Doublecortin Microtubule Affinity Is Regulated by a Balance of Kinase and Phosphatase Activity at the Leading Edge of Migrating Neurons

AbstractDoublecortin (Dcx) is a microtubule-associated protein that is mutated in X-linked lissencephaly (X-LIS), a neuronal migration disorder associated with epilepsy and mental retardation. Although Dcx can bind ubiquitously to microtubules in nonneuronal cells, Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons. We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases. In addition to a consensus MARK site, we identified a serine within a novel sequence that is crucial for the PKA- and MARK-dependent regulation of Dcx's microtubule binding activity in vitro. This serine is mutated in two families affected by X-LIS. Immunostaining neurons with an antibody that recognizes phosphorylated substrates of MARK supports the conclusion that Dcx localization and function are regulated at the leading edge of migrating cells by a balance of kinase and phosphatase activity

Modeling the Transport and Deposition of ¹⁰Be Produced by the Strongest Solar Proton Event During the Holocene

Prominent excursions in the number of cosmogenic nuclides (e.g., ¹⁰Be) around 774 CE/775 document the most severe solar proton event (SPE) throughout the Holocene. Its manifestation in ice cores is valuable for geochronology, but also for solar-terrestrial physics and climate modeling. Using the ECHAM/MESSy Atmospheric Chemistry (EMAC) climate model in combination with the Warning System for Aviation Exposure to SEP (WASAVIES), we investigate the transport, mixing, and deposition of the cosmogenic nuclide ¹⁰Be produced by the 774 CE/775 SPE. By comparing the model results to the reconstructed ¹⁰Be time series from four ice core records, we study the atmospheric pathways of ¹⁰Be from its stratospheric source to its sink at Earth's surface. The reconstructed post-SPE evolution of the ¹⁰Be surface fluxes at the ice core sites is well captured by the model. The downward transport of the ¹⁰Be atoms is controlled by the Brewer-Dobson circulation in the stratosphere and cross-tropopause transport via tropopause folds or large-scale sinking. Clear hemispheric differences in the transport and deposition processes are identified. In both polar regions the ¹⁰Be surface fluxes peak in summertime, with a larger influence of wet deposition on the seasonal ¹⁰Be surface flux in Greenland than in Antarctica. Differences in the peak ¹⁰Be surface flux following the 774 CE/775 SPE at the drilling sites are explained by specific meteorological conditions depending on the geographic locations of the sites

Decoupling in an expanding universe: boundary RG-flow affects initial conditions for inflation

We study decoupling in FRW spacetimes, emphasizing a Lagrangian description throughout. To account for the vacuum choice ambiguity in cosmological settings, we introduce an arbitrary boundary action representing the initial conditions. RG flow in these spacetimes naturally affects the boundary interactions. As a consequence the boundary conditions are sensitive to high-energy physics through irrelevant terms in the boundary action. Using scalar field theory as an example, we derive the leading dimension four irrelevant boundary operators. We discuss how the known vacuum choices, e.g. the Bunch-Davies vacuum, appear in the Lagrangian description and square with decoupling. For all choices of boundary conditions encoded by relevant boundary operators, of which the known ones are a subset, backreaction is under control. All, moreover, will generically feel the influence of high-energy physics through irrelevant (dimension four) boundary corrections. Having established a coherent effective field theory framework including the vacuum choice ambiguity, we derive an explicit expression for the power spectrum of inflationary density perturbations including the leading high energy corrections. In accordance with the dimensionality of the leading irrelevant operators, the effect of high energy physics is linearly proportional to the Hubble radius H and the scale of new physics L= 1/M.Comment: LaTeX plus axodraw figures. v2: minor corrections; refs added. JHEP style: 34 pages + 18 pages appendi

Deformation independent open brane metrics and generalized theta parameters

We investigate the consequences of generalizing certain well established properties of the open string metric to the conjectured open membrane and open Dp-brane metrics. By imposing deformation independence on these metrics their functional dependence on the background fields can be determined including the notorious conformal factor. In analogy with the non-commutativity parameter $\Theta^{\mu\nu}$ in the string case, we also obtain `generalized' theta parameters which are rank q+1 antisymmetric tensors (polyvectors) for open Dq-branes and rank 3 for the open membrane case. The expressions we obtain for the open membrane quantities are expected to be valid for general background field configurations, while the open D-brane quantities are only valid for one parameter deformations. By reducing the open membrane data to five dimensions, we show that they, modulo a subtlety with implications for the relation between OM-theory and NCYM, correctly generate the open string and open D2-data.Comment: 24 pages, LaTe

On isovector meson exchange currents in the Bethe-Salpeter approach

We investigate the nonrelativistic reduction of the Bethe-Salpeter amplitude for the deuteron electrodisintegration near threshold energies. To this end, two assumptions have been used in the calculations: 1) the static approximation and 2) the one iteration approximation. Within these assumptions it is possible to recover the nonrelativistic result including a systematic extension to relativistic corrections. We find that the so-called pair current term can be constructed from the $P$-wave contribution of the deuteron Bethe-Salpeter amplitude. The form factor that enters into the calculation of the pair current is constrained by the manifestly gauge independent matrix elements.Comment: 15 pages, incl. 3 figures, to be published Phys. Rev.

Residential mobility and local housing-market differences

The authors extend previous literature on variations in mobility rates across local housing markets by examining the linkage of mobility rates at the household level to the structure of local housing markets. The results suggest that residential mobility rates differ widely across local housing markets, substantiating the view that residential relocation is intimately intertwined with conditions at the local level. Local housing-market conditions also have different effects on mobility rates for renters and owner-occupiers. The results suggest that variation in residential mobility rates across housing markets can be in part explained by level of urbanization, the tenure structure, the degree of government intervention, and the size of the housing market. Remarkably, these differences in local housing markets cannot be seen to be related to housing-market features only. The results suggest that these differences can also be attributed to the behavior or attitude of households with respect to housing

Covariant description of inelastic electron--deuteron scattering:predictions of the relativistic impulse approximation

Using the covariant spectator theory and the transversity formalism, the unpolarized, coincidence cross section for deuteron electrodisintegration, $d(e,e'p)n$, is studied. The relativistic kinematics are reviewed, and simple theoretical formulae for the relativistic impulse approximation (RIA) are derived and discussed. Numerical predictions for the scattering in the high $Q^2$ region obtained from the RIA and five other approximations are presented and compared. We conclude that measurements of the unpolarized coincidence cross section and the asymmetry $A_\phi$, to an accuracy that will distinguish between different theoretical models, is feasible over most of the wide kinematic range accessible at Jefferson Lab.Comment: 54 pages and 24 figure