Bi-directional Modulation of Hyperpolarization-Activated Cation Currents (Ih) by Ethanol in Rat Hippocampal CA3 Pyramidal Neurons

It is widely acknowledged that ethanol (EtOH) can alter many neuronal functions, including synaptic signaling, firing discharge, and membrane excitability, through its interaction with multiple membrane proteins and intracellular pathways. Previous work has demonstrated that EtOH enhances the firing rate of hippocampal GABAergic interneurons and thus the presynaptic GABA release at CA1 and CA3 inhibitory synapses through a positive modulation of the hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels. Activation of HCN channels produce an inward current, commonly called Ih, which plays an essential role in generating/regulating specific neuronal activities in GABAergic interneurons and principal glutamatergic pyramidal neurons such as those in the CA3 subregion. Since the direct effect of EtOH on HCN channels expressed in CA3 pyramidal neurons was not thoroughly elucidated, we investigated the possible interaction between EtOH and HCN channels and the impact on excitability and postsynaptic integration of these neurons. Patch-clamp recordings were performed in single CA3 pyramidal neurons from acute male rat coronal hippocampal slices. Our results show that EtOH modulates HCN-mediated Ih in a concentration-dependent and bi-directional manner, with a positive modulation at lower (20 mM) and an inhibitory action at higher (60-80 mM) concentrations. The modulation of Ih by EtOH was mimicked by forskolin, antagonized by different drugs that selectively interfere with the AC/cAMP/PKA intracellular pathway, as well as by the selective HCN inhibitor ZD7288. Altogether, these data further support the evidence that HCN channels may represent an important molecular target through which EtOH may regulate neuronal activity

Study of the reflection spectrum of the accreting neutron star GX 3+1 using XMM-Newton and INTEGRAL

Broad emission features of abundant chemical elements, such as Iron, are commonly seen in the X-ray spectra of accreting compact objects and their studies can provide useful information about the geometry of the accretion processes. In this work, we focus our attention on GX 3+1, a bright, persistent accreting low mass X-ray binary, classified as an atoll source. Its spectrum is well described by an accretion disc plus a stable comptonizing, optically thick corona which dominates the X-ray emission in the 0.3-20 keV energy band. In addition, four broad emission lines are found and we associate them with reflection of hard photons from the inner regions of the accretion disc where doppler and relativistic effects are important. We used self-consistent reflection models to fit the spectra of the 2010 XMM-Newton observation and the stacking of the whole datasets of 2010 INTEGRAL observations. We conclude that the spectra are consistent with reflection produced at ~10 gravitational radii by an accretion disc with an ionization parameter of xi~600 erg cm/s and viewed under an inclination angle of the system of ~35{\deg}. Furthermore, we detected for the first time for GX 3+1, the presence of a powerlaw component dominant at energies higher than 20 keV, possibly associated with an optically thin component of non-thermal electrons.Comment: Accepted to appear on MNRAS, 9 pages, 5 figur

Present and future climate simulation of Mediterranean cyclones with a high resolution AOGCMs

Preliminary results are presented of a study aiming at producing a climatology of Mediterranean cyclones making use of a global AOGCM coupled with an interactive high-resolution model of the Mediterranean Sea. Cyclones are analyzed with both the lagrangian and the eulerian approaches, applied to three different simulations: a control one (present climate conditions) and two IPCC scenarios (A1B and A2). Both the North Atlantic stormtrack and cyclone track and genesis density statistics from the control dataset are analyzed compared to ERA40 reanalysis. Cyclones are grouped according to their genesis location and the corresponding lysis regions are identified. Partic- ular attention is devoted to the effects of sea-surface fields (temperature gradients and heat fluxes). The wet season (October–March) is examined in relation to the decrease in the intensity of cyclogenesis events in the region and trends are investigated

Isolation rearing reduces neuronal excitability in dentate gyrus granule cells of adolescent C57BL/6J mice: role of gabaergic tonic currents and neurosteroids

Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3a,5a-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these changes may be consistent with cognitive deficits observed in animals exposed to such type of prolonged stres

Neurosteroidi: i modulatori endogeni delle emozioni

The discovery that facilitation or inhibition of γ aminobutyric acid (GABA)-mediated neurotransmission results in anxiolytic versus anxiogenic, hypnotic versus somnolitic, and anticonvulsant versus convulsant effects, respectively, provided important early insight into the physiology and pharmacology of central GABAergic transmission. This realization, together with subsequent evidence that high-affinity recognition sites for positive and negative allosteric modulators of GABAA receptors are located on these GABA-gated Cl– channels, led to the concept that GABAA receptors contribute directly not only to the pharmacology but also to the neurobiology and physiopathology of a variety of neurological and psychiatric diseases characterized by changes in emotional state, sleep pattern, or neuronal excitability. These findings have suggested the hypothesis that the brain and peripheral organs in mammals might produce endogenous compounds that selectively modulate central GABAA receptor function. Evidence directly supporting this hypothesis has been provided over the last decade by the discovery that steroid hormones synthesized in the brain or in peripheral organs are among the most selective, potent, and efficacious allosteric modulators of GABAA receptors. Neurosteroids are steroid derivatives that are synthesized de novo from cholesterol in the central nervous system (CNS), some of which modulate GABAA receptor function with potencies and efficacies similar to or greater than those of benzodiazepines and barbiturates. These molecules have thus been suggested to be the endogenous modulators of GABAA receptor–mediated neurotransmission. In fact some of these molecules have the capability to modulate synaptic activity by binding to membrane sites associated with ligand-gated ionotropic receptors including GABAA receptors. Here we summarize some of the most recent evidences obtained by our and other laboratories pertaining the role of two neuroactive steroids allopregnanolone (AP) and tetrahydrodeoxycorticosterone (THDOC) actives in modulating the function and plasticity of GABAA receptors in nature

Aware of the Future?: Development and Validation of the Futures Consciousness Scale

Futures Consciousness refers to the capacity that a person has for understanding, anticipating, and preparing for the future. Although the concept is widely used in the field of futures research, no quantitative tool exists yet that assesses it. Drawing from a recent five-dimensional model that considers Time perspective, Agency beliefs, Openness to alternatives, Systems perception, and Concern for others as interrelated sub-dimensions of a general construct of Futures Consciousness, we developed a composite 20-item scale that measures Futures Consciousness as an interindividual difference. The psychometric properties of this new scale were examined through a dual approach of exploratory and confirmatory factorial analyses with a total of 1,301 participants in three languages (English, French, and Finnish). The scale’s structure proved satisfactory and fitted the hypothesized five-dimensional model in all three languages. Measures of internal and external validity (convergent and concurrent) also indicated good psychometric properties. Notably, individuals’ scores were positively related to the adoption of several social future-oriented behaviors such as pro-environmental and civic behavior. As such, the developed scale proves a reliable tool that could be of use for scholars and practitioners in futures studies as well as psychology. </dd

Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract

Type 2 diabetes (T2D) is a progressive metabolic disorder of glucose metabolism. One of the therapeutic approaches for the treatment of T2D is reducing postprandial hyperglycaemia through inhibition of the digestive enzymes α-glucosidase and α-amylase. In this context, aimed at identifying natural products endowed with anti-T2D potential, we focused on Ptilostemon casabonae (L.) Greuter, a species belonging to Asteraceae family. Enzymatic inhibition, antioxidant activity, phenolic composition and cellular assays were performed. This study revealed that the P. casabonae hydroalcoholic extract exerts a potent inhibitory activity against α-glucosidase. This activity is supported by an antioxidant effect, preventing ROS formation in a stressed cellular system. HPLC-PDA-MS/MS analysis, revealed a complex polyphenolic fraction. Among the tested pure compounds, 1,5-dicaffeoylquinic acid, apigenin and rutin displayed good α-glucosidase inhibitory activity. Our study suggested new potential of P. casabonae encouraging us to further testing the possible therapeutic potential of this extract

Terrestrial Laser Scanner and Close Range Photogrammetry point clouds accuracy assessment for the structure deformations monitoring

In this paper we show the results of several tests carried out using methods and instrumentation typical of an architectural survey, along with a set of metrological instrumentation, on a Reinforced Concrete (RC) beam subjected to increasing loads. The goal was to assess the accuracy in the displacements estimated by a medium quality terrestrial laser scanner (TLS) Focus 3d from Faro Technologies, and the low-cost digital camera Canon PowerShot S110 used in a Close Range Photogrammetry (CRP) survey. The software used for scan-data and point clouds processing was Reconstructor JRC Software v. 3.1.0, maintained by Gexcel Ltd, while the images processing was performed with the software Photoscan from Agisoft, which implements Structure from Motion (SfM) approach. Two processing strategies were used in the point clouds comparison: mesh2mesh and modelling the beam behavior fitting the contours of the beam with second order polynomials. Comparisons between the TLS and CRP techniques and the metrological equipment used in parallel highlighted the limits and potentialities of the two geomatic techniques used. It has been shown that modeling the behavior of the beam leads to significantly better results than using the mesh2mesh comparison. For the CRP the increase in accuracy was in the order of 40%, while for the TLS of 50%