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Efficient transportation, a hot topic in nonlinear science, is essential for modern societies and the survival of biological species. Biological evolution has generated a rich variety of successful solutions, which have inspired engineers to design optimized artificial systems. Foraging ants, for example, form attractive trails that support the exploitation of initially unknown food sources in almost the minimum possible time. However, can this strategy cope with bottleneck situations, when interactions cause delays that reduce the overall flow? Here, we present an experimental study of ants confronted with two alternative routes. We find that pheromone-based attraction generates one trail at low densities, whereas at a high level of crowding, another trail is established before traffic volume is affected, which guarantees that an optimal rate of food return is maintained. This bifurcation phenomenon is explained by a nonlinear modelling approach. Surprisingly, the underlying mechanism is based on inhibitory interactions. It points to capacity reserves, a limitation of the density-induced speed reduction, and a sufficient pheromone concentration for reliable trail perception. The balancing mechanism between cohesive and dispersive forces appears to be generic in natural, urban and transportation systems.  相似文献   
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Malignant melanoma is one of the most aggressive human neoplasms which develop from the malignant transformation of normal epithelial melanocytes and share the lineage with retinal cells. cGMP-phosphodiesterase 6 (PDE6) is one of the cancer-retina antigens newly identified in melanoma cells. Normally, PDE6 hydrolyzes the photoreceptor second messenger cGMP allowing the visual signal transduction in photoreceptor cells. cGMP also play an important signaling role in stimulating melanogenesis in human melanocytes. Here, we present evidence that PDE6 is a key enzyme regulating the cGMP metabolism in melanoma cells. Decrease in intracellular cGMP leads to calcium accumulation in melanoma cells. In these cells, cGMP-phosphodiesterase 6 can be activated by another cancer-retina antigen, transducin, through Wnt5a–Frizzled-2 cascade, which leads to a lowering of cGMP and an increase in intracellular calcium mobilization. Thus, the aberrant expression of PDE6 may control cGMP metabolism and calcium homeostasis in melanoma cells.  相似文献   
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To gain insight into the function of DNA methylation at cis-regulatory regions and its impact on gene expression, we measured methylation, RNA polymerase occupancy and histone modifications at 16,000 promoters in primary human somatic and germline cells. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes are methylated in somatic cells, suggesting additional functional selection. These results show that promoter sequence and gene function are major predictors of promoter methylation states. Moreover, we observe that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.  相似文献   
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Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ~20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.  相似文献   
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Eubrachyurans not only exhibit a crab-like body shape, consisting of a mostly wide cephalothorax and a thin, shield-like pleon folded underneath it, but reportedly hold the pleon in this position with the use of specialized holding structures. To further our knowledge of the variability of these holding structures, and investigate their functionality, male and female crabs from five primary freshwater crab and five selected thoracotreme families were examined with stereomicroscopy. Exemplary specimens of each group were documented photographically and with micro-computed tomography to illustrate the holding structures in situ. The results show a press-button mechanism of variable shape in freshwater crabs, where divergent structures possibly support pleon attachment of different effectiveness. The press-button is present in the majority of basal heterotreme lineages, and is therefore regarded as an ancestral character of the Heterotremata. In the Thoracotremata, multiple holding mechanisms are identified: press-button, clasping apparatus, overhanging edge, and increased setae cover on sternal plates, with the last system probably only effective in terrestrial species, due to wet adhesion effects. The ancestral character state in the Thoracotremata is debatable, but most likely also a functional press-button was present. Each holding mechanism requires different pleon movements to engage and disengage. Additionally, in contrast to the most common press-button mechanism, divergent holding mechanisms tend to be present, and likely functional, in adult males and females.  相似文献   
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In an uncertain world, decisions by market participants are based on expectations. Therefore, sentiment indicators reflecting expectations have a proven track record at predicting economic variables. However, survey respondents largely perceive the world through media reports. Here, we want to make use of that. We employ a rich dataset provided by Media Tenor International, based on sentiment analysis of opinion‐leading media in Germany from 2001 to 2014, transformed into several monthly indices. German industrial production is predicted in a real‐time out‐of‐sample forecasting experiment and media indices are compared to a huge set of alternative indicators. Media data turn out to be valuable for 10‐ to 12‐month horizon forecasts, which is in line with the lag between monetary policy announcements and their effect on industrial production. This holds in the period during and after the Great Recession when many models fail. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   
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