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171.
On the basis of the structure of a HslUV complex, a mechanism of allosteric activation of the HslV protease, wherein binding of the HslU chaperone propagates a conformational change to the active site cleft of the protease, has been proposed. Here, the 3.1 A X-ray crystallographic structure of Haemophilus influenzae HslUV complexed with a vinyl sulfone inhibitor is described. The inhibitor, which reacts to form a covalent linkage to Thr1 of HslV, binds in an "antiparallel beta" manner, with hydrogen-bond interactions between the peptide backbone of the protease and that of the inhibitor, and with two leucinyl side chains of the inhibitor binding in the S1 and S3 specificity pockets of the protease. Comparison of the structure of the HslUV-inhibitor complex with that of HslV without inhibitor and in the absence of HslU reveals that backbone interactions would correctly position a substrate for cleavage in the HslUV complex, but not in the HslV protease alone, corroborating the proposed mechanism of allosteric activation. This activation mechanism differs from that of the eukaryotic proteasome, for which binding of activators opens a gated channel that controls access of substrates to the protease, but does not perturb the active site environment. 相似文献
172.
Trenton W. J. Garner Benedikt R. Schmidt Paquita Hoeck Josh Van Buskirk 《Molecular ecology resources》2003,3(2):186-188
We developed a set of di‐ and tetranucleotide microsatellite markers for the Alpine newt, Triturus alpestris. Polymorphism as detected in 39 individuals ranged from 3 to 32 alleles at a locus. Cross‐priming with samples of five other Triturus species showed extremely poor levels of cross‐species utility. Still, these markers are suitable for studies of inter‐ and intrapopulation genetic diversity in the focal species. 相似文献
173.
174.
Seed dispersal will be essential for plants to track future climate space, but dispersal capacity is rarely measured or incorporated into species distribution models. Using the entire alpine flora of the Snowy Mountains, south-eastern Australia, as a case study, we modelled the dispersal capacity of 198 species (93.4% of the flora) using the plant traits dispersal syndrome, seed mass, seed release height and growth form. The modelled maximum dispersal distances were mostly affected by dispersal syndrome of each species. The models reveal that 75% of species disperse up to 10 m, whilst 20% may disperse >100 m. Most species in this flora do not have any specific dispersal strategy, hence their inability to disperse >10 m. However, those species with longer modelled distances were dispersed by animals or wind (>600 and >140 m, respectively). This alpine flora has a low capacity for long-distance seed dispersal and is likely to suffer from migration lag as the local climate undergoes rapid changes. 相似文献
175.
Nick Jagiella Benedikt Müller Margareta Müller Irene E. Vignon-Clementel Dirk Drasdo 《PLoS computational biology》2016,12(2)
We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS) of SK-MES-1 cells, a non-small cell lung cancer (NSCLC) cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM), cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions. We thus ultimately arrive at a model that mimics the MCTS growth under multiple conditions to a great extent. Interestingly, the final model, is a minimal model capable of explaining all data simultaneously in the sense, that the number of mechanisms it contains is sufficient to explain the data and missing out any of its mechanisms did not permit fit between all data and the model within physiological parameter ranges. Nevertheless, compared to earlier models it is quite complex i.e., it includes a wide range of mechanisms discussed in biological literature. In this model, the cells lacking oxygen switch from aerobe to anaerobe glycolysis and produce lactate. Too high concentrations of lactate or too low concentrations of ATP promote cell death. Only if the extracellular matrix density overcomes a certain threshold, cells are able to enter the cell cycle. Dying cells produce a diffusive growth inhibitor. Missing out the spatial information would not permit to infer the mechanisms at work. Our findings suggest that this iterative data integration together with intermediate model sensitivity analysis at each model development stage, provide a promising strategy to infer predictive yet minimal (in the above sense) quantitative models of tumor growth, as prospectively of other tissue organization processes. Importantly, calibrating the model with two nutriment-rich growth conditions, the outcome for two nutriment-poor growth conditions could be predicted. As the final model is however quite complex, incorporating many mechanisms, space, time, and stochastic processes, parameter identification is a challenge. This calls for more efficient strategies of imaging and image analysis, as well as of parameter identification in stochastic agent-based simulations. 相似文献
176.
A potent peptide affinity reagent for the opiate receptor 总被引:2,自引:0,他引:2
The synthesis and characterization of a novel enkephalin analogue, Tyr-D-Ala-Gly-Phe-Leu-chloromethyl ketone, is described. The biological potency of the compound in various assays has been determined to be very high. The compound is an alkylating affinity reagent and irreversibly inactivates a defined population of enkephalin receptors in rat brain membrane preparations, as well as irreversibly inhibiting electrically stimulated contractions in the mouse vas deferens tissue preparation. 相似文献
177.
Angel Angelov Haijuan Li Andreas Geissler Benedikt LeisWolfgang Liebl 《Systematic and applied microbiology》2013
In this work we describe the conditional toxic effect of the expression of enzymes that cleave 5-bromo-4-chloro-3-indolyl (BCI) substrates and its use as a new counterselection principle useful for the generation of clean and unmarked mutations in the genomes of bacteria. The application of this principle was demonstrated in the thermophile Thermus thermophilus HB27 and in a mesophile for which currently no counterselection markers are available, Micrococcus luteus ATCC 27141. For T. thermophilus, the indigogenic substrate BCI-β-glucoside was used in combination with the T. thermophilus β-glucosidase gene (bgl). For M. luteus, a combination of BCI-β-galactoside and the E. coli lacZ gene was implemented. We observed a strong growth-inhibiting effect when the strains were grown on agar plates containing the appropriate BCI substrates, the inhibition being proportional to the substrate concentration and the level of bgl/lacZ expression. The growth inhibition apparently depends on intracellular BCI substrate cleavage and accumulation of toxic indoxyl precipitates. The bgl and lacZ genes were used as counterselection markers for the rapid generation of scar-less chromosomal deletions in T. thermophilus HB27 (both in a Δbgl and in a wild type background) and in M. luteus ATCC 27141. 相似文献
178.
179.
Simon G?chter Benedikt Herrmann 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1518):791-806
Understanding the proximate and ultimate sources of human cooperation is a fundamental issue in all behavioural sciences. In this paper, we review the experimental evidence on how people solve cooperation problems. Existing studies show without doubt that direct and indirect reciprocity are important determinants of successful cooperation. We also discuss the insights from a large literature on the role of peer punishment in sustaining cooperation. The experiments demonstrate that many people are ‘strong reciprocators’ who are willing to cooperate and punish others even if there are no gains from future cooperation or any other reputational gains. We document this in new one-shot experiments, which we conducted in four cities in Russia and Switzerland. Our cross-cultural approach allows us furthermore to investigate how the cultural background influences strong reciprocity. Our results show that culture has a strong influence on positive and in especially strong negative reciprocity. In particular, we find large cross-cultural differences in ‘antisocial punishment’ of pro-social cooperators. Further cross-cultural research and experiments involving different socio-demographic groups document that the antisocial punishment is much more widespread than previously assumed. Understanding antisocial punishment is an important task for future research because antisocial punishment is a strong inhibitor of cooperation. 相似文献
180.
Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial
Ganapathy van Samkar Wietse J. Eshuis Roelof J. Bennink Thomas M. van Gulik Marcel G. W. Dijkgraaf Benedikt Preckel Stefan de Hert Dirk J. Gouma Markus W. Hollmann Olivier R. C. Busch 《PloS one》2015,10(10)