Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP-α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 is required and sufficient for TSP-induced synaptogenesis in vitro and spine formation in vivo, but an α2δ-1 mutant linked to autism cannot rescue these synaptogenesis defects. Finally, we reveal that TSP-α2δ-1 interactions control synaptogenesis postsynaptically via Rac1, suggesting potential molecular mechanisms that underlie both synaptic development and pathology.
The recent development and increased application of automatic external defibrillators have prescribed very strong requirements towards ventricular fibrillation (VF) and fast ventricular tachycardia (VT > 180 bpm) detection from the surface electrocardiogram (ECG). We attempted to use informative parameters from several existing analysis methods and from a method developed in-house. A set of nine parameters was derived initially, with four of them being selected after statistical assessment. Detection of VF against non-shockable rhythms was obtained using the K-nearest neighbours classification method, with 98.6% specificity and 96.7% sensitivity. The detection accuracy remained high after inclusion of VT episodes above and below 180 bpm to shockable and non-shockable rhythms respectively and after the addition of noise. Test signals were taken from the well-known ECG signal databases of the American Heart Association and the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH-'cudb' and 'vfdb' files).
In this article a new acoustic parameter is introduced and it is shown that it may serve as an indicator of laryngeal function. It is termed the turbulent noise index (TNI) and is defined as 100(1 - Rmax), where Rmax is the mean value of the maximum correlation coefficient between each pair of consecutive glottal cycles in the voiced signal. A method for its calculation is described. Experiments with synthetic and natural voice signals show that TNI is almost independent of frequency modulation noise and amplitude modulation noise. TNI is compared with HNR (harmonic-to-noise ratio) and NNE (normalised noise energy) which require high stationarity of the voice signal and are substantially affected by slow changes of frequency and amplitude. When the parameters HNR and NNE are used to discriminate between normal and pathological voices, the overlap area contains 21.5% and 23.5% of the total number of pathological voices, respectively. Using TNI, the normal and pathological voices overlap is 14.8% of the total number of pathological voices, i.e. compared to the other noise parameters TNI has a significant advantage as a diagnostic parameter.
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