Co-expression of Gbeta 5 Enhances the Function of Two Ggamma Subunit-like Domain-containing Regulators of G Protein Signaling Proteins

Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta 5. The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K+ (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of Gbeta 5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta 5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of Gbeta 1, and co-expression of Gbeta 5 alone had no effect on GIRK channel kinetics. Gbeta 5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by Gbeta 5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein

Columbia 1968: the New York Intellectuals’ faculty response to the student sit-ins

This dissertation seeks to extrapolate the broader political and intellectual implications of the New York Intellectuals’ responses to the incidents of student protest that occurred on the Columbia University campus in 1968. Firstly three groups who were involved in the incidents are set up; the students, the faculty and the administration. By exploring how their actions influenced the student strikes and resulting media frenzy, the dissertation seeks to demonstrate three distinct political positions which current academia places these factions in. By analysing the New York Intellectuals’ direct responses to the incidents, focusing primarily on the members of the intellectual cadre who were themselves faculty members at Columbia, it then seeks to analyse their political and intellectual inclinations on a subject that was very close to home, both literally and figuratively. The broader personal, political and intellectual opinions of the figures are then drawn out in order to illuminate any shared ground or ruptures in the New York Intellectual group, at a time traditionally seen as heralding the end of their cohesive unit, the end of the liberal consensus and sometimes a beginning of neo-conservative political thought

Magnetic Resonance Imaging Assessment of Ventricular Dyssynchrony Current and Emerging Concepts

Despite the numerous documented benefits of cardiac resynchronization therapy (CRT), a significant proportion of patients undergoing CRT do not demonstrate symptomatic or morphologic improvement, triggering the search to improve targeting of this therapy. Many studies now support direct assessment of mechanical dyssynchrony as a method to better identify CRT responders. Among the methods used, echo-Doppler imaging has taken center stage and is covered in other articles in this special issue; however, these methods have several inherent limitations, and other alternatives are also being explored such as magnetic resonance imaging (MRI). This review discusses the concepts and clinical use of MRI methods for quantitative assessment of mechanical dyssynchrony, highlighting newer acquisition and analysis methods and focusing on how the data can be synthesized into robust indexes of dyssynchronous heart failure

Columbia 1968: the New York Intellectuals’ faculty response to the student sit-ins

This dissertation seeks to extrapolate the broader political and intellectual implications of the New York Intellectuals’ responses to the incidents of student protest that occurred on the Columbia University campus in 1968. Firstly three groups who were involved in the incidents are set up; the students, the faculty and the administration. By exploring how their actions influenced the student strikes and resulting media frenzy, the dissertation seeks to demonstrate three distinct political positions which current academia places these factions in. By analysing the New York Intellectuals’ direct responses to the incidents, focusing primarily on the members of the intellectual cadre who were themselves faculty members at Columbia, it then seeks to analyse their political and intellectual inclinations on a subject that was very close to home, both literally and figuratively. The broader personal, political and intellectual opinions of the figures are then drawn out in order to illuminate any shared ground or ruptures in the New York Intellectual group, at a time traditionally seen as heralding the end of their cohesive unit, the end of the liberal consensus and sometimes a beginning of neo-conservative political thought

Clinical Outcomes in Patients With Nonobstructive, Labile, and Obstructive Hypertrophic Cardiomyopathy

Background-\u2014Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease characterized by varying degrees of left ventricular outflow tract obstruction. In a large cohort, we compare the outcomes among 3 different hemodynamic groups. Methods and Results-\u2014We prospectively enrolled patients fulfilling standard diagnostic criteria for HCM from January 2005 to June 2015. Detailed phenotypic characterization, including peak left ventricular outflow tract pressure gradients at rest and after provocation, was measured by echocardiography. The primary outcome was a composite cardiovascular end point, which included new-onset atrial fibrillation, new sustained ventricular tachycardia/ventricular fibrillation, new or worsening heart failure, and death. The mean follow-up was 3.42.8 years. Among the 705 patients with HCM (mean age, 5215 years; 62% men), 230 with obstructive HCM were older and had a higher body mass index and New York Heart Association class. The 214 patients with nonobstructive HCM were more likely to have a history of sustained ventricular tachycardia/ventricular fibrillation and implantable cardioverter defibrillator implantation. During follow-up, 121 patients experienced a composite cardiovascular end point. Atrial fibrillation occurred most frequently in the obstructive group. Patients with nonobstructive HCM had more frequent sustained ventricular tachycardia/ventricular fibrillation events. In multivariate analysis, obstructive (hazard ratio, 2.80; 95% confidence interval, 1.64\u20134.80) and nonobstructive (hazard ratio, 1.94; 95% confidence interval, 1.09\u20133.45) HCM were associated with more adverse events compared with labile HCM. Conclusions-\u2014Nonobstructive HCM carries notable morbidity, including a higher arrhythmic risk than the other HCM groups. Patients with labile HCM have a relatively benign clinical course. Our data suggest detailed sudden cardiac death risk stratification in nonobstructive HCM and monitoring with less aggressive management in labile HCM