Development of a Novel Passive Monitoring Technique to Showcase the 3D Distribution of Tritiated Water (HTO) Vapor in Indoor Air of a Nuclear Facility

Tritiated water (HTO), a ubiquitous byproduct of the nuclear industry, is a radioactive contaminant of major concern for environmental authorities. Although understanding spatiotemporal heterogeneity of airborne HTO vapor holds great importance for radiological safety as well as diagnosing a reactor’s status, comprehensive HTO distribution dynamics inside nuclear facilities has not been studied routinely yet due to a lack of appropriate monitoring techniques. For current systems, it is difficult to simultaneously achieve high representativeness, sensitivity, and spatial resolution. Here, we developed a passive monitoring scheme, including a newly designed passive sampler and a tailored analytical protocol for the first comprehensive 3D distribution characterization of HTO inside a nuclear reactor facility. The technique enables linear sampling in any environment at a one-day resolution and simultaneous preparation of hundreds of samples within 1 day. Validation experiments confirmed the method’s good metrological properties and sensitivity to the HTO’s spatial dynamics. The air in TU Wien’s reactor hall exhibits a range of 3H concentrations from 75-946 mBq m-3 in the entire 3D matrix. The HTO release rate estimated by the mass-balance model (3199 ± 306 Bq h-1) matches the theoretical calculation (2947 ± 254 Bq h-1), suggesting evaporation as the dominant HTO source in the hall. The proposed method provides reliable and quality-controlled 3D monitoring at low cost, which can be adopted not only for HTO and may also inspire monitoring schemes of other indoor pollutants

A critical regulatory role of leucin zipper transcription factor c-Maf in Th1-mediated experimental colitis

In this study, we investigated the role of c-Maf, a transcription factor known to induce IL-4 production, in inflammatory bowel diseases and experimental colitis. Although Crohn′s disease (CD) is associated with low IL-4 production by T-bet-expressing Th1 cells in the lamina propria, surprisingly a higher expression of c-Maf in these cells was found as compared with control patients. The relevance of this finding was further evaluated in an animal model of CD induced by adoptive transfer of CD4+CD62L+ T cells in RAG-deficient mice. In this Th1-mediated model, an increase of c-Maf-expressing T lymphocytes in the lamina propria over time was observed. Interestingly, adoptive transfer of c-Maf transgenic CD4+CD62L+ T cells in RAG-1-deficient mice resulted in an IL-4-dependent inability to induce colitis and suppressed colitis activity induced by wild-type CD4+CD62L+ T cells. In contrast, transfer of CD4+CD62L− T cells from c-Maf transgenic, but not wild-type mice induced colitis and augmented colitis induced by CD4+CD62L+ T cells from wild-type mice in an IL-4-independent pathway, as determined by macroscopic, histologic, and endoscopic criteria. This was associated with an accumulation of CD4+ T-bet+ CD25+ effector Th1 cells in the lamina propria of colitic mice. Our results reveal a novel regulatory role of c-Maf in colitis. Although overexpression of c-Maf in naive T cells prevents Th1-mediated colitis, overexpression of c-Maf in memory T-bet+ Th1 cells regulates CD25 expression and augments such colitis. Targeting of c-Maf in memory T cells in CD appears to be an attractive target for therapeutic interventions

Pituitary adenylate cyclase-activating polypeptide ameliorates experimental acute ileitis and extra-intestinal sequelae.

The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) plays pivotal roles in immunity and inflammation. So far, potential immune-modulatory properties of PACAP have not been investigated in experimental ileitis.Mice were perorally infected with Toxoplasma (T.) gondii to induce acute ileitis (day 0) and treated daily with synthetic PACAP38 from day 1 to 6 post infection (p.i.; prophylaxis) or from day 4 to 6 p.i. (therapy). Whereas placebo-treated control mice suffered from acute ileitis at day 7 p.i. and succumbed to infection, intestinal immunopathology was ameliorated following PACAP prophylaxis. PACAP-treated mice exhibited increased abundance of small intestinal FOXP3+ cells, but lower numbers of ileal T lymphocytes, neutrophils, monocytes and macrophages, which was accompanied by less ileal expression of pro-inflammatory cytokines such as IL-23p19, IL-22, IFN-γ, and MCP-1. Furthermore, PACAP-treated mice displayed higher anti-inflammatory IL-4 concentrations in mesenteric lymph nodes and liver and higher systemic anti-inflammatory IL-10 levels in spleen and serum as compared to control animals at day 7 p.i. Remarkably, PACAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments as indicated by reduced pro-inflammatory mediator levels in spleen (TNF-α, nitric oxide) and liver (TNF-α, IFN-γ, MCP-1, IL-6) and less severe histopathological sequelae in lungs and kidneys following prophylactic PACAP treatment. Strikingly, PACAP prolonged survival of T. gondii infected mice in a time-of-treatment dependent manner.Synthetic PACAP ameliorates acute small intestinal inflammation and extra-intestinal sequelae by down-regulating Th1-type immunopathology, reducing oxidative stress and up-regulating anti-inflammatory cytokine responses. These findings provide novel potential treatment options of inflammatory bowel diseases