Predominance of porcine rotavirus G9 in Japanese piglets with diarrhea: Close relationship of their VP7 genes with those of recent human G9 strains

Type G9 of group A rotavirus (GAR) was shown to be predominant in a survey of VP7 (G) and VP4 (P) genotypes among porcine GARs associated with outbreaks of diarrhea in young pigs in Japan between 2000 and 2002. Comparison of the G9 VP7 gene sequences showed that the porcine G9 strains were more closely related to human G9 strains reemerging globally since the mid-1990s than to those from the mid-1980s. The VP7 gene sequences of porcine G9 strains from different farms were divergent (6.1 to 7.2% diference in nucleotides), suggesting that these G9 VP7 genes were not the result of recent introduction into the porcine population. Regarding the P genotype specificities of porcine G9 strains, while the majority of strains were close to unusual porcine P types (P[13] and P[23]), two strains were of the P[6] type, which has closer sequence identity with the human AU19 strain than with the porcine Gottfried strain. These unexpected results suggest that G9 GARs in the porcine population have spread more widely than previously thought and that the VP7 genes of porcine G9 strains and those of some human G9 strains detected recently may have a common progenitor.Facultad de Ciencias Veterinaria

Predominance of porcine rotavirus G9 in Japanese piglets with diarrhea: Close relationship of their VP7 genes with those of recent human G9 strains

Type G9 of group A rotavirus (GAR) was shown to be predominant in a survey of VP7 (G) and VP4 (P) genotypes among porcine GARs associated with outbreaks of diarrhea in young pigs in Japan between 2000 and 2002. Comparison of the G9 VP7 gene sequences showed that the porcine G9 strains were more closely related to human G9 strains reemerging globally since the mid-1990s than to those from the mid-1980s. The VP7 gene sequences of porcine G9 strains from different farms were divergent (6.1 to 7.2% diference in nucleotides), suggesting that these G9 VP7 genes were not the result of recent introduction into the porcine population. Regarding the P genotype specificities of porcine G9 strains, while the majority of strains were close to unusual porcine P types (P[13] and P[23]), two strains were of the P[6] type, which has closer sequence identity with the human AU19 strain than with the porcine Gottfried strain. These unexpected results suggest that G9 GARs in the porcine population have spread more widely than previously thought and that the VP7 genes of porcine G9 strains and those of some human G9 strains detected recently may have a common progenitor.Facultad de Ciencias Veterinaria

Predominance of porcine rotavirus G9 in Japanese piglets with diarrhea: Close relationship of their VP7 genes with those of recent human G9 strains

Type G9 of group A rotavirus (GAR) was shown to be predominant in a survey of VP7 (G) and VP4 (P) genotypes among porcine GARs associated with outbreaks of diarrhea in young pigs in Japan between 2000 and 2002. Comparison of the G9 VP7 gene sequences showed that the porcine G9 strains were more closely related to human G9 strains reemerging globally since the mid-1990s than to those from the mid-1980s. The VP7 gene sequences of porcine G9 strains from different farms were divergent (6.1 to 7.2% diference in nucleotides), suggesting that these G9 VP7 genes were not the result of recent introduction into the porcine population. Regarding the P genotype specificities of porcine G9 strains, while the majority of strains were close to unusual porcine P types (P[13] and P[23]), two strains were of the P[6] type, which has closer sequence identity with the human AU19 strain than with the porcine Gottfried strain. These unexpected results suggest that G9 GARs in the porcine population have spread more widely than previously thought and that the VP7 genes of porcine G9 strains and those of some human G9 strains detected recently may have a common progenitor.Facultad de Ciencias Veterinaria

High Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study

The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤-6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample

Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells

Background Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible fatty acid binding protein 7 (FABP7) increased reactive oxygen species (ROS) in breast cancer cells. ROS are known to induce beige adipocyte differentiation. Methods We investigated the association of tumor hypoxia, FABP7, and UCP1 across breast cancer patients using METABRIC and TCGA data sets. Furthermore, using a breast cancer cell line, HCC1806, we tested the effect of FABP7 knockdown on cellular physiology including thermogenesis. Results We found a strong mutual exclusivity of FABP7 and UCP1 expression both in METABRIC and in TCGA, indicating major metabolic phenotypic differences. FABP7 was preferentially distributed in poorly differentiated-, estrogen receptor (ER) negative tumors. In contrast, UCP1 was highly expressed in normal ducts and well-differentiated-, ER positive-, less hypoxic tumors. In the cell line-based experiments, UCP1 and its transcriptional regulators were upregulated upon FABP7 knockdown. UCP1 was induced in about 20% of cancer cells, and the effect was increased further in hypoxia. UCP1 depolarized mitochondrial membranes at the site of expression. UCP1 induction was associated with the increase in proton leak, glycolysis, and maximal respiration, mimicking the typical energy profile of beige adipocytes. Most importantly, UCP1 induction elevated cancer cell temperature associated with increased vulnerability to hypoxia and gamma-irradiation. Conclusions We demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients' outcomes and the relationship to other metabolic pathways

Detection of Mycobacterium leprae DNA from Archaeological Skeletal Remains in Japan Using Whole Genome Amplification and Polymerase Chain Reaction

BACKGROUND: Identification of pathogen DNA from archaeological human remains is a powerful tool in demonstrating that the infectious disease existed in the past. However, it is very difficult to detect trace amounts of DNA remnants attached to the human skeleton, especially from those buried in a humid atmosphere with a relatively high environmental temperature such as in Asia. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate Mycobacterium leprae DNA from archaeological skeletal remains in Japan by polymerase chain reaction, DNA sequencing and single nucleotide polymorphism (SNP) analysis. In addition, we have established a highly sensitive method of detecting DNA using a combination of whole genome amplification and polymerase chain reaction, or WGA-PCR, which provides superior sensitivity and specificity in detecting DNA from trace amounts of skeletal materials. CONCLUSION/SIGNIFICANCE: We have detected M. leprae DNA in archaeological skeletal remains for the first time in the Far East. Its SNP genotype corresponded to type 1; the first detected case worldwide of ancient M. leprae DNA. We also developed a highly sensitive method to detect ancient DNA by utilizing whole genome amplification

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

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