248 research outputs found

    Expression and role of the orphan nuclear receptor NR5A2 in mouse embryogenesis and female reproductive function

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    The orphan nuclear receptor NR5A2 is implicated in a multitude of biological processes including cholesterol homeostasis and development. Its role in cholesterol metabolism and cell proliferation is now well established in vitro and in vivo. Both in vitro and gene expression studies have suggested a role for NR5A2 in ovarian function. In this study, we provide in vivo evidence for its involvement in reproductive function by demonstrating that heterozygosity for a null mutation of NR5A2 leads to a reduction in female fertility. Furthermore, we showed that NR5A2+/- females display a severe reduction in ovarian progesterone production and that progesterone supplementation can rescue the NR5A2+/- subfertility phenotype. We also provide evidence that one of the mechanisms by which NR5A2 regulates ovarian progesterone production is through modulating the expression of SCAR, which controls one of the rate-limiting steps of progesterone synthesis.A targeted disruption of the NR5A2 gene in the mouse leads to early lethality in utero between embryonic days 6.0 and 7.5, showing that NR5A2 plays a crucial role during early embryogenesis. The molecular mechanisms underlying this early lethality, however, are poorly understood. In this study, we used a morphological and marker gene analysis to characterize the NR5A2-/- embryonic phenotype and showed that although initial axis specification occurs in NR5A2-/- embryos, primitive streak and mesoderm fail to form. Using a chimeric approach, we demonstrated a requirement for NR5A2 function in the visceral endoderm (VE), an extra-embryonic tissue, for proper primitive streak morphogenesis and gastrulation. Our results also indicate a reduction in the expression of VE marker genes involved in the nutritive function of this tissue, suggesting that NR5A2 play a dual role in the VE, being implicated in the mediation of both its patterning and nutritive activity.Taking advantage of the LacZ knock-in approach used to inactivate the NR5A2 gene, we also demonstrated that NR5A2 is expressed during craniofacial and nervous system development, suggesting a novel role for NR5A2 in head formation and neural development

    Use of sodium 4-phenylbutyrate to define therapeutic parameters for reducing intracerebral hemorrhage and myopathy in Col4a1 mutant mice

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    Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers that constitute a major component of nearly all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that includes variable cerebrovascular and skeletal muscle manifestations. The pathogenicity of COL4A1 and COL4A2 mutations is generally attributed to impaired secretion into basement membranes. Sodium 4-phenylbutyrate (4PBA) is a US Food and Drug Administration-approved drug that promotes mutant heterotrimer secretion in vitro and in vivo. Here, we use different 4PBA treatment paradigms to define therapeutic parameters for preventing cerebrovascular and muscular pathologies in Col4a1 mutant mice. We show the efficacy of long-term 4PBA treatment in reducing the severity of intracerebral hemorrhages (ICHs) in Col4a1 mutant mice aged up to 8 months. In addition, we demonstrate that maximal efficacy of 4PBA on ICH and myopathy was achieved when treatment was initiated prenatally, whereby even transient 4PBA administration had lasting benefits after being discontinued. Importantly, postnatal treatment with 4PBA also reduced ICH and skeletal myopathy severities in Col4a1 mutant mice, which has significant clinical implications for patients with COL4A1 and COL4A2 mutations. This article has an associated First Person interview with the first author of the paper

    Distortion correction in magnetic resonance imaging using the simulated point spread function

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    Geometric distortion is a highly prevalent issue for echo-planar imaging (EPI), due to long readout times and field inhomogeneity. Previously, the measured point spread function (PSF) has been shown to be effective in correcting this distortion. In this work, we reconstruct an image quickly and address the distortion with a point spread function that was generated entirely through simulation using the trajectory and measured field map. The distortion correction with this approach is shown to be better than k-space based iterative reconstructions and is robust to high differentials in magnetic field maps when we use an optimal trajectory. In addition, this technique is well-suited to parallel implementation, as the system matrix used is sparse.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2018-05-01The student, Genevieve LaBelle, accepted the attached license on 2016-04-20 at 15:28.The student, Genevieve LaBelle, submitted this Thesis for approval on 2016-04-20 at 15:47.This Thesis was approved for publication on 2016-04-26 at 09:30.DSpace SAF Submission Ingestion Package generated from Vireo submission #9385 on 2016-07-07 at 13:50:29Made available in DSpace on 2016-07-07T20:27:54Z (GMT). No. of bitstreams: 3 LABELLE-THESIS-2016.pdf: 1265524 bytes, checksum: 10dae802c06361067952cc6973b0e53c (MD5) labelle_source.zip: 1771572 bytes, checksum: fbefb05d190e7aea47973b6e60f1ca26 (MD5) LICENSE.txt: 4214 bytes, checksum: 4b4ee2356749dab9713bebc50661d4af (MD5) Previous issue date: 2016-04-26Embargo set by: Seth Robbins for item 93161 Lift date: 2018-07-07T20:28:14Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 93161 Lift date: 2018-07-07T20:35:34Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 93161 on 2018-07-08T09:15:20Z

    La fonction de l’art dans la théologie féministe de Monique Dumais

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    Une des pionnières de la théologie féministe universitaire au Québec, Monique Dumais (1939-2017), a également été une passionnée des arts, critique de maintes performances, mais aussi actrice et productrice, particulièrement de poésie, de théâtre et de littérature. L’objectif de cet article est de présenter une synthèse des éléments-clés de sa théologie féministe sous l’angle de la fonction qu’y a occupée l’art. L’étude présente successivement ses créations conceptuelles et ses créations artistiques, pour ensuite construire des liens entre elles. Une idée force du féminisme chrétien de Monique Dumais est qu’en christianisme, l’on manque d’incarnation. La Pâque des femmes, ce passage de la domination à la libération, repose sur l’intégration de leurs expériences féministes dans une créativité et dans une incarnation en acte de leur corps et de leur souffle. Ce mouvement vital excède les concepts. Les arts, qui appartiennent au domaine des sensations, y suppléent pour briser les logiques patriarcales.One of the pioneers of academic feminist theology in Quebec, Monique Dumais (1939-2017) was also fascinated by arts. As such she has been a performing arts critic, as well as an author and a producer, especially in poetry, theater and literature. This paper is to shortly present key elements of her feminist theology with a focus on the place that art plays in it. This study will successively detail her conceptual and artistic creations to find some links between them. One of the main contentions of Monique Dumais’ Christian feminism is that there is a lack of incarnation in Christianity. Women’s Easter, this passage from domination to liberation, is based on integrating women’s experiences in creativity and in an incarnation in acts of their bodies and their breaths. This vital movement surpasses concepts. Arts, which are from the domain of sensations, help breaking patriarchal logics

    Sonic Agency: Sound and Emergent Forms of Resistance

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    In a world dominated by the visual, could contemporary resistance be auditory? Sonic Agency highlights sound’s invisible, disruptive, and affective qualities, and asks whether the unseen nature of sound can support a political transformation. In this timely and important book, author Brandon LaBelle sets out to engage contemporary social and political crises by way of sonic thought and imagination. He divides sound’s functions into four figures of resistance – the invisible, the overheard, the itinerant and the weak – and argues for their role in creating alternative “unlikely publics” in which to foster mutuality and dissent. He highlights existing sonic cultures and social initiatives that utilize or deploy sound and listening to address conflict, and points to their work as models for a wider movement. By examining the experience of listening and being heard, LaBelle illuminates a path from the margins toward hope, citizenship, and vibrancy. When the current climate has left many feeling they have lost their voice, it may be sound itself which restores it to them

    Sonic Agency : Sound and Emergent Forms of Resistance

    No full text
    "In a world dominated by the visual, could contemporary resistance be auditory? Sonic Agency highlights sound’s invisible, disruptive, and affective qualities, and asks whether the unseen nature of sound can support a political transformation. In this timely and important book, author Brandon LaBelle sets out to engage contemporary social and political crises by way of sonic thought and imagination. He divides sound’s functions into four figures of resistance – the invisible, the overheard, the itinerant and the weak – and argues for their role in creating alternative “unlikely publics” in which to foster mutuality and dissent. He highlights existing sonic cultures and social initiatives that utilize or deploy sound and listening to address conflict, and points to their work as models for a wider movement. By examining the experience of listening and being heard, LaBelle illuminates a path from the margins toward hope, citizenship, and vibrancy. When the current climate has left many feeling they have lost their voice, it may be sound itself which restores it to them." -- Publisher's website

    Support vector machines

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    My first exposure to Support Vector Machines came this spring when heard Sue Dumais present impressive results on text categorization using this analysis technique. This issue's collection of essays should help familiarize our readers with this interesting new racehorse in the Machine Learning stable. Bernhard Scholkopf, in an introductory overview, points out that a particular advantage of SVMs over other learning algorithms is that it can be analyzed theoretically using concepts from computational learning theory, and at the same time can achieve good performance when applied to real problems. Examples of these real-world applications are provided by Sue Dumais, who describes the aforementioned text-categorization problem, yielding the best results to date on the Reuters collection, and Edgar Osuna, who presents strong results on application to face detection. Our fourth author, John Platt, gives us a practical guide and a new technique for implementing the algorithm efficiently
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