Interface connections of a transmembrane voltage sensor

Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are alpha-helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K+ channel [Jiang, et al. (2003) Nature 423, 33-41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to approximately 10 A in the vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein.     

Angioarchitectural Evolution of Clival Dural Arteriovenous Fistulas in Two Patients

Dural arteriovenous fistulas (dAVFs) may present in a variety of ways, including as carotid-cavernous sinus fistulas. The ophthalmologic sequelae of carotid-cavernous sinus fistulas are known and recognizable, but less commonly seen is the rare clival fistula. Clival dAVFs may have a variety of potential anatomical configurations but are defined by the involvement of the venous plexus just overlying the bony clivus. Here we present two cases of clival dAVFs that most likely evolved from carotid-cavernous sinus fistulas.Key Words: Neuro-ophthalmology, Carotid-cavernous sinus fistula, Clivus, Clival fistula, Dural arteriovenous fistula     

Mediterranean Alcohol-Drinking Pattern and the Incidence of Cardiovascular Disease and Cardiovascular Mortality: The SUN Project

Background: We assessed the still unclear effect of the overall alcohol-drinking pattern, beyond the amount of alcohol consumed, on the incidence of cardiovascular clinical disease (CVD). Methods: We followed 14,651 participants during up to 14 years. We built a score assessing simultaneously seven dimensions of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, preference for wine, red wine consumption, wine consumed during meals and avoidance of binge drinking. Results: During 142,177 person-years of follow-up, 127 incident cases of CVD (myocardial infarction, stroke or cardiovascular mortality) were identified. Compared with the category of better conformity with the MADP, the low-adherence group exhibited a non-significantly higher risk (HR) of total CVD ((95% CI) = 1.55 (0.58–4.16)). This direct association with a departure from the traditional MADP was even stronger for cardiovascular mortality (HR (95% CI) = 3.35 (0.77–14.5)). Nevertheless, all these associations were statistically non-significant. Conclusion: Better conformity with the MADP seemed to be associated with lower cardiovascular risk in most point estimates; however, no significant results were found and more powered studies are needed to clarify the role of the MADP on CVD.     

Current status of the rheumatologists’ workforce in Latin America: a PANLAR collaborative study

Clinical Rheumatology - Studies conducted by various scientific societies have shown that the demand for specialized rheumatology care is greater than the projected growth of the workforce. Our...