When it Pays to Rush: Interpreting Morphogen Gradients Prior to Steady-State

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state.Comment: 18 pages, 3 figure

5d-5f Electric-multipole Transitions in Uranium Dioxide Probed by Non-resonant Inelastic X-ray Scattering

Non-resonant inelastic x ray scattering (NIXS) experiments have been performed to probe the 5d-5f electronic transitions at the uranium O(4,5) absorption edges in uranium dioxide. For small values of the scattering vector q, the spectra are dominated by dipole-allowed transitions encapsulated within the giant resonance, whereas for higher values of q the multipolar transitions of rank 3 and 5 give rise to strong and well-defined multiplet structure in the pre-edge region. The origin of the observed non-dipole multiplet structures is explained on the basis of many-electron atomic spectral calculations. The results obtained demonstrate the high potential of NIXS as a bulk-sensitive technique for the characterization of the electronic properties of actinide materials.Comment: Submitted to Physical Review Letters on 31 December 200

Robust formation of morphogen gradients

We discuss the formation of graded morphogen profiles in a cell layer by nonlinear transport phenomena, important for patterning developing organisms. We focus on a process termed transcytosis, where morphogen transport results from binding of ligands to receptors on the cell surface, incorporation into the cell and subsequent externalization. Starting from a microscopic model, we derive effective transport equations. We show that, in contrast to morphogen transport by extracellular diffusion, transcytosis leads to robust ligand profiles which are insensitive to the rate of ligand production

Missing Heritability in the Tails of Quantitative Traits? A Simulation Study on the Impact of Slightly Altered True Genetic Models

Objective: Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in a bimodal mixture situation on the power to detect associations. Methods: We performed simulations of quantitative phenotypes analysed by standard linear regression and dichotomized case-control data sets from the extremes of the quantitative trait analysed by standard logistic regression. Results: Using linear regression, markers with an effect in the extremes of the traits were almost undetectable, whereas analysing extremes by case-control design had superior power even for much smaller sample sizes. Two real data examples are provided to support our theoretical findings and to explore our mixture and parameter assumption. Conclusions: Our findings support the idea to re-analyse the available meta-analysis data sets to detect new loci in the extremes. Moreover, our investigation offers an explanation for discrepant findings when analysing quantitative traits in the general population and in the extremes. Copyright (C) 2011 S. Karger AG, Base

Well-posedness and asymptotic behavior of a multidimensional model of morphogen transport

Morphogen transport is a biological process, occurring in the tissue of living organisms, which is a determining step in cell differentiation. We present rigorous analysis of a simple model of this process, which is a system coupling parabolic PDE with ODE. We prove existence and uniqueness of solutions for both stationary and evolution problems. Moreover we show that the solution converges exponentially to the equilibrium in $C^1\times C^0$ topology. We prove all results for arbitrary dimension of the domain. Our results improve significantly previously known results for the same model in the case of one dimensional domain

Effective Confinement as Origin of the Equivalence of Kinetic Temperature and Fluctuation-Dissipation Ratio in a Dense Shear Driven Suspension

We study response and velocity autocorrelation functions for a tagged particle in a shear driven suspension governed by underdamped stochastic dynamics. We follow the idea of an effective confinement in dense suspensions and exploit a time-scale separation between particle reorganization and vibrational motion. This allows us to approximately derive the fluctuation-dissipation theorem in a "hybrid" form involving the kinetic temperature as an effective temperature and an additive correction term. We show numerically that even in a moderately dense suspension the latter is negligible. We discuss similarities and differences with a simple toy model, a single trapped particle in shear flow

Magnetic Excitations in NpCoGa5

We report the results of inelastic neutron scattering experiments on NpCoGa$_{5}$, an isostructural analogue of the PuCoGa$_{5}$ superconductor. Two energy scales characterize the magnetic response in the antiferromagnetic phase. One is related to a non-dispersive excitation between two crystal field levels. The other at lower energies corresponds to dispersive fluctuations emanating from the magnetic zone center. The fluctuations persist in the paramagnetic phase also, although weaker in intensity. This supports the possibility that magnetic fluctuations are present in PuCoGa$_{5}$, where unconventional d-wave superconductivity is achieved in the absence of magnetic order.Comment: 4 pages, 5 figure