Cosmic Ray Production of 6^6Li by Structure Formation Shocks in the Early Galaxy

We discuss the production of the element $^6$Li in the early Galaxy by cosmic rays accelerated at structure formation shocks, driven by the hierarchical merging of sub-Galactic halos during Galaxy formation. The salient features of this scenario are discussed and compared with observations of $^6$Li in metal-poor halo stars, including a recent Subaru HDS result on the star HD140283. Some unique predictions of the model are clearly testable by future observations and may also provide important insight into how the Galaxy formed.Comment: 4 pages, 1 figure; to appear in Nuc. Phys. A; talk at Nuclei in the Cosmos 7, Fuji-Yoshida, Japan 200

Expression Profiling without Genome Sequence Information in a Non-Model Species, Pandalid Shrimp (Pandalus latirostris), by Next-Generation Sequencing

While the study of phenotypic variation is a central theme in evolutionary biology, the genetic approaches available to understanding this variation are usually limited because of a lack of genomic information in non-model organisms. This study explored the utility of next-generation sequencing (NGS) technologies for studying phenotypic variations between 2 populations of a non-model species, the Hokkai shrimp (Pandalus latirostris; Decapoda, Pandalidae). Before we performed transcriptome analyses using NGS, we examined the genetic and phenotypic differentiation between the populations. Analyses using microsatellite DNA markers suggested that these populations genetically differed from one another and that gene flow is restricted between them. Moreover, the results of our 4-year field observations indicated that the egg traits varied genetically between the populations. Using mRNA extracted from the ovaries of 5 females in each population of Hokkai shrimp, we then performed a transcriptome analysis of the 2 populations. A total of 13.66 gigabases (Gb) of 75-bp reads was obtained. Further, 58,804 and 33,548 contigs for the first and second population, respectively, and 47,467 contigs for both populations were produced by de novo assembly. We detected 552 sequences with the former approach and 702 sequences with the later one; both sets of sequences showed greater than twofold differences in the expression levels between the 2 populations. Twenty-nine sequences were found in both approaches and were considered to be differentially expressed genes. Among them, 9 sequences showed significant similarity to functional genes. The present study showed a de novo assembly approach for the transcriptome of a non-model species using only short-read sequence data, and provides a strategy for identifying sequences showing significantly different expression levels between populations

Limitations in the use of rifampicin-gelatin grafts against virulent organisms

AbstractObjective: Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model. Materials and Methods: Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone. Results: In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 ± 0.3 mm, 36.0 ± 0.2 mm, and 11.8 ± 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 ± 1.1 mm and 7.6 ± 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 ± 0.2 mm and 18.5 ± 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitary concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection. Conclusion: These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitary concentration MRSA strains or poor susceptibility. (J Vasc Surg 2002;35:779-85.

多発性硬化症における髄液中Guanase活性

Thirty-eight CSF specimens obtained from 33 patients with multiple sclerosis (MS) (20 definite, 18 probable; 20 active, 18 inactive) were subjected to the measurement of guanase activity, cell count and concentrations of total protein and Ig G. There was no difference in cell count and total protein concentration between MS and normal controls (n=14). The guanase activity, however, was significantly higher in MS as compared with normal controls (p<0.05). In addition, active MS revealed significantly elevated guanase activity, total protein and Ig G as compared with inactive MS (p<0.05). Serial guanase determinations together with Kurtzke\u27s expanded disability status scales in 5 MS patients supported the idea that CSF guanase activity reflects the disease activity more appropriately than other parameters in CSF

Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC

STUDIES ON THE PRODUCTIVITY OF SOIL ANIMALS IN PASOH FOREST RESERVE, WEST MALAYSIA : V. SEASONAL CHANGE IN THE DENSITY AND BIOMASS OF SOIL MACROFAUNA: OLIGOCHAETA, HIRUDINEA AND ARTHROPODA(Natural science)

本報は,IBP(国際生物学事業計画)のひとつとして,マレーシア・日本・イギリスが共同で研究した熱帯多雨林の研究のひとつで,土壌動物に関する一連の報告のひとつである。1971年4月から1972年8月までの間に,毎月5個,計68個の土壌塊を検査し,次の結果を得た。検査された土壌塊は,面積50cm×50cm,深さ20cmを単位とするものである。1.個体数が最も多いのは,アリを含む膜翅類の動物で全体の85.4%を占め,第2位は鞘翅類の幼虫の4.1%であった。現存量では膜翅類の26.6%,鞘翅類の成虫19.4%となった。2.全土壌大形動物の平均密度は1903個体/m^2,同現存量は3.1g/m^2であった。3.季節変化はすべての生物群について見られる共通点は明瞭ではないが,密度は6～8月に高く,現存量はむしろ7月に高くなっていた。4.Iδ-indexを用いた検討によると,ヒル類・サソリ類が少いが均等に分布し,貧毛類・半翅類・直翅類・鱗翅類・ヤスデ類・ムカデ類・ゴキブリ類についてはいくぶんかたまり気味であったが,かなり分散していることがわかった。アジを含む膜翅類とシロアリ(等翅類)はともに強い集合性を示していた。5.落葉が堆積している場所と,落葉がない場所との密度や現存量を比較してみたが,直翅類や鱗翅類幼虫については差が認められ難く,メクラグモ類・貧毛類・鞘翅類の幼虫と成虫・クモ類は集合性には差がなかったが,落葉のある土壌の方が高密度であった。双翅類の幼虫やアリを含む膜翅類は落葉の多い土壌の方が高い集合性を示した。6.これらの資料とA_(1979)のシロアリの密度や現存量の資料を加えて,この地域の土壌大形動物の密度は5000～5700個体/m^2同現存量は11.8～13.2g/m^2(湿重量)と推定することができる。ここに推定された密度は,今迄の報告にくらべて大きい値をとっているが,アリ・シロアリ以外の動物群のみを比較するとW_ et al. (1966)のタイにおける値とほぼ同様になる

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

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)