The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.

T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells in autoimmune pathogenesis, it is important to understand the factors that control Th17 development. Here we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of Th17 differentiation. Mice with T cell-specific deletion of Atf7ip have impaired Th17 differentiation secondary to the aberrant overproduction of IL-2 with T cell receptor (TCR) stimulation and are resistant to colitis in vivo. ChIP-seq studies identified ATF7ip as an inhibitor of Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il2-Il21 intergenic region. These results demonstrate a new epigenetic pathway by which IL-2 production is constrained, and this may open up new avenues for modulating its production

Microwave solidification development for Rocky Flats waste

The Microwave Engineering Team at the Rocky Flats Plant has developed a production-scale system for the treatment of hazardous, radioactive, and mixed wastes using microwave energy. The system produces a vitreous final form which meets the acceptance criteria for shipment and disposal. The technology also has potential for application on various other waste streams from the public and private sectors. Technology transfer opportunities are being identified and pursued for commercialization of the microwave solidification technology

Large Differences in Small RNA Composition Between Human Biofluids.

Extracellular microRNAs (miRNAs) and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA sequencing (RNA-seq). miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids, but levels of some miRNAs differed markedly between biofluids. tDR populations differed extensively between biofluids. Y RNA fragments were seen in all biofluids and accounted for >10% of reads in blood plasma, serum, and cerebrospinal fluid (CSF). Reads mapping exclusively to Piwi-interacting RNAs (piRNAs) were very rare, except in seminal plasma. These results demonstrate extensive differences in small RNAs between human biofluids and provide a useful resource for investigating extracellular RNA biology and developing biomarkers

Tissue signals imprint ILC2 identity with anticipatory function.

Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life

The ecological footprint remains a misleading metric of global sustainability

Linus Blomqvist, Barry W. Brook, Erle C. Ellis, Peter M. Kareiva, Ted Nordhaus, Michael Shellenberge

Bactericidal activity of human eosinophilic granulocytes against Escherichia coli

Eosinophils participate in allergic inflammation and may have roles in the bodys defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production L-N5-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells