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991.
Allen JV Bardelle C Blades K Buttar D Chapman L Colclough N Dossetter AG Garner AP Girdwood A Lambert C Leach AG Law B Major J Plant H Slater AM 《Bioorganic & medicinal chemistry letters》2011,21(18):5224-5229
A directed screen of a relatively small number of compounds, selected for kinase ATP pocket binding potential, yielded a novel series of hit compounds (1). Hit explosion on two binding residues identified compounds 27 and 43 as the best leads for an optimization program having reduced secondary metabolism, as measured by in vitro rat hepatocytes incubation, leading to oral bio-availability. Structure-activity relationships and molecular modeling have suggested a binding mode for the most potent inhibitor 12. 相似文献
992.
Molecular Characterization of the S-Layer Gene, sbpA, of Bacillus sphaericus CCM 2177 and Production of a Functional S-Layer Fusion Protein with the Ability To Recrystallize in a Defined Orientation while Presenting the Fused Allergen 下载免费PDF全文
Nicola Ilk Christine Vllenkle Eva M. Egelseer Andreas Breitwieser Uwe B. Sleytr Margit Sra 《Applied microbiology》2002,68(7):3251-3260
The nucleotide sequence encoding the crystalline bacterial cell surface (S-layer) protein SbpA of Bacillus sphaericus CCM 2177 was determined by a PCR-based technique using four overlapping fragments. The entire sbpA sequence indicated one open reading frame of 3,804 bp encoding a protein of 1,268 amino acids with a theoretical molecular mass of 132,062 Da and a calculated isoelectric point of 4.69. The N-terminal part of SbpA, which is involved in anchoring the S-layer subunits via a distinct type of secondary cell wall polymer to the rigid cell wall layer, comprises three S-layer-homologous motifs. For screening of amino acid positions located on the outer surface of the square S-layer lattice, the sequence encoding Strep-tag I, showing affinity to streptavidin, was linked to the 5′ end of the sequence encoding the recombinant S-layer protein (rSbpA) or a C-terminally truncated form (rSbpA31-1068). The deletion of 200 C-terminal amino acids did not interfere with the self-assembly properties of the S-layer protein but significantly increased the accessibility of Strep-tag I. Thus, the sequence encoding the major birch pollen allergen (Bet v1) was fused via a short linker to the sequence encoding the C-terminally truncated form rSpbA31-1068. Labeling of the square S-layer lattice formed by recrystallization of rSbpA31-1068/Bet v1 on peptidoglycan-containing sacculi with a Bet v1-specific monoclonal mouse antibody demonstrated the functionality of the fused protein sequence and its location on the outer surface of the S-layer lattice. The specific interactions between the N-terminal part of SbpA and the secondary cell wall polymer will be exploited for an oriented binding of the S-layer fusion protein on solid supports to generate regularly structured functional protein lattices. 相似文献
993.
994.
Non-random sex allocation in relation to parental, ecological and phenological factors has been investigated in several correlational
studies of birds, mostly based on few breeding seasons and relatively small sample sizes, which have led to different results.
We investigated sex ratio of nestling barn swallows (Hirundo rustica) in relation to adult sex ratio, laying date, clutch size, colony size and meteorological conditions in a sample of 553 broods
(>2200 nestlings) during 10 years. At the population level, nestling sex ratio varied among years and deviated from parity
in two years. Sex ratio among adults did not predict offspring sex ratio in the current or the following year. At the within-family
level, the proportion of sons increased with laying date in large clutches, did not vary among clutches of intermediate size,
and tended to decline with laying date in small clutches. Large colonies harbored more sons. The proportion of males increased
with temperature during laying whereas the effects of temperature during the pre- or post-laying periods and that of rainfall
were non-significant. These patterns of variation of offspring sex ratio did not differ between years. Thus, we identified
several potential causal sources of variation in barn swallow offspring sex ratio, including temporal, phenological and ecological factors.
The observation of an association of offspring sex with temperature during laying is novel for birds and may be mediated by effects on maternal steroid hormones profile. The ecological and evolutionary implications
of present findings are discussed in the light of adaptive sex allocation theory. 相似文献
995.
Clustering of hypervariable minisatellites in the proterminal regions of human autosomes 总被引:42,自引:0,他引:42
Six of the human minisatellites detected by DNA fingerprint probes have been localized by in situ hybridization to human metaphase chromosomes. These hypervariable loci are not dispersed at random in the human genome, but show preferential, though not exclusive, localization to terminal G-bands of human autosomes. Two of the proterminal minisatellites are very closely linked to other variable loci. Sequence analysis of one of these additional minisatellites suggests that the two linked minisatellites arose by independent amplification of different repeat units. The proterminal regions of human autosomes may therefore be rich in minisatellites, analogous to the pseudoautosomal terminal pairing region of human sex chromosomes that is similarly abundant in hypervariable minisatellites. 相似文献
996.
R. D’Anastasio J. Viciano M. Di Nicola D.T. Cesana M. Sciubba M. Del Cimmuto A. Paolucci A. Fazio L. Capasso 《HOMO》2014
Recent forensic studies have shown that the hyoid bone is a sexually dimorphic element of the human skeleton. Given the advanced techniques of collecting human remains in archeological and forensic contexts, the recovery of hyoid bones is now more frequent in skeletal samples. For that reason the authors propose a new method for estimating sex based on hyoid bodies from archeological sites. 相似文献
997.
Introduction
Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA.Methods
A multiplex suspension array system (Luminex®) was used to measure levels of MMPs (1, 2, 3, 8 and 9) in sera taken at recruitment of RA patients (n = 487) in a study of factors associated with mortality in RA. Patients were tracked on the National Health Service Central Register for notification of death, and the relationship between baseline MMP levels and mortality was analysed using Cox proportional hazards regression analysis.Results
At the time of follow-up, 204/486 patients had died, of which 94 (46.1%) had died of circulatory diseases, 49 of malignancy (24.0%), and 42 (20.6%) of respiratory diseases. In a stepwise analysis which included all MMPs, only MMP-8 was significantly associated with all cause mortality (P = 0.0007, 0.6% hazard ratio increase per ng/ml). No association was found between MMP levels and mortality due to circulatory disease or malignancy. However MMP-8 levels were strongly associated with mortality due to respiratory disease (P < 0.0001, 1.3% hazard ratio increase per ng/ml). The association with respiratory disease related mortality remained highly significant in multivariate models which included smoking as well as markers of severity and disease activity such as rheumatoid factor, nodular disease, and C-reactive protein (CRP).Conclusions
The serum level of MMP-8 is a strong predictor of mortality in RA, especially that due to respiratory disease. This finding is consistent with increased activation of neutrophils in RA and identifies serum MMP-8 as a useful marker for increased risk of premature death. 相似文献998.
Oliviero G Amato J Borbone N Galeone A Varra M Piccialli G Mayol L 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):739-741
The chemical synthesis of several G-rich bunch-oligonucleotides and the structural characterization of the corresponding monomolecular G-quadruplexes (I-IV) have been reported. The synthetic method allow the achievement of monomolecular DNA quadruplex structures having unusual and predeterminable oligodeoxyribonucleotide (ODN) strand orientation. 相似文献
999.
1000.