The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition

Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a frog pannexin 1 (Panx1) channel at 3.0 A. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique constriction formed by Trp74 in the first extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as important structural motifs for ion selectivity and channel inhibition in Panx1

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Transient electric network analyzer computer program manua

Effects of surface morphology on magnetic properties of Ni nanowire arrays in self-ordered porous alumina

Ni nanowire arrays were produced by electrodeposition of Ni into self-assembled porous anodic alumina templates. With different anodization voltages, the wires show different surface morphologies. The temperature dependence of the coercivity and activation volume of wires with regular shape can be explained by thermal activation over an energy barrier with a 3/2 power dependence on the field. The wires with irregular surface morphologies show abnormal temperature dependences of the coercivity and activation volume. Possible mechanisms for these behaviors are discussed

Properties of LiMnBO3 glasses and nanostructured glass-ceramics

Polycrystalline LiMnBO3 is a promising cathode material for Li-ion batteries. In this work, we investigated the thermal, structural and electrical properties of glassy and nanocrystallized materials having the same chemical composition. The original glass was obtained via a standard meltquenching method. SEM and 7Li solid-state NMR indicate that it contains a mixture of two distinct glassy phases. The results suggest that the electrical conductivity of the glass is dominated by the ionic one. The dc conductivity of initial glass was estimated to be in the order of 10-18 S.cm-1 at room temperature. The thermal nanocrystallization of the glass produces a nanostructured glass-ceramics containing MnBO3 and LiMnBO3 phases. The electric conductivity of this glass-ceramics is increased by 6 orders of magnitude, compared to the starting material at room temperature. Compared to other manganese and borate containing glasses reported in the literature, the conductivity of the nanostructured glass ceramics is higher than that of the previously reported glassy materials. Such improved conductivity stems from the facilitated electronic transport along the grain boundaries

Analysis of Finite Microstrip Structures Using an Efficient Implementation of the Integral Equation Technique

An efficient numerical implementation of the Integral Equation technique (IE) has been developed for the analysis of the electrical characteristics of finite microstrip structures. The technique formulates a volume version of the IE for the finite dielectric objects, and a standard surface IE technique for the metallic areas. The system of integral equations formu- lated are solved with special numerical techniques described in this paper. The input impedances of several microstrip antennas have been computed, showing good agreement with respect mea- surements. The technique has shown to be accurate even for complex geometries containing several stacked dielectric layers. The radiation patterns of the structures have also been com- puted, and measured results from real manufactured hardware confirm that backside radiation and secondary lobes are accurately predicted by the theoretical model. The paper also discuss a suitable excitation model for finite size ground planes, and investigates the possibilities for an independent meshing of the metallic areas and the dielectric objects inside a given geom- etry. The practical value of the approach derived is that microstrip circuits can be designed minimizing the volume and size of the dielectric substrates.This work has been supported bythe Spanish National Project ESP2001-4546-PE, and RegionalSeneca Project PB/4/FS/02

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P \u3c 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted

Production and proteomic characterisation of purified protein derivative from Mycobacterium avium subsp. paratuberculosis

<p>Abstract</p> <p>Background</p> <p>Effective diagnosis of Johne's disease (JD), particularly at the stage of early subclinical infection, remains one of the greatest challenges for the control of JD worldwide. The IFN-γ test of cell mediated immunity is currently one of the most suitable diagnostics for subclinical infections, however a major limitation of this test is the lack of a standardised purified protein derivative (PPD) antigen (also referred to as Johnin PPD or PPDj). While attempting to replace PPDj with more specific individual antigens is an attractive proposition, bacterial culture derived PPDj remains the most effective antigen preparation for the diagnosis of subclinical JD. It may be possible to increase the reproducibility and specificity of PPDj preparations by further characterising and standardising the PPDj production.</p> <p>Results</p> <p>Using a standardised protocol, five in-house preparations of PPDj were prepared from cultures of <it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP). Compared to PPDs obtained from other institutes/laboratories, these preparations appeared to perform similarly well in the IFN-γ test. Although the broad proteomic composition of all PPDj preparations was remarkably similar, the absolute abundance of individual proteins varied markedly between preparations. All PPDj preparations contained common immunogenic proteins which were also observed in PPD preparations from <it>Mycobacterium avium </it>subsp. <it>avium </it>(PPDa) and <it>Mycobacterium bovis </it>(PPDb). Temporal difference in protein secretion of <it>in vitro </it>cultured MAP was observed between 20 and 34 weeks suggesting that the age of MAP culture used for PPDj preparations may markedly influence PPDj composition.</p> <p>Conclusions</p> <p>This study describes a protocol for the production of PPDj and its subsequent proteomic characterisation. The broad proteomic composition of different preparations of PPDj was, for the most part, highly similar. Compositional differences between PPDj preparations were found to be a direct reflection of genetic differences between the MAP strain types used to produce these preparations and the age of MAP cultures they were derived from. A number of conserved immunogenic proteins, such as members of the cutinase-like protein family, were found to be more abundant in PPDj compared to PPDa and should be considered as possible diagnostic antigens for the future.</p