Nuclear Law: The Global Debate

The International Atomic Energy Agency (IAEA) plays a unique role in the development and implementation of international nuclear law. This chapter contains a short examination of the regime of nuclear law and its four pillars, namely safety, security, safeguards and civil liability for nuclear damage. It examines how we got to where we are and where we can take the global debate, taking into account current and emerging peaceful applications of nuclear science and technology such as advanced reactors and nuclear fusion. The chapter also contains an invitation to all stakeholders in the global community, including international organizations, non-governmental organizations, industry, academia and civil society, as well as all those that will be responsible for shaping nuclear law in the future, to let the debate and dialogue on nuclear law begin.

Nuclear Liability and Post-Fukushima Developments

The international community has developed a series of conventions on civil liability for nuclear damage, which aim to ensure compensation is available for damage, including transboundary damage, caused by a nuclear incident. Those conventions have struggled to gain universal adherence, and the “global regime” called for in 2011 is at best a patchwork quilt, with a number of treaties with differing memberships, and many States (including States with large and growing nuclear sectors) not party to any convention. However, the principles of the conventions are reflected in national laws in most States which operate nuclear power reactors and associated facilities. This chapter assesses the current global nuclear liability regime and discusses a series of recommendations made by the International Expert Group on Nuclear Liability (INLEX) to allow the international community to respond to the continued evolution of the nuclear industry.

Potential mutagenic effects of the glyphosate herbicide on Gymnotus inaequilabiatus (Valenciennes, 1839)

This study analyzed the occurrence of nuclear damage in the red blood cells of Gymnotus inaequilabiatus (Valenciennes, 1839), exposed in vivo to the herbicide glyphosate. The fish were distributed in four groups, namely: control (without addition of herbicide) and contaminated groups with application of 65 µg/L (concentration allowed by CONAMA Resolution), 1 mg/L (maximum limit recommended by the World Health Organization - WHO and Food and Agriculture Organization - FAO) and 5 mg/L (overdose, five times higher than that by WHO and FAO). For the analysis of cell damage, the method of Nuclear Erythrocytic Abnormalities (NEA) was used, containing 1000 cells for duplicate elimination. An increase in cell damage was observed for 144 hours (6-days) of exposure in all controls. Even under a small concentration, there was a clear effect on segmented, renal, lobed formation and mainly on the formation of micronuclei. The high damage was caused in the first 48 hours and reduced after 144 hours, where the fish can have the herbicidal effect blocked. Studies that analyze the mechanisms of action of glyphosate-based herbicides are essential to determine the risks caused by biota, since there is a great divergence on the maximum tolerable limits in water, which affect quality and integrity of these ecosystems.

Nuclear lipid droplets and nuclear damage in Caenorhabditis elegans

Fat stored in the form of lipid droplets has long been considered a defining characteristic of cytoplasm. However, recent studies have shown that nuclear lipid droplets occur in multiple cells and tissues, including in human patients with fatty liver disease. The function(s) of stored fat in the nucleus has not been determined, and it is possible that nuclear fat is beneficial in some situations. Conversely, nuclear lipid droplets might instead be deleterious by disrupting nuclear organization or triggering aggregation of hydrophobic proteins. We show here that nuclear lipid droplets occur normally in C. elegans intestinal cells and germ cells, but appear to be associated with damage only in the intestine. Lipid droplets in intestinal nuclei can be associated with novel bundles of microfilaments (nuclear actin) and membrane tubules that might have roles in damage repair. To increase the normal, low frequency of nuclear lipid droplets in wild-type animals, we used a forward genetic screen to isolate mutants with abnormally large or abundant nuclear lipid droplets. Genetic analysis and cloning of three such mutants showed that the genes encode the lipid regulator SEIP-1/seipin, the inner nuclear membrane protein NEMP-1/Nemp1/TMEM194A, and a component of COPI vesicles called COPA-1/α-COP. We present several lines of evidence that the nuclear lipid droplet phenotype of copa-1 mutants results from a defect in retrieving mislocalized membrane proteins that normally reside in the endoplasmic reticulum. The seip-1 mutant causes most germ cells to have nuclear lipid droplets, the largest of which occupy more than a third of the nuclear volume. Nevertheless, the nuclear lipid droplets do not trigger apoptosis, and the germ cells differentiate into gametes that produce viable, healthy progeny. Thus, our results suggest that nuclear lipid droplets are detrimental to intestinal nuclei, but have no obvious deleterious effect on germ nuclei.

New Projections for Dark Matter Searches with Paleo-Detectors

Paleo-detectors are a proposed experimental technique to search for dark matter (DM). In lieu of the conventional approach of operating a tonne-scale real-time detector to search for DM-induced nuclear recoils, paleo-detectors take advantage of small samples of naturally occurring rocks on Earth that have been deep underground (≳5 km), accumulating nuclear damage tracks from recoiling nuclei for O(1)Gyr. Modern microscopy techniques promise the capability to read out nuclear damage tracks with nanometer resolution in macroscopic samples. Thanks to their O(1)Gyr integration times, paleo-detectors could constitute nuclear recoil detectors with keV recoil energy thresholds and 100 kilotonne-yr exposures. This combination would allow paleo-detectors to probe DM-nucleon cross sections orders of magnitude below existing upper limits from conventional direct detection experiments. In this article, we use improved background modeling and a new spectral analysis technique to update the sensitivity forecast for paleo-detectors. We demonstrate the robustness of the sensitivity forecast to the (lack of) ancillary measurements of the age of the samples and the parameters controlling the backgrounds, systematic mismodeling of the spectral shape of the backgrounds, and the radiopurity of the mineral samples. Specifically, we demonstrate that even if the uranium concentration in paleo-detector samples is 10−8 (per weight), many orders of magnitude larger than what we expect in the most radiopure samples obtained from ultra basic rock or marine evaporite deposits, paleo-detectors could still probe DM-nucleon cross sections below current limits. For DM masses ≲ 10 GeV/c2, the sensitivity of paleo-detectors could still reach down all the way to the conventional neutrino floor in a Xe-based direct detection experiment.

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells

The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated autophagy has not been elucidated in cancer cells. The described investigation revealed that active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cell line with high micronucleus (MN) formation. DNA autophagy was identified as selective autophagy of free genomic DNA in the cytoplasm but not nucleophagy. The process of DNA autophagy in the cytosol could be initiate by cGAS and usually cooperates with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA, together with nuclear proteins such as histones, could be derived from DNA replication-induced nuclear damage and MN collapse. The inhibition of autophagy through chemical inhibitors as well as the genomic silencing of cGAS or SQSTM1 could suppress the growth and survival of cancer cells, and induced DNA damage could increase the sensitivity to these inhibitors. Furthermore, expanded observations of several other kinds of human cancer cells indicated that high relative DNA autophagy or enhancement of DNA damage could also increase or sensitize these cells to inhibition of DNA autophagy.

Laser-Induced Nuclear Damage Signaling and Communication in Astrocyte Networks Through Parp-Dependent Calcium Oscillations

Astrocytes are known to respond to various perturbations with oscillations of calcium, including to cellular injury. Less is known about astrocytes’ ability to detect DNA/nuclear damage. This study looks at changes in calcium signaling in response to laser-induced nuclear damage using a NIR Ti:Sapphire laser. Primary astrocytes derived from genetically engineered mice expressing G6Campf genetically encoded calcium indicator were imaged in response to laser induced injury. Combining laser nanosurgery with calcium imaging of primary astrocytes allow for spatial and temporal observation of the astrocyte network in response to nuclear damage. Nuclear damage resulted in a significant increase in calcium peak frequency, in nuclear damaged cells and astrocytes directly attached to it. The increase in calcium event frequency observed in response to damage and the transfer to neighboring cells was not observed in cytoplasm damaged cells. Targeted astrocytes and attached neighboring cells treated with Poly (ADP-ribose) polymerase inhibitor have a significantly lower peak frequency following laser damage to the nucleus. These results indicate the increase in calcium peak frequency following nuclear damage is poly (ADP-ribose) polymerase dependent.