A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca2+ and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca2+, whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement

Aphasia education: speech-language pathologists’ perspectives regarding current and optimal practice

Background: People with aphasia (PWA) and their families (PWA-F) have conveyed that the receipt of information and education is a key component of rehabilitation which supports access to services and participation in healthcare decision-making. Best practice recommendations state that education about aphasia should be tailored, aphasia-friendly, and provided on multiple occasions and in a variety of formats. To date, there has been little research examining the current practices of speech-language pathologists (SLPs) in the provision of education or their perspectives on barriers and facilitators to achieving optimal aphasia education practices. Aims: The aim of this study was to explore current and optimal aphasia education practices from the perspective of Australian SLPs. Methods and Procedures: This study used a cross-sectional survey design, comprising both quantitative and qualitative questions. An online survey was distributed to Australian SLPs via professional networks. Quantitative data were analysed using descriptive statistics and qualitative data using content analysis. Outcomes and Results: This study reports data from 130 Australian SLPs. The majority of SLPs (>70%) reported that they provided information to both PWA and PWA-F about (1) the definition of aphasia, (2) characteristics of aphasia, (3) causes of aphasia, (4) aphasia recovery, (5) strategies to assist communication, and (6) coping strategies. However, the majority of SLPs reported that they did not provide information to friends on any of the presented topics. Many SLPs (>95%) provided both face-to-face and written aphasia information, and approximately half (55%) provided aphasia education that could be accessed via the Internet. All but one SLP reported using pre-prepared written information and less than half (45%) considered those materials to be formatted in an aphasia-friendly way. The majority of SLPs (65%) reported that they did not have a systematic approach to providing aphasia education, they (82%) did not evaluate the effectiveness of aphasia education, and they (92%) did not provide optimal aphasia education. SLPs reported that greater access to aphasia-friendly formatted information (94%) and written information for family members (92%) would assist in optimising aphasia education. Furthermore, 82% of SLPs indicated that they would support an Australia-wide move to use the term aphasia, rather than dysphasia. Conclusions: The majority of SLPs reported providing information to PWA and PWA-F in a variety of formats; however, information provision did not commonly extend to friends. Increased tailoring of information and access to aphasia-friendly information would assist SLPs in meeting best practice recommendations for aphasia education

Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines

Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium

Cholesterol modulates the recruitment of Kv1.5 channels from Rab11-associated recycling endosome in native atrial myocytes

Cholesterol is an important determinant of cardiac electrical properties. However, underlying mechanisms are still poorly understood. Here, we examine the hypothesis that cholesterol modulates the turnover of voltage-gated potassium channels based on previous observations showing that depletion of membrane cholesterol increases the atrial repolarizing current IKur. Whole-cell currents and single-channel activity were recorded in rat adult atrial myocytes (AAM) or after transduction with hKv1.5-EGFP. Channel mobility and expression were studied using fluorescence recovery after photobleaching (FRAP) and 3-dimensional microscopy. In both native and transduced-AAMs, the cholesterol-depleting agent MβCD induced a delayed (≈7 min) increase in IKur; the cholesterol donor LDL had an opposite effect. Single-channel recordings revealed an increased number of active Kv1.5 channels upon MβCD application. Whole-cell recordings indicated that this increase was not dependent on new synthesis but on trafficking of existing pools of intracellular channels whose exocytosis could be blocked by both N-ethylmaleimide and nonhydrolyzable GTP analogues. Rab11 was found to coimmunoprecipitate with hKv1.5-EGFP channels and transfection with Rab11 dominant negative (DN) but not Rab4 DN prevented the MβCD-induced IKur increase. Three-dimensional microscopy showed a decrease in colocalization of Kv1.5 and Rab11 in MβCD-treated AAM. These results suggest that cholesterol regulates Kv1.5 channel expression by modulating its trafficking through the Rab11-associated recycling endosome. Therefore, this compartment provides a submembrane pool of channels readily available for recruitment into the sarcolemma of myocytes. This process could be a major mechanism for the tuning of cardiac electrical properties and might contribute to the understanding of cardiac effects of lipid-lowering drugs