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  • 1
    Publication Date: 2001-01-06
    Description: Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S T -- Benson, B G -- Bramson, H N -- Chapman, D E -- Dickerson, S H -- Dold, K M -- Eberwein, D J -- Edelstein, M -- Frye, S V -- Gampe Jr, R T -- Griffin, R J -- Harris, P A -- Hassell, A M -- Holmes, W D -- Hunter, R N -- Knick, V B -- Lackey, K -- Lovejoy, B -- Luzzio, M J -- Murray, D -- Parker, P -- Rocque, W J -- Shewchuk, L -- Veal, J M -- Walker, D H -- Kuyper, L F -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):134-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. std41085@glaxowellcome.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141566" target="_blank"〉PubMed〈/a〉
    Keywords: Alopecia/*chemically induced/*prevention & control ; Animals ; Animals, Newborn ; Antineoplastic Agents/*toxicity ; Antineoplastic Combined Chemotherapy Protocols/toxicity ; Apoptosis/drug effects ; *CDC2-CDC28 Kinases ; Cell Cycle/drug effects ; Cell Line ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/*antagonists & inhibitors/metabolism ; Cyclophosphamide/toxicity ; Cytoprotection/drug effects ; DNA/biosynthesis ; Doxorubicin/toxicity ; Drug Design ; Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology ; Epithelium/drug effects ; Etoposide/toxicity ; Hair Follicle/cytology/*drug effects ; Humans ; Indoles/chemical synthesis/chemistry/*pharmacology ; Mice ; Mice, SCID ; Phosphorylation ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Rats ; Retinoblastoma Protein/metabolism ; Scalp/transplantation ; Sulfonamides/chemical synthesis/chemistry/*pharmacology ; Transplantation, Heterologous
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hart-Davis, A -- New York, N.Y. -- Science. 2001 Apr 6;292(5514):55-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11294215" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2001-03-27
    Description: Analysis of Global Positioning System (GPS) data demonstrates that ongoing three-dimensional crustal deformation in Fennoscandia is dominated by glacial isostatic adjustment. Our comparison of these GPS observations with numerical predictions yields an Earth model that satisfies independent geologic constraints and bounds both the average viscosity in the upper mantle (5 x 10(20) to 1 x 10(21) pascal seconds) and the elastic thickness of the lithosphere (90 to 170 kilometers). We combined GPS-derived radial motions with Fennoscandian tide gauge records to estimate a regional sea surface rise of 2.1 +/- 0.3 mm/year. Furthermore, ongoing horizontal tectonic motions greater than approximately 1 mm/year are ruled out on the basis of the GPS-derived three-dimensional crustal velocity field.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milne, G A -- Davis, J L -- Mitrovica, J X -- Scherneck, H G -- Johansson, J M -- Vermeer, M -- Koivula, H -- New York, N.Y. -- Science. 2001 Mar 23;291(5512):2381-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geological Sciences, University of Durham, Durham DH1 3LE, UK. g.a.milne@durham.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11264528" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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  • 4
    Publication Date: 2001-07-28
    Description: The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galibert, F -- Finan, T M -- Long, S R -- Puhler, A -- Abola, P -- Ampe, F -- Barloy-Hubler, F -- Barnett, M J -- Becker, A -- Boistard, P -- Bothe, G -- Boutry, M -- Bowser, L -- Buhrmester, J -- Cadieu, E -- Capela, D -- Chain, P -- Cowie, A -- Davis, R W -- Dreano, S -- Federspiel, N A -- Fisher, R F -- Gloux, S -- Godrie, T -- Goffeau, A -- Golding, B -- Gouzy, J -- Gurjal, M -- Hernandez-Lucas, I -- Hong, A -- Huizar, L -- Hyman, R W -- Jones, T -- Kahn, D -- Kahn, M L -- Kalman, S -- Keating, D H -- Kiss, E -- Komp, C -- Lelaure, V -- Masuy, D -- Palm, C -- Peck, M C -- Pohl, T M -- Portetelle, D -- Purnelle, B -- Ramsperger, U -- Surzycki, R -- Thebault, P -- Vandenbol, M -- Vorholter, F J -- Weidner, S -- Wells, D H -- Wong, K -- Yeh, K C -- Batut, J -- GM30962/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 27;293(5530):668-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR6061-CNRS, Laboratoire de Genetique et Developpement, Faculte de Medecine, 2 avenue du Pr. Leon Bernard, F-35043 Rennes cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11474104" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Adhesion ; Bacterial Proteins/genetics ; Carrier Proteins/genetics ; Chromosomes, Bacterial/genetics ; Computational Biology ; DNA Transposable Elements ; Energy Metabolism/genetics ; Evolution, Molecular ; Gene Duplication ; Genes, Bacterial ; Genes, Essential ; Genes, Regulator ; *Genome, Bacterial ; Medicago sativa/microbiology ; Nitrogen/metabolism ; Nitrogen Fixation/genetics ; Plasmids ; Polysaccharides, Bacterial/genetics ; Replicon ; Rhizobiaceae/genetics ; *Sequence Analysis, DNA ; Sinorhizobium meliloti/*genetics/physiology ; Symbiosis/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2001-12-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hotchkiss, R S -- Dunne, W M -- Swanson, P E -- Davis, C G -- Tinsley, K W -- Chang, K C -- Buchman, T G -- Karl, I E -- GM44118/GM/NIGMS NIH HHS/ -- GM55194/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA. hotch@morpheus.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729269" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/genetics/metabolism ; *Apoptosis ; Bronchi/enzymology/metabolism/pathology/ultrastructure ; Caspase 3 ; Caspases/metabolism ; Chromatin/metabolism/pathology/ultrastructure ; DNA, Single-Stranded/analysis ; Endothelium, Vascular/enzymology/metabolism/pathology ; Epithelial Cells/enzymology/metabolism/pathology/ultrastructure ; False Positive Reactions ; Gene Deletion ; In Situ Nick-End Labeling ; Lymphocytes/enzymology/metabolism/pathology ; Mice ; Microscopy, Electron ; Pneumonia, Bacterial/enzymology/metabolism/*pathology ; Pseudomonas Infections/enzymology/metabolism/*pathology ; Pseudomonas aeruginosa/*physiology ; Reproducibility of Results ; Sepsis/enzymology/metabolism/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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  • 6
    Publication Date: 2001-02-07
    Description: Locomotor activity by diving marine mammals is accomplished while breath-holding and often exceeds predicted aerobic capacities. Video sequences of freely diving seals and whales wearing submersible cameras reveal a behavioral strategy that improves energetic efficiency in these animals. Prolonged gliding (greater than 78% descent duration) occurred during dives exceeding 80 meters in depth. Gliding was attributed to buoyancy changes with lung compression at depth. By modifying locomotor patterns to take advantage of these physical changes, Weddell seals realized a 9.2 to 59.6% reduction in diving energetic costs. This energy-conserving strategy allows marine mammals to increase aerobic dive duration and achieve remarkable depths despite limited oxygen availability when submerged.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, T M -- Davis, R W -- Fuiman, L A -- Francis, J -- Le Boeuf, B J -- Horning, M -- Calambokidis, J -- Croll, D A -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):133-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, EMS-A316, University of California, Santa Cruz, CA 95064, USA. williams@darwin.ucsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753116" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diving/*physiology ; Dolphins/*physiology ; Energy Metabolism ; Hydrostatic Pressure ; Lung/physiology ; Lung Volume Measurements ; *Oxygen Consumption ; Seals, Earless/*physiology ; Swimming/*physiology ; Video Recording ; Whales/*physiology
    Print ISSN: 0036-8075
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  • 7
    Publication Date: 2001-12-26
    Description: The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive daily rhythms of behavior by secreting factors that act locally within the hypothalamus. In a systematic screen, we identified transforming growth factor-alpha (TGF-alpha) as a likely SCN inhibitor of locomotion. TGF-alpha is expressed rhythmically in the SCN, and when infused into the third ventricle it reversibly inhibited locomotor activity and disrupted circadian sleep-wake cycles. These actions are mediated by epidermal growth factor (EGF) receptors on neurons in the hypothalamic subparaventricular zone. Mice with a hypomorphic EGF receptor mutation exhibited excessive daytime locomotor activity and failed to suppress activity when exposed to light. These results implicate EGF receptor signaling in the daily control of locomotor activity, and identify a neural circuit in the hypothalamus that likely mediates the regulation of behavior both by the SCN and the retina.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kramer, A -- Yang, F C -- Snodgrass, P -- Li, X -- Scammell, T E -- Davis, F C -- Weitz, C J -- HD-18686/HD/NICHD NIH HHS/ -- MH62589/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2511-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11752569" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/drug effects/physiology ; Body Temperature/drug effects ; Cerebral Ventricles/metabolism ; Circadian Rhythm/drug effects/*physiology ; Cricetinae ; Darkness ; Epidermal Growth Factor/pharmacology ; Female ; Hypothalamus/*metabolism ; Ligands ; Light ; Male ; Mesocricetus ; Mice ; *Motor Activity/drug effects ; Neural Pathways/physiology ; Neurons/metabolism ; Point Mutation ; Receptor, Epidermal Growth Factor/genetics/*metabolism ; Retina/metabolism ; Retinal Ganglion Cells/metabolism ; Signal Transduction ; Sleep/drug effects/*physiology ; Suprachiasmatic Nucleus/*metabolism ; Transforming Growth Factor alpha/administration & ; dosage/genetics/metabolism/pharmacology
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  • 8
    Publication Date: 2001-04-28
    Description: Tree taxa shifted latitude or elevation range in response to changes in Quaternary climate. Because many modern trees display adaptive differentiation in relation to latitude or elevation, it is likely that ancient trees were also so differentiated, with environmental sensitivities of populations throughout the range evolving in conjunction with migrations. Rapid climate changes challenge this process by imposing stronger selection and by distancing populations from environments to which they are adapted. The unprecedented rates of climate changes anticipated to occur in the future, coupled with land use changes that impede gene flow, can be expected to disrupt the interplay of adaptation and migration, likely affecting productivity and threatening the persistence of many species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, M B -- Shaw, R G -- New York, N.Y. -- Science. 2001 Apr 27;292(5517):673-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution and Behavior, University of Minnesota, Saint Paul, MN 55108, USA. mbdavis@ecology.umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11326089" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Biological Evolution ; *Climate ; *Ecosystem ; Genes, Plant ; Genetic Variation ; Genetics, Population ; Pollen ; Time ; Trees/genetics/*growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 9
    Publication Date: 2001-09-15
    Description: Throughout the past four decades, silicon semiconductor technology has advanced at exponential rates in both performance and productivity. Concerns have been raised, however, that the limits of silicon technology may soon be reached. Analysis of fundamental, material, device, circuit, and system limits reveals that silicon technology has an enormous remaining potential to achieve terascale integration (TSI) of more than 1 trillion transistors per chip. Such massive-scale integration is feasible assuming the development and economical mass production of double-gate metal-oxide-semiconductor field effect transistors with gate oxide thickness of about 1 nanometer, silicon channel thickness of about 3 nanometers, and channel length of about 10 nanometers. The development of interconnecting wires for these transistors presents a major challenge to the achievement of nanoelectronics for TSI.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meindl, J D -- Chen, Q -- Davis, J A -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2044-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Electrical and Computer Engineering, Microelectronics Research Center, Georgia Institute of Technology, Atlanta, GA 30332-0269, USA. james.meindl@mirc.gatech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11557881" target="_blank"〉PubMed〈/a〉
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  • 10
    Publication Date: 2001-06-09
    Description: The mushroom bodies of the Drosophila brain are important for olfactory learning and memory. To investigate the requirement for mushroom body signaling during the different phases of memory processing, we transiently inactivated neurotransmission through this region of the brain by expressing a temperature-sensitive allele of the shibire dynamin guanosine triphosphatase, which is required for synaptic transmission. Inactivation of mushroom body signaling through alpha/beta neurons during different phases of memory processing revealed a requirement for mushroom body signaling during memory retrieval, but not during acquisition or consolidation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGuire, S E -- Le, P T -- Davis, R L -- NS19904/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 17;293(5533):1330-3. Epub 2001 Jun 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397912" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/physiology ; Animals ; Brain/physiology ; Conditioning, Classical ; Drosophila/genetics/*physiology ; *Drosophila Proteins ; Dynamins ; Electroshock ; GTP Phosphohydrolases/genetics/physiology ; Gene Targeting ; Genes, Insect ; Memory/*physiology ; Mental Recall/physiology ; Mutation ; Neurons/*physiology ; *Odors ; Signal Transduction ; *Synaptic Transmission ; Temperature ; Transgenes
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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