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Annukka Jouppila Olli T Pentik?inen Luca Settimo Tommi Nyr?nen Jukka-Pekka Haapalahti Milla Lampinen David G Mottershead Mark S Johnson Kari Kein?nen 《European journal of biochemistry》2002,269(24):6261-6270
Previous structural and mutagenesis studies indicate that the invariant alpha-amino and alpha-carboxyl groups of glutamate receptor agonists are engaged in polar interactions with oppositely charged, conserved arginine and glutamate residues in the ligand-binding domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. To examine the role of these residues (R507 and E727 in the GluR-D subunit) in the discrimination between agonists and antagonists, we analyzed the ligand-binding properties of homomeric GluR-D and its soluble ligand-binding domain with mutations at these positions. Filter-binding assays using [3H]AMPA, an agonist, and [3H]Ro 48-8587, a high-affinity antagonist, as radioligands revealed that even a conservative mutation at R507 (R507K) resulted in the complete loss of both agonist and antagonist binding. In contrast, a negative charge at position 727 was necessary for agonist binding, whereas the isosteric mutation, E727Q, abolished all agonist binding but retained high-affinity binding for [3H]Ro 48-8587, displaceable by 7,8-dinitroquinoxaline-2,3-dione. Competition binding studies with antagonists representing different structural classes in combination with ligand docking experiments suggest that the role of E727 is antagonist-specific, ranging from no interaction to weak electrostatic interactions involving indirect and direct hydrogen bonding with the antagonist molecule. These results underline the importance of ion pair interaction with E727 for agonist activity and suggest that an interaction with R507, but not with E727, is essential for antagonist binding. 相似文献
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Fecundity of the autumnal moth depends on pooled geometrid abundance without a time lag: implications for cyclic population dynamics 总被引:1,自引:0,他引:1
1. The abundance and fecundity-related body size variation of the cyclic autumnal moth Epirrita autumnata were monitored from the early increase phase and throughout the outbreak to the end of the density decline in northernmost Norway during 1999-2006. Another geometrid, the winter moth Operophtera brumata, did not increase in density until the autumnal moth had its post-peak in 2004, and was at its own peak concurrent with the steeply declining autumnal moth abundance in 2005-06. 2. The body size variables measured (forewing lengths of males and females and hind femur lengths of males) of the autumnal moth showed a similar density-dependent response, i.e. increasing density was associated with decreasing body size and fecundity. Nevertheless, regression analyses clearly ranked the pooled geometrid abundance without a time lag as the best predictor for the body size variation, ahead of the abundance of the autumnal moth or past abundance of all geometrids. 3. Nondelayed effects of lowered food quality and absolute shortage of foliage under congested conditions are the most plausible reasons for reduced body size. 4. Two most commonly proposed causal factors of the autumnal moth population cycle, i.e. delayed inducible resistance of the host plant (mountain birch Betula pubescens czerepanovii) and delayed density-dependent parasitism by specialized hymenopteran parasitoids, cannot easily explain the diverging population trends between the autumnal and winter moths. 5. We suggest that either the inducible resistance of the host tree or the host utilization of the most important parasitoids and/or pathogens have to be strictly species-specific between these closely related moth species to produce the population dynamics observed. That fecundity of the autumnal moth was best related to the pooled geometrid abundance weakens support for the former hypothesis, while our lack of host-specific information limits conclusions about the role of natural enemies. 相似文献
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Jouni Smed Kari Salonen Mika Johnsson Tommi Johtela Olli S. Nevalainen 《Flexible Services and Manufacturing Journal》2003,15(1):19-35
In printed circuit board (PCB) assembly, the majority of electronic components are inserted by high-speed placement machines. Although the efficient utilization of the machinery is important for a manufacturer, it is hard to fully realize in high-mix low-volume production environments. On the machine level, the component setup strategy adopted by the manufacturer has a significant impact on the overall production efficiency. Usually, the setup strategy is formulated as a part type grouping problem or a minimum setup problem. In this article, we consider a hybridization of these two problems for the single machine case: The object function to be minimized includes a weighted sum of the number of part type groups (giving the number of setup occasions) and the number of feeder changeovers. We present algorithms for the problem and compare their efficiency. 相似文献
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Background
Ecological speciation is a process in which a transiently resource-polymorphic species divides into two specialized sister lineages as a result of divergent selection pressures caused by the use of multiple niches or environments. Ecology-based speciation has been studied intensively in plant-feeding insects, in which both sympatric and allopatric shifts onto novel host plants could speed up diversification. However, while numerous examples of species pairs likely to have originated by resource shifts have been found, the overall importance of ecological speciation in relation to other, non-ecological speciation modes remains unknown. Here, we apply phylogenetic information on sawflies belonging to the 'Higher' Nematinae (Hymenoptera: Tenthredinidae) to infer the frequency of niche shifts in relation to speciation events. 相似文献38.
While electric fields at intermediate frequencies are not widely utilized for industrial technologies, surprisingly, certain toys emit the highest electric fields found in our living environment. These toys, plasma balls, are devices that use high voltage to create ionized light discharges. In this study, we assessed exposure to electric fields and contact/induced current from a recreational plasma ball device. The electric field strength was measured as a function of distance from the device, and the contact/induced current was measured with a current clamp in different exposure situations with point or grasping contact. The characteristic spectra of the electric field and contact current were measured, and both the multiple frequency rule and weighting of the spectra were applied according to the International Commission on Non-Ionizing Radiation Protection (ICNIRP) 1998 and 2010 guidelines. The results indicate that the recommended reference levels for the general public are exceeded at distances <1.2 m, and that the contact currents in the hand may be twice higher than recommended by the general public guidelines. 相似文献
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Reservoir formation in a river system changes a lotic environment to more lacustrine conditions, with impacts throughout the ecosystem. In this study, a river reach containing typical salmonid riffle/run habitat was flooded to create a large, deep pool from June to September in each of 3 years. We test the hypothesis that juvenile Atlantic salmon (Salmo salar) with their preference for run/riffle habitats will respond to the transformation to a lentic environment by moving into adjacent lotic environments. Movements of juvenile Atlantic salmon were monitored using a combination of biotelemetry (radio- and passive integrated transponder-tagging) and electrofishing. Results showed that no tracked fish moved away from the created pool habitat. Mass-specific growth rates showed the created pool habitat resulted in net growth of juveniles. The results confirm that fish may not immediately (i.e., at least for an approximate 2 months) respond to rapid, large-scale habitat alterations by moving to find similar habitat conditions outside the altered habitat. This is most probably related to plasticity of behavior and habitat use, and no change in biological conditions to a point that would negatively impact fish growth and survival, for example food availability, competition, or predation. The results also support the hypothesis that the relative importance of physical habitat variables is not universal among streams and populations, therefore limiting the value of applying standard habitat suitability criteria and use. 相似文献
40.
Teemu Kuosmanen Johannes Cairns Robert Noble Niko Beerenwinkel Tommi Mononen Ville Mustonen 《PLoS computational biology》2021,17(9)
Increasing body of experimental evidence suggests that anticancer and antimicrobial therapies may themselves promote the acquisition of drug resistance by increasing mutability. The successful control of evolving populations requires that such biological costs of control are identified, quantified and included to the evolutionarily informed treatment protocol. Here we identify, characterise and exploit a trade-off between decreasing the target population size and generating a surplus of treatment-induced rescue mutations. We show that the probability of cure is maximized at an intermediate dosage, below the drug concentration yielding maximal population decay, suggesting that treatment outcomes may in some cases be substantially improved by less aggressive treatment strategies. We also provide a general analytical relationship that implicitly links growth rate, pharmacodynamics and dose-dependent mutation rate to an optimal control law. Our results highlight the important, but often neglected, role of fundamental eco-evolutionary costs of control. These costs can often lead to situations, where decreasing the cumulative drug dosage may be preferable even when the objective of the treatment is elimination, and not containment. Taken together, our results thus add to the ongoing criticism of the standard practice of administering aggressive, high-dose therapies and motivate further experimental and clinical investigation of the mutagenicity and other hidden collateral costs of therapies. 相似文献