Oscillometry in Stable Single and Double Lung Allograft Recipients Transplanted for Interstitial Lung Disease: Results of a Multi-Center Australian Study.

Peak spirometry after single lung transplantation (SLTx) for interstitial lung disease (ILD) is lower than after double lung transplantation (DLTx), however the pathophysiologic mechanisms are unclear. We aim to assess respiratory mechanics in SLTx and DLTx for ILD using oscillometry. Spirometry and oscillometry (tremoflo C-100) were performed in stable SLTx and DLTx recipients in a multi-center study.

Complete Horizontal Gaze Paresis Due to Medial Pontine Haemorrhage.

We report a case of bilateral horizontal conjugate gaze palsy due to a dorsal median pontine haemorrhage. The development of horizontal gaze palsy has been attributed to lesions in the pontine tegmentum, and in this case, has occurred in conjunction with other features as part of Foville's syndrome. Complete horizontal gaze palsy is a rare clinical manifestation as bilateral involvement is unusual.

A catalogue of tools and variables from crisis and routine care to support decision-making about allocation of intensive care beds and ventilator treatment during pandemics: Scoping review.

Purpose: This scoping review sought to identify objective factors to assist clinicians and policy-makers in making consistent, objective and ethically sound decisions about resource allocation when healthcare rationing is inevitable.

Materials And Methods: Review of guidelines and tools used in ICUs, hospital wards and emergency departments on how to best allocate intensive care beds and ventilators either during routine care or developed during previous epidemics, and association with patient outcomes during and after hospitalisation.

Results: Eighty publications from 20 countries reporting accuracy or validity of prognostic tools/algorithms, or significant correlation between prognostic variables and clinical outcomes met our eligibility criteria: twelve pandemic guidelines/triage protocols/consensus statements, twenty-two pandemic algorithms, and 46 prognostic tools/variables from non-crisis situations.

Identification of PP2A and S6 Kinase as Modifiers of Leucine-Rich Repeat Kinase-Induced Neurotoxicity.

Mutations in LRRK2 are currently recognized as the most common monogenetic cause of Parkinsonism. The elevation of kinase activity of LRRK2 that frequently accompanies its mutations is widely thought to contribute to its toxicity. Accordingly, many groups have developed LRRK2-specific kinase inhibitors as a potential therapeutic strategy.

The BEACH Domain Is Critical for Blue Cheese Function in a Spatial and Epistatic Autophagy Hierarchy.

Unlabelled: () encodes a BEACH domain adaptor protein that, like its human homolog ALFY, promotes clearance of aggregated proteins through its interaction with Atg5 and p62. mutations lead to age-dependent accumulation of ubiquitinated inclusions and progressive neurodegeneration in the fly brain, but neither the influence of autophagy on -related degeneration, nor placement in the autophagic hierarchy have been shown. We present epistatic evidence in a well-defined larval motor neuron paradigm that in mutants, synaptic accumulation of ubiquitinated aggregates and neuronal death can be rescued by pharmacologically amplifying autophagic initiation.

A critical role of TRPM2 channel in Aβ -induced microglial activation and generation of tumor necrosis factor-α.

Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD.

AF-6 Protects Against Dopaminergic Dysfunction and Mitochondrial Abnormalities in Models of Parkinson's Disease.

Afadin 6 (AF-6) is an F-actin binding multidomain-containing scaffolding protein that is known for its function in cell-cell adhesion. Interestingly, besides this well documented role, we recently found that AF-6 is a Parkin-interacting protein that augments Parkin/PINK1-mediated mitophagy. Notably, mutations in Parkin and PINK1 are causative of recessively inherited forms of Parkinson's disease (PD) and aberrant mitochondrial homeostasis is thought to underlie PD pathogenesis.

Signalling mechanisms mediating Zn-induced TRPM2 channel activation and cell death in microglial cells.

Excessive Zn causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in HO/Zn-induced Ca signalling and cell death in microglial cells. HO/Zn induced concentration-dependent increases in cytosolic Ca concentration ([Ca]), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO).

Modelling C9orf72 dipeptide repeat proteins of a physiologically relevant size.

C9orf72 expansions are the most common genetic cause of FTLD and MND identified to date. Although being intronic, the expansion is translated into five different dipeptide repeat proteins (DPRs) that accumulate within patients' neurons. Attempts have been made to model DPRs in cell and animals.

Purinergic and Store-Operated Ca(2+) Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration.

ATP is an extrinsic signal that can induce an increase in the cytosolic Ca(2+) level ([Ca(2+) ]c ) in mesenchymal stem cells (MSCs). However, the cognate intrinsic mechanisms underlying ATP-induced Ca(2+) signaling in MSCs is still contentious, and their importance in MSC migration remains unknown. In this study, we investigated the molecular mechanisms underlying ATP-induced Ca(2+) signaling and their roles in the regulation of cell migration in human dental pulp MSCs (hDP-MSCs).

Optical control of trimeric P2X receptors and acid-sensing ion channels.

P2X receptors are trimeric membrane proteins that function as ion channels gated by extracellular ATP. We have engineered a P2X2 receptor that opens within milliseconds by irradiation at 440 nm, and rapidly closes at 360 nm. This requires bridging receptor subunits via covalent attachment of 4,4'-bis(maleimido)azobenzene to a cysteine residue (P329C) introduced into each second transmembrane domain.

Functional properties of five Dictyostelium discoideum P2X receptors.

The Dictyostelium discoideum genome encodes five proteins that share weak sequence similarity with vertebrate P2X receptors. Unlike vertebrate P2X receptors, these proteins are not expressed on the surface of cells, but populate the tubules and bladders of the contractile vacuole. In this study, we expressed humanized cDNAs of P2XA, P2XB, P2XC, P2XD, and P2XE in human embryonic kidney cells and altered the ionic and proton environment in an attempt to reflect the situation in amoeba.

Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription.

Background: Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates.

Role of P2X4 receptors in synaptic strengthening in mouse CA1 hippocampal neurons.

P2X4 receptors are calcium-permeable cation channels gated by extracellular ATP. They are found close to subsynaptic sites on hippocampal CA1 neurons. We compared features of synaptic strengthening between wild-type and P2X4 knockout mice (21-26 days old).

Ectodomain lysines and suramin block of P2X1 receptors.

P2X(1) receptors belong to a family of cation channels gated by extracellular ATP; they are found inter alia in smooth muscle, platelets, and immune cells. Suramin has been widely used as an antagonist at P2X receptors, and its analog 4,4',4'',4'''-[carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino))] tetrakis-benzene-1,3-disulfonic acid (NF449) is selective for the P2X(1) subtype. Human and mouse P2X(1) receptors were expressed in human embryonic kidney cells, and membrane currents evoked by ATP were recorded.

Altered hippocampal synaptic potentiation in P2X4 knock-out mice.

P2X4 purinergic receptors are calcium-permeable, ATP-activated ion channels. In the CA1 area of the hippocampus, they are located at the subsynaptic membrane somewhat peripherally to AMPA receptors. The possible role of P2X4 receptors has been difficult to elucidate because of the lack of selective antagonists.

Reanalysis of P2X7 receptor expression in rodent brain.

P2X receptors are cationic-selective ion channels gated by extracellular ATP. There are seven subunits (P2X1-7), the first six of which are expressed throughout the peripheral and central nervous systems. P2X7 receptors are rapidly upregulated and activated as a result of inflammatory stimuli in immune cells, where they act not only as cationic channels but uniquely couple with rapid release of proinflammatory cytokines, cytoskeletal rearrangements, and apoptosis or necrotic cell death.