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271.
Humphries AC Gancia E Gilligan MT Goodacre S Hallett D Merchant KJ Thomas SR 《Bioorganic & medicinal chemistry letters》2006,16(6):1518-1522
8-Fluoroimidazo[1,2-a]pyridine has been established as a physicochemical mimic of imidazo[1,2-a]pyrimidine, using both in silico and traditional techniques. Furthermore, a novel synthesis of a 3,7-disubstituted-8-fluoroimidazopyridine 3 has been developed and the utility of the physicochemical mimicry has been demonstrated in an in vitro system. Here, the 8-fluoroimidazopyridine ring contained in ligand 3 acts as a bioisosteric replacement for imidazopyrimidine in the GABA(A) receptor modulator 2. 相似文献
272.
将C群脑膜炎球菌粗多糖的纯化改进为用1:1容量冷酚提取的生产工艺。结果表明,改进后的方法去除蛋白质效果同样能够达到《中国药典》2005版(三部)的要求,总体结果优于改进前。同时能扩大处理量而降低了生产成本,适合规模化生产。 相似文献
273.
Background
We recently observed an association of resistance with a certain enteropathogenic Escherichia coli (EPEC) serotypes and identified a conjugative plasmid, similar to plasmid pED208, that was conserved among archival O111:H2/NM and O119:H2 strains of diverse geographical origin. In this study, we sought to determine the prevalence and distribution of this plasmid among a collection of EPEC isolates from Brazil, as well as to study the susceptibilities of these isolates to antimicrobial agents. 相似文献274.
Persistence thresholds for phocine distemper virus infection in harbour seal Phoca vitulina metapopulations 总被引:2,自引:0,他引:2
1. This paper explores the concept of the critical community size for persistence of infection in wildlife populations. We use as a case study the 1988 epidemic of phocine distemper virus in the North Sea population of harbour seals, Phoca vitulina .
2. We summarize the available data on this epidemic and use it to parameterize a stochastic compartmental model for an infection spreading through a spatial array of patches coupled by nearest-neighbour mixing, with replacement of susceptibles occurring as a discrete annual event.
3. A combination of analytical and simulation techniques is used to show that the high levels of transmission between different seal subpopulations, combined with the small annual birth cohort, act to make persistence of infection impossible in this harbour seal population at realistic population levels. The well known mechanisms by which metapopulation structures may act to promote persistence can be seen to have an effect only at weaker levels of spatial coupling, and higher levels of host recruitment, than those empirically observed. 相似文献
2. We summarize the available data on this epidemic and use it to parameterize a stochastic compartmental model for an infection spreading through a spatial array of patches coupled by nearest-neighbour mixing, with replacement of susceptibles occurring as a discrete annual event.
3. A combination of analytical and simulation techniques is used to show that the high levels of transmission between different seal subpopulations, combined with the small annual birth cohort, act to make persistence of infection impossible in this harbour seal population at realistic population levels. The well known mechanisms by which metapopulation structures may act to promote persistence can be seen to have an effect only at weaker levels of spatial coupling, and higher levels of host recruitment, than those empirically observed. 相似文献
275.
Molecular evolution of olfactomedin 总被引:2,自引:0,他引:2
Olfactomedin is a secreted polymeric glycoprotein of unknown function,
originally discovered at the mucociliary surface of the amphibian olfactory
neuroepithelium and subsequently found throughout the mammalian brain. As a
first step toward elucidating the function of olfactomedin, its
phylogenetic history was examined to identify conserved structural motifs.
Such conserved motifs may have functional significance and provide targets
for future mutagenesis studies aimed at establishing the function of this
protein. Previous studies revealed 33% amino acid sequence identity between
rat and frog olfactomedins in their carboxyl terminal segments. Further
analysis, however, reveals more extensive homologies throughout the
molecule. Despite significant sequence divergence, cysteines essential for
homopolymer formation such as the CXC motif near the amino terminus are
conserved, as is the characteristic glycosylation pattern, suggesting that
these posttranslational modifications are essential for function.
Furthermore, evolutionary analysis of a region of 53 amino acids of fish,
frog, rat, mouse, and human olfactomedins indicates that an ancestral
olfactomedin gene arose before the evolution of terrestrial vertebrates and
evolved independently in teleost, amphibian, and mammalian lineages.
Indeed, a distant olfactomedin homolog was identified in Caenorhabditis
elegans. Although the amino acid sequence of this invertebrate protein is
longer and highly divergent compared with its vertebrate homologs, the
protein from C. elegans shows remarkable similarities in terms of conserved
motifs and posttranslational modification sites. Six universally conserved
motifs were identified, and five of these are clustered in the carboxyl
terminal half of the protein. Sequence comparisons indicate that evolution
of the N-terminal half of the molecule involved extensive insertions and
deletions; the C-terminal segment evolved mostly through point mutations,
at least during vertebrate evolution. The widespread occurrence of
olfactomedin among vertebrates and invertebrates underscores the notion
that this protein has a function of universal importance. Furthermore,
extensive modification of its N-terminal half and the acquisition of a
C-terminal SDEL endoplasmic-reticulum- targeting sequence may have enabled
olfactomedin to adopt new functions in the mammalian central nervous
system.
相似文献
276.
Matthew R. Gilligan 《Environmental Biology of Fishes》1991,31(3):301-305
Synopsis Bergmann-type ecogeographic patterns are common among small resident rocky-shore fishes in the Gulf of California where triplefin blennies (Tripterygiidae) represent a significant component of the community. Using estimates of adult body size from samples throughout the Gulf, four triplefin species, three more than previously reported, showed significant correlations of body size with latitude. The intensity and form of the relationships are given. Measuring the length of the largest individual in samples rather than using average body weight per individuals in samples offers a better estimate of adult body size. 相似文献
277.
Elliot F. Hahn Charles P. Martucci James P. Gilligan Sydney Spector 《Biochemical and biophysical research communications》1982,107(2):707-713
Continuous and postpartum exposure of SH and WKY rats to naloxone results in a significant increase in their systolic blood pressure relative to respective control animals. After six weeks of age, however, naloxone was no longer effective in sustaining this increase in blood pressure. Chronic exposure to naloxone beginning at three weeks of age failed to produce any significant differences in blood pressure between treated and control animals. Although naloxone has been shown to elevate blood pressure in hypotensive states, this report represents the first example of an increase produced by the narcotic antagonist in the normotensive state. 相似文献
278.
279.
280.
Accumulation of pepstatin in cultured endothelial cells and its effect on endothelial processing 总被引:1,自引:0,他引:1
P P Shields T A Gonzales D Charles J P Gilligan W Stern 《Biochemical and biophysical research communications》1991,177(3):1006-1012
Aspartic acid proteases have been implicated in the processing of ET-1(1-39) to ET-1(1-21). To further understand the role of this class of enzymes in ET-1 synthesis, cultured vascular endothelial cells were incubated with pepstatin, and the accumulation of the inhibitor and its effect on the processing of ET-1(1-39) was examined. Pepstatin accumulated in the cells in a time-dependent manner, to a concentration (greater than 10(-7) M) sufficient to inhibit aspartic acid proteases. Pepstatin did not alter the ratio of ET-1(1-21) to ET-1(1-39), nor did it affect the rate of secretion of either peptide. When endothelial cells were incubated with phosphoramidon under identical conditions, the secretion of ET-1(1-21) was significantly reduced with a concomitant increase in the secretion of ET-1(1-39). These results suggest that the processing of ET-1(1-39) does not involve a pepstatin-sensitive aspartic acid protease, and that the enzyme responsible for generating ET-1(1-21) is sensitive to phosphoramidon. 相似文献