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1.
Space Weather ; 17(10): 1384-1403, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31894181

ABSTRACT

The Community Coordinated Modeling Center has been leading community-wide space science and space weather model validation projects for many years. These efforts have been broadened and extended via the newly launched International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). Its objective is to track space weather models' progress and performance over time, a capability that is critically needed in space weather operations and different user communities in general. The Space Radiation and Plasma Effects Working Team of the aforementioned International Forum works on one of the many focused evaluation topics and deals with five different subtopics (https://ccmc.gsfc.nasa.gov/assessment/topics/radiation-all.php) and varieties of particle populations: Surface Charging from tens of eV to 50-keV electrons and internal charging due to energetic electrons from hundreds keV to several MeVs. Single-event effects from solar energetic particles and galactic cosmic rays (several MeV to TeV), total dose due to accumulation of doses from electrons (>100 keV) and protons (>1 MeV) in a broad energy range, and radiation effects from solar energetic particles and galactic cosmic rays at aviation altitudes. A unique aspect of the Space Radiation and Plasma Effects focus area is that it bridges the space environments, engineering, and user communities. The intent of the paper is to provide an overview of the current status and to suggest a guide for how to best validate space environment models for operational/engineering use, which includes selection of essential space environment and effect quantities and appropriate metrics.

2.
Biochim Biophys Acta ; 1830(11): 5059-67, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23876295

ABSTRACT

BACKGROUND: Genetically encoded photosensitizers are a promising optogenetic instrument for light-induced production of reactive oxygen species in desired locations within cells in vitro or whole body in vivo. Only two such photosensitizers are currently known, GFP-like protein KillerRed and FMN-binding protein miniSOG. In this work we studied phototoxic effects of miniSOG in cancer cells. METHODS: HeLa Kyoto cell lines stably expressing miniSOG in different localizations, namely, plasma membrane, mitochondria or chromatin (fused with histone H2B) were created. Phototoxicity of miniSOG was tested on the cells in vitro and tumor xenografts in vivo. RESULTS: Blue light induced pronounced cell death in all three cell lines in a dose-dependent manner. Caspase 3 activation was characteristic of illuminated cells with mitochondria- and chromatin-localized miniSOG, but not with miniSOG in the plasma membrane. In addition, H2B-miniSOG-expressing cells demonstrated light-induced activation of DNA repair machinery, which indicates massive damage of genomic DNA. In contrast to these in vitro data, no detectable phototoxicity was observed on tumor xenografts with HeLa Kyoto cell lines expressing mitochondria- or chromatin-localized miniSOG. CONCLUSIONS: miniSOG is an excellent genetically encoded photosensitizer for mammalian cells in vitro, but it is inferior to KillerRed in the HeLa tumor. GENERAL SIGNIFICANCE: This is the first study to assess phototoxicity of miniSOG in cancer cells. The results suggest an effective ontogenetic tool and may be of interest for molecular and cell biology and biomedical applications.


Subject(s)
Flavoproteins/genetics , Genetic Therapy/methods , Oxygen/metabolism , Photosensitizing Agents/metabolism , Animals , Caspase 3/genetics , Caspase 3/metabolism , Cell Death/genetics , Cell Line , Cell Line, Tumor , Cell Membrane/genetics , Cell Membrane/metabolism , Chromatin/genetics , Chromatin/metabolism , DNA Damage , DNA Repair , Dermatitis, Phototoxic/etiology , Dermatitis, Phototoxic/genetics , Dermatitis, Phototoxic/metabolism , Female , Flavoproteins/metabolism , HEK293 Cells , HeLa Cells , Humans , Light/adverse effects , Mice , Mice, Nude , Mitochondria/genetics , Mitochondria/metabolism , Riboflavin/genetics , Riboflavin/metabolism , Xenograft Model Antitumor Assays
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