Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation     

Gestwicki JE  Crabtree GR  Graef IA 《Science (New York, N.Y.)》2004,306(5697):865-869

Protein aggregation is involved in the pathogenesis of neurodegenerative diseases and hence is considered an attractive target for therapeutic intervention. However, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric bulk to prevent interactions between large peptide surfaces. To yield potent inhibitors of beta-amyloid (Abeta) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with Abeta. This strategy yields potent inhibitors of Abeta aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.  相似文献   

Statement on scientific publication and security     

Atlas R  Campbell P  Cozzarelli NR  Curfman G  Enquist L  Fink G  Flanagin A  Fletcher J  George E  Hammes G  Heyman D  Inglesby T  Kaplan S  Kennedy D  Krug J  Levinson R  Marcus E  Metzger H  Morse SS  O'Brien A  Onderdonk A  Poste G  Renault B  Rich R  Rosengard A  Salzburg S  Scanlan M  Shenk T  Tabor H  Varmus H  Wimmer E  Yamamoto K;Journal Editors  Authors Group 《Science (New York, N.Y.)》2003,299(5610):1149

  相似文献   

How much more global warming and sea level rise?     

Meehl GA  Washington WM  Collins WD  Arblaster JM  Hu A  Buja LE  Strand WG  Teng H 《Science (New York, N.Y.)》2005,307(5716):1769-1772

Two global coupled climate models show that even if the concentrations of greenhouse gases in the atmosphere had been stabilized in the year 2000, we are already committed to further global warming of about another half degree and an additional 320% sea level rise caused by thermal expansion by the end of the 21st century. Projected weakening of the meridional overturning circulation in the North Atlantic Ocean does not lead to a net cooling in Europe. At any given point in time, even if concentrations are stabilized, there is a commitment to future climate changes that will be greater than those we have already observed.  相似文献   

No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected     

Knox K  Carrigan D  Simmons G  Teque F  Zhou Y  Hackett J  Qiu X  Luk KC  Schochetman G  Knox A  Kogelnik AM  Levy JA 《Science (New York, N.Y.)》2011,333(6038):94-97

  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   

Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster     

Zdobnov EM  von Mering C  Letunic I  Torrents D  Suyama M  Copley RR  Christophides GK  Thomasova D  Holt RA  Subramanian GM  Mueller HM  Dimopoulos G  Law JH  Wells MA  Birney E  Charlab R  Halpern AL  Kokoza E  Kraft CL  Lai Z  Lewis S  Louis C  Barillas-Mury C  Nusskern D  Rubin GM  Salzberg SL  Sutton GG  Topalis P  Wides R  Wincker P  Yandell M  Collins FH  Ribeiro J  Gelbart WM  Kafatos FC  Bork P 《Science (New York, N.Y.)》2002,298(5591):149-159

Comparison of the genomes and proteomes of the two diptera Anopheles gambiae and Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some of these must reflect the selection and subsequent adaptation associated with different ecologies and life strategies. Almost half of the genes in both genomes are interpreted as orthologs and show an average sequence identity of about 56%, which is slightly lower than that observed between the orthologs of the pufferfish and human (diverged about 450 million years ago). This indicates that these two insects diverged considerably faster than vertebrates. Aligned sequences reveal that orthologous genes have retained only half of their intron/exon structure, indicating that intron gains or losses have occurred at a rate of about one per gene per 125 million years. Chromosomal arms exhibit significant remnants of homology between the two species, although only 34% of the genes colocalize in small "microsyntenic" clusters, and major interarm transfers as well as intra-arm shuffling of gene order are detected.  相似文献   

Clinical evaluation of serum alcohol dehydrogenase activity in horses with acute intestinal obstruction     

Naglaa Abdel Megid Gomaa BVSc  MVSc  Gábor Köller Dr rer nat  Gerald Fritz Schusser Dr vet med  DECEIM 《Journal of Veterinary Emergency and Critical Care》2011,21(3):242-252

Objectives – To measure serum alcohol dehydrogenase (ADH) activity in horses with acute intestinal obstruction and to determine the diagnostic and prognostic utility of this analyte. Design – Prospective observational study. Setting – University Veterinary Hospital. Animals – Thirty healthy horses (control group) and 77 horses with acute intestinal obstruction, including 36 horses with nonstrangulating obstruction (23 with left ventral colon impaction and 13 with left dorsal displacement [G1], 22 with small intestinal strangulation [G2], and 19 with colon torsion [G3]). Interventions – Serum ADH activity was assayed spectrophotometerically in all horses. Serum lactate concentration and hepatic enzyme (aspartate aminotransferase, gamma‐glutamyl transferase, glutamate dehydrogenase) activities were measured using an automatic analyzer. Measurements and Main Results – The median [interquartile range] serum ADH activity in healthy horses was 10.5 [8.7 – 11 U/L]. ADH activity was significantly increased (P<0.05) in G1=16.5 [13.8 – 18 U/L], G2=40 [20 – 74.9 U/L], and G3=63.2 [40 – 78 U/L] compared with healthy controls. Aspartate aminotransferase and glutamate dehydrogenase activities were also significantly increased in G3 in comparison with controls. ADH activity was correlated with serum lactate concentration in G1 and G3, respectively (P<0.01, r=0.55 and 0.8). Other liver enzymes did not show any significant correlation with lactate. ADH activity was directly related to the probability of strangulation; odds ratio=1.11. ADH activity >20 U/L had 80.6% specificity and 80.5% sensitivity for discriminating horses with strangulating obstruction. Twelve horses euthanized before surgery were excluded from the outcome analysis. Increasing ADH activity was associated with nonsurvival; odds ratio=1.03. ADH activity <80 U/L had 94.44% specificity and 66.67% sensitivity for survival. Conclusion – Serum ADH activity may be a useful clinical parameter in detecting intestinal strangulation in horses and may provide some prognostic value in horses with acute intestinal obstruction.  相似文献   

Economic benefits of conservation tillage in New Zealand II. Pastoral sheep farms     

Gerald A.G. Frengley 《Soil & Tillage Research》1983,3(4):357-365

The adoption of conservation tillage procedures for pasture renewal and winter forage cropping in New Zealand is shown to be very profitable and to lead to some management simplification. The conservation tillage technique has widespread application to New Zealand sheep farms and the rate of adoption may be expected to increase.  相似文献   

Tissue distribution, elimination, and metabolism of dietary sodium [36Cl]chlorate in beef cattle     

Smith DJ  Anderson RC  Ellig DA  Larsen GL 《Journal of agricultural and food chemistry》2005,53(10):4272-4280

Two steers (approximately 195 kg) were each dosed with 62.5 or 130.6 mg/kg body weight sodium [36Cl]chlorate for three consecutive days. All excreta were collected during the dosing and 8 h withdrawal periods. The apparent radiochlorine absorption was 62-68% of the total dose with the major excretory route being urine. Parent chlorate was 65-100% of the urinary radiochlorine; chloride was the only other radiochlorine species present. Similarly, residues in edible tissues were composed of chloride and chlorate with chloride being the major radiolabeled species present. Chlorate represented 28-57% of the total radioactive residues in skeletal muscle; in liver, kidney, and adipose tissues, chlorate ion represented a smaller percentage of the total residues. Chlorate residues in the low dose steer were 26 ppm in kidney, 14 ppm in skeletal muscle, 2.0 ppm in adipose tissue, and 0.7 ppm in liver. These data indicate that sodium chlorate may be a viable preharvest food safety tool for use by the cattle industry.  相似文献   

Effects of soil pH and soil water content on prosulfuron dissipation   总被引：3，自引：0，他引：3  

Hultgren RP  Hudson RJ  Sims GK 《Journal of agricultural and food chemistry》2002,50(11):3236-3243

The sulfonylurea herbicide prosulfuron, 1-(4-methoxy-6-methyltriazin-2-yl)-3-[2-(3,3,3-trifluoropropyl)phenylsulfonyl]urea, is used for the selective control of broadleaf weeds in corn, sorghum, and cereal grains. To investigate its fate in soils, this study examined the effects of soil pH and water content on the rates of dissipation processes and the products formed under aerobic conditions. Radiometry and chromatography analyses were used to quantify the degradation products and bound residues formed in incubations of 10 different soils. The pH-dependent hydrolysis of the sulfonylurea bridge to form phenyl sulfonamide was the primary transformation process. Significant microbial degradation of prosulfuron occurred in 2 of the 10 soils, yielding (14)CO(2) and desmethyl prosulfuron among the major products. The time required for 50% dissipation of the herbicide (DT(50)) was determined for each soil and water content treatment. At equivalent water contents, prosulfuron DT(50) values were positively correlated with soil pH (P < 0.0001), varying from 6.5 days at pH 5.4 to 122.9 days at pH 7.9. Soil pH and water content strongly influence the fate of sulfonylurea herbicides in agricultural fields. Differences in the effect of soil water content on dissipation kinetics in a comparison of two soils were attributed to differences in soil pH, texture, and the ability of indigenous microorganisms to transform the herbicide.  相似文献