Genetic association study of NF-κB genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy

Treatment-resistant muscle wasting is an increasingly recognized problem in idiopathic inflammatory myopathy (IIM). TNF-α is thought to induce muscle catabolism via activation of nuclear factor-kappa B (NF-κB). Several genes share homology with the NF-κB family of proteins. This study investigated the role of NF-κB-related genes in disease susceptibility in UK Caucasian IIM

Appearances can be deceptive: Revealing a hidden viral infection with deep sequencing in a plant quarantine context

Comprehensive inventories of plant viral diversity are essential for effective quarantine and sanitation efforts. The safety of regulated plant material exchanges presently relies heavily on techniques such as PCR or nucleic acid hybridisation, which are only suited to the detection and characterisation of specific, well characterised pathogens. Here, we demonstrate the utility of sequence-independent next generation sequencing (NGS) of both virus-derived small interfering RNAs (siRNAs) and virion-associated nucleic acids (VANA) for the detailed identification and characterisation of viruses infecting two quarantined sugarcane plants. Both plants originated from Egypt and were known to be infected with Sugarcane streak Egypt Virus (SSEV; Genus Mastrevirus, Family Geminiviridae), but were revealed by the NGS approaches to also be infected by a second highly divergent mastrevirus, here named Sugarcane white streak Virus (SWSV). This novel virus had escaped detection by all routine quarantine detection assays and was found to also be present in sugarcane plants originating from Sudan. Complete SWSV genomes were cloned and sequenced from six plants and all were found to share .91% genomewide identity. With the exception of two SWSV variants, which potentially express unusually large RepA proteins, the SWSV isolates display genome characteristics very typical to those of all other previously described mastreviruses. An analysis of virus-derived siRNAs for SWSV and SSEV showed them to be strongly influenced by secondary structures within both genomic single stranded DNA and mRNA transcripts. In addition, the distribution of siRNA size frequencies indicates that these mastreviruses are likely subject to both transcriptional and post-transcriptional gene silencing. Our study stresses the potential advantages of NGS-based virus metagenomic screening in a plant quarantine setting and indicates that such techniques could dramatically reduce the numbers of non-intercepted virus pathogens passing through plant quarantine stations

Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016)

This article lists the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2016. Changes to virus taxonomy (the Universal Scheme of Virus Classification of the International Committee on Taxonomy of Viruses [ICTV]) now take place annually and are the result of a multi-stage process. In accordance with the ICTV Statutes (http://​www.​ictvonline.​org/​statutes.​asp), proposals submitted to the ICTV Executive Committee (EC) undergo a review process that involves input from the ICTV Study Groups (SGs) and Subcommittees (SCs), other interested virologists, and the EC. After final approval by the EC, proposals are then presented for ratification to the full ICTV membership by publication on an ICTV web site (http://​www.​ictvonline.​org/​) followed by an electronic vote. The latest set of proposals approved by the EC was made available on the ICTV website by January 2016 (https://​talk.​ictvonline.​org/​files/​proposals/​). A list of these proposals was then emailed on 28 March 2016 to the 148 members of ICTV, namely the EC Members, Life Members, ICTV Subcommittee Members (including the SG chairs) and ICTV National Representatives. Members were then requested to vote on whether to ratify the taxonomic proposals (voting closed on 29 April 2016)

Remote Sensing of the Reconnection Electric Field From In Situ Multipoint Observations of the Separatrix Boundary

A remote sensing technique to infer the local reconnection electric field based on in situ multipoint spacecraft observation at the reconnection separatrix is proposed. In this technique, the increment of the reconnected magnetic flux is estimated by integrating the in‐plane magnetic field during the sequential observation of the separatrix boundary by multipoint measurements. We tested this technique by applying it to virtual observations in a two‐dimensional fully kinetic particle‐in‐cell simulation of magnetic reconnection without a guide field and confirmed that the estimated reconnection electric field indeed agrees well with the exact value computed at the X‐line. We then applied this technique to an event observed by the Magnetospheric Multiscale mission when crossing an energetic plasma sheet boundary layer during an intense substorm. The estimated reconnection electric field for this event is nearly 1 order of magnitude higher than a typical value of magnetotail reconnection

Appearances can be deceptive: revealing a hidden viral infection with deep sequencing in a plant quarantine context

Comprehensive inventories of plant viral diversity are essential for effective quarantine and sanitation efforts. The safety of regulated plant material exchanges presently relies heavily on techniques such as PCR or nucleic acid hybridisation, which are only suited to the detection and characterisation of specific, well characterised pathogens. Here, we demonstrate the utility of sequence-independent next generation sequencing (NGS) of both virus-derived small interfering RNAs (siRNAs) and virion-associated nucleic acids (VANA) for the detailed identification and characterisation of viruses infecting two quarantined sugarcane plants. Both plants originated from Egypt and were known to be infected with Sugarcane streak Egypt Virus (SSEV; Genus Mastrevirus, Family Geminiviridae), but were revealed by the NGS approaches to also be infected by a second highly divergent mastrevirus, here named Sugarcane white streak Virus (SWSV). This novel virus had escaped detection by all routine quarantine detection assays and was found to also be present in sugarcane plants originating from Sudan. Complete SWSV genomes were cloned and sequenced from six plants and all were found to share .91% genomewide identity. With the exception of two SWSV variants, which potentially express unusually large RepA proteins, the SWSV isolates display genome characteristics very typical to those of all other previously described mastreviruses. An analysis of virus-derived siRNAs for SWSV and SSEV showed them to be strongly influenced by secondary structures within both genomic single stranded DNA and mRNA transcripts. In addition, the distribution of siRNA size frequencies indicates that these mastreviruses are likely subject to both transcriptional and post-transcriptional gene silencing. Our study stresses the potential advantages of NGS-based virus metagenomic screening in a plant quarantine setting and indicates that such techniques could dramatically reduce the numbers of non-intercepted virus pathogens passing through plant quarantine stations

T cell GM-CSF expression in juvenile arthritis is contingent upon Th17 plasticity.

Objectives Granulocyte monocyte colony stimulating factor (GM-CSF) is a potent inflammatory mediator responsible for recruitment and activation of innate immune cells. Recent murine data have identified Th17 cells as a key source of GM-CSF, and suggest that T cell derived GM-CSF is instrumental in the induction of autoimmune disease. We analysed the expression of T cell derived GM-CSF in the joints of patients with Juvenile idiopathic arthritis (JIA) and investigated the development links between Th17 and GM-CSF+ T helper cells. Methods 24 patients with JIA were analysed for expression of GM-CSF and the Th17 marker CD161 in synovial and peripheral blood compartments using flow cytometry and RT-PCR. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to IL-12 and IL-23. Results The frequency of GM-CSF producing T helper cells were significantly enriched in JIA synovial fluid mononuclear cells (SFMC) compared to PBMC (24.1% vs 2.9% of CD4+ T cells) and closely correlated with ESR levels (r(2) =0.91, p=<0.001). Synovial GM-CSF+ T cells were predominantly CD161 positive and co-expressed interferon gamma (IFNγ) but not IL-17. Culture of Th17 cells in the presence of IL-12 led to rapid upregulation of GM-CSF and IFNγ, recapitulating the phenotype of GM-CSF expressing cells within the joint. Conclusions Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM-CSF expressing T cells found within the JIA joint. The association of GM-CSF expression with systemic inflammation highlights the potential role for Th17 related cytokines in the pathology of JIA. © 2014 American College of Rheumatology