Intraspecific Differentiation of Rana tagoi Elucidated by Electrophoretic Analyses of Enzymes and Blood Proteins

Intraspecific differentiation of Rana tagoi was examined by electrophoretic analyses of 14 enzymes extracted from the skeletal muscles and livers and two blood proteins. A total of 194 Rana tagoi collected from seven stations in the western Japan had 22 loci controlling the enzymes and blood proteins. Of the 22 loci, those of AAT-A, AK and CK showed a single phenotype produced by a single allele. The other loci showed 2∿25 phenotypes produced by 2∿10 alleles. At the 22 loci, there were 6.9 phenotypes produced by 4.3 alleles on the average. The gene frequencies in the seven populations were examined at 19 of the 22 loci, except three loci of AAT-A, AK and CK, which consisted of a single allele. While these three loci were zero in Fst, five of the others were 0.015∿0.068,four were 0.144∿0.208,three were 0.312∿0.377,three were 0.423∿0.462,three were 0.516∿0.621 and the remaining Hb locus was 1.000 in Fst. Of the seven populations, the three island populations, the Yaku, Hirado and Oki populations, were lower in average heterozygosity than the other four land populations, the Nabara, Kurama, Omogo and Ono populations. The proportions of polymorphic loci in the seven populations were 40.9∿63.6%, 55.20n the average. The mean numbers of alleles per locus in the seven populations were 1.6∿2.5,2.0 on the average. The genetic distances among the seven populations were estimated on the basis of gene frequencies at the 22 loci. The largest distance (0.335) was found between the Yaku and Omogo populations, while the smallest (0.031) was found between the Nabara and Omogo populations. A dendrogram was drawn by the UPGMA clustering method. This dendrogram seems to indicate that the Yaku population (Rana tagoi yakushimensis) was differentiated earlier than the other six populations

The shape of disposable diaper affects spontaneous movements of lower limbs in young infants

This study examined the characteristics of young infants\u27 lower limb spontaneous movements based on differences in shape of diapers. Twenty-seven healthy infants (103 +/- 16.3 days old) were enrolled in this study. We measured the spontaneous movements of their lower limbs in four conditions (Naked, wearing Normal type diapers, wearing Type A diapers, and wearing Type B diapers). The Normal diaper has a wider waist belt than the Type A diaper, and the Type B diaper has a narrower crotch area than the Type A diaper. We observed them in seven indices (the velocity of lower limb movements, the trajectory area of knee movement in the sagittal plane and the frontal plane, the distance between both knees and between side of abdomen and knee, and correlation of velocities between side of abdomen and knee and between left and right ankles). The results showed that the velocity of the lower limb movements in the Naked condition was higher than when wearing Normal diapers. The value for the trajectory area of knee movement in sagittal plane, which reflects the range of lower leg lifting movements and closeness of such movements to the trunk, for the Type B diaper condition was higher than that for the Normal diaper condition. This result indicates that the shape of the diaper affects the spontaneous movements of the lower limbs of young infants

Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation

Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that licorice ingestion can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes. Our patient was a 51-year-old female with serious hypertension who had been taking herbal medicine containing licorice for more than one year. She was clinically diagnosed as having licorice intoxication, because she did not present with hypertension after ceasing the herbal medicine. Molecular analysis showed that she carried a missense mutation, c.40C>T, in HSD11B2. In conclusion, licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation

The Tokyo Oldest Old Survey on Total Health (TOOTH): A longitudinal cohort study of multidimensional components of health and well-being

<p>Abstract</p> <p>Background</p> <p>With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study.</p> <p>Methods/Design</p> <p>For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors.</p> <p>Discussion</p> <p>Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.</p> <p>Trial Registration</p> <p>This study has been registered in the UMIN-Clinical Trial Registry (CTR), ID: UMIN000001842.</p

CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis

The deposited article is a post-print version (author's manuscript from PMC and available in PMC 2017 May 9).This publication hasn't any creative commons license associated.This deposit is composed by the main article and the supplementary materials are present in the publisher's page in the following link: https://www.sciencedirect.com/science/article/pii/S0960982216303001?via%3Dihub#sec4Centrioles are essential for the assembly of both centrosomes and cilia. Centriole biogenesis occurs once and only once per cell cycle and is temporally coordinated with cell-cycle progression, ensuring the formation of the right number of centrioles at the right time. The formation of new daughter centrioles is guided by a pre-existing, mother centriole. The proximity between mother and daughter centrioles was proposed to restrict new centriole formation until they separate beyond a critical distance. Paradoxically, mother and daughter centrioles overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant. Here we show that in mitosis, the mitotic kinase CDK1-CyclinB binds STIL and prevents formation of the PLK4-STIL complex and STIL phosphorylation by PLK4, thus inhibiting untimely onset of centriole biogenesis. After CDK1-CyclinB inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL in G1, allowing pro-centriole assembly in the subsequent S phase. Our work shows that complementary mechanisms, such as mother-daughter centriole proximity and CDK1-CyclinB interaction with centriolar components, ensure that centriole biogenesis occurs once and only once per cell cycle, raising parallels to the cell-cycle regulation of DNA replication and centromere formation.ERC grant: (ERC-2010-StG-261344); FCT grants: (FCT Investigator, EXPL/BIM-ONC/0830/2013, PTDC/SAU-BD/105616/2008); EMBO installation grant.info:eu-repo/semantics/publishedVersio

Inhibitory effect of Makomotake components on inflammation

Zizania latifolia (wild rice) is native to Eastern and Southeastern Asia. The fungus Ustilago esculenta penetrates this aquatic perennial grass. Makomotake refers to penetration of the Zizania latifolia shoot by Ustilago esculenta. Recent studies demonstrated that Zizania latifolia extracts exhibit diverse biological activities, such as anti–oxidant effects. The purpose of this study was to investigate the anti–inflammatory effect of Makomotake on endotoxin–induced uveitis (EIU) in mice. After the daily oral administration of Makomotake for 5 days, EIU was induced by the injection of a lipopolysaccharide (LPS) into the footpad of mice. At 24 hours–after injection, the eyes were enucleated and cells infiltrating the anterior chamber and vitreous cavity were counted histologically. Makomotake administration significantly reduced the total number of infiltrating cells. In addition, Makomotake suppressed the production of interleukin (IL)–1 β and tumor necrosis factor (TNF)–α in murine macrophages induced by LPS. Our findings show that Makomotake can be used as an anti–inflammatory agent against EIU, and that it may be useful for the treatment of acute uveitis

Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice

Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP−/−) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP−/− mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP−/− mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP−/− mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP−/− mice, which could in part account for the metabolic phenotype in KRAP−/− mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases

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