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

Design and Synthesis of a Luminescent Cyclometalated Iridium(III) Complex Having <i>N</i>,<i>N</i>‑Diethylamino Group that Stains Acidic Intracellular Organelles and Induces Cell Death by Photoirradiation

Cyclometalated iridium­(III) complexes have received considerable attention and are important candidates for use as luminescent probes for cellular imaging because of their potential photophysical properties. We previously reported that <i>fac</i>-Ir­(atpy)₃ <b>4</b> (atpy = 2-(5′-amino-4′-tolyl)­pyridine) containing three amino groups at the 5′-position of the atpy ligand shows a maximum red emission (at around 600 nm) under neutral and basic conditions and a green emission (at 531 nm) at acidic pH (pH 3–4). In this Article, we report on the design and synthesis of a new pH-sensitive cyclometalated Ir­(III) complex containing a 2-(5′-<i>N</i>,<i>N</i>-diethylamino-4′-tolyl)­pyridine (deatpy) ligand, <i>fac</i>-Ir­(deatpy)₃ <b>5</b>. The complex exhibits a considerable change in emission intensity between neutral and slightly acidic pH (pH 6.5–7.4). Luminescence microscopic studies using HeLa-S3 cells indicate that <b>5</b> can be used to selectively stain lysosome, an acidic organelle in cells. Moreover, complex <b>5</b> is capable of generating singlet oxygen in a pH-dependent manner and inducing the death of HeLa-S3 cells upon photoirradiation at 377 or 470 nm

Inspiratory and Expiratory Computed Tomography Imaging Clusters Reflect Functional Characteristics in Chronic Obstructive Pulmonary Disease

Purpose: Disease probability measure (DPM) is a useful voxel-wise imaging assessment of gas-trapping and emphysematous lesions in patients with chronic obstructive pulmonary disease (COPD). To elucidate the progression of COPD, we performed a cluster analysis using the following DPM parameters: normal (DPMNormal), gas-trapping (DPMGasTrap), and emphysematous lesions (DPMEmph). Our findings revealed the characteristics of each cluster and the 3-year disease progression using imaging parameters. Patients and methods: Inspiratory and expiratory chest computed tomography (CT) images of 131 patients with COPD were examined, of which 84 were followed up for 3 years. The percentage of low attenuation volume (LAV%) and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were quantitatively measured using inspiratory chest CT. A hierarchical cluster analysis was performed using the DPM parameters at baseline. Five clusters were named according to the dominant DPM parameters: normal (NL), normal-GasTrap (NL-GT), GasTrap (GT), GasTrap-Emphysema (GT-EM), and Emphysema (EM). Results: Women were predominantly diagnosed with GT. Forced expiratory volume in 1 s gradually decreased in the following order: NL, NL-GT, GT, GT-EM, and EM. DPMEmph correlated well with LAV%. Four clusters other than NL showed significantly higher values of √Aaw at Pi10 than NL; however, no significant differences were observed among them. In all clusters, DPMEmph increased after 3 years. DPMNormal only increased in the GT cluster. Conclusion: Clusters using DPM parameters may reflect the characteristics of COPD and help understand the pathophysiology of the disease

Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder.

We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD

Involvement of Androgen Receptor in Sex Determination in an Amphibian Species

<div><p>In mice and humans, the androgen receptor (<i>AR</i>) gene, located on the X chromosome, is not known to be involved in sex determination. In the Japanese frog <i>Rana rugosa</i> the <i>AR</i> is located on the sex chromosomes (X, Y, Z and W). Phylogenetic analysis shows that the <i>AR</i> on the X chromosome (<i>X-AR</i>) of the Korean <i>R. rugosa</i> is basal and segregates into two clusters: one containing <i>W-AR</i> of Japanese <i>R. rugosa</i>, the other containing <i>Y</i>-<i>AR</i>. <i>AR</i> expression is twice as high in ZZ (male) compared to ZW (female) embryos in which the <i>W</i>-<i>AR</i> is barely expressed. Higher <i>AR</i>-expression may be associated with male sex determination in this species. To examine whether the <i>Z</i>-<i>AR</i> is involved in sex determination in <i>R. rugosa</i>, we produced transgenic (Tg) frogs carrying an exogenous <i>Z</i>-<i>AR</i>. Analysis of ZW Tg frogs revealed development of masculinized gonads or ‘ovotestes’. Expression of <i>CYP17</i> and <i>Dmrt1</i>, genes known to be activated during normal male gonadal development, were up-regulated in the ZW ovotestis. Testosterone, supplied to the rearing water, completed the female-to-male sex-reversal in the <i>AR</i>-Tg ZW frogs. Here we report that <i>Z</i>-<i>AR</i> is involved in male sex-determination in an amphibian species.</p></div

Primers used for PCR analysis.

<p>F:Forward primer, R:Reverse primer.</p

Immunohistology of ZW ovotestes.

<p>(A) Localization of AR, CYP17 and Vasa in the ovotestis frozen sections of Wt ZW ovary, and Type 1 to 3 ovotestes were stained for AR (1–5), CYP17 (6–10) and Vasa (11–15). A single oocyte and a small Vasa-positive cell are indicated by a yellow and white arrow, respectively. The orange arrows in (3) indicate AR-positive signals. (B) Localization of AR and CYP17 in the Type 2 ovotestis. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093655#pone-0093655-g002" target="_blank">Figures 2</a> and 7 in (A) are enlarged to (a) and (b) in (B), respectively. Frozen sections were stained immunohistologically for AR (a) and CYP17 (b), and counterstained with DAPI. Dashed lines indicate the borders of the gonads. AR- and CYP17-positive signals are indicated by white arrows in (a) and (b), respectively. Bar = 50 µm.</p

Histology of gonads.

<p>(A) Schematic diagram of the Tg vector, pARPAR, 1 of 2 Tg vectors used in this study. (B) Histology of Tg and Wt gonads. Tg and Wt gonads with (+) or without (−) T-treatment were taken after laparotomy (upper figures, a–g; bar = 2 mm). Sections from Wt and Tg right and left gonads (RG and LG) were stained with Hematoxylin & Eosin (middle figures, h–n; bar = 100 µm) and a laminin antibody (lower figures, o–u; bar = 100 µm). Dashed lines indicate the borders of the gonads. In the middle figures, germ and somatic cells are indicated by black and blue arrows, respectively. Magnified images of the area within the square are shown in (l), (m) and (n).</p

Genotype and phenotype of transgenic frogs.

<p>Genotype and phenotype of transgenic frogs.</p

<i>Z-AR/V5</i>, <i>CYP17</i> and <i>Dmrt1</i> mRNA expression and <i>Z-AR/V5</i> and <i>AAT</i> genomic analysis.

<p>Genomic DNA PCR amplification was performed for the transgene (genomic <i>Z-AR/V5</i>). The sex of each frog was determined by genomic amplification of the ATP/ADP translocase (<i>AAT</i>) gene as previously described <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093655#pone.0093655-Yokoyama1" target="_blank">[16]</a>. RT-PCR analysis was used to detect <i>Z-AR/V5</i>, <i>CYP17</i> and <i>Dmrt1</i> mRNA in Wt and Tg gonads treated with (+) or without (−) T. Top panel, <i>Z-AR</i>/<i>V5</i> integration into genomic DNA; 2nd panel, <i>Z-AR</i>/<i>V5</i> expression; 3rd panel, <i>CYP17</i> expression; 4th panel, <i>Dmrt1</i> expression; bottom panel, <i>AAT</i> genetic sex determination of each frog.</p