A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

The identification of QTL controlling ergot sclerotia size in hexaploid wheat implicates a role for the Rht dwarfing alleles

The fungal pathogen Claviceps purpurea infects ovaries of a broad range of temperate grasses and cereals, including hexaploid wheat, causing a disease commonly known as ergot. Sclerotia produced in place of seed carry a cocktail of harmful alkaloid compounds that result in a range of symptoms in humans and animals, causing ergotism. Following a field assessment of C. purpurea infection in winter wheat, two varieties ‘Robigus’ and ‘Solstice’ were selected which consistently produced the largest differential effect on ergot sclerotia weights. They were crossed to produce a doubled haploid mapping population, and a marker map, consisting of 714 genetic loci and a total length of 2895 cM was produced. Four ergot reducing QTL were identified using both sclerotia weight and size as phenotypic parameters; QCp.niab.2A and QCp.niab.4B being detected in the wheat variety ‘Robigus’, and QCp.niab.6A and QCp.niab.4D in the variety ‘Solstice’. The ergot resistance QTL QCp.niab.4B and QCp.niab.4D peaks mapped to the same markers as the known reduced height (Rht) loci on chromosomes 4B and 4D, Rht-B1 and Rht-D1, respectively. In both cases, the reduction in sclerotia weight and size was associated with the semi-dwarfing alleles, Rht-B1b from ‘Robigus’ and Rht-D1b from ‘Solstice’. Two-dimensional, two-QTL scans identified significant additive interactions between QTL QCp.niab.4B and QCp.niab.4D, and between QCp.niab.2A and QCp.niab.4B when looking at sclerotia size, but not between QCp.niab.2A and QCp.niab.4D. The two plant height QTL, QPh.niab.4B and QPh.niab.4D, which mapped to the same locations as QCp.niab.4B and QCp.niab.4D, also displayed significant genetic interactions

Metodika navrhu technicke infrastruktury informacniho systemu na rozhrani Internet/Intranet.

Complex design of IS technical infrastructure with use of sensitivity analysis tools.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Present status and future prospects of plasma sprayed multilayered thermal barrier coating systems

Thermal barrier coatings (TBCs) play a pivotal role in protecting the hot structures of modern turbine engines in aerospace as well as utility applications. To meet the increasing efficiency of gas turbine technology, worldwide research is focused on designing new architecture of TBCs. These TBCs are mainly fabricated by atmospheric plasma spraying (APS) as it is more economical over the electron beam physical vapor deposition (EB-PVD) technology. Notably, bi-layered, multi-layered and functionally graded TBC structures are recognized as favorable designs to obtain adequate coating performance and durability. In this regard, an attempt has been made in this article to highlight the structure, characteristics, limitations and future prospects of bi-layered, multi-layered and functionally graded TBC systems fabricated using plasma spraying and its allied techniques like suspension plasma spray (SPS), solution precursor plasma spray (SPPS) and plasma spray –physical vapor deposition (PS-PVD)

Improved hot corrosion resistance of plasma sprayed YSZ/Gd2Zr2O7 thermal barrier coating over single layer YSZ

In recent years, research is focused on the development of rare earth zirconates based thermal barrier coatings (TBC). In the present study, bilayered 8 wt% yttria stabilized zirconia (YSZ)/gadolinium zirconate (GZO) TBC system has been developed by atmospheric plasma spraying (APS) process from powders prepared by a single step co-precipitation technique. Hot corrosion behavior of all the coatings are tested in fused Na2SO4+ V2O5 mixture at the concentration of approximately 25 mg/cm2 at 910 °C for 30 h. Formation of gadolinium vanadate (GdVO4) is observed to be the corrosion product in YSZ/GZO bilayer coatings from Energy Dispersive X-ray analysis (EDAX) and is further confirmed by X-ray diffractometry (XRD) analysis. FESEM cross-section analysis of the YSZ/GZO bilayer coating after corrosion test affirms the effectiveness of the bilayer design in preventing the penetration of corrosive salts to the YSZ layer. Also, YSZ/GZO bilayer TBC exhibited a higher thermal cyclic life (300 cycles) than the single layer 8YSZ (175 cycles) coatings at 1100 °C

Solution combustion synthesis of calcia-magnesia-aluminosilicate powder and its interaction with yttria-stabilized zirconia and co-doped yttria-stabilized zirconia

Thermal Barrier Coatings (TBCs) play a significant role in improving the efficiency of gas turbines by increasing their operating temperatures. The TBCs in advanced turbine engines are prone to silicate particles attack while operating at high temperatures. The silicate particles impinge on the hot TBC surfaces and melt to form calcia-magnesia-aluminosilicate (CMAS) glass deposits leading to coating premature failure. Fine powder of CMAS with the composition matching the desert sand has been synthesized by solution combustion technique. The present study also demonstrates the preparation of flowable yttria-stabilized zirconia (YSZ) and cluster paired YSZ (YSZ-Ln2O3, Ln = Dy and Gd) powders by single-step solution combustion technique. The as-synthesized powders have been plasma sprayed and the interaction of the free standing TBCs with CMAS at high-temperatures (1200 °C, 1270 °C and 1340 °C for 24 h) has been investigated. X-ray diffraction analysis of CMAS attacked TBCs revealed a reduction in phase transformation of tetragonal to monoclinic zirconia for YSZ-Ln2O3 (m-ZrO2: 44%) coatings than YSZ (m-ZrO2: 67%). The field emission scanning electron microscopic images show improved CMAS resistance for YSZ-Ln2O3 coatings than YSZ coatings