1,892 research outputs found

    New kid on the ID block: Neural functions of the Nab2/ZC3H14 class of Cys3His tandem zinc-finger polyadenosine RNA binding proteins

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    Polyadenosine RNA binding proteins (Pabs) play critical roles in regulating the polyadenylation, nuclear export, stability, and translation of cellular RNAs. Although most Pabs are ubiquitously expressed and are thought to play general roles in post-transcriptional regulation, mutations in genes encoding these factors have been linked to tissue-specific diseases including muscular dystrophy and now intellectual disability (ID). Our recent work defined this connection to ID, as we showed that mutations in the gene encoding the ubiquitously expressed Cys3His tandem zinc-finger (ZnF) Pab, ZC3H14 (Zinc finger protein, CCCH-type, number 14) are associated with non-syndromic autosomal recessive intellectual disability (NS-ARID). This study provided a first link between defects in Pab function and a brain disorder, suggesting that ZC3H14 plays a required role in regulating RNAs in nervous system cells. Here we highlight key questions raised by our study of ZC3H14 and its ortholog in the fruit fly Drosophila melanogaster, dNab2, and comment on future approaches that could provide insights into the cellular and molecular roles of this class of zinc finger-containing Pabs. We propose a summary model depicting how ZC3H14-type Pabs might play particularly important roles in neuronal RNA metabolism

    Three-Dimensional Printed Abdominal Imaging Windows for In Vivo Imaging of Deep-Lying Tissues

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    The ability to microscopically image diseased or damaged tissue throughout a longitudinal study in living mice would provide more insight into disease progression than having just a couple of time points to study. In vivo disease development and monitoring provides more insight than in vitro studies as well. In this study, we developed permanent 3D-printed, surgically implantable abdominal imaging windows (AIWs) to allow for longitudinal imaging of deep-lying tissues or organs in the abdominal cavity of living mice. They are designed to prevent organ movement while allowing the animal to behave normally throughout longitudinal studies. The AIW also acts as its own mounting bracket for attaching them to a custom 3D printed microscope mount that attaches to the stage of a microscope and houses the animal inside. During the imaging of the living animal, cellular and macroscopic changes over time in one location can be observed because markers can be used to find the same spot in each imaging session. We were able to deliver cancer cells to the pancreas and use the AIW to image the disease progression. The design of the AIWs can be expanded to include secondary features, such as delivery and manipulation ports and guides, and to make windows for imaging the brain, subcutaneous implants, and mammary tissue. In all, these 3D-printed AIWs and their microscope mount provide a system for enhancing the ability to image and study cellular and disease progression of deep-lying abdominal tissues of living animals during longitudinal studies

    Problematic mobile phone use and smartphone addiction across generations: the roles of psychopathological symptoms and smartphone use

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    Contemporary technological advances have led to a significant increase in using mobile technologies. Recent research has pointed to potential problems as a consequence of mobile overuse, including addiction, financial problems, dangerous use (i.e. whilst driving) and prohibited use (i.e. use in forbidden areas). The aim of this study is to extend previous findings regarding the predictive power of psychopathological symptoms (depression, anxiety and stress), mobile phone use (i.e. calls, SMS, time spent on the phone, as well as the engagement in specific smartphone activities) across Generations X and Y on problematic mobile phone use in a sample of 273 adults. Findings revealed prohibited use and dependence were predicted by calls/day, time on the phone and using social media. Only for dependent mobile phone use (rather than prohibited), stress appeared as significant. Using social media and anxiety significantly predicted belonging to Generation Y, with calls per day predicted belonging to Generation X. This finding suggests Generation Y are more likely to use asynchronous social media-based communication, whereas Generation X engage more in synchronous communication. The findings have implications for prevention and awareness-raising efforts of possibly problematic mobile phone use for educators, parents and individuals, particularly including dependence and prohibited use

    A probabilistic evaluation procedure for process model matching techniques

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    Process model matching refers to the automatic identification of corresponding activities between two process models. It represents the basis for many advanced process model analysis techniques such as the identification of similar process parts or process model search. A central problem is how to evaluate the performance of process model matching techniques. Current evaluation methods require a binary gold standard that clearly defines which correspondences are correct. The problem is that often not even humans can agree on a set of correct correspondences. Hence, evaluating the performance of matching techniques based on a binary gold standard does not take the true complexity of the matching problem into account and does not fairly assess the capabilities of a matching technique. In this paper, we propose a novel evaluation procedure for process model matching techniques. In particular, we build on the assessments of multiple annotators to define the notion of a non-binary gold standard. In this way, we avoid the problem of agreeing on a single set of correct correspondences. Based on this non-binary gold standard, we introduce probabilistic versions of precision, recall, and F-measure as well as a distance-based performance measure. We use a dataset from the Process Model Matching Contest 2015 and a total of 16 matching systems to assess and compare the insights that can be obtained by using our evaluation procedure. We find that our probabilistic evaluation procedure allows us to gain more detailed insights into the performance of matching systems than a traditional evaluation based on a binary gold standard

    Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

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    Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

    Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

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    <div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

    COMPETITION AMONG HOSPITALS AND ITS MEASUREMENT: THEORY AND A CASE STUDY

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    Our paper provides several insights on the characteristics of the concept of “Poles d’Excellence Rurale” (PER) through bilateral comparisons with that of Competitive Pole (CP) and cluster. The concept of PER is a French government’ initiative designed for the development of rural areas similar to that of the Competitive Pole. We emphasize important particularities of these concepts by analyzing some of their similarities and major differences.Pole d’Excellence Rurale, Competitive Pole, cluster, rural development
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