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941.
Moree WJ Kataoka K Ramirez-Weinhouse MM Shiota T Imai M Tsutsumi T Sudo M Endo N Muroga Y Hada T Fanning D Saunders J Kato Y Myers PL Tarby CM 《Bioorganic & medicinal chemistry letters》2008,18(6):1869-1873
SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC(50) 3.2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; Ca(2+) Flux IC(50) 7.5 nM]. 相似文献
942.
Antonysamy SS Aubol B Blaney J Browner MF Giannetti AM Harris SF Hébert N Hendle J Hopkins S Jefferson E Kissinger C Leveque V Marciano D McGee E Nájera I Nolan B Tomimoto M Torres E Wright T 《Bioorganic & medicinal chemistry letters》2008,18(9):2990-2995
Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with 1–10 mM binding affinity (KD) were iteratively optimized to give leads with 200 nM biochemical activity and low μM cellular activity in a Replicon assay. 相似文献
943.
To understand the differences in the spawning sites among Cyprininae fishes in Lake Biwa, we conducted periodic sampling of
larvae and juveniles at three sites (irrigation ditch, St. 1; river, St. 2; and satellite lake, St. 3). On the basis of species/subspecies
identification by using RAPD analysis, we examined the species composition of the larvae and juveniles at these three sampling
sites. The number of specimens was 616, 68, and 117 at St. 1, St. 2, and St. 3, respectively. Based on morphological and genetic
identification, the specimens were found to include nine fish species/subspecies, namely, Carassius auratus grandoculis, Carassius cuvieri, Carassius auratus langsdorfii, Cyprinus carpio, Sarcocheilichthys sp., Silurus asotus, Oryzias latipes, Odontobutis obscura obscura, and Rhinogobius sp. The species composition at the three sites also differed. Among the Cyprininae fishes, C. auratus grandoculis, C. auratus langsdorfii, and Cyprinus carpio were found in abundance at St. 1; C. cuvieri was not collected from St. 1 but was found at the other two sites, particularly St. 3. Among the other fishes, Rhinogobius sp. was collected at St. 1 and St. 3, whereas the other four occurred only at St. 1. These results suggest that the selection
of spawning sites by C. cuvieri differs to a certain extent from that of the other Cyprininae fishes, and the irrigation ditch in the lake is an important
habitat for the larvae and juveniles of native fish species. 相似文献
944.
Richard L. MAYDEN Kevin L. TANG Robert M. WOOD Wei-Jen CHEN Mary K. AGNEW Kevin W. CONWAY Lei YANG Andrew M. SIMONS Henry L. BART Phillip M. HARRIS Junbing LI Xuzhen WANG Kenji SAITOH Shunping HE Huanzhang LIU Yiyu CHEN Mutsumi NISHIDA Masaki MIYA 《植物分类学报》2008,46(3)
The phylogenetic relationships of species are fundamental to any biological investigation, including all evolutionary studies. Accurate inferences of sister group relationships provide the researcher with an historical framework within which the attributes or geographic origin of species (or supraspecific groups) evolved. Taken out of this phylogenetic context, interpretations of evolutionary processes or origins, geographic distributions, or speciation rates and mechanisms, are subject to nothing less than a biological experiment without controls. Cypriniformes is the most diverse clade of freshwater fishes with estimates of diversity of nearly 3,500 species. These fishes display an amazing array of morphological, ecological, behavioral, and geographic diversity and offer a tremendous opportunity to enhance our understanding of the biotic and abiotic factors associated with diversification and adaptation to environments. Given the nearly global distribution of these fishes, they serve as an important model group for a plethora of biological investigations, including indicator species for future climatic changes. The occurrence of the zebrafish, Danio rerio, in this order makes this clade a critical component in understanding and predicting the relationship between mutagenesis and phenotypic expressions in vertebrates, including humans. With the tremendous diversity in Cypriniformes, our understanding of their phylogenetic relationships has not proceeded at an acceptable rate, despite a plethora of morphological and more recent molecular studies. Most studies are pre-Hennigian in origin or include relatively small numbers of taxa. Given that analyses of small numbers of taxa for molecular characters can be compromised by peculiarities of long-branch attraction and nodal-density effect, it is critical that significant progress in our understanding of the relationships of these important fishes occurs with increasing sampling of species to mitigate these potential problems. The recent Cypriniformes Tree of Life initiative is an effort to achieve this goal with morphological and molecular (mitochondrial and nuclear) data. In this early synthesis of our understanding of the phylogenetic relationships of these fishes, all types of data have contributed historically to improving our understanding, but not all analyses are complementary in taxon sampling, thus precluding direct understanding of the impact of taxon sampling on achieving accurate phylogenetic inferences. However, recent molecular studies do provide some insight and in some instances taxon sampling can be implicated as a variable that can influence sister group relationships. Other instances may also exist but without inclusion of more taxa for both mitochondrial and nuclear genes, one cannot distinguish between inferences being dictated by taxon sampling or the origins of the molecular data. 相似文献
945.
Heterotypy in the N-terminal region of growth/differentiation factor 5 (GDF5) mature protein during teleost evolution 总被引:1,自引:0,他引:1
Fujimura K Terai Y Ishiguro N Miya M Nishida M Okada N 《Molecular biology and evolution》2008,25(5):797-800
Heterotypy is now recognized as a generative force in the formationof new proteins through modification of existing proteins. Wereport that heterotypy in the N-terminal region of the maturegrowth/differentiation factor 5 (GDF5) protein occurred duringevolution of teleosts. N-terminal length variation of GDF5 wasfound among teleost interfamilies and interorders but not withinteleost families or among tetrapods. We further show that increaseof proline and glutamine to the N-terminal region of matureGDF5 occurred in Eurypterygii, the higher lineage of teleosts.Because the basic amino acids, believed to control diffusion,are conserved in this region across all species examined, wesuggest that the N-terminal elongation of the mature GDF5 proteinduring evolution has altered the protein diffusion in Eurypterygii,leading to high concentrations of the protein in the joint ofthe pharyngeal skeleton, the location of cartilage formationduring development. 相似文献
946.
We investigated the effect of population density of compatible neighbours on inbreeding level of Primula sieboldii, a heterostylous clonal herb. Pollinator availability, seed set, selfing rate, diversity of pollen donors, and fitness of
progenies were compared between less and more isolated genets, which differed in the number of compatible opposite-morph genets
within 20 m, the range at which most pollen flow occurred. Although pollinator availability did not differ between the two
groups, seed set and diversity of pollen donors in more isolated genets were significantly lower than in less isolated genets.
Additionally, the mean selfing rates of less and more isolated genets were 1.3 and 36.7%, respectively, and the mean leaf
area of the self-fertilized seedlings was 70 to 40% smaller than that of outcrossed seedlings of the same mother genet. Due
to this large inbreeding depression, it is unlikely that self-fertilized seedlings could successfully establish in natural
habitats and hence the inbreeding level in the next generation around the more isolated genet would not increase rapidly.
However, the possibility of mating between full-sibs would increase because the diversity of pollen donors was low and both
pollen and seed dispersal were spatially restricted. Thus the inbreeding level of the next generations would gradually increase
around the more isolated genets owing to biparental inbreeding. This study suggested that the population density of compatible
neighbours has a critical impact on the future inbreeding level within P. sieboldii populations. 相似文献
947.
Kim YT Yoshida H Kojima M Kurita R Nishii W Muramatsu T Ito H Park SJ Takahashi K 《Journal of biochemistry》2008,143(2):237-242
Escherichia coli signal peptidase I (SPase I) is a membrane-bound serine endopeptidase that catalyses the cleavage of signal peptides from the pre-forms of membrane or secretory proteins. Our previous studies using chemical modification and site-directed mutagenesis suggested that Trp(300) and Arg(77), Arg(222), Arg(315) and Arg(318) are important for the proper and stable conformation of the active site of SPase I. Interestingly, many of these residues reside in the C-terminal region of the enzyme. As a continuation of these studies, we investigated in the present study the effects of mutations in the C-terminal region including amino acid residues at positions from 319 to 323 by deletions and site-directed mutagenesis. As a result, the deletion of the C-terminal His(323) was shown to scarcely affect the enzyme activity of SPase I, whereas the deletion of Gly(321)-His(323) or Ile(319)-His(323) as well as the point mutation of Ile(322) to alanine was shown to decrease significantly both the activity in vitro and in vivo without a big gross conformational change in the enzyme. These results suggest a significant contribution of Ile(322) to the construction and maintenance of the proper and critical local conformation backing up the active site of SPase I. 相似文献
948.
949.
950.
Toshifumi Miyazawa Shino Masaki Kayoko Tanaka Takashi Yamada 《Letters in Peptide Science》2003,10(2):83-87
Bacillus subtilis protease (Amano protease N) was examined as a catalyst for peptide bond formation via both the kinetically and thermodynamically controlled approaches. In general, the latter approach proved to be superior to the former, and a series of dipeptide syntheses and several segment condensations were achieved in good to high yields using the immobilized enzyme on Celite in acetonitrile with low water content. 相似文献