The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol   总被引：1，自引：0，他引：1  

Barrett PJ  Song Y  Van Horn WD  Hustedt EJ  Schafer JM  Hadziselimovic A  Beel AJ  Sanders CR 《Science (New York, N.Y.)》2012,336(6085):1168-1171

C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.  相似文献   

Ocean science. A dive to Challenger Deep     

Lutz RA  Falkowski PG 《Science (New York, N.Y.)》2012,336(6079):301-302

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A major genome region underlying artemisinin resistance in malaria     

Cheeseman IH  Miller BA  Nair S  Nkhoma S  Tan A  Tan JC  Al Saai S  Phyo AP  Moo CL  Lwin KM  McGready R  Ashley E  Imwong M  Stepniewska K  Yi P  Dondorp AM  Mayxay M  Newton PN  White NJ  Nosten F  Ferdig MT  Anderson TJ 《Science (New York, N.Y.)》2012,336(6077):79-82

Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10(-6) to 10(-12)) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.  相似文献   

Early pottery at 20,000 years ago in Xianrendong Cave, China   总被引：1，自引：0，他引：1  

Wu X  Zhang C  Goldberg P  Cohen D  Pan Y  Arpin T  Bar-Yosef O 《Science (New York, N.Y.)》2012,336(6089):1696-1700

The invention of pottery introduced fundamental shifts in human subsistence practices and sociosymbolic behaviors. Here, we describe the dating of the early pottery from Xianrendong Cave, Jiangxi Province, China, and the micromorphology of the stratigraphic contexts of the pottery sherds and radiocarbon samples. The radiocarbon ages of the archaeological contexts of the earliest sherds are 20,000 to 19,000 calendar years before the present, 2000 to 3000 years older than other pottery found in East Asia and elsewhere. The occupations in the cave demonstrate that pottery was produced by mobile foragers who hunted and gathered during the Late Glacial Maximum. These vessels may have served as cooking devices. The early date shows that pottery was first made and used 10 millennia or more before the emergence of agriculture.  相似文献   

The development of C₄rice: current progress and future challenges     

von Caemmerer S  Quick WP  Furbank RT 《Science (New York, N.Y.)》2012,336(6089):1671-1672

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High-resolution protein structure determination by serial femtosecond crystallography     

Boutet S  Lomb L  Williams GJ  Barends TR  Aquila A  Doak RB  Weierstall U  DePonte DP  Steinbrener J  Shoeman RL  Messerschmidt M  Barty A  White TA  Kassemeyer S  Kirian RA  Seibert MM  Montanez PA  Kenney C  Herbst R  Hart P  Pines J  Haller G  Gruner SM  Philipp HT  Tate MW  Hromalik M  Koerner LJ  van Bakel N  Morse J  Ghonsalves W  Arnlund D  Bogan MJ  Caleman C  Fromme R  Hampton CY  Hunter MS  Johansson LC  Katona G  Kupitz C  Liang M  Martin AV  Nass K  Redecke L  Stellato F  Timneanu N  Wang D  Zatsepin NA  Schafer D  Defever J 《Science (New York, N.Y.)》2012,337(6092):362-364

Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.  相似文献   

Continental-scale effects of nutrient pollution on stream ecosystem functioning     

Woodward G  Gessner MO  Giller PS  Gulis V  Hladyz S  Lecerf A  Malmqvist B  McKie BG  Tiegs SD  Cariss H  Dobson M  Elosegi A  Ferreira V  Graça MA  Fleituch T  Lacoursière JO  Nistorescu M  Pozo J  Risnoveanu G  Schindler M  Vadineanu A  Vought LB  Chauvet E 《Science (New York, N.Y.)》2012,336(6087):1438-1440

Excessive nutrient loading is a major threat to aquatic ecosystems worldwide that leads to profound changes in aquatic biodiversity and biogeochemical processes. Systematic quantitative assessment of functional ecosystem measures for river networks is, however, lacking, especially at continental scales. Here, we narrow this gap by means of a pan-European field experiment on a fundamental ecosystem process--leaf-litter breakdown--in 100 streams across a greater than 1000-fold nutrient gradient. Dramatically slowed breakdown at both extremes of the gradient indicated strong nutrient limitation in unaffected systems, potential for strong stimulation in moderately altered systems, and inhibition in highly polluted streams. This large-scale response pattern emphasizes the need to complement established structural approaches (such as water chemistry, hydrogeomorphology, and biological diversity metrics) with functional measures (such as litter-breakdown rate, whole-system metabolism, and nutrient spiraling) for assessing ecosystem health.  相似文献   

Bright coherent ultrahigh harmonics in the keV x-ray regime from mid-infrared femtosecond lasers     

Popmintchev T  Chen MC  Popmintchev D  Arpin P  Brown S  Alisauskas S  Andriukaitis G  Balciunas T  Mücke OD  Pugzlys A  Baltuska A  Shim B  Schrauth SE  Gaeta A  Hernández-García C  Plaja L  Becker A  Jaron-Becker A  Murnane MM  Kapteyn HC 《Science (New York, N.Y.)》2012,336(6086):1287-1291

High-harmonic generation (HHG) traditionally combines ~100 near-infrared laser photons to generate bright, phase-matched, extreme ultraviolet beams when the emission from many atoms adds constructively. Here, we show that by guiding a mid-infrared femtosecond laser in a high-pressure gas, ultrahigh harmonics can be generated, up to orders greater than 5000, that emerge as a bright supercontinuum that spans the entire electromagnetic spectrum from the ultraviolet to more than 1.6 kilo-electron volts, allowing, in principle, the generation of pulses as short as 2.5 attoseconds. The multiatmosphere gas pressures required for bright, phase-matched emission also support laser beam self-confinement, further enhancing the x-ray yield. Finally, the x-ray beam exhibits high spatial coherence, even though at high gas density the recolliding electrons responsible for HHG encounter other atoms during the emission process.  相似文献   

Evaluation of neonicotinoid, organophosphate and avermectin trunk injections for the management of avocado thrips in California avocado groves     

Byrne FJ  Urena AA  Robinson LJ  Krieger RI  Doccola J  Morse JG 《Pest management science》2012,68(5):811-817

BACKGROUND: Trunk injections of systemic insecticides were evaluated for the management of avocado thrips. Insecticide residues were quantified in leaves to determine when after treatment, and for how long, toxic concentrations of the insecticides were present. Residues in fruit were quantified to determine whether trunk injection of insecticides might present a greater risk than traditional application methods for contaminating fruit. RESULTS: Residues of imidacloprid and dinotefuran were at least tenfold higher in leaves when trees were treated via trunk injection compared with soil application. Dinotefuran uptake was more rapid than imidacloprid, and no residues were detected within fruit. Acephate was also mobilized very rapidly and gave good control of thrips in bioassays; however, residues of acephate and its insecticidal metabolite methamidophos were detected in the fruit for up to 4 weeks after injection. Avermectin uptake was very slow, and it was ineffective against avocado thrips. CONCLUSIONS: Trunk injections of acephate and dinotefuran permitted rapid uptake into avocados, and they are strong candidates as control methods for avocado thrips. However, residues of organophosphates in fruit could necessitate increased preharvest intervals. Residues of neonicotinoids were below detection limits in fruit, suggesting that neonicotinoids may be the more suitable control option of the two chemical classes. Copyright © 2012 Society of Chemical Industry  相似文献   

The role of driving energy and delocalized States for charge separation in organic semiconductors     

Bakulin AA  Rao A  Pavelyev VG  van Loosdrecht PH  Pshenichnikov MS  Niedzialek D  Cornil J  Beljonne D  Friend RH 《Science (New York, N.Y.)》2012,335(6074):1340-1344

The electron-hole pair created via photon absorption in organic photoconversion systems must overcome the Coulomb attraction to achieve long-range charge separation. We show that this process is facilitated through the formation of excited, delocalized band states. In our experiments on organic photovoltaic cells, these states were accessed for a short time (<1 picosecond) via infrared (IR) optical excitation of electron-hole pairs bound at the heterojunction. Atomistic modeling showed that the IR photons promote bound charge pairs to delocalized band states, similar to those formed just after singlet exciton dissociation, which indicates that such states act as the gateway for charge separation. Our results suggest that charge separation in efficient organic photoconversion systems occurs through hot-state charge delocalization rather than energy-gradient-driven intermolecular hopping.  相似文献