Collaborating on public health issues     

Ozonoff D  Robbins A 《Science (New York, N.Y.)》2002,296(5572):1400

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Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage   总被引：3，自引：0，他引：3  

Dodd AN  Salathia N  Hall A  Kévei E  Tóth R  Nagy F  Hibberd JM  Millar AJ  Webb AA 《Science (New York, N.Y.)》2005,309(5734):630-633

Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.  相似文献   

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA     

Hegde SS  Vetting MW  Roderick SL  Mitchenall LA  Maxwell A  Takiff HE  Blanchard JS 《Science (New York, N.Y.)》2005,308(5727):1480-1483

Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.  相似文献   

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor     

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   

A conserved family of enzymes that phosphorylate inositol hexakisphosphate     

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   

Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc     

Anthony RM  Nimmerjahn F  Ashline DJ  Reinhold VN  Paulson JC  Ravetch JV 《Science (New York, N.Y.)》2008,320(5874):373-376

It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.  相似文献   

Postsynaptic receptor trafficking underlying a form of associative learning     

Rumpel S  LeDoux J  Zador A  Malinow R 《Science (New York, N.Y.)》2005,308(5718):83-88

To elucidate molecular, cellular, and circuit changes that occur in the brain during learning, we investigated the role of a glutamate receptor subtype in fear conditioning. In this form of learning, animals associate two stimuli, such as a tone and a shock. Here we report that fear conditioning drives AMPA-type glutamate receptors into the synapse of a large fraction of postsynaptic neurons in the lateral amygdala, a brain structure essential for this learning process. Furthermore, memory was reduced if AMPA receptor synaptic incorporation was blocked in as few as 10 to 20% of lateral amygdala neurons. Thus, the encoding of memories in the lateral amygdala is mediated by AMPA receptor trafficking, is widely distributed, and displays little redundancy.  相似文献   

Amalthea's density is less than that of water     

Anderson JD  Johnson TV  Schubert G  Asmar S  Jacobson RA  Johnston D  Lau EL  Lewis G  Moore WB  Taylor A  Thomas PC  Weinwurm G 《Science (New York, N.Y.)》2005,308(5726):1291-1293

Radio Doppler data from the Galileo spacecraft's encounter with Amalthea, one of Jupiter's small inner moons, on 5 November 2002 yield a mass of (2.08 +/- 0.15) x 10(18) kilograms. Images of Amalthea from two Voyager spacecraft in 1979 and Galileo imaging between November 1996 and June 1997 yield a volume of (2.43 +/- 0.22) x 10(6) cubic kilometers. The satellite thus has a density of 857 +/- 99 kilograms per cubic meter. We suggest that Amalthea is porous and composed of water ice, as well as rocky material, and thus formed in a cold region of the solar system, possibly not at its present location near Jupiter.  相似文献   

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo     

Solforosi L  Criado JR  McGavern DB  Wirz S  Sánchez-Alavez M  Sugama S  DeGiorgio LA  Volpe BT  Wiseman E  Abalos G  Masliah E  Gilden D  Oldstone MB  Conti B  Williamson RA 《Science (New York, N.Y.)》2004,303(5663):1514-1516

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.  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