Dwell time of a Brownian interacting molecule in a cellular microdomain

The time spent by an interacting Brownian molecule inside a bounded microdomain has many applications in cellular biology, because the number of bounds is a quantitative signal, which can initiate a cascade of chemical reactions and thus has physiological consequences. In the present article, we propose to estimate the mean time spent by a Brownian molecule inside a microdomain $\Omega$ which contains small holes on the boundary and agonist molecules located inside. We found that the mean time depends on several parameters such as the backward binding rate (with the agonist molecules), the mean escape time from the microdomain and the mean time a molecule reaches the binding sites (forward binding rate). In addition, we estimate the mean and the variance of the number of bounds made by a molecule before it exits $\Omega$. These estimates rely on a boundary layer analysis of a conditional mean first passage time, solution of a singular partial differential equation. In particular, we apply the present results to obtain an estimate of the mean time spent (Dwell time) by a Brownian receptor inside a synaptic domain, when it moves freely by lateral diffusion on the surface of a neuron and interacts locally with scaffolding molecules.Comment: 31 pages, 1 figure. Submitte

Persistent Wnt/β-catenin signaling determines dorsalization of the postnatal subventricular zone and neural Stem cell specification into oligodendrocytes and glutamatergic neurons

In the postnatal and adult central nervous system (CNS), the subventricular zone (SVZ) of the forebrain is the main source of neural stem cells (NSCs) that generate olfactory neurons and oligodendrocytes (OLs), the myelinating cells of the CNS. Here, we provide evidence of a primary role for canonical Wnt/β-catenin signaling in regulating NSC fate along neuronal and oligodendroglial lineages in the postnatal SVZ. Our findings demonstrate that glutamatergic neuronal precursors (NPs) and oligodendrocyte precursors (OPs) are derived strictly from the dorsal SVZ (dSVZ) microdomain under the control of Wnt/β-catenin, whereas GABAergic NPs are derived mainly from the lateral SVZ (lSVZ) microdomain independent of Wnt/β-catenin. Transcript analysis of microdissected SVZ microdomains revealed that canonical Wnt/β-catenin signaling was more pronounced in the dSVZ microdomain. This was confirmed using the β-catenin-activated Wnt-reporter mouse and by pharmacological stimulation of Wnt/β-catenin by infusion of the specific glycogen synthase kinase 3β inhibitor, AR-A014418, which profoundly increased the generation of cycling cells. In vivo genetic/pharmacological stimulation or inhibition of Wnt/β-catenin, respectively, increased and decreased the differentiation of dSVZ-NSCs into glutamatergic NPs, and had a converse effect on GABAergic NPs. Activation of Wnt/β-catenin dramatically stimulated the generation of OPs, but its inhibition had no effect, indicating other factors act in concert with Wnt/β-catenin to fine tune oligodendrogliogenesis in the postnatal dSVZ. These results demonstrate a role for Wnt/β-catenin signaling within the dorsal microdomain of the postnatal SVZ, in regulating the genesis of glutamatergic neurons and OLs

Unfolding Rates for the Diffusion-Collision Model

In the diffusion-collision model, the unfolding rates are given by the likelihood of secondary structural cluster dissociation. In this work, we introduce an unfolding rate calculation for proteins whose secondary structural elements are $\alpha$-helices, modeled from thermal escape over a barrier which arises from the free energy in buried hydrophobic residues. Our results are in good agreement with currently accepted values for the attempt rate.Comment: Shorter version of cond-mat/0011024 accepted for publication in PR

Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation.

Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft-localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways

Pyrochlore microdomain formation in fluorite oxides

The pyrochlore microdomain formation in the fluorite lattice was investigated by means of electron microscope techniques, especially for the system (TbxGd1−x)2 Zr2O7+y (0 x 1; 0 y < 0.25). Specimens with x> 0.2 or specimens with x 0.2 which were quenched from temperatures above the order-disorder transition temperature show diffuse scattering in the electron diffraction images, remarkably similar to diffuse scattering observed for other defect fluorite oxides. The diffuse scattering is discussed in terms of the formation of a small basic cluster in the fluorite lattice. Annealed specimens with x 0.2 show pyrochlore diffraction spots and microdomain formation. The domains have an average diameter ranging from a value smaller than 10 nm for x = 0.2 up to 100 nm for Gd2Zr2O7. The domains grow in a disordered (fluorite) matrix and finally form antiphase boundaries. The transition from the basic cluster to a well-developed microdomain is not yet clear. The observed microdomain structure is used to explain the results of oxygen ion conductivity experiments

Electric-field-induced phase transition of <001> oriented Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystals

oriented 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 single crystals were poled under different electric fields, i.e. Epoling=4 kV/cm and Epoling=13 kV/cm. In addition to the temperature-dependent dielectric constant measurement, X-ray diffraction was also used to identify the poling-induced phase transitions. Results showed that the phase transition significantly depends on the poling intensity. A weaker field (Epoling=4 kV/cm) can overcome the effect of random internal field to perform the phase transition from rhombohedral ferroelectric state with short range ordering (microdomain) FESRO to rhombohedral ferroelectric state with long range ordering (macrodomain) FElRO. But the rhombohedral ferroelectric to tetragonal ferroelectric phase transition originating from to polarization rotation can only be induced by a stronger field (Epoling=13 kV/cm). The sample poled at Epoling=4 kV/cm showed higher piezoelectric constant, d33>1500 pC/N, than the sample poled at Epoling=13 kV/cm.Comment: 7 pages, 2 figure

Acoustical properties of double porosity granular materials

Granular materials have been conventionally used for acoustic treatment due to their sound absorptive and sound insulating properties. An emerging field is the study of the acoustical properties of multiscale porous materials. An example of these is a granular material in which the particles are porous. In this paper, analytical and hybrid analytical-numerical models describing the acoustical properties of these materials are introduced. Image processing techniques have been employed to estimate characteristic dimensions of the materials. The model predictions are compared with measurements on expanded perlite and activated carbon showing satisfactory agreement. It is concluded that a double porosity granular material exhibits greater low-frequency sound absorption at reduced weight compared to a solid-grain granular material with similar mesoscopic characteristics