Boulder size and shape distributions on asteroid Ryugu

In 2018, the Japanese spacecraft Hayabusa2, arrived at the small asteroid Ryugu. The surface of this C-type asteroid is covered with numerous boulders whose size and shape distributions are investigated in this study. Using a few hundred Optical Navigation Camera (ONC) images with a pixel scale of approximately 0.65 m, we focus on boulders greater than 5m in diameter. Smaller boulders are also considered using five arbitrarily chosen ONC close-up images with pixel scales ranging from 0.7 to 6 cm. Across the entire surface area (~2.7 km2) of Ryugu, nearly 4400 boulders larger than 5m were identified. Boulders appear to be uniformly distributed across the entire surface, with some slight differences in latitude and longitude. At ~50 km−2, the number density of boulders larger than 20m is twice as large as on asteroid Itokawa (or Bennu). The apparent shapes of Ryugu's boulders resemble laboratory impact fragments, with larger boulders being more elongated. The ratio of the total volume of boulders larger than 5m to the total excavated volume of craters larger than 20m on Ryugu can be estimated to be ~94%, which is comparatively high. These observations strongly support the hypothesis that most boulders found on Ryugu resulted from the catastrophic disruption of Ryugu's larger parent body, as described in previous papers (Watanabe et al., 2019; Sugita et al.,2019). The cumulative size distribution of boulders larger than 5 m has a power-index of −2.65 ± 0.05, which is comparatively shallow compared with other asteroids visited by spacecraft. For boulders smaller than 4 m, the power-index is even shallower and ranges from −1.65 ± 0.05 to −2.01 ± 0.06. This particularly shallow power-index implies that some boulders are buried in Ryugu's regolith. Based on our observations, we suggest that boulders near the equator might have been buried by the migration of finer material and, as a result, the number density of boulders larger than 5 m in the equatorial region is lower than at higher latitudes

A case of mandibular fracture including coronoid process fracture

The incidence of mandibular fractures is the highest among facial bone fractures. Addi-tionally, most of mandibular fractures occur in the mandibular angle and condylar process. On the other hand, the incidence of fracture of coronoid process is extremely low. We experienced a case of mandibular fractures involving mandibular body, condylar process as well as the coronoid process in a man aged 3₉–years–old who had received strong direct external force to the mandible. Mandibular fractures usually occur in the condylar process and mandibular angle because direct external force is more likely to transmit to these re-gions. Based on the classification of mandibular fractures, the incidence of mandibularfractures involving coronoid process increases with an increased number of fractures lines that means complicated fracture. At the viewpoint of anatomical portion, direct external force dose not transmit to coronoid process; however, it is possible that direct external force may transmit coronoid process in the case of complicated fracture. In this case report, we considered the potential mechanism of fracture of coronoid process by using a three–dimensional finite element model of a human mandible stress distribution analysis

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

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Low molecular weight (C1-C10) monocarboxylic acids, dissolved organic carbon and major inorganic ions in alpine snow pit sequence from a high mountain site, central Japan

Snowpack samples were collected from a snow pit sequence (6 m in depth) at the Murodo-Daira site near the summit of Mt. Tateyama, central Japan, an outflow region of Asian dusts. The snow samples were analyzed for a homologous series of low molecular weight normal (C1-C10) and branched (iC4-iC6) monocarboxylic acids as well as aromatic (benzoic) and hydroxy (glycolic and lactic) acids, together with major inorganic ions and dissolved organic carbon (DOC). The molecular distributions of organic acids were characterized by a predominance of acetic (range 7.8-76.4 ng/g-snow, av. 34.8 ng/g) or formic acid (2.6-48.1 ng/g, 27.7 ng/g), followed by propionic acid (0.6-5.2 ng/g, 2.8 ng/g). Concentrations of normal organic acids generally decreased with an increase in carbon chain length, although nonanoic acid (C9) showed a maximum in the range of C5-C10. Higher concentrations were found in the snowpack samples containing dust layer. Benzoic acid (0.18-4.1 ng/g, 1.4 ng/g) showed positive correlation with nitrate (r = 0.70), sulfate (0.67), Na+ (0.78), Ca2+ (0.86) and Mg+ (0.75), suggesting that this aromatic acid is involved with anthropogenic sources and Asian dusts. Higher concentrations of Ca2+ and SO4^[2-] were found in the dusty snow samples. We found a weak positive correlation (r = 0.43) between formic acid and Ca2+, suggesting that gaseous formic acid may react with Asian dusts in the atmosphere during long-range transport. However, acetic acid did not show any positive correlations with major inorganic ions. Hydroxyacids (0.03-5.7 ng/g, 1.5 ng/g) were more abundant in the granular and dusty snow. Total monocarboxylic acids (16-130 ng/g, 74 ng/g) were found to account for 1-6% of DOC (270-1500 ng/g, 630 ng/g) in the snow samples