Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA

AbstractA major component of the cellular antiviral system is the latent protein kinase PKR, which is activated by binding to either double-stranded RNA (dsRNA) or the cellular PACT protein. Activated PKR phosphorylates the translation initiation factor eIF2, thereby inhibiting viral and cellular protein synthesis and virus replication. To evade the antiviral effects of PKR, many viruses, including influenza A virus, have evolved multiple mechanisms. For influenza A virus, the non-structural (NS1A) protein plays a major role in blocking activation of PKR during virus infection. The mechanism by which the NS1A protein inhibits PKR activation in infected cells has not been established. In the present study, we first carried out a series of in vitro experiments to determine whether the NS1A protein could utilize a common mechanism to inhibit PKR activation by both PACT and dsRNA, despite their different modes of activation. We demonstrated that the direct binding of the NS1A protein to the N-terminal 230 amino acid region of PKR can serve as such a common mechanism and that this binding does not require the RNA-binding activity of the NS1A protein. The lack of requirement for NS1A RNA-binding activity for the inhibition of PKR activation in vivo was established by two approaches. First, we showed that an NS1A protein lacking RNA-binding activity, like the wild-type (wt) protein, blocked PKR activation by PACT in vivo, as well as the downstream effects of PKR activation in cells, namely, eIF2 phosphorylation and apoptosis. In addition, we demonstrated that PKR activation is inhibited in cells infected with a recombinant influenza A virus expressing NS1A mutant protein that cannot bind RNA, as is the case in cells infected with wild-type influenza A virus

Ubiquity, diversity and physiological characteristics of Geodermatophilaceae in Shapotou National Desert Ecological Reserve

The goal of this study was to gain insight into the diversity of culturable actinobacteria in desert soil crusts and to determine the physiological characteristics of the predominant actinobacterial group in these crusts. Culture-dependent method was employed to obtain actinobacterial strains from desert soil samples collected from Shapotou National Desert Ecological Reserve located in Tengger Desert, China. A total of 376 actinobacterial strains were isolated and 16S rRNA gene sequences analysis indicated that these isolates belonged to 29 genera within 18 families, among which the members of the family Geodermatophilaceae were predominant. The combination of 16S rRNA gene information and the phenotypic data allowed these newly-isolated Geodermatophilaceae members to be classified into 33 species clusters, 11 of which represented hitherto unrecognized species. Fermentation broths from 19.7% of the isolated strains showed activity in at least one of the six screens for antibiotic activity. These isolates exhibited bio-diversity in enzymatic characteristics and carbon utilization profiles. The physiological characteristics of the isolates from different types of crusts or bare sand samples were specific to their respective micro-ecological environments. Our study revealed that members of the family Geodermatophilaceae were ubiquitous, abundant, and diverse in Shapotou National Desert Ecological Reserve, and these strains may represent a new major group of potential functional actinobacteria in desert soil

Phase Control on Surface for the Stabilization of High Energy Cathode Materials of Lithium Ion Batteries.

The development of high energy electrode materials for lithium ion batteries is challenged by their inherent instabilities, which become more aggravated as the energy densities continue to climb, accordingly causing increasing concerns on battery safety and reliability. Here, taking the high voltage cathode of LiNi0.5Mn1.5O4 as an example, we demonstrate a protocol to stabilize this cathode through a systematic phase modulating on its particle surface. We are able to transfer the spinel surface into a 30 nm shell composed of two functional phases including a rock-salt one and a layered one. The former is electrochemically inert for surface stabilization while the latter is designated to provide necessary electrochemical activity. The precise synthesis control enables us to tune the ratio of these two phases, and achieve an optimized balance between improved stability against structural degradation without sacrificing its capacity. This study highlights the critical importance of well-tailored surface phase property for the cathode stabilization of high energy lithium ion batteries

Extramedullary Plasmacytoma Involving the Bilateral Adrenal Glands on MR Imaging

We report here on a 64-year-old woman with extramedullary plasmacytoma involving the bilateral adrenal glands. Primary adrenal extramedullary plasmacytoma is extremely rare and only three cases of extramedullary plasmacytoma in the unilateral adrenal gland have currently been reported on. This case is of interest in that the bilateral adrenals were involved. In this article, we present the MRI findings and we briefly review the relevant literature

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus

Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection

Non–contact real–time detection of trace nitro-explosives by MOF composites visible–light chemiresistor

To create an artificial structure to remarkably surpass the sensitivity, selectivity and speed of the olfaction system of animals is still a daunting challenge. Herein, we propose a core-sheath pillar (CSP) architecture with a perfect synergistic interface that effectively integrates the advantages of metal–organic frameworks and metal oxides to tackle the above-mentioned challenge. The sheath material, NH₂-MIL-125, can concentrate target analyte, nitro-explosives, by 10¹² times from its vapour. The perfect band-matched synergistic interface enables the TiO₂ core to effectively harvest and utilize visible light. At room temperature and under visible light, CSP (TiO₂, NH₂-MIL-125) shows an unexpected self-promoting analyte-sensing behaviour. Its experimentally reached limit of detection (～0.8 ppq, hexogeon) is 10³ times lower than the lowest one achieved by a sniffer dog or all sensing techniques without analyte pre-concentration. Moreover, the sensor exhibits excellent selectivity against commonly existing interferences, with a short response time of 0.14 min

Increased expression of heat shock protein 105 in rat uterus of early pregnancy and its significance in embryo implantation

<p>Abstract</p> <p>Background</p> <p>Heat shock proteins (Hsps) are a set of highly conserved proteins, Hsp105, has been suggested to play a role in reproduction.</p> <p>Methods</p> <p>Spatio-temporal expression of Hsp105 in rat uterus during peri-implantation period was examined by immunohistochemistry and Western blot, pseudopregnant uterus was used as control. Injection of antisense oligodeoxynucleotides to Hsp105 into pregnant rat uteri was carried out to look at effect of Hsp105 on embryo implantation.</p> <p>Results</p> <p>Expression of Hsp105 was mainly in the luminal epithelium on day 1 of pregnancy, and reached a peak level on day 5, whereas in stroma cells, adjacent to the implanting embryo, the strongest expression of Hsp105 was observed on day 6. The immunostaining profile in the uterus was consistent with that obtained by Western blot in the early pregnancy. In contrast, no obvious peak level of Hsp105 was observed in the uterus of pseudopregnant rat on day 5 or day 6. Furthermore, injection of antisense oligodeoxynucleotides to Hsp105 into the rat uterine horn on day 3 of pregnancy obviously suppressed the protein expression as expected and reduced number of the implanted embryos as compared with the control.</p> <p>Conclusion</p> <p>Temporal and spatial changes in Hsp105 expression in pregnant rat uterus may play a physiological role in regulating embryo implantation.</p