Conformation of ultra-long-chain fatty acid in lipid bilayer: Molecular dynamics study

Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in the restricted tissues such as retina, testis, and skin. The conformation of a single ULCFA, in which the sn-1 unsaturated chain has 32 carbons, in three types of tensionless phospholipid bilayers is studied by molecular dynamics simulations. It is found that the ultra-long tail of the ULCFA flips between two leaflets and fluctuates among an elongation into the opposite leaflet, lying between two leaflets, and turning back. As the number ratio of lipids in the opposite leaflet increases, the ratio of the elongated shape linearly decreases in all three cases. Thus, ULCFAs can sense the density differences between the two leaflets and respond to these changes

Up-regulation of ICAM-1 expression on human dermal fibroblasts by IFN β in the presence of TNF-α

AbstractUnstimulated human fibroblasts show low or undetectable ICAM-1 expression. Interferon-beta (IFN-β) at concentrations of 10,100, and 1000 IU/ml in the presence of tumor necrosis factor-alpha (TNF-α) significantly increased the ICAM-I expression of fibroblasts in a dose-dependent manner. Treatment with IFN-β alone, however, did not up-regulate the ICAM-1 expression. Furthermore the attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated fibroblasts was increased. This augmented attachment was partly inhibited by anti-ICAM-1 antibody. These results suggest that IFN-β and TNF-α may cooperatively modulate the attachment of PBMCs in the dermis

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC2

AbstractExpanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC2, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC2 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs

Immunization of Mice against Infection with Salmonella blegdam : Especially Protection of Mice from Typhoid Infection by Immunization with Living Rough Variants of Salmonella

It is generally known that immunization with killed bacilli has a protective effect on bacterienda. 11 But typhoid fever, paratyphoid fever and anthrax, which are also accompanied with bacierienda, have been considered to be exceptional cases. For anthrax effective immunity could not be introduced with killed vaccine, though Louis Pasteur1) invented a preventive inoculation method hi 1881, until recently low virulent living organism inoculations have been considered to be the only effectivemethod, as far as anthrax is concerned. Recently Cromartie, Watson, Bloom and others2) have proved why immunization with living bacilli is the only preventive measure for anthrax. Based on their findings, it is now possible to provide protection with vaccines containing no living organisms. Thus one of the exceptional cases has been removed, leaving mechanism of immunity of typhoid diseases as the remaining problem. In typhoid and paratyphoid fever, it is statistically known that preventive inoculation with killed bacilli has lowered morbidity and lethality. But the immunity resulting from this vaccination is not as strong and effective as in immunity after recovery Moreover its effectiveness is not completely supported, either experimentally or theoretically. This Subject has been studied at a high level in our country, particular), by Kobayashi and his collabora- tors3). According to their opinion, the protective power against typhoid and paratyphoid. infectioncan be established by vaccination with living bacilli, whether in smooth or in rough type, but not with killed vaccine. However, Hazato and his collaborators4) have reported that intravenous injectionsof killed bacilli have given satisfactory protection to mice against the infection of Salmonella enteritidis I , equal to those of living bacilli. Hosoya and others5) have recently stated that immunization with theirso-called T.T.T. or T.A.T. vaccine, which contains no living bacilli, has protective effect on infectionof Salmonella enteritidis of mice and Salmonella abortus equi of guinea-pigs. Ominaga6) has denied

Variants at HLA-A , HLA-C , and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiologic and genetic landscapes of global populations. We conducted an initial genome-wide association study and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P = 3.7 × 10−10 and 6.6 × 10−15, respectively). By updating the HLA imputation reference panel of Japanese (n = 908) to expand HLA gene coverage, we fine-mapped the HLA variants associated with PsV risk. Although we confirmed the PsV risk of HLA-C*06:02 (odds ratio = 6.36, P = 0.0015), its impact was relatively small compared with those in other populations due to rare allele frequency in Japanese (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most significant association with PsV (odds ratio = 4.61, P = 1.2 × 10–10). In addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified an independent PsV risk of HLA-DQβ1 Asp57 (odds ratio = 2.19, P = 1.9 × 10–6). Our PsV genome-wide association study in Japanese highlighted the genetic architecture of PsV, including the identification of HLA risk variants

Associations of Nutrient Patterns with the Prevalence of Metabolic Syndrome : Results from the Baseline Data of the Japan Multi-Institutional Collaborative Cohort Study

The association between nutrient patterns and metabolic syndrome (MetS) has not been examined in a Japanese population. A cross-sectional study was performed on 30,108 participants (aged 35–69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Dietary intake was assessed using a 46-item food frequency questionnaire. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009, using body mass index instead of waist circumference. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and three nutrient patterns were extracted: Factor 1 (fiber, potassium and vitamins pattern); Factor 2 (fats and fat-soluble vitamins pattern); and Factor 3 (saturated fatty acids, calcium and vitamin B2 pattern). In multiple logistic regression analysis adjusted for sex, age, and other potential confounders, Factor 1 scores were associated with a significantly reduced odds ratio (OR) of MetS and all five components. Factor 2 scores were associated with significantly increased prevalence of MetS, obesity, and high blood pressure. Factor 3 scores were significantly associated with lower OR of MetS, high blood pressure, high serum triglycerides and low HDL cholesterol levels. Analysis of nutrient patterns may be useful to assess the overall quality of diet and its association with MetS

Breastfeeding history and metabolic syndrome in parous women

Objective The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. Methods The present cross-sectional study included 11,118 women, aged 35–69 years. Participants’ longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. Results Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose–response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. Conclusions Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women

Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults Case-control study

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)—located on the gene encoding for pleiotrophin on chromosome 7—that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing

Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c : population-based cross-sectional and longitudinal studies

Introduction Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population. Research design and methods We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data. Results Overall, PA had a weak inverse association (β=−0.00033, p=0.049) and carbohydrate intake had a strong positive association (β=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (Pinteraction=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (Pinteraction=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study. Conclusions The present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition

Association between plasma levels of homocysteine, folate, and vitamin B12, and dietary folate intake and hypertension in a cross-sectional study

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41–3.96) in men and 1.86 (95% CI 1.11–3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12