Role for TGF-beta superfamily signaling in telencephalic GABAergic neuron development.

Signaling mechanisms mediated by the Transforming Growth Factor-beta (TGF-beta) superfamily regulate a variety of developmental processes. Here we show that components of both bone morphogenetic protein/growth differentiation factor and TGF-beta/activin/Nodal branches of TGF-beta superfamily signaling are expressed in the developing subpallium. Furthermore, Smad proteins, transcriptional effectors of TGF-beta signaling, are co-expressed and physically interact in the basal ganglia with Dlx homeodomain transcription factors, which are critical regulators of the differentiation, migration and survival of telencephalic GABAergic neurons. We also show that Dlx and Smad proteins localize to promoters/enhancers of a number of common telencephalic genes in vivo and that Smad proteins co-activate transcription with Dlx family members, except with certain mutated human DLX proteins identified in autistic individuals. In agreement with these observations, expression of dominant-negative Smads in the developing basal ganglia phenocopies the cell migration defects observed in Dlx1/2-deficient mice. Together, these results suggest that TGF-beta superfamily signaling plays a role in telencephalic GABAergic neuron development through functional interactions with Dlx transcription factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-009-9035-6) contains supplementary material, which is available to authorized users

A Modification and Analysis of Lagrangian Trajectory Modeling and Granular Dynamics of Lunar Dust Particles

A previously developed mathematical model is amended to more accurately incorporate the effects of lift and drag on single dust particles in order to predict their behavior in the wake of high velocity gas flow. The model utilizes output from a CFD or DSMC simulation of exhaust from a rocket nozzle hot gas jet. An extension of the Saffman equation for lift based on the research of McLaughlin (1991) and Mei (1992) is used, while an equation for the Magnus force modeled after the work of Oesterle (1994) and Tsuji et al (1985) is applied. A relationship for drag utilizing a particle shape factor (phi = 0.8) is taken from the work of Haider and Levenspiel (1989) for application to non-spherical particle dynamics. The drag equation is further adjusted to account for rarefaction and compressibility effects in rarefied and high Mach number flows according to the work of Davies (1945) and Loth (2007) respectively. Simulations using a more accurate model with the correction factor (Epsilon = 0.8 in a 20% particle concentration gas flow) given by Richardson and Zaki (1954) and Rowe (1961) show that particles have lower ejection angles than those that were previously calculated. This is more prevalent in smaller particles, which are shown through velocity and trajectory comparison to be more influenced by the flow of the surrounding gas. It is shown that particles are more affected by minor changes to drag forces than larger adjustments to lift forces, demanding a closer analysis of the shape and behavior of lunar dust particles and the composition of the surrounding gas flow

Photogrammetry and ballistic analysis of a high-flying projectile in the STS-124 space shuttle launch

A method combining photogrammetry with ballistic analysis is demonstrated to identify flying debris in a rocket launch environment. Debris traveling near the STS-124 Space Shuttle was captured on cameras viewing the launch pad within the first few seconds after launch. One particular piece of debris caught the attention of investigators studying the release of flame trench fire bricks because its high trajectory could indicate a flight risk to the Space Shuttle. Digitized images from two pad perimeter high-speed 16-mm film cameras were processed using photogrammetry software based on a multi-parameter optimization technique. Reference points in the image were found from 3D CAD models of the launch pad and from surveyed points on the pad. The three-dimensional reference points were matched to the equivalent two-dimensional camera projections by optimizing the camera model parameters using a gradient search optimization technique. Using this method of solving the triangulation problem, the xyz position of the object's path relative to the reference point coordinate system was found for every set of synchronized images. This trajectory was then compared to a predicted trajectory while performing regression analysis on the ballistic coefficient and other parameters. This identified, with a high degree of confidence, the object's material density and thus its probable origin within the launch pad environment. Future extensions of this methodology may make it possible to diagnose the underlying causes of debris-releasing events in near-real time, thus improving flight safety.Comment: 26 pages, 11 figures, 3 table

FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development

<p>Abstract</p> <p>Background</p> <p>Growth, differentiation and regional specification of telencephalic domains, such as the cerebral cortex, are regulated by the interplay of secreted proteins produced by patterning centers and signal transduction systems deployed in the surrounding neuroepithelium. Among other signaling molecules, members of the fibroblast growth factor (FGF) family have a prominent role in regulating growth, differentiation and regional specification. In the mouse telencephalon the rostral patterning center expresses members of the <it>Fgf </it>family (<it>Fgf8</it>, <it>Fgf15</it>, <it>Fgf17</it>, <it>Fgf18</it>). FGF8 and FGF17 signaling have major roles in specification and morphogenesis of the rostroventral telencephalon, whereas the functions of FGF15 and FGF18 in the rostral patterning center have not been established.</p> <p>Results</p> <p>Using <it>Fgf15</it>^-/-mutant mice, we provide evidence that FGF15 suppresses proliferation, and that it promotes differentiation, expression of <it>CoupTF1 </it>and caudoventral fate; thus, reducing <it>Fgf15 </it>and <it>Fgf8 </it>dosage have opposite effects. Furthermore, we show that FGF15 and FGF8 differentially phosphorylate ERK (p42/44), AKT and S6 in cultures of embryonic cortex. Finally, we show that FGF15 inhibits proliferation in cortical cultures.</p> <p>Conclusion</p> <p>FGF15 and FGF8 have distinct signaling properties, and opposite effects on neocortical patterning and differentiation; FGF15 promotes <it>CoupTF1 </it>expression, represses proliferation and promotes neural differentiation.</p

A human antibody against Zika virus crosslinks the E protein to prevent infection

The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes

Return to drug use and overdose after release from prison: a qualitative study of risk and protective factors

BACKGROUND: Former inmates are at high risk for death from drug overdose, especially in the immediate post-release period. The purpose of the study is to understand the drug use experiences, perceptions of overdose risk, and experiences with overdose among former prisoners. METHODS: This qualitative study included former prison inmates (N = 29) who were recruited within two months after their release. Interviewers conducted in-person, semi-structured interviews which explored participants' experiences and perceptions. Transcripts were analyzed utilizing a team-based method of inductive analysis. RESULTS: The following themes emerged: 1) Relapse to drugs and alcohol occurred in a context of poor social support, medical co-morbidity and inadequate economic resources; 2) former inmates experienced ubiquitous exposure to drugs in their living environments; 3) intentional overdose was considered "a way out" given situational stressors, and accidental overdose was perceived as related to decreased tolerance; and 4) protective factors included structured drug treatment programs, spirituality/religion, community-based resources (including self-help groups), and family. CONCLUSIONS: Former inmates return to environments that strongly trigger relapse to drug use and put them at risk for overdose. Interventions to prevent overdose after release from prison may benefit from including structured treatment with gradual transition to the community, enhanced protective factors, and reductions of environmental triggers to use drugs

Multi-scale assembly of hydrogels formed by highly branched arabinoxylans from Plantago ovata seed mucilage studied by USANS/SANS and rheology

© 2018 Elsevier Ltd The structures of two hydrogels formed by purified brush-like polysaccharides from Plantago ovata seed mucilage have been characterised from the nanometre to micrometre scale by using a combination of SANS and USANS techniques. These two hydrogels have distinctly different melting and rheological properties, but the structure of their gel networks bears striking similarity as revealed by USANS/SANS experiments. Surprisingly, we find that the dramatic changes in the rheological properties induced by temperature or change in the solvent quality are accompanied by a small alteration of the network structure as inferred from scattering curves recorded above melting or in a chaotropic solvent (0.7 M KOD). These results suggest that, in contrast to most gel-forming polysaccharides for which gelation depends on a structural transition, the rheological properties of Plantago ovata mucilage gels are dependent on variations in intermolecular hydrogen bonding. By enzymatically cleaving off terminal arabinose residues from the side chains, we have demonstrated that composition of side-chains has a strong effect on intermolecular interactions, which, in turn, has a profound effect on rheological and structural properties of these unique polysaccharides

Frequency Tracking and Parameter Estimation for Robust Quantum State-Estimation

In this paper we consider the problem of tracking the state of a quantum system via a continuous measurement. If the system Hamiltonian is known precisely, this merely requires integrating the appropriate stochastic master equation. However, even a small error in the assumed Hamiltonian can render this approach useless. The natural answer to this problem is to include the parameters of the Hamiltonian as part of the estimation problem, and the full Bayesian solution to this task provides a state-estimate that is robust against uncertainties. However, this approach requires considerable computational overhead. Here we consider a single qubit in which the Hamiltonian contains a single unknown parameter. We show that classical frequency estimation techniques greatly reduce the computational overhead associated with Bayesian estimation and provide accurate estimates for the qubit frequencyComment: 6 figures, 13 page