186,180 research outputs found

    Structural basis of gating of CNG channels

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    AbstractCyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5Å thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed

    A 195.6dBc/Hz peak FoM P-N class-B oscillator with transformer-based tail filtering

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    A complementary p-n class-B oscillator with two magnetically coupled second harmonic tail resonators is presented. For the same oscillation amplitude (constrained by reliability considerations) and the same tank, the p-n oscillator achieves 3-4dB better Figure of Merit (FoM) than an n-only reference one. After frequency division by 2, the p-n oscillator has a measured phase noise that ranges from -150.8 to -151.5 dBc/Hz at 10MHz offset from the carrier when the frequency of oscillation is varied from 3.64 to 4.15GHz. With a power consumption of 6.3mW, a peak FoM of 195.6 dBc/Hz is achieved.This work was supported by the European Marie Curie Grant Agreement No 251399. Paulo Mendes research was partially supported by grant SFRH/BSAB/1245/2012.info:eu-repo/semantics/publishedVersio

    Structural Basis of Gating of CNG channel

    No full text
    Cyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5A thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed

    Analysis and design of a 195.6 dBc/Hz peak FoM P-N class-B oscillator with transformer-based tail filtering

    No full text
    A complementary p-n class-B oscillator with two magnetically coupled second harmonic tail resonators is presented and compared to an N-only reference one. An in depth analysis of phase noise, based on direct derivation of the Impulse Sensitivity Function (ISF), provides design insights on the optimization of the tail resonators. In principle the complementary p-n oscillator has the same optimum Figure of Merit (FoM) of the N-only at half the voltage swing. At a supply voltage of 1.5 V, the maximum allowed oscillation amplitude of the N-only is constrained, by reliability considerations, to be smaller than the value that corresponds to the optimum FoM even when 1.8 V thick oxide transistors are used. For an oscillation amplitude that ensures reliable operation and the same tank, the p-n oscillator achieves a FoM 2 to 3 dB better than the N, only depending on the safety margin taken in the design. After frequency division by 2, the p-n oscillator has a measured phase noise that ranges from -150.8 to -151.5 dBc/Hz at 10 MHz offset from the carrier when the frequency of oscillation is varied from 7.35 to 8.4 GHz. With a power consumption of 6.3 mW, a peak FoM of 195.6 dBc/Hz is achieved.This work was supported by the European Marie Curie IAPP Grant Agreement N 251399.info:eu-repo/semantics/publishedVersio

    Dental pain threshold and angina pectoris in patients with coronary artery disease

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    AbstractOne hundred eight consecutive patients with proved coronary artery disease and reproducible exercise-induced myocardial ischemia were studied. During repeated exercise testing, 52 patients (Group I) had myocardial ischemia in the absence of pain (silent ischemia) whereas 56 patients (Group II) experienced anginal symptoms in the presence of electrocardiographic signs of ischemia. A puipal test was carried out in all patients using an electrical dental stimulator commonly used in dentistry. Electrical current was delivered in increasing intensity from 10 to 500 mA, and the dental pain threshold and the reaction of the patients to maximal stimulation were determined.During the puipal test, 71.2% of the patients in Group I did not experience pain, even at maximal stimulation (threshold 0), 11.5% were sensitive at threshold I (10 to 200 mA) and 17.3% felt pain at threshold II (210 to 500 mA). In Group 11, 69.7% of the patients complained of dental pain at the low intensity test current (threshold I), 10.7% at threshold II and 19.6% at threshold 0. In Group I, 71.2% of patients did not have discomfort (reaction −), even at maximal stimulation, 21.1% had a mild reaction (reaction +) and 7.7% had an intense painful reaction (reaction ++). In Group II, 80.4% of patients were sensitive to the pulpar test (67.9% reported intense painful sensation at maximal stimulation, 12.5% had a mild reaction); 19.6% of patients had no reaction.The two groups of patients were similar with respect to age, sex and angiographic features. Patients in Group I (silent ischemia) achieved a significantly longer duration of exercise (p < 0.01) in the presence of more pronounced ST segment depression (p < 0.001) and had a higher rate-pressure product at peak exercise (p < 0.01).The significant difference in dental pain threshold (p < 0.0005) and reaction (p < 0.0005) in patients with and those without anginal symptoms during exercise testing suggests that a generalized, nonsegmental hyposensitivity to pain may partly explain the lack of symptoms in patients with silent myocardial ischemia

    Locking CNGA1 Channels in the Open and Closed State

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    AbstractWith the aim of understanding the relation between structure and gating of CNGA1 channels from bovine rod, an extensive cysteine scanning mutagenesis was performed. Each residue from Phe-375 to Val-424 was mutated into a cysteine one at a time and the modification caused by various sulfhydryl reagents was analyzed. The addition of the mild oxidizing agent copper phenanthroline (CuP) in the open (presence of 1mM cGMP) or closed state locked the channel in the respective states. A subsequent treatment with the reducing agent DTT restored normal gating fully in the open state and partially in the closed state. This action of CuP was not observed when F380 was mutated into a cysteine in the cysteine-free CNGA1 channel and in the double mutant C314S&F380C. These observations suggest that these effects are mediated by the formation of a disulfide bond (S-S) between F380C and the endogenous Cys-314 in the S5 segment. It can be rationalized by supposing that during gating the S6 segment rotates anticlockwise—when viewed from the extracellular side—by ∼30°
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