17 research outputs found

    Current role of portable MRI in diagnosis of acute neurological conditions

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    Neuroimaging is an inevitable component of the assessment of neurological emergencies. Magnetic resonance imaging (MRI) is the preferred imaging modality for detecting neurological pathologies and provides higher sensitivity than other modalities. However, difficulties such as intra-hospital transport, long exam times, and availability in strict access-controlled suites limit its utility in emergency departments and intensive care units (ICUs). The evolution of novel imaging technologies over the past decades has led to the development of portable MRI (pMRI) machines that can be deployed at point-of-care. This article reviews pMRI technologies and their clinical implications in acute neurological conditions. Benefits of pMRI include timely and accurate detection of major acute neurological pathologies such as stroke and intracranial hemorrhage. Additionally, pMRI can be potentially used to monitor the progression of neurological complications by facilitating serial measurements at the bedside

    Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.

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    To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence. The induction of P53 appeared to affect dendritic branching in Rett neurons, as P53 inhibition restored dendritic complexity. The induction of P53 targets was also detectable in analyses of human Rett patient brain, suggesting that this disease-in-a-dish model can provide relevant insights into the human disorder

    Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation

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    Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXaintermediate. Together, these findings identify a cell culture system for functionally exploring the two X chromosome dosage compensation processes in early human development: X dampening and X inactivation. However, remaining differences between naive hESCs and embryonic cells related to mono-allelic XIST expression and non-random X inactivation highlight the need for further culture improvement. As the naive state resets Xiabnormalities seen in primed hESCs, it may provide cells better suited for downstream applications
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