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  • Wiley  (36)
  • Nature Publishing Group (NPG)  (9)
  • 2010-2014  (35)
  • 1990-1994  (5)
  • 1975-1979  (4)
  • 1955-1959  (1)
  • 1940-1944
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  • 1
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    Atmospheric loading effects on free-draining lysimeters (2011)
    Wiley
    Details
    Publication Date: 2011-05-27
    Description: Temporal atmospheric pressure variations introduce an artifact into percolation measurements in free-draining lysimeters. This anomaly is associated with transient pressure gradients that occur as fluid and gas pressures within the lysimeter equilibrate with atmospheric pressure changes at the drain. On the basis of harmonic (Fourier) analysis of a large (20 m × 10 m × 1.8 m) free-draining lysimeter, hourly percolation was maximally affected by pressure variations of ∼2 cycles per day, with the effect decreasing with decreasing frequency. Compared to the calculated pressure differences at the drain, the measured phase delay between percolation and the atmospheric pressure was less by ∼45°, which we attribute to an additional phase lag existing between the percolation and pressure difference at the drain. These pressure-induced changes in percolation rate can influence the outcome of water balances conducted via free-draining lysimeters.
    Print ISSN: 0043-1397
    Electronic ISSN: 1944-7973
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 2
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    Oligocene-Miocene back-thrusting in southern Mexico linked to the rapid subduction erosion of a large forearc block (2012)
    Wiley
    In: Tectonics
    Details
    Publication Date: 2012-03-21
    Description: Both the timing and mechanism for the removal of a ∼150–250 km wide forearc block from southern Mexico during the Cenozoic are controversial. Principal competing hypotheses are (1) removal due to sinistral strike-slip shear, in which slow, diachronous removal of the Chortis Block throughout the Cenozoic is inferred, and (2) removal due to subduction erosion, in which rapid removal of a large forearc block during the late Oligocene/early Miocene is inferred to be synchronous with the rapid landward migration of the southern Mexican arc. New data indicate northeast-directed back-thrusting in (1) the Chacalapa shear zone west of −96.5°E, with the timing of shear deformation bracketed by a 25.5 ± 0.5 Ma U/Pb zircon age and a 20.7 ± 0.6 Ma Ar/Ar biotite age, and (2) in an unnamed shear zone to the south, with the timing of deformation bracketed by a 27.5 ± 0.5 Ma U/Pb zircon age and a 25.1 ± 0.2 Ma Ar/Ar biotite age. Zircon and biotite ages date the emplacement and cooling of deformed plutons, respectively. The observed back-thrusting is consistent with a model of forearc removal due to subduction-erosion processes because it is evidence for subduction-orthogonal shortening occurring within the upper plate just before the landward migration of the southern Mexican arc. Rapid subduction of the southern Mexican forearc could have recycled continental lithosphere into the upper mantle at a rate up to half the global average rate of subduction erosion during the late Oligocene/early Miocene.
    Print ISSN: 0278-7407
    Electronic ISSN: 1944-9194
    Topics: Geosciences
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
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    Measurement and Interpretation of Subtle Deformation Signals at Unimak Island from 2003 to 2010 Using Weather Model-Assisted Time Series InSAR (2014)
    Wiley
    Details
    Publication Date: 2014-12-31
    Description: A seven-year time series of satellite radar images over Unimak Island, Alaska-site of Westdahl Volcano, Fisher Caldera and Shishaldin Volcano-was processed using a model-free Persistent Scatterer Interferometry (PSI) technique assisted by Numerical Weather Prediction (NWP) model. The deformation-only signals were optimally extracted from atmosphere-contaminated phase records. The reconstructed deformation time series maps are compared with campaign and continuous Global Positioning System (GPS) measurements as well as Small Baseline Subset (SBAS) InSAR results for quality assessment and geophysical interpretation. We observed subtle surface inflation at Westdahl Volcano that can be fit by a Mogi source located at approximately 3.6 km north of Westdahl peak and at depth of about 6.9 km that is consistent to the GPS estimated depth for the 1998 to 2001 time period. The magma chamber volume change decays during the period of 2003 to 2010. The deformation field over Fisher Caldera is steadily subsiding over time. Its best-fit analytical model is a sill source that is about 7.9 km in length, 0.54 km in width, and locates at about 5.5 km BSL underneath the center of Fisher Caldera with strike angle of N52°E. Very little deformation was detected near Shishaldin peak, however, a region approximately 15 km east of Shishaldin, as well as an area at the Tugamak range at about 30 km northwest of Shishaldin, show evidence for movement towards the satellite, with a temporal signature correlated with the 2004 Shishaldin eruption. The cause of these movements is unknown.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
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    The mutation spectrum revealed by paired genome sequences from a lung cancer patient (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-28
    Description: Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60x coverage) and adjacent normal tissue (46x). Comparing the two genomes, we identify a wide variety of somatic variations, including 〉50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, William -- Jiang, Zhaoshi -- Liu, Jinfeng -- Haverty, Peter M -- Guan, Yinghui -- Stinson, Jeremy -- Yue, Peng -- Zhang, Yan -- Pant, Krishna P -- Bhatt, Deepali -- Ha, Connie -- Johnson, Stephanie -- Kennemer, Michael I -- Mohan, Sankar -- Nazarenko, Igor -- Watanabe, Colin -- Sparks, Andrew B -- Shames, David S -- Gentleman, Robert -- de Sauvage, Frederic J -- Stern, Howard -- Pandita, Ajay -- Ballinger, Dennis G -- Drmanac, Radoje -- Modrusan, Zora -- Seshagiri, Somasekar -- Zhang, Zemin -- England -- Nature. 2010 May 27;465(7297):473-7. doi: 10.1038/nature09004.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505728" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma, Non-Small-Cell Lung/*genetics ; DNA Mutational Analysis ; Genome, Human/*genetics ; Humans ; Lung Neoplasms/*genetics ; Male ; Middle Aged ; Models, Biological ; Point Mutation/*genetics ; Selection, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-20
    Description: Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19(Arf)-p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19(Arf)-p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928066/" 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/PMC2928066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Hui-Kuan -- Chen, Zhenbang -- Wang, Guocan -- Nardella, Caterina -- Lee, Szu-Wei -- Chan, Chia-Hsin -- Yang, Wei-Lei -- Wang, Jing -- Egia, Ainara -- Nakayama, Keiichi I -- Cordon-Cardo, Carlos -- Teruya-Feldstein, Julie -- Pandolfi, Pier Paolo -- R01 CA082328/CA/NCI NIH HHS/ -- R01 CA082328-13/CA/NCI NIH HHS/ -- R01 MD004038/MD/NIMHD NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):374-9. doi: 10.1038/nature08815.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237562" target="_blank"〉PubMed〈/a〉
    Keywords: Activating Transcription Factor 4/metabolism ; Adenovirus E1A Proteins/genetics/metabolism ; Animals ; *Cell Aging/drug effects ; *Cell Transformation, Neoplastic/drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Fibroblasts ; Male ; Mice ; PTEN Phosphohydrolase/deficiency/genetics/metabolism ; Prostate/cytology/metabolism ; Prostatic Neoplasms/drug therapy/pathology/prevention & control ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; S-Phase Kinase-Associated Proteins/antagonists & inhibitors/genetics/*metabolism ; SKP Cullin F-Box Protein Ligases/metabolism ; Tumor Suppressor Protein p53/deficiency/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Creation and diagnosis of a solid-density plasma with an X-ray free-electron laser (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-27
    Description: Matter with a high energy density (〉10(5) joules per cm(3)) is prevalent throughout the Universe, being present in all types of stars and towards the centre of the giant planets; it is also relevant for inertial confinement fusion. Its thermodynamic and transport properties are challenging to measure, requiring the creation of sufficiently long-lived samples at homogeneous temperatures and densities. With the advent of the Linac Coherent Light Source (LCLS) X-ray laser, high-intensity radiation (〉10(17) watts per cm(2), previously the domain of optical lasers) can be produced at X-ray wavelengths. The interaction of single atoms with such intense X-rays has recently been investigated. An understanding of the contrasting case of intense X-ray interaction with dense systems is important from a fundamental viewpoint and for applications. Here we report the experimental creation of a solid-density plasma at temperatures in excess of 10(6) kelvin on inertial-confinement timescales using an X-ray free-electron laser. We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the timescales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vinko, S M -- Ciricosta, O -- Cho, B I -- Engelhorn, K -- Chung, H-K -- Brown, C R D -- Burian, T -- Chalupsky, J -- Falcone, R W -- Graves, C -- Hajkova, V -- Higginbotham, A -- Juha, L -- Krzywinski, J -- Lee, H J -- Messerschmidt, M -- Murphy, C D -- Ping, Y -- Scherz, A -- Schlotter, W -- Toleikis, S -- Turner, J J -- Vysin, L -- Wang, T -- Wu, B -- Zastrau, U -- Zhu, D -- Lee, R W -- Heimann, P A -- Nagler, B -- Wark, J S -- England -- Nature. 2012 Jan 25;482(7383):59-62. doi: 10.1038/nature10746.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, UK. sam.vinko@physics.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22278059" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Heat dissipation in atomic-scale junctions (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-06-15
    Description: Atomic and single-molecule junctions represent the ultimate limit to the miniaturization of electrical circuits. They are also ideal platforms for testing quantum transport theories that are required to describe charge and energy transfer in novel functional nanometre-scale devices. Recent work has successfully probed electric and thermoelectric phenomena in atomic-scale junctions. However, heat dissipation and transport in atomic-scale devices remain poorly characterized owing to experimental challenges. Here we use custom-fabricated scanning probes with integrated nanoscale thermocouples to investigate heat dissipation in the electrodes of single-molecule ('molecular') junctions. We find that if the junctions have transmission characteristics that are strongly energy dependent, this heat dissipation is asymmetric--that is, unequal between the electrodes--and also dependent on both the bias polarity and the identity of the majority charge carriers (electrons versus holes). In contrast, junctions consisting of only a few gold atoms ('atomic junctions') whose transmission characteristics show weak energy dependence do not exhibit appreciable asymmetry. Our results unambiguously relate the electronic transmission characteristics of atomic-scale junctions to their heat dissipation properties, establishing a framework for understanding heat dissipation in a range of mesoscopic systems where transport is elastic--that is, without exchange of energy in the contact region. We anticipate that the techniques established here will enable the study of Peltier effects at the atomic scale, a field that has been barely explored experimentally despite interesting theoretical predictions. Furthermore, the experimental advances described here are also expected to enable the study of heat transport in atomic and molecular junctions--an important and challenging scientific and technological goal that has remained elusive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Woochul -- Kim, Kyeongtae -- Jeong, Wonho -- Zotti, Linda Angela -- Pauly, Fabian -- Cuevas, Juan Carlos -- Reddy, Pramod -- England -- Nature. 2013 Jun 13;498(7453):209-12. doi: 10.1038/nature12183.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23765496" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Biomimetic self-templating supramolecular structures (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-10-21
    Description: In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Woo-Jae -- Oh, Jin-Woo -- Kwak, Kyungwon -- Lee, Byung Yang -- Meyer, Joel -- Wang, Eddie -- Hexemer, Alexander -- Lee, Seung-Wuk -- R21DE018360/DE/NIDCR NIH HHS/ -- England -- Nature. 2011 Oct 19;478(7369):364-8. doi: 10.1038/nature10513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22012394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteriophage M13/chemistry/*physiology ; Biomimetic Materials/chemical synthesis/*chemistry ; Cell Line ; Macromolecular Substances/chemistry ; Mice ; Optical Rotation ; Tissue Culture Techniques/instrumentation ; Virion/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Wnt activation in nail epithelium couples nail growth to digit regeneration (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-06-14
    Description: The tips of mammalian digits can regenerate after amputation, like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail. Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, beta-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936678/" 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/PMC3936678/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeo, Makoto -- Chou, Wei Chin -- Sun, Qi -- Lee, Wendy -- Rabbani, Piul -- Loomis, Cynthia -- Taketo, M Mark -- Ito, Mayumi -- 1R01AR059768-01A1/AR/NIAMS NIH HHS/ -- 5P30CA0016087-32/CA/NCI NIH HHS/ -- P30 CA016087-30/CA/NCI NIH HHS/ -- R01 AR059768/AR/NIAMS NIH HHS/ -- S10 RR023704-01A1/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):228-32. doi: 10.1038/nature12214. Epub 2013 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Ronald O. Perelman Department of Dermatology, New York University, School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23760480" target="_blank"〉PubMed〈/a〉
    Keywords: Amputation ; Animals ; Bone and Bones/cytology/metabolism ; Cell Differentiation ; Cells, Cultured ; Epithelium/metabolism ; Extremities/growth & development/innervation/*physiology ; Hoof and Claw/cytology/*growth & development/metabolism ; Mesoderm/cytology/metabolism ; Mice ; Regeneration/*physiology ; Stem Cells/cytology/metabolism ; Wnt Proteins/*metabolism ; Wnt Signaling Pathway ; 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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  • 10
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    Selective killing of cancer cells by a small molecule targeting the stress response to ROS (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-07-15
    Description: Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316487/" 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/PMC3316487/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raj, Lakshmi -- Ide, Takao -- Gurkar, Aditi U -- Foley, Michael -- Schenone, Monica -- Li, Xiaoyu -- Tolliday, Nicola J -- Golub, Todd R -- Carr, Steven A -- Shamji, Alykhan F -- Stern, Andrew M -- Mandinova, Anna -- Schreiber, Stuart L -- Lee, Sam W -- 5 RC2 CA148399-02/CA/NCI NIH HHS/ -- CA080058/CA/NCI NIH HHS/ -- CA085681/CA/NCI NIH HHS/ -- CA127247/CA/NCI NIH HHS/ -- CA142805/CA/NCI NIH HHS/ -- P01 CA080058/CA/NCI NIH HHS/ -- P01 CA080058-02/CA/NCI NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 CA085681/CA/NCI NIH HHS/ -- R01 CA085681-06/CA/NCI NIH HHS/ -- R01 CA142805/CA/NCI NIH HHS/ -- R01 CA142805-01/CA/NCI NIH HHS/ -- RL1CA133834/CA/NCI NIH HHS/ -- RL1GM084437/GM/NIGMS NIH HHS/ -- RL1HG004671/HG/NHGRI NIH HHS/ -- UL1RR024924/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 13;475(7355):231-4. doi: 10.1038/nature10167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149 13th Street, Charlestown, Massachusetts 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21753854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*drug effects ; Breast Neoplasms/*drug therapy/genetics/metabolism/*pathology ; Cell Line ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Comet Assay ; DNA Damage/drug effects ; Dioxolanes/adverse effects/chemistry/*pharmacology ; Genotype ; Mice ; Neoplasm Metastasis/drug therapy/pathology ; Oxidative Stress/*drug effects ; Reactive Oxygen Species/*metabolism ; Small Molecule Libraries/chemistry ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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