Illusory vowels in Spanish-English sequential bilinguals: Evidence that accurate L2 perception is neither necessary nor sufficient for accurate L2 production

Spanish native speakers are known to pronounce onset /sC/ clusters in English with a prothetic vowel, as in esport for sport, due to their native language phonotactic constraints. We assessed whether accurate production of e.g. spi instead of espi was related to accurate perceptual discrimination of this contrast in second language (L2) speech of Spanish–English sequential bilinguals. A same–different discrimination task in stimulus pairs such as spi–espi assessed speech perception and a phonemic verbal fluency task elicited speech production. Logistic mixed model regressions revealed significant differences in accuracy between the bilinguals and the English monolinguals, although some bilinguals performed within the monolingual range. For the production task, but not for the perception task, bilinguals with more exposure to English and greater grammatical knowledge of English performed significantly more accurately than those with less exposure and lower grammatical knowledge. There was no significant correlation between production accuracy and perception accuracy. Through examining phonotactic constraints, these results expand a growing body of research into single sounds which suggests dissociations between L2 perception and production. In contrast to predictions made by L2 speech models, the findings indicate that accurate L2 perception is neither necessary nor sufficient for accurate L2 production, and instead are interpreted to indicate that the two capacities recruit different executive control mechanisms and are acquired – at least to a certain extent – independently in L2 acquisition.Peer Reviewe

Many-particle Brownian and Langevin Dynamics Simulations with the Brownmove package

<p>Abstract</p> <p>Background</p> <p>Brownian Dynamics (BD) is a coarse-grained implicit-solvent simulation method that is routinely used to investigate binary protein association dynamics, but due to its efficiency in handling large simulation volumes and particle numbers it is well suited to also describe many-protein scenarios as they often occur in biological cells.</p> <p>Results</p> <p>Here we introduce our "brownmove" simulation package which was designed to handle many-particle problems with varying particle numbers and allows for a very flexible definition of rigid and flexible protein and polymer models. Both a Brownian and a Langevin dynamics (LD) propagation scheme can be used and hydrodynamic interactions are treated efficiently with our recently introduced TEA-HI ansatz [Geyer, Winter, JCP 130 (2009) 114905]. With simulations of constrained polymers and flexible models of spherical proteins we demonstrate that it is crucial to include hydrodynamics when multi-bead models are used in BD or LD simulations. Only then both the translational and the rotational diffusion coefficients and the timescales of the internal dynamics can be reproduced correctly. In the third example project we show how constant density boundary conditions [Geyer et al, JCP 120 (2004) 4573] can be used to set up a non-equilibrium simulation of diffusional transport across an array of fixed obstacles. Finally, we demonstrate how the agglomeration dynamics of multiple particles with attractive patches can be analysed conveniently with the help of a dynamic interaction network.</p> <p>Conclusions</p> <p>Combining BD and LD propagation, fast hydrodynamics, a flexible protein model, and interfaces for "open" simulation settings, our freely available "brownmove" simulation package constitutes a new platform for coarse-grained many-particle simulations of biologically relevant diffusion and transport processes.</p

Intrinsically determined cell death of developing cortical interneurons

Cortical inhibitory circuits are formed by GABAergic interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis1-5, is that cortical interneurons are overproduced, and then following their migration into cortex, excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we have characterized the developmental cell death of mouse cortical interneurons in vivo, in vitro, and following transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax- (Bcl-2 associated X-) dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Remarkably, over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by central nervous system (CNS) neurons6-8. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Together, our findings indicate that interneuron cell death is intrinsically determined, either cell-autonomously, or through a population-autonomous competition for survival signals derived from other interneurons

Diffusion in crowded biological environments: applications of Brownian dynamics

Biochemical reactions in living systems occur in complex, heterogeneous media with total concentrations of macromolecules in the range of 50 - 400 mgml. Molecular species occupy a significant fraction of the immersing medium, up to 40% of volume. Such complex and volume-occupied environments are generally termed 'crowded' and/or 'confined'. In crowded conditions non-specific interactions between macromolecules may hinder diffusion - a major process determining metabolism, transport, and signaling. Also, the crowded media can alter, both qualitatively and quantitatively, the reactions in vivo in comparison with their in vitro counterparts. This review focuses on recent developments in particle-based Brownian dynamics algorithms, their applications to model diffusive transport in crowded systems, and their abilities to reproduce and predict the behavior of macromolecules under in vivo conditions

Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations

Solution model of the intrinsically disordered polyglutamine tract-binding protein-1

AbstractPolyglutamine tract-binding protein-1 (PQBP-1) is a 265-residue nuclear protein that is involved in transcriptional regulation. In addition to its role in the molecular pathology of the polyglutamine expansion diseases, mutations of the protein are associated with X-linked mental retardation. PQBP-1 binds specifically to glutamine repeat sequences and proline-rich regions, and interacts with RNA polymerase II and the spliceosomal protein U5-15kD. In this work, we obtained a biophysical characterization of this protein by employing complementary structural methods. PQBP-1 is shown to be a moderately compact but largely disordered molecule with an elongated shape, having a Stokes radius of 3.7 nm and a maximum molecular dimension of 13 nm. The protein is monomeric in solution, has residual β-structure, and is in a premolten globule state that is unaffected by natural osmolytes. Using small-angle x-ray scattering data, we were able to generate a low-resolution, three-dimensional model of PQBP-1

Solution Model of the Intrinsically Disordered Polyglutamine Tract-Binding Protein-1

Polyglutamine tract-binding protein-1 (PQBP-1) is a 265-residue nuclear protein that is involved in transcriptional regulation. In addition to its role in the molecular pathology of the polyglutamine expansion diseases, mutations of the protein are associated with X-linked mental retardation. PQBP-1 binds specifically to glutamine repeat sequences and proline-rich regions, and interacts with RNA polymerase II and the spliceosomal protein U5-15kD. In this work, we obtained a biophysical characterization of this protein by employing complementary structural methods. PQBP-1 is shown to be a moderately compact but largely disordered molecule with an elongated shape, having a Stokes radius of 3.7 nm and a maximum molecular dimension of 13 nm. The protein is monomeric in solution, has residual β-structure, and is in a premolten globule state that is unaffected by natural osmolytes. Using small-angle x-ray scattering data, we were able to generate a low-resolution, three-dimensional model of PQBP-1