Replicated association of the single nucleotide polymorphism in EDG1 with marbling in three general populations of Japanese Black beef cattle

<p>Abstract</p> <p>Background</p> <p>Marbling, defined by the amount and the distribution of intramuscular fat and measured as beef marbling score (BMS), is an economically important trait of beef cattle in Japan. We recently reported that a single nucleotide polymorphism (SNP), namely, <it>c.-312A>G</it>, in the <it>endothelial differentiation</it>, <it>sphingolipid G-protein-coupled receptor</it>, <it>1 </it>(<it>EDG1</it>) gene was associated with the BMS level in the Japanese Black beef cattle population of Oita prefecture, with the <it>G </it>allele being associated with a high level of the BMS. Thus, the <it>c.-312A>G </it>SNP seems to be a candidate marker for marker-assisted selection. In this study, we investigated whether this association could be replicated in 3 other independent Japanese Black cattle populations and analyzed the effect of the SNP genotypes on the carcass traits other than the BMS.</p> <p>Findings</p> <p>Statistically significant differences in the BMS level were detected among the genotypes of the <it>c.-312A>G </it>SNP in the Japanese black beef cattle populations of Miyazaki (<it>P </it>= 0.0377) and Nagasaki (<it>P </it>= 0.0012) prefectures, and marginal difference was detected in the Kagoshima prefecture population (<it>P </it>= 0.0786). The <it>G </it>allele in the SNP was associated with an increase in the BMS level.</p> <p>The <it>G </it>allele also seemed to have a favorable influence, if any, on the carcass weight, rib eye area and rib thickness of the cattle populations.</p> <p>Conclusions</p> <p>These findings suggest that the association of the <it>c.-312A>G </it>SNP with the BMS level in the Japanese Black beef cattle population was replicated in other beef cattle populations, and revealed favorable effects of the <it>G </it>allele on the beef productivity in the general Japanese Black beef cattle population. Thus, we concluded that the <it>c.-312A>G </it>SNP is useful for effective marker-assisted selection to increase the BMS level in Japanese Black beef cattle.</p

PROPOSAL OF UNILATERAL SINGLE-FLUX-QUANTUM LOGIC GATE

A new type of single flux quantum logic gate is proposed, which can perform unilateral propagation of signal without using three-phase clock. This gate is designed to be built with bridge-type Josephson junctions. A basic logic gate consists of two one-junction interferometers coupled by superconducting interconnecting lines, and the logical states are represented by zero or one quantized fluxoid in one of one-junction interferometers. The bias current of the unequal magnitude to each of the two one-junction interferometers results in unilateral signal flow. By adjusting design parameters such as the ratio of the critical current of Josephson junctions and the inductances, circuits with the noise immunity of greater than 50% with respect to the bias current have been designed. Three cascaded gates were modeled and simulated on a computer, and the unilateral signal flow was confirmed. The simulation also shows that a switching delay about 2 picoseconds is feasible

Reconciling biodiversity conservation and flood risk reduction : The new strategy for freshwater protected areas

Aim: Natural disaster risk reduction (DRR) is becoming a more important function of protected area (PAs) for current and future global warming. However, biodiversity conservation and DRR have been handled separately and their interrelationship has not been explicitly addressed. This is mainly because, due of prevailing strategies and criteria for PA placement, a large proportion of PAs are currently located far from human-occupied areas, and habitats in human-occupied areas have been largely ignored as potential sites for conservation despite their high biodiversity. If intensely developed lowland areas with high flooding risk overlap with important sites for biodiversity conservation, it would be reasonable to try to harmonize biodiversity conservation and human development in human-inhabited lowland areas. Here, we examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and whether human-inhabited lowland flood risk management sites might be suitable to designate as freshwater protected areas (FPAs). Location: Across Japan. Methods: We examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and analysed the relationship between candidate sites for new FPAs and flood disaster risk and land use intensity at a national scale across Japan based on distribution data for 131 freshwater fish species and 1395 macroinvertebrate species. Results: We found that extant PAs overlapped with approximately 30% of conservation-priority grid cells (1 km2) for both taxa. Particularly for red-listed species, only one species of freshwater fish and three species of macroinvertebrate achieved the representation target within extant PAs. Moreover, more than 40% of candidate conservation-priority grid cells were located in flood risk and human-occupied areas for both taxa. Main conclusions: Floodplain conservation provides suitable habitat for many freshwater organisms and helps control floodwaters, so establishing new FPAs in areas with high flood risk could be a win-win strategy for conserving freshwater biodiversity and enhancing ecosystem-based DRR (eco-DRR)

Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

Prognostic Model for Hepatocellular Carcinoma with Time-Dependent Factors

The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n＝336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n＝227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time-dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC

In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production

Clostridium perfringens type A is a common source of food poisoning (FP) and non-food-borne (NFB) gastrointestinal diseases in humans. In the intestinal tract, the vegetative cells sporulate and produce a major pathogenic factor, C. perfringens enterotoxin (CPE). Most type A FP isolates carry a chromosomal cpe gene, whereas NFB type A isolates typically carry a plasmid-encoded cpe. In vitro, the purified CPE protein binds to a receptor and forms pores, exerting a cytotoxic activity in epithelial cells. However, it remains unclear if CPE is indispensable for C. perfringens cytotoxicity. In this study, we examined the cytotoxicity of cpe-harboring C. perfringens isolates co-cultured with human intestinal epithelial Caco-2 cells. The FP strains showed severe cytotoxicity during sporulation and CPE production, but not during vegetative cell growth. While Caco-2 cells were intact during co-culturing with cpe-null mutant derivative of strain SM101 (a FP strain carrying a chromosomal cpe gene), the wild-type level cytotoxicity was observed with cpe-complemented strain. In contrast, both wild-type and cpe-null mutant derivative of the NFB strain F4969 induced Caco-2 cell death during both vegetative and sporulation growth. Collectively, the Caco-2 cell cytotoxicity caused by C. perfringens strain SM101 is considered to be exclusively dependent on CPE production, whereas some additional toxins should be involved in F4969-mediated in vitro cytotoxicity.Keywords: Cytotoxicity, Enterotoxin, Food poisoning, Caco-2 cells, Clostridium perfringensKeywords: Cytotoxicity, Enterotoxin, Food poisoning, Caco-2 cells, Clostridium perfringen

CFHandVIPR2as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy

中心性漿液性網脈絡膜症に関わる遺伝子変異を発見 --日本人に多い特殊なタイプの加齢黄斑変性の原因も解明--. 京都大学プレスリリース. 2018-05-31.Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3, 418 individuals followed by TaqMan assays in 2, 692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10−10 and 6.75 × 10−8, respectively). Case–control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10−5 and 5.14 × 10−5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology

Genetic Isolation between the Western and Eastern Pacific Populations of Pronghorn Spiny Lobster Panulirus penicillatus

The pronghorn spiny lobster, Panulirus penicillatus, is a circumtropical species which has the widest global distribution among all the species of spiny lobster, ranging throughout the entire Indo-Pacific region. Partial nucleotide sequences of mitochondrial DNA COI (1,142–1,207 bp) and 16S rDNA (535–546 bp) regions were determined for adult and phyllosoma larval samples collected from the Eastern Pacific (EP)(Galápagos Islands and its adjacent water), Central Pacific (CP)(Hawaii and Tuamotu) and the Western Pacific (WP)(Japan, Indonesia, Fiji, New Caledonia and Australia). Phylogenetic analyses revealed two distinct large clades corresponding to the geographic origin of samples (EP and CP+WP). No haplotype was shared between the two regional samples, and average nucleotide sequence divergence (Kimura's two parameter distance) between EP and CP+WP samples was 3.8±0.5% for COI and 1.0±0.4% for 16S rDNA, both of which were much larger than those within samples. The present results indicate that the Pacific population of the pronghorn spiny lobster is subdivided into two distinct populations (Eastern Pacific and Central to Western Pacific), with no gene flow between them. Although the pronghorn spiny lobster have long-lived teleplanic larvae, the vast expanse of Pacific Ocean with no islands and no shallow substrate which is known as the East Pacific Barrier appears to have isolated these two populations for a long time (c.a. 1MY)

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