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排序方式: 共有164条查询结果,搜索用时 31 毫秒
141.
Anagnostou E Kosmopoulou MN Chrysina ED Leonidas DD Hadjiloi T Tiraidis C Zographos SE Györgydeák Z Somsák L Docsa T Gergely P Kolisis FN Oikonomakos NG 《Bioorganic & medicinal chemistry》2006,14(1):181-189
Structure-based inhibitor design has led to the discovery of a number of potent inhibitors of glycogen phosphorylase b (GPb), N-acyl derivatives of beta-D-glucopyranosylamine, that bind at the catalytic site of the enzyme. The first good inhibitor in this class of compounds, N-acetyl-beta-D-glucopyranosylamine (NAG) (K(i) = 32 microM), has been previously characterized by biochemical, biological and crystallographic experiments at 2.3 angstroms resolution. Bioisosteric replacement of the acetyl group by trifluoroacetyl group resulted in an inhibitor, N-trifluoroacetyl-beta-D-glucopyranosylamine (NFAG), with a K(i) = 75 microM. To elucidate the structural basis of its reduced potency, we determined the ligand structure in complex with GPb at 1.8 angstroms resolution. To compare the binding mode of N-trifluoroacetyl derivative with that of the lead molecule, we also determined the structure of GPb-NAG complex at a higher resolution (1.9 angstroms). NFAG can be accommodated in the catalytic site of T-state GPb at approximately the same position as that of NAG and stabilize the T-state conformation of the 280 s loop by making several favourable contacts to Asn284 of this loop. The difference observed in the K(i) values of the two analogues can be interpreted in terms of subtle conformational changes of protein residues and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interaction, and desolvation effects. 相似文献
142.
A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27 总被引:4,自引:0,他引:4 下载免费PDF全文
Auranen M Vanhala R Varilo T Ayers K Kempas E Ylisaukko-Oja T Sinsheimer JS Peltonen L Järvelä I 《American journal of human genetics》2002,71(4):777-790
To identify genetic loci for autism-spectrum disorders, we have performed a two-stage genomewide scan in 38 Finnish families. The detailed clinical examination of all family members revealed infantile autism, but also Asperger syndrome (AS) and developmental dysphasia, in the same set of families. The most significant evidence for linkage was found on chromosome 3q25-27, with a maximum two-point LOD score of 4.31 (Z(max )(dom)) for D3S3037, using infantile autism and AS as an affection status. Six markers flanking over a 5-cM region on 3q gave Z(max dom) >3, and a maximum parametric multipoint LOD score (MLS) of 4.81 was obtained in the vicinity of D3S3715 and D3S3037. Association, linkage disequilibrium, and haplotype analyses provided some evidence for shared ancestor alleles on this chromosomal region among affected individuals, especially in the regional subisolate. Additional potential susceptibility loci with two-point LOD scores >2 were observed on chromosomes 1q21-22 and 7q. The region on 1q21-22 overlaps with the previously reported candidate region for infantile autism and schizophrenia, whereas the region on chromosome 7q provided evidence for linkage 58 cM distally from the previously described autism susceptibility locus (AUTS1). 相似文献
143.
Polyakov NE Leshina TV Konovalova TA Hand EO Kispert LD 《Free radical biology & medicine》2004,36(7):872-880
Direct evidence of carotenoid/cyclodextrin inclusion complex formation was obtained for the water-soluble sodium salt of beta-caroten-8'-oic acid (IV) by using 1H NMR and UV-Vis absorption spectroscopy. It was shown that this carotenoid forms a stable 1:1 inclusion complex with beta-cyclodextrin (stability constant K11 approximately 1500 M(-1)). All other carotenoids under study in the presence of cyclodextrins (CDs) form large aggregates in aqueous solution as demonstrated by very broad absorption spectra and considerable change in color. By using the EPR spin trapping technique, the scavenging ability of IV toward OOH radicals was compared in DMSO and in the aqueous CD solution. A considerable decrease in PBN/OOH spin adduct yield was detected in the presence of uncomplexed IV because of a competing reaction of the carotenoid with OOH radical. No such decrease occurred in the presence of the IV/CD complex. Moreover, a small increase in spin adduct yield (pro-oxidant effect) is most likely due to the reaction of the carotenoid with Fe3+ to regenerate Fe2+, which in turn regenerates the OOH radical. Our data show that CD protects the carotenoid from reactive oxygen species. On the other hand, complexation with CD results in considerable decrease in antioxidant ability of the carotenoid. 相似文献
144.
Conservation of a domestic metapopulation structured into related and partly admixed strains 下载免费PDF全文
Jelena Ramljak Gjoko Bunevski Hysen Bytyqi Božidarka Marković Muhamed Brka Ante Ivanković Kristaq Kume Srđan Stojanović Vasil Nikolov Mojca Simčič Johann Sölkner Elisabeth Kunz Sophie Rothammer Doris Seichter Hans‐Peter Grünenfelder Elli T. Broxham Waltraud Kugler Ivica Medugorac 《Molecular ecology》2018,27(7):1633-1650
Preservation of genetic diversity is one of the most pressing challenges in the planetary boundaries concept. Within this context, we focused on genetic diversity in a native, unselected and highly admixed domesticated metapopulation. A set of 1,828 individuals from 60 different cattle breeds was analysed using a medium density SNP chip. Among these breeds, 14 Bu?a strains formed a metapopulation represented by 350 individuals, while the remaining 46 breeds represented the global cattle population. Genetic analyses showed that the scarcely selected and less differentiated Bu?a metapopulation contributed a substantial proportion (52.6%) of the neutral allelic diversity to this global taurine population. Consequently, there is an urgent need for synchronized maintenance of this highly fragmented domestic metapopulation, which is distributed over several countries without sophisticated infrastructure and highly endangered by continuous replacement crossing as part of the global genetic homogenization process. This study collected and evaluated samples, data and genomewide information and developed genome‐assisted cross‐border conservation concepts. To detect and maintain genetic integrity of the metapopulation strains, we designed and applied a composite test that combines six metrics based on additive genetic relationships, a nearest neighbour graph and the distribution of semiprivate alleles. Each metric provides distinct information components about past admixture events and offers an objective and powerful tool for the detection of admixed outliers. The here developed conservation methods and presented experiences could easily be adapted to comparable conservation programmes of domesticated or other metapopulations bred and kept in captivity or under some other sort of human control. 相似文献
145.
Hosta-Rigau L Chandrawati R Saveriades E Odermatt PD Postma A Ercole F Breheney K Wark KL Städler B Caruso F 《Biomacromolecules》2010,11(12):3548-3555
We report the synthesis of poly(methacrylic acid)-co-(oleyl methacrylate) with three different amounts of oleyl methacrylate and compare the ability of these polymers with that of poly(methacrylic acid)-co-(cholesteryl methacrylate) (PMA(c)) to noncovalently anchor liposomes to polymer layers. We subsequently assembled ~1 μm diameter PMA(c)-based capsosomes, polymer hydrogel capsules that contain up to ~2000 liposomal subcompartments, and investigate the potential of these carriers to deliver water-insoluble drugs by encapsulating two different antitumor compounds, thiocoraline or paclitaxel, into the liposomes. The viability of lung cancer cells is used to substantiate the cargo concentration-dependent activity of the capsosomes. These findings cover several crucial aspects for the application of capsosomes as potential drug delivery vehicles. 相似文献
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148.
S Levidiotou D Papamichael E Gessouli S Golegou S Anagnostou E Galanakis C Papadopoulou G Antoniadis 《Microbiological research》1999,154(2):151-155
The recovery rates of mycobacteria strains isolated from 1200 clinical specimens using the mycobacteria growth indicator tube (MGIT) system and the conventional Lowenstein Jensen medium (LJ) were assessed. Of the 87 mycobacterial isolates recovered, 54 belonged to the M. tuberculosis complex (MTB) and 33 to the non-tuberculosis complex (NTM). MGIT recovered 78 (89.65%) mycobacteria isolates (51 MTB (94.44%) and 27 NTM (81.81%) and LJ recovered 70 (80.46%) mycobacteria isolates (49 MTB (90.74%) and 21 NTM (63.63%). Sixty one (70.1%) of the total mycobacteria isolates were recovered with both systems (46 (85.2%) MTB and 15 (45.5%) NTM). No significant difference was found between MGIT and LJ (p > 0.05) in both MTB and NTM recoveries. The average detection time for MTB was significantly shorter with MGIT than with LJ, in both the smear-positive specimens (8 vs 30 days: p < 0.0001) and smear-negative specimens (15 vs 30 days: p < 0.001). The average detection time of NTM was also shorter for MGIT (15 vs 30 days: p < 0.0001). However, the contamination rate was higher in MGIT (8.5%) than in LJ (3%). The results suggest that the use of MGIT contributes to a more rapid and effective diagnosis of mycobacterial infections particularly when combined with the classical LJ. 相似文献
149.
150.
Jean-Marie Salmon Elli Kohen Cahide Kohen Gunnar Bengtsson 《Histochemistry and cell biology》1974,42(1):61-74
Summary The use of a microspectrofluorometer in conjunction with the microelectrophoretic intracellular injection of glycolytic intermediates, for the study of carcinogen metabolization (i.e. Benzo(a)pyrene (BP) and Dibenzo(a, h)anthracene) by single living EL2 ascites cells, has allowed the detection of fluorescence attributable to the metabolites of BP and DBA.The results obtained are in agreement with those yielded by more conventional methods: i.e. in vivo assay and in vitro reconstitution of intracellular environment. Thus, it is observed that NADPH is more active in the metabolization of BP. Furthermore, in the case of BP the fluorescence attributable to a BP metabolite, exhibits a strong similarity to 3-OH benzo(a) pyrene. 相似文献