Plos One
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Existing concepts can be a major barrier to learning new counterintuitive concepts that contradict pre-existing experience-based beliefs or misleading perceptual cues. When reasoning about counterintuitive concepts, inhibitory control is thought to enable the suppression of incorrect concepts. ⋯ Better response inhibition was associated with longer reaction times in counterintuitive trials, while better semantic inhibition was associated with higher accuracy in counterintuitive trials. This novel finding suggests that different aspects of inhibitory control may offer unique contributions to counterintuitive reasoning during adolescence and provides further support for the hypothesis that inhibitory control plays a role in science and maths reasoning.
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Antisense-mediated exon skipping has made significant progress as a therapeutic platform in recent years, especially in the case of Duchenne muscular dystrophy (DMD). Despite FDA approval of eteplirsen-the first-ever antisense drug clinically marketed for DMD-exon skipping therapy still faces the significant hurdles of limited applicability and unknown truncated protein function. In-frame exon skipping of dystrophin exons 45-55 represents a significant approach to treating DMD, as a large proportion of patients harbor mutations within this "hotspot" region. ⋯ Here, we demonstrate that a cocktail of phosphorodiamidate morpholino oligomers can effectively skip dystrophin exons 45-55 in vitro in myotubes transdifferentiated from DMD patient fibroblast cells. This is the first report of substantive exons 45-55 skipping in DMD patient cells. These findings help validate the use of transdifferentiated patient fibroblast cells as a suitable cell model for dystrophin exon skipping assays and further emphasize the feasibility of dystrophin exons 45-55 skipping in patients.
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Mutations in mitochondrial DNA are an important source of severe and incurable human diseases. The vast majority of these mutations are heteroplasmic, meaning that mutant and wild-type genomes are present simultaneously in the same cell. Only a very high proportion of mutant mitochondrial DNA (heteroplasmy level) leads to pathological consequences. ⋯ Quantification of mtDNA copy number in transfected cells revealed the absence of a non-specific effect on wild type mtDNA replication, indicating that the decreased proportion between mutant and wild type mtDNA molecules is not a consequence of a random repopulation of depleted pool of mtDNA genomes. The heteroplasmy change could be also modulated by cell growth conditions, namely increased by cells culturing in a carbohydrate-free medium, thus forcing them to use oxidative phosphorylation and providing a selective advantage for cells with improved respiration capacities. We discuss the advantages and limitations of this approach and propose further development of the anti-replicative strategy based on the RNA import into human mitochondria.
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Conflicting results have been obtained regarding the association between X-ray repair cross complementation group 1 (XRCC1) and susceptibility to hepatocellular carcinoma (HCC). In this study, associations between HCC and three polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) were evaluated using a meta-analysis approach. PubMed, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang standard database were systematically searched to identify all relevant case-control studies published through March 2018. ⋯ Trial sequential analysis (TSA), false-positive report probabilities (FPRP), and combined genotype analysis revealed that XRCC1 Arg399Gln is mainly associated with susceptibility to liver cancer. However, there was no association between Arg194Trp or Arg280His and the risk of HCC. These results, indicating that the Arg399Gln polymorphism of XRCC1 is associated with the risk of HCC in the Chinese population, provide a basis for the development of improved detection and treatment approaches.
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3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. ⋯ This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review and post-hoc evaluation survey with experts was completed to evaluate the likely effectiveness of the herein suggested QbD framework.