Plasma SOMAmer proteomics of postoperative delirium.

BACKGROUND: Postoperative delirium is prevalent in older adults and has been shown to increase the risk of long-term cognitive decline. Plasma biomarkers to identify the risk for postoperative delirium and the risk of Alzheimer's disease and related dementias are needed. METHODS: This biomarker discovery case-control study aimed to identify plasma biomarkers associated with postoperative delirium. Patients aged ≥65 years undergoing major elective noncardiac surgery were recruited. The preoperative plasma proteome was interrogated with SOMAmer-based technology targeting 1433 biomarkers. RESULTS: In 40 patients (20 with vs. 20 without postoperative delirium), a preoperative panel of 12 biomarkers discriminated patients with postoperative delirium with an accuracy of 97.5%. The final model of five biomarkers delivered a leave-one-out cross-validation accuracy of 80%. Represented biological pathways included lysosomal and immune response functions. CONCLUSION: In older patients who have undergone major surgery, plasma SOMAmer proteomics may provide a relatively non-invasive benchmark to identify biomarkers associated with postoperative delirium.

Microglia play beneficial roles in multiple experimental seizure models.

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.

Microglia play beneficial roles in multiple experimental seizure models.

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.

Localization, induction, and cellular effects of tau phosphorylated at threonine 217.

INTRODUCTION: Tau phosphorylation at T217 is a promising Alzheimer's disease (AD) biomarker, but its functional consequences were unknown. METHODS: Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, taupT217 , taupT181 , taupT231 , and taupS396/pS404 . Direct stochastic optical reconstruction microscopy (dSTORM) super resolution microscopy was used to localize taupT217 in cultured neurons. Enhanced green fluorescent protein (EGFP)-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules. RESULTS: In the brain, taupT217 appears in neurons at Braak stages I and II, becomes more prevalent later, and co-localizes partially with other phospho-tau epitopes. In cultured neurons, taupT217 is increased by extracellular tau oligomers (xcTauOs) and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tauT217E . CONCLUSION: TaupT217 increases in the brain as AD progresses and is induced by xcTauOs. Post-synaptic taupT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau's affinity for microtubules. HIGHLIGHTS: Validation of anti-tau phosphorylated at threonine-217 (taupT217 ) specificity is essential due to epitope redundancy. taupT217 increases as Alzheimer's disease progresses and is found throughout diseased neurons. taupT217 is associated with developing post-synaptic sites in cultured neurons. Extracellular oligomers of tau, but not amyloid beta, increase intracellular taupT217 . T217E pseudo-phosphorylation reduces tau's affinity for microtubules.

Panama: An Open-Source Educational App for Ion Channel Biophysics Simulation.

This article describes an open-source educational software, called Panama, developed using R, that simulates the biophysics of voltage-gated ion channels. It is made publicly available as an R package called Panama and as a web app at http://www.neuronsimulator.com. A need for such a tool was observed after surveying available software packages. Available packages are either not robust enough to simulate multiple ion channels, too complicated, usable only as desktop software, not optimized for mobile devices, not interactive, lack intuitive graphical controls, or not appropriate for educational purposes. This app simulates the physiology of voltage-gated sodium, potassium, and chlorine channels; A channel; M channel; AHP channel; calcium-activated potassium channel; transient-calcium channel; and leak-calcium channel, under current-clamp or voltage-clamp conditions. As the input values on the app are changed, the output can be instantaneously visualized on the web browser and downloaded as a data table to be further analyzed in a spreadsheet program. This app is a first-of-its-kind, mobile-friendly, and touchscreen-friendly online tool that can be used as an installable R package. It has intuitive touch-optimized controls, instantaneous graphical output, and yet is pedagogically robust for educational purposes.