869 research outputs found

    The Interweaving of Poetry and Dance in Ben Jonson\u27s Masques

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    The masked noblemen prepare to preform one of their intricate dances for King James I and his court; they aim to make the complex floor patterns and body movements appear ordered, adroit, and effortless. Their dances are just one element of the highly elaborate Stuart court masque with integrates dance, poetry, scenic design, costume design and music into a three-hour dramatic spectacle. All that remains today of the lavish event is a text of twelve pages, some short descriptions of the choreography, a handful of sketches, and several short pieces of music. Although we can never fully reconstruct Pleasure Reconciled to Virtue or any other Stuart masque, we can piece together the evidence, and attempt to understand how jonson conceives and constructs his masques

    Tn5 synaptic complex formation : role of transposase residue W450

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    Author Posting. Ā© American Society for Microbiology, 2008. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Journal of Bacteriology 190 (2008): 1484-1487, doi:10.1128/JB.01488-07.A series of Tn5 transposases (Tnp's) with mutations at the conserved amino acid position W450, which was structurally predicted to be important for synapsis, have been generated and characterized. This study demonstrates that W450 is involved in hydrophobic (and possibly aromatic) contacts within the Tnp monomer that negatively regulate synaptic complex formation.This work was supported by the NIH (grant no. GM50693) and the University of Wisconsinā€”Madison (grant no. WIS04792) and through the Evelyn Mercer Professorship in Biochemistry and Molecular Biology

    Phosphate coordination and movement of DNA in the Tn5 synaptic complex: role of the (R)YREK motif

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    Bacterial DNA transposition is an important model system for studying DNA recombination events such as HIV-1 DNA integration and RAG-1-mediated V(D)J recombination. This communication focuses on the role of proteinā€“phosphate contacts in manipulating DNA structure as a requirement for transposition catalysis. In particular, the participation of the nontransferred strand (NTS) 5ā€² phosphate in Tn5 transposition strand transfer is analyzed. The 5ā€² phosphate plays no direct catalytic role, nonetheless its presence stimulates strand transfer āˆ¼30-fold. X-ray crystallography indicates that transposaseā€“DNA complexes formed with NTS 5ā€² phosphorylated DNA have two properties that contrast with structures formed with complexes lacking the 5ā€² phosphate or complexes generated from in-crystal hairpin cleavage. Transposase residues R210, Y319 and R322 of the (R)YREK motif coordinate the 5ā€² phosphate rather than the subterminal NTS phosphate, and the 5ā€² NTS end is moved away from the 3ā€² transferred strand end. Mutation R210A impairs the 5ā€² phosphate stimulation. It is posited that DNA phosphate coordination by R210, Y319 and R322 results in movement of the 5ā€² NTS DNA away from the 3ā€²-end thus allowing efficient target DNA binding. It is likely that this role for the newly identified RYR triad is utilized by other transposase-related proteins

    P-624: Changes in plasma renin match the antihypertensive effects of aliskiren in patients with hypertension: Placebo/irbesartan-controlled trial with the orally active renin inhibitor aliskiren

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    For several decades, the lack of oral availability and poor antihypertensive effects of renin inhibitors (RI), despite seemingly powerful inhibition of conventionally measured plasma renin activity (PRA), have discredited RI as cardiovascular drugs. Aliskiren is a novel orally effective RI with antihypertensive potency comparable to losartan or irbesartan. The present study investigated the effects of aliskiren and irbesartan on PRA, measured by the reliable antibody trapping technique, as well as on plasma active renin concentration (ARC) and sitting systolic blood pressure (SBP). In 569 patients with mild to moderate hypertension (baseline sphygmomanometric sitting blood pressure 152Ā±12/99Ā±4 mmHg, meanĀ±SD), PRA and ARC, as well as SBP were measured before and after 8 weeks of treatment with once daily oral doses of aliskiren (150, 300 or 600mg), irbesartan 150mg or placebo. The effects of study treatments on PRA, ARC and SBP are summarized in the Table. Treatment N PRA (ng/mL/h) ARC (pg/mL) SBP (mmHg) Baseline Week 8 Baseline Week 8 Baseline Week 8 Placebo 111 0.72 0.64 6.2 5.6 152 Ā± 12 147 Ā± 18 Aliskiren 150mg 112 0.66 0.20 6.0 15.3 151 Ā± 11 140 Ā± 14 Aliskiren 300mg 115 0.59 0.17 6.1 21.0 152 Ā± 10 137 Ā± 14 Aliskiren 600mg 113 0.64 0.16 5.8 34.9 153 Ā± 12 137 Ā± 16 Irbesartan 150mg 118 0.64 1.33 5.5 11.3 153 Ā± 11 140 Ā± 16 PRA and ARC values are geometric means; SBP values are mean Ā± SD Aliskiren reduced PRA by 69%, 71% and 75% at 150, 300 and 600mg respectively, while irbesartan doubled PRA. Most of the antihypertensive effect of aliskiren was obtained with the lowest dose, but higher doses slightly further decreased SBP. Aliskiren 150mg and irbesartan 150mg provided similar increases in ARC and hence comparably blocked the renin-angiotensin system (RAS), and the achieved SBP was also the same. Aliskiren 300mg and 600mg caused greater increases in ARC compared with irbesartan 150mg (p<0.05), and further decreases in SBP. The dose-dependent increases in ARC observed with aliskiren document increasing blockade of the RAS. In conclusion, aliskiren provides a parallel reduction in PRA and SBP, a dose-dependent blockade of the RAS and is at least as effective as irbesartan at comparable dosages (150mg

    Difficult-to-Treat or Resistant Hypertension: Etiology, Pathophysiology, and Innovative Therapies

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    Despite the many therapeutic options available today for the treatment of hypertension, a sizable number of patients still remain resistant to treatment. The prevalence of resistant hypertension in the general population under optimal conditions is about 3ā€“5%. Although several factors and conditions can be identified and corrected a percentage of hypertensive patients remain with unacceptably high blood pressure levels. The high prevalence of hypertension in the general population renders this small percentage significant, in terms of actual patient numbers. This special issue of the journal expoars a whole spectrum of topics related to resistant hypertension: several articles address pathophysiolog and secondary causes of resistant hypertension and modern approaches to therapy. Of interest is the referance to the newer interventional approaches, that is, Baroreceptor stimulation therapy and catheter based sympathetic renal denervation

    Predictors of uncontrolled hypertension and antihypertensive medication nonadherence

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    http://www.jcdronline.com/text.asp?2010/1/4/196/74263Background: Although hypertension is, in most cases, a controllable major risk factor in the development of cardiovascular disease, studies have demonstrated that hypertension remains poorly controlled in Portugal. Our aim was to evaluate the covariates associated with poor blood pressure (BP) control in a Portuguese hypertensive population. Patients and Results: We conducted a cross-sectional survey in a hospital hypertension outpatient clinic, located in the Eastern Central Region of Portugal. Patients attending the clinic from July to September 2009 were asked to participate in a structured interview including medication adherence and knowledge about hypertension. Eligible participants were all adults aged 18 or over with an established diagnosis of arterial hypertension and had been on antihypertensive drug treatment for at least 6 months. Exclusion criteria were dementia, pregnancy, and breastfeeding. Detailed clinical information was prospectively obtained from medical records. A total of 197 patients meeting the inclusion criteria and consenting to participate completed the interview. Of these, only 33.0% had their BP controlled according to the JNC 7 guidelines. Logistic regression analysis revealed three independent predictors of poor BP control: living alone (OR = 5.3, P = 0.004), medication nonadherence (OR = 4.8, P < 0.001), and diabetes (OR = 4.4, P = 0.011). Predictors of medication nonadherence were: unawareness of target BP values (OR = 3.7, P < 0.001), a report of drug side effects (OR = 3.7, P = 0.002), lack of BP monitoring (OR = 2.5, P = 0.015) and unawareness of medication indications (OR = 2.4, P = 0.021), and of hypertension risks (OR = 2.1, P = 0.026). Conclusions: Poor medication adherence, lack of information about hypertension, and side effects should be considered as possible underlying causes of uncontrolled BP and must be addressed in any intervention aimed to improve BP control

    Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

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    Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users
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