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71.
Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S‐phase transition 下载免费PDF全文
72.
The role of ungulates in nowadays temperate forests. A response to Fløjgaard et al. (DOI:10.1111/gcb.14029) 下载免费PDF全文
73.
Aminoglycosides are known to bind and perturb the function of catalytic RNA. Here we show that they also are potent inhibitors of protein-based catalysis using Escherichia coli Klenow polymerase (pol) and mammalian poly(A)-specific ribonuclease (PARN) as model enzymes. The inhibition was pH dependent and released in a competitive manner by Mg2+. Kinetic analysis showed that neomycin B behaved as a mixed noncompetitive inhibitor. Iron-mediated hydroxyl radical cleavage was used to show that neomycin B interfered with metal-ion binding in the active sites of both enzymes. Our analysis suggests a mechanism of inhibition where the aminoglycoside binds in the active site of the enzyme and thereby displaces catalytically important divalent metal ions. The potential causes of aminoglycoside toxicity and the usage of aminoglycosides to probe, characterize, and perturb metalloenzymes are discussed. 相似文献
74.
Questions: Is the red fox a potential vector for epizoochorous seed dispersal? Can seed attachment and retention be predicted from plant and seed traits? Location: Grasslands in southern Norway. Methods: Epizoochorous seed attachment on the red fox was studied by walking a dummy fox through the vegetation and comparing seeds found on the dummy with the estimated seed availability in the vegetation. Seed retention, i.e. the ability of different seeds to stay on the fox, was estimated in a separate experiment. Seed attachment and retention were related to plant and seed traits using statistical models that account for heteroscedasticity and zero‐inflated data. Results: The majority of seeds attached to the fox originated from a few species, but also species without specific seed traits that are supposed to enhance epizoochory attached at least some seeds to the fox. The probability of seed attachment was positively related to plant height, bristle and hooked seed appendages, and negatively related to winged appendages, seed mass, and seed sphericity. Seed retention was positively related to the seed traits bristles, hooks and pappus. For several species, the results indicate a high potential for dispersal over long distances. Conclusions: In modern agricultural landscapes, large herbivores are often restricted in their mobility or are found at low densities, and other animal vectors may therefore be important for seed dispersal. In our study, a range of plant species were able to disperse by attaching seeds to, and having their seeds retained in, the fox fur some distance. We suggest that the red fox may be an important vector for epizoochorous seed dispersal in the agricultural landscape. 相似文献
75.
Lampa A Ehrenberg AE Vema A Åkerblom E Lindeberg G Danielson UH Karlén A Sandström A 《Bioorganic & medicinal chemistry》2011,19(16):4917-4927
Macrocyclization is a commonly used strategy to preorganize HCV NS3 protease inhibitors in their bioactive conformation. Moreover, macrocyclization generally leads to greater stability and improved pharmacokinetic properties. In HCV NS3 protease inhibitors, it has been shown to be beneficial to include a vinylated phenylglycine in the P2 position in combination with alkenylic P1' substituents. A series of 14-, 15- and 16-membered macrocyclic HCV NS3 protease inhibitors with the linker connecting the P2 phenylglycine and the alkenylic P1' were synthesized by ring-closing metathesis, using both microwave and conventional heating. Besides formation of the expected macrocycles in cis and trans configuration as major products, both ring-contracted and double-bond migrated isomers were obtained, in particular during formation of the smaller rings (14- and 15-membered rings). All inhibitors had K(i)-values in the nanomolar range, but only one inhibitor type was improved by rigidification. The loss in inhibitory effect can be attributed to a disruption of the beneficial π-π interaction between the P2 fragment and H57, which proved to be especially deleterious for the d-phenylglycine epimers. 相似文献
76.
The glandular kininogenase kallikrein is known to occur in many mammalian organs and glands but direct histochemical localization has been achieved in only a few cases. We have now been able to localize porcine kallikrein in the acinar cells of the pancreas and in the striated and collecting duct cells of the submandibular gland. Incubation of frozen and fixed sections with one of the crossreacting antibodies, anti-pancreatic, anti-submandibular or anti-urinary kallikrein IgG resulted in the same immunofluorescence pattern. There was evidence of a specific fluorescence neither in the acinar cells, nor in the interstitial tissue or blood cells of the submandibular gland nor in the islets of Langerhans, the interlobular ducts or blood vessels of the pancreas. From all data now available about glandular kallikreins, it seems that the kallikreins in these organs are very similar. 相似文献
77.
Hugo M. Botelho Sónia S. Leal Isabel Cardoso Kiran Yanamandra Ludmilla A. Morozova-Roche Günter Fritz Cláudio M. Gomes 《The Journal of biological chemistry》2012,287(50):42233-42242
S100A6 is a small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics. It is overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS). Following recent reports of amyloid formation by S100 proteins, we investigated the aggregation properties of S100A6. Computational analysis using aggregation predictors Waltz and Zyggregator revealed increased propensity within S100A6 helices HI and HIV. Subsequent analysis of Thioflavin-T binding kinetics under acidic conditions elicited a very fast process with no lag phase and extensive formation of aggregates and stacked fibrils as observed by electron microscopy. Ca2+ exerted an inhibitory effect on the aggregation kinetics, which could be reverted upon chelation. An FT-IR investigation of the early conformational changes occurring under these conditions showed that Ca2+ promotes anti-parallel β-sheet conformations that repress fibrillation. At pH 7, Ca2+ rendered the fibril formation kinetics slower: time-resolved imaging showed that fibril formation is highly suppressed, with aggregates forming instead. In the absence of metals an extensive network of fibrils is formed. S100A6 oligomers, but not fibrils, were found to be cytotoxic, decreasing cell viability by up to 40%. This effect was not observed when the aggregates were formed in the presence of Ca2+. Interestingly, native S1006 seeds SOD1 aggregation, shortening its nucleation process. This suggests a cross-talk between these two proteins involved in ALS. Overall, these results put forward novel roles for S100 proteins, whose metal-modulated aggregation propensity may be a key aspect in their physiology and function. 相似文献
78.
Anders Stigebrandt 《Palaeogeography, Palaeoclimatology, Palaeoecology》1985,50(1):303-321
A theoretical investigation of the hydrographic conditions in the northern North Atlantic (N of the Greenland—Scotland Ridge) for different forcing conditions is undertaken. First a simple dynamical model for the “mediterranean” circulation in the Greenland and Norwegian seas (the Subpolar Sea) is developed. The calculated contemporary rate of deepwater formation (about 2.5 × 106 m3/s) seems to be quite realistic. It is concluded that the mediterranean circulation is possible as long as the cyclonal atmospheric circulation in the Subpolar Sea is strong enough to prevent the fresher water in the coastal currents along the eastern and western boundaries from spreading over the interior.Utilizing the Arctic Ocean model in Stigebrandt (1981) the hydrographic and ice conditions in the Subpolar Sea and the Arctic Ocean during different phases of a glaciation are, finally, investigated. As so many parameters are involved the derivations are, by necessity, rather uncertain. However, it seems possible that the hydrographic state in the Subpolar Sea changes between mediterranean and estuarine circulation several times during a glacial cycle. 相似文献
79.
80.