Allosteric modulation of retinal GABA receptors by ascorbic acid

Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vickers, Evan. Oregon Health and Science University; Estados UnidosFil: Cid, Gustavo Moraga. Universidad de Concepción; ChileFil: Aguayo, Luis G.. Universidad de Concepción; ChileFil: von Gersdorff, Henrique. Oregon Health and Science University; Estados UnidosFil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

MODELFY: A Model-driven Solution for Decision Making based on Fuzzy Information

There exist areas, such as the disease prevention or inclement weather protocols, in which the analysis of the information based on strict protocols require a high level of rigor and security. In this situation, it would be desirable to apply formal methodologies that provide these features. In this scope, recently, it has been proposed a formalism, fuzzy automaton, that captures two relevant aspects for fuzzy information analysis: imprecision and uncertainty. However, the models should be designed by domain experts, who have the required knowledge for the design of the processes, but do not have the necessary technical knowledge. To address this limitation, this paper proposes MODELFY, a novel model-driven solution for designing a decision-making process based on fuzzy automata that allows users to abstract from technical complexities. With this goal in mind, we have developed a framework for fuzzy automaton model design based on a Domain- Specific Modeling Language (DSML) and a graphical editor. To improve the interoperability and functionality of this framework, it also includes a model-to-text transformation that translates the models designed by using the graphical editor into a format that can be used by a tool for data analysis. The practical value of this proposal is also evaluated through a non-trivial medical protocol for detecting potential heart problems. The results confirm that MODELFY is useful for defining such a protocol in a user-friendly and rigorous manner, bringing fuzzy automata closer to domain expert

Extreme value distributions and Renormalization Group

In the classical theorems of extreme value theory the limits of suitably rescaled maxima of sequences of independent, identically distributed random variables are studied. So far, only affine rescalings have been considered. We show, however, that more general rescalings are natural and lead to new limit distributions, apart from the Gumbel, Weibull, and Fr\'echet families. The problem is approached using the language of Renormalization Group transformations in the space of probability densities. The limit distributions are fixed points of the transformation and the study of the differential around them allows a local analysis of the domains of attraction and the computation of finite-size corrections.Comment: 16 pages, 5 figures. Final versio

Picolinic and Isonicotinic Acids: A Fourier Transform Microwave Spectroscopy Study

Producción CientíficaThe rotational spectra of laser ablated picolinic and isonicotinic acids have been studied using broadband chirped pulse (CP-FTMW) and narrowband molecular beam (MB-FTMW) Fourier transform microwave spectroscopies. Two conformers of picolinic acid, s-cis-I and s-cis-II, and one conformer of isonicotinic acid have been identified through the analysis of their rotational spectra. The values of the inertial defect and the quadrupole coupling constants obtained for the most stable s-cis-I conformer of picolinic acid, evidence the formation of an O–H···N hydrogen bond between the acid group and the endocyclic N atom. The stabilization provided by this hydrogen bond compensates the destabilization energy due to the adoption of a −COOH trans configuration in this conformer. Its rs structure has been derived from the rotational spectra of several 13C, 15N, and 18O species observed in their natural abundances. Mesomeric effects have been revealed by comparing the experimental values of the 14N nuclear quadrupole coupling constants in the isomeric series of picolinic, isonicotinic, and nicotinic acids.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA175U13

Bayesian spatio-temporal model with INLA for dengue fever risk prediction in Costa Rica

Due to the rapid geographic spread of the Aedes mosquito and the increase in dengue incidence, dengue fever has been an increasing concern for public health authorities in tropical and subtropical countries worldwide. Significant challenges such as climate change, the burden on health systems, and the rise of insecticide resistance highlight the need to introduce new and cost-effective tools for developing public health interventions. Various and locally adapted statistical methods for developing climate-based early warning systems have increasingly been an area of interest and research worldwide. Costa Rica, a country with micro-climates and endemic circulation of the dengue virus (DENV) since 1993, provides ideal conditions for developing projection models with the potential to help guide public health efforts and interventions to control and monitor future dengue outbreaks

Necesidades psicológicas básicas, motivación y compromiso en educación física

Tomando como marco la teoría de la autodeterminación, el objetivo del presente estudio fue analizar las relaciones entre satisfacción y frustración de las tres necesidades psicológicas básicas (autonomía, competencia y relación), la motivación autónoma, la motivación controlada y el compromiso agéntico en adolescentes (n = 377) en el contexto de educación física. Se testó un modelo de ecuaciones estructurales que reveló que la satisfacción de las tres necesidades psicológicas predijo la motivación autónoma y ésta, a su vez, predijo el compromiso agéntico (β = .26, p < .01). Igualmente, la satisfacción de autonomía predijo de forma directa el compromiso agéntico (β = .38, p < .01). Por otro lado, la frustración de autonomía y de relación predijeron positivamente la motivación controlada, mientras que la frustración de competencia predijo negativamente la motivación autónoma (β = -.50, p < .01). No se halló relación significativa entre la motivación controlada y el compromiso agéntico. Estos resultados subrayan la importancia de satisfacer las necesidades psicológicas y la motivación autónoma en clase de educación física, para favorecer la participación constructiva que los alumnos efectúan al flujo de consejos e informaciones del profesor durante el proceso de aprendizaje

Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1G93A (mSOD1) has also been reported. Here we have investigated the excitability, the ion currents, and the kinetics of the exocytotic fusion pore in chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when motor deficits are already established. With respect to wild-type (WT), mSOD1 chromaffin cells had a decrease in the following parameters: 95% in spontaneous action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na+ current, 40% in Ca2+-dependent K+ current, and 53% in voltage-dependent K+ current. Ca2+ current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca2+ was unchanged. Single exocytotic spike events triggered by ACh had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal size. The expression of the α3-subtype of nicotinic receptors and proteins of the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1, with respect to WT mice. A slower fusion pore opening, expansion, and closure are likely linked to the pronounced reduction in cell excitability and in the ion currents driving action potentials in mSOD1, compared with WT chromaffin cells.This work was funded by: (1) SAF-2010-21795, MINECO; (2) SAF-2010-792 18837, MINECO; (3) CABICYC, UAM/Bioibérica; (4) Fundación Teófilo 793 Hernando, Madrid, Spai

Generalized Central Limit Theorem and Renormalization Group

We introduce a simple instance of the renormalization group transformation in the Banach space of probability densities. By changing the scaling of the renormalized variables we obtain, as fixed points of the transformation, the L\'evy strictly stable laws. We also investigate the behavior of the transformation around these fixed points and the domain of attraction for different values of the scaling parameter. The physical interest of a renormalization group approach to the generalized central limit theorem is discussed.Comment: 16 pages, to appear in J. Stat. Phy