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排序方式: 共有1212条查询结果,搜索用时 15 毫秒
91.
Changelian PS Flanagan ME Ball DJ Kent CR Magnuson KS Martin WH Rizzuti BJ Sawyer PS Perry BD Brissette WH McCurdy SP Kudlacz EM Conklyn MJ Elliott EA Koslov ER Fisher MB Strelevitz TJ Yoon K Whipple DA Sun J Munchhof MJ Doty JL Casavant JM Blumenkopf TA Hines M Brown MF Lillie BM Subramanyam C Shang-Poa C Milici AJ Beckius GE Moyer JD Su C Woodworth TG Gaweco AS Beals CR Littman BH Fisher DA Smith JF Zagouras P Magna HA Saltarelli MJ Johnson KS Nelms LF Des Etages SG Hayes LS Kawabata TT 《Science (New York, N.Y.)》2003,302(5646):875-878
Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings. 相似文献
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94.
Phenotypic variation among organisms is central to evolutionary adaptations underlying natural and artificial selection, and also determines individual susceptibility to common diseases. These types of complex traits pose special challenges for genetic analysis because of gene-gene and gene-environment interactions, genetic heterogeneity, low penetrance, and limited statistical power. Emerging genome resources and technologies are enabling systematic identification of genes underlying these complex traits. We propose standards for proof of gene discovery in complex traits and evaluate the nature of the genes identified to date. These proof-of-concept studies demonstrate the insights that can be expected from the accelerating pace of gene discovery in this field. 相似文献
95.
Mulugu S Bai W Fridy PC Bastidas RJ Otto JC Dollins DE Haystead TA Ribeiro AA York JD 《Science (New York, N.Y.)》2007,316(5821):106-109
Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6. 相似文献
96.
Fortunel NO Otu HH Ng HH Chen J Mu X Chevassut T Li X Joseph M Bailey C Hatzfeld JA Hatzfeld A Usta F Vega VB Long PM Libermann TA Lim B 《Science (New York, N.Y.)》2003,302(5644):393; author reply 393
97.
Dorigo B Schalch T Kulangara A Duda S Schroeder RR Richmond TJ 《Science (New York, N.Y.)》2004,306(5701):1571-1573
Chromatin folding determines the accessibility of DNA constituting eukaryotic genomes and consequently is profoundly important in the mechanisms of nuclear processes such as gene regulation. Nucleosome arrays compact to form a 30-nanometer chromatin fiber of hitherto disputed structure. Two competing classes of models have been proposed in which nucleosomes are either arranged linearly in a one-start higher order helix or zigzag back and forth in a two-start helix. We analyzed compacted nucleosome arrays stabilized by introduction of disulfide cross-links and show that the chromatin fiber comprises two stacks of nucleosomes in accord with the two-start model. 相似文献
98.
Houghton J Stoicov C Nomura S Rogers AB Carlson J Li H Cai X Fox JG Goldenring JR Wang TC 《Science (New York, N.Y.)》2004,306(5701):1568-1571
Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression. 相似文献
99.
Ferguson SM Brasnjo G Hayashi M Wölfel M Collesi C Giovedi S Raimondi A Gong LW Ariel P Paradise S O'toole E Flavell R Cremona O Miesenböck G Ryan TA De Camilli P 《Science (New York, N.Y.)》2007,316(5824):570-574
Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity, branched, tubular plasma membrane invaginations accumulated, capped by clathrin-coated pits, in synapses of dynamin 1-knockout mice. Synaptic vesicle endocytosis was severely impaired during strong exogenous stimulation but resumed efficiently when the stimulus was terminated. Thus, dynamin 1-independent mechanisms can support limited synaptic vesicle endocytosis, but dynamin 1 is needed during high levels of neuronal activity. 相似文献
100.
A transient rise in tropical sea surface temperature during the Paleocene-Eocene thermal maximum 总被引:1,自引:0,他引:1
Zachos JC Wara MW Bohaty S Delaney ML Petrizzo MR Brill A Bralower TJ Premoli-Silva I 《Science (New York, N.Y.)》2003,302(5650):1551-1554
The Paleocene-Eocene Thermal Maximum (PETM) has been attributed to a rapid rise in greenhouse gas levels. If so, warming should have occurred at all latitudes, although amplified toward the poles. Existing records reveal an increase in high-latitude sea surface temperatures (SSTs) (8 degrees to 10 degrees C) and in bottom water temperatures (4 degrees to 5 degrees C). To date, however, the character of the tropical SST response during this event remains unconstrained. Here we address this deficiency by using paired oxygen isotope and minor element (magnesium/calcium) ratios of planktonic foraminifera from a tropical Pacific core to estimate changes in SST. Using mixed-layer foraminifera, we found that the combined proxies imply a 4 degrees to 5 degrees C rise in Pacific SST during the PETM. These results would necessitate a rise in atmospheric pCO2 to levels three to four times as high as those estimated for the late Paleocene. 相似文献