排序方式: 共有45条查询结果,搜索用时 109 毫秒
11.
Benson JD Chen YN Cornell-Kennon SA Dorsch M Kim S Leszczyniecka M Sellers WR Lengauer C 《Nature》2006,441(7092):451-456
A cancer drug target is only truly validated by demonstrating that a given therapeutic agent is clinically effective and acts through the target against which it was designed. Nevertheless, it is desirable to declare an early-stage drug target as 'validated' before investing in a full-scale drug discovery programme dedicated to it. Although the outcome of validation studies can guide cancer research programmes, strictly defined universal validation criteria have not been established. 相似文献
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Tenesa A Farrington SM Prendergast JG Porteous ME Walker M Haq N Barnetson RA Theodoratou E Cetnarskyj R Cartwright N Semple C Clark AJ Reid FJ Smith LA Kavoussanakis K Koessler T Pharoah PD Buch S Schafmayer C Tepel J Schreiber S Völzke H Schmidt CO Hampe J Chang-Claude J Hoffmeister M Brenner H Wilkening S Canzian F Capella G Moreno V Deary IJ Starr JM Tomlinson IP Kemp Z Howarth K Carvajal-Carmona L Webb E Broderick P Vijayakrishnan J Houlston RS Rennert G Ballinger D Rozek L Gruber SB 《Nature genetics》2008,40(5):631-637
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. 相似文献
13.
Summary The normal symbiotic aster leafhoppers,Macrosteles fascifrons, were reared under aseptic conditions on the holidic diet through 5 successive generations with normal rates of development, survival and reproduction. Thus the artificial diet is completely adequate for normal insects and dependence on gut organisms is not part of the physiology of this species. 相似文献
14.
Summary Hypophysectomy has no effect on the O2 consumption of minced brain and white muscle tissue, while liver tissue shows a marked reduction. This reduction in liver O2 consumption is attributed to the increased glycogen content that follows hypophysectomy which has the effect of increasing the nonmetabolizing dry weight component of the cells.Supported by the National Research Council of Canada, Grant Number A-3744 to P. H. J. 相似文献
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Chapman HN Hau-Riege SP Bogan MJ Bajt S Barty A Boutet S Marchesini S Frank M Woods BW Benner WH London RA Rohner U Szöke A Spiller E Möller T Bostedt C Shapiro DA Kuhlmann M Treusch R Plönjes E Burmeister F Bergh M Caleman C Huldt G Seibert MM Hajdu J 《Nature》2007,448(7154):676-679
Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging can be used to achieve high resolution, beyond radiation damage limits for biological samples. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion. 相似文献
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Marion Depla Rustem Uzbekov Christophe Hourioux Emmanuelle Blanchard Amélie Le Gouge Ludovic Gillet Philippe Roingeard 《Cellular and molecular life sciences : CMLS》2010,67(18):3151-3161
Hepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected
cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells
producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature
core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum
membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed
cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due,
at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further
studies of the mechanisms involved in HCV-induced steatosis. 相似文献
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Gezari S Chornock R Rest A Huber ME Forster K Berger E Challis PJ Neill JD Martin DC Heckman T Lawrence A Norman C Narayan G Foley RJ Marion GH Scolnic D Chomiuk L Soderberg A Smith K Kirshner RP Riess AG Smartt SJ Stubbs CW Tonry JL Wood-Vasey WM Burgett WS Chambers KC Grav T Heasley JN Kaiser N Kudritzki RP Magnier EA Morgan JS Price PA 《Nature》2012,485(7397):217-220
The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core. 相似文献
20.
Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways 总被引:2,自引:0,他引:2
Grimm D Streetz KL Jopling CL Storm TA Pandey K Davis CR Marion P Salazar F Kay MA 《Nature》2006,441(7092):537-541