1,490 research outputs found

    Fourth clivar workshop on the evaluation of ENSO processes in climate models: ENSO in a changing climate

    Get PDF
    n/aThe organizers acknowledge the generous support of the World Climate Research Programme/CLIVAR, the Centre National de la Recherche Scientifique–Institut National des Sciences de l’Univers (CNRS-INSU), the LabEx L-IPSL, and Sorbonne Universités and wish to thank Lei Han, from the International CLIVAR Global Project Office in Qingdao, China, for his invaluable help in organizing this workshop

    Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity

    Get PDF
    Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo

    Socio-cognitive scaffolding with collaboration scripts: a meta-analysis

    Get PDF
    Scripts for computer-supported collaborative learning (CSCL) offer socio-cognitive scaffolding for learners to engage in collaborative activities that are considered beneficial for learning. Yet, CSCL scripts are often criticized for hampering naturally emerging collaboration. Research on the effectiveness of CSCL scripts has shown divergent results. This article reports a meta-analysis about the effects of CSCL scripts on domain-specific knowledge and collaboration skills. Results indicate that CSCL scripts as a kind of socio-cognitive scaffolding can enhance learning outcomes substantially. Learning with CSCL scripts leads to a small positive effect on domain-specific knowledge (d = 0.20) and a large positive effect on collaboration skills (d = 0.95) compared to unstructured CSCL. Further analyses reveal that CSCL scripts are particularly effective for domain-specific learning when they prompt transactive activities (i.e., activities in which a learner’s reasoning builds on the contribution of a learning partner) and when they are combined with additional content-specific scaffolding (worked examples, concept maps, etc.). Future research on CSCL scripts should include measures of learners’ internal scripts (i.e., prior collaboration skills) and the transactivity of the actual learning process

    Pacific climate variability and the possible impact on global surface CO2 flux

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Climate variability modifies both oceanic and terrestrial surface CO2 flux. Using observed/assimilated data sets, earlier studies have shown that tropical oceanic climate variability has strong impacts on the land surface temperature and soil moisture, and that there is a negative correlation between the oceanic and terrestrial CO2 fluxes. However, these data sets only cover less than the most recent 20 years and are insufficient for identifying decadal and longer periodic variabilities. To investigate possible impacts of interannual to interdecadal climate variability on CO2 flux exchange, the last 125 years of an earth system model (ESM) control run are examined.</p> <p>Results</p> <p>Global integration of the terrestrial CO2 flux anomaly shows variation much greater in amplitude and longer in periodic timescale than the oceanic flux. The terrestrial CO2 flux anomaly correlates negatively with the oceanic flux in some periods, but positively in others, as the periodic timescale is different between the two variables. To determine the spatial pattern of the variability, a series of composite analyses are performed. The results show that the oceanic CO2 flux variability peaks when the eastern tropical Pacific has a large sea surface temperature anomaly (SSTA). By contrast, the terrestrial CO2 flux variability peaks when the SSTA appears in the central tropical Pacific. The former pattern of variability resembles the ENSO-mode and the latter the ENSO-modoki<sup>1</sup>.</p> <p>Conclusions</p> <p>Our results imply that the oceanic and terrestrial CO2 flux anomalies may correlate either positively or negatively depending on the relative phase of these two modes in the tropical Pacific.</p

    Push-me-pull-you: how microtubules organize the cell interior

    Get PDF
    Dynamic organization of the cell interior, which is crucial for cell function, largely depends on the microtubule cytoskeleton. Microtubules move and position organelles by pushing, pulling, or sliding. Pushing forces can be generated by microtubule polymerization, whereas pulling typically involves microtubule depolymerization or molecular motors, or both. Sliding between a microtubule and another microtubule, an organelle, or the cell cortex is also powered by molecular motors. Although numerous examples of microtubule-based pushing and pulling in living cells have been observed, it is not clear why different cell types and processes employ different mechanisms. This review introduces a classification of microtubule-based positioning strategies and discusses the efficacy of pushing and pulling. The positioning mechanisms based on microtubule pushing are efficient for movements over small distances, and for centering of organelles in symmetric geometries. Mechanisms based on pulling, on the other hand, are typically more elaborate, but are necessary when the distances to be covered by the organelles are large, and when the geometry is asymmetric and complex. Thus, taking into account cell geometry and the length scale of the movements helps to identify general principles of the intracellular layout based on microtubule forces

    Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1) and association with bipolar affective disorder in Taiwan

    Get PDF
    BACKGROUND: Disturbances in serotonin neurotransmission are implicated in the etiology of many psychiatric disorders, including bipolar affective disorder (BPD). The tryptophan hydroxylase gene (TPH), which codes for the enzyme catalyzing the rate-limiting step in serotonin biosynthetic pathway, is one of the leading candidate genes for psychiatric and behavioral disorders. In a preliminary study, we found that TPH1 intron7 A218C polymorphism was associated with BPD. This study was designed to investigate sequence variants of the TPH1 gene in Taiwanese and to test whether the TPH1 gene is a susceptibility factor for the BPD. METHODS: Using a systematic approach, we have searched the exons and promoter region of the TPH1 gene for sequence variants in Taiwanese Han and have identified five variants, A-1067G, G-347T, T3804A, C27224T, and A27237G. These five variants plus another five taken from the literature and a public database were examined for an association in 108 BPD patients and 103 controls; no association was detected for any of the 10 variants. RESULTS: Haplotype constructions using these 10 SNPs showed that the 3 most common haplotypes in both patients and controls were identical. One of the fourth common haplotype in the patient group (i.e. GGGAGACCCA) was unique and showed a trend of significance with the disease (P = 0.028). However, the significance was abolished after Bonferroni correction thus suggesting the association is weak. In addition, three haplotype-tagged SNPs (htSNPs) were selected to represent all haplotypes with frequencies larger than 2% in the Taiwanese Han population. The defined TPH1 htSNPs significantly reduce the marker number for haplotype analysis thus provides useful information for future association studies in our population. CONCLUSION: Results of this study did not support the role of TPH1 gene in BPD etiology. As the current studies found the TPH1 gene under investigation belongs to the peripheral serotonin system and may link to a cardiac dysfunction phenotype, a second TPH gene that functions predominantly in the brain (i.e., nTPH or TPH2) should be the target for the future association study

    Hydrogen physisorption based on the dissociative hydrogen chemisorption at the sulphur vacancy of MoS2 surface

    Get PDF
    We provide a new insight that the sulphur-depleted MoS2 surface can store hydrogen gas at room temperature. Our findings reveal that the sulphur-vacancy defects preferentially serve as active sites for both hydrogen chemisorption and physisorption. Unexpectedly the sulphur vacancy instantly dissociates the H-2 molecules and strongly binds the split hydrogen at the exposed Mo atoms. Thereon the additional H-2 molecule is adsorbed with enabling more hydrogen physisorption on the top sites around the sulphur vacancy. Furthermore, the increase of the sulphur vacancy on the MoS2 surface further activates the dissociative hydrogen chemisorption than the H-2 physisorption
    corecore