Potassium (K) channels have been evolutionarily tuned for activation by diverse biological stimuli, and pharmacological activation is thought to target these specific gating mechanisms. Here we report a class of negatively charged activators (NCAs) that bypass the specific mechanisms but act as master keys to open K channels gated at their selectivity filter (SF), including many two-pore domain K (K2P) channels, voltage-gated hERG (human ether-à-go-go–related gene) channels and calcium (Ca2)–activated big-conductance potassium (BK)–type channels. Functional analysis, x-ray crystallography, and molecular dynamics simulations revealed that the NCAs bind to similar sites below the SF, increase pore and SF K occupancy, and open the filter gate. These results uncover an unrecognized polypharmacology among K channel activators and highlight a filter gating machinery that is conserved across different families of K channels with implications for rational drug design.
This paper presents an electronic system that extracts the periodicity of a sound. It uses three analogue VLSI building blocks: a silicon cochlea, two inner-hair-cell circuits and two spiking neuron chips. The silicon cochlea consists of a cascade of filters. Because of the delay between two outputs from the silicon cochlea, spike trains created at these outputs are synchronous only for a narrow range of periodicities. In contrast to traditional bandpass filters,where an increase in' selectivity has to be traded off against a decrease in response time, the proposed system responds quickly, independent of selectivity. 1 Introduction The human ear transduces airborne sounds into a neural signal using three stages in the inner ear's cochlea: (i) the mechanical filtering of the Basilar Membrane (BM), (ii) the transduction of membrane vibration into neurotransmitter release by the Inner Hair Cells (IHCs), and (iii) spike generation by the Spiral Ganglion Cells (SGCs), whose axons form the auditory nerve.
Direct methane functionalization to value-added products remains a challenge because of the propensity for overoxidation in many reaction environments. Sulfonation has emerged as an attractive approach for achieving the necessary selectivity. Here, we report a practical process for the production of methanesulfonic acid (MSA) from only two reactants: methane and sulfur trioxide. We have achieved 99% selectivity and yield of MSA. The electrophilic initiator based on a sulfonyl peroxide derivative is protonated under superacidic conditions, producing a highly electrophilic oxygen atom capable of activating a C–H bond of methane.
Mass extinction events spanning two global warming periods in Earth's history wiped out huge amounts of ocean life and destroyed reef ecosystems, a new study warns. It's previously been suggested that the Late Triassic and Early Toarcian extinctions, both linked to massive volcanism and the resulting climate changes, simply intensified extinction rates that were already underway. But according to new research, this was not the case. An analysis of background extinction rates and those experienced during the two events suggests extinction patterns changed dramatically each time due to rising ocean temperatures, acidification, and oxygen-starved waters. It's previously been suggested that the Late Triassic and Early Toarcian extinctions, both linked to massive volcanism and the resulting climate changes, simply intensified extinction rates that were already underway.