Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.

On the Informational Role of Term Structure in the U.S. Monetary Policy Rule

This paper uses a structural approach based on the indirect inference principle to estimate a standard version of the new Keynesian monetary (NKM) model augmented with term structure using both revised and real-time data. The estimation results show that the term spread and policy inertia are both important determinants of the U.S. estimated monetary policy rule whereas the persistence of shocks plays a small but significant role when revised and real-time data of output and inflation are both considered. More importantly, the relative importance of term spread and persistent shocks in the policy rule and the shock transmission mechanism drastically change when it is taken into account that real-time data are not well behaved.

Dealing with Energy-QoE Trade-Offs in Mobile Video

Scalable video coding allows an efficient provision of video services at different quality levels with different energy demands. According to the specific type of service and network scenario, end users and/or operators may decide to choose among different energy versus quality combinations. In order to deal with the resulting trade-off, in this paper we analyze the number of video layers that are worth to be received taking into account the energy constraints. A single-objective optimization is proposed based on dynamically selecting the number of layers, which is able to minimize the energy consumption with the constraint of a minimal quality threshold to be reached. However, this approach cannot reflect the fact that the same increment of energy consumption may result in different increments of visual quality. Thus, a multiobjective optimization is proposed and a utility function is defined in order to weight the energy consumption and the visual quality criteria. Finally, since the optimization solving mechanism is computationally expensive to be implemented in mobile devices, a heuristic algorithm is proposed. This way, significant energy consumption reduction will be achieved while keeping reasonable quality levels.

What mechanism of niche segregation allows the coexistence of sympatric sibling rhinolophid bats?

Introduction: Our purpose was to assess how pairs of sibling horseshoe bats coexists when their morphology and echolocation are almost identical. We collected data on echolocation, wing morphology, diet, and habitat use of sympatric Rhinolophus mehelyi and R. euryale. We compared our results with literature data collected in allopatry with similar protocols and at the same time of the year (breeding season). Results:Echolocation frequencies recorded in sympatry for R. mehelyi (mean = 106.8 kHz) and R. euryale (105.1 kHz) were similar to those reported in allopatry (R. mehelyi 105–111 kHz; R. euryale 101–109 kHz). Wing parameters were larger in R. mehelyi than R. euryale for both sympatric and allopatric conditions. Moths constitute the bulk of the diet of both species in sympatry and allopatry, with minor variation in the amounts of other prey. There were no inter-specific differences in the use of foraging habitats in allopatry in terms of structural complexity, however we found inter-specific differences between sympatric populations: R. mehelyi foraged in less complex habitats. The subtle inter-specific differences in echolocation frequency seems to be unlikely to facilitate dietary niche partitioning; overall divergences observed in diet may be explained as a consequence of differential prey availability among foraging habitats. Inter-specific differences in the use of foraging habitats in sympatry seems to be the main dimension for niche partitioning between R. mehelyi and R. euryale, probably due to letter differences in wing morphology. Conclusions: Coexistence between sympatric sibling horseshoe bats is likely allowed by a displacement in spatial niche dimension, presumably due to the wing morphology of each species, and shifts the niche domains that minimise competition. Effective measures for conservation of sibling/similar horseshoe bats should guarantee structural diversity of foraging habitats.

Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier

[EN] The aims of this work were (i) to evaluate the potential of nanostructured lipid carriers (NLCs) as a tool to 24 enhance the oral bioavailability of poorly soluble compounds using saquinavir (SQV), a BCS class IV drug 25 and P-gp substrate as a model drug, and (ii) to study NLC transport mechanisms across the intestinal barrier. 26 Three different NLC formulations were evaluated. SQV transport across Caco-2 monolayers was enhanced up 27 to 3.5-fold by NLCs compared to SQV suspension. M cells did not enhance the transport of NLCs loaded with 28 SQV. The size and amount of surfactant in the NLCs influenced SQV's permeability, the transcytosis pathway 29 and the efflux of SQV by P-gp. An NLC of size 247 nm and 1.5% (w/v) surfactant content circumvented P-gp 30 efflux and used both caveolae- and clathrin-mediated transcytosis, in contrast to the other NLC formulations, 31 which used only caveolae-mediated transcytosis. By modifying critical physicochemical parameters of the 32 NLC formulation, we were thus able to overcome the P-gp drug efflux and alter the transcytosis mechanism 33 of the nanoparticles. These findings support the use of NLCs approaches for oral delivery of poorly 34 water-soluble P-gp substrates.

Inoculation of Triatoma Virus (Dicistroviridae: Cripavirus) elicits a non-infective immune response in mice

Background: Dicistroviridae is a new family of small, non-enveloped, +ssRNA viruses pathogenic to both beneficial arthropods and insect pests. Little is known about the dicistrovirus replication mechanism or gene function, and any knowledge on these subjects comes mainly from comparisons with mammalian viruses from the Picornaviridae family. Due to its peculiar genome organization and characteristics of the per os viral transmission route, dicistroviruses make good candidates for use as biopesticides. Triatoma virus (TrV) is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of the human trypanosomiasis disease called Chagas disease. TrV was postulated as a potential control agent against Chagas' vectors. Although there is no evidence that TrV nor other dicistroviruses replicate in species outside the Insecta class, the innocuousness of these viruses in humans and animals needs to be ascertained. Methods: In this study, RT-PCR and ELISA were used to detect the infectivity of this virus in Mus musculus BALB/c mice. Results: In this study we have observed that there is no significant difference in the ratio IgG2a/IgG1 in sera from animals inoculated with TrV when compared with non-inoculated animals or mice inoculated only with non-infective TrV protein capsids. Conclusions: We conclude that, under our experimental conditions, TrV is unable to replicate inmice. This study constitutes the first test to evaluate the infectivity of a dicistrovirus in a vertebrate animal model.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

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La pobreza laboral

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Is inbreeding avoidance driving female mate choice in Verreaux's sifaka lemurs?

Females of different species might exert female mate choice for different reasons, one of them the aim of avoiding inbreeding. In this study I examine the implication of inbreeding avoidance as a mechanism driving female mate choice in Verreaux’s sifaka lemurs (Propithecus verreauxi). In fact, in this species females are dominant and appear to be able to choose certain males to mate with, while observations indicate that rank, body size, canine size and proportions of fights won are not factors influencing female mate choice. So I hypothesized that females mate choice is driven by inbreeding avoidance in Verreaux’s sifaka lemurs. Tissue and fecal samples were collected in the Kirindy Mitea National Park in western Madagascar as a source of DNA. Parentage was assigned for a sample of the population and relatedness coefficients between dams and sires were estimated and compared to those of between random female and male pairs, dams and other candidate sires within the population and within the groups were the offspring were conceived. I found that there were no significant differences in none of the comparisons which means that Verreaux’s sifaka females do not mate more with males that are more distantly related to them. I concluded that inbreeding avoidance does not appear to be the main force driving female mate choice in Verreaux’s sifaka lemurs and I addressed explanations for these findings. With this study I contribute to our knowledge of female mate choice in lemurs.