74 research outputs found

    Pennsylvania Folklife Vol. 15, No. 2

    Get PDF
    • Dutch Country Burls and Bowls • The Pennsylvania Barn in the South • Tales of the Block House • Official Religion Versus Folk Religionhttps://digitalcommons.ursinus.edu/pafolklifemag/1022/thumbnail.jp

    Pennsylvania Folklife Vol. 16, No. 1

    Get PDF
    • Indian Readers and Healers by Prayer • Bayard Taylor\u27s Portrait of Pennsylvania Quakerism • Gypsy Stories from the Swatara Valley • Stump-Pulling • Occult Tales from Union County • Beekeeping and Bee Lore in Pennsylvania • New Materials on the 18th Century Emigration from the Speyer State Archives • The Snake-Bitten Dutchman • Notes and Documents: A Letter to Germany (1806) ; Midwestern Diary of Joel Vale Garretson (1863-1864) • Questionnaire on Hominyhttps://digitalcommons.ursinus.edu/pafolklifemag/1025/thumbnail.jp

    Pennsylvania Folklife Vol. 23, No. 4

    Get PDF
    • Cultural Learning Through Game Structure: A Study of Pennsylvania German Children\u27s Games • Nipsy : The Ethnography of a Traditional Game of Pennsylvania\u27s Anthracite Region • The Game as Creator of the Group in an Italian-American Community • Pennsylvania Town Views of a Century Ago • The Barber\u27s Ghost : A Legend Becomes a Folktale • Grain Harvesting in the Nineteenth Century • My Experience With the Dialect • Harvest on the Pennsylvania Farm: Folk-Cultural Questionnaire No. 34https://digitalcommons.ursinus.edu/pafolklifemag/1058/thumbnail.jp

    Pennsylvania Folklife Vol. 14, No. 1

    Get PDF
    • The Oley Valley Basketmaker • The Sheen of Copper • Pennsylvania Corncribs • Land-Clearing in Lycoming County, Pennsylvania • Funerals in My Childhood Days • Folk Medicine from Western Pennsylvania • Peddlers I Rememberhttps://digitalcommons.ursinus.edu/pafolklifemag/1017/thumbnail.jp

    Pennsylvania Folklife Vol. 14, No. 3

    Get PDF
    • Buckwheat Music • The Domestic Encyclopaedia of 1803-1804 • Taming the Land • Jacob Taylor and His Almanacs • Italian Immigrant Life in Northampton County, Pennsylvania, 1890-1915 • Uni Day\u27s Herb Gardenhttps://digitalcommons.ursinus.edu/pafolklifemag/1019/thumbnail.jp

    Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner

    Get PDF
    Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-Îł-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins

    Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission.</p> <p>Methods/design</p> <p>The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) <abbrgrp><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes.</p> <p>Trial registration</p> <p>The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.</p

    Mapping anhedonia onto reinforcement learning: A behavioural meta-analysis

    Get PDF
    BACKGROUND: Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. METHODS: Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. RESULTS: MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. CONCLUSION: Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior

    Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

    Get PDF
    The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for Îł astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of Îł cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of Îł absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z=2 and to constrain or detect Îł halos up to intergalactic-magnetic-field strengths of at least 0.3 pG . Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from Îł astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of Îł cosmology.</p
    • …
    corecore