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

John Webster’s The Duchess of Malfi is a dramatization of the unsanctioned marriage and disappearance of an Italian Duchess approximately one hundred years before the play’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 – Antonio – which had been overlooked in other accounts of the Duchess’s life. Through Webster’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 James’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 Duchess’s bold marriage to her steward and her subversion of both her family and the church’s authority over her. The consequences of the Duchess’s independence and her violation of cultural taboos are brought about by her brothers’ vengeful punishment and execution of her. While the historical record does not recount the Duchess’s fate, Webster’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

Copyright © 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 Children’s Hope Scale; CHS), and symptoms of mental distress (as measured by the Young Person’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

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, p = 0.002). 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 Científicas y Técnicas; 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 Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Conwell, Darwin. Brigham and Women’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

DNA Hypomethylation, Ambient Particulate Matter, and Increased Blood Pressure: Findings From Controlled Human Exposure Experiments

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144592/1/jah3232.pd

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

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

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 DNA–histone binding by 2 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 hMSH2–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

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al