Enhanced formation of aerenchyma and induction of a barrier to radial oxygen loss in adventitious roots of Zea nicaraguensis contribute to its waterlogging tolerance as compared with maize (Zea mays ssp. mays)

Enhancement of oxygen transport from shoot to root tip by the formation of aerenchyma and also a barrier to radial oxygen loss (ROL) in roots is common in waterlogging‐tolerant plants. Zea nicaraguensis (teosinte), a wild relative of maize (Zea mays ssp. mays), grows in waterlogged soils. We investigated the formation of aerenchyma and ROL barrier induction in roots of Z. nicaraguensis, in comparison with roots of maize (inbred line Mi29), in a pot soil system and in hydroponics. Furthermore, depositions of suberin in the exodermis/hypodermis and lignin in the epidermis of adventitious roots of Z. nicaraguensis and maize grown in aerated or stagnant deoxygenated nutrient solution were studied. Growth of maize was more adversely affected by low oxygen in the root zone (waterlogged soil or stagnant deoxygenated nutrient solution) compared with Z. nicaraguensis. In stagnant deoxygenated solution, Z. nicaraguensis was superior to maize in transporting oxygen from shoot base to root tip due to formation of larger aerenchyma and a stronger barrier to ROL in adventitious roots. The relationships between the ROL barrier formation and suberin and lignin depositions in roots are discussed. The ROL barrier, in addition to aerenchyma, would contribute to the waterlogging tolerance of Z. nicaraguensis.     

MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.     

Virulence genotypes and drug resistance of Helicobacter pylori from Vladivostok, Russia: another feature in the Far East

Helicobacter pylori in Vladivostok, Far Eastern Russia, was investigated during 2004 to 2009. The genotype cagA(+) vacA(+) (s1/m1 or m2) accounted for 74.7%, with cagA(-) vacA(+) (s2/m2) at 11.2%. The CagA EPIYA type was mainly Western ABC, with minor types (ABCCC and novel AAABC) or non-Western/non-East Asia type (AB). Regarding drug resistance, metronidazole resistance was the highest, with a marked decrease in 6 years (from 71.4% to 30.8%); in contrast, levofloxacin and clarithromycin resistance increased. The data indicate that in Vladivostok, H. pylori was mainly the Western (not East Asian) type and dynamic changes in drug resistance occurred during 6 years.     

Isolation and molecular characterization of methicillin-resistant Staphylococcus aureus from public transport

Methicillin-resistant Staphylococcus aureus (MRSA) not only causes disease in hospitals, but also in the community. The characteristics of MRSA transmission in the environment remain uncertain. In this study, MRSA were isolated from public transport in Tokyo and Niigata, Japan. Of 349 trains examined, eight (2.3%) were positive for MRSA. The MRSA isolated belonged to sequence types (STs) 5, 8, 88, and 89, and included community infection-associated ST8 MRSA (with novel type IV staphylococcal cassette chromosome mec) and the ST5 New York/Japan hospital clone. The data indicate that public transport could contribute to the spread of community-acquired MRSA, and awareness of this mode of transmission is necessary.     

Therapeutic administration of IL-11 exhibits the postconditioning effects against ischemia-reperfusion injury via STAT3 in the heart

Activation of cardiac STAT3 by IL-6 cytokine family contributes to cardioprotection. Previously, we demonstrated that IL-11, an IL-6 cytokine family, has the therapeutic potential to prevent adverse cardiac remodeling after myocardial infarction; however, it remains to be elucidated whether IL-11 exhibits postconditioning effects. To address the possibility that IL-11 treatment improves clinical outcome of recanalization therapy against acute myocardial infarction, we examined its postconditioning effects on ischemia/reperfusion (I/R) injury. C57BL/6 mice were exposed to ischemia (30 min) and reperfusion (24 h), and IL-11 was intravenously administered at the start of reperfusion. I/R injury mediated the activation of STAT3, which was enhanced by IL-11 administration. IL-11 treatment reduced I/R injury, analyzed by triphenyl tetrazolium chloride staining [PBS, 46.7 ± 14.4%; IL-11 (20 μg/kg), 28.6 ± 7.5% in the ratio of infarct to risk area]. Moreover, echocardiographic and hemodynamic analyses clarified that IL-11 treatment preserved cardiac function after I/R. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining revealed that IL-11 reduced the frequency of apoptotic cardiomyocytes after I/R. Interestingly, IL-11 reduced superoxide production assessed by in situ dihydroethidium fluorescence analysis, accompanied by the increased expression of metallothionein 1 and 2, reactive oxygen species (ROS) scavengers. Importantly, with the use of cardiac-specific STAT3 conditional knockout (STAT3 CKO) mice, it was revealed that cardiac-specific ablation of STAT3 abrogated IL-11-mediated attenuation of I/R injury. Finally, IL-11 failed to suppress the ROS production after I/R in STAT3 CKO mice. IL-11 administration exhibits the postconditioning effects through cardiac STAT3 activation, suggesting that IL-11 has the clinical therapeutic potential to prevent I/R injury in heart.     

The ddY mouse: a model of postprandial hypertriglyceridemia in response to dietary fat

Postprandial hyperlipidemia (lipemia) is a risk factor for atherosclerosis. However, mouse models of postprandial hyperlipidemia have not been reported. Here, we report that ddY mice display marked postprandial hypertriglyceridemia in response to dietary fat. In ddY mice, the fasting serum total triacylglyceride (TG) concentration was 134 mg/dl, which increased to 571 mg/dl after an intragastric safflower oil load (0.4 ml/mouse). In C57BL/6J mice, these concentrations were 57 and 106 mg/dl, respectively. By lipoprotein analysis, ddY mice showed increases in chylomicron- and VLDL-sized TG fractions (remnants and VLDL) after fat load. In C57BL/6J mice, post-heparin plasma LPL activity after fat load was increased 4.8-fold relative to fasting. However, in ddY mice, the increase of LPL activity after fat load was very small (1.2-fold) and not significant. High fat feeding for 10 weeks led to obesity in ddY mice. A difference in LPL amino acid composition between C57BL/6J and ddY mice was detected but was deemed unlikely to cause hypertriglyceridemia because hypertriglyceridemia was not evident in other strains harboring the ddY-type LPL sequence. These findings indicate that postprandial hypertriglyceridemia in ddY mice is induced by decreased LPL activity after fat load and is associated with obesity induced by a high-fat diet.     

Involvement of stress kinase mitogen-activated protein kinase kinase 7 in regulation of mammalian circadian clock

The stress kinase mitogen-activated protein kinase kinase 7 (MKK7) is a specific activator of c-Jun N-terminal kinase (JNK), which controls various physiological processes, such as cell proliferation, apoptosis, differentiation, and migration. Here we show that genetic inactivation of MKK7 resulted in an extended period of oscillation in circadian gene expression in mouse embryonic fibroblasts. Exogenous expression in cultured mammalian cells of an MKK7-JNK fusion protein that functions as a constitutively active form of JNK induced phosphorylation of PER2, an essential circadian component. Furthermore, JNK interacted with PER2 at both the exogenous and endogenous levels, and MKK7-mediated JNK activation increased the half-life of PER2 protein by inhibiting its ubiquitination. Notably, the PER2 protein stabilization induced by MKK7-JNK fusion protein reduced the degradation of PER2 induced by casein kinase 1ε. Taken together, our results support a novel function for the stress kinase MKK7 as a regulator of the circadian clock in mammalian cells at steady state.     

Induction of Cardiac Fibrosis by β-Blocker in G Protein-independent and G Protein-coupled Receptor Kinase 5/β-Arrestin2-dependent Signaling Pathways

G-protein coupled receptors (GPCRs) have long been known as receptors that activate G protein-dependent cellular signaling pathways. In addition to the G protein-dependent pathways, recent reports have revealed that several ligands called “biased ligands” elicit G protein-independent and β-arrestin-dependent signaling through GPCRs (biased agonism). Several β-blockers are known as biased ligands. All β-blockers inhibit the binding of agonists to the β-adrenergic receptors. In addition to β-blocking action, some β-blockers are reported to induce cellular responses through G protein-independent and β-arrestin-dependent signaling pathways. However, the physiological significance induced by the β-arrestin-dependent pathway remains much to be clarified in vivo. Here, we demonstrate that metoprolol, a β₁-adrenergic receptor-selective blocker, could induce cardiac fibrosis through a G protein-independent and β-arrestin2-dependent pathway. Metoprolol, a β-blocker, increased the expression of fibrotic genes responsible for cardiac fibrosis in cardiomyocytes. Furthermore, metoprolol induced the interaction between β₁-adrenergic receptor and β-arrestin2, but not β-arrestin1. The interaction between β₁-adrenergic receptor and β-arrestin2 by metoprolol was impaired in the G protein-coupled receptor kinase 5 (GRK5)-knockdown cells. Metoprolol-induced cardiac fibrosis led to cardiac dysfunction. However, the metoprolol-induced fibrosis and cardiac dysfunction were not evoked in β-arrestin2- or GRK5-knock-out mice. Thus, metoprolol is a biased ligand that selectively activates a G protein-independent and GRK5/β-arrestin2-dependent pathway, and induces cardiac fibrosis. This study demonstrates the physiological importance of biased agonism, and suggests that G protein-independent and β-arrestin-dependent signaling is a reason for the diversity of the effectiveness of β-blockers.     

Evaluation of the astringency of black tea by a taste sensor system: scope and limitation

Grading the astringency of black tea by a taste sensor system was studied. The black tea samples manufactured in India and Sri Lanka were classified into ten steps on the basis of two standard solutions (0.65 mM and 0.26 mM EGCg aqueous solutions). An organoleptic test demonstrated that the sensor output was correlative to the human gustatory sense.     

Effect of Val92Met and Arg163Gln variants of the MC1R gene on freckles and solar lentigines in Japanese

Melanocortin-1 receptor (MC1R) is a highly polymorphic gene. The variety of the variants is dependent on the ethnic background of the individual. In Caucasians, specific variants, such as Arg151Cys, Arg160Trp, and Asp294His, are strongly associated with red hair, skin cancer and pigmented lesions. In Asians, there is no report so far indicating an association such as that observed in Caucasians. Here, we performed an association study on melanogenic phenotypes in 245 Japanese individuals. We focused on freckles and solar lentigines as melanogenic phenotypes. The 92Met allele and the 163Arg allele were positively associated with freckles and severe solar lentigines; the 163Gln allele showed a negative association. Those subjects who were homozygous for both the 92Met and 163Arg alleles had a highly elevated risk of developing freckles (OR: 7.92; 95% CI: 1.52-39.6) and severe solar lentigines (OR: 4.08; 95% CI: 1.34-13.1). Our study is the first report to show a clear association of MC1R variants on melanogenic phenotypes in Asians and also indicates the importance of Arg163Gln. In vitro studies by other groups demonstrated that Val92Met impaired MC1R function but Arg163Gln did not. Based on these in vitro studies, we believe that the result we observed for Val92Met could be attributed to impaired MC1R function, while, for Arg163Gln, other factors, e.g. effect of other loci, need to be considered.