FM1-43 reveals membrane recycling in adult inner hair cells of the mammalian cochlea

Neural transmission of complex sounds demands fast and sustained rates of synaptic release from the primary cochlear receptors, the inner hair cells (IHCs). The cells therefore require efficient membrane recycling. Using two-photon imaging of the membrane marker FM1-43 in the intact sensory epithelium within the cochlear bone of the adult guinea pig, we show that IHCs possess fast calcium-dependent membrane uptake at their apical pole. FM1-43 did not permeate through the stereocilial mechanotransducer channel because uptake kinetics were neither changed by the blockers dihydrostreptomycin and D-tubocurarine nor by treatment of the apical membrane with BAPTA, known to disrupt mechanotransduction. Moreover, the fluid phase marker Lucifer Yellow produced a similar labeling pattern to FM1-43, consistent with FM1-43 uptake via endocytosis. We estimate the membrane retrieval rate at similar to0.5% of the surface area of the cell per second. Labeled membrane was rapidly transported to the base of IHCs by kinesin-dependent trafficking and accumulated in structures that resembled synaptic release sites. Using confocal imaging of FM1-43 in excised strips of the organ of Corti, we show that the time constants of fluorescence decay at the basolateral pole of IHCs and apical endocytosis were increased after depolarization of IHCs with 40 mM potassium, a stimulus that triggers calcium influx and increases synaptic release. Blocking calcium channels with either cadmium or nimodipine during depolarization abolished the rate increase of apical endocytosis. We suggest that IHCs use fast calcium-dependent apical endocytosis for activity-associated replenishment of synaptic membrane

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review

INTRODUCTION: 'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. METHODS AND ANALYSIS: The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. ETHICS AND DISSEMINATION: This scoping review of the previously published literature does not require research ethics approval. The results will be used to inform a consensus-based process to develop definitions of clinically important perioperative blood loss and transfusion. The results of the scoping review will be published in a peer-reviewed scientific journal

Genes Suggest Ancestral Colour Polymorphisms Are Shared across Morphologically Cryptic Species in Arctic Bumblebees

email Suzanne orcd idCopyright: © 2015 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Science Case for ALMA Band 2 and Band 2+3

We discuss the science drivers for ALMA Band 2 which spans the frequency range from 67 to 90 GHz. The key science in this frequency range are the study of the deuterated molecules in cold, dense, quiescent gas and the study of redshifted emission from galaxies in CO and other species. However, Band 2 has a range of other applications which are also presented. The science enabled by a single receiver system which would combine ALMA Bands 2 and 3 covering the frequency range 67 to 116 GHz, as well as the possible doubling of the IF bandwidth of ALMA to 16 GHz, are also considered

Get Organised: The 'Do's' Preceding Successful Field Research

There is no shortage in the political science literature on field research regarding issues of research design, methodology, and data evaluation. Yet, the practical and organisational intricacies that precede successful fieldwork are frequently overlooked. This lack of methodical advice may be due to the impression that field research is highly contextual, and so case-specific that general guidelines, which apply to all field research endeavours alike, are inconceivable. While we acknowledge the organisational complexity of field research, we disagree with the notion that the preparatory dimension of fieldwork is by necessity unique for every undertaking. Rather, recommendations for common challenges that occur during the preparation and organisation phase of a field trip can be identified and formulated. Consequently, we present and discuss ten organisational ?do's? preceding successful field research. Current graduate students and future field researchers will regard these ten pointers as useful hints in the organisation of their own endeavour. While the list is by no means exhaustive, the ten recommendations will lower the organisational entry costs of aspiring field researchers, and enable them to hit the ground running when arriving in the field

Benzamil inhibits neuronal and heterologously expressed small conductance Ca2²⁺-activated K⁺ channels

Small conductance Ca^{2+}-activated K^{+} (SK) channels are expressed throughout the soma and dendrites of pyramidal neurons in the neocortex and hippocampal formation, where they participate in the local regulation of membrane excitability and synaptic signals. Through their inter-play with Ca^{2+} channels, SK channels regulate Ca^{2+} influx triggered by back-propagating action potentials in dendrites. Inhibition of SK channels affects both the amplitude and duration of Ca^{2+} transients, but the role of Ca^{2+} clearance mechanisms and their link to SK channel activity has not been established. Here we report the effect of the Na^{+}/Ca^{2+} exchanger (NCX) inhibitor benzamil on Ca^{2+} extrusion and SK channels in the regulation of dendritic Ca^{2+} signals. Benzamil increased the duration and amplitude of dendritic Ca^{2+} transients elicited by back-propagating action potentials in hippocampal pyramidal neurons. This data is consistent with previous studies with SK channel blockers and suggests that benzamil inhibits SK channels in addition to the Na^{+}/Ca^{2+} exchanger. Here we show that indeed both the neuronal SK-mediated IAHP current and the currents mediated by heterologously expressed SK channels were inhibited by benzamil. The inhibition of recombinant SK channels was seen with different K+ concentration gradients, and was stronger at negative voltages. The suppression of SK channels by benzamil is consistent with previous findings on the modulation of Ca^{2+} signals by SK channels in neurons. We additionally show that benzamil inhibits neuronal voltage-gated calcium currents. The results prompt a careful reassessment of the effects of benzamil on Ca^{2+} transients in native systems, given the spectrum of ion channels and exchangers this compound targets within a similar range of concentrations

“Avoiding or approaching eyes”? Introversion/extraversion affects the gaze-cueing effect

We investigated whether the extra-/introversion personality dimension can influence processing of others’ eye gaze direction and emotional facial expression during a target detection task. On the basis of previous evidence showing that self-reported trait anxiety can affect gaze-cueing with emotional faces, we also verified whether trait anxiety can modulate the influence of intro-/extraversion on behavioral performance. Fearful, happy, angry or neutral faces, with either direct or averted gaze, were presented before the target appeared in spatial locations congruent or incongruent with stimuli’s eye gaze direction. Results showed a significant influence of intra-/extraversion dimension on gaze-cueing effect for angry, happy, and neutral faces with averted gaze. Introverts did not show the gaze congruency effect when viewing angry expressions, but did so with happy and neutral faces; extraverts showed the opposite pattern. Importantly, the influence of intro-/extraversion on gaze-cueing was not mediated by trait anxiety. These findings demonstrated that personality differences can shape processing of interactions between relevant social signals

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal