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91.
Most studies on photosynthetic production of aquatic macrophytes have been made on detached leaves and algal thalli. This may have given the false impression that production is often saturated by light and that inorganic carbon and nutrients are more important limiting factors. However, studies on the more relevant ecological scale of macrophyte communities lead to a completely different perception because community production is light limited due to intense self‐shading. Relatively high irradiances are needed for photosynthesis to balance respiratory costs and not even maximum irradiances at noon during summer saturate photosynthetic production. The fundamental importance of light is confirmed by the close coupling to community light absorptance of both maximum production in high‐light environments and efficiency of light use in low‐light environments. The upper boundaries of light‐limited and light‐saturated production are distinctly and linearly related to community absorptance. Moreover, higher diversity in the community has a positive and stabilizing influence on light absorptance and production because different species supplement each other temporally and spatially. Close predictions of actual production rates in macroalgal communities throughout the year are possible solely from determinations of incident and absorbed irradiance. Along with the increasing regulating role of light from leaves or thalli to entire communities the importance of temperature, inorganic carbon and other resources decreases. Thus, ten‐fold rise of CO2 relative to atmospheric saturation does not enhance maximum production in dense communities of efficient HCO3?‐users and only doubles production of pure CO2‐users. A challenge therefore exists establishing the importance of light for photosynthetic production of macrophytes from individuals to communities and re‐evaluating the postulated main importance of inorganic carbon and temperature in the scenarios of globally rising CO2 and temperature. 相似文献
92.
Réty S Sopková-de Oliveira Santos J Dreyfuss L Blondeau K Hofbauerová K Raguénès-Nicol C Kerboeuf D Renouard M Russo-Marie F Lewit-Bentley A 《Journal of molecular biology》2005,345(5):1131-1139
Annexin A8 is a relatively infrequent and poorly studied member of this large family of calcium-binding and membrane-binding proteins. It is, however, associated with a specific disease, acute promyelocytic leukemia. We have solved its three-dimensional structure, which includes a moderately long and intact N terminus. The structure is closest to that of annexin A3 and highlights several important regions of inherent flexibility in the annexin molecule. The N terminus resembles that of annexin A3, as it lies along the concave surface of the molecule and inserts partially into the hydrophilic channel in its centre. Since both annexins A3 and A8 are expressed in promyelocytic cells during their differentiation, the similarity in their structures might suggest a functional relationship. 相似文献
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94.
Marchais-Oberwinkler S Nowicki B Pike VW Halldin C Sandell J Chou YH Gulyas B Brennum LT Farde L Wikström HV 《Bioorganic & medicinal chemistry》2005,13(3):883-893
WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)ethyl))-N-(2-pyridinyl)cyclohexanecarboxamide] 1 and its O-desmethyl derivative DWAY 2 are well-known high affinity 5-HT(1A) receptor antagonists, which when labeled with carbon-11 (beta+; t(1/2) = 20.4 min) in the carbonyl group are effective radioligands for imaging brain 5-HT(1A) receptors with positron emission tomography (PET). In a search for new 5-HT(1A) antagonists with different pharmacokinetic and metabolic properties, the pyridinyl N-oxide moiety was incorporated into analogs of 1 and 2. NOWAY 3, in which the pyridinyl ring of 1 was oxidized to the pyridinyl N-oxide, was prepared via nucleophilic substitution of 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamine on 2-chloropyridine-N-oxide followed by acylation with cyclohexanecarbonyl chloride. 6Cl-NOWAY 4, a more lipophilic (pyridinyl-6)-chloro derivative of 3, was prepared by treating 1-(2-methoxyphenyl)-4-(2-(2-(6-bromo)aminopyridinyl-N-oxide)ethyl)piperazine with cyclohexanecarbonyl chloride for acylation and concomitant chloro for bromo substitution. NEWWAY 5, in which the 2-hydroxy-phenyl group of 2 is replaced with a 2-pyridinyl N-oxide group with the intention of mimicking the topology of 2, was prepared in five steps from 2-(chloroacetylamino)pyridine. N-Oxides 3-5 were found to be high affinity antagonists at 5-HT(1A) receptors, with 3 having the highest affinity and a Ki value (0.22 nM) comparable to that of 1 (0.17 nM). By calculation the lipophilicity of 3 (LogP = 1.87) is lower than that of 1 by 1.25 LogP units while TLC and reverse phase HPLC indicate that 3 has slightly lower lipophilicity than 1. On the basis of these encouraging findings, the N-oxide 3 was selected for labeling with carbon-11 in its carbonyl group and for evaluation as a radioligand with PET. After intravenous injection of [carbonyl-11C]3 into cynomolgus monkey there was very low uptake of radioactivity into brain and no PET image of brain 5-HT(1A) receptors was obtained. Either 3 inadequately penetrates the blood-brain barrier or it is excluded from brain by an active efflux mechanism. Rapid deacylation of 3 was not apparent in vivo; in cynomolgus monkey plasma radioactive metabolites of [carbonyl-11C]3 appeared less rapidly than from the radioligands [carbonyl-11C]1 and [carbonyl-11C]2, which are known to be primarily metabolized by deacylation. Ligand 3 may have value as a new pharmacological tool, but not as a radioligand for brain imaging. 相似文献
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Binderup E Björkling F Hjarnaa PV Latini S Baltzer B Carlsen M Binderup L 《Bioorganic & medicinal chemistry letters》2005,15(10):2491-2494
To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo. 相似文献
98.
The relationship between amino acid sequence and intrinsic disorder in proteins is investigated. Two databases, one of disordered proteins and the other of globular proteins, are analyzed and compared in order to extract simple sequence patterns of a few amino acids or amino acid properties that characterize disordered segments. It is found that a number of reliable, nonrandom associations exists. In particular, two types of patterns appear to be recurrent: a proline-rich pattern and a (positively or negatively) charged pattern. These results indicate that local sequence information can determine disordered regions in proteins. The derived patterns provide some insights into the physical reasons for disordered structures. They should also be helpful in improving currently available prediction methods. 相似文献
99.
Tan Q Christiansen L Bathum L Zhao JH Yashin AI Vaupel JW Christensen K Kruse TA 《Human heredity》2005,59(2):88-97
Association-based linkage disequilibrium (LD) mapping is an increasingly important tool for localizing genes that show potential influence on human aging and longevity. As haplotypes contain more LD information than single markers, a haplotype-based LD approach can have increased power in detecting associations as well as increased robustness in statistical testing. In this paper, we develop a new statistical model to estimate haplotype relative risks (HRRs) on human survival using unphased multilocus genotype data from unrelated individuals in cross-sectional studies. Based on the proportional hazard assumption, the model can estimate haplotype risk and frequency parameters, incorporate observed covariates, assess interactions between haplotypes and the covariates, and investigate the modes of gene function. By introducing population survival information available from population statistics, we are able to develop a procedure that carries out the parameter estimation using a nonparametric baseline hazard function and estimates sex-specific HRRs to infer gene-sex interaction. We also evaluate the haplotype effects on human survival while taking into account individual heterogeneity in the unobserved genetic and nongenetic factors or frailty by introducing the gamma-distributed frailty into the survival function. After model validation by computer simulation, we apply our method to an empirical data set to measure haplotype effects on human survival and to estimate haplotype frequencies at birth and over the observed ages. Results from both simulation and model application indicate that our survival analysis model is an efficient method for inferring haplotype effects on human survival in population-based association studies. 相似文献
100.
The E71 residue is buried near the selectivity filter in the KcsA K+ channel and forms a carboxyl-carboxylate bridge with D80. We have investigated the importance of E71 by examining neutralization mutants at this position using biochemical and electrophysiological methods. E71 mutations differentially destabilize the detergent-solubilized tetramer; among them, the E71V neutralization mutant has a relatively subtle effect. The E71V channel displays electrical activity when reconstituted into planar lipid bilayers. In single channel recordings, the mutant retains K+/Na+ selectivity, and its conductance in the outward direction is unaltered. Some conduction properties are changed: inward conductance is increased. Our results show that that the E71 side chain is not a primary determinant of ion selectivity or conduction in the wild-type channel, either directly or through the E71:D80 carboxyl-carboxylate bridge. 相似文献