Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration

Coordinated migration of neurons in the developing and adult brain is essential for its proper function. The secreted glycoprotein Reelin (also known as RELN) guides migration of neurons by binding to two lipoprotein receptors, the very-low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2, also known as LRP8). Loss of Reelin function in humans results in the severe developmental disorder lissencephaly and it has also been associated with other neurological disorders such as epilepsy, schizophrenia and Alzheimer's disease. The molecular mechanisms by which Reelin activates its receptors and controls cellular functions are largely unknown. Here we show that the neuronal guidance cues ephrin B proteins are essential for Reelin signalling during the development of laminated structures in the brain. We show that ephrin Bs genetically interact with Reelin. Notably, compound mouse mutants (Reln(+/-); Efnb3(-/-) or Reln(+/-); Efnb2(-/-)) and triple ephrin B1, B2, B3 knockouts show neuronal migration defects that recapitulate the ones observed in the neocortex, hippocampus and cerebellum of the reeler mouse. Mechanistically, we show that Reelin binds to the extracellular domain of ephrin Bs, which associate at the membrane with VLDLR and ApoER2 in neurons. Clustering of ephrin Bs leads to the recruitment and phosphorylation of Dab1 which is necessary for Reelin signalling. Conversely, loss of function of ephrin Bs severely impairs Reelin-induced Dab1 phosphorylation. Importantly, activation of ephrin Bs can rescue the reeler neuronal migration defects in the absence of Reelin protein. Together, our results identify ephrin Bs as essential components of the Reelin receptor/signalling pathway to control neuronal migration during the development of the nervous system.     

Linking mantle plumes, large igneous provinces and environmental catastrophes

Large igneous provinces (LIPs) are known for their rapid production of enormous volumes of magma (up to several million cubic kilometres in less than a million years), for marked thinning of the lithosphere, often ending with a continental break-up, and for their links to global environmental catastrophes. Despite the importance of LIPs, controversy surrounds even the basic idea that they form through melting in the heads of thermal mantle plumes. The Permo-Triassic Siberian Traps--the type example and the largest continental LIP--is located on thick cratonic lithosphere and was synchronous with the largest known mass-extinction event. However, there is no evidence of pre-magmatic uplift or of a large lithospheric stretching, as predicted above a plume head. Moreover, estimates of magmatic CO(2) degassing from the Siberian Traps are considered insufficient to trigger climatic crises, leading to the hypothesis that the release of thermogenic gases from the sediment pile caused the mass extinction. Here we present petrological evidence for a large amount (15?wt%) of dense recycled oceanic crust in the head of the plume and develop a thermomechanical model that predicts no pre-magmatic uplift and requires no lithospheric extension. The model implies extensive plume melting and heterogeneous erosion of the thick cratonic lithosphere over the course of a few hundred thousand years. The model suggests that massive degassing of CO(2) and HCl, mostly from the recycled crust in the plume head, could alone trigger a mass extinction and predicts it happening before the main volcanic phase, in agreement with stratigraphic and geochronological data for the Siberian Traps and other LIPs.     

A massive protocluster of galaxies at a redshift of z ≈ 5.3

Massive clusters of galaxies have been found that date from as early as 3.9 billion years (3.9 Gyr; z = 1.62) after the Big Bang, containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter model predict that these systems should descend from 'protoclusters'-early overdensities of massive galaxies that merge hierarchically to form a cluster. These protocluster regions themselves are built up hierarchically and so are expected to contain extremely massive galaxies that can be observed as luminous quasars and starbursts. Observational evidence for this picture, however, is sparse because high-redshift protoclusters are rare and difficult to observe. Here we report a protocluster region that dates from 1 Gyr (z = 5.3) after the Big Bang. This cluster of massive galaxies extends over more than 13 megaparsecs and contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of more than 4 × 10(11) solar masses of dark and luminous matter in this region, consistent with that expected from cosmological simulations for the earliest galaxy clusters.     

Stable isotopes of lithium: dissimilar biochemical and behavioral effects

Summary Lithium, which is used routinely in the treatment of mania, is composed of two stable isotopes, lithium-7 (92.58%) and lithium-6 (7.42%). Usually there is minimal physiological or biochemical differentiation between isotopes of an element, but lithium is an exception. Data derived from a variety of biochemical and behavioral experiments are reviewed to support this idea. Additionally, the clinical implications of this work are presented.     

The reactivity of anti-peptide antibodies is a function of the atomic mobility of sites in a protein

To study the nature of antigenic recognition, antibodies have been prepared against a set of peptide sequences representing both highly mobile and well-ordered regions of myohaemerythrin, based on X-ray crystallographic temperature factors. Anti-peptide antibodies against highly mobile regions react strongly with the native protein; anti-peptide antibodies from well-ordered regions do not. Mobility is a major factor in the recognition of the native protein by anti-peptide antibodies; this may be of general significance in protein-protein interactions.     

Eine Fehlinterpretation mit Folgen: Albert Einstein und der Welle-Teilchen Dualismus

Ohne Zusammenfassung Vorgelegt von M. J. Klein     

不同粉粒体积分率下超声速气粉流的理论研究

根据拉伐尔喷嘴中气粉流的数学模型，并采用威布尔分布作为粒径分布，在不同粉粒体积分率下，对喷嘴中气粉流的行为作了数值计算，计算结果表明，在亚声速区中，气流参数不随粉粒体积分率的变化而变化；在超声速区中，气体速度随粉粒体积分率的减小而增大，而气体温度则随粉粒体积分率的增大而升高。     

Planning to Plan-Integrating Control Flow

In many planning situations, computation itself becomes a resource to be planned and scheduled.We model such computational resources as conventional resources which are used by control-flow actions,e.g., to direct the planning process. Control-flow actions and conventional actions are planned/scheduled in an integrated way and can interact with each other. Control-flow actions are then executed by the planning engine itself. The approach is illustrated by examples, e. g., for hierarchical planning, in which tasks that are temporally still far away impose only rough constraints on the current schedule, and control-flow tasks ensure that these tasks are refined as they approach the current time. Using the same mechanism, anytime algorithms can change appropriate search methods or parameters over time, and problems like scheduling critical time-outs for garbage collection can be made part of the planning itself.