The Durability of Adaptation: Fate and Fortune in Romeo and Juliet

Romeo and Juliet, like many of William Shakespeare’s works, is widely known in the Western literary and dramatic traditions. However, it is not a text that is firmly cemented in its textual veracity—even the earliest published editions of the play, and others in the Shakespeare canon, are dissimilar. Additionally, different versions of Romeo and Juliet have been interpreted, adapted, and performed in the 400 years since its entrance into popular culture. This reveals the uniquely fluid quality of dramatic works in literature. How, for a work as familiar as Romeo and Juliet, do different interpretations affect the enduring subjects of the play? This paper examines the theme of fate, the importance of the Prologue, and the character of Rosaline in this play, as magnified by a 1752 adaptation by J. and R. Tonson and S. Draper that changes the ways in which each of these preeminent motifs operates, as well as the action of the tragedy more generally. This 1752 version is a performance adaptation that does not include the Prologue, removes the character of Rosaline, and thereby affects the ways in which fate governs the actions, characters, and plotline of the play. Ultimately, this project explores how the nuanced construction of Romeo and Juliet’s fate plot weaves through the well-known drama’s storyline, and how different approaches to its delicate formulation by rhetorical alterations and drastic plot changes disrupt this destiny-driven narrative

The Philosophy of Ecology in John Steinbeck\u27s The Grapes of Wrath

This thesis explores the possibilities for ecocritical study in fiction through John Steinbeck’s 1939 novel The Grapes of Wrath. Major ecocritical interpretation has yet to gain much traction in novels; by focusing on human nature, this form’s “anthropocentric” posture seems itself to be antithetical to ecocritical efforts, which aim to unseat humans as the center of the moral universe. However, by analyzing The Grapes of Wrath’s formal, narratorial, and thematic valences, I argue that principles of social justice concurrently imply environmental justice in the philosophical currents of the text. Tenets of deep ecology and Aldo Leopold’s “land ethic” inform the novel’s overall environmental outlook. The key to my interpretation is the value of community at the center of Steinbeck’s world. To expand principles of the collectivism and compassion in the social community to include the broader ecological community, I focus on the narrative’s unique Judeo-Christian spirituality and humanistic discourse. Ultimately I identify cohesion in The Grapes of Wrath’s composition that makes a single narrative of both the natural and the human worlds, and that creates a moral universe that guides ethical behavior towards others, both human and non-human; in doing so, I argue Steinbeck’s novel both enacts and represents an ecologically minded ethic

The CIPRUS study, a nurse-led psychological treatment for patients with undifferentiated somatoform disorder in primary care: study protocol for a randomised controlled trial

Background: Up to a third of patients presenting medically unexplained physical symptoms in primary care may have a somatoform disorder, of which undifferentiated somatoform disorder (USD) is the most common type. Psychological interventions can reduce symptoms associated with USD and improve functioning. Previous research has either been conducted in secondary care or interventions have been provided by general practitioners (GPs) or psychologists in primary care. As efficiency and cost-effectiveness are imperative in primary care, it is important to investigate whether nurse-led interventions are effective as well. The aim of this study is to examine the effectiveness and cost-effectiveness of a short cognitive behavioural therapy (CBT)-based treatment for patients with USD provided by mental health nurse practitioners (MHNPs), compared to usual care. Methods: In a cluster randomised controlled trial, 212 adult patients with USD will be assigned to the intervention or care as usual. The intervention group will be offered a short, individual CBT-based treatment by the MHNP in addition to usual GP care. The main goal of the intervention is that patients become less impaired by their physical symptoms and cope with symptoms in a more effective way. In six sessions patients will receive problem-solving treatment. The primary outcome is improvement in physical functioning, measured by the physical component summary score of the RAND-36. Secondary outcomes include health-related quality of life measured by the separate subscales of the RAND-36, somatization (PHQ-15) and symptoms of depression and anxiety (HADS). Problem-solving skills, health anxiety, illness perceptions, coping, mastery and working alliance will be assessed as potential mediators. Assessments will be done at 0, 2, 4, 8 and 12 months. An economic evaluation will be conducted from a societal perspective with quality of life as the primary outcome measure assessed by the EQ-5D-5L. Health care, patient and lost productivity costs will be assessed with the Tic-P. Discussion: We expect that the intervention will improve physical functioning and is cost-effective compared to usual care. If so, more patients might successfully be treated in general practice, decreasing the number of referrals to specialist care. Trial registration: Dutch Trial Registry, identifier: NTR4686, Registered on 14 July 2014. © 2017 The Author(s)

GUCY2C Opposes Systemic Genotoxic Tumorigenesis by Regulating AKT-Dependent Intestinal Barrier Integrity

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c−/−) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous and carcinogen-induced systemic tumorigenesis in Gucy2c−/− mice. GUCY2C regulated barrier integrity by repressing AKT1, associated with increased junction proteins occludin and claudin 4 in mice and Caco2 cells in vitro. Thus, GUCY2C defends the intestinal barrier, opposing colitis and systemic genotoxicity and tumorigenesis. The therapeutic potential of this observation is underscored by the emerging clinical development of oral GUCY2C ligands, which can be used for chemoprophylaxis in inflammatory bowel disease and cancer

Prediction of activity-related energy expenditure under free-living conditions using accelerometer-derived physical activity

The purpose of the study was to develop prediction models to estimate physical activity (PA)-related energy expenditure (AEE) based on accelerometry and additional variables in free-living adults. In 50 volunteers (20-69 years) PA was determined over 2 weeks using the hip-worn Actigraph GT3X + as vector magnitude (VM) counts/minute. AEE was calculated based on total daily EE (measured by doubly-labeled water), resting EE (indirect calorimetry), and diet-induced thermogenesis. Anthropometry, body composition, blood pressure, heart rate, fitness, sociodemographic and lifestyle factors, PA habits and food intake were assessed. Prediction models were developed by context-grouping of 75 variables, and within-group stepwise selection (stage I). All significant variables were jointly offered for second stepwise regression (stage II). Explained AEE variance was estimated based on variables remaining significant. Alternative scenarios with different availability of groups from stage I were simulated. When all 11 significant variables (selected in stage I) were jointly offered for stage II stepwise selection, the final model explained 70.7% of AEE variance and included VM-counts (33.8%), fat-free mass (26.7%), time in moderate PA + walking (6.4%) and carbohydrate intake (3.9%). Alternative scenarios explained 53.8-72.4% of AEE. In conclusion, accelerometer counts and fat-free mass explained most of variance in AEE. Prediction was further improved by PA information from questionnaires. These results may be used for AEE prediction in studies using accelerometry

Homeostatic Control of the Crypt-Villus Axis by the Bacterial Enterotoxin Receptor Guanylyl Cyclase C Restricts the Proliferating Compartment in Intestine

Guanylyl cyclase C (GC-C), the receptor for diarrheagenic enterotoxins and the paracrine ligands guanylin and uroguanylin, regulates intestinal secretion. Beyond volume homeostasis, its importance in modulating cancer cell proliferation and its uniform dysregulation early in colon carcinogenesis, reflecting loss of ligand expression, suggests a role for GC-C in organizing the crypt-villus axis. Here, eliminating GC-C expression in mice increased crypt length along a decreasing rostral-caudal gradient by disrupting component homeostatic processes. Crypt expansion reflected hyperplasia of the proliferating compartment with reciprocal increases in rapidly cycling progenitor cells and reductions in differentiated cells of the secretory lineage, including Paneth and goblet cells, but not enteroendocrine cells. GC-C signaling regulated proliferation by restricting the cell cycle at the G1/S transition. Moreover, crypt expansion in GC-C−/− mice was associated with adaptive increases in cell migration and apoptosis. Reciprocal alterations in proliferation and differentiation resulting in expansion associated with adaptive responses in migration and apoptosis suggest that GC-C coordinates component processes maintaining homeostasis of the crypt progenitor compartment. In the context of uniform loss of GC-C signaling during tumorigenesis, dysregulation of those homeostatic processes may contribute to mechanisms underlying colon cancer

Enterotoxin preconditioning restores calcium-sensing receptor-mediated cytostasis in colon cancer cells

Guanylyl cyclase C (GCC), the receptor for diarrheagenic bacterial heat-stable enterotoxins (STs), inhibits colorectal cancer cell proliferation by co-opting Ca2+ as the intracellular messenger. Similarly, extracellular Ca2+ (Ca2+o) opposes proliferation and induces terminal differentiation in intestinal epithelial cells. In that context, human colon cancer cells develop a phenotype characterized by insensitivity to cytostasis imposed by Ca2+o. Here, preconditioning with ST, mediated by GCC signaling through cyclic nucleotide-gated channels, restored Ca2+o-dependent cytostasis, reflecting posttranscriptional regulation of calcium-sensing receptors (CaRs). ST-induced GCC signaling deployed CaRs to the surface of human colon cancer cells, whereas elimination of GCC signaling in mice nearly abolished CaR expression in enterocytes. Moreover, ST-induced Ca2+o-dependent cytostasis was abrogated by CaR-specific antisense oligonucleotides. Importantly, following ST preconditioning, newly expressed CaRs at the cell surface represented tumor cell receptor targets for antiproliferative signaling by CaR agonists. Since expression of the endogenous paracrine hormones for GCC is uniformly lost early in carcinogenesis, these observations offer a mechanistic explanation for the Ca2+o-resistant phenotype of colon cancer cells. Restoration of antitumorigenic CaR signaling by GCC ligand replacement therapy represents a previously unrecognized paradigm for the prevention and treatment of human colorectal cancer employing dietary Ca2+ supplementation