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  • 1
    Publication Date: 2015-07-03
    Description: Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain Cell Death and Disease 6, e1804 (July 2015). doi:10.1038/cddis.2015.118 Authors: J-S Kim, B Ku, T-G Woo, A-Y Oh, Y-S Jung, Y-M Soh, J-H Yeom, K Lee, B-J Park, B-H Oh & N-C Ha
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 2
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    Society of Exploration Geophysicists (SEG)
    Publication Date: 2013-09-05
    Description: Laplace-domain full-waveform inversion is used to estimate subsurface macro-velocity models from seismic data. This method can be applied to marine or land data and combined with the frequency-domain technique for a higher resolution. Laplace-domain full-waveform inversion is robust with respect to a lack of low-frequency information in the seismic data. This method can be used as an alternative or complement to conventional full-waveform inversion methods; however, several important aspects must be considered when inverting data in the Laplace domain. This article provides an overview of the Laplace-domain full-waveform inversion method and related techniques that have been developed to date.
    Print ISSN: 1070-485X
    Electronic ISSN: 1938-3789
    Topics: Geosciences
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  • 3
    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
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  • 4
    Publication Date: 2012-08-17
    Description: Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690621/" 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/PMC3690621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seshagiri, Somasekar -- Stawiski, Eric W -- Durinck, Steffen -- Modrusan, Zora -- Storm, Elaine E -- Conboy, Caitlin B -- Chaudhuri, Subhra -- Guan, Yinghui -- Janakiraman, Vasantharajan -- Jaiswal, Bijay S -- Guillory, Joseph -- Ha, Connie -- Dijkgraaf, Gerrit J P -- Stinson, Jeremy -- Gnad, Florian -- Huntley, Melanie A -- Degenhardt, Jeremiah D -- Haverty, Peter M -- Bourgon, Richard -- Wang, Weiru -- Koeppen, Hartmut -- Gentleman, Robert -- Starr, Timothy K -- Zhang, Zemin -- Largaespada, David A -- Wu, Thomas D -- de Sauvage, Frederic J -- R00 CA151672/CA/NCI NIH HHS/ -- R01 CA134759/CA/NCI NIH HHS/ -- R01-CA134759/CA/NCI NIH HHS/ -- T32 CA009138/CA/NCI NIH HHS/ -- England -- Nature. 2012 Aug 30;488(7413):660-4. doi: 10.1038/nature11282.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. sekar@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895193" target="_blank"〉PubMed〈/a〉
    Keywords: Ataxia Telangiectasia Mutated Proteins ; Base Sequence ; Cell Cycle Proteins/genetics ; Colonic Neoplasms/*genetics/metabolism/pathology ; DNA Copy Number Variations/genetics ; DNA-Binding Proteins/genetics ; Dioxygenases/genetics ; Exome/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics ; Gene Fusion/*genetics ; Genes, APC ; Genes, Neoplasm/*genetics ; Humans ; Insulin-Like Growth Factor II/genetics ; Intercellular Signaling Peptides and Proteins/*genetics ; Molecular Sequence Data ; Mutation/genetics ; Polymorphism, Single Nucleotide/genetics ; Protein-Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins/genetics ; Receptor, ErbB-3/genetics ; Sequence Analysis, RNA ; Signal Transduction/genetics ; Thrombospondins/*genetics ; Transcription Factor 7-Like 2 Protein/genetics ; Tumor Suppressor Proteins/genetics ; Wnt Proteins/metabolism
    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: 2013-11-23
    Description: We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉IceCube Collaboration -- Aartsen, M G -- Abbasi, R -- Abdou, Y -- Ackermann, M -- Adams, J -- Aguilar, J A -- Ahlers, M -- Altmann, D -- Auffenberg, J -- Bai, X -- Baker, M -- Barwick, S W -- Baum, V -- Bay, R -- Beatty, J J -- Bechet, S -- Becker Tjus, J -- Becker, K-H -- Benabderrahmane, M L -- BenZvi, S -- Berghaus, P -- Berley, D -- Bernardini, E -- Bernhard, A -- Bertrand, D -- Besson, D Z -- Binder, G -- Bindig, D -- Bissok, M -- Blaufuss, E -- Blumenthal, J -- Boersma, D J -- Bohaichuk, S -- Bohm, C -- Bose, D -- Boser, S -- Botner, O -- Brayeur, L -- Bretz, H-P -- Brown, A M -- Bruijn, R -- Brunner, J -- Carson, M -- Casey, J -- Casier, M -- Chirkin, D -- Christov, A -- Christy, B -- Clark, K -- Clevermann, F -- Coenders, S -- Cohen, S -- Cowen, D F -- Cruz Silva, A H -- Danninger, M -- Daughhetee, J -- Davis, J C -- Day, M -- De Clercq, C -- De Ridder, S -- Desiati, P -- de Vries, K D -- de With, M -- DeYoung, T -- Diaz-Velez, J C -- Dunkman, M -- Eagan, R -- Eberhardt, B -- Eichmann, B -- Eisch, J -- Ellsworth, R W -- Euler, S -- Evenson, P A -- Fadiran, O -- Fazely, A R -- Fedynitch, A -- Feintzeig, J -- Feusels, T -- Filimonov, K -- Finley, C -- Fischer-Wasels, T -- Flis, S -- Franckowiak, A -- Frantzen, K -- Fuchs, T -- Gaisser, T K -- Gallagher, J -- Gerhardt, L -- Gladstone, L -- Glusenkamp, T -- Goldschmidt, A -- Golup, G -- Gonzalez, J G -- Goodman, J A -- Gora, D -- Grandmont, D T -- Grant, D -- Gross, A -- Ha, C -- Haj Ismail, A -- Hallen, P -- Hallgren, A -- Halzen, F -- Hanson, K -- Heereman, D -- Heinen, D -- Helbing, K -- Hellauer, R -- Hickford, S -- Hill, G C -- Hoffman, K D -- Hoffmann, R -- Homeier, A -- Hoshina, K -- Huelsnitz, W -- Hulth, P O -- Hultqvist, K -- Hussain, S -- Ishihara, A -- Jacobi, E -- Jacobsen, J -- Jagielski, K -- Japaridze, G S -- Jero, K -- Jlelati, O -- Kaminsky, B -- Kappes, A -- Karg, T -- Karle, A -- Kelley, J L -- Kiryluk, J -- Klas, J -- Klein, S R -- Kohne, J-H -- Kohnen, G -- Kolanoski, H -- Kopke, L -- Kopper, C -- Kopper, S -- Koskinen, D J -- Kowalski, M -- Krasberg, M -- Krings, K -- Kroll, G -- Kunnen, J -- Kurahashi, N -- Kuwabara, T -- Labare, M -- Landsman, H -- Larson, M J -- Lesiak-Bzdak, M -- Leuermann, M -- Leute, J -- Lunemann, J -- Madsen, J -- Maggi, G -- Maruyama, R -- Mase, K -- Matis, H S -- McNally, F -- Meagher, K -- Merck, M -- Meures, T -- Miarecki, S -- Middell, E -- Milke, N -- Miller, J -- Mohrmann, L -- Montaruli, T -- Morse, R -- Nahnhauer, R -- Naumann, U -- Niederhausen, H -- Nowicki, S C -- Nygren, D R -- Obertacke, A -- Odrowski, S -- Olivas, A -- O'Murchadha, A -- Paul, L -- Pepper, J A -- Perez de los Heros, C -- Pfendner, C -- Pieloth, D -- Pinat, E -- Posselt, J -- Price, P B -- Przybylski, G T -- Radel, L -- Rameez, M -- Rawlins, K -- Redl, P -- Reimann, R -- Resconi, E -- Rhode, W -- Ribordy, M -- Richman, M -- Riedel, B -- Rodrigues, J P -- Rott, C -- Ruhe, T -- Ruzybayev, B -- Ryckbosch, D -- Saba, S M -- Salameh, T -- Sander, H-G -- Santander, M -- Sarkar, S -- Schatto, K -- Scheriau, F -- Schmidt, T -- Schmitz, M -- Schoenen, S -- Schoneberg, S -- Schonwald, A -- Schukraft, A -- Schulte, L -- Schulz, O -- Seckel, D -- Sestayo, Y -- Seunarine, S -- Shanidze, R -- Sheremata, C -- Smith, M W E -- Soldin, D -- Spiczak, G M -- Spiering, C -- Stamatikos, M -- Stanev, T -- Stasik, A -- Stezelberger, T -- Stokstad, R G -- Stossl, A -- Strahler, E A -- Strom, R -- Sullivan, G W -- Taavola, H -- Taboada, I -- Tamburro, A -- Tepe, A -- Ter-Antonyan, S -- Tesic, G -- Tilav, S -- Toale, P A -- Toscano, S -- Unger, E -- Usner, M -- van Eijndhoven, N -- Van Overloop, A -- van Santen, J -- Vehring, M -- Voge, M -- Vraeghe, M -- Walck, C -- Waldenmaier, T -- Wallraff, M -- Weaver, Ch -- Wellons, M -- Wendt, C -- Westerhoff, S -- Whitehorn, N -- Wiebe, K -- Wiebusch, C H -- Williams, D R -- Wissing, H -- Wolf, M -- Wood, T R -- Woschnagg, K -- Xu, D L -- Xu, X W -- Yanez, J P -- Yodh, G -- Yoshida, S -- Zarzhitsky, P -- Ziemann, J -- Zierke, S -- Zoll, M -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):1242856. doi: 10.1126/science.1242856.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264993" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2017-10-06
    Description: At the core of the "proton radius puzzle" is a four–standard deviation discrepancy between the proton root-mean-square charge radii ( r p ) determined from the regular hydrogen (H) and the muonic hydrogen (µp) atoms. Using a cryogenic beam of H atoms, we measured the 2S-4P transition frequency in H, yielding the values of the Rydberg constant R = 10973731.568076(96) per meter and r p = 0.8335(95) femtometer. Our r p value is 3.3 combined standard deviations smaller than the previous H world data, but in good agreement with the µp value. We motivate an asymmetric fit function, which eliminates line shifts from quantum interference of neighboring atomic resonances.
    Keywords: Physics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-12-23
    Description: The coma and the comet–solar wind interaction of comet 67P/Churyumov–Gerasimenko changed dramatically from the initial Rosetta spacecraft encounter in 2014 August through perihelion in 2015 August. Just before equinox (at 1.6 au from the Sun), the solar wind signal disappeared and two regions of different cometary ion characteristics were observed. These ‘outer’ and ‘inner’ regions have cometary ion characteristics similar to outside and inside the ion pileup region observed during the Giotto approach to comet 1P/Halley. Rosetta /Double-Focusing Mass Spectrometer ion mass spectrometer observations are used here to investigate the H 3 O + /H 2 O + ratio in the outer and inner regions at 67P/ Churyumov–Gerasimenko. The H 3 O + /H 2 O + ratio and the H 3 O + signal are observed to increase in the transition from the outer to the inner region and the H 3 O + signal appears to be weakly correlated with cometary ion energy. These ion composition changes are similar to the ones observed during the 1P/Halley flyby. Modelling is used to determine the importance of neutral composition and transport of neutrals and ions away from the nucleus. This modelling demonstrates that changes in the H 3 O + /H 2 O + ratio appear to be driven largely by transport properties and only weakly by neutral composition in the coma.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 8
    Publication Date: 2016-12-29
    Description: We analyse the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) – the Double Focusing Mass Spectrometer data between 2014 August and 2016 February to examine the effect of seasonal variations on the four major species within the coma of 67P/Churyumov-Gerasimenko (H 2 O, CO 2 , CO, and O 2 ), resulting from the tilt in the orientation of the comet's spin axis. Using a numerical data inversion, we derive the non-uniform activity distribution at the surface of the nucleus for these species, suggesting that the activity distribution at the surface of the nucleus has not significantly been changed and that the differences observed in the coma are solely due to the variations in illumination conditions. A three-dimensional Direct Simulation Monte Carlo model is applied where the boundary conditions are computed with a coupling of the surface activity distributions and the local illumination. The model is able to reproduce the evolution of the densities observed by ROSINA including the changes happening at equinox. While O 2 stays correlated with H 2 O as it was before equinox, CO 2 and CO, which had a poor correlation with respect to H 2 O pre-equinox, also became well correlated with H 2 O post-equinox. The integration of the densities from the model along the line of sight results in column densities directly comparable to the VIRTIS-H observations. Also, the evolution of the volatiles’ production rates is derived from the coma model showing a steepening in the production rate curves after equinox. The model/data comparison suggests that the seasonal effects result in the Northern hemisphere of 67P's nucleus being more processed with a layered structure while the Southern hemisphere constantly exposes new material.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 9
    Publication Date: 2017-02-04
    Description: This paper presents the scientific investigation of three Lemnian sphragides ( terra sigillata , stamped earth), a famed medicinal clay in antiquity, dated to the sixteenth–seventeenth centuries, and presently in the Museum for the History of Pharmacy, University of Basel. The three specimens are compared with clays from the purported locality of its extraction, at Kotsinas, NE Lemnos, Greece. The study suggests a local origin for the Basel samples; it also demonstrates, for the first time, that the three Lemnian sphragides have a significant antibacterial effect against Staphylococcus aureus , a common Gram-positive pathogen, but have no such effect against Pseudomonas aeruginosa , a Gram-negative microorganism. Clay samples from the purported locality of extraction showed no antibacterial effect against S. aureus . Subsequent analysis with ultra-performance liquid-chromatography mass spectrometry (UPLC-MS) revealed the presence of organic constituents in one sphragis which were absent from a sample of modern clay. A fungal secondary metabolite is proposed here as the active ingredient but other factors may also play a role. The ongoing investigation into the bioactivity of some medicinal clays might aid in the re-evaluation of Belon's statement included at the start of this paper, namely, that the Lemnian earth worked only because people in the past wished it to work.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
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  • 10
    Publication Date: 2013-09-06
    Description: RecA is a DNA-dependent ATPase and mediates homologous recombination by first forming a filament on a single-stranded (ss) DNA. RecA binds preferentially to TGG repeat sequence, which resembles the recombination hot spot Chi (5'-GCTGGTGG-3') and is the most frequent pattern (GTG) of the codon usage in Escherichia coli . Because of the highly dynamic nature of RecA filament formation, which consists of filament nucleation, growth and shrinkage, we need experimental approaches that can resolve each of these processes separately to gain detailed insights into the molecular mechanism of sequence preference. By using a single-molecule fluorescence assay, we examined the effect of sequence on individual stages of nucleation, monomer binding and dissociation. We found that RecA does not recognize the Chi sequence as a nucleation site. In contrast, we observed that it is the reduced monomer dissociation that mainly determines the high filament stability on TGG repeats. This sequence dependence of monomer dissociation is well-correlated with that of ATP hydrolysis, suggesting that DNA sequence dictates filament stability through modulation of ATP hydrolysis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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