VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling

The spatial and temporal regulation of intracellular signaling is determined by the spatial and temporal organization of complexes assembled on scaffold proteins, which can be modulated by their interactions with additional proteins as well as subcellular localization. The scaffold KSR1 protein interacts with MAPK forming a complex that conveys a differential signaling in response to growth factors. The aim of this work is to determine the unknown mechanism by which VRK2A downregulates MAPK signaling. We have characterized the multiprotein complex formed by KSR1 and the Ser-Thr kinase VRK2A. VRK2A is a protein bound to the endoplasmic reticulum (ER) and retains a fraction of KSR1 complexes on the surface of this organelle. Both proteins, VRK2A and KSR1, directly interact by their respective C-terminal regions. In addition, MEK1 is also incorporated in the basal complex. MEK1 independently interacts with the CA5 region of KSR1 and with the N-terminus of VRK2A. Thus, VRK2A can form a high molecular size (600–1,000?kDa) stable complex with both MEK1 and KSR1. Knockdown of VRK2A resulted in disassembly of these high molecular size complexes. Overexpression of VRK2A increased the amount of KSR1 in the particulate fraction and prevented the incorporation of ERK1/2 into the complex after stimulation with EGF. Neither VRK2A nor KSR1 interact with the VHR, MKP1, MKP2, or MKP3 phosphatases. The KSR1 complex assembled and retained by VRK2A in the ER can have a modulatory effect on the signal mediated by MAPK, thus locally affecting the magnitude of its responses, and can explain differential responses depending on cell type.     

具有不确定参数的温度传感器的动态相对校准(英文)

存在动态偏差情况下的传感器校准,与多个传感器的相对校准类似.实现相对校准对许多控制问题都很重要,比如需要产生精确温度梯度的问题、保持均匀与稳定温度场的问题.本文以温度传感器为例,对静态(稳态)校准与动态校准从理论和实验两个角度进行了对比.动态校准的一个优势是其适用于任何测量数据,但其需要建立一个测量仪器的动态模型.尽管本文只研究了一个由三个传感器构成的简单设备,但其结果也适用于更复杂的情况.这正是因为动态校准的另一个显著优势,即其能在任何设备上进行校准,校准的一个前提是所用的动态模型与传感器具有相同的阶次.本文证明了可辨识性(可校准性)条件,并通过以迭代方式求解一个非线性加权最小二乘问题,实现了校准.对解的收敛性、一致性和渐近效率,不但给予了理论证明,且通过蒙特卡罗模拟实验进行了验证.     

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.     

High temperatures in the Late Cretaceous Arctic Ocean

To understand the climate dynamics of the warm, equable greenhouse world of the Late Cretaceous period, it is important to determine polar palaeotemperatures. The early palaeoceanographic history of the Arctic Ocean has, however, remained largely unknown, because the sea floor and underlying deposits are usually inaccessible beneath a cover of floating ice. A shallow piston core taken from a drifting ice island in 1970 fortuitously retrieved unconsolidated Upper Cretaceous organic-rich sediment from Alpha ridge, a submarine elevated feature of probable oceanic origin. A lack of carbonate in the sediments from this core has prevented the use of traditional oxygen-isotope palaeothermometry. Here we determine Arctic palaeotemperatures from these Upper Cretaceous deposits using TEX86, a new palaeothermometer that is based on the composition of membrane lipids derived from a ubiquitous component of marine plankton, Crenarchaeota. From these analyses we infer an average sea surface temperature of approximately 15 degrees C for the Arctic Ocean about 70 million years ago. This calibration point implies an Equator-to-pole gradient in sea surface temperatures of approximately 15 degrees C during this interval and, by extrapolation, we suggest that polar waters were generally warmer than 20 degrees C during the middle Cretaceous (approximately 90 million years ago).     

Pervasive alteration of tree communities in undisturbed Amazonian forests

Amazonian rainforests are some of the most species-rich tree communities on earth. Here we show that, over the past two decades, forests in a central Amazonian landscape have experienced highly nonrandom changes in dynamics and composition. Our analyses are based on a network of 18 permanent plots unaffected by any detectable disturbance. Within these plots, rates of tree mortality, recruitment and growth have increased over time. Of 115 relatively abundant tree genera, 27 changed significantly in population density or basal area--a value nearly 14 times greater than that expected by chance. An independent, eight-year study in nearby forests corroborates these shifts in composition. Contrary to recent predictions, we observed no increase in pioneer trees. However, genera of faster-growing trees, including many canopy and emergent species, are increasing in dominance or density, whereas genera of slower-growing trees, including many subcanopy species, are declining. Rising atmospheric CO2 concentrations may explain these changes, although the effects of this and other large-scale environmental alterations remain uncertain. These compositional changes could have important impacts on the carbon storage, dynamics and biota of Amazonian forests.     

Perennial water ice identified in the south polar cap of Mars

The inventory of water and carbon dioxide reservoirs on Mars are important clues for understanding the geological, climatic and potentially exobiological evolution of the planet. From the early mapping observation of the permanent ice caps on the martian poles, the northern cap was believed to be mainly composed of water ice, whereas the southern cap was thought to be constituted of carbon dioxide ice. However, recent missions (NASA missions Mars Global Surveyor and Odyssey) have revealed surface structures, altimetry profiles, underlying buried hydrogen, and temperatures of the south polar regions that are thermodynamically consistent with a mixture of surface water ice and carbon dioxide. Here we present the first direct identification and mapping of both carbon dioxide and water ice in the martian high southern latitudes, at a resolution of 2 km, during the local summer, when the extent of the polar ice is at its minimum. We observe that this south polar cap contains perennial water ice in extended areas: as a small admixture to carbon dioxide in the bright regions; associated with dust, without carbon dioxide, at the edges of this bright cap; and, unexpectedly, in large areas tens of kilometres away from the bright cap.     

Optimal traffic organization in ants under crowded conditions

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.     

Arctic Ocean: hydrothermal activity on Gakkel Ridge

In the hydrothermal circulation at mid-ocean ridges, sea water penetrates the fractured crust, becomes heated by its proximity to the hot magma, and returns to the sea floor as hot fluids enriched in various chemical elements. In contradiction to earlier results that predict diminishing hydrothermal activity with decreasing spreading rate, a survey of the ultra-slowly spreading Gakkel Ridge (Arctic Ocean) by Edmonds et al. and Michael et al. suggests that, instead of being rare, the hydrothermal activity is abundant--exceeding by at least a factor of two to three what would be expected by extrapolation from observation on faster spreading ridges. Here we use helium-3 (3He), a hydrothermal tracer, to show that this abundance of venting sites does not translate, as would be expected, into an anomalous hydrothermal 3He output from the ridge. Because of the wide implications of the submarine hydrothermal processes for mantle heat and mass fluxes to the ocean, these conflicting results call for clarification of the link between hydrothermal activity and crustal production at mid-ocean ridges.