Increased expression of cystine/glutamate antiporter in multiple sclerosis

Background: Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter x(c)(-), an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system x(c)(-) in glutamate homeostasis alterations in MS pathology. -- Methods: Primary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and in samples of MS patients. -- Results and discussion: We show here that human activated monocytes release glutamate through cystine/glutamate antiporter x(c)(-) and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS) and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes. -- Conclusions: Together, these results reveal that increased expression of the cystine/glutamate antiporter system x(c)(-) in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.

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.

Interface electronics for an RF resonance-based displacement sensor

6 p. Paper of the 17th Conference on Sensors and Their Applications held in Dubrovnik, Croatia. Sep 16-18, 2013

Defects structure characterization of NiMnGa alloys by PALS

16th International Conference on Positron Annihilation (ICPA) Univ Bristol, H H Wills Phys Lab, Bristol, ENGLAND AUG 19-24, 2012 Edited by:Alam, A; Coleman, P; Dugdale, S; Roussenova, M

Is General Relativity a simplified theory?

IARD 8th Biennial Conference on Classical and Quantum Relativistic Dynamics of Particles and Fields - Galileo Galilei Inst Theoret Phys (GGI), Florence, ITALY - MAY 29-JUN 01, 2012. Edited by:Horowitz, LP

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.

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

A new adaptive marine policy toolbox to support ecosystem-based approach to management

4 p.

Spinal circuits can accommodate interaction torques during multijoint limb movements

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

Unveiling the factors shaping the distribution of widely distributed alpine vertebrates, using multi-scale ecological niche modelling of the bat Plecotus macrobullaris

Several alpine vertebrates share a distribution pattern that extends across the South-western Palearctic but is limited to the main mountain massifs. Although they are usually regarded as cold-adapted species, the range of many alpine vertebrates also includes relatively warm areas, suggesting that factors beyond climatic conditions may be driving their distribution. In this work we first recognize the species belonging to the mentioned biogeographic group and, based on the environmental niche analysis of Plecotus macrobullaris, we identify and characterize the environmental factors constraining their ranges. Distribution overlap analysis of 504 European vertebrates was done using the Sorensen Similarity Index, and we identified four birds and one mammal that share the distribution with P. macrobullaris. We generated 135 environmental niche models including different variable combinations and regularization values for P. macrobullaris at two different scales and resolutions. After selecting the best models, we observed that topographic variables outperformed climatic predictors, and the abruptness of the landscape showed better predictive ability than elevation. The best explanatory climatic variable was mean summer temperature, which showed that P. macrobullaris is able to cope with mean temperature ranges spanning up to 16 degrees C. The models showed that the distribution of P. macrobullaris is mainly shaped by topographic factors that provide rock-abundant and open-space habitats rather than climatic determinants, and that the species is not a cold-adapted, but rather a cold-tolerant eurithermic organism. P. macrobullaris shares its distribution pattern as well as several ecological features with five other alpine vertebrates, suggesting that the conclusions obtained from this study might be extensible to them. We concluded that rock-dwelling and open-space foraging vertebrates with broad temperature tolerance are the best candidates to show wide alpine distribution in the Western Palearctic.

Learning to perceive in the sensor motor approach: Piaget's theory of equilibration interpreted dynamically

Learning to perceive is faced with a classical paradox: if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the "laws" of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget's theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget's theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level.

Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain

Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-kappa B)p65 levels were not different between the groups. Interleukin-1beta (IL-1 beta) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder.

A genealogical map of the concept of habit

The notion of information processing has dominated the study of the mind for over six decades. However, before the advent of cognitivism, one of the most prominent theoretical ideas was that of Habit. This is a concept with a rich and complex history, which is again starting to awaken interest, following recent embodied, enactive critiques of computationalist frameworks. We offer here a very brief history of the concept of habit in the form of a genealogical network-map. This serves to provide an overview of the richness of this notion and as a guide for further re-appraisal. We identify 77 thinkers and their influences, and group them into seven schools of thought. Two major trends can be distinguished. One is the associationist trend, starting with the work of Locke and Hume, developed by Hartley, Bain, and Mill to be later absorbed into behaviorism through pioneering animal psychologists (Morgan and Thorndike). This tradition conceived of habits atomistically and as automatisms (a conception later debunked by cognitivism). Another historical trend we have called organicism inherits the legacy of Aristotle and develops along German idealism, French spiritualism, pragmatism, and phenomenology. It feeds into the work of continental psychologists in the early 20th century, influencing important figures such as Merleau-Ponty, Piaget, and Gibson. But it has not yet been taken up by mainstream cognitive neuroscience and psychology. Habits, in this tradition, are seen as ecological, self-organizing structures that relate to a web of predispositions and plastic dependencies both in the agent and in the environment. In addition, they are not conceptualized in opposition to rational, volitional processes, but as transversing a continuum from reflective to embodied intentionality. These are properties that make habit a particularly attractive idea for embodied, enactive perspectives, which can now re-evaluate it in light of dynamical systems theory and complexity research.