DUBA: a deubiquitinase that regulates type I interferon production     

Kayagaki N  Phung Q  Chan S  Chaudhari R  Quan C  O'Rourke KM  Eby M  Pietras E  Cheng G  Bazan JF  Zhang Z  Arnott D  Dixit VM 《Science (New York, N.Y.)》2007,318(5856):1628-1632

Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA-based screen as a regulator of IFN-I production. Reduction of DUBA augmented the PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect. DUBA bound tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I response. TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses.  相似文献   

An academic transformation: the american college and the culture of aspiration, 1915-1940     

Karen D 《Science (New York, N.Y.)》1987,235(4790):798-799

  相似文献   

Phytolith evidence for early Holocene Cucurbita domestication in southwest Ecuador     

Piperno DR  Stothert KE 《Science (New York, N.Y.)》2003,299(5609):1054-1057

Cucurbita (squash and gourd) phytoliths recovered from two early Holocene archaeological sites in southwestern Ecuador and directly dated to 10,130 to 9320 carbon-14 years before the present (about 12,000 to 10,000 calendar years ago) are identified as derived from domesticated plants because they are considerably larger than those from modern wild taxa. The beginnings of plant husbandry appear to have been preceded by the exploitation of a wild species of Cucurbita during the terminal Pleistocene. These data provide evidence for an independent emergence of plant food production in lowland South America that was contemporaneous with or slightly before that in highland Mesoamerica.  相似文献   

The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction     

Lahiri SD  Zhang G  Dunaway-Mariano D  Allen KN 《Science (New York, N.Y.)》2003,299(5615):2067-2071

Enzymes provide enormous rate enhancements, unmatched by any other type of catalyst. The stabilization of high-energy states along the reaction coordinate is the crux of the catalytic power of enzymes. We report the atomic-resolution structure of a high-energy reaction intermediate stabilized in the active site of an enzyme. Crystallization of phosphorylated beta-phosphoglucomutase in the presence of the Mg(II) cofactor and either of the substrates glucose 1-phosphate or glucose 6-phosphate produced crystals of the enzyme-Mg(II)-glucose 1,6-(bis)phosphate complex, which diffracted x-rays to 1.2 and 1.4 angstroms, respectively. The structure reveals a stabilized pentacovalent phosphorane formed in the phosphoryl transfer from the C(1)O of glucose 1,6-(bis)phosphate to the nucleophilic Asp8 carboxylate.  相似文献   

Widespread intense turbulent mixing in the Southern Ocean     

Garabato AC  Polzin KL  King BA  Heywood KJ  Visbeck M 《Science (New York, N.Y.)》2004,303(5655):210-213

Observations of internal wave velocity fluctuations show that enhanced turbulent mixing over rough topography in the Southern Ocean is remarkably intense and widespread. Mixing rates exceeding background values by a factor of 10 to 1000 are common above complex bathymetry over a distance of 2000 to 3000 kilometers at depths greater than 500 to 1000 meters. This suggests that turbulent mixing in the Southern Ocean may contribute crucially to driving the upward transport of water closing the ocean's meridional overturning circulation, and thus needs to be represented in numerical simulations of the global ocean circulation and the spreading of biogeochemical tracers.  相似文献   

Ectoderm to mesoderm lineage switching during axolotl tail regeneration     

Echeverri K  Tanaka EM 《Science (New York, N.Y.)》2002,298(5600):1993-1996

Foreign environments may induce adult stem cells to switch lineages and populate multiple tissue types, but whether this mechanism is used for tissue repair remains uncertain. Urodele amphibians can regenerate fully functional, multitissue structures including the limb and tail. To determine whether lineage switching is an integral feature of this regeneration, we followed individual spinal cord cells live during tail regeneration in the axolotl. Spinal cord cells frequently migrate into surrounding tissue to form regenerating muscle and cartilage. Thus, in axolotls, cells switch lineage during a real example of regeneration.  相似文献   

Causal protein-signaling networks derived from multiparameter single-cell data     

Sachs K  Perez O  Pe'er D  Lauffenburger DA  Nolan GP 《Science (New York, N.Y.)》2005,308(5721):523-529

Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.  相似文献   

Constraints on neon and argon isotopic fractionation in solar wind     

Meshik A  Mabry J  Hohenberg C  Marrocchi Y  Pravdivtseva O  Burnett D  Olinger C  Wiens R  Reisenfeld D  Allton J  McNamara K  Stansbery E  Jurewicz AJ 《Science (New York, N.Y.)》2007,318(5849):433-435

To evaluate the isotopic composition of the solar nebula from which the planets formed, the relation between isotopes measured in the solar wind and on the Sun's surface needs to be known. The Genesis Discovery mission returned independent samples of three types of solar wind produced by different solar processes that provide a check on possible isotopic variations, or fractionation, between the solar-wind and solar-surface material. At a high level of precision, we observed no significant inter-regime differences in 20Ne/22Ne or 36Ar/38Ar values. For 20Ne/22Ne, the difference between low- and high-speed wind components is 0.24 +/- 0.37%; for 36Ar/38Ar, it is 0.11 +/- 0.26%. Our measured 36Ar/38Ar ratio in the solar wind of 5.501 +/- 0.005 is 3.42 +/- 0.09% higher than that of the terrestrial atmosphere, which may reflect atmospheric losses early in Earth's history.  相似文献   

The convergence of synthetic organic and polymer chemistries     

Hawker CJ  Wooley KL 《Science (New York, N.Y.)》2005,309(5738):1200-1205

Several recent conceptual advances, which take advantage of the design criteria and practical techniques of molecular-level control in organic chemistry, allow preparation of well-defined polymers and nanostructured materials. Two trends are clear: the realization that synthesis of complex macromolecules poses major challenges and opportunities and the expectation that such materials will exhibit distinctive properties and functions. Polymer synthesis methods now being developed will yield well-defined synthetic macromolecules that are capable of mimicking many of the features of proteins (for example, three-dimensional folded structure) and other natural materials. These macromolecules have far-reaching potential for the study of molecular-level behavior at interfaces, in thin films, and in solution, while also enabling the development of encapsulation, drug-delivery, and nanoscale-patterning technologies.  相似文献   

A delicate balance in Amazonia     

Bruna EM  Kainer KA 《Science (New York, N.Y.)》2005,307(5712):1044-5; author reply 1044-5

  相似文献