Hydrogen sulfide inhibits Cav3.2 T-type Ca2+ channels

The importance of H2S as a physiological signaling molecule continues to develop, and ion channels are emerging as a major family of target proteins through which H2S exerts many actions. The purpose of the present study was to investigate its effects on T-type Ca2+ channels. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS (10 μM-1 mM) selectively inhibits Cav3.2 T-type channels heterologously expressed in HEK293 cells, whereas Cav3.1 and Cav3.3 channels were unaffected. The sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ with N,N,N',N'-tetra-2-picolylethylenediamine prevented channel inhibition by H2S and also reversed H2S inhibition when applied after H2S exposure, suggesting that H2S may act via increasing the affinity of the channel for extracellular Zn2+ binding. Inhibition of native T-type channels in 3 cell lines correlated with expression of Cav3.2 and not Cav3.1 channels. Notably, H2S also inhibited native T-type (primarily Cav3.2) channels in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2, and suggest that such modulation cannot account for the pronociceptive effects of this gasotransmitter.

Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+ -sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

B-spline neural network based single-carrier frequency domain equalisation for Hammerstein channels

A practical single-carrier (SC) block transmission with frequency domain equalisation (FDE) system can generally be modelled by the Hammerstein system that includes the nonlinear distortion effects of the high power amplifier (HPA) at transmitter. For such Hammerstein channels, the standard SC-FDE scheme no longer works. We propose a novel Bspline neural network based nonlinear SC-FDE scheme for Hammerstein channels. In particular, we model the nonlinear HPA, which represents the complex-valued static nonlinearity of the Hammerstein channel, by two real-valued B-spline neural networks, one for modelling the nonlinear amplitude response of the HPA and the other for the nonlinear phase response of the HPA. We then develop an efficient alternating least squares algorithm for estimating the parameters of the Hammerstein channel, including the channel impulse response coefficients and the parameters of the two B-spline models. Moreover, we also use another real-valued B-spline neural network to model the inversion of the HPA’s nonlinear amplitude response, and the parameters of this inverting B-spline model can be estimated using the standard least squares algorithm based on the pseudo training data obtained as a byproduct of the Hammerstein channel identification. Equalisation of the SC Hammerstein channel can then be accomplished by the usual one-tap linear equalisation in frequency domain as well as the inverse Bspline neural network model obtained in time domain. The effectiveness of our nonlinear SC-FDE scheme for Hammerstein channels is demonstrated in a simulation study.

Low complexity equalization of HCM systems with DPFFT demodulation over doubly-selective channels

To mitigate the inter-carrier interference (ICI) of doubly-selective (DS) fading channels, we consider a hybrid carrier modulation (HCM) system employing the discrete partial fast Fourier transform (DPFFT) demodulation and the banded minimum mean square error (MMSE) equalization in this letter. We first provide the discrete form of partial FFT demodulation, then apply the banded MMSE equalization to suppress the residual interference at the receiver. The proposed algorithm has been demonstrated, via numerical simulations, to be its superior over the single carrier modulation (SCM) system and circularly prefixed orthogonal frequency division multiplexing (OFDM) system over a typical DS channel. Moreover, it represents a good trade-off between computational complexity and performance.

Sodium hydroxide enhances extractability and analysis of proanthocyanidins in ensiled sainfoin (onobrychis viciifolia)

Little information exists on the effects of ensiling on condensed tannins or proanthocyanidins. The acetone–butanol–HCl assay is suitable for measuring proanthocyanidin contents in a wide range of samples, silages included, but provides limited information on proanthocyanidin composition, which is of interest for deciphering the relationships between tannins and their bioactivities in terms of animal nutrition or health. Degradation with benzyl mercaptan (thiolysis) provides information on proanthocyanidin composition, but proanthocyanidins in several sainfoin silages have proved resistant to thiolysis. We now report that a pretreatment step with sodium hydroxide prior to thiolysis was needed to enable their analysis. This alkaline treatment increased their extractability from ensiled sainfoin and facilitated especially the release of larger proanthocyanidins. Ensiling reduced assayable proanthocyanidins by 29%, but the composition of the remaining proanthocyanidins in silage resembled that of the fresh plants.

Monitoring scan asymmetry of microwave humidity sounding channels using simultaneous all angle collocations (SAACs)

Simultaneous all angle collocations (SAACs) of microwave humidity sounders (AMSU-B and MHS) on-board polar orbiting satellites are used to estimate scan-dependent biases. This method has distinct advantages over previous methods, such as that the estimated scan-dependent biases are not influenced by diurnal differences between the edges of the scan and the biases can be estimated for both sides of the scan. We find the results are robust in the sense that biases estimated for one satellite pair can be reproduced by double differencing biases of these satellites with a third satellite. Channel 1 of these instruments shows the least bias for all satellites. Channel 2 has biases greater than 5 K, thus needs to be corrected. Channel 3 has biases of about 2 K and more and they are time varying for some of the satellites. Channel 4 has the largest bias which is about 15 K when the data are averaged for 5 years, but biases of individual months can be as large as 30 K. Channel 5 also has large and time varying biases for two of the AMSU-Bs. NOAA-15 (N15) channels are found to be affected the most, mainly due to radio frequency interference (RFI) from onboard data transmitters. Channel 4 of N15 shows the largest and time varying biases, so data of this channel should only be used with caution for climate applications. The two MHS instruments show the best agreement for all channels. Our estimates may be used to correct for scan-dependent biases of these instruments, or at least used as a guideline for excluding channels with large scan asymmetries from scientific analyses.

Modulation of potassium channels inhibits bunyavirus infection

Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K+) channels to infect cells. Time of addition assays using K+ channel modulating agents demonstrated that K+ channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K+ channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, twin-pore domain K+ channels (K2P) were identified as the K+ channel family mediating BUNV K+ channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease.

Tissue damage after sodium hypochlorite extrusion during root canal treatment

Sodium hypochlorite solution is toxic to vital tissues, causing severe effects if extruded during endodontic treatment. This paper presents a report on the tissue damage related to inadvertent extrusion of concentrated sodium hypochlorite solution during root canal treatment. A 65-year-old woman was referred with moderate pain, ecchymosis, and severe swelling of the right side of the face. These symptoms appeared immediately after a root canal treatment of the maxillary right canine, which had been started 21 hours earlier. It was diagnosed as air emphysema related to sodium hypochlorite solution extravasation during the endodontic treatment. To avoid this, an initial radiograph should be taken to determine the correct canal working length and confirm root canal integrity. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e46-e49)

Inhibition of Sodium Hypochlorite Antimicrobial Activity in the Presence of Bovine Serum Albumin

Introduction: This study investigated the inhibition of the antimicrobial activity of sodium hypochlorite (NaOCl) by bovine serum albumin (BSA). The killing of Enterococcus faecalis, Candida albicans, Staphylococcus epidermidis, and Escherichia coil by NaOCl in concentrations from 2% to 0.03% was measured in the presence of BSA in concentrations between 6.7% and 0.1%. Methods: NaOCl, BSA, and microorganism suspensions were mixed, and, after 30 seconds, 6 minutes, and 30 minutes, samples were taken and NaOCl was inactivated by 5% sodium thiosulphate. The microbes were incubated in tryptic soy broth broth for up to 7 days for the detection of growth. Results: All microorganisms were killed within 30 seconds by 0.03% NaOCl when BSA was not present. High concentrations of BSA significantly reduced the antimicrobial activity of NaOCl against the four species. Conclusions: The inhibition of sodium hypochlorite by BSA was directly dependent on their quantitative relationships. The result partly explains the poorer performance in vivo of NaOCl as compared to in vitro experiments. (J Endod 2010;36:268-271)