Plos One
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The CRISPR/Cas9 system is an RNA guided nuclease system that evolved as a mechanism of adaptive immunity in bacteria. This system has been adopted for numerous genome engineering applications in research and recently, therapeutics. The CRISPR/Cas9 system has been largely implemented by delivery of Cas9 as protein, RNA, or plasmid along with a chimeric crRNA-tracrRNA guide RNA (gRNA) under the expression of a pol III promoter, such as U6. ⋯ To augment the capability and accessibility of multiplexed genome engineering, we developed an efficient golden gate based method to assemble gRNAs linked by optimal Csy4 ribonuclease sequences to deliver up to 10 gRNAs as a single gRNA array transcript. Here we report the optimal expression of our guide RNA array under a strong pol II promoter. This system can be implemented alongside the myriad of CRISPR applications, allowing users to model complex biological processes requiring numerous gRNAs.
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Functional magnetic resonance imaging (fMRI) is an important tool for pre-surgical evaluation of eloquent cortex. Classic task-based paradigms require patient participation and individual imaging sequence acquisitions for each functional domain that is being assessed. Resting state fMRI (rs-fMRI), however, enables functional localization without patient participation and can evaluate numerous functional domains with a single imaging session. ⋯ In conclusion, at Washington University in St. Louis, rs-fMRI has become an integral part of standard imaging for neurosurgical planning. Resting state fMRI can be used in all patients, and due to its lower failure rate than task-based fMRI, it is useful for patients who are unable to cooperate with task-based studies.
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The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. ⋯ During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy.
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Fabry disease (FD) results from X-linked inheritance of a mutation in the GLA gene, encoding for alpha galactosidase A, and is characterized by heterogeneous clinical manifestations. Two phenotypes have been described "Classic" and "late onset" which cannot be predicted exclusively by genotype. The latter has been considered an attenuated form of the disease often affecting a single organ system commonly the heart. Recent studies have demonstrated that cardiac outcomes are similar in patients with classic and late onset mutations. In this study we investigate the relationship between clinical heterogeneity and plasma lyso-Gb3 in a large single centre cohort of N215S patients and compare this to patients with other mutations. ⋯ These results demonstrate that the N215S mutation results in a late onset phenotype involving the heart and other organs. Correlations between clinical manifestations and plasma lyso-Gb3 variations in this group suggest a Fabry-relevant disease mechanism for the heterogeneity observed in this group.
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Regulating health behavior change often occurs in a dyadic context of romantic relationships. Dyadic approaches to standard health behavior change models are, however, barely considered. We investigated volitional processes of the Health Action Process Approach model for two health behaviors within a dyadic context of romantic couples. Specifically, we tested whether day-to-day volitional self-regulation predicted one's own and one's partner's cigarettes smoked (Study 1) and physical activity (Study 2). ⋯ Behavioral self-regulation is not only relevant for individuals themselves, but some volitional processes may spill over to their partners. This highlights the need to specify couple-level processes involved in health behavior change, and to consider a social context of self-regulation.