675-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, 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/17673665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; DNA/metabolism ; Female ; Half-Life ; Immune Tolerance ; Immunity, Innate ; Lipopolysaccharides/immunology ; Macrophage Activation ; Macrophages, Peritoneal/*immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B p50 Subunit/*metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/*metabolism ; *Signal Transduction ; Toll-Like Receptors/*metabolism ; Transcription Factor RelA/metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; Tumor Necrosis Factor-alpha/genetics/metabolism ; Ubiquitin/metabolism
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  • 68
    Publication Date: 2007-08-04
    Description: The cellular immune response to tissue damage and infection requires the recruitment of blood leukocytes. This process is mediated through a classical multistep mechanism, which involves transient rolling on the endothelium and recognition of inflammation followed by extravasation. We have shown, by direct examination of blood monocyte functions in vivo, that a subset of monocytes patrols healthy tissues through long-range crawling on the resting endothelium. This patrolling behavior depended on the integrin LFA-1 and the chemokine receptor CX(3)CR1 and was required for rapid tissue invasion at the site of an infection by this "resident" monocyte population, which initiated an early immune response and differentiated into macrophages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Auffray, Cedric -- Fogg, Darin -- Garfa, Meriem -- Elain, Gaelle -- Join-Lambert, Olivier -- Kayal, Samer -- Sarnacki, Sabine -- Cumano, Ana -- Lauvau, Gregoire -- Geissmann, Frederic -- G0900867/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):666-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Nationale de la Sante et de la Recherche Medicale (INSERM) U838, Laboratory of Biology of the Mononuclear Phagocyte System, and Cellular and Molecular imaging core facility, Institut Federatif de Recherche Necker-Enfants Malades, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673663" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/*immunology ; Cell Adhesion ; Cell Differentiation ; Cell Movement ; Dermis/immunology ; Endothelium, Vascular/*immunology ; Gene Expression Regulation ; Immunity, Innate ; Inflammation/*immunology ; Listeria monocytogenes ; Listeriosis/immunology ; Lymphocyte Function-Associated Antigen-1/physiology ; Macrophages/cytology/immunology ; Mesenteric Arteries/immunology ; Mesenteric Veins/immunology ; Mice ; Microscopy, Confocal ; Monocytes/cytology/*immunology/physiology ; Receptors, Chemokine/analysis/physiology
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  • 69
    Publication Date: 2007-11-17
    Description: CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Ana C -- Anderson, David E -- Bregoli, Lisa -- Hastings, William D -- Kassam, Nasim -- Lei, Charles -- Chandwaskar, Rucha -- Karman, Jozsef -- Su, Ee W -- Hirashima, Mitsuomi -- Bruce, Jeffrey N -- Kane, Lawrence P -- Kuchroo, Vijay K -- Hafler, David A -- R01 AI067544/AI/NIAID NIH HHS/ -- R01 AI067544-01A2/AI/NIAID NIH HHS/ -- R56 AI067544/AI/NIAID NIH HHS/ -- R56 AI067544-01A1/AI/NIAID NIH HHS/ -- R56 AI067544-02/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1141-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006747" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD11b/immunology ; Astrocytes/immunology ; Central Nervous System Neoplasms/immunology ; Dendritic Cells/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Galectins/immunology ; Glioblastoma/immunology ; Humans ; Immunity, Innate ; Inflammation Mediators/*immunology ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Membrane Proteins/biosynthesis/*immunology ; Mice ; Microglia/immunology ; Multiple Sclerosis/immunology ; Rats ; Receptors, Immunologic/biosynthesis/*immunology ; Receptors, Virus/biosynthesis/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Th1 Cells/*immunology ; Toll-Like Receptors
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  • 70
    Publication Date: 2007-10-13
    Description: Jacobs et al. (Reports, 23 March 2007, p. 1723) reported that plasticity in the mammalian visual system permitted the emergence of "a new dimension of sensory experience" in mice genetically engineered to express a human long-wavelength-sensitive cone photopigment. However, neither neural plasticity nor a new dimension of sensory experience is required to explain their results.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Makous, Walter -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):196; author reply 196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Visual Science, University of Rochester, Rochester, NY 14627, USA. walt@cvs.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932271" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Color Perception/genetics ; Genetic Engineering ; Humans ; Light ; Mice ; *Neuronal Plasticity ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Pigments/*genetics/*physiology
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  • 71
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; *Embryonic Stem Cells ; Humans ; *Intellectual Property ; Mice ; *Patents as Topic/legislation & jurisprudence ; Primates ; Wisconsin
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  • 72
    Publication Date: 2007-03-03
    Description: Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945222/" 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/PMC2945222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, Arya -- Radhakrishnan, Jayaram -- Wang, He -- Mani, Alaleh -- Mani, Mohammad-Ali -- Nelson-Williams, Carol -- Carew, Khary S -- Mane, Shrikant -- Najmabadi, Hossein -- Wu, Dan -- Lifton, Richard P -- K08 HD041481/HD/NICHD NIH HHS/ -- K08 HD041481-01/HD/NICHD NIH HHS/ -- P01DK68229/DK/NIDDK NIH HHS/ -- P50 HL55007/HL/NHLBI 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 AR051476-04/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1278-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA. arya.mani@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332414" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Animals ; Chromosomes, Human, Pair 12/genetics ; Coronary Disease/*genetics/metabolism ; Family Health ; Female ; Genetic Linkage ; *Genetic Predisposition to Disease ; Humans ; LDL-Receptor Related Proteins/*genetics/physiology ; Lipids/blood ; Low Density Lipoprotein Receptor-Related Protein-6 ; Male ; Metabolic Syndrome X/*genetics/metabolism ; Mice ; Middle Aged ; *Mutation, Missense ; NIH 3T3 Cells ; Osteoporosis/genetics ; Pedigree ; Risk Factors ; Signal Transduction ; Wnt Proteins/metabolism
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  • 73
    Publication Date: 2007-10-06
    Description: Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Azzalin, Claus M -- Reichenbach, Patrick -- Khoriauli, Lela -- Giulotto, Elena -- Lingner, Joachim -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):798-801. Epub 2007 Oct 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916692" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Cells, Cultured ; Chromosomes, Human ; Chromosomes, Mammalian ; HeLa Cells ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; Molecular Sequence Data ; Proteins/metabolism ; RNA/*genetics ; Repetitive Sequences, Nucleic Acid ; Telomerase/physiology ; Telomere/*genetics ; Transcription, Genetic ; Tumor Cells, Cultured
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):760-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289957" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology/transplantation ; Animals ; Bone Marrow Cells/*cytology ; Bone Marrow Transplantation ; Cell Culture Techniques ; Cell Differentiation ; Cell Fusion ; Embryonic Stem Cells/cytology ; Hematopoiesis ; Humans ; Mice ; Multipotent Stem Cells/*cytology/transplantation ; Pluripotent Stem Cells/cytology ; Stromal Cells/*cytology/transplantation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1211-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332387" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/metabolism/*therapeutic use ; Apoptosis ; Clinical Trials as Topic ; Drug Screening Assays, Antitumor ; *Genes, p53 ; Genetic Engineering ; Humans ; Imidazolines/therapeutic use ; Mice ; Mutation ; Neoplasm Transplantation ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Proto-Oncogene Proteins c-mdm2/metabolism ; Pyrimidines/metabolism/therapeutic use ; Tumor Suppressor Protein p53/*metabolism
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  • 76
    Publication Date: 2007-02-27
    Description: MicroRNAs (miRNAs) are approximately 22-nucleotide RNAs that can pair to sites within messenger RNAs to specify posttranscriptional repression of these messages. Aberrant miRNA expression can contribute to tumorigenesis, but which of the many miRNA-target relationships are relevant to this process has been unclear. Here, we report that chromosomal translocations previously associated with human tumors disrupt repression of High Mobility Group A2 (Hmga2) by let-7 miRNA. This disrupted repression promotes anchorage-independent growth, a characteristic of oncogenic transformation. Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556962/" 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/PMC2556962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayr, Christine -- Hemann, Michael T -- Bartel, David P -- R01 DK068348/DK/NIDDK NIH HHS/ -- R01 DK068348-01/DK/NIDDK NIH HHS/ -- R01 DK068348-02/DK/NIDDK NIH HHS/ -- R01 DK068348-03/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 16;315(5818):1576-9. Epub 2007 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17322030" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic/*genetics ; Gene Expression Regulation ; Genes, Tumor Suppressor ; HMGA2 Protein/*genetics ; HeLa Cells ; Humans ; Mice ; Mice, Nude ; MicroRNAs/*genetics ; NIH 3T3 Cells ; Neoplasms, Experimental/etiology/genetics ; Oncogenes ; Transfection ; *Translocation, Genetic
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faustman, Denise L -- P30 DK040561/DK/NIDDK NIH HHS/ -- P30 DK040561-12/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):196.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626866" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes Mellitus, Type 1/*therapy ; Freund's Adjuvant/*therapeutic use ; Mice ; Mice, Inbred NOD ; Research Design
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bannerman, David M -- Sprengel, Rolf -- 087736/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):50-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK. david.bannerman@psy.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning (Psychology) ; Cues ; Dentate Gyrus/cytology/*physiology ; Discrimination (Psychology) ; Fear ; Hippocampus/cytology/physiology ; Learning/*physiology ; Maze Learning ; Memory/*physiology ; Mice ; *Neuronal Plasticity ; Neurons/physiology ; *Pattern Recognition, Physiological ; Pyramidal Cells/physiology ; Receptors, N-Methyl-D-Aspartate/genetics/*physiology ; Synapses/*physiology
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  • 79
    Publication Date: 2007-04-28
    Description: Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barabe, Frederic -- Kennedy, James A -- Hope, Kristin J -- Dick, John E -- New York, N.Y. -- Science. 2007 Apr 27;316(5824):600-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463288" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Transplantation ; Cell Transformation, Neoplastic ; *Disease Models, Animal ; Disease Progression ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Genes, Immunoglobulin ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/metabolism ; Humans ; Immunoglobulin Heavy Chains/genetics ; *Leukemia, Lymphoid/pathology/physiopathology ; *Leukemia, Myeloid/pathology/physiopathology ; Mice ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Oncogene Proteins, Fusion/*genetics ; Transduction, Genetic ; Tumor Cells, Cultured
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  • 80
    Publication Date: 2007-01-06
    Description: MicroRNAs (miRNAs) negatively regulate partially complementary target messenger RNAs. Target selection in animals is dictated primarily by sequences at the miRNA 5' end. We demonstrated that despite their small size, specific miRNAs contain additional sequence elements that control their posttranscriptional behavior, including their subcellular localization. We showed that human miR-29b, in contrast to other studied animal miRNAs, is predominantly localized to the nucleus. The distinctive hexanucleotide terminal motif of miR-29b acts as a transferable nuclear localization element that directs nuclear enrichment of miRNAs or small interfering RNAs to which it is attached. Our results indicate that miRNAs sharing common 5' sequences, considered to be largely redundant, might have distinct functions because of the influence of cis-acting regulatory motifs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hwang, Hun-Way -- Wentzel, Erik A -- Mendell, Joshua T -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):97-100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204650" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Apoptosis ; Base Sequence ; Cell Nucleus/*metabolism ; HeLa Cells ; Humans ; Mice ; MicroRNAs/*chemistry/*metabolism ; Mitosis ; Mutation ; NIH 3T3 Cells ; Oligoribonucleotides/chemistry/*metabolism ; RNA Processing, Post-Transcriptional ; RNA Stability ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonuclease III/metabolism ; Transcription, Genetic
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferber, Dan -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):191-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Communication ; Chemotaxis, Leukocyte/drug effects ; Dendritic Cells/*physiology ; Humans ; Lymphocyte Activation ; Mice ; Receptors, Antigen, T-Cell/physiology ; Receptors, Lymphocyte Homing/physiology ; Sheep ; T-Lymphocytes/*physiology
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  • 82
    Publication Date: 2007-06-09
    Description: Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-d-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McHugh, Thomas J -- Jones, Matthew W -- Quinn, Jennifer J -- Balthasar, Nina -- Coppari, Roberto -- Elmquist, Joel K -- Lowell, Bradford B -- Fanselow, Michael S -- Wilson, Matthew A -- Tonegawa, Susumu -- G0501146/Medical Research Council/United Kingdom -- MH62122/MH/NIMH NIH HHS/ -- P50-MH58880/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):94-9. Epub 2007 Jun 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Department of Biology and Department of Brain and Cognitive Sciences, 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/17556551" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Conditioning (Psychology) ; Cues ; Dentate Gyrus/cytology/*physiology ; Discrimination (Psychology) ; Excitatory Postsynaptic Potentials ; Fear ; Hippocampus/cytology/*physiology ; Learning/*physiology ; Maze Learning ; Memory/*physiology ; Mice ; Mice, Knockout ; *Neuronal Plasticity ; *Pattern Recognition, Physiological ; Perforant Pathway ; Pyramidal Cells/physiology ; Receptors, N-Methyl-D-Aspartate/genetics/*physiology ; Recombination, Genetic ; Synaptic Transmission
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  • 83
    Publication Date: 2007-04-28
    Description: Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity, branched, tubular plasma membrane invaginations accumulated, capped by clathrin-coated pits, in synapses of dynamin 1-knockout mice. Synaptic vesicle endocytosis was severely impaired during strong exogenous stimulation but resumed efficiently when the stimulus was terminated. Thus, dynamin 1-independent mechanisms can support limited synaptic vesicle endocytosis, but dynamin 1 is needed during high levels of neuronal activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferguson, Shawn M -- Brasnjo, Gabor -- Hayashi, Mitsuko -- Wolfel, Markus -- Collesi, Chiara -- Giovedi, Silvia -- Raimondi, Andrea -- Gong, Liang-Wei -- Ariel, Pablo -- Paradise, Summer -- O'toole, Eileen -- Flavell, Richard -- Cremona, Ottavio -- Miesenbock, Gero -- Ryan, Timothy A -- De Camilli, Pietro -- CA46128/CA/NCI NIH HHS/ -- D.061/Telethon/Italy -- DA018343/DA/NIDA NIH HHS/ -- DA17297/DA/NIDA NIH HHS/ -- DK45735/DK/NIDDK NIH HHS/ -- NS036942/NS/NINDS NIH HHS/ -- NS36251/NS/NINDS NIH HHS/ -- P30 DA018343/DA/NIDA NIH HHS/ -- R01 NS036942/NS/NINDS NIH HHS/ -- RR-000592/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 27;316(5824):570-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Kavli Institute for Neuroscience, 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/17463283" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Cell Membrane/ultrastructure ; Clathrin-Coated Vesicles/metabolism/ultrastructure ; Dynamin I/genetics/*physiology ; Dynamin II ; Dynamin III/physiology ; Electric Stimulation ; *Endocytosis ; Excitatory Postsynaptic Potentials ; Exocytosis ; Inhibitory Postsynaptic Potentials ; Mice ; Mice, Knockout ; Microscopy, Electron ; Neurons/*physiology/ultrastructure ; Patch-Clamp Techniques ; Presynaptic Terminals/physiology/ultrastructure ; Synapses/*physiology/ultrastructure ; Synaptic Transmission ; Synaptic Vesicles/*physiology/ultrastructure
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  • 84
    Publication Date: 2007-11-24
    Description: Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic beta cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP7 or IP7). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP7 were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in beta cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP7 in the pancreatic beta cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Illies, Christopher -- Gromada, Jesper -- Fiume, Roberta -- Leibiger, Barbara -- Yu, Jia -- Juhl, Kirstine -- Yang, Shao-Nian -- Barma, Deb K -- Falck, John R -- Saiardi, Adolfo -- Barker, Christopher J -- Berggren, Per-Olof -- GM31278/GM/NIGMS NIH HHS/ -- MC_U122680443/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Nov 23;318(5854):1299-302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18033884" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cricetinae ; Electric Capacitance ; *Exocytosis ; Inositol Phosphates/*metabolism ; Insulin/*secretion ; Insulin-Secreting Cells/*metabolism/secretion ; Islets of Langerhans/metabolism ; Mice ; Patch-Clamp Techniques ; Phosphotransferases (Phosphate Group Acceptor)/genetics/metabolism ; Phytic Acid/metabolism ; RNA Interference ; Rats ; Secretory Vesicles/*metabolism ; Transfection
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLaren, Anne -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):339.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446356" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Embryo Research ; Embryonic Stem Cells/*cytology/physiology ; Female ; Humans ; Male ; Mice ; Nuclear Transfer Techniques ; *Oocyte Donation/ethics ; Ovum/*cytology/physiology ; Spermatozoa/cytology/physiology
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  • 86
    Publication Date: 2007-06-16
    Description: alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan. In mice, we found the molecular association of alpha-Klotho (alpha-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an alpha-Kl- and Na+,K+-ATPase-dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of alpha-Kl in the regulation of calcium metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imura, Akihiro -- Tsuji, Yoshihito -- Murata, Miyahiko -- Maeda, Ryota -- Kubota, Koji -- Iwano, Akiko -- Obuse, Chikashi -- Togashi, Kazuya -- Tominaga, Makoto -- Kita, Naoko -- Tomiyama, Ken-ichi -- Iijima, Junko -- Nabeshima, Yoko -- Fujioka, Makio -- Asato, Ryo -- Tanaka, Shinzo -- Kojima, Ken -- Ito, Juichi -- Nozaki, Kazuhiko -- Hashimoto, Nobuo -- Ito, Tetsufumi -- Nishio, Takeshi -- Uchiyama, Takashi -- Fujimori, Toshihiko -- Nabeshima, Yo-ichi -- New York, N.Y. -- Science. 2007 Jun 15;316(5831):1615-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17569864" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/cerebrospinal fluid/*metabolism ; Cell Membrane/enzymology/metabolism ; Choroid Plexus/metabolism ; Cytoplasm/enzymology/metabolism ; Endoplasmic Reticulum/metabolism ; Endosomes/metabolism ; Enzyme Inhibitors/pharmacology ; Feedback, Physiological ; Glucuronidase/genetics/metabolism/*physiology ; Golgi Apparatus/metabolism ; HeLa Cells ; *Homeostasis ; Humans ; Ion Transport ; Kidney/enzymology/metabolism ; Mice ; Ouabain/pharmacology ; Parathyroid Glands/enzymology/metabolism ; Parathyroid Hormone/secretion ; Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors/metabolism
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):33-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204619" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/immunology ; Crohn Disease/genetics/immunology/microbiology ; Flagellin/immunology ; Humans ; *Immunity, Innate ; Inflammatory Bowel Diseases/drug therapy/genetics/*immunology/microbiology ; Interleukin-17/biosynthesis/immunology ; Interleukin-23/*immunology ; Intestines/immunology/microbiology ; Mice ; Mutation ; Nod2 Signaling Adaptor Protein/genetics/physiology ; Polymorphism, Single Nucleotide ; T-Lymphocyte Subsets/*immunology ; T-Lymphocytes, Helper-Inducer/*immunology ; Toll-Like Receptor 5/genetics/physiology
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  • 88
    Publication Date: 2007-06-16
    Description: The inflammatory toxicity of lipopolysaccharide (LPS), a component of bacterial cell walls, is driven by the adaptor proteins myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta (TRIF), which together mediate signaling by the endotoxin receptor Toll-like receptor 4 (TLR4). Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with useful immunostimulatory properties, which is nearing regulatory approval for use as a human vaccine adjuvant. We report here that, in mice, the low toxicity of MPLA's adjuvant function is associated with a bias toward TRIF signaling, which we suggest is likely caused by the active suppression, rather than passive loss, of proinflammatory activity of this LPS derivative. This finding may have important implications for the development of future vaccine adjuvants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mata-Haro, Veronica -- Cekic, Caglar -- Martin, Michael -- Chilton, Paula M -- Casella, Carolyn R -- Mitchell, Thomas C -- AI059023/AI/NIAID NIH HHS/ -- AI51377/AI/NIAID NIH HHS/ -- K02 AI059023/AI/NIAID NIH HHS/ -- R01 AI051377/AI/NIAID NIH HHS/ -- R01 AI071047/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 15;316(5831):1628-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cellular Therapeutics, University of Louisville, 570 South Preston Street, Louisville, KY 40202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17569868" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/*metabolism ; *Adjuvants, Immunologic/administration & dosage/toxicity ; Adoptive Transfer ; Animals ; Cytokines/biosynthesis ; Immunization ; Lipid A/administration & dosage/*analogs & derivatives/immunology/toxicity ; Lipopolysaccharides/immunology ; Lymphocyte Activation ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Monocytes/immunology ; Myeloid Differentiation Factor 88/metabolism ; Oligonucleotide Array Sequence Analysis ; Ovalbumin/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; Toll-Like Receptor 4/*agonists/*immunology/metabolism
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  • 89
    Publication Date: 2007-05-05
    Description: The adapter protein ADAP regulates T lymphocyte adhesion and activation. We present evidence for a previously unrecognized function for ADAP in regulating T cell receptor (TCR)-mediated activation of the transcription factor NF-kappaB. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-kappaB, a reduced DNA binding, and delayed degradation and decreased phosphorylation of IkappaB (inhibitor of NF-kappaB). TCR-stimulated assembly of the CARMA1-BCL-10-MALT1 complex was substantially impaired in the absence of ADAP. We further identified a region of ADAP that is required for association with the CARMA1 adapter and NF-kappaB activation but is not required for ADAP-dependent regulation of adhesion. These findings provide new insights into ADAP function and the mechanism by which CARMA1 regulates NF-kappaB activation in T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Medeiros, Ricardo B -- Burbach, Brandon J -- Mueller, Kristen L -- Srivastava, Rupa -- Moon, James J -- Highfill, Sarah -- Peterson, Erik J -- Shimizu, Yoji -- F32 AI063793/AI/NIAID NIH HHS/ -- F32 AI063793-01A1/AI/NIAID NIH HHS/ -- F32AI063793/AI/NIAID NIH HHS/ -- R01AI038474/AI/NIAID NIH HHS/ -- R01AI056016/AI/NIAID NIH HHS/ -- T32DE007288/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2007 May 4;316(5825):754-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478723" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism ; Animals ; Antigens, CD28/immunology ; Antigens, CD3/immunology ; Apoptosis Regulatory Proteins/*metabolism ; CARD Signaling Adaptor Proteins/*metabolism ; Caspases/metabolism ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Humans ; I-kappa B Proteins/metabolism ; Isoenzymes/metabolism ; Jurkat Cells ; Lymphocyte Activation ; Mice ; Mutation ; Neoplasm Proteins/metabolism ; Protein Kinase C/metabolism ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell/immunology ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; T-Lymphocytes/*immunology/*metabolism ; Transcription Factor RelA/*metabolism
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chng, Wee J -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):762; author reply 764-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics ; Colorectal Neoplasms/*genetics ; Consensus Sequence ; Disease Models, Animal ; *Genes, Neoplasm ; Genome, Human ; Humans ; Mice ; Mutagenesis ; *Mutation ; Neoplasms/*genetics ; Sequence Analysis, DNA
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  • 91
    Publication Date: 2007-07-28
    Description: MicroRNAs (miRNAs) play an important role in gene regulatory networks in animals. Yet, the mechanistic details of their function in translation inhibition or messenger RNA (mRNA) destabilization remain controversial. To directly examine the earliest events in this process, we have developed an in vitro translation system using mouse Krebs-2 ascites cell-free extract that exhibits an authentic miRNA response. We show here that translation initiation, specifically the 5' cap recognition process, is repressed by endogenous let-7 miRNAs within the first 15 minutes of mRNA exposure to the extract when no destabilization of the transcript is observed. Our results indicate that inhibition of translation initiation is the earliest molecular event effected by miRNAs. Other mechanisms, such as mRNA degradation, may subsequently consolidate mRNA silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathonnet, Geraldine -- Fabian, Marc R -- Svitkin, Yuri V -- Parsyan, Armen -- Huck, Laurent -- Murata, Takayuki -- Biffo, Stefano -- Merrick, William C -- Darzynkiewicz, Edward -- Pillai, Ramesh S -- Filipowicz, Witold -- Duchaine, Thomas F -- Sonenberg, Nahum -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1764-7. Epub 2007 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada, H3G 1Y6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17656684" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Krebs 2 ; Cell Extracts ; Encephalomyocarditis virus/genetics ; Eukaryotic Initiation Factor-4F/*physiology ; Gene Expression Regulation/*physiology ; Luciferases, Renilla/genetics ; Mice ; MicroRNAs/*physiology ; Protein Biosynthesis/*physiology ; RNA Caps/*physiology ; Ribosomes/metabolism
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-10-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):178-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryonic Stem Cells ; *Genetic Techniques/history ; Great Britain ; History, 20th Century ; History, 21st Century ; Mice ; *Mice, Knockout ; *Nobel Prize ; United States
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  • 93
    Publication Date: 2007-01-16
    Description: alphabeta and gammadelta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gammadelta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gammadelta T cell development while opposing alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gammadelta T cells but not alphabeta T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melichar, Heather J -- Narayan, Kavitha -- Der, Sandy D -- Hiraoka, Yoshiki -- Gardiol, Noemie -- Jeannet, Gregoire -- Held, Werner -- Chambers, Cynthia A -- Kang, Joonsoo -- R01CA100382/92614/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 12;315(5809):230-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17218525" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/genetics ; Autoantigens/genetics/*metabolism ; Cell Line ; Cell Lineage ; Cell Proliferation ; Embryonic Development ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Rearrangement, T-Lymphocyte ; High Mobility Group Proteins/genetics/*metabolism ; Humans ; *Lymphopoiesis ; Mice ; Mice, Transgenic ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; Receptors, Antigen, T-Cell, gamma-delta/*analysis/genetics ; Signal Transduction ; T Cell Transcription Factor 1/physiology ; T-Lymphocyte Subsets/*cytology/immunology/metabolism ; Wnt Proteins/metabolism
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  • 94
    Publication Date: 2007-05-26
    Description: Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuoka, Shuhei -- Ballif, Bryan A -- Smogorzewska, Agata -- McDonald, E Robert 3rd -- Hurov, Kristen E -- Luo, Ji -- Bakalarski, Corey E -- Zhao, Zhenming -- Solimini, Nicole -- Lerenthal, Yaniv -- Shiloh, Yosef -- Gygi, Steven P -- Elledge, Stephen J -- 1U19A1067751/PHS HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1160-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525332" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ataxia Telangiectasia Mutated Proteins ; Binding Sites ; Cell Cycle/physiology ; Cell Cycle Proteins/*physiology ; Cell Line ; Computational Biology ; Consensus Sequence ; *DNA Damage ; *DNA Repair ; DNA Replication/physiology ; DNA-Binding Proteins/*physiology ; Humans ; Immunoprecipitation ; Isotope Labeling ; Mice ; NIH 3T3 Cells ; Phosphorylation ; Protein-Serine-Threonine Kinases/*physiology ; Proteome/isolation & purification/physiology ; RNA, Small Interfering ; Signal Transduction ; Substrate Specificity ; Tumor Suppressor Proteins/*physiology
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  • 95
    Publication Date: 2007-11-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- Holden, Constance -- New York, N.Y. -- Science. 2007 Nov 23;318(5854):1224-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18033853" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Animals ; *Cell Line ; *Cellular Reprogramming ; *Cloning, Organism ; Embryonic Stem Cells/*cytology ; Female ; Gene Transfer Techniques ; Humans ; Macaca mulatta ; Male ; Mice ; Pluripotent Stem Cells/*cytology ; Skin/*cytology/embryology
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  • 96
    Publication Date: 2007-08-19
    Description: Carbon dioxide (CO2) is an important environmental cue for many organisms but is odorless to humans. It remains unclear whether the mammalian olfactory system can detect CO2 at concentrations around the average atmospheric level (0.038%). We demonstrated the expression of carbonic anhydrase type II (CAII), an enzyme that catabolizes CO2, in a subset of mouse olfactory neurons that express guanylyl cyclase D (GC-D+ neurons) and project axons to necklace glomeruli in the olfactory bulb. Exposure to CO2 activated these GC-D+ neurons, and exposure of a mouse to CO2 activated bulbar neurons associated with necklace glomeruli. Behavioral tests revealed CO2 detection thresholds of approximately 0.066%, and this sensitive CO2 detection required CAII activity. We conclude that mice detect CO2 at near-atmospheric concentrations through the olfactory subsystem of GC-D+ neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Ji -- Zhong, Chun -- Ding, Cheng -- Chi, Qiuyi -- Walz, Andreas -- Mombaerts, Peter -- Matsunami, Hiroaki -- Luo, Minmin -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):953-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Biological Sciences, Beijing, 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Dioxide/administration & dosage/*analysis/metabolism ; Carbonic Anhydrase II/antagonists & inhibitors/genetics/metabolism ; Cyclic GMP/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 2 ; Cyclic Nucleotide-Gated Cation Channels ; Gene Expression Profiling ; Guanylate Cyclase/metabolism ; Ion Channels/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation ; Neurons/*physiology ; Odors ; Olfactory Bulb/cytology/enzymology/*physiology ; Olfactory Mucosa/cytology/enzymology ; Olfactory Receptor Neurons/enzymology/*physiology ; Phosphoric Diester Hydrolases/metabolism
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cibelli, Jose -- New York, N.Y. -- Science. 2007 Dec 21;318(5858):1879-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Sciences, Cellular Reprogramming Laboratory, Michigan State University, East Lansing, MI 48824, USA. cibelli@msu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18096796" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sickle Cell/therapy ; Animals ; Cell Dedifferentiation ; Cell Differentiation ; *Cellular Reprogramming ; Embryonic Stem Cells/cytology ; Fibroblasts/*cytology ; Gene Transfer Techniques ; Genetic Vectors ; Hematopoietic Stem Cells/cytology ; Humans ; Mice ; *Nuclear Transfer Techniques ; Pluripotent Stem Cells/*cytology ; Primates ; Transcription Factors/*genetics/metabolism
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  • 98
    Publication Date: 2007-11-03
    Description: Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Menuz, Karen -- Stroud, Robert M -- Nicoll, Roger A -- Hays, Franklin A -- GM078754/GM/NIGMS NIH HHS/ -- P50 GM73210/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):815-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975069" target="_blank"〉PubMed〈/a〉
    Keywords: 6-Cyano-7-nitroquinoxaline-2,3-dione/chemistry/*pharmacology ; Animals ; Benzodiazepines/pharmacology ; Binding, Competitive ; Cell Line ; Cerebellum/cytology ; Crystallography, X-Ray ; *Drug Partial Agonism ; Hippocampus/cytology ; Humans ; In Vitro Techniques ; Interneurons/drug effects ; Mice ; Models, Molecular ; Patch-Clamp Techniques ; Protein Conformation ; Protein Subunits/*physiology ; Pyramidal Cells/drug effects/metabolism ; Quinoxalines/pharmacology ; Receptors, AMPA/*agonists/*antagonists & inhibitors ; Structure-Activity Relationship ; Synaptic Transmission/drug effects ; Trichlormethiazide/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behringer, Richard R -- New York, N.Y. -- Science. 2007 May 4;316(5825):697-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. rrb@mdanderson.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478706" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology/physiology ; Blastocyst Inner Cell Mass/cytology ; Blastomeres/cytology/*physiology ; Body Patterning ; Cell Division ; Cell Lineage ; Cell Movement ; *Embryonic Development ; Green Fluorescent Proteins ; Mice ; Mice, Transgenic ; Microscopy, Fluorescence ; Motion Pictures as Topic ; Zona Pellucida/physiology/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2007-12-08
    Description: Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrens, M Margarita -- Ali, Sameh S -- Dao, Diep N -- Lucero, Jacinta -- Shekhtman, Grigoriy -- Quick, Kevin L -- Dugan, Laura L -- New York, N.Y. -- Science. 2007 Dec 7;318(5856):1645-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Geriatric Medicine, University of California San Diego, La Jolla, CA 92093-0746, USA. mbehrens@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18063801" target="_blank"〉PubMed〈/a〉
    Keywords: Acetophenones/pharmacology ; Animals ; Brain/*drug effects/enzymology/metabolism ; Cells, Cultured ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Glutamate Decarboxylase/metabolism ; Interneurons/*drug effects/enzymology/*metabolism ; Ketamine/*pharmacology ; Male ; Membrane Glycoproteins/*metabolism ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase/*metabolism ; Oxidation-Reduction ; Parvalbumins/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Superoxides/*metabolism ; Synaptic Transmission/drug effects ; Synaptosomes/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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