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There has been a long-term decline in spring and fall numbers of Clethrionomys rufocanus in boreal Sweden in 1971–2005. Previous studies on permanent sampling plots in the centre of 2.5 × 2.5 km landscapes suggested that habitat fragmentation (sensu destruction) could have contributed to the decline. Therefore, we tested these findings in a field study and compared trapping results on the central sampling plots of landscapes with a low degree of fragmentation (LDF) and of “hot spot” type with trapping results in managed forest landscapes with a high degree of fragmentation (HDF). We predicted that C. rufocanus would be more common on the LDF plots. We used our permanent plots supplemented with a new sample of plots, mainly of the rare LDF type, inside or just outside the long-term study area. Very few voles were trapped on both plot types, and no difference was found. However, a subsequent pilot study with trapping in a national park with large areas of pristine, unfragmented forest yielded more voles than in the managed, more fragmented, areas. Consequently, the initial field study data and some other recent data were also re-analysed from a “local patch quality” perspective. This alternative approach revealed the positive importance of large focal patches of forest >60 years old and their content of old-growth (pine) forest (>100 years). Interestingly, at the landscape level, the frequency distribution of patches of forest >60 years old, old-growth (>100 years), and especially of old-growth pine forest (>100 years), relative to the properties of plots with C. rufocanus, suggested that there are few forest patches left that are suitable for C. rufocanus. Our current results suggest that habitat fragmentation cannot be excluded as a contributing cause to the long-term decline of C. rufocanus in boreal Sweden.  相似文献   
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All entomological traps have a capturing bias, and amber, viewed as a trap, is no exception. Thus the fauna trapped in amber does not represent the total existing fauna of the former amber forest, rather the fauna living in and around the resin producing tree. In this paper we compare arthropods from a forest very similar to the reconstruction of the Miocene Mexican amber forest, and determine the bias of different trapping methods, including amber. We also show, using cluster analyses, measurements of the trapped arthropods, and guild distribution, that the amber trap is a complex entomological trap not comparable with a single artificial trap. At the order level, the most similar trap to amber is the sticky trap. However, in the case of Diptera, at the family level, the Malaise trap is also very similar to amber. Amber captured a higher diversity of arthropods than each of the artificial traps, based on our study of Mexican amber from the Middle Miocene, a time of climate optimum, where temperature and humidity were probably higher than in modern Central America. We conclude that the size bias is qualitatively independent of the kind of trap for non–extreme values. We suggest that frequent specimens in amber were not necessarily the most frequent arthropods in the former amber forest. Selected taxa with higher numbers of specimens appear in amber because of their ecology and behavior, usually closely related with a tree–inhabiting life. Finally, changes of diversity from the Middle Miocene to Recent time in Central and South America can be analyzed by comparing the rich amber faunas from Mexico and the Dominican Republic with the fauna trapped using sticky and Malaise traps in Central America.  相似文献   
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The time-dependent stress-strain behavior of spider dragline silk was already observed decades ago, and has been attributed to the disordered sequences in silk proteins, which compose the soft amorphous matrix. However, the actual molecular origin and magnitude of internal friction within the amorphous matrix has remained inaccessible, because experimentally decomposing the mechanical response of the amorphous matrix from the embedded crystalline units is challenging. Here, we used atomistic molecular dynamics simulations to obtain friction forces for the relative sliding of peptide chains of Araneus diadematus spider silk within bundles of these chains as a representative unit of the amorphous matrix in silk fibers. We computed the friction coefficient and coefficient of viscosity of the amorphous phase to be in the order of 10−6 Ns/m and 104 Ns/m2, respectively, by extrapolating our simulation data to the viscous limit. Finally, we used a finite element method for the amorphous phase, solely based on parameters derived from molecular dynamics simulations including the newly determined coefficient of viscosity. With this model the time scales of stress relaxation, creep, and hysteresis were assessed, and found to be in line with the macroscopic time-dependent response of silk fibers. Our results suggest the amorphous phase to be the primary source of viscosity in silk and open up the avenue for finite element method studies of silk fiber mechanics including viscous effects.  相似文献   
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Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain. In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo. This suggests the existence of neuron‐type specific signalling pathways activated by different subpopulations of CB1. In this study, we analysed CB1 expression, binding and signalling in the hippocampus of conditional mutant mice, bearing CB1 deletion in GABAergic (GABA‐CB1‐KO mice) or cortical glutamatergic neurons (Glu‐CB1‐KO mice). Compared to their wild‐type littermates, Glu‐CB1‐KO displayed a small decrease of CB1 mRNA amount, immunoreactivity and [³H]CP55,940 binding. Conversely, GABA‐CB1‐KO mice showed a drastic reduction of these parameters, confirming that CB1 is present at much higher density on hippocampal GABAergic interneurons than glutamatergic neurons. Surprisingly, however, saturation analysis of HU210‐stimulated [35S]GTPγS binding demonstrated that ‘glutamatergic’ CB1 is more efficiently coupled to G protein signalling than ‘GABAergic’ CB1. Thus, the minority of CB1 on glutamatergic neurons is paradoxically several fold more strongly coupled to G protein signalling than ‘GABAergic’ CB1. This selective signalling mechanism raises the possibility of designing novel cannabinoid ligands that differentially activate only a subset of physiological effects of CB1 stimulation, thereby optimizing therapeutic action.  相似文献   
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As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala) protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of 50Å ps−1 derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.  相似文献   
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Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.  相似文献   
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The present study aimed at analyzing the odor properties of a group of physiological human metabolites of the odorant 1,8‐cineole: 2,3‐dehydro‐, α2,3‐epoxy‐, α/β2‐hydroxy‐, α3‐hydroxy‐, 4‐hydroxy‐, 7‐hydroxy‐, 9‐hydroxy‐, 2‐oxo‐, and 3‐oxo‐1,8‐cineole. These metabolites constitute a group of structurally closely related molecules, which differ mainly in nature and position of O‐containing functional groups. They thus offer the possibility to correlate odor properties with molecular structure, i.e., to establish structure? odor relationships of compounds that are biologically generated from a potent odorant as parent substance. Generally, the metabolites preserved the eucalyptus‐like odor quality of 1,8‐cineole but showed additional odor notes such as sweet, citrus‐like, plastic‐like, earthy, musty, and faecal, which made them distinguishable. The individual enantiomers of chiral molecules also exhibited different odors. With the exception of 2,3‐dehydro‐1,8‐cineole, all metabolites showed a highly decreased odor threshold in comparison to 1,8‐cineole. The determination of odor qualities and odor thresholds was accomplished by gas chromatography/olfactometry (GC/O) on achiral and chiral GC capillaries. The results were correlated with common theories on structure? odor relationships.  相似文献   
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