Mutational analysis of the tyrosine kinome in colorectal cancers     

Bardelli A  Parsons DW  Silliman N  Ptak J  Szabo S  Saha S  Markowitz S  Willson JK  Parmigiani G  Kinzler KW  Vogelstein B  Velculescu VE 《Science (New York, N.Y.)》2003,300(5621):949

  相似文献   

Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk     

Abtahian F  Guerriero A  Sebzda E  Lu MM  Zhou R  Mocsai A  Myers EE  Huang B  Jackson DG  Ferrari VA  Tybulewicz V  Lowell CA  Lepore JJ  Koretzky GA  Kahn ML 《Science (New York, N.Y.)》2003,299(5604):247-251

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.  相似文献   

Metal chelation and inhibition of bacterial growth in tissue abscesses     

Corbin BD  Seeley EH  Raab A  Feldmann J  Miller MR  Torres VJ  Anderson KL  Dattilo BM  Dunman PM  Gerads R  Caprioli RM  Nacken W  Chazin WJ  Skaar EP 《Science (New York, N.Y.)》2008,319(5865):962-965

  相似文献   

Biomedical research publication system     

Wang YL  Burridge K  Dembo M  Gabbiani G  Hanks SK  Hosoya H  Janmey P  Karlsson R  Lindberg U  Mabuchi I  Otey C  Rottner K  Small JV  Wang CL  Zigmond S 《Science (New York, N.Y.)》2004,303(5666):1974-1976

  相似文献   

Extended Boltzmann kinetic equation for turbulent flows     

Chen H  Kandasamy S  Orszag S  Shock R  Succi S  Yakhot V 《Science (New York, N.Y.)》2003,301(5633):633-636

Complex fluid physics can be modeled using an extended kinetic (Boltzmann) equation in a more efficient way than using the continuum Navier-Stokes equations. Here, we explain this method for modeling fluid turbulence and show its effectiveness with the use of a computationally efficient implementation in terms of a discrete or "lattice" Boltzmann equation.  相似文献   

Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling     

Walmsley MJ  Ooi SK  Reynolds LF  Smith SH  Ruf S  Mathiot A  Vanes L  Williams DA  Cancro MP  Tybulewicz VL 《Science (New York, N.Y.)》2003,302(5644):459-462

The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.  相似文献   

Experimental identification of downhill protein folding     

Garcia-Mira MM  Sadqi M  Fischer N  Sanchez-Ruiz JM  Muñoz V 《Science (New York, N.Y.)》2002,298(5601):2191-2195

Theory predicts the existence of barrierless protein folding. Without barriers, folding should be noncooperative and the degree of native structure should be coupled to overall protein stability. We investigated the thermal unfolding of the peripheral subunit binding domain from Escherichia coli's 2-oxoglutarate dehydrogenase multienzyme complex (termed BBL) with a combination of spectroscopic techniques and calorimetry. Each technique probed a different feature of protein structure. BBL has a defined three-dimensional structure at low temperatures. However, each technique showed a distinct unfolding transition. Global analysis with a statistical mechanical model identified BBL as a downhill-folding protein. Because of BBL's biological function, we propose that downhill folders may be molecular rheostats, in which effects could be modulated by altering the distribution of an ensemble of structures.  相似文献   

Kilimanjaro ice core records: evidence of holocene climate change in tropical Africa   总被引：1，自引：0，他引：1  

Thompson LG  Mosley-Thompson E  Davis ME  Henderson KA  Brecher HH  Zagorodnov VS  Mashiotta TA  Lin PN  Mikhalenko VN  Hardy DR  Beer J 《Science (New York, N.Y.)》2002,298(5593):589-593

Six ice cores from Kilimanjaro provide an approximately 11.7-thousand-year record of Holocene climate and environmental variability for eastern equatorial Africa, including three periods of abrupt climate change: approximately 8.3, approximately 5.2, and approximately 4 thousand years ago (ka). The latter is coincident with the "First Dark Age," the period of the greatest historically recorded drought in tropical Africa. Variable deposition of F- and Na+ during the African Humid Period suggests rapidly fluctuating lake levels between approximately 11.7 and 4 ka. Over the 20th century, the areal extent of Kilimanjaro's ice fields has decreased approximately 80%, and if current climatological conditions persist, the remaining ice fields are likely to disappear between 2015 and 2020.  相似文献   

Isotopic evidence for massive oxidation of organic matter following the great oxidation event     

Kump LR  Junium C  Arthur MA  Brasier A  Fallick A  Melezhik V  Lepland A  Crne AE  Luo G 《Science (New York, N.Y.)》2011,334(6063):1694-1696

The stable isotope record of marine carbon indicates that the Proterozoic Eon began and ended with extreme fluctuations in the carbon cycle. In both the Paleoproterozoic [2500 to 1600 million years ago (Ma)] and Neoproterozoic (1000 to 542 Ma), extended intervals of anomalously high carbon isotope ratios (δ(13)C) indicate high rates of organic matter burial and release of oxygen to the atmosphere; in the Neoproterozoic, the high δ(13)C interval was punctuated by abrupt swings to low δ(13)C, indicating massive oxidation of organic matter. We report a Paleoproterozoic negative δ(13)C excursion that is similar in magnitude and apparent duration to the Neoproterozoic anomaly. This Shunga-Francevillian anomaly may reflect intense oxidative weathering of rocks as the result of the initial establishment of an oxygen-rich atmosphere.  相似文献   

Biological activity of peanut (Arachis hypogaea) phytoalexins and selected natural and synthetic Stilbenoids     

Sobolev VS  Khan SI  Tabanca N  Wedge DE  Manly SP  Cutler SJ  Coy MR  Becnel JJ  Neff SA  Gloer JB 《Journal of agricultural and food chemistry》2011,59(5):1673-1682

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities.  相似文献