Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains.

Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABAAR. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse-chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions.

Tyrosinase-Based Proximity Labeling in Living Cells and In Vivo.

Characterizing the protein constituents of a specific organelle and protein neighbors of a protein of interest (POI) is essential for understanding the function and state of the organelle and protein networks associated with the POI. Proximity labeling (PL) has emerged as a promising technology for specific and efficient spatial proteomics. Nevertheless, most enzymes adopted for PL still have limitations: APEX requires cytotoxic H2O2 for activation and thus is poor in biocompatibility for in vivo application, BioID shows insufficient labeling kinetics, and TurboID suffers from high background biotinylation. Here, we introduce a bacterial tyrosinase (BmTyr) as a new PL enzyme suitable for H2O2-free, fast (≤10 min in living cells), and low-background protein tagging. BmTyr is genetically encodable and enables subcellular-resolved PL and proteomics in living cells. We further designed a strategy of ligand-tethered BmTyr for in vivo PL, which unveiled the surrounding proteome of a neurotransmitter receptor (Grm1 and Drd2) in its resident synapse in a live mouse brain. Overall, BmTyr is one promising enzyme that can improve and expand PL-based applications and discoveries.

Association of blood pressure and body mass index with intraocular pressure in middle-aged and older Japanese residents: a cross-sectional and longitudinal study.

To clarify whether high blood pressure (BP) and high body mass index (BMI) are associated with elevated intraocular pressure (IOP), a cross-sectional and longitudinal study was conducted. This epidemiological study analyzed health examination data obtained between 2001 and 2005 from 896 Japanese individuals (aged 32-79 years) who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, or glaucoma. Multiple-regression analysis of our cross-sectional data showed that systolic and diastolic BP (SBP and DBP) and BMI had significant and near-significant positive associations with IOP in men (p＜0.05) and women (p＜0.1). Our longitudinal study from analyses of covariance found that the adjusted mean level of changes in IOP tended to increase with increased levels of SBP, DBP, and BMI in men (p＜0.1). In women also, changes in SBP and BMI tended to be positively related with that of IOP (p＜0.1). The results of this study suggested that BP and BMI were positively associated with IOP in middle-aged and older Japanese. Therefore, management of BP and improvement of obesity might be especially important to Japanese patients with open-angle glaucoma or ocular hypertension as they have a higher incidence of normal-tension glaucoma than Europeans and Americans.

Association of smoking with intraocular pressure in middle-aged and older Japanese residents.

OBJECTIVES: To clarify whether smoking was associated with elevated intraocular pressure (IOP) and to evaluate the interrelationship among IOP, blood viscosity, and smoking. METHODS: This cross-sectional study analyzed health examination data obtained between 2001 and 2004 from 1113 individuals (829 men and 284 women), ranging in age from 28 to 79 years, who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, and glaucoma. RESULTS: Multiple-regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and number of cigarettes smoked per day had a significantly positive association with IOP in men (P < 0.05). In women also, SBP, DBP, and BMI were positively related to IOP (P < 0.05). On the contrary, age had a significant negative association with IOP in both sexes (P < 0.01). Analysis of covariance and multiple logistic regression analyses showed that the adjusted mean IOP and the multivariate odds ratios for IOP increased with increasing cigarette consumption in men (P for trend = 0.01 and 0.06, respectively). Analysis of covariance found that smoking was significantly associated with both high IOP and high hematocrit in men (P for trend <0.05); however, the adjusted mean IOP values were higher in smokers than in nonsmokers, regardless of the hematocrit level. CONCLUSIONS: The results of this study suggested that the IOP level may be substantially affected by smoking habit in middle-aged and older Japanese men.

Unexpected combined effects of NADH dehydrogenase subunit-2 237 Leu/Met polymorphism and green tea consumption on renal function in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees. RESULTS: For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR. CONCLUSION: The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: Prevention of chronic kidney disease (CKD) is a major public health issue. Although several studies have been performed on the association between alcohol consumption and CKD or renal function, it remains controversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney function. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in Japanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension, serum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal function in male Japanese health check-up examinees. METHODS: A total of 394 male subjects aged 29-76 years were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m(2)) was conducted. RESULTS: For Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of mildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005). The crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092, 95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does not appear to affect eGFR. CONCLUSION: The present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Transcranial direct current stimulation to dorsolateral prefrontal cortex improves performance of obstacle avoidance gait task.

We aimed to investigate the effect of dual-task interference between cognitive and obstacle avoidance walking tasks, and the effect of transcranial direct current stimulation (tDCS) on the performance of this cognitive-motor dual task. The healthy young subjects participated in a single task consisting of a three-digit subtraction task (e.g. 783 - 7) or a 15-m track with six 7.5-cm high obstacles. Then, the subjects performed two single tasks simultaneously as dual tasks, before and after sham and anodal tDCS (2 mA, 20 min) to left dorsolateral prefrontal cortex (DLPFC, the F3 region of the 10/20 electroencephalogram electrode placement system). The effect of tDCS on each outcome (number of correct answers, the clearance height above the obstacle, and foot placement position) was analyzed using repeated-measures analysis of variance. Model effects included tDCS (real, sham), time (pre-, post-tDCS), and task (single task, dual task) conditions. A significant difference in the tDCS, time, and task conditions was observed; the correct number of subtraction tasks increased, and the clearance height and the distance between the obstacle and foot decreased in front of the obstacle. Our findings suggest that dual task performance is causally related to left DLPFC activation under complicated walking tasks and tDCS over this cortical area increases overloaded its information processing capacity.

Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes.

Various small molecules have been used as functional probes for tissue imaging in medical diagnosis and pharmaceutical drugs for disease treatment. The spatial distribution, target selectivity, and diffusion/excretion kinetics of small molecules in structurally complicated specimens are critical for function. However, robust methods for precisely evaluating these parameters in the brain have been limited. Herein, we report a new method termed "fixation-driven chemical cross-linking of exogenous ligands (FixEL)," which traps and images exogenously administered molecules of interest (MOIs) in complex tissues. This method relies on protein-MOI interactions and chemical cross-linking of amine-tethered MOI with paraformaldehyde used for perfusion fixation. FixEL is used to obtain images of the distribution of the small molecules, which addresses selective/nonselective binding to proteins, time-dependent localization changes, and diffusion/retention kinetics of MOIs such as the scaffold of PET tracer derivatives or drug-like small molecules.

Combined effect of longevity-associated mitochondrial DNA 5178 c/a polymorphism and green tea consumption on risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 cytosine/adenine (Mt5178C/A) polymorphism is reported to be associated with longevity and to modify the effects of alcohol consumption or coffee consumption on the risk of hypertension in the Japanese population. The objective of this study was to investigate whether Mt5178C/A polymorphism modifies the effects of green tea consumption on blood pressure or risk of hypertension in middle-aged Japanese men. A total of 394 male subjects (age, 53.9±7.9 years; mean±SD) was selected among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as systolic blood pressure (SBP)≥140 mmHg, diastolic blood pressure (DBP)≥90 mmHg, and/or undergoing antihypertensive drug treatment. After adjustment, irrespective of antihypertensive drug treatment, the association between Mt5178C genotype and hypertension was dependent on green tea consumption (P for trend=0.043 and P for trend=0.011, respectively). In particular, among subjects≥50 years old with Mt5178C, excluding those taking antihypertensive drugs, a significant association between green tea consumption and risk of hypertension was observed (P for trend=0.019), and the odds ratio for hypertension was significantly lower in those who consumed≥6 cups of green tea per day than in those who consumed≤1 cup per day (odds ratio=0.167, 95% confidence interval: 0.033-0.832). On the other hand, the association between Mt5178A genotype and hypertension did not depend on green tea consumption. No consistent association between green tea consumption and blood pressure was observed in either genotype. The present results suggest a joint effect for Mt5178C/A polymorphism and green tea consumption on the risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

BACKGROUND: Several genetic polymorphisms have been reported to modify the effects of smoking on serum lipid levels. The objective of this study was to investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese subjects. METHODS: A total of 394 male subjects (age, 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effect of Mt5178 C/A polymorphism and cigarette smoking on the risk of hypo-high-density lipoprotein (HDL) cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or hypertriglyceridemia was conducted. RESULTS: For subjects with Mt5178C, the risk of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily (P for trend = 0.001). On the other hand, the association between Mt5178A genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P for trend = 0.017 and P for trend = 0.002, respectively). However, the association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or hypertriglyceridemia did not depend on the number of cigarettes smoked daily. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modulates the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

Influence of mitochondrial DNA 5178 C/A polymorphism on serum cholesterol changes: a short-term follow-up in middle-aged Japanese men.

OBJECTIVE: The mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may exert anti-atherogenic effects. The aim of this study was to determine whether there were longitudinal differences in serum lipid levels between carriers of the Mt5178C genotype and those of the Mt5178A genotype and to assess the impact of these genotypes on serum cholesterol levels. METHODS: The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were measured and the Mt5178 C/A genotypes determined in 110 Japanese men aged 41-66 (mean 52.3) years who had received medical checkups twice in the period 1999-2005. The longitudinal changes of TC, HDLC, and LDLC were calculated according to genotype. RESULTS: The serum levels of TC at baseline and follow-up were significantly different, whereas those of HDLC and LDLC were not. The changes in HDLC differed significantly between the two Mt5178 C/A genotype groups, with the changes in HDLC level being significantly greater in the Mt5178A genotype group than in the Mt5178C group (p = 0.015). CONCLUSIONS: The Mt5178 C/A genotype may modify longitudinal changes in serum TC and HDLC levels in middle-aged Japanese men.

Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

BACKGROUND: Combined effects between mitochondrial DNA 5178 (Mt5178) C/A polymorphism and alcohol consumption on the risk of hypertension or hyperuricemia have been reported. The objective of this study was to investigate whether Mt5178 C/A polymorphism modulates the effects of alcohol consumption on the risk of dyslipidemia. METHODS: A total of 394 male subjects were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effect of Mt5178 polymorphism and alcohol consumption on the risk of dyslipidemia was conducted. RESULTS: For men with Mt5178C, alcohol consumption was significantly and negatively associated with the risk of hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol ≥ 140 mg/dl) (P for trend = 0.015). After adjustment for age, body mass index (BMI), habitual smoking, coffee consumption and use of antihypertensive medicine, the odds ratio (OR) for hyper-LDL cholesterolemia was significantly lower in daily drinkers with Mt5178C than non-drinkers with Mt5178C (OR = 0.360, 95% confidence intervals: 0.153-0.847). A significant and negative association between alcohol consumption and serum LDL cholesterol levels was also observed in Mt5178C genotypic men (P for trend < 0.01). On the other hand, the association between Mt5178A genotype and risk of hyper-LDL cholesterolemia does not appear to depend on alcohol consumption. CONCLUSIONS: For Mt5178C genotypic men, alcohol consumption may reduce the risk of hyper-LDL cholesterolemia.

Combined effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and coffee consumption on the risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

The objective of this study was to investigate whether the mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modifies the effects of coffee consumption on serum lipid levels and the risk of dyslipidemia in middle-aged Japanese men. A total of 397 male subjects (age, 53.9±7.8 years; mean±s.d.) were selected from among individuals visiting the hospital for regular medical check-ups. After adjustment for age, body mass index, habitual alcohol consumption, habitual smoking and use of antihypertensive medication, among subjects who consumed <1 cup of coffee per day, the odds ratio (OR) for hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol > or =140 mg per 100 ml) was significantly lower in those with Mt5178A than in those with Mt5178C (OR=0.378, 95% confidence interval: 0.153-0.919). After adjustment, the association between the Mt5178A genotype and hyper-LDL cholesterolemia depended on coffee consumption (P for trend=0.018). Coffee consumption was positively associated with serum LDL cholesterol levels only in subjects with Mt5178A. However, in subjects with Mt5178C, serum LDL cholesterol level or risk of hyper-LDL cholesterolemia did not seem to depend on coffee consumption. These results suggest that for men with Mt5178A, coffee consumption negates the genetic benefit of lower risk for hyper-LDL cholesterolemia.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modulates the effects of coffee consumption on the risk of hypertension in middle-aged Japanese men.

BACKGROUND: Habitual coffee consumption has been reported to lower blood pressure in the Japanese population. The NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity and modifies the effects of alcohol consumption on blood pressure in the Japanese population. The objective of this study was to determine whether this polymorphism also modifies the effects of coffee consumption on blood pressure or the risk of hypertension in middle-aged Japanese men. METHODS: A total of 398 men (mean age +/- standard deviation, 53.8 +/- 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as a systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, or antihypertensive drug treatment. Polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme AluI was performed to determine ND2-237 Leu/Met genotype. RESULTS: In subjects with ND2-237Leu, coffee consumption was significantly and negatively associated with diastolic blood pressure (P = 0.007). The odds ratio (OR) for hypertension was significantly lower in subjects with ND2-237Leu who consumed 2 or 3 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.517; 95% confidence interval [CI], 0.276 to 0.968; P = 0.039). After adjustment, the OR remained significant (OR = 0.399; 95% CI, 0.184 to 0.869; P = 0.020). Moreover, after adjustment, the OR was significantly lower in subjects with ND2-237Leu who consumed more than 4 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.246; 95% CI, 0.062 to 0.975; P = 0.046). However, the association between ND2-237Met genotype and hypertension did not depend on coffee consumption. CONCLUSIONS: The present results suggest that the ND2-237 Leu/Met polymorphism modulates the effects of coffee consumption on hypertension risk in middle-aged Japanese men.

Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modulates the effects of daily alcohol drinking on yearly changes in serum total and LDL cholesterol in Japanese men.

Reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism, is reportedly associated with longevity in the Japanese population. The ND2-237Met genotype may exert resistance to atherogenic diseases, such as myocardial infarction or cerebrovascular disorders. To investigate whether ND2-237 Leu/Met polymorphism is associated with yearly changes in serum lipid levels, we conducted a longitudinal study of 107 healthy Japanese male subjects. Analysis of covariance revealed that the interaction between the ND2-237 Leu/Met genotypes and habitual drinking was significantly associated with yearly changes in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels (p=0.036 and p=0.006, respectively). In multiple regression analysis, daily drinking was significantly and positively associated with yearly changes in serum LDLC levels in men with ND2-237Met (p=0.026). After adjusting for covariates, yearly changes in serum LDLC levels were significantly lower in non-daily drinkers with ND2-237Met than in those with ND2-237Leu (p=0.047). These results suggest that ND2-237Met has a beneficial impact on yearly changes in serum LDLC in non-daily drinkers but not in daily drinkers.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modifies effect of aging on renal function in male Japanese health checkup examinees: an exploratory cross-sectional study.

BACKGROUND: Mitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population. The objective of this study was to investigate whether Mt5178 C/A polymorphism influences the effect of physiological aging on renal function in male Japanese health checkup examinees. METHODS: A total of 404 male subjects (mean age ± SD, 53.9 ± 7.8 years; range, 29-76 years) were selected from among individuals visiting the hospital for regular medical checkups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and aging on renal function was then conducted. Renal function was evaluated by estimated glomerular filtration rate (eGFR). Subjects were divided into three age groups (< 50, 50-59, ≥ 60 years). RESULTS: In simple linear regression analysis, a significant negative association between aging and eGFR was observed in both Mt5178C and Mt5178A genotypic men (P < 0.001 and P = 0.003, respectively). However, in multiple linear regression analysis, a significant effect of aging on reduced eGFR was observed only in Mt5178C genotypic men (P < 0.001). Logistic regression analysis showed that, in the case of reduced eGFR defined as < 75 mL/min/1.73 m2, reduced eGFR was dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.002, respectively). After adjusting for smoking status and alcohol consumption, reduced eGFR was also dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.014, respectively). However, in reduced eGFR defined as < 90 mL/min/1.73 m2, reduced eGFR was dependent on aging only in Mt5178C genotypic men (P for trend < 0.001). CONCLUSIONS: This cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.

Permafrost is warming at a global scale.

Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.

NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup Examinees: An Exploratory Cross-Sectional Analysis.

BACKGROUND: Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the association of coffee consumption with the risk of hypertension, dyslipidemia, and abnormal glucose tolerance, and low serum chloride levels have been shown to be associated with all-cause and cardiovascular disease mortality. Therefore, the purpose of the present study was to investigate whether ND2-237 Leu/Met polymorphism influences the association of coffee consumption with serum chloride levels in male Japanese health checkup examinees. METHODS: From among individuals visiting the hospital for a regular medical checkup, 402 men (mean age ± standard deviation, 53.9 ± 7.8 years) were selected for inclusion in the study. After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional study to examine the combined association of ND2-237 Leu/Met polymorphism and coffee consumption with serum electrolyte levels. RESULTS: After adjusting for age, body mass index, habitual smoking, alcohol consumption, green tea consumption, and antihypertensive medication, coffee consumption significantly increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu genotype. After these adjustments, the odds ratios (ORs) for low levels of serum chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption (p for trend = 0.001). In addition, the OR for low levels of serum chloride was significantly lower in men with the ND2-237Leu genotype who consumed ≥4 compared with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010⁻0.934; p = 0.044). However, neither serum chloride levels nor risk of low levels of serum chloride appeared to be dependent on coffee consumption. CONCLUSIONS: The results suggest that ND2-237 Leu/Met polymorphism modifies the association of coffee consumption with serum chloride levels in middle-aged Japanese men.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies the effects of alcohol consumption on risk for hypertension in middle-aged Japanese men.

NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in the Japanese population, and the ND2-237Met genotype may exert antiatherogenic effects. To investigate whether ND2-237 Leu/Met polymorphism is associated with risk of hypertension, we conducted a cross-sectional study of 398 Japanese male subjects. The frequency of hypertension was significantly higher in ND2-237Leu genotypic men than in ND2-237Met genotypic men. On analysis of covariance, the interaction between ND2-237 Leu/Met polymorphism and habitual drinking was significantly associated with both systolic blood pressure and diastolic blood pressure. Multiple logistic regression analysis revealed that the ND2-237Met genotype, particularly in younger subjects (age <60 years), had a lower odds ratio for hypertension than the ND2-237Leu genotype. Moreover, the association of ND2-237 Leu/Met polymorphism with hypertension may depend on the frequency of alcohol consumption. The odds ratio for hypertension was significantly higher in daily drinkers with ND2-237Leu when compared with non- or ex-drinkers with ND2-237Leu. However, the association between the ND2-237Met genotype and hypertension may not depend on the frequency of alcohol consumption. The present results suggest that ND2-237 Leu/Met polymorphism is associated with hypertension and that modification of hypertension risk is dependent on alcohol consumption in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

BACKGROUND: Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. RESULTS: For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.