Shakespeare in Action

Scholarly introduction to co-edited special issu

‘A sea-change’: representations of the marine in Jacobean drama and visual culture

This thesis is concerned with exploring different forms of Jacobean drama and performances that span across different sites, from the commercial stages of London, to the civic pageants that took place on the Thames and in the City, and the court entertainments held at Whitehall Palace. My research necessarily casts a wide net over its subject matter in order to illustrate how these different modes of performance engage with representations of the marine through the technologies available to them, whether poetic, material, or both. While the sea had long been a receptacle for literary and poetic attention and can repeatedly be found as the stronghold of adventure, wonder, danger, and exile in the English narrative tradition, it is specifically at the beginning of the seventeenth century that the sea takes a hold of the literary imagination with particular force. The cultural, political, and economic predominance of the marine in early modern England found numerous means of expression in drama, where the different facets of marine identity and occupation create on-stage marine spaces. The thesis elucidates how these modes of performance often invoke and exploit the dramatic potential of the marine and its commercial, political, and iconographical meanings. Commercial drama, written for a pre-proscenial stage, realises the marine through language and metaphor, appealing to a collective imaginary in bodying forth the limitless watery expanses on which the action takes place. This imaginative embodiment finds a very different—and indeed a more material—means of expression in civic drama and the court masque, where the extensive and elaborate pageant devices and stage machinery were largely indebted to and shaped by continental theatrical design. The material means of expressing the marine that are found in the civic performances and the court masques discussed in this study necessitates a consideration of European trends in theatre design and the decorative arts. In looking to visual and material culture this thesis explicates the interdependence between different modes of creating on-stage marine spaces and the ways in which the material presence inflects both language and action in Jacobean drama

An entrepreneurship model for assessing the investment attractiveness of regions

Аналіз результатів моделювання показав, що занадто багато показників усувають розбіжності в рівнях підприємницької моделі інвестиційної привабливості регіонів, тому при проведенні аналітичної роботи доцільно деталізувати напрям інвестицій. Отже, якщо врахувати рівень інвестиційної привабливості регіонів за факторами, ми можемо визначити чітких лідерів. Доведено, що при оцінці інвестиційної привабливості територіальних одиниць необхідно враховувати фактор "Захищеність інвестиційної діяльності" (криміногенний, екологічний, політичний). До останніх двох факторів слід віднести такі показники, як туристичний потенціал та національна самосвідомість населення регіону, які можна виразити в лінгвістичній формі та дослідити за допомогою нечіткої логічної апаратури.Analysis of the simulation results showed that too many indicators eliminate differences in an levels of entrepreneurship model the investment attractiveness of the regions, therefore, when conducting analytical work, it is advisable to detail the direction of investment. So, if we consider the level of investment attractiveness of the regions by factors, we can identify clear leaders. It is proved that in assessment the investment attractiveness of territorial units, it is necessary to take into account the factor "Security of investment activity" (criminogenic, environmental, political). The last two factors should be attributed to such indicators as tourism potential and national self-awareness of the population of the region, which can be expressed in linguistic form and investigated using fuzzy logic apparatus

Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

Modelling maternal obesity: the effects of a chronic high-fat, high-cholesterol diet on uterine expression of contractile-associated proteins and ex vivo contractile activity during labour in the rat

Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present study investigated the effects of an adiposity-inducing high fat, high-cholesterol (HFHC) diet on uterine contractile associated protein (CAP) expression and ex vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n = 20) or HFHC (n = 20) diet 6 weeks before conception and during pregnancy. On gestational day 21(TNL) or day 22 (TL) CON and HFHC (n = 10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX-43) and it’s phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P 0.001), plasma cholesterol (P 0.001) and triacylglycerol (P = 0.039) concentrations. Stage of labour effected uterine expression of CAV-1 (P < 0.02), pCX43 and COX-2 (both P < 0.03). CAV-1 and pCX43 decreased but COX-2 increased with parturition. Significant diet- and labour-stage interactions were evident for CX-43 and pCX43 (P < 0.03 and P < 0.004 respectively). CX-43 decreased with TL in HFHC animals but was unaltered in CON. pCX-43 fell with labour in CON but remained high in HFHC. OXTR expression was significantly higher in HFHC compared with CON animals (P < 0.03). Progesterone was higher in HFHC rats at term (P < 0.014) but fell significantly with labour to similar concentrations as CON. Contractility studies identified synchronous contractions of stable amplitude in lean animals, but unstable asynchronous contractions with obesity. Uterine dose response to oxytocin was blunted during labour in HFHC rats with a log EC50 of −8.84 compared with −10.25 M in CON for integral activity (P < 0.05). In conclusion, our adiposity model exhibits adverse effects on contractile activity during labour that can be investigated further to unravel the mechanisms causing uterine dystocia in obese women

Contraction and Intracellular Calcium Transport in Epicardial and Endocardial Ventricular Myocytes from Streptozotocin-Induced Diabetic Rat

Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045. Although diabetes can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. Diabetic patients frequently suffer from systolic and diastolic dysfunction. Within the ventricles, the electromechanical properties of cardiac myocytes vary transmurally. The aim of this study was to investigate contraction and Ca2+ transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle in the streptozotocin (STZ)-induced diabetic rat heart. Experiments were performed 5–6 months after STZ treatment. Ventricular myocytes were isolated by enzymic and mechanical dispersal techniques from EPI and ENDO regions of the left ventricle. Contraction and free intracellular Ca2+ concentration (Ca2+)i were measured by video edge detection and fl uorescence photometry techniques, respectively. Myocyte length and calculated surface area were smaller in EPI-STZ compared to EPI-CON. Time to peak (TPK) shortening was prolonged in EPI-STZ compared to EPI-CON and in ENDO-STZ compared to ENDO-CON myocytes. Time to half (THALF) relaxation of shortening was prolonged in EPI-STZ compared to EPI-CON. TPK Ca2+ transient was prolonged in EPI-STZ compared to EPI-CON, ENDO-STZ compared to ENDO-CON, ENDO-STZ compared to EPI-STZ and in ENDO-CON compared to EPI-CON myocytes. THALF decay of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Fractional release of Ca2+ was increased in ENDO-STZ compared to ENDO-CON and in ENDO-STZ compared to EPI-STZ. Recovery of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. In conclusion, the kinetics of contraction and Ca2+ transient, fractional release of Ca2+ from the sarcoplasmic reticulum are altered to different extents in EPI and ENDO myocytes from STZ-induced diabetic rat

Reconstruction of cell surface densities of ion pumps, exchangers, and channels from mRNA expression, conductance kinetics, whole-cell calcium, and current-clamp voltage recordings, with an application to human uterine smooth muscle cells

Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the ‘conductance repertoire’ being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations

Calcium Signaling in the Ventricular Myocardium of the Goto-Kakizaki Type 2 Diabetic Rat

The association between diabetes mellitus (DM) and high mortality linked to cardiovascular disease (CVD) is a major concern worldwide. Clinical and preclinical studies have demonstrated a variety of diastolic and systolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with the severity of abnormalities depending on the patients’ age and duration of diabetes. The cellular basis of hemodynamic dysfunction in type 2 diabetic heart is still not well understood. The aim of this review is to evaluate our current understanding of contractile dysfunction and disturbances of Ca2+ transport in the Goto-Kakizaki (GK) diabetic rat heart. The GK rat is a widely used non-obese, non-hypertensive genetic model of T2DM which is characterized by insulin resistance, elevated blood glucose, alterations in blood lipid profile and cardiac dysfunction

Contraction and Intracellular Calcium Transport in Epicardial and Endocardial Ventricular Myocytes from Streptozotocin-Induced Diabetic Rat

Introduction: Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045. Although diabetes can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. Diabetic patients frequently suffer from systolic and diastolic dysfunction. Within the ventricles, the electromechanical properties of cardiac myocytes vary transmurally. Aims and Objectives: The aim of this study was to investigate contraction and Ca2+ transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle in the streptozotocin (STZ) “ induced diabetic rat heart. Materials and Methods: Experiments were performed 5-6 months after STZ treatment. Ventricular myocytes were isolated by enzymic and mechanical dispersal techniques from EPI and ENDO regions of the left ventricle. Contraction and free intracellular Ca2+ concentration [Ca2+]i were measured by video edge detection and fluorescence photometry techniques, respectively. Results: Myocyte length and calculated surface area were smaller in EPI-STZ compared to EPI-CON. Time to peak (TPK) shortening was prolonged in EPI-STZ compared to EPI-CON and in ENDO-STZ compared to ENDO-CON myocytes. Time to half (THALF) relaxation of shortening was prolonged in EPI-STZ compared to EPI-CON. TPK Ca2+ transient was prolonged in EPI-STZ compared to EPI-CON, ENDO-STZ compared to ENDO-CON, ENDO-STZ compared to EPI-STZ and in ENDO-CON compared to EPI-CON myocytes. THALF decay of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Fractional release of Ca2+ was increased in ENDO-STZ compared to ENDO-CON and in ENDO-STZ compared to EPI-STZ. Recovery of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Conclusion: In conclusion the kinetics of contraction and Ca2+ transient and fractional release of Ca2+ from the sarcoplasmic reticulum are altered to different extents in EPI and ENDO myocytes from STZ-induced diabetic rat

Maternal obesity-induced decreases in plasma, hepatic and uterine polyunsaturated fatty acids during labour is reversed through improved nutrition at conception

Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decreased synthesis of prostaglandins that stimulate myometrial contractions. We assessed the impact of maternal obesity on concentrations of precursor fatty acids (FA) for prostaglandin synthesis and whether any changes could be reversed by improved nutrition post-conception. Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6 weeks before mating. At conception half the dams switched diets providing 4 dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During parturition rats were euthanized and FA composition of plasma, liver and uterus determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations were halved in HFHC versus CON rats, but all other FAs were similar. Switching from HFHC to CON diet at conception restored all FA profles to those seen in CON rats. The increased MUFA and decreased PUFA concentrations in obese HFHC dams may contribute to aberrant prostaglandin synthesis and dysfunctional myometrial activity and it may be possible to reverse these changes, and potentially improve labour outcomes, by improving nutrition at conception