881 research outputs found

    Mindsets and Failures : Neural Differences in Reactions to Mistakes among 2nd Grade Finnish Girls

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    Mindsets have been identified as an important factor in explaining learning differences among students. Growth mindset students have been shown to recover from mistakes easier than fixed mindset students, and recent neuroscientific research has shown differences in the brain’s event-related potentials to errors in fixed and growth mindset participants. The purpose of this study was to examine and evaluate these differences in the Finnish elementary school context. To achieve this, event-related potentials of five fixed and five growth mindset 8-9-year-old female students were recorded during a go/no-go task. Differences between the two groups emerged, however, they were different from the results of some previous studies in the field. These findings are discussed in the light of earlier neuroscientific research related to mindsets, including limitations and suggestions for future research in the field.Peer reviewe

    E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I

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    p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation's effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases. © 2013 Gao et al

    Female patients with follicular lymphoma have a better prognosis if primary remission lasts over 24 months

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    Findings regarding the role of sex in follicular lymphoma (FL) are contradictory and the prognostic value of sex among patients with early progression of disease (POD) remains unclear. We collected real-life data from nine hospitals in Finland and Spain including 1020 FL patients to study the influence of sex on disease outcome. The median follow-up duration was 67 months (range 0-226 months). Female patients showed better progression-free survival (PFS) (hazard ratio [HR], 0.720; 95% confidence interval [CI], 0.588-0.881), disease-specific survival (DSS) (HR, 0.653; 95% CI, 0.448-0.951), and overall survival (OS) (HR, 0.653; 95% CI, 0.501-0.853) than male patients. However, there were no significant sex differences in prognosis in patients with early POD. This study strengthens the understanding that male sex is an adverse prognostic factor for FL. However, this difference does not apply to patients with early POD.Peer reviewe

    The Transcription Factor Twist1 Has a Significant Role in Mycosis Fungoides (MF) Cell Biology: An RNA Sequencing Study of 40 MF Cases

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    The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from 40 MF patients with stage I–IV disease. Immunohistochemistry (IHC) was used to determinate the protein expression levels of Twist1 and Zeb1. Based on RNA sequencing, principal component analysis (PCA), differential expression (DE) analysis, ingenuity pathway analysis (IPA), and hub gene analysis were performed between the high and low Twist1 IHC expression cases. The DNA from 28 samples was used to analyze the TWIST1 promoter methylation level. In the PCA, Twist1 IHC expression seemed to classify cases into different groups. The DE analysis yielded 321 significant genes. In the IPA, 228 significant upstream regulators and 177 significant master regulators/causal networks were identified. In the hub gene analysis, 28 hub genes were found. The methylation level of TWIST1 promoter regions did not correlate with Twist1 protein expression. Zeb1 protein expression did not show any major correlation with global RNA expression in the PCA. Many of the observed genes and pathways associated with high Twist1 expression are known to be involved in immunoregulation, lymphocyte differentiation, and aggressive tumor biology. In conclusion, Twist1 might be an important regulator in the disease progression of MF

    Effects of low temperature on photoinhibition and singlet oxygen production in four natural accessions of Arabidopsis

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    Main conclusionsLow temperature decreases PSII damage in vivo, confirming earlier in vitro results. Susceptibility to photoinhibition differs among Arabidopsis accessions and moderately decreases after 2-week cold-treatment. Flavonols may alleviate photoinhibition.AbstractThe rate of light-induced inactivation of photosystem II (PSII) at 22 and 4 degrees C was measured from natural accessions of Arabidopsis thaliana (Rschew, Tenela, Columbia-0, Coimbra) grown under optimal conditions (21 degrees C), and at 4 degrees C from plants shifted to 4 degrees C for 2 weeks. Measurements were done in the absence and presence of lincomycin (to block repair). PSII activity was assayed with the chlorophyll a fluorescence parameter F-v/F-m and with light-saturated rate of oxygen evolution using a quinone acceptor. When grown at 21 degrees C, Rschew was the most tolerant to photoinhibition and Coimbra the least. Damage to PSII, judged from fitting the decrease in oxygen evolution or F-v/F-m to a first-order equation, proceeded more slowly or equally at 4 than at 22 degrees C. The 2-week cold-treatment decreased photoinhibition at 4 degrees C consistently in Columbia-0 and Coimbra, whereas in Rschew and Tenela the results depended on the method used to assay photoinhibition. The rate of singlet oxygen production by isolated thylakoid membranes, measured with histidine, stayed the same or slightly decreased with decreasing temperature. On the other hand, measurements of singlet oxygen from leaves with Singlet Oxygen Sensor Green suggest that in vivo more singlet oxygen is produced at 4 degrees C. Under high light, the PSII electron acceptor Q(A) was more reduced at 4 than at 22 degrees C. Singlet oxygen production, in vitro or in vivo, did not decrease due to the cold-treatment. Epidermal flavonols increased during the cold-treatment and, in Columbia-0 and Coimbra, the amount correlated with photoinhibition tolerance

    Evaluating snow models with varying process representations for hydrological applications

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    Much effort has been invested in developing snow models over several decades, resulting in a wide variety of empirical and physically based snow models. For the most part, these models are built on similar principles. The greatest differences are found in how each model parameterizes individual processes (e.g., surface albedo and snow compaction). Parameterization choices naturally span a wide range of complexities. In this study, we evaluate the performance of different snow model parameterizations for hydrological applications using an existing multimodel energy-balance framework and data from two well-instrumented alpine sites with seasonal snow cover. We also include two temperature-index snow models and an intensive, physically based multilayer snow model in our analyses. Our results show that snow mass observations provide useful information for evaluating the ability of a model to predict snowpack runoff, whereas snow depth data alone are not. For snow mass and runoff, the energy-balance models appear transferable between our two study sites, a behavior which is not observed for snow surface temperature predictions due to site-specificity of turbulent heat transfer formulations. Errors in the input and validation data, rather than model formulation, seem to be the greatest factor affecting model performance. The three model types provide similar ability to reproduce daily observed snowpack runoff when appropriate model structures are chosen. Model complexity was not a determinant for predicting daily snowpack mass and runoff reliably. Our study shows the usefulness of the multimodel framework for identifying appropriate models under given constraints such as data availability, properties of interest and computational cost

    Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week

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    Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving

    Polyteam Semantics

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    Team semantics is the mathematical framework of modern logics of dependence and independence in which formulae are interpreted by sets of assignments (teams) instead of single assignments as in first-order logic. In order to deepen the fruitful interplay between team semantics and database dependency theory, we define "Polyteam Semantics" in which formulae are evaluated over a family of teams. We begin by defining a novel polyteam variant of dependence atoms and give a finite axiomatisation for the associated implication problem. We also characterise the expressive power of poly-dependence logic by properties of polyteams that are downward closed and definable in existential second-order logic (ESO). The analogous result is shown to hold for poly-independence logic and all ESO-definable properties.Peer reviewe

    \u3ci\u3eTrans\u3c/i\u3e-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at the ANGPTL8 HDL-C GWAS Locus

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    Recent genome-wide association studies (GWAS) have identified variants associated with highdensity lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8 gene. Given the extensive sharing of GWAS loci across populations, we hypothesized that at least one shared variant at this locus affects HDL-C. The HDL-C–associated variants are coincident with expression quantitative trait loci for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8 expression levels are associated with HDL-C levels. We identified a 400-bp promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to regulating expression in liver and adipose. To identify variants functionally responsible for the HDL-C association, we performed fine-mapping analyses and selected 13 candidate variants that overlap putative regulatory regions to test for allelic differences in regulatory function. Of these variants, rs12463177-G increased transcriptional activity (1.5-fold, P = 0.004) and showed differential protein binding. Six additional variants (rs17699089, rs200788077, rs56322906, rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in transcriptional activity and/or protein binding. Taken together, these data suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue-selective expression and at least one functional variant
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