357 research outputs found

    Note on Comparability of MicroCog Test Forms

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    This study investigated the differences between the Standard and Short forms of MicroCog by comparing Domain scores for a clinical sample of 351 substance abusers which gave a significant difference between scores on the Spatial Processing Domain. Implications for research and clinical use are discussed

    On the Truncated Pareto Distribution with applications

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    The Pareto probability distribution is widely applied in different fields such us finance, physics, hydrology, geology and astronomy. This note deals with an application of the Pareto distribution to astrophysics and more precisely to the statistical analysis of mass of stars and of diameters of asteroids. In particular a comparison between the usual Pareto distribution and its truncated version is presented. Finally a possible physical mechanism that produces Pareto tails for the distribution of the masses of stars is suggested.Comment: 10 pages 6 figure

    DNA damage alters nuclear mechanics through chromatin reorganization

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    DNA double-strand breaks drive genomic instability. However, it remains unknown how these processes may affect the biomechanical properties of the nucleus and what role nuclear mechanics play in DNA damage and repair efficiency. Here, we have used Atomic Force Microscopy to investigate nuclear mechanical changes, arising from externally induced DNA damage. We found that nuclear stiffness is significantly reduced after cisplatin treatment, as a consequence of DNA damage signalling. This softening was linked to global chromatin decondensation, which improves molecular diffusion within the organelle. We propose that this can increase recruitment for repair factors. Interestingly, we also found that reduction of nuclear tension, through cytoskeletal relaxation, has a protective role to the cell and reduces accumulation of DNA damage. Overall, these changes protect against further genomic instability and promote DNA repair. We propose that these processes may underpin the development of drug resistance

    DNA damage alters nuclear mechanics through chromatin reorganization

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    AbstractDNA double-strand breaks drive genomic instability. However, it remains unknown how these processes may affect the biomechanical properties of the nucleus and what role nuclear mechanics play in DNA damage and repair efficiency. Here, we have used Atomic Force Microscopy to investigate nuclear mechanical changes, arising from externally induced DNA damage. We found that nuclear stiffness is significantly reduced after cisplatin treatment, as a consequence of DNA damage signalling. This softening was linked to global chromatin decondensation, which improves molecular diffusion within the organelle. We propose that this can increase recruitment for repair factors. Interestingly, we also found that reduction of nuclear tension, through cytoskeletal relaxation, has a protective role to the cell and reduces accumulation of DNA damage. Overall, these changes protect against further genomic instability and promote DNA repair. We propose that these processes may underpin the development of drug resistance

    Smooth Muscle Cell Phenotype Modulation and Contraction on Native and Cross-Linked Polyelectrolyte Multilayers

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    Smooth muscle cells convert between a motile, proliferative “synthetic ” phenotype and a sessile, “contractile ” phenotype. The ability to manipulate the phenotype of aortic smooth muscle cells with thin biocompatible polyelectrolyte multilayers (PEMUs) with common surface chemical characteristics but varying stiffness was investigated. The stiffness of (PAH/ PAA) PEMUs was varied by heating to form covalent amide bond cross-links between the layers. Atomic force microscopy (AFM) showed that cross-linked PEMUs were thinner than those that were not cross-linked. AFM nanoindentation demonstrated that the Young’s modulus ranged from 6 MPa for hydrated native PEMUs to more than 8 GPa for maximally cross-linked PEMUs. Rat aortic A7r5 smooth muscle cells cultured on native PEMUs exhibited morphology and motility of synthetic cells and expression of the synthetic phenotype markers vimentin, tropomyosin 4, and nonmuscle myosin heavy chain IIB (nmMHCIIB). In comparison, cells cultured on maximally cross-linked PEMUs exhibited the phenotype markers calponin, smooth muscle myosin heavy chain (smMHC), myocardin, transgelin, and smooth muscle R-actin (smActin) that are characteristic of the smooth muscle “contractile ” phenotype. Consistent with those cells being “contractile”, A7r5 cells grown on cross-linked PEMUs produced contractile force when stimulated with a Ca2+ ionophore

    Morphological and Physiological Responses to Drought Stress of European Provenances of Scots Pine

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    Increased frequency and intensity of drought episodes as a consequence of current and predicted climatic changes require an understanding of the intra-specific variability in structural and physiological characteristics of forest trees. Adaptive plasticity and genotypic variability are considered two of the main processes by which trees can either be selected or can acclimate to changing conditions. We tested for the relative importance of genotypic variability, phenotypic plasticity and their interaction by comparing the growth and physiological performance of 15 provenances of Scots pine (Pinus sylvestris L.), under two contrasting irrigation regimes. Selected provenances representing the distribution range of the species in Anatolia, Turkey, were contrasted with seed sources spanning the range from Spain to the UK, in Europe. We found a strong latitudinal differentiation among the 15 provenances for survival after drought, largely the result of the higher mortality of some western and central European provenances. Differentiation in diameter and height growth was also clear with the worst provenance coming from Western Europe (UK). Among the Turkish provenances, the more extreme southern high-elevation populations showed greater survival and lower growth rates overall. Differences in growth and survival were related to differences in photosynthetic pigment and nutrient contents and in the photosynthetic efficiency of photosystem II. Plasticity was strongest for growth characters and pigment contents.WoSScopu

    Seedling emergence and establishment of Pinus sylvestris in the Mongolian forest-steppe ecotone

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    Syftet med studien Ă€r att undersöka och beskriva pedagogers uppfattningar av hur de skapar delaktighet och inflytande, i en kommuns förskoleverksamhet och organisation.Mina frĂ„gestĂ€llningar Ă€r hur pedagogerna beskriver sina möjligheter och hinder för att fĂ„ och skapa delaktighet och inflytande, samt vilka inre och yttre faktorer som finns som pĂ„verkar möjligheten för delaktighet och inflytande.För att undersöka detta har jag valt en kvalitativ forskningsansats. Jag har genomfört semistrukturerade intervjuer med sju pedagoger. Det empiriska materialet har bearbetats kvalitativt i en empirinĂ€ra ansats.I resultatet sĂ„g jag att ett större fokus pĂ„ processkvaliteten behöver lĂ€ggas och medvetenheten behöver ökas, kring den pedagogiska dokumentationens betydelse.Sammanfattningsvis behöver den undersökta kommunens förskolor en gemensam samsyn i hela systemet i ett förstĂ„elsebaserat och tolkande perspektiv som gynnar en lĂ„ngsiktig och hĂ„llbar utveckling.Participation and influence in the preschool, a study with teachers in one municipality.The purpose of this study is to explore and describe teacher’s perceptions of how they create participation and influence, in a municipalityÂŽs preschool and organization.My questions are how teachers describe their opportunities and barriers to get and create participation and influence, and what internal and external factors that affecting the ability of participation and influence.To examine this, I have chosen a qualitative research approach. I have conducted semi structured interviews, with seven teachers. The empirical data have been processed in a qualitative empirical closely approach.In the result, I found that a greater focus on process quality needs to be added and awareness needs to be increased, on the pedagogic documentations significances.In conclusion, needs the municipal preschools, which have been examined, get a common consensus of the entire system in a understanding based and interpretive perspective, that support a long term and sustainable development

    Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

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    <p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (<it>SMN1</it>) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil.</p> <p>Methods</p> <p>Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at <it>P </it>< 0.05. For the remaining analyses, the Student's two-tail <it>t </it>test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at <it>P </it>< 0.05.</p> <p>Results</p> <p>Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific.</p> <p>Conclusions</p> <p>Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA and for other degenerative diseases characterized by muscular atrophy and postsynaptic immaturity.</p
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