Role and Specificity of LGI4-ADAM22 Interactions in Peripheral Nerve Myelination

In the peripheral nervous system, large caliber axons are ensheathed and myelinated by Schwann cells. Myelin is crucial for a faster signal transduction along the nerve. Hence it is not surprising that defects in this myelination process cause serious neurological disease. Despite the medical importance of these cells, our understanding of the cellular and molecular mechanisms that control Schwann cell development and myelination is still incomplete. Continuous communication between Schwann cells and neurons is essential for the development, differentiation and myelination of peripheral nerves. Previous studies showed that LGI4 is a secreted protein that is crucial for myelination and might be a key player in this communication process. The main aim of this thesis is to elucidate the mechanism of LGI4 function in peripheral nerve myelination and to identify its interaction partners. Chapter 1 of this thesis presents an overview of the different types of cells in the peripheral nervous system with an emphasis on Schwann cell development and myelination

The Probability Distribution Function of Column Density in Molecular Clouds

(Abridged) We discuss the probability distribution function (PDF) of column density resulting from density fields with lognormal PDFs, applicable to isothermal gas (e.g., probably molecular clouds). We suggest that a ``decorrelation length'' can be defined as the distance over which the density auto-correlation function has decayed to, for example, 10% of its zero-lag value, so that the density ``events'' along a line of sight can be assumed to be independent over distances larger than this, and the Central Limit Theorem should be applicable. However, using random realizations of lognormal fields, we show that the convergence to a Gaussian is extremely slow in the high- density tail. Thus, the column density PDF is not expected to exhibit a unique functional shape, but to transit instead from a lognormal to a Gaussian form as the ratio $\eta$ of the column length to the decorrelation length increases. Simultaneously, the PDF's variance decreases. For intermediate values of $\eta$, the column density PDF assumes a nearly exponential decay. We then discuss the density power spectrum and the expected value of $\eta$ in actual molecular clouds. Observationally, our results suggest that $\eta$ may be inferred from the shape and width of the column density PDF in optically-thin-line or extinction studies. Our results should also hold for gas with finite-extent power-law underlying density PDFs, which should be characteristic of the diffuse, non-isothermal neutral medium (temperatures ranging from a few hundred to a few thousand degrees). Finally, we note that for $\eta \gtrsim 100$, the dynamic range in column density is small ($\lesssim$ a factor of 10), but this is only an averaging effect, with no implication on the dynamic range of the underlying density distribution.Comment: 13 pages, 7 figures (10 postscript files). Accepted in ApJ. Eliminated implication that ratio of column length to correlation length necessarily increases with resolution, and thus that 3D simulations are unresolved. Added discussion of dependence of autocorrelation function with parameters of the turbulenc

Interplay between elastic fields due to gravity and a partial dislocation for a hard-sphere crystal coherently grown under gravity: driving force for defect disappearance

We previously observed that an intrinsic staking fault shrunk through a glide of a Shockley partial dislocation terminating its lower end in a hard-sphere crystal under gravity coherently grown in by Monte Carlo simulations [Mori et al., Molec. Phys. 105, 1377 (2007)]; it was an answer to a one-decade long standing question why the stacking disorder in colloidal crystals reduced under gravity [Zhu et al., Nature 387, 883 (1997)]. Here, we present an elastic energy calculation; in addition to the self-energy of the partial dislocation [Mori et al., Prog. Theor. Phys. Suppl. 178, 33 (2009)] we calculate the cross-coupling term between elastic field due to gravity and that due to a Shockley partial dislocation. The cross term is a increasing function of the linear dimension R over which the elastic field expands, showing that a driving force arises for the partial dislocation moving toward the upper boundary of a grain.Comment: 8pages, 4figures, to be published in Molecular Physic

Simulation studies of a phenomenological model for elongated virus capsid formation

We study a phenomenological model in which the simulated packing of hard, attractive spheres on a prolate spheroid surface with convexity constraints produces structures identical to those of prolate virus capsid structures. Our simulation approach combines the traditional Monte Carlo method with a modified method of random sampling on an ellipsoidal surface and a convex hull searching algorithm. Using this approach we identify the minimum physical requirements for non-icosahedral, elongated virus capsids, such as two aberrant flock house virus (FHV) particles and the prolate prohead of bacteriophage $\phi_{29}$, and discuss the implication of our simulation results in the context of recent experimental findings. Our predicted structures may also be experimentally realized by evaporation-driven assembly of colloidal spheres

LGI proteins in the nervous system

The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucinerich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions

Geographical Indication as a vector of regional development and the possibility of its application in the artisanal crystal sector of Vale do Itajaí

In a context marked by the deepening of globalization, geographic dispersion of industrial production and international division of labor, the sector of crystal craft of the Vale of Itajaí in the State of Santa Catarina/ Brazil, has been facing different challenges and looking for new perspectives of competitiveness. The aim of the paper is to address, more specifically, the question of Geographic Indication as a key factor in the strategy of regional development, linking the productive organization and performance in the industrial sector to the socioeconomic situation of the region and its development. To this end, the paper discussed the feasibility of obtaining Geographic Indication and its impacts on restructuring of territories, reorganization of production thru clusters and regional development. Finally, the study pointed out to which extent geographical proximity and territorial economic activity may affect the strategy of competitiveness and international integration of the firms connected with the crystal industry in the regio

Thermal noise properties of two aging materials

In this lecture we review several aspects of the thermal noise properties in two aging materials: a polymer and a colloidal glass. The measurements have been performed after a quench for the polymer and during the transition from a fluid-like to a solid-like state for the gel. Two kind of noise has been measured: the electrical noise and the mechanical noise. For both materials we have observed that the electric noise is characterized by a strong intermittency, which induces a large violation of the Fluctuation Dissipation Theorem (FDT) during the aging time, and may persist for several hours at low frequency. The statistics of these intermittent signals and their dependance on the quench speed for the polymer or on sample concentration for the gel are studied. The results are in a qualitative agreement with recent models of aging, that predict an intermittent dynamics. For the mechanical noise the results are unclear. In the polymer the mechanical thermal noise is still intermittent whereas for the gel the violation of FDT, if it exists, is extremely small.Comment: to be published in the Proceedings of the XIX Sitges Conference on ''Jammming, Yielding and Irreversible Deformation in Condensed Matter'', M.-C.Miguel and M. Rubi eds.,Springer Verlag, Berli

Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model

Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production

Anomalous quantum confined Stark effects in stacked InAs/GaAs self-assembled quantum dots

Vertically stacked and coupled InAs/GaAs self-assembled quantum dots (SADs) are predicted to exhibit a strong non-parabolic dependence of the interband transition energy on the electric field, which is not encountered in single SAD structures nor in other types of quantum structures. Our study based on an eight-band strain-dependent ${\bf k}\cdot{\bf p}$ Hamiltonian indicates that this anomalous quantum confined Stark effect is caused by the three-dimensional strain field distribution which influences drastically the hole states in the stacked SAD structures.Comment: 4 pages, 4 figure

Absence of correlation between built-in electric dipole moment and quantum Stark effect in InAs/GaAs self-assembled quantum dots

We report significant deviations from the usual quadratic dependence of the ground state interband transition energy on applied electric fields in InAs/GaAs self-assembled quantum dots. In particular, we show that conventional second-order perturbation theory fails to correctly describe the Stark shift for electric field below $F = 10$ kV/cm in high dots. Eight-band ${\bf k}\cdot{\bf p}$ calculations demonstrate this effect is predominantly due to the three-dimensional strain field distribution which for various dot shapes and stoichiometric compositions drastically affects the hole ground state. Our conclusions are supported by two independent experiments.Comment: 4 pages, 4 figure