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.
Purpose To clarify the inefficiency of wide-based walking from kinematic and exercise physiology perspectives. Participants and Methods Participants consisted of 20 healthy male university students ...who performed treadmill walking under conditions of normal walking and wide-based walking (20-cm stride width). The lateral center of gravity movement, gluteus medius muscle myoelectric activity, oxygen uptake, minute ventilation (tidal volume, respiratory rate), heart rate, blood pressure, and rating perceived exertion just before the end of constant load exercise (4.0 km/h) were compared between the two walking conditions. Results All the measured parameters except for tidal volume and diastolic blood pressure were significantly higher during wide-based walking than during normal walking. However, when Δ is the difference between the two conditions, no correlation was found between Δlateral center of gravity movement, Δgluteus medius muscle myoelectric activity, Δcardiopulmonary parameters, and Δrating perceived exertion. Conclusion Although the precise mechanisms underlying the inefficiency of wide-based walking could not be clarified, cardiopulmonary indices such as oxygen uptake were significantly higher during wide-based walking than during normal walking. This suggests that improvement of wide-based gait is warranted from a kinematic perspective and an exercise physiology perspective.
Synthesis of the JKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the causative toxin of ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. ...Key to the synthesis are a 2,3-sigmatropic rearrangement to construct a seven-membered α-hydroxy exo-enol ether, stereoselective construction of an angular tetrasubstituted stereogenic center on the seven-membered M-ring by a hydrogen atom transfer-based reductive olefin coupling, Suzuki–Miyaura coupling of the KLMN-ring enol phosphate with a highly congested M-ring, and silica gel-mediated epoxide ring opening to form the J-ring. Comparison of the nuclear magnetic resonance spectroscopic data for the synthesized fragment with those for the natural product provided support for the formerly assigned structure of the N-ring in the right-hand terminal of C-CTX-1.
Total Synthesis of (−)‐Enigmazole A Sakurai, Keisuke; Sasaki, Makoto; Fuwa, Haruhiko
Angewandte Chemie International Edition,
April 23, 2018, Letnik:
57, Številka:
18
Journal Article
Recenzirano
Total synthesis of (−)‐enigmazole A, a marine macrolide natural product with cytotoxic activity, has been accomplished. The tetrahydropyran moiety was constructed by means of a domino olefin ...cross‐metathesis/intramolecular oxa‐Michael addition of a δ‐hydroxy olefin. After coupling of advanced intermediates, the macrocycle was formed through gold‐catalyzed rearrangement of a propargylic benzoate, followed by ring‐closing metathesis of the resultant α,β‐unsaturated ketone.
An enigma resolved: Total synthesis of (−)‐enigmazole A has been achieved. Highlights of the synthesis include olefin cross‐metathesis/intramolecular oxa‐Michael addition for stereoselective construction of the tetrahydropyran ring and gold‐catalyzed propargylic benzoate rearrangement/ring‐closing metathesis for closure of the macrocycle.
Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social ...isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE).
We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (< 12 of LSNS-6) at two time points, participants were categorized into four groups: "not socially isolated," "improved socially isolated," "newly socially isolated," and "continuously socially isolated." At the follow-up survey, a CES-D score of ≥ 16 indicates the presence of depressive symptoms. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using the logistic regression analysis to examine the influence of the change in social isolation over four years on depressive symptoms.
Participants who were newly socially isolated had a significantly higher prevalence of depressive symptoms than those who were not socially isolated (AOR = 1.89, 95% CI = 1.61 - 2.23). In addition, AORs were highest for those who were continuously socially isolated and had experienced house damage (AOR = 2.17, 95% CI = 1.73 - 2.72) and those who were newly socially isolated and had not experienced the death of family members due to the GEJE (AOR = 1.88, 95%CI = 1.60 - 2.22).
Our longitudinal findings suggest that being newly or continuously socially isolated is associated with a risk of depressive symptoms, not only among those who had experienced house damage or the death of a family member, but also those who had not, in the disaster-affected area. Our study underlines the clinical importance of social isolation after a large-scale natural disaster and draws attention to the need for appropriate prevention measures.
To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ...ancestry). We identified 88 type 2 diabetes-associated loci (P < 5.0 × 10
) with 115 independent signals (P < 5.0 × 10
), of which 28 loci with 30 signals were novel. Twenty-eight missense variants were in linkage disequilibrium (r
> 0.6) with the lead variants. Among the 28 missense variants, three previously unreported variants had distinct minor allele frequency (MAF) spectra between people of Japanese and European ancestry (MAF
> 0.05 versus MAF
< 0.01), including missense variants in genes related to pancreatic acinar cells (GP2) and insulin secretion (GLP1R). Transethnic comparisons of the molecular pathways identified from the GWAS results highlight both ethnically shared and heterogeneous effects of a series of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells).
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.
Purpose This study aimed to examine whether trunk stability is related to closed kinetic chain motor performance of the upper and lower limbs. Participants and Methods In this study, 27 healthy male ...university students participated. Trunk stability was measured under two conditions, with and without rhythmic stabilization, as a proprioceptive neuromuscular facilitation procedure. The shortest time required to perform 20 push-ups and lateral step-up/-downs (closed kinetic chain motor performances) immediately after rhythmic stabilization or sitting rest (without rhythmic stabilization) was measured. Results Left and right trunk stabilities were significantly higher, and the time required to perform the closed kinetic chain motor task was significantly shorter under the rhythmic stabilization condition than that of the non-rhythmic stabilization condition. Regarding the relationship between the difference between the two trunk stability conditions and difference between upper/lower limbs closed kinetic chain exercise capacity conditions, left trunk stability correlated with each closed kinetic chain movement, whereas right trunk stability did not correlate with either movement. Conclusion Trunk stability was shown to improve closed kinetic chain exercise capacity in the upper and lower limbs, and stability of the trunk’s dominant side (here, left side) seemed to regulate.
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