Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

The Role of LGR4 (GPR48) in Normal and Cancer Processes

Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor that belongs to the superfamily of G protein-coupled receptors that can be activated by R-spondins (RSPOs), Norrin, circLGR4, and the ligand of the receptor activator of nuclear factor kappa-B (RANKL) ligands to regulate signaling pathways in normal and pathological processes. LGR4 is widely expressed in different tissues where it has multiple functions such as tissue development and maintenance. LGR4 mainly acts through the Wnt/β-catenin pathway to regulate proliferation, survival, and differentiation. In cancer, LGR4 participates in tumor progression, invasion, and metastasis. Furthermore, recent evidence reveals that LGR4 is essential for the regulation of the cancer stem cell population by controlling self-renewal and regulating stem cell properties. This review summarizes the function of LGR4 and its ligands in normal and malignant processes.     

Gaussian,Lobatto and Radau positive quadrature rules with a prescribed abscissa

For a given $\theta \in (a,b)$ , we investigate the question whether there exists a positive quadrature formula with maximal degree of precision which has the prescribed abscissa $\theta $ plus possibly $a$ and/or $b$ , the endpoints of the interval of integration. This study relies on recent results on the location of roots of quasi-orthogonal polynomials. The above positive quadrature formulae are useful in studying problems in one-sided polynomial $L_1$ approximation.     

A 2D algorithm with asymmetric workload for the UPC conjugate gradient method

This paper examines four different strategies, each one with its own data distribution, for implementing the parallel conjugate gradient (CG) method and how they impact communication and overall performance. Firstly, typical 1D and 2D distributions of the matrix involved in CG computations are considered. Then, a new 2D version of the CG method with asymmetric workload, based on leaving some threads idle during part of the computation to reduce communication, is proposed. The four strategies are independent of sparse storage schemes and are implemented using Unified Parallel C (UPC), a Partitioned Global Address Space (PGAS) language. The strategies are evaluated on two different platforms through a set of matrices that exhibit distinct sparse patterns, demonstrating that our asymmetric proposal outperforms the others except for one matrix on one platform.     

Bayesian bivariate generalized Lindley model for survival data with a cure fraction

The cure fraction models have been widely used to analyze survival data in which a proportion of the individuals is not susceptible to the event of interest. In this article, we introduce a bivariate model for survival data with a cure fraction based on the three-parameter generalized Lindley distribution. The joint distribution of the survival times is obtained by using copula functions. We consider three types of copula function models, the Farlie–Gumbel–Morgenstern (FGM), Clayton and Gumbel–Barnett copulas. The model is implemented under a Bayesian framework, where the parameter estimation is based on Markov Chain Monte Carlo (MCMC) techniques. To illustrate the utility of the model, we consider an application to a real data set related to an invasive cervical cancer study.     

Methanol oxidation on Au/TiO2 catalysts

We have investigated the adsorption and reaction of methanol with Au/TiO₂ catalysts using a pulsed flow reactor, DRIFTS and TPD. The TiO₂ (P25) surface adsorbed a full monolayer of methanol, much of it in a dissociative manner, forming methoxy groups associated with the cationic sites, and hydroxyl groups at the anions. The methoxy is relatively stable until 250 °C, at which point decomposition occurs, producing mainly dimethyl ether by a bimolecular surface reaction. As the concentration of methoxy on the surface diminishes, so the mechanism reverts to a de-oxygenation pathway, producing mainly methane and water (at ~330 °C in TPD), but also with some coincident CO and hydrogen. Au catalysts were prepared by the deposition-precipitation method to give Au loadings between 0.5–3 wt %. The effect of low levels of Au on the reactivity is marked. The pathway which gives methane, which is characteristic of titania, remains, but a new feature of the reaction is the evolution of CO₂ and H₂ at lower temperature (a peak is seen in TPD at 220 °C), and the elimination of the DME-producing state. Clearly this is associated with the presence of Au and appears to be due to the production of a formate species on the surface of the Au component. This formate species is mainly involved in the reaction of methanol with the Au/TiO₂ catalysts which results in a combustion pathway being followed, with complete conversion occurring by ~130 °C.     

Size exclusion behavior of polymers in amide solvents

Summary The size exclusion chromatography of neutral polymers and polymers containing ionic groups was investigated using N,N-dimethylacetamide (DMA) as mobile phase. As reported previously for N,N-dimethylformamide (DMF), acrylonitrile polymers containing charges, even those at terminal end groups, showed markedly small retention volumes and multimodal peaks by refractive index and 280 nm UV detectors. In DMA containing small amounts of LiBr the peaks of the ionic polymers were shifted to small retention volumes while neutral polymers with analogous chemical structures did not show the same behavior. As in the case of DMF the peculiarities observed in DMA were attributed to the formation of supramolecular structures by the interaction of the ionic groups in the polymer and the ionic species from DMA decomposition.     

Ultrasonic Dispersion of Ceramic Powders

Ultrasonication is very effective in dispersing alumina and barium titanate slurries. When optimum conditions are used, very short durations (2 to 3 min) are enough to achieve well-dispersed, stable suspensions.     

Dynamic behaviour of viologen-activated nanostructured TiO2: correlation between kinetics of charging and coloration

The dynamic response of viologen-activated nanostructured titanium dioxide has been studied by means of electrical and electro-optical measurements. We show that the state of charge of the semiconductor network is the key factor mediating between the electrode potential and colouration of viologen. Theoretically, we relate the electrode potential to the statistics of occupancy of both TiO₂ nanoparticles and oxidized viologen molecules attached to the surface, on the assumption of quasi-equilibrium of Fermi levels in these contacting phases. Experimentally, we determine the statistical function from steady-state measurements (electrochemical impedance spectroscopy) of the capacitance of the semiconductor film. From this understanding we explain the main features that correlate the simultaneous voltammetry and transmittance responses. Finally, the redox process of viologen is resolved separately from the TiO₂ response by means of transmittance data.