Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the alpha II-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative alpha II-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes

Formation of the BiAg2 surface alloy on lattice-mismatched interfaces

We report on the growth of a monolayer-thick BiAg2 surface alloy on thin Ag films grown on Pt(111) and Cu(111). Using low energy electron diffraction (LEED), angle resolved photoemission spectroscopy (ARPES), and scanning tunneling microscopy (STM) we show that the surface structure of the 13 ML Bi/x-ML Ag/Pt(111) system (x≥2) is strongly affected by the annealing temperature required to form the alloy. As judged from the characteristic (3×3)R30 LEED pattern, the BiAg2 alloy is partially formed at room temperature. A gentle, gradual increase in the annealing temperatures successively results in the formation of a pure BiAg2 phase, a combination of that phase with a (2×2) superstructure, and finally the pure (2×2) phase, which persists at higher annealing temperatures. These results complement recent work reporting the (2×2) as a predominant phase, and attributing the absence of BiAg2 alloy to the strained Ag/Pt interface. Likewise, we show that the growth of the BiAg2 alloy on similarly lattice-mismatched 1 and 2 ML Ag-Cu(111) interfaces also requires a low annealing temperature, whilst higher temperatures result in BiAg2 clustering and the formation of a BiCu2 alloy. The demonstration that the BiAg2 alloy can be formed on thin Ag films on different substrates presenting a strained interface has the prospect of serving as bases for technologically relevant systems, such as Rashba alloys interfaced with magnetic and semiconductor substrates.This work was supported by the Spanish Gouvernment (Grant No. MAT2013-46593-C6-4-P), the Basque Gouvernment (Grant No. IT621-13), and the Spanish Research Council (Grant No. CSIC-201560I022). Z.M.A. would like to acknowledge funding from DAAD and DIPC. P.L. would also like to acknowledge funding from the Deutsche Forschungsgemeinschaft via Project No.RE 1469/8-1.Peer Reviewe

Precise engineering of quantum dot array coupling through their barrier widths

Quantum dots are known to confine electrons within their structure. Whenever they periodically aggregate into arrays and cooperative interactions arise, novel quantum properties suitable for technological applications show up. Control over the potential barriers existing between neighboring quantum dots is therefore essential to alter their mutual crosstalk. Here we show that precise engineering of the barrier width can be experimentally achieved on surfaces by a single atom substitution in a haloaromatic compound, which in turn tunes the confinement properties through the degree of quantum dot intercoupling. We achieved this by generating self-assembled molecular nanoporous networks that confine the twodimensional electron gas present at the surface. Indeed, these extended arrays form up on bulk surface and thin silver films alike, maintaining their overall interdot coupling. These findings pave the way to reach full control over two-dimensional electron gases by means of self-assembled molecular networks

Hallazgo de la traducción perdida del "Orlando furioso" (1604) de Gonzalo de Oliva, ms 000.029 de la Biblioteca de la Universidad de Navarra, y comparación con las otras traducciones contemporáneas

El presente artículo tiene por objeto dar a conocer el hallazgo de un manuscrito perdido que contiene una traducción áurea del Orlando furioso. A la vista del panorama de circulación del poema de Ariosto en español durante el Siglo de Oro, ofreceremos una descripción codicológica del manuscrito, señalaremos la procedencia de los diversos paratextos que lo integran, lo compararemos con las otras traducciones áureas del texto –centrándonos en la de Jiménez de Urrea–, incidiremos en la tarea de reescritura llevada a cabo sobre él, y, por último, enjuiciaremos el valor que esta traducción tiene tanto para los estudiosos del Siglo de Oro como para cualquier lector.The purpose of this article is to announce the finding of a lost manuscript that contains a 17th century Spanish translation of the Orlando furioso. Considering the circulation of Ariosto’s poem in Spain during this period, we offer a codicological description of the manuscript, we indicate the origin of the various paratexts that make it up, we compare it with the other golden translations of the text –focusing on the one of Jiménez de Urrea–, we focus on the task of rewriting carried out on it, and, finally, we judge the value that this translation has for both the Golden Age scholars and for any reader

Los límites al crecimiento, el cambio climático y la innovación

The purpose of this article is to analyze what the environment and its’ management represents in terms of social innovation; the restrictions that the environment and planet care imply, the actions that have been adopted, the ways in which the different companies have reacted and what the future still holds. We will present this analysis by using to main examples: on the first hand, the problem concerning the limits to growth; on the other hand, the problem of climate changes. The solutions that are being proposed, from the mitigation, the use of market incentives (prices and taxes), the creation of markets for the rights to pollution, the “geo-engineer” solutions, the impulse for technologic innovation, are all clear examples of the ways in which society is confronting the problem.Este artículo tiene como objetivo analizar lo que el medio ambiente y su gestión representa en términos de innovación social; las restricciones que el cuidado del medio ambiente y del planeta plantean, las medidas que se han adoptado, la forma en que las empresas han reaccionado y lo que nos depara todavía el futuro. Lo haremos utilizando dos ejemplos básicos: por un lado, el problema de los Límites al Crecimiento y por otro, el problema del Cambio Climático. Las soluciones que se están proponiendo, desde la mitigación, el uso de incentivos de mercado (precios e impuestos), creación de mercados de derechos de contaminación, soluciones “geo-ingeniereles”, impulso a la innovación tecnológica son claros exponentes de la forma en que la sociedad está enfrentándose al problema

Sequential ring-closing metathesis-vinyl halide Heck cyclization reactions: access to the tetracyclic ring system of ervitsine

A chemoselective indole-templated ring-closing metathesis is used to assemble the cyclohepta[b]indole substructure of the indole alkaloid ervitsine. A subsequent intramolecular Heck coupling of the resulting alkene functionality with an amino-tethered vinyl halide accomplishes the closure of the unique 2- azabicyclo[4.3.1]decane framework of the alkaloid with concomitant incorporation of the exocyclic Eethylidene substituent

Rapid Synthesis of the Ervitsine Alkaloid Skeleton by a Sequential RCM-Heck Cyclization Approach

An efficient approach to the bridged framework of the indole alkaloid ervitsine, featuring a ring-closing metathesis reaction from a 2,3-disubstituted indole followed by a vinyl halide Heck cyclization upon the resulting cycloheptene ring, is described

Facile synthesis of azocino[4,3-b]indoles by ring-closing metathesis

The azocino[4,3-b]indole system, tricyclic substructure of the indole alkaloids apparicine and ervaticine, is efficiently assembled by ring-closing metathesis of 2-allyl-3-(allylaminomethyl)indoles. The metathesis sites are introduced into the indole nucleus by reductive amination of a 3-formyl derivative with allylamine, followed by a-lithiation with subsequent electrophilic trapping with acrolein

Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107