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  • 1
    Publication Date: 2001-10-06
    Description: We synthesized multimetal microrods intrinsically encoded with submicrometer stripes. Complex striping patterns are readily prepared by sequential electrochemical deposition of metal ions into templates with uniformly sized pores. The differential reflectivity of adjacent stripes enables identification of the striping patterns by conventional light microscopy. This readout mechanism does not interfere with the use of fluorescence for detection of analytes bound to particles by affinity capture, as demonstrated by DNA and protein bioassays.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicewarner-Pena, S R -- Freeman, R G -- Reiss, B D -- He, L -- Pena, D J -- Walton, I D -- Cromer, R -- Keating, C D -- Natan, M J -- HG02228/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):137-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, 152 Davey Laboratory, University Park, PA 16802, USA., SurroMed Inc., 2375 Garcia Avenue, Mountain View, CA 94043, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biochemistry/*methods ; Chemistry Techniques, Analytical/*methods ; Electrochemistry ; Fluorescence ; Fluorescent Antibody Technique ; Humans ; Immunoassay/*methods ; Immunoglobulin G/analysis ; *Metals ; Microscopy ; Miniaturization ; Nucleic Acid Hybridization/*methods ; Oligonucleotide Probes ; Optics and Photonics ; Rabbits ; Templates, 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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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-04-17
    Description: Examples of multiplication by neurons or neural circuits are scarce, although many computational models use this basic operation. The owl's auditory system computes interaural time (ITD) and level (ILD) differences to create a two-dimensional map of auditory space. Space-specific neurons are selective for combinations of ITD and ILD, which define, respectively, the horizontal and vertical dimensions of their receptive fields. A multiplication of separate postsynaptic potentials tuned to ITD and ILD, rather than an addition, can account for the subthreshold responses of these neurons to ITD-ILD pairs. Other nonlinear processes improve the spatial tuning of the spike output and reduce the fit to the multiplicative model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pena, J L -- Konishi, M -- DC00134/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2001 Apr 13;292(5515):249-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA. jose@etho.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11303092" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Action Potentials ; Animals ; Auditory Pathways ; Auditory Perception/*physiology ; Female ; Inferior Colliculi/cytology/*physiology ; Male ; Mathematics ; Membrane Potentials ; Neurons/*physiology ; Sound Localization/*physiology ; Strigiformes/*physiology ; *Synaptic Transmission
    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: 2008-12-02
    Description: MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thum, Thomas -- Gross, Carina -- Fiedler, Jan -- Fischer, Thomas -- Kissler, Stephan -- Bussen, Markus -- Galuppo, Paolo -- Just, Steffen -- Rottbauer, Wolfgang -- Frantz, Stefan -- Castoldi, Mirco -- Soutschek, Jurgen -- Koteliansky, Victor -- Rosenwald, Andreas -- Basson, M Albert -- Licht, Jonathan D -- Pena, John T R -- Rouhanifard, Sara H -- Muckenthaler, Martina U -- Tuschl, Thomas -- Martin, Gail R -- Bauersachs, Johann -- Engelhardt, Stefan -- R01 CA059998/CA/NCI NIH HHS/ -- R01 CA78711/CA/NCI NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):980-4. doi: 10.1038/nature07511. Epub 2008 Nov 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine I, Interdisziplinares Zentrum fur Klinische Forschung (IZKF), University of Wuerzburg, 97080 Wuerzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19043405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiomyopathies/*genetics/*metabolism/pathology/therapy ; Cell Line ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblasts/*metabolism ; Gene Silencing ; Humans ; *MAP Kinase Signaling System ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/*genetics ; Myocytes, Cardiac/cytology/metabolism ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-11-13
    Description: The pressures on honeybee (Apis mellifera) populations, resulting from threats by modern pesticides, parasites, predators and diseases, have raised awareness of the economic importance and critical role this insect plays in agricultural societies across the globe. However, the association of humans with A. mellifera predates post-industrial-revolution agriculture, as evidenced by the widespread presence of ancient Egyptian bee iconography dating to the Old Kingdom (approximately 2400 BC). There are also indications of Stone Age people harvesting bee products; for example, honey hunting is interpreted from rock art in a prehistoric Holocene context and a beeswax find in a pre-agriculturalist site. However, when and where the regular association of A. mellifera with agriculturalists emerged is unknown. One of the major products of A. mellifera is beeswax, which is composed of a complex suite of lipids including n-alkanes, n-alkanoic acids and fatty acyl wax esters. The composition is highly constant as it is determined genetically through the insect's biochemistry. Thus, the chemical 'fingerprint' of beeswax provides a reliable basis for detecting this commodity in organic residues preserved at archaeological sites, which we now use to trace the exploitation by humans of A. mellifera temporally and spatially. Here we present secure identifications of beeswax in lipid residues preserved in pottery vessels of Neolithic Old World farmers. The geographical range of bee product exploitation is traced in Neolithic Europe, the Near East and North Africa, providing the palaeoecological range of honeybees during prehistory. Temporally, we demonstrate that bee products were exploited continuously, and probably extensively in some regions, at least from the seventh millennium cal BC, likely fulfilling a variety of technological and cultural functions. The close association of A. mellifera with Neolithic farming communities dates to the early onset of agriculture and may provide evidence for the beginnings of a domestication process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roffet-Salque, Melanie -- Regert, Martine -- Evershed, Richard P -- Outram, Alan K -- Cramp, Lucy J E -- Decavallas, Orestes -- Dunne, Julie -- Gerbault, Pascale -- Mileto, Simona -- Mirabaud, Sigrid -- Paakkonen, Mirva -- Smyth, Jessica -- Soberl, Lucija -- Whelton, Helen L -- Alday-Ruiz, Alfonso -- Asplund, Henrik -- Bartkowiak, Marta -- Bayer-Niemeier, Eva -- Belhouchet, Lotfi -- Bernardini, Federico -- Budja, Mihael -- Cooney, Gabriel -- Cubas, Miriam -- Danaher, Ed M -- Diniz, Mariana -- Domboroczki, Laszlo -- Fabbri, Cristina -- Gonzalez-Urquijo, Jesus E -- Guilaine, Jean -- Hachi, Slimane -- Hartwell, Barrie N -- Hofmann, Daniela -- Hohle, Isabel -- Ibanez, Juan J -- Karul, Necmi -- Kherbouche, Farid -- Kiely, Jacinta -- Kotsakis, Kostas -- Lueth, Friedrich -- Mallory, James P -- Manen, Claire -- Marciniak, Arkadiusz -- Maurice-Chabard, Brigitte -- Mc Gonigle, Martin A -- Mulazzani, Simone -- Ozdogan, Mehmet -- Peric, Olga S -- Peric, Slavisa R -- Petrasch, Jorg -- Petrequin, Anne-Marie -- Petrequin, Pierre -- Poensgen, Ulrike -- Pollard, C Joshua -- Poplin, Francois -- Radi, Giovanna -- Stadler, Peter -- Stauble, Harald -- Tasic, Nenad -- Urem-Kotsou, Dushka -- Vukovic, Jasna B -- Walsh, Fintan -- Whittle, Alasdair -- Wolfram, Sabine -- Zapata-Pena, Lydia -- Zoughlami, Jamel -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 Nov 12;527(7577):226-30. doi: 10.1038/nature15757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Organic Geochemistry Unit, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK. ; CEPAM - Cultures et Environnements. Prehistoire, Antiquite, Moyen Age, UMR 7264, Universite Nice Sophia Antipolis - CNRS, 06300 Nice, France. ; Department of Archaeology, University of Exeter, Laver Building, North Park Road, Exeter, Devon EX4 4QE, UK. ; Department of Archaeology and Anthropology, University of Bristol, 43 Woodland Road, Bristol BS8 1UU, UK. ; Universite Bordeaux Montaigne, 33607 Pessac, France. ; Laboratoire du Centre de Recherche et de Restauration des Musees de France (C2RMF), UMR 171, Palais du Louvre, Porte des Lions, 14 Quai Francois Mitterrand, 75001 Paris, France. ; Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. ; Department of Anthropology, University College London, London WC1H 0BW, UK. ; Institut fur Prahistorische Archaologie, Freie Universitat Berlin, Altensteinstr. 15, Berlin 14195, Germany. ; Department of Archaeology, University of Turku, 20014 Turun Yliopisto, Finland. ; University of Ljubljana, Faculty of Arts, Department of Archaeology, Askerceva 2, box 580, 1000 Ljubljana, Slovenia. ; Department of Geography, Prehistory and Archaeology. University of Basque Country (EHU-UPV), Francisco Tomas y Valiente s/n, 01006 Vitoria-Gasteiz, Spain. ; Institute of Prehistory, Adam Mickiewicz University, Umultowska 89d, 61-614 Poznan, Poland. ; Museum Quintana - Archaologie in Kunzing, Partnermuseum der Archaologischen Staatssammlung Munchen, Osterhofener Str. 2, 94550 Kunzing, Germany. ; Musee Archeologique de Sousse, Rue Marshall Tito, 4000 Sousse, Tunisia. ; Centro Fermi, Museo Storico della Fisica e Centro di Studi e Ricerche Enrico Fermi, 00184 Rome, Italy. ; Multidisciplinary Laboratory, The Abdus Salam International Centre for Theoretical Physics, 34151 Trieste, Italy. ; UCD School of Archaeology, University College Dublin, Dublin 4, Ireland. ; International Institute for Prehistoric Research of Cantabria, University of Cantabria, Avd de los Castros s/n, 39005 Santander, Spain. ; Department of Archaeology, University College Galway, Galway, Ireland. ; UNIARQ-Departamento de Historia, Faculdade de Letras de Lisboa, Universidade de Lisboa, 1600-214 Lisboa, Portugal. ; Istvan Dobo Castle Museum, Var ut 1, 3300 Eger, Hungary. ; Dipartimento Civilta e Forme del Sapere, Universita di Pisa, Via Galvani 1, 56126 Pisa, Italy. ; CNRS - UMR 5608 - TRACES, Maison de la recherche, Universite Toulouse Jean Jaures, 5 Allee Antonio Machado, 31058 Toulouse cedex 9, France. ; CNRPAH, Centre National de Recherche Prehistorique, Anthropologique et Historique, Algiers, Algeria. ; School of Geography, Archaeology and Palaeoecology, Queen's University Belfast, Belfast BT7 1NN, UK. ; Universitat Hamburg, Archaologisches Institut, Edmund-Siemers-Allee 1, Flugel West, 20146 Hamburg, Germany. ; a.r.t.e.s. Graduate School for the Humanities Cologne, Graduiertenschule der Philosophischen Fakultat, Aachener Str. 217, 50931 Cologne, Germany. ; IMF-CSIC, Egipciacas 15, 08001 Barcelona, Spain. ; Istanbul University, Faculty of Letters, Department of Prehistory, 34434 Laleli Istanbul, Turkey. ; Eachtra Archaeological Projects, Lickybeg, Clashmore, County Waterford, Ireland. ; School of History and Archaeology, Faculty of Philosophy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. ; German Archaeological Institute, Podbielskiallee 69-71, 14 195 Berlin, Germany. ; Musee Rolin, 3 rue des Bancs, 71400 Autun, France. ; John Cronin &Associates, 28 Upper Main Street, Buncrana, County Donegal, Ireland. ; Aix-Marseille Universite, CNRS, Ministere de la Culture et de la Communication, UMR 7269 LAMPEA, LabexMed, 13284 Marseille, France. ; Dipartimento di Biologia Ambientale, Universita degli Studi di Roma La Sapienza, Rome 00185, Italy. ; Institute of Archaeology Belgrade, Kneza Mihaila 35/4 11000 Belgrade, Serbia. ; Eberhard-Karls-Universitat Tubingen, Institut fur Ur- und Fruhgeschichte und Archaologie des Mittelalters - Abt. Jungere Urgeschichte und Fruhgeschichte - Schloss Hohentubingen, 72070 Tubingen, Germany. ; Maison des Sciences de l'Homme et de l'Environnement C.N. Ledoux, CNRS &Universite de Franche-Comte, 32 rue Megevand, 25030 Besancon Cedex, France. ; Kampfenstr. 20, 78315 Radolfzell, Germany. ; Department of Archaeology, Faculty of Humanities, University of Southampton, Avenue Campus, Highfield, Southampton SO17 1BF, UK. ; Museum National d'Histoire Naturelle, 55 rue de Buffon, 75005 Paris, France. ; Department of Pre- and Protohistory, University of Vienna, 1190 Vienna, Austria. ; Landesamt fur Archaeologie, Zur Wetterwarte 7, 01109 Dresden, Germany. ; Department of Archaeology, Faculty of Philosophy, Belgrade University, 18-20 Cika Ljubina Street, 11000 Belgrade, Serbia. ; Department of History and Ethnology, Democritus University of Thrace, Komotini, Greece. ; Irish Archaeological Consultancy, Unit G1, Network Enterprise Park, Kilcoole, County Wicklow, Ireland. ; Department of Archaeology and Conservation, Cardiff University, John Percival Building, Colum Drive, Cardiff CF10 3EU, UK. ; State Museum of Archaeology Chemnitz, Stefan-Heym-Platz 1, 09111 Chemnitz, Germany. ; Institut National du Patrimoine de Tunis - Musee archeologique de Carthage, Carthage, Tunisia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560301" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Northern ; Animals ; Archaeology ; Beekeeping/*history ; *Bees ; Ceramics/chemistry/history ; Europe ; Farmers/history ; Geographic Mapping ; History, Ancient ; Lipids/analysis/chemistry ; Middle East ; Spatio-Temporal Analysis ; Waxes/*analysis/chemistry/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-08-04
    Description: Despite considerable current interest in biological invasions, the common life-history characteristics of successful invaders remain elusive. The widely held hypothesis that successful invaders have high reproductive rates has received little empirical support; however, alternative possibilities are seldom considered. Combining a global comparative analysis of avian introductions (〉2700 events) with demographic models and phylogenetic comparative methods, we show that although rapid population growth may be advantageous during invasions under certain circumstances, more generally successful invaders are characterized by life-history strategies in which they give priority to future rather than current reproduction. High future breeding expectations reduce the costs of reproductive failure under uncertain conditions and increase opportunities to explore the environment and respond to novel ecological pressures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sol, Daniel -- Maspons, Joan -- Vall-Llosera, Miquel -- Bartomeus, Ignasi -- Garcia-Pena, Gabriel E -- Pinol, Josep -- Freckleton, Robert P -- New York, N.Y. -- Science. 2012 Aug 3;337(6094):580-3. doi: 10.1126/science.1221523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Ecological Research and Forestry Applications, 08193 Cerdanyola del Valles, Spain. d.sol@creaf.uab.cat〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/classification/*physiology ; *Introduced Species ; Phylogeny ; Population Growth ; *Reproduction
    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: 1998-06-20
    Description: The apical ectodermal ridge (AER) is an essential structure for vertebrate limb development. Wnt3a is expressed during the induction of the chick AER, and misexpression of Wnt3a induces ectopic expression of AER-specific genes in the limb ectoderm. The genes beta-catenin and Lef1 can mimic the effect of Wnt3a, and blocking the intrinsic Lef1 activity disrupts AER formation. Hence, Wnt3a functions in AER formation through the beta-catenin/LEF1 pathway. In contrast, neither beta-catenin nor Lef1 affects the Wnt7a-regulated dorsoventral polarity of the limb. Thus, two related Wnt genes elicit distinct responses in the same tissues by using different intracellular pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kengaku, M -- Capdevila, J -- Rodriguez-Esteban, C -- De La Pena, J -- Johnson, R L -- Izpisua Belmonte, J C -- Tabin, C J -- New York, N.Y. -- Science. 1998 May 22;280(5367):1274-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9596583" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Avian Proteins ; Base Sequence ; *Body Patterning ; Chick Embryo ; Cloning, Molecular ; Cytoskeletal Proteins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Ectoderm/*metabolism ; Fibroblast Growth Factor 4 ; Fibroblast Growth Factor 8 ; Fibroblast Growth Factors/biosynthesis/genetics ; *Gene Expression Regulation, Developmental ; Glucosyltransferases ; Growth Substances/biosynthesis/genetics ; Homeodomain Proteins/genetics ; Intercellular Signaling Peptides and Proteins ; Limb Buds/embryology/*metabolism ; Lymphoid Enhancer-Binding Factor 1 ; Mesoderm/metabolism ; Molecular Sequence Data ; Morphogenesis ; Protein Biosynthesis ; Proteins/*genetics/physiology ; Proto-Oncogene Proteins/biosynthesis/*genetics/physiology ; Signal Transduction ; *Trans-Activators ; Transcription Factors/genetics/metabolism ; Up-Regulation ; Wnt Proteins ; Wnt3 Protein ; Wnt3A Protein ; beta Catenin
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-03-20
    Description: Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385933/" 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/PMC3385933/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Zhao -- Cheng, Katherine -- Walton, Zandra -- Wang, Yuchuan -- Ebi, Hiromichi -- Shimamura, Takeshi -- Liu, Yan -- Tupper, Tanya -- Ouyang, Jing -- Li, Jie -- Gao, Peng -- Woo, Michele S -- Xu, Chunxiao -- Yanagita, Masahiko -- Altabef, Abigail -- Wang, Shumei -- Lee, Charles -- Nakada, Yuji -- Pena, Christopher G -- Sun, Yanping -- Franchetti, Yoko -- Yao, Catherine -- Saur, Amy -- Cameron, Michael D -- Nishino, Mizuki -- Hayes, D Neil -- Wilkerson, Matthew D -- Roberts, Patrick J -- Lee, Carrie B -- Bardeesy, Nabeel -- Butaney, Mohit -- Chirieac, Lucian R -- Costa, Daniel B -- Jackman, David -- Sharpless, Norman E -- Castrillon, Diego H -- Demetri, George D -- Janne, Pasi A -- Pandolfi, Pier Paolo -- Cantley, Lewis C -- Kung, Andrew L -- Engelman, Jeffrey A -- Wong, Kwok-Kin -- 1U01CA141576/CA/NCI NIH HHS/ -- CA122794/CA/NCI NIH HHS/ -- CA137008/CA/NCI NIH HHS/ -- CA137008-01/CA/NCI NIH HHS/ -- CA137181/CA/NCI NIH HHS/ -- CA140594/CA/NCI NIH HHS/ -- CA147940/CA/NCI NIH HHS/ -- K23 CA157631/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50 CA090578-06/CA/NCI NIH HHS/ -- P50CA090578/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA122794-01/CA/NCI NIH HHS/ -- R01 CA137008/CA/NCI NIH HHS/ -- R01 CA137008-01/CA/NCI NIH HHS/ -- R01 CA137181/CA/NCI NIH HHS/ -- R01 CA137181-01A2/CA/NCI NIH HHS/ -- R01 CA140594/CA/NCI NIH HHS/ -- R01 CA140594-01/CA/NCI NIH HHS/ -- R01 CA163896/CA/NCI NIH HHS/ -- RC2 CA147940/CA/NCI NIH HHS/ -- RC2 CA147940-01/CA/NCI NIH HHS/ -- U01 CA141576/CA/NCI NIH HHS/ -- U01 CA141576-01/CA/NCI NIH HHS/ -- England -- Nature. 2012 Mar 18;483(7391):613-7. doi: 10.1038/nature10937.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22425996" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Combined Chemotherapy Protocols ; Benzimidazoles/*pharmacology/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; *Clinical Trials, Phase II as Topic ; *Disease Models, Animal ; Drug Evaluation, Preclinical ; Fluorodeoxyglucose F18 ; Genes, p53/genetics ; Humans ; Lung Neoplasms/*drug therapy/enzymology/*genetics/metabolism ; MAP Kinase Signaling System/drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors ; Mutation/genetics ; Pharmacogenetics/*methods ; Positron-Emission Tomography ; Protein-Serine-Threonine Kinases/deficiency/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Taxoids/*therapeutic use ; Tomography, X-Ray Computed ; Treatment Outcome ; ras Proteins/genetics/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-11-11
    Description: beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis--as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257892/" 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/PMC4257892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Caroline -- Feng, Jian -- Sun, Haosheng -- Shao, Ning Yi -- Mazei-Robison, Michelle S -- Damez-Werno, Diane -- Scobie, Kimberly -- Bagot, Rosemary -- LaBonte, Benoit -- Ribeiro, Efrain -- Liu, XiaoChuan -- Kennedy, Pamela -- Vialou, Vincent -- Ferguson, Deveroux -- Pena, Catherine -- Calipari, Erin S -- Koo, Ja Wook -- Mouzon, Ezekiell -- Ghose, Subroto -- Tamminga, Carol -- Neve, Rachael -- Shen, Li -- Nestler, Eric J -- P50 MH096890/MH/NIMH NIH HHS/ -- R00 MH094405/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):51-5. doi: 10.1038/nature13976. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Psychiatry, University of Texas Southwestern, Dallas, Texas 75390, USA. ; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383518" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics ; Animals ; DEAD-box RNA Helicases/*genetics/metabolism ; Depression/physiopathology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*genetics/metabolism ; Neurons/metabolism ; *Resilience, Psychological ; Ribonuclease III/*genetics/metabolism ; Signal Transduction ; Stress, Physiological/*genetics ; beta Catenin/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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  • 9
    Publication Date: 2007-03-03
    Description: Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892797/" 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/PMC1892797/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalley, Jeffrey W -- Fryer, Tim D -- Brichard, Laurent -- Robinson, Emma S J -- Theobald, David E H -- Laane, Kristjan -- Pena, Yolanda -- Murphy, Emily R -- Shah, Yasmene -- Probst, Katrin -- Abakumova, Irina -- Aigbirhio, Franklin I -- Richards, Hugh K -- Hong, Young -- Baron, Jean-Claude -- Everitt, Barry J -- Robbins, Trevor W -- 076244/Wellcome Trust/United Kingdom -- G0001354/Medical Research Council/United Kingdom -- G0401068/Medical Research Council/United Kingdom -- G0600196/Medical Research Council/United Kingdom -- G0600986/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1267-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Behavioral and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. jwd20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332411" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Ganglia/metabolism/radionuclide imaging ; Benzamides/metabolism ; Cocaine/*administration & dosage ; *Cocaine-Related Disorders/metabolism/psychology ; Corpus Striatum/metabolism/radionuclide imaging ; Dopamine/metabolism ; Dopamine Antagonists/metabolism/pharmacology ; *Impulsive Behavior ; Male ; Nucleus Accumbens/*metabolism/radionuclide imaging ; Positron-Emission Tomography ; Pyrrolidines/metabolism ; Rats ; Reaction Time ; Receptors, Dopamine D2/*metabolism ; Receptors, Dopamine D3/*metabolism ; *Reinforcement (Psychology) ; Self Administration ; Synaptic Transmission
    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: 2008-12-20
    Description: Perforin-like proteins are expressed by many bacterial and protozoan pathogens, yet little is known about their function or mode of action. Here, we describe Toxoplasma perforin-like protein 1 (TgPLP1), a secreted perforin-like protein of the intracellular protozoan pathogen Toxoplasma gondii that displays structural features necessary for pore formation. After intracellular growth, TgPLP1-deficient parasites failed to exit normally, resulting in entrapment within host cells. We show that this defect is due to an inability to rapidly permeabilize the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1 ablation had little effect on growth in culture but resulted in a reduction greater than five orders of magnitude of acute virulence in mice. Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662845/" 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/PMC2662845/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kafsack, Bjorn F C -- Pena, Janethe D O -- Coppens, Isabelle -- Ravindran, Sandeep -- Boothroyd, John C -- Carruthers, Vern B -- R01 AI021423/AI/NIAID NIH HHS/ -- R01 AI046675/AI/NIAID NIH HHS/ -- R01 AI046675-06/AI/NIAID NIH HHS/ -- R01 AI046675-07/AI/NIAID NIH HHS/ -- R01 AI046675-08/AI/NIAID NIH HHS/ -- R01 AI046675-09/AI/NIAID NIH HHS/ -- R01 AI46675/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):530-3. doi: 10.1126/science.1165740. Epub 2008 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095897" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcimycin/pharmacology ; Cell Membrane/*metabolism ; Cell Membrane Permeability ; Cells, Cultured ; Host-Parasite Interactions ; Humans ; Intracellular Membranes/*metabolism ; Ionophores/pharmacology ; Models, Molecular ; Molecular Sequence Data ; Perforin/chemistry/genetics/*metabolism ; Permeability ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/genetics/*metabolism ; Toxoplasma/genetics/growth & development/*metabolism/pathogenicity ; Vacuoles/*metabolism/*parasitology
    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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