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.     

Assessment of the environmental quality of two urbanized lotic systems using multiple indicators

Urbanization impacts ecosystems through loss and fragmentation of habitat, loss of diversity, increase in runoff, and contaminant discharges, and the invasion of exotic species. Potrero de los Funes Village (San Luis, Argentina) is experiencing not only a population increase during summer months due to tourism but also an accelerated growth of its permanent population. In order to evaluate the potential effects of urbanization, the environmental quality of Potrero de los Funes River and Las Chacras Stream was assessed, using physical–chemical and biological indicators. Macroinvertebrates, through the application of the Biotic Index for San Luis Sierras (BISLS), anuran amphibian richness and relative abundance, and riparian vegetation were used as bioindicators. While the Simplified Index of Water Quality (SIWQ) was used to characterize the physical–chemical quality of water at each site. SIWQ and BISLS scores were significantly different between sites (F_7,28 = 9.88, p < .001 and F_7,28 = 24.18, p < .001, respectively). SIWQ was significantly correlated with BISLS (Spearman correlation coefficient = 0.8, p < .001). Four anuran species were registered along Potrero River, with no significant differences in the intensity of vocalizations between sites. No species were detected in Las Chacras Stream. Average total plant species richness, exotic plants richness, and vegetation cover were higher at the most impaired system, Las Chacras Stream. The principal component analysis showed that the first two principal components (PCs) explained 76.3% of the total variance. PC1, with strong loadings of SIWQ, BISLS, and amphibian richness, was principally driven by chemical water quality and biological conditions. PC2 was mainly determined by plant richness. The chemical and biological water quality of Potrero and Las Chacras is somewhat impaired, being the upper Las Chacras Stream the most compromised area. This study provides information that will certainly be used to manage future impacts of urbanization on aquatic resources.     

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.     

An Algorithm Template for Domain-Based Parallel Irregular Algorithms

The parallelization of irregular algorithms has not been as widely studied as the one of regular codes. In particular, while there are many proposals of parallel skeletons and libraries very well suited to regular algorithms, this is not the case for irregular ones. This is probably due to the complexity of finding common patterns, behaviors and semantics in these algorithms. This is unfortunate, as the parallelization of irregular algorithms would benefit even more than that of regular codes from the higher degree of abstraction provided by skeletons. This work proposes to exploit the concept of domain defined on some property of the elements to process in order to enable the simple and effective parallelization of irregular applications. Namely, we propose to use such domains both to decompose the computations in parallel tasks and to detect and avoid conflicts between these tasks. A generic C++ library providing a skeleton for multicore systems built on this idea is described and evaluated. Our experimental results show that this library is a very practical tool for the parallelization of irregular algorithms with little programming effort.     

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.     

Pervaporation of 50 wt % ethanol–water mixtures with poly(1‐trimethylsilyl‐1‐propyne) membranes at high temperatures

Poly(1‐trimethylsilyl‐1‐propyne) (PTMSP) membranes have been used to separate ethanol–water mixtures by pervaporation. This polyacetylene is known to present high affinity toward ethanol, showing high selectivity and ethanol permeation flux. The performance of this polymer in the separation of alcohol–water solutions has been evaluated over long periods (572 h) at a high temperature (75°C) to examine the deterioration of the transport properties in the separation of 50 wt % ethanol–water solutions. Although PTMSP membranes present good characteristics for the separation of gases and liquid mixtures, their organic selectivity decrease with the operating time because of the relaxation processes of the polymeric chains, which affect the free volume of the polymer, the deterioration being more evident for concentrated solutions. The effects of the operation temperature on the characteristic parameters of pervaporation have also been studied to establish how this variable affects the performance of PTMSP membranes. The selectivity increases slightly with the operation temperature, but the effect of the temperature on the separation factor decreases as membranes are degraded with the operation time. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2843–2848, 2007     

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.