Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin¿induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Late and post-Hercyniam low temperature veins in the Catalonian Coastal Ranges

Many of the veins enclosed within the Paleozoic basement of the Catalonian Coastal Ranges show severa1 common characteristics: low temperature of formation (between 75 and 200C), the presence of complex polisaline fluids and a certain relationship to the pretriassic paleosurface. Mineralogical composition and age are variable, ranging from Pb-Zn veins with carbonate gangue of late Hercynian age through metal poor fluorite rich veins to barite rich veins of Triasssic age. Mineralizing fluids are not related to late Hercynianmagmatism and deposition took place in active fractures developed either in extensional as in compressive regimes.

Growth and externalities across economies : an empirical analysis using spatial econometrics

Recent theoretical models of economic growth have emphasised the role of external effects on the accumulation of factors of production. Although most of the literature has considered the externalities across firms within a region, in this paper we go a step further and consider the possibility that these externalities cross the barriers of regional economies. We assess the role of these external effects in explaining growth and economic convergence. We present a simple growth model, which includes externalities across economies, developing a methodology for testing their existence and estimating their strength. In our view, spatial econometrics is naturally suited to an empirical consideration of these externalities. We obtain evidence on the presence of significant externalities both across Spanish and European regions.

Specialisation in Europe and asymmetric shocks: potential risks of EMU

Most optimistic views, based on Optimum Currency Areas (OCA) literature, have concluded that the probability of asymmetric shocks to occur at anational level will tend to diminish in the Economic and Monetary Union (EMU)as a result of the intensification of the integration process during the most recent years. Therefore, since Economic Geography Theories predict a higherspecialisation of regions, it is expected that asymmetric shocks will increase.Previous studies have examined to what extent asymmetric shocks have been relevant in the past using, mainly, static measures of asymmetries such as the correlation coefficients between series of shocks previously calculated from astructural VAR model (Bayoumi and Eichengreen, 1992).In this paper, we study the evolution of manufacturing specific asymmetries in Europe from a dynamic point of view (applying the modelproposed by Haldane and Hall, 1991) in order to obtain new evidence about potential risks of EMU.

Regional economic dynamics and convergence in the european union

Deepening in the European Union (EU) integration process has enhanced the question of economic disparities at a regional level. Theconvergence process observed until the late seventies was exhausted onwards incoincidence with important changes in the economic activity. The paper showshow these factors would have provoked a regional differenciated response that,despite being important, would have not strengthened the decrease in regionalinequalities. We use an alternative and (in our opinion) richer approach to thetraditional convergence analysis, where the evolution of the whole regionaldistribution is what matters and not that of a representative economy. Moreover,when analysing inequalities among regional economies, the geographical spaceacquire an outstanding role. Hence, we apply spatial association tests and relatethem to the convergence analysis

Are commuting and residential mobility decisions simultaneous? : the case of Catalonia (Spain)

In this paper we study the commuting and moving decisions of workers in Catalonia (Spain) and its evolution in the 1986-1996 period. Using a microdata sample from the 1991 Spanish Population Census, we estimate a simultaneous, discrete choice model of commuting and moves, thus indirectly addressing the home and job location decisions. The econometrical framework is a simultaneous, binary probit model with a commute equation and a move equation

Industrial agglomerations and wage gradients: the Spanish economy in the interwar period

This paper gives new evidence on the relationship between integration and industrial agglomeration in the presence of scale economies, by testing directly one of the predictions that can be derived from Krugman (1991), that is, the existence of regional nominal wage gradients and its transformation following changes in trade regimes. Our case study analyzes the effects of the substitution of an open economy by a closed economy regime, exactly the opposite process studied by Hanson (1996, 1997). In Spain, during the interwar period, protectionist policies would have favored the loss of centrality of the coastal location (Barcelona) and the relative rise of central locations (such as Madrid). Our results indicate the existence of a wage gradient centered in Barcelona during the interwar period (1914-1930) and its weakening after 1925.

Authors', Institutions' and Countries' rankings in regional and urban science : an analysis for nine top international journals from 1991 to 2000

This paper examines the most productive authors, institutions and countries in regional and urban science from 1991 to 2000 using information on published articles (and pages) from a sample of widely recognized journals in this field: ARS, JUE, JRS, IJURR, IRSR, PRS, RSUE, RS and US. We also consider the relation between the country of the institution named in articles and the country in which the journal is published, in order to know if there are a home publication bias in regional and urban science. Analysis was made for the whole decade and by subperiods, this allowed us to make a more dynamic interpretation of the results

Topics, techniques and applications in urban and regional science in the nineties: a bibliometric analysis

The current state of regional and urban science has been much discussed and a number of studies have speculated on possible future trends in the development of the discipline. However, there has been little empirical analysis of current publication patterns in regional and urban journals. This paper studies the kinds of topics, techniques and data used in articles published in nine top international journals during the 1990s with the aim of identifying current trends in this research field

Public health expenditure and spatial interactions in a decentralized national health system

One of the limitations of cross-country health expenditure analysis refers to the fact that the financing, the internal organization and political restraints of health care decision-making are country-specific and heterogeneous. Yet, a potential solution is to examine the influence of such effects in those countries that have undertaken decentralization processes. In such a setting, it is possible to examine potential expenditure spillovers across the geography of a country as well as the influence of the political ideology of regional incumbents on public health expenditure. This paper examines the determinants of public health expenditure within Spanish region-states (Autonomous Communities, ACs), most of them subject to similar financing structures although exhibiting significant heterogeneity as a result of the increasing decentralization, region-specific political factors along with different use of health care inputs, economic dimension and spatial interactions

Ownership structure and innovation: Is there a real link?

This work focuses on the study of the relationship between ownership and control structure of the company and its innovative activity. Its aim consists of analysing the role that may be played by determinants within the company related to ownership structure when the decision to incur research and development activities is taken as well as on the output of this innovate process. Among these determinants we may think of issues such as who owns the firm and how the control of decision-making is distributed, the nature of this control and the level of concentration of ownership, among others. The study is carried out for the year 2001 using a representative sample of Spanish manufacturing industries.

Regional integration and specialisation patterns in Spain

The aim of this paper is to analyse how economic integration in Europe has affected industrial geographical concentration in Spain and explain what the driving forces behind industry location are. Firstly, we construct regional specialisation and geographical concentration indices for Spanish 50 provinces and 30 industrial sectors in 1979, 1986 and 1992. Secondly, we carry out an econometric analysis of the determinants of geographical concentration of industries. Our main conclusion is that there is no evidence of increasing specialisation in Spain between 1979 and 1992 and that the most important determinant of Spain¿s economic geography is scale economies. Furthermore, traditional trade theory has no effects in explaining the pattern of industrial concentration

Tax differentials and agglomeration economies in intraregional firm location

This paper analyses empirically how differences in local taxes affect the intraregional location of new manufacturing plants. These effects are examined within the random profit maximization framework while accounting for the presence of different types of agglomeration economies (localization/ urbanization/ Jacobs¿ economies) at the municipal level. We look at the location decision of more than 10,000 establishments locating between 1996 and 2003 across more than 400 municipalities in Catalonia, a Spanish region. It is necessary to restrict the choice set to the local labor market and, above all, to control for agglomeration economies so as to identify the effects of taxes on the location of new establishments.