A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.

AtNHX5 and AtNHX6, the endosomal Na+,K+/H+ antiporters in Arabidopsis, play an important role in plant growth and development. However, their function in K+ and pH homeostasis remains unclear. In this report, we characterized the function of AtNHX5 and AtNHX6 in K+ and H+ homeostasis in Arabidopsis. Using a yeast expression system, we found that AtNHX5 and AtNHX6 recovered tolerance to high K+ or salt. We further found that AtNHX5 and AtNHX6 functioned at high K+ at acidic pH while AtCHXs at low K+ under alkaline conditions. In addition, we showed that the nhx5 nhx6 double mutant contained less K+ and was sensitive to low K+ treatment. Overexpression of AtNHX5 or AtNHX6 gene in nhx5 nhx6 recovered root growth to the wild-type level. Three conserved acidic residues, D164, E188, and D193 in AtNHX5 and D165, E189, and D194 in AtNHX6, were essential for K+ homeostasis and plant growth. nhx5 nhx6 had a reduced vacuolar and cellular pH as measured with the fluorescent pH indicator BCECF or semimicroelectrode. We further show that AtNHX5 and AtNHX6 are localized to Golgi and TGN. Taken together, AtNHX5 and AtNHX6 play an important role in K+ and pH homeostasis in Arabidopsis. Three conserved acidic residues are essential for K+ transport.

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Orf virus (ORFV) OV20.0L is an ortholog of vaccinia virus (VACV) gene E3L. The function of VACV E3 protein as a virulence factor is well studied, but OV20.0 has received less attention. Here we show that like VACV E3L, OV20.0L encodes two proteins, a full-length protein and a shorter form (sh20). The shorter sh20 is an N-terminally truncated OV20.0 isoform generated when a downstream AUG codon is used for initiating translation. These isoforms differed in cellular localization, with full-length OV20.0 and sh20 found throughout the cell and predominantly in the cytoplasm, respectively. Nonetheless, both OV20.0 isoforms were able to bind double-stranded RNA (dsRNA)-activated protein kinase (PKR) and dsRNA. Moreover, both isoforms strongly inhibited PKR activation as shown by decreased phosphorylation of the translation initiation factor eIF2␣ subunit and protection of Sindbis virus infection against the activity of interferon (IFN). In spite of this apparent conservation of function in vitro, a recombinant ORFV that was able to express only the sh20 isoform was attenuated in a mouse model. IMPORTANCEThe OV20.0 protein of orf virus (ORFV) has two isoforms and contributes to virulence, but the roles of the two forms are not known. This study shows that the shorter isoform (sh20) arises due to use of a downstream initiation codon and is amino-terminally truncated. The sh20 form also differs in expression kinetics and cellular localization from full-length OV20.0. Similar to the full-length isoform, sh20 is able to bind dsRNA and PKR, inactivate PKR, and thus act as an antagonist of the interferon response in vitro. In vivo, however, wild-type OV20.0 could not be replaced with sh20 alone without a loss of virulence, suggesting that the functions of the isoforms are not simply redundant. Orf virus (ORFV), a member of the Parapoxvirus genus and the Poxviridae family, is the causative agent of contagious ecthyma in sheep, goats, and other ruminants. The disease is characterized by the development of pustular lesions around the nostrils and mouth with a high incidence rate and a low mortality rate in healthy adult animals. In contrast, infection in immunosuppressed animals or in lambs may be fatal (1). ORFV is also of concern as a source of zoonotic infection because it can cause cutaneous lesions in humans in contact with infected animals. Persistent infection with ORFV can be observed in goats and sheep, and while the severity of lesions is reduced compared with that seen in primary infection, this persistence suggests that the virus is able to evade host immunity (2-4). In line with this observation, ORFV has been shown to encode several proteins that modulate the host response to infection. These include viral homologues of ovine cytokines, such as vascular endothelial growth factor, interleukin-10 (IL-10), and a granulocyte-macrophage colony-stimulating factor (GM-CSF)-inhibiting protein, as well as an apoptosis inhibitor (5-7). ORFV also antagonizes interferon (IFN) signaling, and this is done by the product...

The Chinese BCTQ is a reliable, valid and responsive disease-specific measure for assessment of symptoms and functional status in patients with CTS.

BackgroundRespiratory variations in the inferior vena cava diameter (ΔIVCD) have been studied extensively with respect to their value in predicting fluid responsiveness, but the results are conflicting. The aim of this meta-analysis was to explore the value of ΔIVCD for predicting fluid responsiveness in patients with circulatory shock receiving mechanical ventilation.MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. The diagnostic OR (DOR), sensitivity, and specificity were calculated. The summary ROC curve was estimated, and the area under the ROC curve (AUROC) was calculated.ResultsOverall, 603 patients were included in this review, 324 (53.7%) of whom were fluid-responsive. The cutoff values of ΔIVCD varied across studies, ranging from 8% to 21%. Heterogeneity between studies was assessed with an overall Q = 0.069, I2 = 0%, and P = 0.483. The pooled sensitivity and specificity for the overall population were 0.69 (95% CI, 0.51–0.83) and 0.80 (95% CI, 0.66–0.89), respectively. The DOR was 9.28 (95% CI, 2.33–36.98). AUROCs were reported in five studies. Overall, the pooled AUROC was 0.82 (95% CI, 0.79–0.85).ConclusionsThe findings of this study suggest that the ΔIVCD performed moderately well in predicting fluid responsiveness in patients with circulatory shock receiving mechanical ventilation.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2063-4) contains supplementary material, which is available to authorized users.

No abstract

The present paper systematically investigated pore scale thermal hydraulics characteristics of molten salt cooled high temperature pebble bed reactor. By using computational fluid dynamics (CFD) methods and employing simplified body center cubic (BCC) and face center cubic (FCC) model, pressure drop and local mean Nusselt number are calculated. The simulation result shows that the high Prandtl number molten salt in packed bed has unique fluid-dynamics and thermodynamic properties. There are divergences between CFD results and empirical correlations' predictions of pressure drop and local Nusselt numbers. Local pebble surface temperature distributions in several default conditions are investigated. Thermal removal capacities of molten salt are confirmed in the case of nominal condition; the pebble surface temperature under the condition of local power distortion shows the tolerance of pebble in extreme neutron dose exposure. The numerical experiments of local pebble insufficient cooling indicate that in the molten salt cooled pebble bed reactor, the pebble surface temperature is not very sensitive to loss of partial coolant. The methods and results of this paper would be useful for optimum designs and safety analysis of molten salt cooled pebble bed reactors.