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81.
John J.M. Wiener Alvah Tyson Wickboldt Steven Nguyen Siquan Sun Raymond Rynberg Michele Rizzolio Lars Karlsson James P. Edwards Cheryl A. Grice 《Bioorganic & medicinal chemistry letters》2013,23(4):1070-1074
Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1′/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described. 相似文献
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Will B. Kirby Guy Q.A. Anderson Phil V. Grice Louise Soanes Catherine Thompson Will J. Peach 《Bird Study》2013,60(4):383-393
Capsule Yellow Wagtails successfully raised two consecutive broods in landscapes dominated by autumn-sown crops and did not require spring crops or fallow plots for later nesting. Aims To assess whether arable landscapes dominated by winter cropping provide habitats that allow Yellow Wagtails to raise two successful broods. To assess the utility of spring cultivated agri-environment fallow plots as a nesting and foraging habitat for Yellow Wagtails. Methods Nesting success and foraging behaviour of Yellow Wagtails was monitored on lowland arable farmland dominated by winter cropping during two successive breeding seasons. Results Yellow Wagtails successfully raised first and second broods mainly in winter cereals, with later nests being more successful. Some nests were initiated in bean fields where egg-stage failure rates were high, probably as a consequence of depredation. Fallow plots were not used for nesting but, along with other areas of sparse vegetation, were regularly used for foraging. Conclusions Yellow Wagtails breeding at relatively low densities achieved high rates of reproductive success in a landscape dominated by winter cereals and with few spring-sown crops. This study suggests that spring-sown crops may not be necessary for Yellow Wagtails to rear two successful broods each summer within arable landscapes. 相似文献
87.
Subregions of a conserved part of the HIV gp41 transmembrane protein are differentially recognized by antibodies of infected individuals. 总被引:20,自引:8,他引:20 下载免费PDF全文
U Certa W Bannwarth D Stüber R Gentz M Lanzer S Le Grice F Guillot I Wendler G Hunsmann H Bujard et al. 《The EMBO journal》1986,5(11):3051-3056
A 240-bp DNA fragment encoding a peptide, designated ENV(80), homologous to a conserved part of the gp41 transmembrane glycoprotein of human immunodeficiency virus (HIV) was chemically synthesized and inserted into different plasmid expression vectors. Escherichia coli transformants containing these plasmid constructs produced upon induction high amounts of either an ENV(80) peptide of relative molecular mass (Mr) of 10,000 or the same ENV(80) peptide N-terminally fused to E. coli chloramphenicol acetyltransferase (CAT) or to mouse dihydrofolate reductase (DHFR) having Mr of 36,000 and 31,000 respectively. All polypeptides containing the ENV(80) sequences were strongly reactive with antibodies present in sera from AIDS virus-infected individuals, but not with control sera. The strategy of gene assembly allowed the expression of ENV(80) subfragments fused to DHFR. The serodiagnosis of 15 positive sera by Western blot analysis using these bacterially synthesized ENV(80) subfragments revealed the presence of several immunoreactive epitopes on the 80-amino acid polypeptide which were recognized differently by the various patients. 相似文献
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Ciara Gimblet Michael A. Loesche Lucas Carvalho Edgar M. Carvalho Elizabeth A. Grice David Artis Phillip Scott 《PloS one》2015,10(8)
Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22
-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology. 相似文献
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Significance of nucleotide sequence alignments: a method for random sequence permutation that preserves dinucleotide and codon usage 总被引:10,自引:0,他引:10
The similarity of two nucleotide sequences is often expressed in terms of
evolutionary distance, a measure of the amount of change needed to
transform one sequence into the other. Given two sequences with a small
distance between them, can their similarity be explained by their base
composition alone? The nucleotide order of these sequences contributes to
their similarity if the distance is much smaller than their average
permutation distance, which is obtained by calculating the distances for
many random permutations of these sequences. To determine whether their
similarity can be explained by their dinucleotide and codon usage, random
sequences must be chosen from the set of permuted sequences that preserve
dinucleotide and codon usage. The problem of choosing random dinucleotide
and codon-preserving permutations can be expressed in the language of graph
theory as the problem of generating random Eulerian walks on a directed
multigraph. An efficient algorithm for generating such walks is described.
This algorithm can be used to choose random sequence permutations that
preserve (1) dinucleotide usage, (2) dinucleotide and trinucleotide usage,
or (3) dinucleotide and codon usage. For example, the similarity of two
60-nucleotide DNA segments from the human beta-1 interferon gene
(nucleotides 196-255 and 499-558) is not just the result of their nonrandom
dinucleotide and codon usage.
相似文献
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