Study on the relationship between the dispersal of wild boar (Sus scrofa) and the associated variability of Cesium-137 concentrations in its muscle Post-Fukushima Daiichi Nuclear Power Plant accident.

After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011, the wild boar (Sus scrofa) population within the Fukushima Evacuation Zone (FEZ) increased substantially in size and distribution. This growing population and their potential dispersal from the FEZ, where they are exposed to high levels of radionuclides, into the surrounding landscape underscores the need to better understand boar movement patterns in order to establish policies for managing shipping restrictions for boar meat and develop management strategies. In this study, we quantified the genetic population structure of boar in and around Fukushima prefecture using sequence data of the mitochondrial DNA control region and MIG-seq analysis using 348 boar samples to clarify boar dispersal patterns. Among boar samples, seven Asian haplotypes and one European haplotype were detected. The European haplotype originated from hybridization between domestic pigs and native boar in the evacuation zone after the accident and was detected in 15 samples across a broad geographic area. Our MIG-seq analysis revealed genetic structure of boar was significantly different between boar inhabiting the eastern (including FEZ. i.e., East clade) and western (i.e., West clade) regions in Fukushima prefecture. In addition, we investigated the relationships between boar dispersal and Cesium (Cs)-137 activity concentrations in boar muscle using MIG-seq genetic data in Nihonmatsu city, located in the central-northern region of Fukushima. High Cs-137 activity concentrations, exceeding 1000 Bq/kg, in boar muscle had a significantly high probability of belonging to the East clade within localized regions. Thus, our results provide evidence of the spatial scale of dispersal of individuals or offspring of boar from the FEZ. Results of this research also indicate that dispersal of individuals between areas with different Cs-137 contamination levels is one of the biggest factors contributing to variation in Cs-137 activity concentration in boar muscle within localized regions.

Primary spinal cord gliomas: Pathologic features associated with prognosis.

Primary spinal cord gliomas are rare and are associated with high mortality. Unlike brain tumors, the clinicopathological features of spinal cord gliomas are not well defined. We analyzed clinical, histopathology, and immunohistochemical features and overall survival (OS) of 25 patients with primary spinal cord gliomas treated between 1994 and 2023 at 4 institutions. IDH1 R132H, H3K27M, and p53 were assessed by immunohistochemistry (IHC). Four (16%), 5 (20%), 2 (8%), and 13 (52%) patients were diagnosed as having grades 1, 2, 3, and 4 gliomas according to the World Health Organization (WHO) 2021 classification, respectively. One case (4%), with a circumscribed diffuse midline glioma, H3K27-altered, had a rare molecular profile and could not be graded. IHC demonstrated H3K27M positivity, indicative of H3F3A K27M or HIST1H3B K27M mutation, in 9 (36%) patients. H3K27me3-loss was evident in 13 (52%) patients. In one patient with a grade 1 tumor that showed negative staining for H3K27M and H3K27me3 loss, numbers of EZHIP-positive cells were increased, suggesting diffuse midline glioma, H3K27-altered (WHO grade 4). H3K27me3 loss, frequency of p53 positive cells (≥10%), MIB-1 index (≥10%), and high histopathological grades significantly correlated with poor OS. These results indicate the pathological and immunohistochemical characteristics of primary spinal cord gliomas that impact prognosis.

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.