Pleiotropic Ankyrins: Scaffolds for Ion Channels and Transporters.

The ankyrin proteins (Ankyrin-R, Ankyrin-B, and Ankyrin-G) are a family of scaffolding, or membrane adaptor proteins necessary for the regulation and targeting of several types of ion channels and membrane transporters throughout the body. These include voltage-gated sodium, potassium, and calcium channels in the nervous system, heart, lungs, and muscle. At these sites, ankyrins recruit ion channels, and other membrane proteins, to specific subcellular domains, which are then stabilized through ankyrin's interaction with the submembranous spectrin-based cytoskeleton.

Ankyrin-R Links Kv3.3 to the Spectrin Cytoskeleton and Is Required for Purkinje Neuron Survival.

Ankyrin scaffolding proteins are critical for membrane domain organization and protein stabilization in many different cell types including neurons. In the cerebellum, Ankyrin-R (AnkR) is highly enriched in Purkinje neurons, granule cells, and in the cerebellar nuclei (CN). Using male and female mice with a floxed allele for in combination with and mice, we found that ablation of AnkR from Purkinje neurons caused ataxia, regional and progressive neurodegeneration, and altered cerebellar output.

Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K channels.

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv fast-spiking interneurons in mouse and human.

Ankyrins and neurological disease.

Ankyrins are scaffolding proteins widely expressed throughout the nervous system. Ankyrins recruit diverse membrane proteins, including ion channels and cell adhesion molecules, into specialized subcellular membrane domains. These domains are stabilized by ankyrins interacting with the spectrin cytoskeleton.

Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism.

Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature myelin is traditionally considered metabolically inert. Surprisingly, we discovered that mature myelin lipids undergo rapid turnover, and quaking (Qki) is a major regulator of myelin lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted in rapid demyelination, within 1 week, and gradually neurological deficits in adult mice.

Nodal β spectrins are required to maintain Na channel clustering and axon integrity.

Clustered ion channels at nodes of Ranvier are critical for fast action potential propagation in myelinated axons. Axon-glia interactions converge on ankyrin and spectrin cytoskeletal proteins to cluster nodal Na channels during development. However, how nodal ion channel clusters are maintained is poorly understood.

Developmental Changes in Expression of βIV Spectrin Splice Variants at Axon Initial Segments and Nodes of Ranvier.

Axon initial segments (AIS) and nodes of Ranvier are highly specialized axonal membrane domains enriched in Na channels. These Na channel clusters play essential roles in action potential initiation and propagation. AIS and nodal Na channel complexes are linked to the actin cytoskeleton through βIV spectrin.

An evidence synthesis of the international knowledge base for new care models to inform and mobilise knowledge for multispecialty community providers (MCPs).

Background: NHS England's Five Year Forward View (NHS England, Five Year Forward View, 2014) formally introduced a strategy for new models of care driven by simultaneous pressures to contain costs, improve care and deliver services closer to home through integrated models. This synthesis focuses on a multispecialty community provider (MCP) model. This new model of care seeks to overcome the limitations in current models of care, often based around single condition-focused pathways, in contrast to patient-focused delivery (Royal College of General Practitioners, The 2022 GP: compendium of evidence, 2012) which offers greater continuity of care in recognition of complex needs and multimorbidity.

Galnt1 is required for normal heart valve development and cardiac function.

Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals.

Rapid detection of Enterococcus spp. direct from blood culture bottles using Enterococcus QuickFISH method: a multicenter investigation.

The performance of a diagnostic method for detection and identification of Enterococcus spp. directly from positive blood culture was evaluated in a clinical study. The method, Enterococcus QuickFISH BC, is a second-generation peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) test, which uses a simplified, faster assay procedure.

Multicenter evaluation of the Staphylococcus QuickFISH method for simultaneous identification of Staphylococcus aureus and coagulase-negative staphylococci directly from blood culture bottles in less than 30 minutes.

A novel rapid peptide nucleic acid fluorescence in situ hybridization (FISH) method, Staphylococcus QuickFISH, for the direct detection of Staphylococcus species from positive blood culture bottles was evaluated in a multicenter clinical study. The method utilizes a microscope slide with predeposited positive- and negative-control organisms and a self-reporting 15-min hybridization step, which eliminates the need for a wash step. Five clinical laboratories tested 722 positive blood culture bottles containing gram-positive cocci in clusters.