Mass Measurement of the Decaying Bino at the LHC

In some class of supersymmetric (SUSY) models, the neutral Wino becomes the lightest superparticle and the Bino decays into the Wino and standard-model particles. In such models, we show that the measurement of the Bino mass is possible if the short charged tracks (with the length of O(10 cm)) can be identified as a signal of the charged-Wino production. We pay particular attention to the anomaly-mediated SUSY-breaking (AMSB) model with a generic form of K\"ahler potential, in which only the gauginos are kinematically accessible superparticles to the LHC, and discuss the implication of the Bino mass measurement for the test of the AMSB model.Comment: 13 pages, 3 figures, 1 tabl

Ecotoxicological assessment of palm oil mill effluent final discharge by zebrafish (Danio rerio) embryonic assay

Most palm oil mills adopted conventional ponding system, including anaerobic, aerobic, facultative and algae ponds, for the treatment of palm oil mill effluent (POME). Only a few mills installed a bio-polishing plant to treat POME further before its final discharge. The present study aims to determine the quality and toxicity levels of POME final discharge from three different mills by using conventional chemical analyses and fish (Danio rerio) embryo toxicity (FET) test. The effluent derived from mill A which installed with a bio-polishing plant had lower values of BOD, COD and TSS at 45 mg/L, 104 mg/L, and 27 mg/L, respectively. Only mill A nearly met the industrial effluent discharge standard for BOD. In FET test, effluent from mill A recorded low lethality and most of the embryos were malformed after hatching (half-maximal effective concentration (EC50) = 20%). The highest toxicity was observed from the effluent of mill B and all embryos were coagulated after 24 h in samples greater than 75% of effluent (38% of half-maximal lethal concentration (LC50) at 96 h). The embryos in the effluent from mill C recorded high mortality after hatching, and the survivors were malformed after 96 h exposure (LC50 = 26%). Elemental analysis of POME final discharge samples showed Cu, Zn, and Fe concentrations were in the range of 0.10–0.32 mg/L, 0.01–0.99 mg/L, and 0.94–4.54 mg/L, respectively and all values were below the effluent permissible discharge limits. However, the present study found these metals inhibited D. rerio embryonic development at 0.12 mg/L of Cu, and 4.9 mg/L of Fe for 96 h-EC50. The present study found that bio-polishing plant installed in mill A effectively removing pollutants especially BOD and the FET test was a useful method to monitor quality and toxicity of the POME final discharge samples

Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients

Objectives Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years. Methods Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. Results In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. Conclusions Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia

当科が報告したインシデントレポートの分析

当院では 2010年7月からコンピューターを用いたインシデント報告システムを導入し,職員が匿名でインシデントを報告できる体制となっている.本体制運用開始後10年間に当科で報告されたインシデントレポート55件を患者影響レベルに従って8段階に分類した.レベル0は6件(10.9%),レベル1は14件 (25.5%),レベル2は13件(23.6%),レベル 3a は10件(18.2%),レベル3bは8件(14.5%),レベル4aは0件(0%),レベ4bは3件(5.4%),レベ5は1 件(1.8%)であった.当科におけるレベル別報告件数の比率は，重大なアクシデントと中等度のエラーと300のヒヤリ・ハットの比率が1：29：300であるというハインリッヒの法則に則っていなかった.しかし当科では2010年から2020年にかけてヒヤリ・ハット報告数は増加しているため,インシデントを報告する習慣が身につきつつあると考えられた.今後,より積極的に報告を行うように，職員へのさらなる啓蒙活動が医療事故の防止のために重要であると考えられた.In July 2010,we introduced a computerized incident reporting system, which allows staff to report incidents anonymously. The 55 incidents reported in our department during the first 10 years of operation of this system were classified into 8 levels according to the patient impact level. Level 0 was 6 incidents (10.9%),level 1 was 14 incidents (25.5%),level 2 was 13 incidents (23.6%),level 3a was 10 incidents (18.2%),level 3b was 8 incidents (14.5%),level 4a was 0 incidents (0%),level 4b was 3 incidents (5.4%),and level 5 was 1 incident (1.8%).The ratio of the number of reports by level in our department did not follow Heinrich\u27s law, which states that the ratio of serious incidents to moderate errors and 300 near-misses is 1:29:300.However,the number of Hiyari-Hatto reports increased from 2010 to 2020 in our department, suggesting that the habit of reporting incidents is becoming more common. In the future, it will be important to educate the staff to report more actively in order to prevent medical accidents

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Freshwater mussels (Bivalvia: Unionidae) from the rising sun (Far East Asia): phylogeny, systematics, and distribution

Freshwater mussels (Bivalvia: Unionidae) is a diverse family with around 700 species being widespread in the Northern Hemisphere and Africa. These animals fulfill key ecological functions and provide important services to humans. Unfortunately, populations have declined dramatically over the last century, rendering Unionidae one of the world’s most imperiled taxonomic groups. In Far East Asia (comprising Japan, Korea, and Eastern Russia), conservation actions have been hindered by a lack of basic information on the number, identity, distribution and phylogenetic relationships of species. Available knowledge is restricted to studies on national and sub-national levels. The present study aims to resolve the diversity, biogeography and evolutionary relationships of the Far East Asian Unionidae in a globally comprehensive phylogenetic and systematic context.We reassessed the systematics of all Unionidae species in the region, including newly collected specimens from across Japan, South Korea, and Russia, based on molecular (including molecular species delineation and a COI + 28S phylogeny) and comparative morphological analyses. Biogeographical patterns were then assessed based on available species distribution data from the authors and previous reference works.We revealed that Unionidae species richness in Far East Asia is 30% higher than previously assumed, counting 43 species (41 native + 2 alien) within two Unionidae subfamilies, the Unioninae (32 + 1) and Gonideinae (9 + 1). Four of these species are new to science, i.e. Beringiana gosannensis sp. nov., Beringiana fukuharai sp. nov., Buldowskia kamiyai sp. nov., and Koreosolenaia sitgyensis gen. & sp. nov. We also propose a replacement name for Nodularia sinulata, i.e. Nodularia breviconcha nom. nov. and describe a new tribe (Middendorffinaiini tribe nov.) within the Unioninae subfamily. Biogeographical patterns indicate that this fauna is related to that from China south to Vietnam until the Mekong River basin. The Japanese islands of Honshu, Shikoku, Kyushu, Hokkaido, and the Korean Peninsula were identified as areas of particularly high conservation value, owing to high rates of endemism, diversity and habitat loss. The genetically unique species within the genera Amuranodonta, Obovalis, Koreosolenaia gen. nov., and Middendorffinaia are of high conservation concern

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

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

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