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排序方式: 共有873条查询结果,搜索用时 62 毫秒
91.
Thorstensson F Wångsell F Kvarnström I Vrang L Hamelink E Jansson K Hallberg A Rosenquist S Samuelsson B 《Bioorganic & medicinal chemistry》2007,15(2):827-838
Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the P1-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K(i) value of 1.1nM. 相似文献
92.
Max Bylesjö Daniel Eriksson Andreas Sjödin Stefan Jansson Thomas Moritz Johan Trygg 《BMC bioinformatics》2007,8(1):207
Background
During generation of microarray data, various forms of systematic biases are frequently introduced which limits accuracy and precision of the results. In order to properly estimate biological effects, these biases must be identified and discarded. 相似文献93.
94.
Ohlsson C Wallaschofski H Lunetta KL Stolk L Perry JR Koster A Petersen AK Eriksson J Lehtimäki T Huhtaniemi IT Hammond GL Maggio M Coviello AD;EMAS Study Group Ferrucci L Heier M Hofman A Holliday KL Jansson JO Kähönen M Karasik D Karlsson MK Kiel DP Liu Y Ljunggren O Lorentzon M Lyytikäinen LP Meitinger T Mellström D Melzer D Miljkovic I Nauck M Nilsson M Penninx B Pye SR Vasan RS Reincke M Rivadeneira F Tajar A Teumer A Uitterlinden AG Ulloor J Viikari J Völker U Völzke H Wichmann HE Wu TS 《PLoS genetics》2011,7(10):e1002313
Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone''s high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG''s affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. 相似文献
95.
Johan Kroon Tore Ericsson Gunnar Jansson Bengt Andersson 《Tree Genetics & Genomes》2011,7(6):1099-1111
We reviewed the genetic parameter estimates carried out from 1992 to 2006 for height increment in genetic tests of Norway
spruce and Scots pine, to describe patterns of genetic variation, heritability, and genetic correlations. The material included
seedling and clonal tests in Sweden, aged between 5 and 20 years. Multiple regression was used to explore relationships between
parameter values and test environments. Results showed moderate narrow-sense heritabilities ([^(h)]2 {\hat{h}^2} : mean =0.29 in Norway spruce; mean =0.23 in Scots pine) that decreased with test site latitude for both species. In Norway
spruce, [^(h)]2 {\hat{h}^2} increased with better growth and decreased with tree age, while for Scots pine, [^(h)]2 {\hat{h}^2} increased with tree age and southward transfer. The additive genetic coefficient of variation (; mean 15%), in Norway spruce, decreased with growth as well as site latitude. in Scots pine (mean =8.5%) increased with southward transfer and more southerly test latitude. Additive and genotypic within-site
genetic age-age correlations in Norway spruce were high, with mean r
A
and r
G
of 0.92 and 0.85, respectively. Corresponding across-sites estimates were on average lower. Genetic parameters were better
expressed on favorable sites, at younger ages in Norway spruce and at older ages in Scots pine. The results imply that gain
calculations should be based on different parameters in the two species. For maximizing genetic gain in the Swedish breeding
program, testing times could be shorter for Norway spruce than for Scots pine. The investigation showed a large variation
in parameter estimates from different field experiments, highlighting the importance of testing over multiple sites. 相似文献
96.
Cantarel BL Erickson AR VerBerkmoes NC Erickson BK Carey PA Pan C Shah M Mongodin EF Jansson JK Fraser-Liggett CM Hettich RL 《PloS one》2011,6(11):e27173
Accurate protein identification in large-scale proteomics experiments relies upon a detailed, accurate protein catalogue, which is derived from predictions of open reading frames based on genome sequence data. Integration of mass spectrometry-based proteomics data with computational proteome predictions from environmental metagenomic sequences has been challenging because of the variable overlap between proteomic datasets and corresponding short-read nucleotide sequence data. In this study, we have benchmarked several strategies for increasing microbial peptide spectral matching in metaproteomic datasets using protein predictions generated from matched metagenomic sequences from the same human fecal samples. Additionally, we investigated the impact of mass spectrometry-based filters (high mass accuracy, delta correlation), and de novo peptide sequencing on the number and robustness of peptide-spectrum assignments in these complex datasets. In summary, we find that high mass accuracy peptide measurements searched against non-assembled reads from DNA sequencing of the same samples significantly increased identifiable proteins without sacrificing accuracy. 相似文献
97.
Background
Transgenic mice with low levels of global insulin-like growth factor-I (IGF-I) throughout their life span, including pre- and postnatal development, have increased longevity. This study investigated whether specific deficiency of liver-derived, endocrine IGF-I is of importance for life span.Methods and Findings
Serum IGF-I was reduced by approximately 80% in mice with adult, liver-specific IGF-I inactivation (LI-IGF-I-/- mice), and body weight decreased due to reduced body fat. The mean life span of LI-IGF-I-/- mice (n = 84) increased 10% vs. control mice (n = 137) (Cox''s test, p<0.01), mainly due to increased life span (16%) of female mice [LI-IGF-I-/- mice (n = 31): 26.7±1.1 vs. control (n = 67): 23.0±0.7 months, p<0.001]. Male LI-IGF-I-/- mice showed only a tendency for increased longevity (p = 0.10). Energy expenditure, measured as oxygen consumption during and after submaximal exercise, was increased in the LI-IGF-I-/- mice. Moreover, microarray and RT-PCR analyses showed consistent regulation of three genes (heat shock protein 1A and 1B and connective tissue growth factor) in several body organs in the LI-IGF-I-/- mice.Conclusions
Adult inactivation of liver-derived, endocrine IGF-I resulted in moderately increased mean life span. Body weight and body fat decreased in LI-IGF-I-/- mice, possibly due to increased energy expenditure during exercise. Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms that could underlie the increased mean life span in the LI-IGF-I-/- mice. 相似文献98.
99.
Mörner T Eriksson H Bröjer C Nilsson K Uhlhorn H Agren E af Segerstad CH Jansson DS Gavier-Widén D 《Journal of wildlife diseases》2005,41(2):298-303
Ninety-eight brown bears (Ursus arctos), 20 gray wolves (Canis lupus), and 27 wolverines (Gulo gulo), all free-ranging, were submitted to the National Veterinary Institute, Uppsala, Sweden, during 1987-2001 for investigation of diseases and causes of mortality. The most common cause of natural death in brown bears was infanticide. Infanticide also was observed in wolverines but not in wolves. Traumatic injuries, originating from road or railway accidents, were the most common cause of death in wolves and occurred occasionally in brown bears. Most wolverines were submitted as forensic cases in which illegal hunting/poaching was suspected. Sarcoptic mange was observed in several wolves but not in brown bears or wolverines. Sarcoptic mange most likely was acquired from infected red foxes (Vulpes vulpes) that were killed by wolves. Other parasites and infectious diseases were only found sporadically. 相似文献
100.
Algesten G Sobek S Bergström AK Jonsson A Tranvik LJ Jansson M 《Microbial ecology》2005,50(4):529-535
We measured sediment production of carbon dioxide (CO2) and methane (CH4) and the net flux of CO2 across the surfaces of 15 boreal and subarctic lakes of different humic contents. Sediment respiration measurements were
made in situ under ambient light conditions. The flux of CO2 between sediment and water varied between an uptake of 53 and an efflux of 182 mg C m−2 day−1 from the sediments. The mean respiration rate for sediments in contact with the upper mixed layer (SedR) was positively correlated
to dissolved organic carbon (DOC) concentration in the water (r2 = 0.61). The net flux of CO2 across the lake surface [net ecosystem exchange (NEE)] was also closely correlated to DOC concentration in the upper mixed
layer (r2 = 0.73). The respiration in the water column was generally 10-fold higher per unit lake area compared to sediment respiration.
Lakes with DOC concentrations <5.6 mg L−1 had net consumption of CO2 in the sediments, which we ascribe to benthic primary production. Only lakes with very low DOC concentrations were net autotrophic
(<2.6 mg L−1) due to the dominance of dissolved allochthonous organic carbon in the water as an energy source for aquatic organisms. In
addition to previous findings of allochthonous organic matter as an important driver of heterotrophic metabolism in the water
column of lakes, this study suggests that sediment metabolism is also highly dependent on allochthonous carbon sources. 相似文献