280 research outputs found

    How Not to Resolve Moral Conflicts in Politics

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    Published in cooperation with the American Bar Association Section of Dispute Resolutio

    Democractic Schools and Moral Education

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    Religious Freedom and Civic Responsibility

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    President\u27s Message: 125 Years of Innovation, Discovery and Service

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    A Message From President Amy Gutmann

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    Educating for Individual Freedom and Democratic Citizenship: In Unity and Diversity There Is Strength

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    This article addresses contentious questions concerning individual freedom and democratic citizenship education in the contemporary circumstances of multiculturalism. It suggests that educating children for civic equality is an ambitious aim for any democracy and not one that can ever be realized once and for all. It provides evidence that multicultural conditions can challenge the very aim of educating children for civic equality. It explains that democracies are variously multicultural and the varieties of groups make a difference in the kind of education and the progress toward civic equality that can realistically be expected at any time

    MicroRNA profiling reveals marker of motor neuron disease in ALS models

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    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p
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