Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-XL induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-XL anticipates and enhances DAn generation.

Assessment of expected damage on buildings subjected to Lorca earthquake through an energy-based seismic index method and nonlinear dynamic response analyses

The city of Lorca (Spain) was hit on May 11th, 2011, by two consecutive earth-quakes of magnitudes 4.6 and 5.2 Mw, causing casualties and important damage in buildings. Many of the damaged structures were reinforced concrete frames with wide beams. This study quantifies the expected level of damage on this structural type in the case of the Lorca earth-quake by means of a seismic index Iv that compares the energy input by the earthquake with the energy absorption/dissipation capacity of the structure. The prototype frames investigated represent structures designed in two time periods (1994–2002 and 2003–2008), in which the applicable codes were different. The influence of the masonry infill walls and the proneness of the frames to concentrate damage in a given story were further investigated through nonlinear dynamic response analyses. It is found that (1) the seismic index method predicts levels of damage that range from moderate/severe to complete collapse; this prediction is consistent with the observed damage; (2) the presence of masonry infill walls makes the structure very prone to damage concentration and reduces the overall seismic capacity of the building; and (3) a proper hierarchy of strength between beams and columns that guarantees the formation of a strong column-weak beam mechanism (as prescribed by seismic codes), as well as the adoption of counter-measures to avoid the negative interaction between non-structural infill walls and the main frame, would have reduced the level of damage from Iv=1 (collapse) to about Iv=0.5 (moderate/severe damage)

The Imaging and Slitless Spectroscopy Instrument for Surveys (ISSIS): expected radiometric performance, operation modes and data handling

ISSIS is the instrument for imaging and slitless spectroscopy on-board WSO-UV. In this article, a detailed comparison between ISSIS expected radiometric performance and other ultraviolet instruments is shown. In addition, we present preliminary information on the performance verification tests and on the foreseen procedures for in-flight operation and data handling.

Brown trout thermal niche and climate change: expected changes in the distribution of cold-water fish in central Spain

This paper addresses the determination of the realized thermal niche and the effects of climate change on the range distribution of two brown trout populations inhabiting two streams in the Duero River basin (Iberian Peninsula) at the edge of the natural distribution area of this species. For reaching these goals, new methodological developments were applied to improve reliability of forecasts. Water temperature data were collected using 11 thermographs located along the altitudinal gradient, and they were used to model the relationship between stream temperature and air temperature along the river continuum. Trout abundance was studied using electrofishing at 37 sites to determine the current distribution. The RCP4.5 and RCP8.5 change scenarios adopted by the International Panel of Climate Change for its Fifth Assessment Report were used for simulations and local downscaling in this study. We found more reliable results using the daily mean stream temperature than maximum daily temperature and their respective seven days moving-average to determine the distribution thresholds. Thereby, the observed limits of the summer distribution of brown trout were linked to thresholds between 18.1ºC and 18.7ºC. These temperatures characterise a realised thermal niche narrower than the physiological thermal range. In the most unfavourable climate change scenario, the thermal habitat loss of brown trout increased to 38% (Cega stream) and 11% (Pirón stream) in the upstream direction at the end of the century; however, at the Cega stream, the range reduction could reach 56% due to the effect of a ?warm-window? opening in the piedmont reach.