The career of the MP and poet Christopher Brooke, in particular
his The ghost of
Richard the third (1614) and his activity in the 1614 ‘addled’
parliament, forms the basis of this
study of Jacobean ...political culture. Brooke's career foregrounds the
close interaction of political and
literary cultures in the period; he was a leading member of the political
circle,
the ‘Sireniacs’, which
had strong parliamentary ties, and was one of the Inns of Court-based
‘oppositional’ Spenserian
poets. Together with his fellow ‘Sireniac’ MPs, Brooke
vehemently opposed the definition of
impositions as the domain of absolute rather than ordinary powers of
the crown because of the threat
this posed to the rights of parliament and the subject. The ghost of
Richard the third provides an
example of parliamentary debates entering a wider print culture, where
impositions merged with
broader civic issues. Political language in this period was not confined
to the realms of high theory and
Brooke's poem illustrates the complex mediation of political
discourses through literary forms. A
humanist discourse of tyranny provided Brooke with a coded language,
enabling him to articulate his
concern for the health of the commonwealth and to address areas of
ideological conflict in early Stuart political culture.
Thomas Middleton is one of the major English Renaissance dramatists alongside Marlowe, Shakespeare and Jonson. Middleton continues to fascinate audiences and readers with his black humour, his wry ...and witty treatment of sexuality, morality, and politics. He is a consummate professional dramatist, experimenting with stagecraft in a manner that combines the visual and the verbal to startling effect.
This book brings together these aspects of Middleton's craft through a detailed study of his major plays. Middleton experimented with, and helped to shape, a range of dramatic genres: city comedy, tragicomedy, romance, and revenge tragedy. This new guide analyses in detail how the plays work in terms of the early modern theatre and dramatic genres, as well as elucidating the broader cultural issues shaping the plays. It provides an introduction to critical readings of Middleton's works as well as modern performances, demonstrating how modern critics, producers, dramatists and film makers see Middleton's dark, playful and challenging plays as speaking to our times.
Key Features
Ideal student guide with its wide ranging introduction to Middleton's city comedies, tragedies, and collaborative plays and its readings of key texts such asThe Roaring Girl,Chaste Maid in Cheapside,Revenger's Tragedy,Women Beware Women, andThe ChangelingUses the most recent edition available, the Oxford Middleton (2007)Provides background contexts guiding readers through criticism of the plays as well as recent work on early modern theatre and cultureEmphasis on Middleton's stagecraft and its assessment of modern adaptations and film versions of his plays
The intercalated disc (ICD) is a unique membrane structure that is indispensable to normal heart function, yet its structural organization is not completely understood. Previously, we showed that the ...ICD-bound transmembrane protein 65 (Tmem65) was required for connexin43 (Cx43) localization and function in cultured mouse neonatal cardiomyocytes. Here, we investigate the functional and cellular effects of Tmem65 reductions on the myocardium in a mouse model by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 shRNA, which reduces Tmem65 expression by 90% in mouse ventricles compared to scrambled shRNA injection. Tmem65 knockdown (KD) results in increased mortality which is accompanied by eccentric hypertrophic cardiomyopathy within 3 weeks of injection and progression to dilated cardiomyopathy with severe cardiac fibrosis by 7 weeks post-injection. Tmem65 KD hearts display depressed hemodynamics as measured echocardiographically as well as slowed conduction in optical recording accompanied by prolonged PR intervals and QRS duration in electrocardiograms. Immunoprecipitation and super-resolution microscopy demonstrate a physical interaction between Tmem65 and sodium channel β subunit (β1) in mouse hearts and this interaction appears to be required for both the establishment of perinexal nanodomain structure and the localization of both voltage-gated sodium channel 1.5 (NaV1.5) and Cx43 to ICDs. Despite the loss of NaV1.5 at ICDs, whole-cell patch clamp electrophysiology did not reveal reductions in Na
currents but did show reduced Ca
and K
currents in Tmem65 KD cardiomyocytes in comparison to control cells. We conclude that disrupting Tmem65 function results in impaired ICD structure, abnormal cardiac electrophysiology, and ultimately cardiomyopathy.
Cell-based models that mimic in vivo heart physiology are poised to make significant advances in cardiac disease modeling and drug discovery. In these systems, cardiomyocyte (CM) contractility is an ...important functional metric, but current measurement methods are inaccurate and low-throughput or require complex setups. To address this need, we developed a standalone noninvasive, label-free ultrasound technique operating at 40–200 MHz to measure the contractile kinetics of cardiac models, ranging from single adult CMs to 3D microtissue constructs in standard cell culture formats. The high temporal resolution of 1000 fps resolved the beat profile of single mouse CMs paced at up to 9 Hz, revealing limitations of lower speed optical based measurements to resolve beat kinetics or characterize aberrant beats. Coupling of ultrasound with traction force microscopy enabled the measurement of the CM longitudinal modulus and facile estimation of adult mouse CM contractile forces of 2.34 ± 1.40 μN, comparable to more complex measurement techniques. Similarly, the beat rate, rhythm, and drug responses of CM spheroid and microtissue models were measured, including in configurations without optical access. In conclusion, ultrasound can be used for the rapid characterization of CM contractile function in a wide range of commonly studied configurations ranging from single cells to 3D tissue constructs using standard well plates and custom microdevices, with applications in cardiac drug discovery and cardiotoxicity evaluation.
The use of probiotics such as Lactobacillus and Bifidobacterium spp. as a therapeutic against inflammatory bowel disease (IBD) is of significant interest. Lactobacillus salivarus strain UCC118sup.TM ...is a commensal that has been shown to possess probiotic properties in vitro and anti-infective properties in vivo. However, the usefulness of UCC118 sup.TM as a therapeutic against colitis remains unclear. This study investigates the probiotic potential of Lactobacillus salivarius, UCC118™ in a mouse model of colitis. DSS-induced colitis was coupled with pre-treatment or post-treatment with UCC118sup.TM by daily oral gavage. In the pre-treatment model of colitis, UCC118sup.TM reduced the severity of the disease in the early stages. Improvement in disease severity was coupled with an upregulation of tissue IL-10 levels and increased expression of macrophage M2 markers. This anti-inflammatory activity of UCC118sup.TM was further confirmed in vitro, using a model of LPS-treated bone marrow-derived macrophages. Taken together, these results suggest that UCC118sup.TM may promote the resolution of inflammation. This was supported in a mouse model of established DSS-induced colitis whereby UCC118sup.TM treatment accelerated recovery, as evidenced by weight, stool, histological markers and the recovery of microbiome-associated dysbiosis with an increased abundance of beneficial commensal species. These results demonstrate the potential of Lactobacillus salivarius UCC118sup.TM as a probiotic-based therapeutic strategy to promote health through the upregulation of anti-inflammatory IL-10 and protect against dysbiosis during IBD.
Handbook of Citizen Science in Ecology and Conservation is the first practical and comprehensive manual for creating, implementing, or improving natural science research and monitoring projects that ...involve collaboration between scientists and the general public. As citizen science projects become increasingly common, project leaders are seeking information on concrete best practices for planning and implementing projects-practices that allow them to guide and gauge success while also ensuring the collection of high-quality data and rewarding experiences for volunteers. In this handbook, citizen science practitioners from around the world and with decades of experience provide step-by-step instructions, insights, and advice, and they explore real-world applications through case studies from a variety of citizen science projects. This is the definitive reference guide for anyone interested in starting or improving a citizen science project with ecological or conservation applications, from professors and graduate students to agency staff and nongovernmental organizations.
Ciprofloxacin and prednisolone, but not an aminoglycoside and dexamethasone, were previously found to be effective in killing bacteria and reducing inflammation for the treatment of Pseudomonas ...keratitis. We investigated the therapeutic effectiveness of tobramycin/prednisolone and ciprofloxacin/dexamethasone in a rabbit model of experimental keratitis to increase our understanding of the effectiveness of antibiotic/steroid combinations. To our knowledge, this is the first analysis of the effectiveness of a combination of ciprofloxacin and dexamethasone for experimental keratitis. Two experiments were conducted. In the first experiment, 36 rabbits were divided into six groups: 1) untreated; 2) prednisolone acetate, 1.0%; 3) prednisolone phosphate, 1.0%; 4) tobramycin, 1.36%; 5) tobramycin plus prednisolone acetate; 6) tobramycin plus prednisolone phosphate. In the second experiment, 23 rabbits were divided into four groups: 1) untreated; 2) ciprofloxacin, 0.3%, plus dexamethasone alcohol, 0.1%; 3) ciprofloxacin; 4) dexamethasone alcohol. Topical antibiotic and/or steroid was given for 10 h, from 16 to 26 h postinfection, one drop every 15 min for the first hour and then every 30 min for the remaining 9 h. At 27 h postinfection, eyes were evaluated by slit lamp examination (SLE) and assayed for the presence of bacteria in terms of colony forming units (CFU) per cornea. Both prednisolone acetate and prednisolone phosphate reduced ocular inflammation (as determined by SLE), compared with no treatment (P < or = 0.036); the phosphate was more effective (P = 0.005). Tobramycin alone and in combination with prednisolone also significantly reduced SLE, compared with no treatment (P < or = 0.006). The bactericidal activity of tobramycin was not affected by either steroid formulation.
