A Cation–π Interaction between Extracellular TEA and an Aromatic Residue in Potassium Channels

Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an aromatic amino acid at a position that sits at the external entrance of the permeation pathway (residue 449 in the eukaryotic voltage-gated potassium channel Shaker). We investigated whether a cation–{pi} interaction between TEA and such an aromatic residue contributes to TEA block using the in vivo nonsense suppression method to incorporate a series of increasingly fluorinated Phe side chains at position 449. Fluorination, which is known to decrease the cation–{pi} binding ability of an aromatic ring, progressively increased the inhibitory constant Ki for the TEA block of Shaker. A larger increase in Ki was observed when the benzene ring of Phe449 was substituted by nonaromatic cyclohexane. These results support a strong cation–{pi} component to the TEA block. The data provide an empirical basis for choosing between Shaker models that are based on two classes of reported crystal structures for the bacterial channel KcsA, showing residue Tyr82 in orientations either compatible or incompatible with a cation–{pi} mechanism. We propose that the aromatic residue at this position in Shaker is favorably oriented for a cation–{pi} interaction with the permeation pathway. This choice is supported by high level ab initio calculations of the predicted effects of Phe modifications on TEA binding energy

Making the Most of the Peer Review Process

In this brief mentoring corner article, we focus on defining what different editorial decisions mean (e.g., accept with revisions; revise and resubmit; reject: revise and resubmit), discussing factors you might consider when deciding what to do after receiving a decision (e.g., resubmit or move on) and considering how to best approach the revisions. We also provide guidance on effective communication with editors, including an example of a successful response to review table and cover letter

Search for X-Ray Emission Associated with the Shapley Supercluster with Suzaku

Suzaku performed observations of 3 regions in and around the Shapley supercluster: a region located between A3558 and A3556, at ~0.9 times the virial radii of both clusters, and two other regions at 1{\deg}and 4{\deg}away from the first pointing. The 4{\deg}-offset observation was used to evaluate the Galactic foreground emission. We did not detect significant redshifted Oxygen emission lines (O VII and O VIII) in the spectra of all three pointings, after subtracting the contribution of foreground and background emission. An upper limit for the redshifted O VIII Ka line intensity of the warm-hot intergalactic medium (WHIM) is 1.5 \times 10^-7 photons s^-1 cm^-2 arcmin^-2, which corresponds to an overdensity of ~380 (Z/0.1 Z_solar)^{-1/2} (L/3 Mpc)^{-1/2}, assuming T=3\times10^6 K. We found excess continuum emission in the 1{\deg}-offset and on-filament regions, represented by thermal models with kT ~1 keV and ~2 keV, respectively. The redshifts of both 0 and that of the supercluster (0.048) are consistent with the observed spectra. The ~1 keV emission can be also fitted with Ne-rich Galactic (zero redshift) thin thermal emission. Radial intensity profile of 2 keV component suggests contribution from A3558 and A3556, but with significant steepening of the intensity slope in the outer region of A3558. Finally, we summarized the previous Suzaku search for the WHIM and discussed the feasibility of constraining the WHIM. An overdensity of < 400 can be detectable using O VII and O VIII emission lines in a range of 1.4\times10^6 K < T < 5\times10^6 K or a continuum emission in a relatively high temperature range T > 5\times10^6 K with the Suzaku XIS. The non detection with Suzaku suggests that typical line-of-sight average overdensity is < 400

Reliability training

Discussed here is failure physics, the study of how products, hardware, software, and systems fail and what can be done about it. The intent is to impart useful information, to extend the limits of production capability, and to assist in achieving low cost reliable products. A review of reliability for the years 1940 to 2000 is given. Next, a review of mathematics is given as well as a description of what elements contribute to product failures. Basic reliability theory and the disciplines that allow us to control and eliminate failures are elucidated