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Objective
Defective mitochondrial function attributed to optic atrophy 1 (OPA1) mutations causes primarily optic atrophy and, less commonly, neurodegenerative syndromes. The pathomechanism by which OPA1 mutations trigger diffuse loss of neurons in some, but not all, patients is unknown. Here, we used a tractable induced pluripotent stem cell (iPSC)‐based model to capture the biology of OPA1 haploinsufficiency...
Electrical coupling mediated by gap junctions is widespread in the mammalian CNS, and the interplay between chemical and electrical synapses on the millisecond timescale is crucial for determining patterns of synchrony in many neural circuits. Here we show that activation of glutamatergic synapses drives long-term depression of electrical coupling between neurons of the inferior olive. We demonstrate...
Inferior olive neurons regulate plasticity and timing in the cerebellar cortex via the climbing fiber pathway, but direct characterization of the output of this nucleus has remained elusive. We show that single somatic action potentials in olivary neurons are translated into a burst of axonal spikes. The number of spikes in the burst depends on the phase of subthreshold oscillations and, therefore,...
Twenty-five patients with histologically proven malignant mesothelioma participated in a trial of imatinib mesylate (Glivec) with a starting dose of 400mg per day taken orally, up to a maximal dose of 800mg. No responses were observed in the patient group, while three patients showed prolonged (>6 months) stabilization of disease. The median survival time was 398 days (range 88–840); the median...
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