Fibrinogen-Derived γ377-395 Peptide Improves Cognitive Performance and Reduces Amyloid-β Deposition, without Altering Inflammation, in AβPP/PS1 Mice

Fibrinogen has emerged as a promising therapeutic target against Alzheimer's disease because of its dual role in altered vascular function and amyloid-β aggregation. Here we provide evidence regarding cognitive improvement and reduction of brain parenchyma amyloid-β deposition in AβPP/PS1 mice after treatment for one month with the fibrinogen-blocking peptide Fibγ377-395. No alteration in glial response or other neuroinflammatory markers was observed in the cortex of treated animals. Considering these results and the fact that Fibγ377-395 does not affect coagulation function, this peptide could be considered as a promising and safe candidate for chronic treatment of Alzheimer's disease

Benthic litter distribution on circalittoral and deep sea bottoms of the southern Bay of Biscay: Analysis of potential drivers

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Gender and corporal expression activity in physical education: Effect of an intervention on students’ motivational processes

Grounded in Self-Determination Theory and Achievement Goal Theory, the objective of this study was to assess the effectiveness of an intervention programme on a series of motivational variables in a corporal expression teaching unit. An analysis was also conducted in terms of whether the impact of the intervention would be effective in boys and girls, given the social stereotypes inherent to this type of expression activity. A sample of 224 students, with ages varying from 12 to 14 years old (105 boys, 119 girls) participated in 10 sessions. A quasi-experimental design was carried out, dividing the total sample into two groups: control (n = 115) and experimental (n = 109). The intervention programme was applied in the experimental group via specific strategies based on the TARGET areas. In the experimental group, the results showed significantly higher values in perceived task-oriented climate, autonomy, competence, intrinsic motivation, identified regulation and enjoyment, as well as significantly lower values in ego-oriented climate. The intervention programme proved to be effective in boys and girls and the results were even better in boys. The importance of developing and applying specific motivational strategies in corporal expression activities should be stressed in order for this to have an impact on variables such as motivation and enjoyment in boys and girls, thus achieving more positive experiences

To what extent is fishing effort affecting the trophic level of the demersal communities at small scale? Preliminary results of a new food web indicator

Due to the complexity of benthic and demersal ecosystems, to be really helpful, a food web indicator should summarize, in a single number, a variety of complex processes that are otherwise hard to apprehend. The present work assesses the direct impact of bottom fishing gears on the trophic level (TL) of benthic and demersal communities dwelling in the continental shelf of the southern Bay of Biscay. Using a spatio-temporal approach at small scale, we tackle two main objectives: 1) to evaluate temporal trends in mean TL at community scale per sampling rectangle (5 x 5 miles grid resolution), and 2) to assess to what extent these trends are related to fishing effort. Two types of data are involved in the analyses: 1) TL data (mean trophic level by sampling rectangle), and 2) VMS data (number of fishing days by sampling rectangle). TL data were calculated using stomach contents sampled for demersal fish species during the Demersales surveys (IBTS), carried out every autumn in the southern Bay of Biscay since 1983, and combined with data from Fishbase and local references for those species which lacked empirical data. We only considered species that appeared in a minimum of 5 years and were consistently well identified along the whole historical series, in order to keep consistency in the community spatiotemporal sampling. Preliminary results point to a significant increase in TL in most of the sampling rectangles, suggesting that the trend observed globally is spatially homogeneous. A clear relationship between fishing effort and TL was also identified, particularly in those areas where fishing effort (mainly otter trawl fisheries) has been decreasing in recent years

Software Tool for Acausal Physical Modelling and Simulation

Modelling and simulation are key tools for analysis and design of systems and processes from almost any scientific or engineering discipline. Models of complex systems are typically built on acausal Differential-Algebraic Equations (DAE) and discrete events using Object-Oriented Modelling (OOM) languages, and some of their key concepts can be explained as symmetries. To obtain a computer executable version from the original model, several algorithms, based on bipartite symmetric graphs, must be applied for automatic equation generation, removing alias equations, computational causality assignment, equation sorting, discrete-event processing or index reduction. In this paper, an open source tool according to OOM paradigm and developed in MATLAB is introduced. It implements such algorithms adding an educational perspective about how they work, since the step by step results obtained after processing the model equations can be shown. The tool also allows to create models using its own OOM language and to simulate the final executable equation set. It was used by students in a modelling and simulation course of the Automatic Control and Industrial Electronics Engineering degree, showing a significant improvement in their understanding and learning of the abovementioned topics after their assessment

Aberrant repair and fibrosis development in skeletal muscle

The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair

METADOCK 2: a high-throughput parallel metaheuristic scheme for molecular docking

[EN] Motivation Molecular docking methods are extensively used to predict the interaction between protein-ligand systems in terms of structure and binding affinity, through the optimization of a physics-based scoring function. However, the computational requirements of these simulations grow exponentially with: (i) the global optimization procedure, (ii) the number and degrees of freedom of molecular conformations generated and (iii) the mathematical complexity of the scoring function. Results In this work, we introduce a novel molecular docking method named METADOCK 2, which incorporates several novel features, such as (i) a ligand-dependent blind docking approach that exhaustively scans the whole protein surface to detect novel allosteric sites, (ii) an optimization method to enable the use of a wide branch of metaheuristics and (iii) a heterogeneous implementation based on multicore CPUs and multiple graphics processing units. Two representative scoring functions implemented in METADOCK 2 are extensively evaluated in terms of computational performance and accuracy using several benchmarks (such as the well-known DUD) against AutoDock 4.2 and AutoDock Vina. Results place METADOCK 2 as an efficient and accurate docking methodology able to deal with complex systems where computational demands are staggering and which outperforms both AutoDock Vina and AutoDock 4.This work was partially supported by the Fundación Séneca del Centro de Coordinación de la Investigación de la Región de Murcia [Projects 20813/PI/ 18, 20988/PI/18, 20524/PDC/18] and by the Spanish Ministry of Science, Innovation and Universities [TIN2016-78799-P (AEI/FEDER, UE), CTQ2017-87974-R]. 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Differential regulation of the muscle-specific GLUT4 enhancer in regenerating and adult skeletal muscle

We have reported a novel functional co-operation among MyoD, myocyte enhancer factor-2 (MEF2), and the thyroid hormone receptor in a muscle-specific enhancer of the rat GLUT4 gene in muscle cells. Here, we demonstrate that the muscle-specific enhancer of the GLUT4 gene operates in skeletal muscle and is muscle fiber-dependent and innervation-independent. Under normal conditions, both in soleus and in extensor digitorum longus muscles, the activity of the enhancer required the integrity of the MEF2-binding site. Cancellation of the binding site of thyroid hormone receptor enhanced its activity, suggesting an inhibitory role. Muscle regeneration of the soleus and extensor digitorum longus muscles caused a marked induction of GLUT4 and stimulation of the enhancer activity, which was independent of innervation. During muscle regeneration, the enhancer activity was markedly inhibited by cancellation of the binding sites of MEF2, MyoD, or thyroid hormone receptors. Different MEF2 isoforms expressed in skeletal muscle (MEF2A, MEF2C, and MEF2D) and all members of the MyoD family had the capacity to participate in the activity of the GLUT4 enhancer as assessed by transient transfection in cultured cells. Our data indicate that the GLUT4 enhancer operates in muscle fibers and its activity contributes to the differences in GLUT4 gene expression between oxidative and glycolytic muscle fibers and to the GLUT4 up-regulation that occurs during muscle regeneration. The activity of the enhancer is maintained in adult muscle by MEF2, whereas during regeneration the operation of the enhancer depends on MEF2, myogenic transcription factors of the MyoD family, and thyroid hormone receptors