Higher-order transient membrane protein structures.

This study shows that five membrane proteins-three GPCRs, an ion channel, and an enzyme-form self-clusters under natural expression levels in a cardiac-derived cell line. The cluster size distributions imply that these proteins self-oligomerize reversibly through weak interactions. When the concentration of the proteins is increased through heterologous expression, the cluster size distributions approach a critical distribution at which point a phase transition occurs, yielding larger bulk phase clusters.

Higher-order transient structures and the principle of dynamic connectivity in membrane signaling.

We examine the role of higher-order transient structures (HOTS) in M2R regulation of GIRK channels. Electron microscopic membrane protein location maps show that both proteins form HOTS that exhibit a statistical bias to be near each other. Theoretical calculations and electrophysiological measurements suggest that channel activity is isolated near larger M2R HOTS.

The missing pieces: an investigation into the parallels between Charles Bonnet, phantom limb and tinnitus syndromes.

Charles Bonnet syndrome (CBS) is a condition characterised by visual hallucinations of varying complexity on a background of vision loss. CBS research has gained popularity only in recent decades, despite evidence dating back to 1760. Knowledge of CBS among both the patient and professional populations unfortunately remains poor, and little is known of its underlying pathophysiology.

A Novel, Low-Fidelity, Low-Cost Residency "Simulation Festival" Competition.

Introduction: Simulation has rapidly expanded in obstetrics and gynecology (OB/GYN) for teaching surgical skills, reinforcing medical knowledge and assessing surgical proficiency. Low-fidelity simulations are typically lower cost to produce and have been proven to be beneficial for surgical training. The aim of this study is to describe an innovative simulation competition among residency programs to develop, present, and share low-cost, low-fidelity surgical simulation.

Acute freshwater CO exposure does not impair seawater transfer in three different sizes of Atlantic salmon (Salmo salar) subjected to different photoperiod manipulations.

There is a growing interest in Atlantic salmon (Salmo salar) aquaculture to extend the time fish are reared in freshwater (FW) recirculating aquaculture systems (RAS), producing larger FW salmon that can then be induced to undergo smoltification before transfer into marine net pens for grow-out and harvest. Smolts can be produced by photoperiod (PT) manipulation in RASs, but little is known about how delaying smoltification to larger body sizes affects susceptibility to elevated CO levels (hypercapnia), which can occur at high stocking densities in FW RAS or during transport from FW RAS rearing facilities to marine net pens. To address this, Atlantic salmon were reared from hatch to one of three different sizes (~230, ~580, or ~1300 g) in FW (3 ppt) under continuous light (24:0, light:dark).

Paediatric mass casualty response through the lens of Functional Resonance Analytical Methodology- lessons learned.

Background: Mass Casualty Incidents are rare but can significantly stress healthcare systems. Functional Resonance Analytical Methodology (FRAM) is a systematic approach to model and explore how complex systems adapt to variations and to understand resilient properties in the face of perturbations. The aim of this study was to use FRAM to create a model of a paediatric trauma system during the initial response to the Manchester Arena Attack to provide resilience-based insights for the management of future Mass Casualty Incidents (MCI).

Evaluating cancer patient-reported experience measures against health literacy best practices.

Purpose: Positive patient experiences can lead to better adherence to cancer treatment and greater patient health outcomes. The primary aim of this descriptive study was to determine whether commonly used cancer PREMs have been developed according to health literacy best practices. The secondary and third aims were to examine the development of PREMs and to assess their comprehensiveness against principles of patient-centered care.

Structure of the flotillin complex in a native membrane environment.

In this study, we used cryoelectron microscopy to determine the structures of the Flotillin protein complex, part of the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) superfamily, from cell-derived vesicles without detergents. It forms a right-handed helical barrel consisting of 22 pairs of Flotillin1 and Flotillin2 subunits, with a diameter of 32 nm at its wider end and 19 nm at its narrower end. Oligomerization is stabilized by the C terminus, which forms two helical layers linked by a β-strand, and coiled-coil domains that enable strong charge-charge intersubunit interactions.

Freestanding bilayer microscope for single-molecule imaging of membrane proteins.

Integral membrane proteins (IMPs) constitute a large fraction of organismal proteomes, playing fundamental roles in physiology and disease. Despite their importance, the mechanisms underlying dynamic features of IMPs, such as anomalous diffusion, protein-protein interactions, and protein clustering, remain largely unknown due to the high complexity of cell membrane environments. Available methods for in vitro studies are insufficient to study IMP dynamics systematically.

Impact of a Mentorship Program to Prepare Medical Students for the Military Residency Match.

Introduction: Mentorship programs have well-documented benefits to both mentees and mentors. Military medical students face unique challenges in medical school given their service-specific requirements and separate military match process. We therefore aimed to determine whether military medical students' participation in a mentorship program impacts their confidence in applying to obstetrics and gynecology (OB/GYN) residency.

The mechanism of regulation of -catalyzed hydrolysis.

() enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein phosphorylation by protein kinase C, respectively. enzymes are under the control of G protein coupled receptor signaling through direct interactions with G proteins and and have been shown to be coincidence detectors for dual stimulation of and -coupled receptors.

The mechanism of regulation of -catalyzed hydrolysis.

Unlabelled: enzymes cleave producing IP3 and DAG. modulates the function of many ion channels, while IP3 and DAG regulate intracellular Ca levels and protein phosphorylation by protein kinase C, respectively. enzymes are under the control of GPCR signaling through direct interactions with G proteins and and have been shown to be coincidence detectors for dual stimulation of and G coupled receptors.

Associations of Health Literacy and Health Outcomes Among Populations with Limited Language Proficiency: A Scoping Review.

Unlabelled: Populations with limited language proficiency (LLP) experience difficulties understanding health information and accessing care. This study aimed to explore health literacy and LLP by examining the published literature on the barriers and facilitators to health care.

Methods: A scoping review of studies with populations in countries and regions where they have LLP in the locally dominant language was conducted.

The membrane electric field regulates the PIP-binding site to gate the KCNQ1 channel.

Voltage-dependent ion channels underlie the propagation of action potentials and other forms of electrical activity in cells. In these proteins, voltage sensor domains (VSDs) regulate opening and closing of the pore through the displacement of their positive-charged S4 helix in response to the membrane voltage. The movement of S4 at hyperpolarizing membrane voltages in some channels is thought to directly clamp the pore shut through the S4-S5 linker helix.

activates hydrolysis by recruiting and orienting on the membrane surface.

catalyze the hydrolysis of phosphatidylinositol 4, 5-bisphosphate [Formula: see text] into [Formula: see text] [Formula: see text] and [Formula: see text]  [Formula: see text]. [Formula: see text] regulates the activity of many membrane proteins, while and lead to increased intracellular Ca levels and activate protein kinase C, respectively. are regulated by G protein-coupled receptors through direct interaction with [Formula: see text] and [Formula: see text] and are aqueous-soluble enzymes that must bind to the cell membrane to act on their lipid substrate.

Membrane protein isolation and structure determination in cell-derived membrane vesicles.

Integral membrane protein structure determination traditionally requires extraction from cell membranes using detergents or polymers. Here, we describe the isolation and structure determination of proteins in membrane vesicles derived directly from cells. Structures of the ion channel Slo1 from total cell membranes and from cell plasma membranes were determined at 3.

Freestanding lipid bilayer tensiometer for the study of mechanosensitive ion channels.

Mechanical forces modify the cell membrane potential by opening mechanosensitive ion channels. We report the design and construction of a lipid bilayer tensiometer to study channels that respond to lateral membrane tension, [Formula: see text] , in the range 0.2 to 1.

State of polycyclic aromatic hydrocarbon (PAH) contamination in the Saint John Harbour, New Brunswick, Canada.

This study examined the concentrations and compositions of polycyclic aromatic hydrocarbon (PAH) contaminants in the surficial sediments of the Saint John Harbour (SJH) and assessed PAH exposure to local aquatic biota. Our findings suggest that sedimentary PAH contamination is heterogeneous and widespread in the SJH, with several sites exceeding the Canadian and NOAA recommended guidelines for the protection of aquatic life. Despite high concentrations of PAHs at some sites, there was no indication that local nekton was affected.

Piezo1 as a force-through-membrane sensor in red blood cells.

Piezo1 is the stretch activated Ca channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave 'dimple'.

Voltage-sensor movements in the Eag Kv channel under an applied electric field.

Voltage-dependent ion channels regulate the opening of their pores by sensing the membrane voltage. This process underlies the propagation of action potentials and other forms of electrical activity in cells. The voltage dependence of these channels is governed by the transmembrane displacement of the positive charged S4 helix within their voltage-sensor domains.

Structural and functional analyses of a GPCR-inhibited ion channel TRPM3.

G-protein coupled receptors (GPCRs) govern the physiological response to stimuli by modulating the activity of downstream effectors, including ion channels. TRPM3 is an ion channel inhibited by GPCRs through direct interaction with G protein (Gβγ) released upon their activation. This GPCR-TRPM3 signaling pathway contributes to the analgesic effect of morphine.

Elastic properties and shape of the Piezo dome underlying its mechanosensory function.

We show in the companion paper that the free membrane shape of lipid bilayer vesicles containing the mechanosensitive ion channel Piezo can be predicted, with no free parameters, from membrane elasticity theory together with measurements of the protein geometry and vesicle size [C. A. Haselwandter, Y.

Quantitative prediction and measurement of Piezo's membrane footprint.

Piezo proteins are mechanosensitive ion channels that can locally curve the membrane into a dome shape [Y. R. Guo, R.