Effect of activation of canonical Wnt signaling by the Wnt-3a protein on the susceptibility of PC12 cells to oxidative and apoptotic insults

Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid β-peptide (Aβ25-35; 50 µM). Cells (1 x 10(6) cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer’s and Huntington’s diseases.

Nonnulla momenta controversiae illustris: an recentioribus vel antiquioribus palma eruditionis sit tribuenda

Invokaatio: Inceptis Jesu adesto.

Canonical syllable reduplication in infants with sensorineural hearing loss. 'Reduplicación y mezcla de sílabas balbuceadas en niños con hipoacusia'.

Resumen en español. Resumen basado en el de la publicación

Wnt6 controls amniote neural crest induction through the non-canonical signaling pathway

The neural crest is a multipotent embryonic cell population that arises from neural ectoderm and forms derivatives essential for vertebrate function. Neural crest induction requires an ectodermal signal, thought to be a Writ ligand, but the identity of the Wnt that performs this function in amniotes is unknown. Here, we demonstrate that Wnt6, derived from the ectoderm, is necessary for chick neural crest induction. Crucially, we also show that Wnt6 acts through the non-canonical pathway and not the beta-catenin-dependant pathway. Surprisingly, we found that canonical Wnt signaling inhibited neural crest production in the chick embryo. In light of studies in anamniotes demonstrating that canonical Wnt signaling induces neural crest, these results indicate a significant and novel change in the mechanism of neural crest induction during vertebrate evolution. These data also highlight a key role for noncanonical Wnt signaling in cell type specification from a stem population during development.

Canonical description of the perspective projections

A unique parameterization of the perspective projections in all whole-numbered dimensions is reported. The algorithm for generating a perspective transformation from parameters and for recovering parameters from a transformation is a modification of the Givens orthogonalization algorithm. The algorithm for recovering a perspective transformation from a perspective projection is a modification of Roberts' classical algorithm. Both algorithms have been implemented in Pop-11 with call-out to the NAG Fortran libraries. Preliminary monte-carlo tests show that the transformation algorithm is highly accurate, but that the projection algorithm cannot recover magnitude and shear parameters accurately. However, there is reason to believe that the projection algorithm might improve significantly with the use of many corresponding points, or with multiple perspective views of an object. Previous parameterizations of the perspective transformations in the computer graphics and computer vision literature are discussed.

Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration

Satellite cells represent the stem cell population of adult skeletal muscle. The molecular mechanisms that control the proliferation of satellite cells are not well understood. In this study, we show that in response to injury, myofibres activate Wnt ligand transcription and activate a reporter cell line that is sensitive to the canonical Wnt-signalling pathway. Activated satellite cells on isolated cultured myofibres show robust expression of activated-β-catenin (Act-β-Cat), a key downstream transcriptional coactivator of canonical Wnt signalling. We provide evidence that the Wnt family of secreted glycoproteins act on satellite cells in a ligand-specific manner. Overexpression of Wnt1, Wnt3a or Wnt5a protein causes a dramatic increase in satellite-cell proliferation. By contrast, exposure of satellite cells to Wnt4 or Wnt6 diminishes this process. Moreover, we show that the prolonged satellite-cell quiescence induced by inhibitory Wnt is reversible and exposing inhibited satellite cells to stimulatory Wnt signalling restores their proliferation rate. Stimulatory Wnt proteins induce premature satellite cell BrdU incorporation as well as nuclear translocation of Act-β-Cat. Finally, we provide evidence that the Act-β-Cat translocation observed in single fibres during in vitro culture also occurs in cases of acute and chronic skeletal muscle regeneration in rodents and humans. We propose that Wnt proteins may be key factors that regulate the rate of satellite-cell proliferation on adult muscle fibres during the wound-healing response.

The influence of the carbon surface chemical composition on Dubinin-Astakhov equation parameters calculated from SF(6) adsorption data-grand canonical Monte Carlo simulation

Using grand canonical Monte Carlo simulation we show, for the first time, the influence of the carbon porosity and surface oxidation on the parameters of the Dubinin-Astakhov (DA) adsorption isotherm equation. We conclude that upon carbon surface oxidation, the adsorption decreases for all carbons studied. Moreover, the parameters of the DA model depend on the number of surface oxygen groups. That is why in the case of carbons containing surface polar groups, SF(6) adsorption isotherm data cannot be used for characterization of the porosity.

Testing isotherm models and recovering empirical relationships for adsorption in microporous carbons using virtual carbon models and grand canonical Monte Carlo simulations

Using the plausible model of activated carbon proposed by Harris and co-workers and grand canonical Monte Carlo simulations, we study the applicability of standard methods for describing adsorption data on microporous carbons widely used in adsorption science. Two carbon structures are studied, one with a small distribution of micropores in the range up to 1 nm, and the other with micropores covering a wide range of porosity. For both structures, adsorption isotherms of noble gases (from Ne to Xe), carbon tetrachloride and benzene are simulated. The data obtained are considered in terms of Dubinin-Radushkevich plots. Moreover, for benzene and carbon tetrachloride the temperature invariance of the characteristic curve is also studied. We show that using simulated data some empirical relationships obtained from experiment can be successfully recovered. Next we test the applicability of Dubinin's related models including the Dubinin-Izotova, Dubinin-Radushkevich-Stoeckli, and Jaroniec-Choma equations. The results obtained demonstrate the limits and applications of the models studied in the field of carbon porosity characterization.

A novel, non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3)

The canonical pathway of regulation of the germinal centre kinase (GCK) III subgroup member, mammalian Sterile20-related kinase 3 (MST3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr178-), induction of Ser-/Thr-protein kinase activity and nuclear localisation. We identified an alternative ‘non-canonical’ pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein, GOLGA2/gm130. Activation of MST3 by calyculin A (a protein Ser-/Thr- phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr178-) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr328-) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr178-) phosphorylation increased MST3 kinase activity but this activity was independent of MST3(Thr328-) phosphorylation. Interestingly, MST3(Thr328-) lies immediately C-terminal to a STRAD pseudokinase-like site recently identified as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr178- /Thr328-) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr328-) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex.

On wave action and phase in the non-canonical Hamiltonian formulation

The long time–evolution of disturbances to slowly–varying solutions of partial differential equations is subject to the adiabatic invariance of the wave action. Generally, this approximate conservation law is obtained under the assumption that the partial differential equations are derived from a variational principle or have a canonical Hamiltonian structure. Here, the wave action conservation is examined for equations that possess a non–canonical (Poisson) Hamiltonian structure. The linear evolution of disturbances in the form of slowly varying wavetrains is studied using a WKB expansion. The properties of the original Hamiltonian system strongly constrain the linear equations that are derived, and this is shown to lead to the adiabatic invariance of a wave action. The connection between this (approximate) invariance and the (exact) conservation laws of pseudo–energy and pseudomomentum that exist when the basic solution is exactly time and space independent is discussed. An evolution equation for the slowly varying phase of the wavetrain is also derived and related to Berry's phase.

Extending the use of canonical and microcanonical Monte Carlo algorithms to spin models

We describe the canonical and microcanonical Monte Carlo algorithms for different systems that can be described by spin models. Sites of the lattice, chosen at random, interchange their spin values, provided they are different. The canonical ensemble is generated by performing exchanges according to the Metropolis prescription whereas in the microcanonical ensemble, exchanges are performed as long as the total energy remains constant. A systematic finite size analysis of intensive quantities and a comparison with results obtained from distinct ensembles are performed and the quality of results reveal that the present approach may be an useful tool for the study of phase transitions, specially first-order transitions. (C) 2009 Elsevier B.V. All rights reserved.

Canonical quantum potential scattering theory

A new formulation of potential scattering in quantum mechanics is developed using a close structural analogy between partial waves and the classical dynamics of many non-interacting fields. Using a canonical formalism we find nonlinear first-order differential equations for the low-energy scattering parameters such as scattering length and effective range. They significantly simplify typical calculations, as we illustrate for atom-atom and neutron-nucleus scattering systems. A generalization to charged particle scattering is also possible.