175 research outputs found

    The Duchess's "New World" : marriage and its consequences in "The Duchess of Malfi"

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    John Websterā€™s The Duchess of Malfi is a dramatization of the unsanctioned marriage and disappearance of an Italian Duchess approximately one hundred years before the playā€™s 1613 performance in England. Although Webster had numerous sources for his production, he made significant modifications in his version of the story that are reflective of anxieties surrounding the cultural, economic, and political changes in seventeenth-century England. In particular, the playwright augmented the marriage scene between the Duchess and her steward ā€“ Antonio ā€“ which had been overlooked in other accounts of the Duchessā€™s life. Through Websterā€™s treatment, the Duchess and Antonio invoke growing trends in Protestant philosophy that emphasize companionate marriage over the arrangement of financially motivated nuptials. Furthermore, the loosening of restrictions for gaining entrance into the gentry because of King Jamesā€™s lenient view of preferment led to aristocratic anxiety regarding position. The relaxed standards for preferment combined with the changing perspectives on marriage are reflected in the play, particularly by the Duchessā€™s bold marriage to her steward and her subversion of both her family and the churchā€™s authority over her. The consequences of the Duchessā€™s independence and her violation of cultural taboos are brought about by her brothersā€™ vengeful punishment and execution of her. While the historical record does not recount the Duchessā€™s fate, Websterā€™s presentation of the highly ceremonialized emotional torture of the Duchess prior to her murder underscores the social instability brought about by the irregular marriage. Finally, the fact that the son of Antonio and the Duchess ascends to the duchy at the conclusion of the play is another significant alteration by Webster as it reflects the new order that the social changes have established

    The Hummingbird Project Year 2: Decreasing Distress and Fostering Flourishing in a Pragmatic Pre-Post Study

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    Copyright Ā© 2024 Platt, Hochard, Tytherleigh, Kannangara, Carson, McFaul and North. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsMulti-component Positive Psychology Interventions (mPPIs) in secondary schools have been shown to improve mental health outcomes for young people. The Hummingbird Project mPPI is a six-week program of workshops designed to introduce a variety of positive psychology (PP) concepts to secondary school aged children in schools to improve well-being, resilience, and hope. The effects on mental distress, however, were not explored. The current study, therefore, was designed to replicate the effects of the Hummingbird Project mPPI on positive mental health and to also explore the effects on symptoms of mental distress. Secondary school-aged children (N = 614; mean age = 11.46 years) from a sample of secondary schools located across the North West of England (N = 7) participated in the study; the majority of children were in Year 7 (94%). The PP concepts explored included happiness, hope, resilience, mindfulness, character strengths, growth mindset, and gratitude. The results showed significant improvements associated with the mPPI in well-being (as measured by the World Health Organization Well-Being Index; WHO-5), hope (as measured by the Childrenā€™s Hope Scale; CHS), and symptoms of mental distress (as measured by the Young Personā€™s Clinical Outcomes in Routine Evaluation; YP-CORE) from pre- to post-intervention. While acknowledging the limits due to pragmatic concerns regarding the implementation of a control group, the effectiveness of the Hummingbird Project mPPI on well-being was replicated alongside reducing the symptoms of mental distress. Future evaluation, however, will need to implement more robust designs and consider follow-up duration to assess the longer-term effects of the Hummingbird Project mPPI

    Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

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    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, pā€Š=ā€Š0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.Fil: LaRusch, Jessica. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Jung, Jinsei. Yonsei University College of Medicine; Corea del SurFil: General, Ignacio. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones CientĆ­ficas y TĆ©cnicas; ArgentinaFil: Lewis, Michele D.. Mayo Clinic. Division of Gastroenterology and Hepatology; Estados UnidosFil: Park, Hyun Woo. Yonsei University College of Medicine; Corea del SurFil: Brand, Randall E.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Gelrud, Andres. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Anderson, Michelle A.. University of Michigan; Estados UnidosFil: Banks, Peter A.. Brigham and Womenā€™s Hospital. Division of Gastroenterology; Estados UnidosFil: Conwell, Darwin. Brigham and Womenā€™s Hospital. Division of Gastroenterology; Estados UnidosFil: Lawrence, Christopher. Medical University of South Carolina; Estados UnidosFil: Romagnuolo, Joseph. Medical University of South Carolina; Estados UnidosFil: Baillie, John. University of Duke; Estados UnidosFil: Alkaade, Samer. St. Louis University. School of Medicine; Estados UnidosFil: Cote, Gregory. Indiana University; Estados UnidosFil: Gardner, Timothy B.. Dartmouth-Hitchcock Medical Center; Estados UnidosFil: Amann, Stephen T.. North Mississippi Medical Center; Estados UnidosFil: Slivka, Adam. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Sandhu, Bimaljit. Virginia Commonwealth University Medical Center; Estados UnidosFil: Aloe, Amy. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Kienholz, Michelle L.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Yadav, Dhiraj. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Barmada, M. Michael. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Bahar, Ivet. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Lee, Min Goo. Yonsei University College of Medicine; Corea del SurFil: Whitcomb, David C.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: North American Pancreatitis Study Group. No especifica

    Suspected lead poisoning in two captive cheetahs (Acinonyx jubatus jubatus) in South Africa, in 2008 and 2013

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    CITATION: North, M. A. et al. 2015. Suspected lead poisoning in two captive cheetahs (Acinonyx jubatus jubatus) in South Africa, in 2008 and 2013. Journal of the South African Veterinary Association, 86(1), Art. #1286, doi:10.4102/jsava.v86i1.1286.The original publication is available at http://www.jsava.co.zaWhilst lead poisoning in raptors, scavenging birds and waterfowl is well studied and common knowledge, there is surprisingly little literature detailing the risk to mammalian scavengers and captive carnivores fed hunted meat. This case report describes the death of two captive cheetahs (Acinonyx jubatus jubatus) following acute onset of nervous symptoms. Clinical signs included hyper-excitability, seizures, arched back, tail held abnormally high and hyper-salivation. Necropsy findings included bullets or a bullet in their stomachs. Kidney and liver lead levels from one cheetah (15.6 ppm and 17 ppm respectively) were consistent with a diagnosis of lead poisoning; liver from the second cheetah was not available for testing. Both animals were routinely fed hunted antelope or game birds. This is the first report of oral lead poisoning in captive large carnivores, although these are unlikely to be the first cases. Without awareness of the risks of feeding hunted game, lead exposure will continue to be an underdiagnosed reality in the rehabilitation of endangered carnivores.http://www.jsava.co.za/index.php/jsava/article/view/1286Publisher's versio

    Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling

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    Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of transcription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNAā€“histone binding by 2ā€‰kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2ā€“hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions
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