Current Measures on Radioactive Contamination in Japan: A Policy Situation Analysis.

BACKGROUND: The Great East Japan Earthquake on 11th March 2011 and the subsequent Fukushima Dai-ichi nuclear power plant disaster caused radioactive contamination in the surrounding environment. In the immediate aftermath of the accident the Government of Japan placed strict measures on radio-contamination of food, and enhanced radio-contamination monitoring activities. Japan is a pilot country in the WHO Foodborne Disease Burden Epidemiology Reference Group (FERG), and through this initiative has an opportunity to report on policy affecting chemicals and toxins in the food distribution network. Nuclear accidents are extremely rare, and a policy situation analysis of the Japanese government's response to the Fukushima Dai-ichi nuclear accident is a responsibility of Japanese scientists. This study aims to assess Japan government policies to reduce radio-contamination risk and to identify strategies to strengthen food policies to ensure the best possible response to possible future radiation accidents. METHODS AND FINDINGS: We conducted a hand search of all publicly available policy documents issued by the Cabinet Office, the Food Safety Commission, the Ministry of Health, Labor and Welfare (MHLW), the Ministry of Agriculture, Forestry and Fishery (MAFF) and prefectural governments concerning food safety standards and changes to radiation and contamination standards since March 11th, 2011. We extracted information on food shipment and sales restrictions, allowable radio-contamination limits, monitoring activities and monitoring results. The standard for allowable radioactive cesium (Cs-134 and Cs-137) of 100 Bq/Kg in general food, 50 Bq/Kg in infant formula and all milk products, and 10 Bq/Kg in drinking water was enforced from April 2012 under the Food Sanitation Law, although a provisional standard on radio-contamination had been applied since the nuclear accident. Restrictions on the commercial sale and distribution of specific meat, vegetable and fish products were released for areas at risk of radioactive contamination. Monitoring of radioactive materials in food products in the prefectures has been mainly conducted before shipment to restrict the distribution of radio-contaminated foods. Between March 2011 and March 2012, 133,832 tests of non-commercial and commercial products were conducted, and 1,204 tests (0.9%) were found to violate the provisional standards. Since April 2012, 278,275 tests were conducted, and 2,372 tests (0.9%) were found to violate the revised standards. MHLW assessment of representative market baskets of foodstuffs at 15 locations throughout Japan between February and March 2014 found very low estimated dietary intake of radioactive cesium (0.0007-0.019 mSv/year), as did assessments of the contents of an average day's food. Monitoring of fisheries products in coastal areas affected by the nuclear accident found very limited and declining radio-contamination of live fish outside of Fukushima prefecture. Fisheries monitoring is of limited geographical scope and covers only certain fishes. CONCLUSIONS: Area-specific bans on production and distribution have been effective in preventing radioactive contamination in the Japanese food market. Currently there is no major concern about radioactive cesium concentrations in retail foodstuffs in Japan, and very low levels of contamination at the production and wholesale stage. However, because the residue limits and food safety policies were revised on an ad hoc, emergency basis after the nuclear accident, the monitoring procedure needs to be reviewed based on objective and scientifically rational criteria. A transparent and objective scientific framework is needed for prioritizing foodstuffs for inspection and revising Prefecture-specific restrictions. Monitoring of fishes and other seafood products in the wild should be regularized and the information made more publicly accessible, and monitoring activities expanded to identify foodstuffs that are no longer a food safety risk. Consultation with producers and consumers should be more formalized to ensure their concerns are incorporated into regular policy reviews in an appropriate and transparent manner. However, despite the limited available knowledge on best practice in food control and enforcement of provisional radio-contamination limits after the accident, current Japanese policy is sufficient to protect the Japanese public from major risk of radio-contamination from the commercial food market.

Natural product-like macrocyclic N-methyl-peptide inhibitors against a ubiquitin ligase uncovered from a ribosome-expressed de novo library.

Naturally occurring peptides often possess macrocyclic and N-methylated backbone. These features grant them structural rigidity, high affinity to targets, proteolytic resistance, and occasionally membrane permeability. Because such peptides are produced by either nonribosomal peptide synthetases or enzymatic posttranslational modifications, it is yet a formidable challenge in degenerating sequence or length and preparing libraries for screening bioactive molecules. Here, we report a new means of synthesizing a de novo library of "natural product-like" macrocyclic N-methyl-peptides using translation machinery under the reprogrammed genetic code, which is coupled with an in vitro display technique, referred to as RaPID (random nonstandard peptides integrated discovery) system. This system allows for rapid selection of strong binders against an arbitrarily chosen therapeutic target. Here, we have demonstrated the selection of anti-E6AP macrocyclic N-methyl-peptides, one of which strongly inhibits polyubiqutination of proteins such as p53.

E6AP ubiquitin ligase mediates ubiquitin-dependent degradation of peroxiredoxin 1.

E6-associated protein (E6AP) is a cellular ubiquitin protein ligase that mediates ubiquitylation and degradation of tumor suppressor p53 in conjunction with the high-risk human papillomavirus E6 protein. We previously reported that E6AP targets annexin A1 protein for ubiquitin-dependent proteasomal degradation. To gain a better understanding of the physiological function of E6AP, we have been seeking to identify novel substrates of E6AP. Here, we identified peroxiredoxin 1 (Prx1) as a novel E6AP-binding protein using a tandem affinity purification procedure coupled with mass spectrometry. Prx1 is a 25-kDa member of the Prx family, a ubiquitous family of antioxidant peroxidases that regulate many cellular processes through intracellular oxidative signal transduction pathways. Immunoprecipitation analysis showed that E6AP binds Prx1 in vivo. Pull-down experiments showed that E6AP binds Prx1 in vitro. Ectopic expression of E6AP enhanced the degradation of Prx1 in vivo. In vivo and in vitro ubiquitylation assays revealed that E6AP promoted polyubiquitylation of Prx1. RNAi-mediated downregulation of endogenous E6AP increased the level of endogenous Prx1 protein. Taken together, our data suggest that E6AP mediates the ubiquitin-dependent proteasomal degradation of Prx1. Our findings raise a possibility that E6AP may play a role in regulating Prx1-dependent intracellular oxidative signal transduction pathways.