Mixed Type of Malignant Mesothelioma in an Aged Male ICR Mouse

Multiple whitish nodules in the thoracic cavity at the site of the thymus were observed in a 101-week-old male ICR mouse. In a histopathological examination, the neoplastic cells were predominantly fusiform in shape and proliferated in sarcomatoid growth patterns. Some neoplastic cells showed epithelial growth patterns, such as the ductal structures. Mitotic figures were frequently seen, and small necrotic foci and invasion to adjacent thoracic organs were noted. In Alcian blue staining, bluish materials were observed between fusiform-shaped cells and in some of the lumens of the ductal structures. In immunohistochemistry, both fusiform-shaped and ductal structure-forming cells were positive for vimentin and weakly positive to positive for cytokeratin. Based on the aforementioned findings, the thoracic nodules were diagnosed as a mixed type of malignant mesothelioma. This case was thought to be rare because of the very low occurrence of spontaneous mesothelioma in mice

Finding Desirable Substitution Box with SASQUATCH

This paper presents ``SASQUATCH\u27\u27, an open-source tool, that aids in finding an unknown substitution box (SBox) given its properties. The inspiration of our work can be directly attributed to the DCC 2022 paper by Lu, Mesnager, Cui, Fan and Wang. Taking their work as the foundation (i.e., converting the problem of SBox search to a satisfiability modulo theory instance and then invoking a solver), we extend in multiple directions (including -- but not limiting to -- coverage of more options, imposing time limit, parallel execution for multiple SBoxes, non-bijective SBox), and package everything within an easy-to-use interface. We also present ASIC benchmarks for some of the SBoxes

The mass determination of TOI-519 b: a close-in giant planet transiting a metal-rich mid-M dwarf

We report the mass determination of TOI-519 b, a transiting substellar object around a mid-M dwarf. We carried out radial velocity measurements using Subaru / InfraRed Doppler (IRD), revealing that TOI-519 b is a planet with a mass of $0.463^{+0.082}_{-0.088}~M_{\rm Jup}$. We also find that the host star is metal rich ($\rm [Fe/H] = 0.27 \pm 0.09$ dex) and has the lowest effective temperature ($T_{\rm eff}=3322 \pm 49$ K) among all stars hosting known close-in giant planets based on the IRD spectra and mid-resolution infrared spectra obtained with NASA Infrared Telescope Facility / SpeX. The core mass of TOI-519 b inferred from a thermal evolution model ranges from $0$ to $\sim30~M_\oplus$, which can be explained by both the core accretion and disk instability models as the formation origins of this planet. However, TOI-519 is in line with the emerging trend that M dwarfs with close-in giant planets tend to have high metallicity, which may indicate that they formed in the core accretion model. The system is also consistent with the potential trend that close-in giant planets around M dwarfs tend to be less massive than those around FGK dwarfs.Comment: 10 pages, 5 figures. Accepted for publication in PAS

Chemical constituents of the leaves of rabbiteye blueberry (Vaccinium ashei) and characterisation of polymeric proanthocyanidins containing phenylpropanoid units and A-type linkages

Chemical constituents of the leaves of rabbiteye blueberry (Vaccinium ashei READE) were investigated in detail. The major phenolic components were caffeoyl quinic acids, flavonol glycosides, flavan-3-ols and proanthocyanidins. Catechins and proanthocyanidins having additional phenylpropanoid units, such as cinchonains, kandelins and mururins, characterised the polyphenols of this plant. Among them, vaccinin A, an isomer of mururin A, was found to be a new compound, and the structure was characterised by spectroscopic methods. The most abundant polyphenols (11.3% of freeze-dried leaves) were oligomeric proanthocyanidins. Thiol degradation with mercaptoethanol indicated that the polymer was constituted of (+)-catechin and (-)-epicatechin as the terminal units and (-)-epicatechin, procyanidin A-2, and cinchonains Ia and Ib as the extension units. Mass spectral analysis suggested the presence of at least dodecamers with A-type linkages and phenylpropanoid moieties

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts