Alteracions de l’excitabilitat cortico-espinal en pacients amb dany axonal difús d’origen traumàtic

Aquest treball ha estat dirigit a investigar les característiques de l’excitabilitat cortical del sistema motor en el dany axonal difús (DAD), conseqüència d’un Traumatisme Cranioencefàlic greu (TCE). Hem aplicat diversos paradigmes d'estimulació magnètica transcranial (TMS) de polsos simples, sobre l'escorça motora, per avaluar l'excitabilitat cortical i els mecanismes excitatoris i inhibitoris. Els paràmetres inclouen el llindar motor en repòs (MT), l’àrea sota la corba dels potencials motors evocats compostos (MEP), corbes d’estímul resposta, la variabilitat dels MEPs i la durada del període de silenci (SP). El grup de pacients en general va mostrar un MT més alt que els pacients, àrees dels MEPs més petites, i menor increment en les corbes en comparació amb els controls normals (p <0,05). Les alteracions en l'excitabilitat van ser significativament més pronunciades amb l'augment de la gravetat del DAD (p <0,005) i la presència de deteriorament motor (p <0,05), mentre que la coexistència de lesions focals no va afectar el grau dels canvis del MEPs. La variabilitat dels MEPs va ser significativament menor en el grup que presentava sols dèficit motor (P<0,05). La inhibició cortical, segons mostrava la durada del SP, no va mostrar diferències significatives en cap dels grups de pacients. En conclusió, les nostres troballes reforcen el concepte de que l’alteració dels fenòmens excitatoris i inhibitoris en l'escorça motora no son processos paral•lels, i aporten informació sobre els diferents patrons d’alteració en el DAD. A més, aquestes dades suggereixen que les alteracions en els mecanismes excitatoris corticoespinals es determinen principalment per la gravetat del DAD i mostren una relació significativa amb l’afectació clínica en relació a la funció motora després d'un TCE greu que afecta difusament les connexions corticals del sistema motor. Des d'un punt de vista clínic, aquest estudi indica que la neurofisiologia hauria de ser considerada com una exploració complementaria a l’exploració neurològica en el TCE greu.

Constant interest rate projections without the curse of indeterminacy

Constant interest rate (CIR) projections are often criticized on the grounds that they are inconsistent with the existence of a unique equilibrium in a variety of forward-looking models. This note shows howto construct CIR projections that are not subject to that criticism, using a standard New Keynesian model as a reference framework.

Nogo, myelin and axonal regeneration

Adult mammalian central nervous system (CNS) axons have very limited capacity of regrowth after injury. In recent years, advances in the field of axonal regeneration have proved that neurons do not regenerate, mainly because of the presence of inhibitory molecules. Myelin-associated proteins limit axonal outgrowth and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo, MAG and OMgp, share a common neuronal receptor (NgR), and together represent one of the main hindrances to neuronal regeneration. The recent molecular cloning of Nogo and its receptors opened a new door to the study of axon regeneration. However, many of the elements involved in the myelin inhibitory pathway are still unknown, and the preliminary experiments with knockout mice are rather contradictory. Because of this complexity, Nogo and NgR need to be characterized before precise strategies to promote axon regeneration in the CNS can be designed.

Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections

Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.

Toxic neurofilamentous axonopathies accumulation of neurofilaments and axonal degeneration

A number of neurotoxic chemicals induce accumulation of neurofilaments in axonal swellings that appear at varying distances from the cell body. This pathology is associated with axonal degeneration of different degrees. The clinical manifestation is most commonly that of a mixed motor-sensory peripheral axonopathy with a disto-proximal pattern of progression, as in cases of chronic exposure to n-hexane and carbon disulphide. It has been demonstrated that protein adduct formation is a primary molecular mechanism of toxicity in these axonopathies, but how this mechanism leads to neurofilament accumulation and axonal degeneration remains unclear. Furthermore, little is known regarding the mechanisms of neurofilamentous axonopathy caused by 3,3′-iminodipropionitrile, an experimental toxin that induces proximal axon swelling that is strikingly similar to that found in early amyotrophic lateral sclerosis. Here, we review the available data and main hypotheses regarding the toxic axonopathies and compare them with the current knowledge of the biological basis of neurofilament transport. We also review recent studies addressing the question of how these axonopathies may cause axonal degeneration. Understanding the mechanisms underlying the toxic axonopathies may provide insight into the relationship between neurofilament behaviour and axonal degeneration, hopefully enabling the identification of new targets for therapeutic intervention. Because neurofilament abnormalities are a common feature of many neurodegenerative diseases, advances in this area may have a wider impact beyond toxicological significance

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Niche Differentiation and Fine-Scale Projections for Argentine Ants Based on Remotely Sensed Data

Modeling ecological niches of species is a promising approach for predicting the geographic potential of invasive species in new environments. Argentine ants (Linepithema humile) rank among the most successful invasive species: native to South America, they have invaded broad areas worldwide. Despite their widespread success, little is known about what makes an area susceptible - or not - to invasion. Here, we use a genetic algorithm approach to ecological niche modeling based on high-resolution remote-sensing data to examine the roles of niche similarity and difference in predicting invasions by this species. Our comparisons support a picture of general conservatism of the species' ecological characteristics, in spite of distinct geographic and community contexts

Projeccions de canvi climatic per a Catalunya (NE Península Ibèrica). Part II: sintetitzant diverses metodologies = Climate change projections for Catalonia (NE Iberian Peninsula). Part II: Integrating several methodologies

The publication of the fourth IPCC report, as well as the number of research results reported in recent years about the regionalization of climate projections, were the driving forces to justify the update of the report on climate change in Catalonia. Specifically, the new IPCC report contains new climate projections at global and continental scales, while several international projects (especially European projects PRUDENCE and ENSEMBLES) have produced continental-scale climate projections, which allow for distinguishing between European regions. For Spain, some of these results have been included in a document commissioned by the“State Agency of Meteorology”. In addition, initiatives are being developed within Catalonia (in particular, by the Meteorological Service of Catalonia) to downscale climate projections in this area. The present paper synthesizes results of these and other previously published studies, as well as our own analysis of results of the ENSEMBLES project. The aim is to propose scenarios of variation in temperature and rainfall in Catalonia during the 21st Century. Thus, by the middle of this century temperatures could rise up to 2 C compared with that of the late 20th Century. These increases would probably be higher in summer than in winter, generalized across the territory but less pronounced in coastal areas. Rainfall, however, would not change much, but it could slightly decrease. Towards the end of the 21st Century, temperatures could rise to about 5 C above that of the last century, while the average rainfall could decrease by more than 10%. Increases in temperature would be higher in summer and in areas further from the coast. Rainfall would decrease especially during the summer, while it could even increase in winter in mountainous areas such as the Pyrenees.

Real rank zero algebras have the corona factorization property

The purpose of this short note is to prove that a stable separable C*-algebra with real rank zero has the so-called corona factorization property, that is, all the full multiplier projections are properly in finite. Enroute to our result, we consider conditions under which a real rank zero C*-algebra admits an injection of the compact operators (a question already considered in [21]).

Tendències temporals de la mortalitat per càncer de fetge a Catalunya: periode 1983-2002 i projeccions pel 2005

Estudi elaborat a partir d’una estada al Finnish Cancer Registry a Helsinki, Finlandia entre setembre i novembre del 2006. Davant l’increment dels tumors hepàtics en països industrialitzats, s’avaluen les tendències temporals de la malaltia hepàtica a Catalunya durant el període 1983-2002 i s’estima la tendència futura a partir de l’any 2005. L’estudi s’ha basat en dades del Registre de Mortalitat de Catalunya i de l’Institut d’Estadística de Catalunya. La malaltia hepàtica inclou diverses tipologies de tumors hepàtics i la cirrosi hepàtica. Els models edad-període-cohort s’han emprat per estimar els efectes període de mortalitat i cohort de naixement. Els resultats han mostrat que les taxes de mortalitat per cirrosi han disminuït en ambdós sexes, exceptuant els homes d’entre els 35-50 anys, pels quals la mortalitat es mantingué estable. S’han observat increments en la mortalitat per carcinoma hepatocel•lular i en els tumors de vies biliars intrahepàtiques, mentre que les projeccions mostren estabilitat en la tendència d’aquestes malalties durant el període 2005-2009. Les tendències de la mortalitat per malaltia hepàtica constatades poden ser degudes a la implementació de teràpies noves, nous mètodes de diagnòstic, infecció pel virus de l’hepatitis C d’altres factors desconeguts.

Addressing the net balances problem as a prerequisite for EU budget reform: a proposal

Conflict among member states regarding the distribution of net financial burdens has been allowed to contaminate the entire design of the EU budget with very negative consequences in terms of equity, efficiency and transparency. To get around this problem and pave the way for a substantive budget reform, we propose to decouple distributional negotiations from the rest of the budget process by linking member state net balances in a rigid manner to relative prosperity. This would be achieved through the introduction of a system of compensating horizontal transfers that would take to its logical conclusion the Commission's proposal for a generalized compensation mechanism. We discuss the impact of the proposed scheme on member states? incentives and illustrate its financial implications using revenue and expenditure projections for 2013 that are based on the current Financial Perspectives and Own Resources Decision.

Spanish pension system: population aging and immigration policy

There is a widespread consensus in the literature that, as consequence of the demographic transition, the current Spanish pension system will become unsustainable in the next decades. In this article we evaluate the sustainability of the contributory pensions' sub-system, taking into account the demographic projections by the Spanish Statistical Office (INE). A baseline scenario is projected as well as several reforms are simulated, focusing on: (i) selective immigration policy, (ii) changes in the way of setting the pensions and (iii) increase of the legal age of retirement up to 68. The main results are the following. The current system would not incur deficits until 2018, from then deficits will begin to be accumulated. The expenditure in pensions practically would double (from 8.3 % in 2005 to 17.2 % in 2050). A selective immigration policy -towards foreign young people- would help, but does not solve the long-term sustainability of the current system. A policy that combines a pensions' growth at a pace lower than productivity growth and extends the legal age of retirement up to 68 would give solvency to the system beyond 2029

Analisi espacial del canvi climàtic al continent europeu. Incerteses i exposicions principals

El canvi climàtic del segle XXI és una realitat, hi ha moltes evidències científiques que indiquen que l’escalfament del sistema climàtic és inequívoc. Malgrat això, també hi ha moltes incerteses respecte els impactes que pot comportar aquest canvi climàtic global. L’objectiu d’aquest projecte és estudiar la possible evolució futura de tres variables climàtiques, que són el rang de la temperatura diürna a prop de la superfície (DTR), la temperatura mitjana a prop de la superfície (MT) i la precipitació mensual (PL_mes) i valorar l’exposició que poden experimentar diferents cobertes del sòl i diferents regions biogeogràfiques del continent europeu davant d’aquests possibles patrons de canvi. Per això s’han utilitzat Models Climàtics Globals que fan projeccions de variables climàtiques que permeten preveure el possible clima futur. Mitjançant l’aplicatiu informàtic Tetyn s’han extret els paràmetres climàtics dels conjunts de dades del Tyndall Centre for Climate Change Research, del futur (TYN SC) i del passat (CRU TS). Les variables obtingudes s’han processat amb eines de sistemes d’informació geogràfica (SIG) per obtenir els patrons de canvi de les variables a cada coberta del sòl. Els resultats obtinguts mostren que hi ha una gran variabilitat, que augmenta amb el temps, entre els diferents models climàtics i escenaris considerats, que posa de manifest la incertesa associada a la modelització climàtica, a la generació d’escenaris d’emissions i a la naturalesa dinàmica i no determinista del sistema climàtic. Però en general, mostren que les glaceres seran una de les cobertes més exposades al canvi climàtic, i la mediterrània, una de les regions més vulnerables