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161.
Ding L Ley TJ Larson DE Miller CA Koboldt DC Welch JS Ritchey JK Young MA Lamprecht T McLellan MD McMichael JF Wallis JW Lu C Shen D Harris CC Dooling DJ Fulton RS Fulton LL Chen K Schmidt H Kalicki-Veizer J Magrini VJ Cook L McGrath SD Vickery TL Wendl MC Heath S Watson MA Link DC Tomasson MH Shannon WD Payton JE Kulkarni S Westervelt P Walter MJ Graubert TA Mardis ER Wilson RK DiPersio JF 《Nature》2012,481(7382):506-510
Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions. 相似文献
162.
Prideaux GJ Long JA Ayliffe LK Hellstrom JC Pillans B Boles WE Hutchinson MN Roberts RG Cupper ML Arnold LJ Devine PD Warburton NM 《Nature》2007,445(7126):422-425
How well the ecology, zoogeography and evolution of modern biotas is understood depends substantially on knowledge of the Pleistocene. Australia has one of the most distinctive, but least understood, Pleistocene faunas. Records from the western half of the continent are especially rare. Here we report on a diverse and exceptionally well preserved middle Pleistocene vertebrate assemblage from caves beneath the arid, treeless Nullarbor plain of south-central Australia. Many taxa are represented by whole skeletons, which together serve as a template for identifying fragmentary, hitherto indeterminate, remains collected previously from Pleistocene sites across southern Australia. A remarkable eight of the 23 Nullarbor kangaroos are new, including two tree-kangaroos. The diverse herbivore assemblage implies substantially greater floristic diversity than that of the modern shrub steppe, but all other faunal and stable-isotope data indicate that the climate was very similar to today. Because the 21 Nullarbor species that did not survive the Pleistocene were well adapted to dry conditions, climate change (specifically, increased aridity) is unlikely to have been significant in their extinction. 相似文献
163.
There are five known taste modalities in humans: sweet, bitter, sour, salty and umami (the taste of monosodium glutamate). Although the fruitfly Drosophila melanogaster tastes sugars, salts and noxious chemicals, the nature and number of taste modalities in this organism is not clear. Previous studies have identified one taste cell population marked by the gustatory receptor gene Gr5a that detects sugars, and a second population marked by Gr66a that detects bitter compounds. Here we identify a novel taste modality in this insect: the taste of carbonated water. We use a combination of anatomical, calcium imaging and behavioural approaches to identify a population of taste neurons that detects CO2 and mediates taste acceptance behaviour. The taste of carbonation may allow Drosophila to detect and obtain nutrients from growing microorganisms. Whereas CO2 detection by the olfactory system mediates avoidance, CO2 detection by the gustatory system mediates acceptance behaviour, demonstrating that the context of CO2 determines appropriate behaviour. This work opens up the possibility that the taste of carbonation may also exist in other organisms. 相似文献
164.
165.
Daniel Kümmel Julia Walter Martin Heck Udo Heinemann Michael Veit 《Cellular and molecular life sciences : CMLS》2010,67(15):2653-2664
Bet3, a transport protein particle component involved in vesicular trafficking, contains a hydrophobic tunnel occupied by
a fatty acid linked to cysteine 68. We reported that Bet3 has a unique self-palmitoylating activity. Here we show that mutation
of arginine 67 reduced self-palmitoylation of Bet3, but the effect was compensated by increasing the pH. Thus, arginine helps
to deprotonate cysteine such that it could function as a nucleophile in the acylation reaction which is supported by the structural
analysis of non-acylated Bet3. Using fluorescence spectroscopy we show that long-chain acyl-CoAs bind with micromolar affinity
to Bet3, whereas shorter-chain acyl-CoAs do not interact. Mutants with a deleted acylation site or a blocked tunnel bind to
Pal-CoA, only the latter with slightly reduced affinity. Bet3 contains three binding sites for Pal-CoA, but their number was
reduced to two in the mutant with an obstructed tunnel, indicating that Bet3 contains binding sites on its surface. 相似文献
166.
通过第一性原理研究了基于II-IV-V2族CKP半导体中CdSiAs2的非临界位相匹配二次谐波材料.根据量化双折射性同应力的线性关系,它的负双折射性使之能够通过应力、温度调节以及同CdGeAs2混合来设计非临界位相匹配材料.计算显示,少量的掺杂Ge(<5%),CdSi1-xGexAs2能够实现非临界位相匹配I类二次谐波产生(SHG)在CO2激光谱线范围可调谐,它可能具有很高的有效χ(2). 相似文献
167.
Broderick P Chubb D Johnson DC Weinhold N Försti A Lloyd A Olver B Ma YP Dobbins SE Walker BA Davies FE Gregory WA Child JA Ross FM Jackson GH Neben K Jauch A Hoffmann P Mühleisen TW Nöthen MM Moebus S Tomlinson IP Goldschmidt H Hemminki K Morgan GJ Houlston RS 《Nature genetics》2012,44(1):58-61
To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights. 相似文献
168.
Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
169.
J. Walter Moura R. C. Stocco dos Santos M. L. Z. Dagli J. L. D'Angelino E. H. Birgel W. Beçak 《Cellular and molecular life sciences : CMLS》1988,44(9):785-788
Summary Thirteen cows maintained on natural bracken fern (Pteridium aquilinum) were analyzed cytogenetically. The frequency of structural chromosome aberrations detected in peripheral blood cells was significantly higher when compared to that detected in animals raised on pasture containing no bracken fern. We discuss the clastogenic action of fern and its synergistic action with infection by type 2 and 4 papilloma virus in the same animals.Acknowledgments. We are grateful to Dr F. J. Benesi, Dr J. L. Guerra and Dr I. L. Sinhorini for performing some of the clinical and pathological analyses; O. P. Ferraz, L. A. Tadeu Dias, L. F. Feitosa and A. M. N. Paiva for technical assistance; and to Dr N. H. C. Castro and Dr C. de Araujo Peres for critical and statistics review, respectively. Research was supported by CNPq FAPESP and CAPES. 相似文献
170.