Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Surface Expression and Subunit Specific Control of Steady Protein Levels by the Kv7.2 Helix A-B Linker

12 p.

The Influence of the Val158Met Catechol-O-Methyltransferase Polymorphism on the Personality Traits of Bipolar Patients

6 p.

The First Occurrence in the Fossil Record of an Aquatic Avian Twig-Nest with Phoenicopteriformes Eggs: Evolutionary Implication

14 p.

The cross layer RMPA handover: a reliable mobility pattern aware handover strategy for broadband wireless communication in a high-speed railway domain

Enhancing the handover process in broadband wireless communication deployment has traditionally motivated many research initiatives. In a high-speed railway domain, the challenge is even greater. Owing to the long distances covered, the mobile node gets involved in a compulsory sequence of handover processes. Consequently, poor performance during the execution of these handover processes significantly degrades the global end-to-end performance. This article proposes a new handover strategy for the railway domain: the RMPA handover, a Reliable Mobility Pattern Aware IEEE 802.16 handover strategy "customized" for a high-speed mobility scenario. The stringent high mobility feature is balanced with three other positive features in a high-speed context: mobility pattern awareness, different sources for location discovery techniques, and a previously known traffic data profile. To the best of the authors' knowledge, there is no IEEE 802.16 handover scheme that simultaneously covers the optimization of the handover process itself and the efficient timing of the handover process. Our strategy covers both areas of research while providing a cost-effective and standards-based solution. To schedule the handover process efficiently, the RMPA strategy makes use of a context aware handover policy; that is, a handover policy based on the mobile node mobility pattern, the time required to perform the handover, the neighboring network conditions, the data traffic profile, the received power signal, and current location and speed information of the train. Our proposal merges all these variables in a cross layer interaction in the handover policy engine. It also enhances the handover process itself by establishing the values for the set of handover configuration parameters and mechanisms of the handover process. RMPA is a cost-effective strategy because compatibility with standards-based equipment is guaranteed. The major contributions of the RMPA handover are in areas that have been left open to the handover designer's discretion. Our simulation analysis validates the RMPA handover decision rules and design choices. Our results supporting a high-demand video application in the uplink stream show a significant improvement in the end-to-end quality of service parameters, including end-to-end delay (22%) and jitter (80%), when compared with a policy based on signal-to-noise-ratio information.

The interactive brain hypothesis

Enactive approaches foreground the role of interpersonal interaction in explanations of social understanding. This motivates, in combination with a recent interest in neuroscientific studies involving actual interactions, the question of how interactive processes relate to neural mechanisms involved in social understanding. We introduce the Interactive Brain Hypothesis (IBH) in order to help map the spectrum of possible relations between social interaction and neural processes. The hypothesis states that interactive experience and skills play enabling roles in both the development and current function of social brain mechanisms, even in cases where social understanding happens in the absence of immediate interaction. We examine the plausibility of this hypothesis against developmental and neurobiological evidence and contrast it with the widespread assumption that mindreading is crucial to all social cognition. We describe the elements of social interaction that bear most directly on this hypothesis and discuss the empirical possibilities open to social neuroscience. We propose that the link between coordination dynamics and social understanding can be best grasped by studying transitions between states of coordination. These transitions form part of the self-organization of interaction processes that characterize the dynamics of social engagement. The patterns and synergies of this self-organization help explain how individuals understand each other. Various possibilities for role-taking emerge during interaction, determining a spectrum of participation. This view contrasts sharply with the observational stance that has guided research in social neuroscience until recently. We also introduce the concept of readiness to interact to describe the practices and dispositions that are summoned in situations of social significance (even if not interactive). This latter idea links interactive factors to more classical observational scenarios.

Manipulation of domain wall dynamics in amorphous microwires through the magnetoelastic anisotropy

We studied the effect of magnetoelastic anisotropy on domain wall (DW) dynamics and remagnetization process of magnetically bistable Fe-Co-rich microwires with metallic nucleus diameters (from 1.4 to 22 mu m). We manipulated the magnetoelastic anisotropy applying the tensile stresses and changing the magnetostriction constant and strength of the internal stresses. Microwires of the same composition of metallic nucleus but with different geometries exhibit different magnetic field dependence of DW velocity with different slopes. Application of stresses resulted in decrease of the DW velocity, v, and DW mobility, S. Quite fast DW propagation (v until 2,500 m/s at H about 30 A/m) has been observed in low magnetostrictive magnetically bistable Co56Fe8Ni10Si10B16 microwires. Consequently, we observed certain correlation between the magnetoelastic energy and DW dynamics in microwires: decreasing the magnetoelastic energy, K (me), DW velocity increases.

Valuing Expansions of the Electricity Transmission Network under Uncertainty: The Binodal Case

Transmission investments are currently needed to meet an increasing electricity demand, to address security of supply concerns, and to reach carbon-emissions targets. A key issue when assessing the benefits from an expanded grid concerns the valuation of the uncertain cash flows that result from the expansion. We propose a valuation model that accommodates both physical and economic uncertainties following the Real Options approach. It combines optimization techniques with Monte Carlo simulation. We illustrate the use of our model in a simplified, two-node grid and assess the decision whether to invest or not in a particular upgrade. The generation mix includes coal-and natural gas-fired stations that operate under carbon constraints. The underlying parameters are estimated from observed market data.

Downscaling of surface moisture flux and precipitation in the Ebro Valley (Spain) using analogues and analogues followed by random forests and multiple linear regression

In this paper, reanalysis fields from the ECMWF have been statistically downscaled to predict from large-scale atmospheric fields, surface moisture flux and daily precipitation at two observatories (Zaragoza and Tortosa, Ebro Valley, Spain) during the 1961-2001 period. Three types of downscaling models have been built: (i) analogues, (ii) analogues followed by random forests and (iii) analogues followed by multiple linear regression. The inputs consist of data (predictor fields) taken from the ERA-40 reanalysis. The predicted fields are precipitation and surface moisture flux as measured at the two observatories. With the aim to reduce the dimensionality of the problem, the ERA-40 fields have been decomposed using empirical orthogonal functions. Available daily data has been divided into two parts: a training period used to find a group of about 300 analogues to build the downscaling model (1961-1996) and a test period (19972001), where models' performance has been assessed using independent data. In the case of surface moisture flux, the models based on analogues followed by random forests do not clearly outperform those built on analogues plus multiple linear regression, while simple averages calculated from the nearest analogues found in the training period, yielded only slightly worse results. In the case of precipitation, the three types of model performed equally. These results suggest that most of the models' downscaling capabilities can be attributed to the analogues-calculation stage.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

STM study on the self-assembly of oligothiophene-based organic semiconductors

The self-assembly properties of a series of functionalized regioregular oligo(3-alkylthiophenes) were investigated by using scanning tunneling microscopy (STM) at the liquid-solid interface under ambient conditions. The characteristics of the 2-D crystals formed on the (0001) plane of highly ordered pyrolitic graphite (HOPG) strongly depend on the length of the p-conjugated oligomer backbone, on the functional groups attached to it, and on the alkyl substitution pattern on the individual thiophene units. Theoretical calculations were performed to analyze the geometry and electronic density of the molecular orbitals as well as to analyze the intermolecular interactions, in order to obtain models of the 2-D molecular ordering on the substrate.

The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study

Despite being the most effective treatment for Parkinson's disease, L-DOPA causes a development of dyskinetic movements in the majority of treated patients. L-DOPA-induced dyskinesia is attributed to a dysregulated dopamine transmission within the basal ganglia, but serotonergic and noradrenergic systems are believed to play an important modulatory role. In this study, we have addressed the role of the locus coeruleus nucleus (LC) in a rat model of L-DOPA-induced dyskinesia. Single-unit extracellular recordings in vivo and behavioural and immunohistochemical approaches were applied in rats rendered dyskinetic by the destruction of the nigrostriatal dopamine neurons followed by chronic treatment with L-DOPA. The results showed that L-DOPA treatment reversed the change induced by 6-hydroxydopamine lesions on LC neuronal activity. The severity of the abnormal involuntary movements induced by L-DOPA correlated with the basal firing parameters of LC neuronal activity. Systemic administration of the LC-selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not modify axial, limb, and orolingual dyskinesia, whereas chemical destruction of the LC with ibotenic acid significantly increased the abnormal involuntary movement scores. These results are the first to demonstrate altered LC neuronal activity in 6-OHDA lesioned rats treated with L-DOPA, and indicate that an intact noradrenergic system may limit the severity of this movement disorder.

The IRYSS-COPD appropriateness study: objectives, methodology, and description of the prospective cohort

Background: Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of the disease that require hospitalization. Current guidelines offer little guidance for identifying patients whose clinical situation is appropriate for admission to the hospital, and properly developed and validated severity scores for COPD exacerbations are lacking. To address these important gaps in clinical care, we created the IRYSS-COPD Appropriateness Study. Methods/Design: The RAND/UCLA Appropriateness Methodology was used to identify appropriate and inappropriate scenarios for hospital admission for patients experiencing COPD exacerbations. These scenarios were then applied to a prospective cohort of patients attending the emergency departments (ED) of 16 participating hospitals. Information was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up after admission or discharge home. While complete data were generally available at the time of ED admission, data were often missing at the time of decision making. Predefined assumptions were used to impute much of the missing data. Discussion: The IRYSS-COPD Appropriateness Study will validate the appropriateness criteria developed by the RAND/UCLA Appropriateness Methodology and thus better delineate the requirements for admission or discharge of patients experiencing exacerbations of COPD. The study will also provide a better understanding of the determinants of outcomes of COPD exacerbations, and evaluate the equity and variability in access and outcomes in these patients.

Effect of Molecular Flexibility on the Nematic-to-Isotropic Phase Transition for Highly Biaxial Molecular Non-Symmetric Liquid Crystal Dimers

In this work, a study of the nematic (N)-isotropic (I) phase transition has been made in a series of odd non-symmetric liquid crystal dimers, the alpha-(4-cyanobiphenyl-4'-yloxy)-omega-(1-pyrenimine-benzylidene-4'-oxy) alkanes, by means of accurate calorimetric and dielectric measurements. These materials are potential candidates to present the elusive biaxial nematic (N-B) phase, as they exhibit both molecular biaxiality and flexibility. According to the theory, the uniaxial nematic (N-U)-isotropic (I) phase transition is first-order in nature, whereas the N-B-I phase transition is second-order. Thus, a fine analysis of the critical behavior of the N-I phase transition would allow us to determine the presence or not of the biaxial nematic phase and understand how the molecular biaxiality and flexibility of these compounds influences the critical behavior of the N-I phase transition.

Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Lambda beta (amyloid beta-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to A beta accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.