Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and ...low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants (SLC27A3 and CYP26B1; P
< 2.5 × 10
). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations.
Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly ...associated with obesity (P < 5.0 × 10
), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19
cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 × 10
, r
= 0.18) and between BMI and multiple complex diseases. These findings provide genetic evidence that lymphocytes are relevant to body weight regulation and offer insights into the pathogenesis of obesity.
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IJS, NUK, SBMB, UL, UM, UPUK
The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, ...it will be useful to construct population-level allele frequency panels with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first large-scale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.
Gut microbiota influence the host immune system and are associated with various diseases. In recent years, postmenopausal bone loss has been suggested to be related to gut microbiota. In the present ...study, we investigated the treatment effect of the probiotic Bacillus subtilis C-3102 (C-3102) on bone mineral density (BMD) and its influence on gut microbiota in healthy postmenopausal Japanese women. Seventy-six healthy postmenopausal Japanese women were treated with a placebo or C-3102 spore-containing tablets for 24 weeks. When compared with the placebo, C-3102 significantly increased total hip BMD (placebo = 0.83 ± 0.63%, C-3102 = 2.53 ± 0.52%, p=0.043). There was a significant group-by-time interaction effect for urinary type I collagen cross-linked N-telopeptide (uNTx) (p=0.033), a marker of bone resorption. Specifically, the C-3102 group showed significantly lower uNTx when compared with the placebo group at 12 weeks of treatment (p=0.015). In addition, in the C-3102 group, there was a trend towards a decrease in the bone resorption marker tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) when compared with the placebo group at 12 weeks of treatment (p=0.052). The relative abundance of genus Bifidobacterium significantly increased at 12 weeks of treatment compared with the baseline in the C-3102 group. The relative abundance of genus Fusobacterium was significantly decreased in the C-3102 group at 12 and 24 weeks of treatment compared with the baseline. These data suggested that C-3102 improves BMD by inhibiting bone resorption and modulating gut microbiota in healthy postmenopausal women.
Postoperative peritoneal adhesion (PPA) is a prevalent incidence that generally happens during the healing process of traumatized tissues. It causes multiple severe complications such as intestinal ...obstruction, chronic abdominal pain, and female infertility. To prevent PPA, several antiadhesion materials and drug delivery systems composed of biomaterials are used clinically, and clinical antiadhesive is one of the important applications nowadays. In addition to several commercially available materials, like film, spray, injectable hydrogel, powder, or solution type have been energetically studied based on natural and synthetic biomaterials such as alginate, hyaluronan, cellulose, starch, chondroitin sulfate, polyethylene glycol, polylactic acid, etc. Moreover, many kinds of animal adhesion models, such as cecum abrasion models and unitary horn models, are developed to evaluate new materials’ efficacy. A new animal adhesion model based on hepatectomy and conventional animal adhesion models is recently developed and a new adhesion barrier by this new model is also developed. In summary, many kinds of materials and animal models are studied; thus, it is quite important to overview this field's current progress. Here, PPA is reviewed in terms of the species of biomaterials and animal models and several problems to be solved to develop better antiadhesion materials in the future are discussed.
Postoperative peritoneal adhesion (PPA) is a prevalent and severe pathological condition. Different preventive strategies based on natural polysaccharides and their derivatives with synthetic polymers are available in the injectable hydrogel, solid sheet, sponge, and solutions. The antiadhesion efficacy of materials evaluates using different animal models. The effectiveness of antiadhesion barriers with better handling is expected in clinical application.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of ...efficient isolation methods and the loss of innate characteristics in vitro. We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs. We performed a 'two-step' microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-3'-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium. However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.
Abstract
In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference ...Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. At that time, jMorp mainly consisted of metabolome data; however, now genome, methylome, and transcriptome data have been integrated in addition to the enhancement of the number of samples for the metabolome data. For genomic data, jMorp provides a Japanese reference sequence obtained using de novo assembly of sequences from three Japanese individuals and allele frequencies obtained using whole-genome sequencing of 8,380 Japanese individuals. In addition, the omics data include methylome and transcriptome data from ∼300 samples and distribution of concentrations of more than 755 metabolites obtained using high-throughput nuclear magnetic resonance and high-sensitivity mass spectrometry. In summary, jMorp now provides four different kinds of omics data (genome, methylome, transcriptome, and metabolome), with a user-friendly web interface. This will be a useful scientific data resource on the general population for the discovery of disease biomarkers and personalized disease prevention and early diagnosis.
A simple method for estimating the contributions of mineral dust to PM2.5, PM10, or TSP is presented. The method is based on the assumption of external mixing of two types of particles with different ...PM2.5/PM10 ratios, The method was applied to local and transported dust events observed in Tsukuba, Japan, and was compared with collocated polarization lidar measurements. The method was then applied to three dust events that occurred in Oki, Rishiri, and Ochiishi,Japan, in 2012. The results showed that the method was useful for detecting mineral dust and for qualitatively describing the mixing of dust with anthropogenic aerosols.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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•Dynamical stability of one-dimensional fullerene polymers is investigated.•Using the Tersoff potential, the phonon dispersion relations are computed.•Among 54 models previously ...proposed, only seven models are stable.•Low-temperature specific heat is also discussed.
We theoretically investigate the dynamical stability of one-dimensional fullerene polymers by computing the phonon dispersion relations within the atomistic approach. We find that only seven models among 54 models proposed previously (Noda et al., 2015) are dynamically stable. We show that the low temperature specific heat of them is proportional to the square root of the temperature in a wider range of temperature compared to the case of single-walled carbon nanotubes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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