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The inner centromere protein, INCENP, is crucial for correct chromosome segregation during mitosis. It connects the kinase Aurora B to the inner centromere allowing this kinase to dynamically access its kinetochore targets. However, the function of its central, 440-residue long intrinsically disordered region (IDR) and its multiple phosphorylation sites is unclear. Here, we determined the conformational ensemble of INCENP’s IDR, systematically varying the level of phosphorylation, using all-atom and coarse-grain molecular dynamics simulations. Our simulations show that phosphorylation expands INCENP’s IDR, both locally and globally, mainly by increasing its overall net charge. The disordered region undergoes critical globule-to-coil conformational transitions and the transition temperature non-monotonically depends on the degree of phosphorylation, with a mildly phosphorylated case of neutral net charge featuring the highest collapse propensity. The IDR transitions from a multitude of globular states, accompanied by several specific internal contacts that reduce INCENP length by loop formation, to weakly interacting and highly extended coiled conformations. Phosphorylation critically shifts the population between these two regimes. It thereby influences cohesiveness and phase behavior of INCENP IDR assemblies, a feature presumably relevant for INCENP’s function in the chromosomal passenger complex. Overall, we propose the disordered region of INCENP to act as a phosphorylation-regulated and length-variable component, within the previously defined “dog-leash” model, that thereby regulates how Aurora B reaches its targets for proper chromosome segregation.  相似文献   
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The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.  相似文献   
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Arctic shrubs have a strong potential for climate and environmental reconstructions in the chronically understudied regions of the high northern latitudes. The climate dynamics of these regions are important to understand because of large-scale feedbacks to the global climate system. However, little is known about other factors influencing shrub ring growth, possibly obscuring their climate signal. For example, as of yet we are not able to differentiate between herbivory or climatically induced growth depressions. Here, we use one of the most common Arctic shrubs, Alnus viridis as a test case to address this question. We sampled Alnus in Kobbefjord, Greenland, measured shrub-ring width and cell wall thickness and built site chronologies of each parameter. We analysed climate-growth relationships, tested their stability over time and employed a pointer-year analysis to detect growth depressions. We employed bootstrapped transfer function stability tests (BTFS) to assess the suitability of our shrub chronologies for climate reconstruction. Correlations with climate data showed strong significantly positive and stable correlations between summer temperature and ring-width with the exception of the recent decade. A climate reconstruction model failed stability tests, when the complete period of record was used for calibration and verification. Wood anatomy analysis uncovered the occurrence of unusual cell structure (very thin cell walls) in the exceptionally narrow ring of 2004, a recorded insect outbreak year in other parts of Greenland. When excluding the affected ring and a recovery period, the reconstruction model passed all tests, suggesting that the unusual 2004 ring was not climate driven, but rather the result of an insect attack. When combining anatomical analysis with traditional ring-width measurements, we move a step further in potentially distinguishing small rings caused by insect attacks from small rings formed in climatically challenging years. While this study does not provide unambiguous evidence, it does provide potential useful methodological combinations to enable more robust climate reconstructions in areas where climatic records are extremely sparse.  相似文献   
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Many authors have estimated the virtual water content of good and services traded internationally, and many have calculated national water footprints that account for the volumes of virtual water imported and exported. Some authors have suggested that international trade of virtual water has been harmful to selected exporting countries with limited water endowments. Some suggest also that current patterns of international trade should be rearranged to make better use of global water resources. Yet, countries do not actually trade in virtual water. They trade in goods and services for which water is one of many inputs. Wise choices regarding water resources and smart strategies regarding international trade cannot be determined by focusing on water alone. The notions of virtual water and water footprints are not helpful indicators of optimal strategies regarding water resources, particularly when considering issues such as water scarcity or international trade. I describe four perspectives regarding virtual water and water footprints, with the goal of demonstrating the inadequacies of these notions in policy discussions and in efforts to determine the optimal allocation and use of water resources. The four perspectives are: (1) international trade should not be modified or regulated to reflect the virtual water content of traded commodities or water footprints in the countries of trading partners, (2) countries do not save water by engaging in virtual water trade, (3) consumers in one country cannot alleviate water scarcity or improve water quality in other countries, and (4) water footprints are not analogous to carbon or ecological footprints.  相似文献   
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