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Long Interspersed Nucleotide Element 1 (LINE-1) retrotransposons are heavily methylated and are the most abundant transposable elements in mammalian genomes. Here, we investigated the differential DNA methylation within the LINE-1 under normal conditions and in response to environmentally relevant doses of sparsely and densely ionizing radiation. We demonstrate that DNA methylation of LINE-1 elements in the lungs of C57BL6 mice is dependent on their evolutionary age, where the elder age of the element is associated with the lower extent of DNA methylation. Exposure to 5-aza-2′-deoxycytidine and methionine-deficient diet affected DNA methylation of selective LINE-1 elements in an age- and promoter type-dependent manner. Exposure to densely IR, but not sparsely IR, resulted in DNA hypermethylation of older LINE-1 elements, while the DNA methylation of evolutionary younger elements remained mostly unchanged. We also demonstrate that exposure to densely IR increased mRNA and protein levels of LINE-1 via the loss of the histone H3K9 dimethylation and an increase in the H3K4 trimethylation at the LINE-1 5′-untranslated region, independently of DNA methylation. Our findings suggest that DNA methylation is important for regulation of LINE-1 expression under normal conditions, but histone modifications may dictate the transcriptional activity of LINE-1 in response to exposure to densely IR.

Interest in deep space exploration underlines the needs to investigate the effects of exposure to combined sources of space radiation. The lung is a target organ for radiation, and exposure to protons and heavy ions as radiation sources may lead to the development of degenerative disease and cancer. In this study, we evaluated the pro-fibrotic and epigenetic effects of exposure to protons (150 MeV/nucleon, 0.1 Gy) and heavy iron ions ((56)Fe, 600 MeV/nucleon, 0.5 Gy) alone or in combination (protons on Day 1 and (56)Fe on Day 2) in C57BL/6 male mice 4 weeks after irradiation. Exposure to (56)Fe, proton or in combination, did not result in histopathological changes in the murine lung. At the same time, combined exposure to protons and (56)Fe resulted in pronounced molecular alterations in comparison with either source of radiation alone. Specifically, we observed a substantial increase in the expression of cytokine Il13, loss of expression of DNA methyltransferase Dnmt1, and reactivation of LINE-1, SINE B1 retrotransposons, and major and minor satellites. Given the deleterious potential of the observed effects that may lead to development of chronic lung injury, pulmonary fibrosis, and cancer, future studies devoted to the investigation of the long-term effects of combined exposures to proton and heavy ions are clearly needed.

Nowadays, construction projects are typically carried out by several main contractors as equal partners and dozens of subcontractors, mainly SMEs, organised in hierarchical contractual and responsibility structures of several subcontracting levels. Hierarchical centralized planning down to individual tasks with exact time scheduling is also done in advance, but due to the high networking complexity and, especially, the multi-project participation of many of the actors this often leads to very high planning risks with regard to resources and time. Moreover, many ad-hoc decisions are taken by the project manager on the job site, without a proper update of the process plan. Due to this very common scenario, there are two specific issues that need to be put at the front of the 21st century construction site: quality and safety. To achieve that, capabilities for distributed teamwork management and on-site decision making are required, coupled with adequate services enabling just-in-time goal-driven information delivery and capable to support the needed on-site dynamicity in terms of quality assurance and safety on site management. Two specific technologies which were used in other sectors during the last decades, such as RFID have shown to be powerful enabling technologies for construction sector. As it will be explained in this article, three aplications have been implemented by ACCIONA in its sites. On one hand, RFID tags have been used to assure safety inside tunnels during its construction, tracking workers location. On the other hand, an RFID-based wireless sensor network has been deployed in order to remotely monitor concrete mechanical properties in real time, being able to optimize execution times of all the successive construction phases (excavation under a slab, advancing in shuttering truck tunnels, etc).

Intracellular oxygen concentration ([O2]i.c.) regulates key biological functions such as HIF-1α activation, glucose transport, potassium pumps, intracellular calcium concentration, P450 family enzymes and HMGR expression. However, the mechanisms regulating [O2]i.c remain to be defined. Here, we provide direct evidence of the mitochondrion's role in [O2]i.c. regulation. We used bis(2-(2′-benzothienyl)-pyridianto-N,C3’irridium(acetylacetonate) (BTP) to measure [O2]i.c. in living cells via microscopy.5 Well-differentiated cancers, LNCaP and MCF-7 showed intracellular hypoxia without exogenous hypoxia. In contrast, poorly-differentiated cancers exhibited intracellular normoxia, and exogenous hypoxia could induce hypoxia. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content increased in [O2]i.c,, indicating that [O2]i.c. is regulated by mitochondrial respiratory activity. [O2]i.c. is additionally regulated by glucose, but the dose-dependent relationship is parabolic. The no glucose condition induced normoxia, and the low concentration glucose condition (0.045mg/ml) induced strong hypoxia. [O2]i.c. was found to be additionally determined by the presence of FCS in the growth medium, and this effect was mimicked by an androgen analog, R1881, suggesting that androgen, glucose concentration and respiratory function are important regulators of [O2]i.c.. Citation Format: Sara Prior, Ara Kim, Seiji Tobita, Toshiyuki Takeuchi, Masahiro Higuchi. Intracellular hypoxia is dominantly determined by mitochondrial respiratory activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1693. doi:10.1158/1538-7445.AM2013-1693