32 research outputs found

    Pharmacogenetic Modulation of STEP improves motor and cognitive function in a mouse model of Huntington's disease.

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    Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, which results in an aberrant form of the protein (mhtt). This leads to motor and cognitive deficits associated with corticostriatal and hippocampal alterations. The levels of STriatal-Enriched protein tyrosine Phosphatase (STEP), a neural-specific tyrosine phosphatase that opposes the development of synaptic strengthening, are decreased in the striatum of HD patients and also in R6/1 mice, thereby contributing to the resistance to excitotoxicity described in this HD mouse model. Here, we aimed to analyze whether STEP inactivation plays a role in the pathophysiology of HD by investigating its effect on motor and cognitive impairment in the R6/1 mouse model of HD. We found that genetic deletion of STEP delayed the onset of motor dysfunction and prevented the appearance of cognitive deficits in R6/1 mice. This phenotype was accompanied by an increase in pERK1/2 levels, a delay in the decrease of striatal DARPP-32 levels and a reduction in the size of mhtt aggregates, both in the striatum and CA1 hippocampal region. We also found that acute pharmacological inhibition of STEP with TC-2153 improved cognitive function in R6/1 mice. In conclusion, our results show that deletion of STEP has a beneficial effect on motor coordination and cognition in a mouse model of HD suggesting that STEP inhibition could be a good therapeutic strategy in HD patients

    Splicing regulator SLU7 is essential for maintaining liver homeostasis

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    A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence

    Seasonal dynamics in social behaviour and spacing patterns of the Little Owl Athene noctua

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    Most owl species exhibit territorial behaviour in order to have sufficient resources to maintain their fitness and biological success. The Little Owl (Athene noctua) has been considered a territorial species, although some authors have pointed to movements and social interactions outside a particular territory. We hypothesise that the spatial behaviour and social organisation of Little Owl follows a complex pattern, which varies throughout the year. We radio-tracked nine Little Owls in an area of 10 km(2) over nine months, paying particular attention to home range variation, social interaction and vocal behaviour. Home range size and overlap varied markedly throughout the year, with maximums in winter, and minimum size and overlap during the breeding season. Little Owls showed exclusive home ranges during the breeding season, whereas home range overlap was frequent in winter. Owls which had lost clutches increased their home ranges and shared the same foraging areas with other owls. Vocal activity was low all year round, except in the months immediately prior to courtship. Increase of vocal behaviour was therefore also associated with a reduction in home range

    Design of high-temperature solar-selective coatings based on aluminium titanium oxynitrides AlyTi1-y(OxN1-x). Part 1: Advanced microstructural characterisation and optical simulation

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    Aluminium titanium oxynitrides were studied as candidate materials for high temperature absorbers in solar selective coatings due to their excellent stability and their tuneable optical behaviour. A set of individual AlyTi1-y(OxN1-x) layers with different oxygen content was prepared by cathodic vacuum arc (CVA) deposition. The composition, morphology, phase structure and microstructure of the films were characterized by elastic recoil detection (ERD), scanning and transmission electron microscopy and X-ray diffraction. An fcc phase structure is found in a broad compositional range of AlyTi1-y(OxN1-x). Simultaneously, sample microstructure and morphology undergo systematic changes from a columnar growth to the development of a heterogeneous structure with spherical nanoparticle inclusions when the oxygen concentration is increased. The optical properties were determined by spectroscopic ellipsometry and UV–Vis–NIR and FTIR spectrophotometry. A comprehensive analysis of the film properties allowed an accurate modelling of the optical constants of the AlyTi1-y(OxN1-x) in the whole wavelength range of solar interest (from 190 nm to 25 ”m). It points to a transition from metallic to dielectric behaviour with increasing oxygen content. Consequently, it is demonstrated that the optical properties of these AlyTi1-y(OxN1-x) deposited films can be controlled in a wide range from metallic to dielectric character by adjusting the oxygen concentration, opening a huge range of possibilities for the design of solar selective coatings (SSC) based on this material. Complete SSC, including a TiN layer as IR reflector, were designed by applying optical simulations, obtaining excellent optical selective properties of α=94.0% and ΔRT = 4.8%

    Two cases of cooperative breeding in Eurasian Hobbies

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    Volume: 37Start Page: 342End Page: 34

    Occupancy and abundance of Little Owl Athene noctua in an intensively managed forest area in Biscay

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    We censused a population of Little Owls in Biscay (North Iberian Peninsula) using playback calls. We modelled their distribution using Geographic Information System (GIS), extracting data on land use and landscape composition in occupied and unoccupied areas at two different scales. Little Owl presence and habitat selection were mainly governed by land use practice. The species was linked to traditional agri-pastoral exploitations. Variables such as topography, altitude, road density and urban areas had an effect at the lower scale, whilst density of predator species had an effect only over habitat selection but not over occupancy. At larger scales, the occupancy of apparently suitable areas was related to the structure and spatial composition of land use and, especially, to the proportion of forest plantations. Current policies of land management pay no attention to traditional exploitations and associated wildlife, and the promotion of forest cultures is responsible for the decline of the species in many areas

    Design of high-temperature solar-selective coatings based on aluminium titanium oxynitrides AlyTi1-y(OxN1-x). Part 2: Experimental validation and durability tests at high temperature

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    The durability of two solar-selective aluminium titanium oxynitride multilayer coatings was studied under conditions simulating realistic operation of central receiver power plants. The coatings were deposited by cathodic vacuum arc applying an optimized design concept for complete solar-selective coating (SSC) stacks. Compositional, structural and optical characterization of initial and final stacks was performed by scanning electron microscopy, elastic recoil detection, UV-Vis-NIR-IR spectrophotometry and X-Ray diffraction. The design concept of the solar selective coatings was validated by an excellent agreement between simulated and initial experimental stacking order, composition and optical properties. Both SSC stacks were stable in single stage tests of 12 hours at 650°C. At 800°C, they underwent a structural transformation by full oxidation and they lost their solar selectivity. During cyclic durability tests, multilayer 1, comprised of TiN, Al0.64Ti0.36N and an Al1.37Ti0.54O top layer, fulfilled the performance criterion (PC) ≀ 5% for 300 symmetric, 3 hours long cycles at 600°C in air. Multilayer 2, which was constituted of four AlyTi1-y(OxN1-x) layers, met the performance criterion for 250 cycles (750 hours), but was more sensitive to these harsh conditions. With regard to the degradation mechanisms, the coarser microstructure of multilayer 1 is more resistant against oxidation than multilayer 2 with its graded oxygen content. These results confirm that the designed SSCs based on AlyTi1-y(OxN1-x) materials withstand breakdown at 600ÂșC in air. Therefore, they can be an exciting candidate material for concentrated solar power applications at high temperature

    Design of high-temperature solar-selective coatings based on aluminium titanium oxynitrides AlyTi1−y(OxN1−x). Part 1: Advanced microstructural characterization and optical simulation

    No full text
    Aluminium titanium oxynitrides were studied as candidate materials for high temperature absorbers in solar selective coatings due to their excellent stability and their tuneable optical behaviour. A set of individual AlyTi1−y(OxN1−x) layers with different oxygen content was prepared by cathodic vacuum arc (CVA) deposition. The composition, morphology, phase structure and microstructure of the films were characterized by elastic recoil detection (ERD), scanning and transmission electron microscopy and X-ray diffraction. An fcc phase structure is found in a broad compositional range of AlyTi1−y(OxN1−x). Simultaneously, sample microstructure and morphology undergo systematic changes from a columnar growth to the development of a heterogeneous structure with spherical nanoparticle inclusions when the oxygen concentration is increased. The optical properties were determined by spectroscopic ellipsometry and UV–Vis–NIR and FTIR spectrophotometry. A comprehensive analysis of the film properties allowed an accurate modelling of the optical constants of the AlyTi1−y(OxN1−x) in the whole wavelength range of solar interest (from 190 nm to 25 ”m). It points to a transition from metallic to dielectric behaviour with increasing oxygen content. Consequently, it is demonstrated that the optical properties of these AlyTi1−y(OxN1−x) deposited films can be controlled in a wide range from metallic to dielectric character by adjusting the oxygen concentration, opening a huge range of possibilities for the design of solar selective coatings (SSC) based on this material. Complete SSC, including a TiN layer as IR reflector, were designed by applying optical simulations, obtaining excellent optical selective properties of α = 94.0% and ΔRT = 4.8%
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