Chaperone activity and structure of monomeric polypeptide binding domains of GroEL

The chaperonin GroEL is a large complex composed of 14 identical 57-kDa subunits that requires ATP and GroES for some of its activities. We find that a monomeric polypeptide corresponding to residues 191 to 345 has the activity of the tetradecamer both in facilitating the refolding of rhodanese and cyclophilin A in the absence of ATP and in catalyzing the unfolding of native barnase. Its crystal structure, solved at 2.5 A resolution, shows a well-ordered domain with the same fold as in intact GroEL. We have thus isolated the active site of the complex allosteric molecular chaperone, which functions as a "minichaperone." This has mechanistic implications: the presence of a central cavity in the GroEL complex is not essential for those representative activities in vitro, and neither are the allosteric properties. The function of the allosteric behavior on the binding of GroES and ATP must be to regulate the affinity of the protein for its various substrates in vivo, where the cavity may also be required for special functions

Tako-tsubo cardiomyopathy after administration of ergometrine following elective caesarean delivery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tako-tsubo cardiomyopathy (stress-induced cardiomyopathy or transient left ventricular ballooning) is characterized by clinical suspicion of an acute myocardial infarction with transient apical or midventricular dyskinesia of the left ventricle without significant coronary stenosis on angiography. The etiology of this disease remains obscure. One of the possible causes is myocardial ischemia induced by coronary vasospasm due to sympathetic activation. It has been hypothesized that the application of ergometrine could induce tako-tsubo cardiomyopathy.</p> <p>Case presentation</p> <p>We report the case of a 28-year-old Turkish woman who developed tako-tsubo cardiomyopathy after administration of ergometrine for release of placenta and prevention of bleeding during the post-partum phase in the course of an elective caesarean delivery. Tako-tsubo cardiomyopathy was diagnosed by echocardiography and urgent cardiac magnetic resonance imaging. A coronary angiography was not performed because of the absence of myocardial necrosis or ischemia and signs of myocarditis on cardiac magnetic resonance imaging.</p> <p>Conclusion</p> <p>This life-threatening disease should be excluded in the differential diagnosis by comparing the symptoms with those of typical heart failure, particularly after use of ergometrine.</p

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Hemispheric specialisation within the superior anterior temporal cortex for social and non-social concepts

Abstract Studies of semantic dementia, imaging, and repetitive TMS have suggested that the bilateral anterior temporal lobes (ATLs) underpin a modality-invariant representational hub within the semantic system. Questions remain, however, regarding functional specialization across a variety of knowledge domains within the ATL region. We investigated direct evidence for the functional relevance of the superior ATL in processing social concepts. Using converging evidence from noninvasive brain stimulation and neuropsychology, we demonstrate graded differentiation of right and left superior anterior temporal areas in social cognition. Whereas the left superior ATL is necessary for processing both social and nonsocial abstract concepts, social conceptual processing predominates in the right superior ATL. This graded hemispheric specialization is mirrored in the patient results. Our data shed new light on the classic debate about hemispheric differences in semantic and social cognition. These results are considered in the context of models of semantic representation and the emerging data on connectivity for left and right ATL regions.</jats:p

Chaperone activity and structure of monomeric polypeptide binding domains of GroEL

The chaperonin GroEL is a large complex composed of 14 identical 57-kDa subunits that requires ATP and GroES for some of its activities. We find that a monomeric polypeptide corresponding to residues 191 to 345 has the activity of the tetradecamer both in facilitating the refolding of rhodanese and cyclophilin A in the absence of ATP and in catalyzing the unfolding of native barnase. Its crystal structure, solved at 2.5 A resolution, shows a well-ordered domain with the same fold as in intact GroEL. We have thus isolated the active site of the complex allosteric molecular chaperone, which functions as a "minichaperone." This has mechanistic implications: the presence of a central cavity in the GroEL complex is not essential for those representative activities in vitro, and neither are the allosteric properties. The function of the allosteric behavior on the binding of GroES and ATP must be to regulate the affinity of the protein for its various substrates in vivo, where the cavity may also be required for special functions

Biogenic silica, TOC, CaCO3, and diatom records of sediment core MD02-2588

The hydrography of the Indian‐Atlantic Ocean gateway has been connected to high‐latitude climate dynamics by oceanic and atmospheric teleconnections on orbital and suborbital timescales. A wealth of sedimentary records aiming at reconstructing the late Pleistocene paleoceanography around the southern African continent has been devoted to understanding these linkages. Most of the records are, however, clustered close to the southern South African tip, with comparatively less attention devoted to areas under the direct influence of frontal zones of the Southern Ocean/South Atlantic. Here we present data of the composition and concentration of the diatom assemblage together with bulk biogenic content and the alkenone‐based sea surface temperature (SST) variations for the past 350 kyr in the marine sediment core MD02‐2588 (approximately 41°S, 26°E) recovered from the southern Agulhas Plateau. Variations in biosiliceous productivity show a varying degree of coupling with Southern Hemisphere paleoclimate records following a glacial‐interglacial cyclicity. Ecologically well‐constrained groups of diatoms record the glacial‐interglacial changes in water masses dynamics, nutrient availability, and stratification of the upper ocean. The good match between the glacial maxima of total diatoms concentration, Chaetoceros spores abundance, and opal content with the maximum seasonal cover of Antarctic ice and the atmospheric dust records points to a dominant Southern Hemisphere forcing of diatom production. Suborbital variability of SST suggests rapid latitudinal migrations of the Subtropical Front and associated water masses over the southern Agulhas Plateau, following millennial contractions and expansions of the subtropical gyres. Warmings of the upper ocean over site MD02‐2588 during terminations IV to I occurred earlier than that in the Antarctic Vostok, which is indicative of a Northern Hemisphere lead. Our multiparameter reconstruction highlights how high‐latitude atmospheric and hydrographic processes modulated orbital highs and lows in primary production and SST as triggered by northward transport of Si, eolian dust input, and latitudinal migrations of frontal zones