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21.
The common carp Cyprinus carpio introduced in two drainages in eastern Australia are largely descended from European common carp, and in a third drainage they descend largely from East Asian common carp. The partial genetic differentiation among the species in those drainages is consistent with their origins. 相似文献
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Margaret I Butler Jeremy Gray Timothy JD Goodwin Russell TM Poulter 《BMC evolutionary biology》2006,6(1):42-26
Background
We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal. 相似文献24.
Gilligan PJ Baldauf C Cocuzza A Chidester D Zaczek R Fitzgerald LW McElroy J Smith MA Shen HS Saye JA Christ D Trainor G Robertson DW Hartig P 《Bioorganic & medicinal chemistry》2000,8(1):181-189
Structure activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazo lo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki = 1.0+/-0.2 nM (n = 8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50= 10.0+/-0.01 nM versus 10 nM r/hCRF, n = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286+/-63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4+/-7.6 h. 0.49+/-0.08 L/kg/h and 23.0+/-4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax t1/2 and bioavailability values were equal to 1260+/-290 nM, 0.75+/-0.25 h. 45.1+/-10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability. 相似文献
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Hartz RA Gilligan PJ Nanda KK Tebben AJ Fitzgerald LW Miller K 《Bioorganic & medicinal chemistry letters》2002,12(3):291-294
A novel series of imidazo[1,5-a]pyrazines was synthesized and evaluated as corticotropin releasing hormone (CRH) receptor ligands. SAR studies focused primarily on dialkylamino side chain optimization. SAR of the aryl and small alkyl substituents was also explored. 相似文献
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Although of practical importance, the relationship between the duration of an epidemic and host spatial structure is poorly understood. Here we use a stochastic metapopulation model for the transmission of infection in a spatially structured host population. There are three qualitatively different regimes for the extinction time, which depend on patch population size, the within‐patch basic reproductive number and the strength of coupling between patches. In the first regime, the extinction time for the metapopulation (i.e. from all patches) is approximately equal to the extinction time for a single patch. In the second regime, the metapopulation extinction time is maximal but also highly variable. In the third regime, the extinction time for the metapopulation (TE) is given by TE = a + bn1/2 where a is the local extinction time (i.e. from last patch), b is the transit time (i.e. the time taken for infection to spread from one patch to another) and n is the total number of patches. 相似文献
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Beck JP Arvanitis AG Curry MA Rescinito JT Fitzgerald LW Gilligan PJ Zaczek R Trainor GL 《Bioorganic & medicinal chemistry letters》1999,9(7):967-972
A series of purin-8-ones was prepared and discovered to have excellent binding affinity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants. 相似文献