Paper de RIP140 en la fisiopatogenia de la adrenoleucodistròfia lligada a l'X.

La adrenoleucodistrofia ligada al X (X-ALD) es un enfermedad neurometabólica fatal caracterizada por una desmielinización cerebral progresiva infantil (CCALD) o por una neurodegeneración de la médula espinal (adrenomieloneuropatía, AMN), insuficiencia adrenal y acumulación de ácidos grasos de cadena muy larga (AGCML) como el ácido hexacosanoico (C26:0) en tejidos. La enfermedad está causada por mutaciones en el gen ABCD1 el cual codifica para un transportador peroxisomoal que importa AGCML. El ratón knockout para Abcd1 (Abcd1-) desarrolla alteraciones en la médula espinal que mimetizan el modelo de enfermedad AMN con inicio de los síntomas a los 20 meses. Previamente, nuestro grupo evidenció mediante análisis de transcriptómica, una desregulación mitocondrial en el modelo murino Abcd1- . En este trabajo demostramos que tanto en el ratón Abcd1- como en la sustancia blanca afectada de pacientes X-ALD hay una depleción mitocondrial. Para poder explicar esta depleción, estudiamos los niveles de un repressor de la biogenesis mitocondrial, RIP140. En cultivo organotípico de cortes de médula espinal observamos un aumento de los niveles proteicos de RIP140 en el ratón Abcd1- y también un aumento mediado por C26:0. Estos resultados indican que la sobreexpresión de RIP140 puede ser la responsable de la depleción mitocondrial presente en el ratón Abcd1- y una posible nueva diana terapèutica para la X-ALD.

Supernumerary premolars. Report of 10 cases

Supernumerary premolars are 'extra' teeth morphologically belonging to the premolar group. Hyperdontia affecting premolars can be single (when only one supernumerary tooth is found), multiple (if several teeth are involved) or related to a syndrome such as cleidocranial dysplasia. Supernumerary premolars are the third most frequent group of supernumerary teeth, following mesiodens and fourth molars; the prevalence among the general population ranges from 0.09-0.64%. The present study describes 10 cases of supernumerary premolars treated in our Service of Oral and Maxillofacial Surgery of the Dental Clinic of the University of Barcelona. A late onset was demonstrated in one case, contrasting the present pantomograph with another obtained 5 years before. In only one case did the presence of a supernumerary premolar alter normal tooth eruption. Two supernumerary premolars were affected by follicular cysts

Late bloomer or language impaired? Screening the speech of a Spanish-English bilingual toddler for early signs of language impairment

This case study presents corpus data gathered from a Spanish-English bilingual child with expressive language delay. Longitudinal data on the child’s linguistic development was collected from the onset of productive speech at age 1;1 until age 4 over the course of 28 video-taped sessions with the child’s principal caregivers. A literature review focused on the relationship between language delay and persisting disorders—including a discussion of the frequent difficulty in distinguishing between the two at early stages of bilingual development—is followed by an analysis of the child’s productive development in 2 distinct phases. An attempt is made to assess the child’s speech at age 4 for preliminary signs of SLI and to consider techniques for identifying ‘at risk’ bilingual children (that is, those with productive language delay, poor oral fluency, and family history of language problems) based on samples of recorded and transcribed speech.

Ecological conflicts and valuation - mangroves vs. shrimp in the late 1990s

Shrimps are produced in two different ways. They are fished in the sea (sometimes at the cost of turtle destruction) or they are "farmed" in ponds in coastal areas. Such aquaculture is increasing around the world as shrimps become a valuable item of world trade. Mangrove forests are sacrificed for commercial shrimp farming. This paper considers the conflict between mangrove conservation and shrimp exports in different countries.Who has title to the mangroves, who wins and who loses in this tragedy of enclosures? Which languages of valuation are used by different actors in order to compare the increase in shrimp exports and the losses in livelihoods and in environmental services? The economic valuation of damages is only one of the possible languages of valuation which are relevant in practice. Who has the power to impose a particular language of valuation?

Book production and the onset of modern economic growth

Endogenous growth theory suggests that human capital formation plays a significant role for the wealth and poverty of nations. In contrast to previous studies which denied the role of human capital as a crucial determinant of for really long-term growth, we confirm its importance. Indicators of human capital like literacy rates are lacking for the period of 1450-1913; hence, we use per capita book production as a proxy for advanced literacy skills. This study explains how, and to what extent, growth disparities are a function of human capital formation.

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.

A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes

Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.

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.

Late Neogene lacustrine record and paleogeography in the Quillagua-Llamara basin, Central Andean fore-arc (Northern Chile)

The Cenozoic QuillaguaLlamara basin (northern Chile, Central Andes) is an asymmetrical, intramassif fore-arc basin with a relatively wide northern sector separated from a narrower southward extension by a basement threshold. The north- ern sector was characterised by a noticeable Oligocene?late Neogene alluvial-fan and lacustrine dominated deposition which resulted in sequences up to 900 m thick, whereas the southern sector was often a bypass zone with thinner fluvial and lacustrine sediment accumulation.

Photon spectrum produced by the late decay of a cosmic neutrino background

We obtain the photon spectrum induced by a cosmic background of unstable neutrinos. We study the spectrum in a variety of cosmological scenarios and also we allow for the neutrinos having a momentum distribution (only a critical matter-dominated universe and neutrinos at rest have been considered until now). Our results can be helpful when extracting bounds on neutrino electric and magnetic moments from cosmic photon background observations.

Percolation transition and the onset of nonexponential relaxation in fully frustrated models

We numerically study the dynamical properties of fully frustrated models in two and three dimensions. The results obtained support the hypothesis that the percolation transition of the Kasteleyn-Fortuin clusters corresponds to the onset of stretched exponential autocorrelation functions in systems without disorder. This dynamical behavior may be due to the large scale effects of frustration, present below the percolation threshold. Moreover, these results are consistent with the picture suggested by Campbell et al. [J. Phys. C 20, L47 (1987)] in the space of configurations.