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101.
The single-dose kinetics of the enantiomers of citalopram (CIT) and its metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT), were investigated after administration of 10, 20, or 100 mg/kg (s.c.) rac-CIT to rats. Samples from serum and two brain regions were collected 1, 3, 10, or 20 h postdose for HPLC analysis. In the 100 mg/kg rats, the enantiomeric (S/R) serum concentration ratios of CIT decreased during the study period (0.93 at 1 h vs. 0.59 at 20 h; P < 0.001). In the 10 and 20 mg/kg rats, the decrease in serum S/R CIT ratios was not so evident as in the 100 mg/kg rats. In all three groups the S/R CIT ratio was almost the same in the brain as in serum, although both CIT enantiomer levels in the brain were found to be 5-10 times higher than the levels in serum. The serum and brain metabolite levels were low in the 10 and 20 mg/kg rats, whereas the levels increased during the study period in the 100 mg/kg rats. In conclusion, the CIT enantiomers were shown for the first time to be stereoselectively metabolized after single-dose administration to rats, as previously shown in steady-state dosing studies in humans and rats. 相似文献
102.
A simple system for monitoring biodiversity in protected areas of a developing country 总被引:7,自引:3,他引:4
Finn Danielsen Danilo S. Balete Michael K. Poulsen Martin Enghoff Cristi M. Nozawa Arne E. Jensen 《Biodiversity and Conservation》2000,9(12):1671-1705
The achievements of initiatives to strengthen biodiversity conservation in developing countries may be difficult to assess, since most countries have no system for monitoring biodiversity. This paper describes a simple and cost-effective, field-based biodiversity monitoring system developed specifically for areas where specialist staff is lacking. We discuss the preliminary lessons learned from protected areas in the Philippines. Whilst the monitoring system aims to identify trends in biodiversity and its uses so as to guide management action, it also promotes the participation of local people in the management, stimulates discussions about conservation amongst stakeholders and builds the capacity of park staff and communities in management skills. In addition, it seeks to provide people with direction regarding the aims of protected areas, and reinforces the consolidation of existing livelihoods through strengthening community-based resource management systems. The field methods are: (1) standardised recording of routine observations, (2) fixed point photographing, (3) line transect survey, and (4) focus group discussion. Both bio-physical and socio-economic data are used and given equal importance. The system can be sustained using locally available resources. The approach is useful in countries embarking on shared management of park resources with local communities, where rural people depend on use of natural ecosystems, and where the economic resources for park management are limited. We hope this paper will encourage other countries to develop their own biodiversity monitoring system, letting its development become a means for capacity building whilst at the same time supporting the creation of ownership. 相似文献
103.
Induced Levels of Heat Shock Proteins in a dnaK Mutant of Lactococcus lactis 总被引:1,自引:0,他引:1 下载免费PDF全文
Birgit Koch Mogens Kilstrup Finn K. Vogensen Karin Hammer 《Journal of bacteriology》1998,180(15):3873-3881
The bacterial heat shock response is characterized by the elevated expression of a number of chaperone complexes and proteases, including the DnaK-GrpE-DnaJ and the GroELS chaperone complexes. In order to investigate the importance of the DnaK chaperone complex for growth and heat shock response regulation in Lactococcus lactis, we have constructed two dnaK mutants with C-terminal deletions in dnaK. The minor deletion of 65 amino acids in the dnaKΔ2 mutant resulted in a slight temperature-sensitive phenotype. BK6, containing the larger deletion of 174 amino acids (dnaKΔ1), removing the major part of the inferred substrate binding site of the DnaK protein, exhibited a pronounced temperature-sensitive phenotype and showed altered regulation of the heat shock response. The expression of the heat shock proteins was increased at the normal growth temperature, measured as both protein synthesis rates and mRNA levels, indicating that DnaK could be involved in the regulation of the heat shock response in L. lactis. For Bacillus subtilis, it has been found (A. Mogk, G. Homuth, C. Scholz, L. Kim, F. X. Schmid, and W. Schumann, EMBO J. 16:4579–4590, 1997) that the activity of the heat shock repressor HrcA is dependent on the chaperone function of the GroELS complex and that a dnaK insertion mutant has no effect on the expression of the heat shock proteins. The present data from L. lactis suggest that the DnaK protein could be involved in the maturation of the homologous HrcA protein in this bacterium. 相似文献
104.
Ratan V. Bhat Thomas M. Engber James P. Finn Elizabeth J. Koury Patricia C. Contreras Matthew S. Miller Craig A. Dionne Kevin M. Walton 《Journal of neurochemistry》1998,70(2):558-571
Abstract: In vitro studies indicate that p42/p44MAPK phosphorylate both nuclear and cytoplasmic proteins. However, the functional targets of p42/p44MAPK activation in vivo remain unclear. To address this question, we localized activated p42/p44MAPK in hippocampus and cortex and determined their signaling effects after electroconvulsive shock treatment (ECT) in rats. Phosphorylated p42/p44MAPK content increased in the cytoplasm of hippocampal neurons in response to ECT. Consistent with this cytoplasmic localization, inhibition of ECT-induced p42/p44MAPK activation by the extracellular signal-regulated kinase kinase inhibitor PD098059 blocked phosphorylation of the cytoplasmic protein microtubule-associated protein 2c (MAP2c), but failed to inhibit the induction of the nuclear protein c-Fos in response to ECT. In contrast to hippocampal neurons, cortical neurons exhibited an increase in amount of phosphorylated p42/p44MAPK in both the nucleus and cytoplasm after ECT. Accordingly, PD098059 blocked the induction of Fos-like immunoreactivity in the nuclei of cortical neurons as well as MAP2c phosphorylation in the cytoplasm. Our data indicate that both nuclear and cytoplasmic substrates can be activated by p42/p44MAPK in vivo. However, the functional targets of p42/p44MAPK signaling depend on the precise location of p42/p44MAPK within different subcellular compartments of brain regions. These results indicate unique functional pathways of p42/p44MAPK -mediated signal transduction within different brain regions in vivo. 相似文献
105.
106.
107.
?ivind ?rstavik Ornella Manfra Kjetil Wessel Andressen Geir ?ystein Andersen Tor Skomedal Jan-Bj?rn Osnes Finn Olav Levy Kurt Allen Krobert 《PloS one》2015,10(3)
Aims
We recently published that the positive inotropic response (PIR) to levosimendan can be fully accounted for by phosphodiesterase (PDE) inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD), levosimendan and other PDE inhibitors.Methods
Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.Results
OR-1896 evoked a maximum PIR of 33±10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89±14%) and absent in the presence of the PDE3 inhibitors cilostamide (0.5±5.3%) or milrinone (3.2±4.4%). The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.Conclusion
The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic) effect of levosimendan, nor of its main metabolite OR-1896. 相似文献108.
Astrid Cruaud Roula Jabbour‐Zahab Gwenaëlle Genson Corinne Cruaud Arnaud Couloux Finn Kjellberg Simon Van Noort Jean‐Yves Rasplus 《Cladistics : the international journal of the Willi Hennig Society》2010,26(4):359-387
A phylogeny of the Agaonidae (Chalcidoidea) in their restricted sense, pollinators of Ficus species (Moraceae), is estimated using 4182 nucleotides from six genes, obtained from 101 species representing 19 of the 20 recognized genera, and four outgroups. Data analysed by parsimony and Bayesian inference methods demonstrate that Agaonidae are monophyletic and that the previous classification is not supported. Agaonidae are partitioned into four groups: (i) Tetrapus, (ii) Ceratosolen + Kradibia, (iii) some Blastophaga + Wiebesia species, and (iv) all genera associated with monoecious figs and a few Blastophaga and Wiebesia. The latter group is subdivided into subgroups: (i) Pleistodontes, (ii) Blastophaga psenes and neocaledonian Dolichoris, (iii) some Blastophaga and Wiebesia species, and (iv) Platyscapa, all afrotropical genera and all genera associated with section Conosycea. Eleven genera were recovered as monophyletic, six were para‐ or polyphyletic, and two cannot be tested with our data set. Based on our phylogeny we propose a new classification for the Agaonidae. Two new subfamilies are proposed: Tetrapusiinae for the genus Tetrapus, and Kradibiinae for Ceratosolen + Kradibia. Liporrhopalum is synonymized with Kradibia and the subgenus Valisia of Blastophaga is elevated to generic rank. These changes resulted in 36 new combinations. Finally, we discuss the hypothesis of co‐speciation between the pollinators and their host species by comparing the two phylogenies. © The Willi Hennig Society 2009. 相似文献
109.
Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR 总被引:1,自引:0,他引:1
Dreher A Rossing M Kaczkowski B Nielsen FC Norrild B 《Biochemical and biophysical research communications》2010,403(3-4):357-362
Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory tract leading to condylomas and respiratory papillomatosis. HPV infections are restricted to epithelial tissue and the progression through the virus lifecycle is tightly coordinated to the differentiation of the host cell. The changes of cellular microRNAs by HPV-11 gene expression were investigated in a cell culture model of HaCaT cells transfected with HPV-11, with the goal of understanding which cellular processes were affected by the virus. Human microRNA profiling was conducted on three different array platform systems and because very few microRNAs (miR-663, -638, -149* and -92b*) were consistently found in all three array data sets we performed extensive statistical analyses of the array data and the qRT-PCR validation. We assume that the most reliable differentially expressed microRNAs are the ones identified by more than one array platform. We also show that TaqMan? qRT-PCR validation is of limited use for less abundant microRNAs. 相似文献
110.
Dung fauna plays an important role in dung decomposition, a key ecosystem process in nutrient cycling in grazed grasslands. The diversity of a three‐species community (dung beetles, dung flies and epigeic earthworms) was systematically manipulated to produce different relative abundance distributions (evenness levels) and the resulting communities were introduced to standardised dung pats in laboratory experiments. Dung decomposition was modelled using an analysis that disentangled species identity effects and the interactions among species that contribute to the diversity effect. This revealed that the net diversity effect was composed of positive (fly–earthworm), negative (beetle–earthworm) and neutral (fly–beetle) effects of species interaction. These pairwise interactions resulted in complex, but systematically varying and predictable effects on dung decomposition as the relative abundances of species changed. Decomposition was consistently greater in communities with higher decomposer biomass. The utility of the adopted analytical approach was emphasised by comparison with an ANOVA that found that dung decomposition did not differ among evenness levels. Thus, the averaging of decomposition across different community structures within evenness levels masked the different effects of species interactions. These results highlight methodological insights into the quantification of diversity–function relationships. 相似文献