294 research outputs found

    Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties.

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    The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling. Furthermore, βarr2-biased D2R agonism enhances firing of cortical fast-spiking interneurons. This enhanced cortical agonism of the biased ligand can be attributed to a lack of G-protein signaling and elevated expression of βarr2 and G protein-coupled receptor (GPCR) kinase 2 in the cortex versus the striatum. Therefore, we propose that βarr2-biased D2R ligands that exert region-selective actions could provide a path to develop more effective antipsychotic therapies

    Digital archiving and retrieval tool

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    Our poster will present DART, the Digital Archiving and Retrieval Tool, a system intended to support engineers in archiving digital data developed over the course of the design process. DART is a direct product of recent experiences in adding collaboration, archiving, and version control systems to project components of university-level engineering curricula. The primary insights include the necessity of minimal disruption to the workflow and the utility of a basic, data-grabbing, "cyber-forensics" approach to digital archiving. The system incorporates those principles, providing a tool by which useful data and context may be stored while imposing minimal learning curve or workflow change. An explicit tradeoff is made between the ability to easily manage and analyze archived data versus adoption of the tool and successful data archiving

    Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

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    Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin-secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non-prevascularized islet organoids. This is caused by paracrine signaling between the β-cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo, the prevascularized islet organoids are rapidly blood-perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation

    1954: Abilene Christian College Bible Lectures - Full Text

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    Preface The 1954 Abilene Christian College Lectureship was one of the best attended and most successful in the history of the school. Considerable interest was manifested in the timely theme, “Overcoming Dangerous Tendencies,” and in the two special topics, “Ways and Means of Doing Mission Work,” and “Caring For Widows and Orphans.” The reports from the mission fields were highly stimulating, and all in all, the speeches were unusually high caliber. The Panel Discussions were also on timely subjects and well presented. They received a warm response, as did also the thirty classes that were conducted each day. These classes were taught by persons expert in their particular fields, and covered a wide range of interests to the faithful, working Christian. We at Abilene Christian College predict for this book of Lectures a wide and hearty reception, and believe that its reading will issue in profit to the individual and to the church at large. J. D. Thomas Lectureship Directo

    Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apnea

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    Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some patients with obstructive sleep apnea (OSA). A pooled analysis of two 12-week, randomized, double-blind studies in nCPAP-adherent patients with ES associated with OSA evaluated the effect of armodafinil on wakefulness and cognition. Three hundred and ninety-one patients received armodafinil (150 or 250 mg) and 260 patients received placebo once daily for 12 weeks. Efficacy assessments included the Maintenance of Wakefulness Test (MWT), Cognitive Drug Research cognitive performance battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. Adverse events were monitored. Armodafinil increased mean MWT sleep latency from baseline to final visit by 2.0 min vs a decrease of 1.5 min with placebo (P < 0.0001). Compared with placebo, armodafinil significantly improved quality of episodic secondary memory (P < 0.05) and patients’ ability to engage in activities of daily living (P < 0.0001) and reduced fatigue (P < 0.01). The most common adverse events were headache, nausea, and insomnia. Armodafinil did not adversely affect desired nighttime sleep, and nCPAP use remained high (approximately 7 h/night). Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients’ ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. Armodafinil also reduced patient-reported fatigue and was well tolerated

    Habitat preferences by individual humpback whale mothers in the Hawaiian breeding grounds vary with the age and size of their calves

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    We investigated whether calf age and calf size influence habitat choice by humpback whale motherecalf pairs in their breeding grounds. During 1997e2008, we conducted focal follows of motherecalf pairs in Hawaiian waters. Tail-fluke identification photographs and calf lengths (measured through video-grammetry) were obtained. Water depth and sea-bed terrain type were derived from GPS data. Identification photographs were matched so that the habitat choices could be established within breeding seasons. Across 72 motherecalf pairs resighted over various intervals within a breeding season, magnitude of depth change between initial and final sightings increased significantly with resighting interval. There was a significant increase from initial depth to final depth for relatively long resighting intervals (27e51 days), but no significant difference for relatively short resighting intervals (2e26 days). Although there was no preference for sea-bed terrain type by motherecalf pairs at their initial sighting, there was a preference for rugged terrain at their final resighting. A resource selection model indicated that the relative probability of a location being used by a motherecalf pair increased (as a function of water depth and rugged sea-bed terrain type) from initial to final sighting; a finding supported by subsequent tests of habitat preference versus availability. For 96 measured calves, calf length and water depth were positively correlated, even when ordinal day of measurement was controlled for statistically; a finding confirmed by a general linear model that simultaneously investigated the relationship between water depth, sea-bed terrain type, number of escorts, ordinal day and calf size. Thus, both calf age and size influence habitat choice by motherecalf pairs in their breeding grounds. The movement of mothers and their maturing calves into deeper waters where they favour rugged sea-bed terrain appears to be part of a suite of behavioural changes during the pre-migratory phase of residency in the breeding grounds
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