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  • 1
    Publication Date: 2016-03-23
    Description: A major challenge in volcanology is determining the factors that control the frequency and magnitude of eruptions at hazardous caldera volcanoes. Understanding the critical sequence of events that may lead to future eruptions is vital for volcanic monitoring and risk assessment. Here we use magma chemistry and mineral diffusion modeling to interpret the magmatic processes and time scales involved in the youngest three eruptions (2.15–1.7 ka) from Taupo volcano (New Zealand), which peaked with the voluminous A.D. 232 eruption. Of the rhyolites erupted since ca. 12 ka, the 〈2.15 ka magmas have the lowest whole-rock SiO 2 content and reversely zoned crystals, yet with high-SiO 2 melt inclusions. Mineral zonations and compositional shifts reflect a 30–40 °C temperature increase over the immediately preceding (〉2.75 ka) rhyolites that were tapped from the same magma reservoir. Orthopyroxene Fe-Mg diffusion time scales indicate that the onset of rapid heating and priming of the host silicic mush occurred 〈120 yr prior to the 〈2.15 ka eruptions, with subsequent melt accumulation occurring in only decades. Elevated mafic magma supply to the silicic mush pile, rapid melt accumulation, and high differential tectonic stress built up and culminated in the ~105 km 3 A.D. 232 eruption, one of the largest and most violent Holocene eruptions globally. These youngest eruptions demonstrate how Taupo’s magmatic system can rapidly change behavior to generate large eruptible melt bodies on time scales of direct relevance to humans and monitoring initiatives.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 2
    Publication Date: 2015-04-25
    Description: New in situ major and trace element analytical data are presented for crystals (sanidine, plagioclase, biotite, orthopyroxene, clinopyroxene) and matrix glasses from juvenile materials representing the full Bishop Tuff sequence from the earliest fall unit (F1) to the latest ignimbrite package (Ig2Nc). These data are combined with published information to investigate the nature and zonation of the pre-eruptive Bishop magma chamber. Our data confirm that this magma chamber was a single unitary body that was thermally and compositionally zoned. The zonation was largely established prior to the growth of crystals, and also prior to mixing in the lower parts of the chamber induced by late-stage intrusion of a magma of contrasting composition and slightly higher temperature (the ‘bright-rim’ magma). Sparse mixed swirly and dacitic pumices show enrichments in Ba, Sr and Ti that identify these pumices as possible representatives of the ‘bright-rim’ magma. A model (revised from previously published work) for the pre-eruptive magma chamber comprises three main parts: (1) an upper, volumetrically dominant (~2/3), relatively unzoned region that was the source of the earlier, eastern-erupted ignimbrite units and their coeval fall units; (2) a volumetrically minor transition zone that shows evidence for minor degrees of mixing and was the dominant source for the latest, eastern-erupted part of Ig1Eb (Sherwin subunit) and the earlier part of the northern-erupted ignimbrite (Ig 2Na); (3) a lower, volumetrically subordinate (~1/3) region that was affected by mixing with the ‘bright-rim’ invasive magma in the lead-up to the eruption, and fed later northern-erupted units. Ingress of the ‘bright-rim’ magma introduced orthopyroxene and bright-rimmed zircon crystals, and induced partial resorption then overgrowth of rims enriched in Ti, Sr and Ba on sanidine and quartz, and development of zoning in clinopyroxene. Based on pumice proportions and associated crystal and glass chemistries through the eruptive sequence, we infer that the roof and floor of the magma chamber were stepped down to the north, such that the transition zone magma formed the floor of the southern part of the melt-dominant chamber and the roof of the northern part. Our data reinforce the previous concept of a single compositionally and thermally zoned Bishop magma chamber and additionally support a temporally constrained role for pre-eruptive magma mixing and the introduction of melts and minerals with contrasting compositions to the resident Bishop magma.
    Print ISSN: 0022-3530
    Electronic ISSN: 1460-2415
    Topics: Geosciences
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  • 3
    Publication Date: 2013-01-17
    Description: The geochemistry of pyroclasts sampled from four volcanoes along the Kermadec arc in the SW Pacific is used to investigate the genesis of silicic magmas in a young (〈2 Myr), archetypical intra-oceanic arc setting. Raoul, Macauley and Raoul SW volcanoes in the northern Kermadec arc, and Healy volcano in the southern Kermadec arc have all recently erupted dacitic to rhyolitic crystal-poor pumice. In addition to whole-rock analyses, we present a detailed study of mineral and glass chemistries to highlight the complex structure of the Kermadec magmatic systems. Major and trace element bulk-rock compositions mostly fall into relatively narrow compositional ranges, forming discrete groups by eruption for Raoul, and varying with relative crystal contents for Healy. In contrast, pumices from Macauley cover a wide range of compositions, between 66 and 72·5 wt % SiO 2 . At all four volcanoes the trace element patterns of pumice are subparallel to both those of previously erupted basalts and/or whole mafic blebs found both as discrete pyroclasts and as inclusions within pumices. Pb and Sr isotopic compositions have limited ranges within single volcanoes, but vary considerably along the arc, being more radiogenic in the southern volcanoes. Distinctive crystal populations and zonation patterns in pumices, mafic blebs and plutonic xenoliths indicate that many crystals did not grow in the evolved magmas, but are instead mixed from other sources including gabbros and hydrothermally altered tonalites. Such open-system mixing is ubiquitous at the four volcanoes. Oxygen isotope compositions of both phenocrysts (silicic origin) and xenocrysts or antecrysts (mafic origin) are typical for mantle-derived melts. Whole-rock, glass and mineral chemistries are consistent with evolved magmas being generated at each volcano through ~70–80% crystal fractionation of a basaltic parent. Our results are not consistent with silicic magma generation via crustal anatexis, as previously suggested for these Kermadec arc volcanoes. Although crystallization is the dominant process driving melt evolution in the Kermadec volcanoes, we show that the magmatic systems are open to contributions from both newly arriving melts and wholly crystalline plutonic bodies. Such processes occur in variable proportions between magma batches, and are largely reflected in small-scale chemical variations between eruption units.
    Print ISSN: 0022-3530
    Electronic ISSN: 1460-2415
    Topics: Geosciences
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  • 4
    Publication Date: 2011-09-13
    Description: Regions of warm, thin, discontinuous permafrost have been observed to be experiencing rapid changes in lake and pond dynamics in recent decades. Even though surface water and groundwater interactions are thought to play a significant role in heat transport in these regions, the effect of these interactions on permafrost remains largely unquantified. In order to examine the influence of groundwater flow on permafrost dynamics, we modeled the development of a sub-lake talik under permafrost conditions similar to those observed in the southern-central Seward Peninsula region of Alaska using a numerical solution that couples heat transport and groundwater flow, including the effect of water phase changes on soil permeability and latent heat content. A comparison of model simulations, with and without near surface subpermafrost groundwater flow, indicates that stable permafrost thicknesses are 2 to 5 times greater in the absence of groundwater flow. Simulations examining the thermal influence of lakes on underlying permafrost suggest that a through-going talik can develop in a matter of decades and that the incorporation of advective heat transport reduces the time to complete loss of ice beneath the lake by half, relative to heat transport by conduction alone. This work presents the first quantitative assessment of the rates of sub-lake permafrost response to thermal disturbances, such as talik development, in systems with near-surface groundwater flow. The results highlight the importance of coupled thermal and hydrologic processes on discontinuous permafrost dynamics.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
    Publication Date: 2014-11-10
    Description: In this study, the Hillslope River Routing (HRR) model was modified for arctic river basin applications and used to route surface and subsurface runoff from the Community Land Model (CLM) in the Mackenzie River Basin (MRB) for the period 2000-2004. The HRR modeling framework performs lateral surface and subsurface runoff routing from hillslopes and channel/floodplain routing. The HRR model was modified here to include a variable subsurface Active Layer Thickness (ALT; permafrost) to enable subsurface water to re-surface, a distributed surface storage component to store and attenuate the rapid generation of snowmelt water, compound hillslopes to account for the low relief near rivers and floodplains, and reservoir routing to complete the total surface and subsurface water storage accounting. To illustrate the new HRR model components, a case study is presented for the MRB. The basin is discretized into 5,077 sub-basins based on a drainage network derived from the global Digital Elevation Model (DEM) developed from the ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) sensor on board NASA's Terra satellite and river widths extracted from LandSat images. The median hillslope land area is 68.5 km 2 with a flow length of 2.8 km. Gridded CLM surface and subsurface runoffs are re-mapped to the HRR model's irregular sub-basins. The role of each new model component is quantified in terms of peak annual streamflow (magnitude and timing) at select locations and basin-wide total water storage anomalies. The role of distributed surface storage is shown to attenuate the relatively rapid generation of snowmelt water, impact the annual peak hydrograph (reduced peaks by 〉30% and detailed peak by 〉20 days) and account for 20% of the monthly total water storage anomalies averaged over the year and ranging from 14 to 25% (-10 to 30 mm) throughout the year. Although additional research is needed to dynamically link spatially distributed ALT to HRR, the role of ALT is shown to be important. A basin-wide, uniform 1 m ALT impacts the annual peak hydrograph (reduced peaks by 9% and detailed peak by 8 days) and trends in total water storage anomalies. This article is protected by copyright. All rights reserved.
    Print ISSN: 0885-6087
    Electronic ISSN: 1099-1085
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley
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  • 6
    Publication Date: 2014-11-21
    Description: Adult body height is a quantitative trait for which genome-wide association studies (GWAS) have identified numerous loci, primarily in European populations. These loci, comprising common variants, explain 〈10% of the phenotypic variance in height. We searched for novel associations between height and common (minor allele frequency, MAF ≥5%) or infrequent (0.5% 〈 MAF 〈 5%) variants across the exome in African Americans. Using a reference panel of 1692 African Americans and 471 Europeans from the National Heart, Lung, and Blood Institute's (NHLBI) Exome Sequencing Project (ESP), we imputed whole-exome sequence data into 13 719 African Americans with existing array-based GWAS data (discovery). Variants achieving a height-association threshold of P 〈 5E–06 in the imputed dataset were followed up in an independent sample of 1989 African Americans with whole-exome sequence data (replication). We used P 〈 2.5E–07 (=0.05/196 779 variants) to define statistically significant associations in meta-analyses combining the discovery and replication sets ( N = 15 708). We discovered and replicated three independent loci for association: 5p13.3/ C5orf22 /rs17410035 (MAF = 0.10, β = 0.64 cm, P = 8.3E–08), 13q14.2/ SPRYD7 /rs114089985 (MAF = 0.03, β = 1.46 cm, P = 4.8E–10) and 17q23.3/ GH2 /rs2006123 (MAF = 0.30; β = 0.47 cm; P = 4.7E–09). Conditional analyses suggested 5p13.3 (C5orf22/rs17410035) and 13q14.2 (SPRYD7/rs114089985) may harbor novel height alleles independent of previous GWAS-identified variants ( r 2 with GWAS loci 〈0.01); whereas 17q23.3/ GH2 /rs2006123 was correlated with GWAS-identified variants in European and African populations. Notably, 13q14.2/rs114089985 is infrequent in African Americans (MAF = 3%), extremely rare in European Americans (MAF = 0.03%), and monomorphic in Asian populations, suggesting it may be an African-American-specific height allele. Our findings demonstrate that whole-exome imputation of sequence variants can identify low-frequency variants and discover novel variants in non-European populations.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2014-07-17
    Description: New zircon U–Th model-age and trace element datasets are presented from Taupo volcano (New Zealand), which are used to investigate the timescales and broad-scale magmatic processes involving zircon crystallization after the caldera-forming 25·4 ka Oruanui supereruption. Detailed 14 C-based chronologies and controls on vent locations allow the timing and location of post-caldera eruptions to be spatially and temporally constrained to an extent not possible for any other supervolcano. After ~5 kyr of post-Oruanui quiescence, Taupo erupted three dacitic units, followed by another ~5 kyr break, and then a sequence of rhyolitic units in three subgroups (SG1–SG3) from 12 ka onwards. Despite overlapping vent sites and crustal source domains between the Oruanui and post-Oruanui eruptions, U–Th zircon model ages in Taupo SG1 rhyolites (erupted from 12 to 10 ka) indicate only minor inheritance of crystals from the Oruanui magma source. Post-Oruanui model-age spectra are instead typically centred close to eruption ages with subordinate older pre-300 ka equiline grains in some units. U–Pb dating of these older grains shows that both 300–450 ka plutonic-derived and pre-100 Ma greywacke basement-derived zircons are present. The former largely coincide in age with zircons from the 350 ka Whakamaru eruption products, and are dominant over greywacke in young units that were vented within the outline of the Whakamaru caldera. Despite multiple ages and vent sites, trace element compositions are broadly similar in zircons, regardless of their ages. However, a small subset of zircons analysed from SG1 rhyolite (Units B and C) have notably high concentrations of U, Th, P, Y + (REE) 3+ and Nb but with only minor variations in Hf and Ti. SG2 zircons typically have higher Sc contents, reflecting large-scale changes in melt chemistry and crystallizing mineral phases with time. The age spectra indicate that most Oruanui zircons were removed by thermally induced dissolution immediately following the supereruption. U–Th ages from single post-Oruanui eruptions show consistent inheritance of post-Oruanui grains with model ages that centre between the temporally separated but geographically overlapping eruption groups, generating model-age modes. Within the statistical limitations of the isotopic measurements, we interpret these repeated modes to be significant, resulting from incorporation of crystal populations from cyclic post-Oruanui periods of magmatic cooling and crystallization, acting within a crustal protolith chemically independent of that which was dominant in the Oruanui system. These periods of cooling and crystallization alternate with times of rejuvenation and eruption, sometimes demonstrably accompanying syn-eruptive regional rifting and mafic magma injection. Not only were the processes that developed the supersized Oruanui magma body rapid, but this huge magma system was effectively reset and rebuilt on a comparably short timescale.
    Print ISSN: 0022-3530
    Electronic ISSN: 1460-2415
    Topics: Geosciences
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  • 8
    Publication Date: 2000-12-23
    Description: Understanding how DNA binding proteins control global gene expression and chromosomal maintenance requires knowledge of the chromosomal locations at which these proteins function in vivo. We developed a microarray method that reveals the genome-wide location of DNA-bound proteins and used this method to monitor binding of gene-specific transcription activators in yeast. A combination of location and expression profiles was used to identify genes whose expression is directly controlled by Gal4 and Ste12 as cells respond to changes in carbon source and mating pheromone, respectively. The results identify pathways that are coordinately regulated by each of the two activators and reveal previously unknown functions for Gal4 and Ste12. Genome-wide location analysis will facilitate investigation of gene regulatory networks, gene function, and genome maintenance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, B -- Robert, F -- Wyrick, J J -- Aparicio, O -- Jennings, E G -- Simon, I -- Zeitlinger, J -- Schreiber, J -- Hannett, N -- Kanin, E -- Volkert, T L -- Wilson, C J -- Bell, S P -- Young, R A -- New York, N.Y. -- Science. 2000 Dec 22;290(5500):2306-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11125145" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Cycle ; DNA, Fungal/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Fungal Proteins/*metabolism ; Galactose/metabolism ; *Gene Expression Profiling ; *Gene Expression Regulation, Fungal ; Genes, Fungal ; *Genome, Fungal ; Oligonucleotide Array Sequence Analysis ; Peptides/pharmacology ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/*genetics/metabolism/physiology ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*metabolism ; Transcriptional Activation
    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
    Publication Date: 2010-11-26
    Description: Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed approximately 600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058384/" 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/PMC3058384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johannessen, Cory M -- Boehm, Jesse S -- Kim, So Young -- Thomas, Sapana R -- Wardwell, Leslie -- Johnson, Laura A -- Emery, Caroline M -- Stransky, Nicolas -- Cogdill, Alexandria P -- Barretina, Jordi -- Caponigro, Giordano -- Hieronymus, Haley -- Murray, Ryan R -- Salehi-Ashtiani, Kourosh -- Hill, David E -- Vidal, Marc -- Zhao, Jean J -- Yang, Xiaoping -- Alkan, Ozan -- Kim, Sungjoon -- Harris, Jennifer L -- Wilson, Christopher J -- Myer, Vic E -- Finan, Peter M -- Root, David E -- Roberts, Thomas M -- Golub, Todd -- Flaherty, Keith T -- Dummer, Reinhard -- Weber, Barbara L -- Sellers, William R -- Schlegel, Robert -- Wargo, Jennifer A -- Hahn, William C -- Garraway, Levi A -- CA134502/CA/NCI NIH HHS/ -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- K08 CA115927/CA/NCI NIH HHS/ -- K08 CA115927-05/CA/NCI NIH HHS/ -- P50 CA093683/CA/NCI NIH HHS/ -- R01 CA134502/CA/NCI NIH HHS/ -- R33 CA128625/CA/NCI NIH HHS/ -- RC2 CA148268/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 16;468(7326):968-72. doi: 10.1038/nature09627. Epub 2010 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21107320" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Cell Line, Tumor ; Clinical Trials as Topic ; *Drug Resistance, Neoplasm/drug effects/genetics ; Enzyme Activation/drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Indoles/pharmacology/therapeutic use ; MAP Kinase Kinase Kinases/genetics/*metabolism ; *MAP Kinase Signaling System ; Melanoma/drug therapy/enzymology/genetics/metabolism ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Open Reading Frames/genetics ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins B-raf/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Proto-Oncogene Proteins c-raf/genetics/metabolism ; Sulfonamides/pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-09-18
    Description: The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition. Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Shih-Min A -- Mishina, Yuji M -- Liu, Shanming -- Cheung, Atwood -- Stegmeier, Frank -- Michaud, Gregory A -- Charlat, Olga -- Wiellette, Elizabeth -- Zhang, Yue -- Wiessner, Stephanie -- Hild, Marc -- Shi, Xiaoying -- Wilson, Christopher J -- Mickanin, Craig -- Myer, Vic -- Fazal, Aleem -- Tomlinson, Ronald -- Serluca, Fabrizio -- Shao, Wenlin -- Cheng, Hong -- Shultz, Michael -- Rau, Christina -- Schirle, Markus -- Schlegl, Judith -- Ghidelli, Sonja -- Fawell, Stephen -- Lu, Chris -- Curtis, Daniel -- Kirschner, Marc W -- Lengauer, Christoph -- Finan, Peter M -- Tallarico, John A -- Bouwmeester, Tewis -- Porter, Jeffery A -- Bauer, Andreas -- Cong, Feng -- England -- Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759537" target="_blank"〉PubMed〈/a〉
    Keywords: Axin Protein ; Cell Division/drug effects ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Proteomics ; Repressor Proteins/chemistry/*metabolism ; Signal Transduction/*drug effects ; Tankyrases/*antagonists & inhibitors/metabolism ; Transcription, Genetic/drug effects ; Ubiquitin/metabolism ; Ubiquitination ; Wnt Proteins/*antagonists & inhibitors/metabolism ; beta Catenin/antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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