Publications by authors named "Naoya Kataoka"

83 Publications

Drastic Cardiac Reverse Remodeling Following Catheter Ablation in Patients with Atrial Fibrillation and Heart Failure.

Medicina (Kaunas) 2021 May 20;57(5). Epub 2021 May 20.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

In the management of atrial fibrillation in patients with heart failure, rate control is recommended, whereas the implication of rhythm control remains controversial. We experienced a 65-year-old man who had compensated heart failure due to hypertensive heart disease and atrial fibrillation with well-controlled heart rate (<100 bpm). At three months following the catheter ablation procedure, the left ventricular ejection fraction improved from 40% up to 65%. The implication of rhythm control using catheter ablation in improving cardiac reverse remodeling should be validated in large-scale clinical studies.
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http://dx.doi.org/10.3390/medicina57050511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160769PMC
May 2021

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart Vessels 2021 May 6. Epub 2021 May 6.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani Toyama, Toyama, 930-0194, Japan.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.
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http://dx.doi.org/10.1007/s00380-021-01864-5DOI Listing
May 2021

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever.

Elife 2021 May 4;10. Epub 2021 May 4.

Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States.

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAAs) are essential amino acids needed for anabolic processes, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever in rodents. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E (PGE) and psychological stress in mice and rats. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.
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http://dx.doi.org/10.7554/eLife.66865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137140PMC
May 2021

Thermal adaptation of acetic acid bacteria for practical high-temperature vinegar fermentation.

Biosci Biotechnol Biochem 2021 Apr;85(5):1243-1251

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.

Thermotolerant microorganisms are useful for high-temperature fermentation. Several thermally adapted strains were previously obtained from Acetobacter pasteurianus in a nutrient-rich culture medium, while these adapted strains could not grow well at high temperature in the nutrient-poor practical culture medium, "rice moromi." In this study, A. pasteurianus K-1034 originally capable of performing acetic acid fermentation in rice moromi was thermally adapted by experimental evolution using a "pseudo" rice moromi culture. The adapted strains thus obtained were confirmed to grow well in such the nutrient-poor media in flask or jar-fermentor culture up to 40 or 39 °C; the mutation sites of the strains were also determined. The high-temperature fermentation ability was also shown to be comparable with a low-nutrient adapted strain previously obtained. Using the practical fermentation system, "Acetofermenter," acetic acid production was compared in the moromi culture; the results showed that the adapted strains efficiently perform practical vinegar production under high-temperature conditions.
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http://dx.doi.org/10.1093/bbb/zbab009DOI Listing
April 2021

Characterization of a cryptic, pyrroloquinoline quinone-dependent dehydrogenase of Gluconobacter sp. strain CHM43.

Biosci Biotechnol Biochem 2021 Mar;85(4):998-1004

Graduate School of Science and Technology for Innovation, Yamaguchi University, Yamaguchi, Japan.

We characterized the pyrroloquinoline quinone (PQQ)-dependent dehydrogenase 9 (PQQ-DH9) of Gluconobacter sp. strain CHM43, which is a homolog of PQQ-dependent glycerol dehydrogenase (GLDH). We used a plasmid construct to express PQQ-DH9. The expression host was a derivative strain of CHM43, which lacked the genes for GLDH and the membrane-bound alcohol dehydrogenase and consequently had minimal ability to oxidize primary and secondary alcohols. The membranes of the transformant exhibited considerable d-arabitol dehydrogenase activity, whereas the reference strain did not, even if it had PQQ-DH9-encoding genes in the chromosome and harbored the empty vector. This suggests that PQQ-DH9 is not expressed in the genome. The activities of the membranes containing PQQ-DH9 and GLDH suggested that similar to GLDH, PQQ-DH9 oxidized a wide variety of secondary alcohols but had higher Michaelis constants than GLDH with regard to linear substrates such as glycerol. Cyclic substrates such as cis-1,2-cyclohexanediol were readily oxidized by PQQ-DH9.
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http://dx.doi.org/10.1093/bbb/zbab005DOI Listing
March 2021

Major aldehyde dehydrogenase AldFGH of Gluconacetobacter diazotrophicus is independent of pyrroloquinoline quinone but dependent on molybdopterin for acetic acid fermentation.

Appl Microbiol Biotechnol 2021 Mar 16;105(6):2341-2350. Epub 2021 Feb 16.

Graduate School of Sciences and Technology for Innovation, Yamaguchi University, Yamaguchi, 753-8515, Japan.

Acetic acid fermentation involves the oxidation of ethanol to acetic acid via acetaldehyde as the intermediate and is catalyzed by the membrane-bound alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) of acetic acid bacteria. Although ADH depends on pyrroloquinoline quinone (PQQ), the prosthetic group associated with ALDH remains a matter of debate. This study aimed to address the dependency of ALDH of Gluconacetobacter diazotrophicus strain PAL5 on PQQ and the physiological role of ALDH in acetic acid fermentation. We constructed deletion mutant strains for both the ALDH gene clusters of PAL5, aldFGH and aldSLC. In addition, the adhAB operon for ADH was eliminated, since it shows ALDH activity. The triple-deletion derivative ΔaldFGH ΔaldSLC ΔadhAB failed to show ALDH activity, which suggested that ALDH activity in PAL5 is derived from these three enzyme complexes. Since the single-gene cluster deletion derivative ΔaldFGH lost most ALDH activity, and accumulated much higher acetaldehyde than wild type under acetic acid fermentation conditions, we concluded that AldFGH functions as the major ALDH in PAL5. Furthermore, deletion of the PQQ biosynthesis gene cluster (pqqABCDE) abolished ADH activity completely, but did not affect ALDH activity. Instead, the molybdopterin biosynthesis gene deletion derivatives lost ALDH activity. Thus, we concluded that the AldFGH and AldSLC complexes of Ga. diazotrophicus PAL5 require a form of molybdopterin but not PQQ for ALDH activity. KEY POINTS: • AldFGH is the major aldehyde dehydrogenase in Gluconacetobacter diazotrophicus PAL5. • Acetaldehyde accumulated from ethanol in the absence of AldFGH. • Molybdopterin, rather than pyrroloquinoline quinone, is required for AldFGH.
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http://dx.doi.org/10.1007/s00253-021-11144-xDOI Listing
March 2021

Three ATP-dependent phosphorylating enzymes in the first committed step of dihydroxyacetone metabolism in Gluconobacter thailandicus NBRC3255.

Appl Microbiol Biotechnol 2021 Feb 21;105(3):1227-1236. Epub 2021 Jan 21.

Faculty of Agriculture, Yamaguchi University, Yamaguchi, 753-8515, Japan.

Dihydroxyacetone (DHA), a chemical suntan agent, is produced by the regiospecific oxidation of glycerol with Gluconobacter thailandicus NBRC3255. However, this microorganism consumes DHA produced in the culture medium. Here, we attempted to understand the pathway for DHA metabolism in NBRC3255 to minimize DHA degradation. The two gene products, NBRC3255_2003 (DhaK) and NBRC3255_3084 (DerK), have been annotated as DHA kinases in the NBRC 3255 draft genome. Because the double deletion derivative for dhaK and derK showed ATP-dependent DHA kinase activity similar to that of the wild type, we attempted to purify DHA kinase from ∆dhaK ∆derK cells to identify the gene for DHA kinase. The identified gene was NBRC3255_0651, of which the product was annotated as glycerol kinase (GlpK). Mutant strains with several combinations of deletions for the dhaK, derK, and glpK genes were constructed. The single deletion strain ∆glpK showed approximately 10% of wild-type activity and grew slower on glycerol than the wild type. The double deletion strain ∆derK ∆glpK and the triple deletion strain ∆dhaK ∆derK ∆glpK showed DHA kinase activity less than a detection limit and did not grow on glycerol. In addition, although ΔderK ΔglpK consumed a small amount of DHA in the late phase of growth, ∆dhaK ΔderK ΔglpK did not show DHA consumption on glucose-glycerol medium. The transformants of the ∆dhaK ΔderK ΔglpK strain that expresses one of the genes from plasmids showed DHA kinase activity. We concluded that all three DHA kinases, DhaK, DerK, and GlpK, are involved in DHA metabolism of G. thailandicus. KEY POINTS: • Dihydroxyacetone (DHA) is produced but degraded by Gluconobacter thailandicus. • Phosphorylation rather than reduction is the first committed step in DHA metabolism. • Three kinases are involved in DHA metabolism with the different properties.
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http://dx.doi.org/10.1007/s00253-021-11092-6DOI Listing
February 2021

The Auxiliary NADH Dehydrogenase Plays a Crucial Role in Redox Homeostasis of Nicotinamide Cofactors in the Absence of the Periplasmic Oxidation System in Gluconobacter oxydans NBRC3293.

Appl Environ Microbiol 2021 01 4;87(2). Epub 2021 Jan 4.

Graduate School of Sciences and Technology for Innovation, Yamaguchi University, Yamaguchi, Japan

has the unique property of a glucose oxidation system in the periplasmic space, where glucose is oxidized incompletely to ketogluconic acids in a nicotinamide cofactor-independent manner. Elimination of the gene for membrane-bound glucose dehydrogenase, the first enzyme for the periplasmic glucose oxidation system, induces a metabolic change whereby glucose is oxidized in the cytoplasm to acetic acid. strain NBRC3293 possesses two molecular species of type II NADH dehydrogenase (NDH), the primary and auxiliary NDHs that oxidize NAD(P)H by reducing ubiquinone in the cell membrane. The substrate specificities of the two NDHs are different from each other: primary NDH (p-NDH) oxidizes NADH specifically but auxiliary NDH (a-NDH) oxidizes both NADH and NADPH. We constructed NBRC3293 derivatives defective in the gene for a-NDH, in the gene, and in both. Our Δ derivative yielded higher cell biomass on glucose, as reported previously, but grew at a lower rate than the wild-type strain. The Δ derivative showed growth behavior on glucose similar to that of the wild type. The Δ Δ double mutant showed greatly delayed growth on glucose, but its cell biomass was similar to that of the Δ strain. The double mutant accumulated intracellular levels of NAD(P)H and thus shifted the redox balance to reduction. Accumulated NAD(P)H levels might repress growth on glucose by limiting oxidative metabolisms in the cytoplasm. We suggest that a-NDH plays a crucial role in redox homeostasis of nicotinamide cofactors in the absence of the periplasmic oxidation system in Nicotinamide cofactors NAD and NADP mediate redox reactions in metabolism. , a member of the acetic acid bacteria, oxidizes glucose incompletely in the periplasmic space-outside the cell. This incomplete oxidation of glucose is independent of nicotinamide cofactors. However, if the periplasmic oxidation of glucose is abolished, the cells oxidize glucose in the cytoplasm by reducing nicotinamide cofactors. Reduced forms of nicotinamide cofactors are reoxidized by NADH dehydrogenase (NDH) on the cell membrane. We found that two kinds of NDH in have different substrate specificities: the primary enzyme is NADH specific, and the auxiliary one oxidizes both NADH and NADPH. Inactivation of the latter enzyme in cells in which we had induced cytoplasmic glucose oxidation resulted in elevated intracellular levels of NAD(P)H, limiting cell growth on glucose. We suggest that the auxiliary enzyme is important if grows independently of the periplasmic oxidation system.
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http://dx.doi.org/10.1128/AEM.02155-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783338PMC
January 2021

Improved Risk Stratification of Patients With Brugada Syndrome by the New Japanese Circulation Society Guideline - A Multicenter Validation Study.

Circ J 2020 11 17;84(12):2158-2165. Epub 2020 Oct 17.

Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center.

Background: The new guideline (NG) published by the Japanese Circulation Society (JCS) places emphasis on previous arrhythmic syncope and inducibility of ventricular fibrillation (VF) by ≤2 extrastimuli during programmed electrical stimulation (PES) for deciding the indication of an implantable cardioverter-defibrillator in patients with Brugada syndrome (BrS). This study evaluated the usefulness of the NG and compared it with the former guideline (FG) for risk stratification of patients with BrS.Methods and Results:This was a multicenter (7 Japanese hospitals) retrospective study involving 234 patients with BrS who underwent PES at baseline (226 males; mean age at diagnosis: 44.9±13.4 years). At diagnosis, 46 patients (20%) had previous VF, 100 patients (43%) had previous syncope, and 88 patients (37%) were asymptomatic. We evaluated the difference in the incidence of VF in each indication according to the new and FGs. During the follow-up period (mean: 6.9±5.2 years), the incidence of VF was higher in patients with Class IIa indication according to the NG (NG: 16/45 patients [35.6%] vs. FG: 16/104 patients [15.4%]), while the incidence of VF in patients with other than class I or IIa indication was similarly low in both guidelines (NG: 2/143 patients [1.4%] vs. FG: 2/84 patients [2.4%]).

Conclusions: This study validated the usefulness of the NG for risk stratification of BrS patients.
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http://dx.doi.org/10.1253/circj.CJ-19-0910DOI Listing
November 2020

Taro of enabling hydrolysis of konjac polysaccharides to various biotechnological interest.

Biosci Biotechnol Biochem 2020 Oct 30;84(10):2160-2173. Epub 2020 Jun 30.

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University , Yamaguchi, Japan.

Due to the indigestibility, utilization of konjac taro, has been limited only to the Japanese traditional konjac food. preparation with konjac taro was examined to utilize konjac taro as a source of utilizable carbohydrates. AKU 3302 was selected as a favorable strain for preparation, while used extensively in brewing industry was not so effective. grew well over steamed konjac taro by extending hyphae with least conidia formation. preparation was completed after 3-day incubation at 30°C. D-Mannose and D-glucose were the major monosaccharides found in a hydrolyzate giving the total sugar yield of 50 g from 100 g of dried konjac taro. An apparent extent of konjac taro hydrolysis at 55°C for 24 h seemed to be completed. Since konjac taro is hydrolyzed into monosaccharides, utilization of konjac taro carbohydrates may become possible to various products of biotechnological interest.
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http://dx.doi.org/10.1080/09168451.2020.1787812DOI Listing
October 2020

Intra-day change in occurrence of out-of-hospital ventricular fibrillation in Japan: The JCS-ReSS study.

Int J Cardiol 2020 Nov 20;318:54-60. Epub 2020 Jun 20.

National Cerebral and Cardiovascular Center, Suita, Japan.

Background: Real-world evidence of out-of-hospital ventricular fibrillation (VF), especially regarding intra-day change, remains unclear. We aimed to investigate that age- and gender-dependent difference of intra-day change of VF occurrence.

Method: We enrolled 71,692 patients (males: 56,419 [78.7%], females: 15,273 [21.3%]) in whom cardiac VF had been documented from the 2005-2015 All-Japan Utstein Registry data. Subjects were divided into four groups: group-I (<18 years old), group-II (18-39), group-III (40-69), and group-IV (≥70). Among four groups in each of male and female, we compared the intra-day change of VF occurrence, and evaluated the risk factors of the unfavorable neurologic outcomes at 1 month after VF.

Results: Regardless of age, the incidence of VF was significantly greater in male than in female subjects. In male subjects, VF in group-I, III and IV occurred higher at daytime, however, group-II had no intra-day difference because group-II had a higher VF events at midnight~ early morning compared with other aged groups (Poisson regression analysis, p = .03). While in female, each group showed similar intra-day pattern of VF occurrence. Logistic regression analysis revealed that some of the clinical parameters such as time periods from call receipt to first shock and the presence of bystander cardiopulmonary resuscitation were important for risk of 30-day neurologically unfavorable outcomes.

Conclusions: The intra-day change of VF occurrence was age-dependently different in males but not in females, suggesting age- and gender-dependent differences in underlying cardiac diseases. These might affect the significant difference in unfavorable neurologic outcome.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.014DOI Listing
November 2020

A multicenter study comparing the outcome of catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation in patients with heart failure (CRABL-HF): Study design.

J Arrhythm 2020 Jun 15;36(3):449-455. Epub 2020 Mar 15.

Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

Background: Catheter ablation of atrial fibrillation (AF) is increasingly performed worldwide in patients with heart failure (HF). However, it has been recently emphasized that AF ablation in patients with HF is associated with increased risks of procedure-related complications and mortality. There are little data about the differences in the efficacy and safety between cryoballoon (CB) and radiofrequency (RF) ablation of AF in patients with HF.

Methods: The CRABL-HF study is designed as a prospective, multicenter, open-label, controlled, and randomized clinical trial comparing the efficacy and safety of AF ablation between CB and RF ablation in patients with HF (LVEF ≤40%) (UMIN Clinical Trials Registry UMIN000032433). The CRABL-HF study will consist of 110 patients at multicenter in Japan. The patients will be registered and randomly assigned to either the CB ablation or RF ablation group with a 1:1 allocation. The primary endpoint of this study is the occurrence of atrial tachyarrhythmias (ATs) at 1 year with a blanking period of 90 days after ablation. Key secondary endpoints are the success rate of the pulmonary vein isolation, total procedural time, left atrial dwelling time, total fluoroscopy time, radiation exposure, complication rate, composite of all-cause mortality or HF hospitalizations, cardiovascular events, change in left ventricular ejection fraction, and change in quality of life.

Results: The results of this study are currently under investigation.

Conclusion: The CRABL-HF study is being conducted to compare the efficacy and safety of catheter ablation of AF between CB and RF ablation in patients with HF.
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http://dx.doi.org/10.1002/joa3.12322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279987PMC
June 2020

5-Keto-D-fructose production from sugar alcohol by isolated wild strain CHM 43.

Biosci Biotechnol Biochem 2020 Aug 19;84(8):1745-1747. Epub 2020 May 19.

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University , Yamaguchi, Japan.

Gluconobacter Frateurii: CHM 43 have D-mannitol dehydrogenase (quinoprotein glycerol dehydrogenase) and flavoprotein D-fructose dehydrogenase in the membranes. When the two enzymes are functional, D-mannitol is converted to 5-keto-D-fructose with 65% yield when cultivated on D-mannitol. 5-Keto-D-fructose production with almost 100% yield was realized with the resting cells. The method proposed here should give a smart strategy for 5-keto-D-fructose production.
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http://dx.doi.org/10.1080/09168451.2020.1767500DOI Listing
August 2020

The membrane-bound sorbosone dehydrogenase of Gluconacetobacter liquefaciens is a pyrroloquinoline quinone-dependent enzyme.

Enzyme Microb Technol 2020 Jun 28;137:109511. Epub 2020 Jan 28.

Division of Agricultural Science, Graduate School of Science and Technology for Innovation, Yamaguchi University, Yamaguchi 753-8515, Japan; Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan; Research Center for Thermotolerant Microbial Resources, Yamaguchi University, Yamaguchi 753-8515, Japan.

Membrane-bound sorbosone dehydrogenase (SNDH) of Gluconacetobacter liquefaciens oxidizes l-sorbosone to 2-keto-l-gulonic acid (2KGLA), a key intermediate in vitamin C production. We constructed recombinant Escherichia coli and Gluconobacter strains harboring plasmids carrying the sndh gene from Ga. liquefaciens strain RCTMR10 to identify the prosthetic group of SNDH. The membranes of the recombinant E. coli showed l-sorbosone oxidation activity, only after the holo-enzyme formation with pyrroloquinoline quinone (PQQ), indicating that SNDH is a PQQ-dependent enzyme. The sorbosone-oxidizing respiratory chain was thus heterologously reconstituted in the E. coli membranes. The membranes that contained SNDH showed the activity of sorbosone:ubiquinone analogue oxidoreductase. These results suggest that the natural electron acceptor for SNDH is membranous ubiquinone, and it functions as the primary dehydrogenase in the sorbosone oxidation respiratory chain in Ga. liquefaciens. A biotransformation experiment showed l-sorbosone oxidation to 2KGLA in a nearly quantitative manner. Phylogenetic analysis for prokaryotic SNDH homologues revealed that they are found only in the Proteobacteria phylum and those of the Acetobacteraceae family are clustered in a group where all members possess a transmembrane segment. A three-dimensional structure model of the SNDH constructed with an in silico fold recognition method was similar to the crystal structure of the PQQ-dependent pyranose dehydrogenase from Coprinopsis cinerea. The structural similarity suggests a reaction mechanism under which PQQ participates in l-sorbosone oxidation.
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http://dx.doi.org/10.1016/j.enzmictec.2020.109511DOI Listing
June 2020

Lack of UCP1 stimulates fatty liver but mediates UCP1-independent action of beige fat to improve hyperlipidemia in Apoe knockout mice.

Biochim Biophys Acta Mol Basis Dis 2020 07 13;1866(7):165762. Epub 2020 Mar 13.

Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan. Electronic address:

Brown adipose tissue (BAT) plays a critical role in lipid metabolism and may protect from hyperlipidemia; however, its beneficial effect appears to depend on the ambient temperature of the environment. In this study, we investigated the effects of uncoupling protein 1 (UCP1) deficiency on lipid metabolism, including the pathophysiology of hyperlipidemia, in apolipoprotein E knockout (APOE-KO) mice at a normal (23 °C) and thermoneutral (30 °C) temperature. Unexpectedly, UCP1 deficiency caused improvements in hyperlipidemia, atherosclerosis, and glucose metabolism, regardless of an increase in hepatic lipid deposition, in Ucp1/Apoe double-knockout (DKO) mice fed a high-fat diet at 23 °C, with BAT hyperplasia and robust browning of inguinal white adipose tissue (IWAT) observed. Proteomics and gene expression analyses revealed significant increases in many proteins involved in energy metabolism and strong upregulation of brown/beige adipocyte-related genes and fatty acid metabolism-related genes in browned IWAT, suggesting an induction of beige fat formation and stimulation of lipid metabolism in DKO mice at 23 °C. Conversely, mRNA levels of fatty acid oxidation-related genes decreased in the liver of DKO mice. The favorable phenotypic changes were lost at 30 °C, with BAT whitening and disappearance of IWAT browning, while fatty liver further deteriorated in DKO mice compared with that in APOE-KO mice. Finally, longevity analysis revealed a significant lifespan extension of DKO mice compared with that of APOE-KO mice at 23 °C. Irrespective of the fundamental role of UCP1 thermogenesis, our results highlight the importance of beige fat for the improvement of hyperlipidemia and longevity under the atherogenic status at normal room temperature.
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http://dx.doi.org/10.1016/j.bbadis.2020.165762DOI Listing
July 2020

A central master driver of psychosocial stress responses in the rat.

Science 2020 03;367(6482):1105-1112

Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.
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http://dx.doi.org/10.1126/science.aaz4639DOI Listing
March 2020

Comparative Genomic Analysis of Closely Related Strains Provides Evidence of Horizontal Gene Transfer and Reveals Factors Necessary for Thermotolerance.

J Bacteriol 2020 03 26;202(8). Epub 2020 Mar 26.

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.

is an industrial strain used for the vinegar production. Many strains with different phenotypic characteristics have been isolated so far. To understand the genetic background underpinning these phenotypes, a comparative genomic analysis of strains was conducted. Based on bioinformatics and experimental results, we report the following. (i) The gene repertoire related to the respiratory chains showed that several horizontal gene transfer events occurred after the divergence of these strains, indicating that the respiratory chain in has the diversity to adapt to its environment. (ii) There is a clear difference in thermotolerance even between 12 closely related strains. NBRC 3279, NBRC 3284, and NBRC 3283, in particular, which have only 55 mutations in total, showed differences in thermotolerance. The Na/H antiporter gene was mutated in the thermosensitive NBRC 3279 and NBRC 3284 strains and not in the thermotolerant NBRC 3283 strain. The Na/H antiporter activity of the three strains and expression of gene from NBRC 3283 in the two thermosensitive strains showed that these mutations are critical for thermotolerance. These results suggested that horizontal gene transfer events and several mutations have affected the phenotypes of these closely related strains., an industrial vinegar-producing strain, exhibits diverse phenotypic differences such as respiratory activity related to acetic acid production, acetic acid resistance, or thermotolerance. In this study, we investigated the correlations between genome sequences and phenotypes among closely related strains. The gene repertoire related to the respiratory chains showed that the respiratory components of has a diversity caused by several horizontal gene transfers and mutations. In three closely related strains with clear differences in their thermotolerances, we found that the insertion or deletion that occurred in the Na/H antiporter gene is directly related to their thermotolerance. Our study suggests that a relatively quick mutation has occurred in the closely related due to its genetic instability and that this has largely affected its phenotype.
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http://dx.doi.org/10.1128/JB.00553-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099137PMC
March 2020

sp. nov., a glutamate producing bacterium isolated from soil and its complete genome-based analysis.

Int J Syst Evol Microbiol 2020 Mar 23;70(3):1903-1911. Epub 2020 Jan 23.

Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

Strain N24 was isolated from soil contaminated with starling's feces collected from Roi-Et province, Thailand. Cells of N24 were Gram-stain-positive rods, aerobic and non-spore-forming. N24 was positive for catalase, urease, citrate utilization, nitrate reduction and Methyl Red (MR) test but negative for oxidase, casein, gelatin liquefaction, tyrosine, Voges-Proskauer (VP) reaction and starch hydrolysis. -diaminopimelic acid, rhamnose, ribose, arabinose and galactose were detected in its whole-cell hydrolysates. The results of the 16S rRNA gene sequence analysis indicated that N24 represented a member of the genus . N24 was closely related to ATCC 13032, with 99.0 % 16S rRNA gene sequence similarity. According to results obtained using DNA-DNA hybridization approaches, N24 showed highest DNA-DNA relatedness (27.6 %) and average nucleotide identity (84.1 %) to ATCC 13032. The DNA G+C content of N24 was 51.8 mol% (genome based). The major cellular fatty acids of N24 were C, and Cω9. N24 had the nine isoprenes unit, MK-9(H) as the predominant menaquinone. The predominant polar lipids were phosphatidylglycerol, phosphatidylinositol and diphosphatidylglycerol. Mycolic acids were also present. According to the complete genome sequence data, strain N24 and ATCC 13032 are close phylogenetic neighbours, but have different genome characteristics. On the basis of the results of the genotypic and genomic studies and phenotypic characteristics including chemotaxonomy, strain N24 should be classified as representing a novel species of the genus , for which the name sp. nov. is proposed. The type strain is N24 (TBRC 5845=NBRC 113465).
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http://dx.doi.org/10.1099/ijsem.0.003993DOI Listing
March 2020

P-wave vector magnitude predicts the left atrial low-voltage area in patients with paroxysmal atrial fibrillation.

J Electrocardiol 2020 Mar - Apr;59:35-40. Epub 2019 Dec 28.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Background: P-wave amplitude (PWA) parameters can be the surrogate measures of the left atrial low-voltage areas (LVAs).

Methods: We measured PWAs using an automated system in 50 patients with paroxysmal atrial fibrillation (AF). We examined the relationships between left atrial LVAs and PWA parameters, including P-wave vector magnitude, calculated as the square root of the sum of lead II PWA squared, lead V6 PWA squared, and a one-half lead V2 PWA squared.

Results: Lead I PWA was most strongly correlated with LVAs in the anterior wall and appendage (anterior wall, R = -0.391, P = 0.006; appendage, R = -0.342, P = 0.016), whereas lead II PWA was most strongly correlated with LVAs in the septum, posterior wall, and bottom wall (septum, R = -0.413, P = 0.003; posterior wall, R = -0.297, P = 0.039; bottom wall; R = -0.288, P = 0.045). Although maximum, minimum, mean, and lead I PWAs were not correlated with total LVA, P-wave vector magnitude and lead II PWA were significantly correlated with total LVA (P-wave vector magnitude, R = -0.430, P = 0.002; lead II PWA, R = -0.323, P = 0.023). P-wave vector magnitude achieved the highest accuracy for predicting significant LVA (total LVA > 10%) with an area under the curve of 0.772; sensitivity, specificity, and positive and negative predictive values were 64%, 88%, 85%, and 69%, respectively, for the cutoff value of 0.130 mV.

Conclusion: P-wave vector magnitude is a useful electrocardiographic predictor of left atrial LVAs.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.12.015DOI Listing
June 2021

thermal adaptation of mesophilic NBRC 3283 generates thermotolerant strains with evolutionary trade-offs.

Biosci Biotechnol Biochem 2020 Apr 18;84(4):832-841. Epub 2019 Dec 18.

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.

Thermotolerant strains are critical for low-cost high temperature fermentation. In this study, we carried out the thermal adaptation of IFO 3283-32 under acetic acid fermentation conditions using an experimental evolution approach from 37ºC to 40ºC. The adapted strain exhibited an increased growth and acetic acid fermentation ability at high temperatures, however, with the trade-off response of the opposite phenotype at low temperatures. Genome analysis followed by PCR sequencing showed that the most adapted strain had 11 mutations, a single 64-kb large deletion, and a single plasmid loss. Comparative phenotypic analysis showed that at least the large deletion (containing many ribosomal RNAs and tRNAs genes) and a mutation of DNA polymerase (one of the 11 mutations) critically contributed to this thermotolerance. The relationship between the phenotypic changes and the gene mutations are discussed, comparing with another thermally adapted strains obtained previously.
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http://dx.doi.org/10.1080/09168451.2019.1703638DOI Listing
April 2020

Efficacy and safety of new-generation atrial antitachycardia pacing for atrial tachyarrhythmias in patients implanted with cardiac resynchronization therapy devices.

J Cardiol 2020 05 29;75(5):559-566. Epub 2019 Oct 29.

Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: Atrial tachyarrhythmias (ATAs) have a significant negative impact on the prognosis of patients implanted with cardiac resynchronization therapy (CRT) devices. New-generation atrial antitachycardia pacing (Reactive ATP, Medtronic Inc., Minneapolis, MN, USA) is effective in managing ATAs in patients implanted with pacemakers. The purpose of this study was to evaluate the efficacy and safety of Reactive ATP in patients implanted with CRT devices.

Methods: This was a single-center retrospective study involving 72 CRT patients with a history of ATAs [44 patients with a device capable of Reactive ATP (ATP group) and 28 patients with a device without ATP function (Control group)]. The atrial fibrillation (AF) burden, the biventricular pacing rate, and clinical outcomes were compared between the two groups.

Results: At baseline, there was no significant difference in the AF burden and biventricular pacing rate between the ATP and Control groups. During the 832±489 days of the follow-up period, 23 of the 44 patients (52%) received a total of 2862 ATP deliveries and the median ATP success rate was 23.6% (interquartile range: 12.5-50.0%) in the ATP group. The AF burden was significantly decreased only in the ATP group 6 months after ATP was programmed (from 6.1±18.2% to 2.0±5.4%, p=0.0083) and maintained low throughout the follow-up period. Moreover, there were no Reactive ATP-related complications observed. Patients in the ATP group showed a significantly lower incidence of heart failure (HF) hospitalization (log-rank, p=0.041) and ventricular arrhythmias (log-rank, p=0.039) than those reported in the Control group.

Conclusions: Reactive ATP successfully and safely reduced AF burden, and was associated with a lower incidence of HF hospitalization in patients implanted with CRT devices.
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http://dx.doi.org/10.1016/j.jjcc.2019.10.001DOI Listing
May 2020

Efficacy of a Device-Based Continuous Optimization Algorithm for Patients With Cardiac Resynchronization Therapy.

Circ J 2019 12 26;84(1):18-25. Epub 2019 Oct 26.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center.

Background: Cardiac resynchronization therapy (CRT) is less effective in patients with mildly wide QRS or non-left bundle branch block (non-LBBB). A new algorithm of every minute's optimization (adaptive CRT: aCRT algorithm) is effective in patients with CRT devices. This study investigated the clinical effect of the aCRT algorithm, especially in mildly wide QRS (120≤QRS<150 ms) or non-LBBB patients receiving CRT.Methods and Results:This study included 104 CRT patients (48 patients using the aCRT algorithm [adaptive group] and 56 patients not using the aCRT algorithm [non-adaptive group]). The primary endpoint was a composite clinical outcome of cardiac death and/or heart failure (HF) hospitalization. During a median follow-up of 700 days (interquartile range 362-1,173 days), aCRT reduced the risk of the clinical outcome, even in patients with mildly wide QRS or non-LBBB (log-rank P=0.0030 and P=0.0077, respectively) by Kaplan-Meier analysis. Use of the aCRT algorithm was an independent predictor of clinical outcomes in the multivariate analysis (hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.096-0.78, P=0.015), the same as in patients with mildly wide QRS (HR 0.12, 95% CI: 0.006-0.69, P=0.015).

Conclusions: The new aCRT algorithm was useful and significantly reduced the risk of the clinical outcome, even in patients with mildly wide QRS.
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http://dx.doi.org/10.1253/circj.CJ-19-0691DOI Listing
December 2019

Correlation between the left atrial low-voltage area and the cardiac function improvement after catheter ablation for paroxysmal atrial fibrillation.

J Arrhythm 2019 Oct 11;35(5):725-732. Epub 2019 Jul 11.

Second Department of Internal Medicine University of Toyama Toyama Japan.

Background: The impact of the left atrial low-voltage area (LVA) on the cardiac function improvement following ablation for atrial fibrillation (AF) is unclear.

Methods: In 49 patients with paroxysmal AF who underwent ablation, the left ventricular stroke volume index (SVI) was repeatedly measured using an impedance cardiography until 6 months after ablation. We defined the cardiac function improvement as a 20% increase in the SVI. The LVA (the area with the voltage amplitude of <0.5 mV) was assessed before ablation.

Results: The reduced baseline SVI (<33 mL/m) was observed in 18 (37%) patients. The SVI increased following ablation (from 36 ± 5 to 39 ± 6 mL/m,  < .001). We observed the cardiac function improvement in 14 (29%) patients. The LVA was smaller in patients with the improved cardiac function than in those without (8.3% ± 5.2% vs 14.0% ± 8.5%,  = .026). The multivariate analysis revealed that only the LVA was independently associated with the cardiac function improvement (odds ratio, 0.878; 95% confidence interval: 0.778-0.991,  = .036). Furthermore, LVAs of the anterior (7.9% ± 7.6% vs 18.2% ± 15.5%,  = .022), septal (12.0 ± 7.3% vs 20.7% ± 13.8%,  = .031), and roof walls (6.9% ± 6.0% vs 16.9% ± 15.2%,  = .022) were smaller in patients with the improved cardiac function than in those without.

Conclusions: The LVA was related to the cardiac function improvement following ablation in patients with paroxysmal AF.
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http://dx.doi.org/10.1002/joa3.12221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787158PMC
October 2019

Left atrial wall thickness is associated with the low-voltage area in patients with paroxysmal atrial fibrillation.

J Interv Card Electrophysiol 2020 Sep 13;58(3):315-321. Epub 2019 Aug 13.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Purpose: To identify a potential morphological marker of remodeling and electrophysiological dysfunction, we investigated if low wall thickness is associated with low-voltage areas (LVAs) in the left atrium.

Methods: Wall thickness was measured by computed tomography and LVA (% area with bipolar voltage < 0.5 mV) by voltage mapping in 43 paroxysmal AF patients. The left atrium was divided into five segments: septal wall, anterior wall, roof wall, posterior wall, and bottom wall in regional analysis.

Results: Left atrial wall thickness and LVA were 3.2 ± 0.6 mm and 14% ± 9%, respectively. Multivariate analysis identified left atrial wall thickness and volume as independent determinants of left atrial LVA (thickness, standardized β - 0.374, 95%CI - 23.289 to - 4.534, P = 0.005; volume, standardized β 0.452, 95%CI 0.049-0.214, P = 0.002). In regional analysis, significant LVA (> 10% of segment surface area) was observed in 123 of 215 segments (57%). Segments in the low tertile of wall thickness (< 1.76 mm) had larger LVAs compared with segments in middle (1.76-2.14 mm) and high tertiles (≥ 2.14 mm) (low tertile, 20.3% ± 14.9%; middle tertile, 12.6% ± 11.2%; high tertile, 12.5% ± 12.1%; low vs. middle tertile, P = 0.001; low vs. high tertile, P = 0.001). Area under the receiver operating curve of wall thickness was 0.706 for prediction of significant LVA. A thickness cut-off of 1.90 mm yielded 62% sensitivity, 73% specificity, 75% positive predictive value, and 59% negative predictive value for significant LVA.

Conclusion: A thin left atrial wall is an independent predictor of LVA in patients with paroxysmal AF.
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http://dx.doi.org/10.1007/s10840-019-00611-1DOI Listing
September 2020

Left atrial posterior wall isolation affects complex fractionated atrial electrograms in persistent atrial fibrillation.

J Arrhythm 2019 Jun 12;35(3):528-534. Epub 2019 Apr 12.

Second Department of Internal Medicine University of Toyama Toyama Japan.

Background: The impact of left atrial posterior wall isolation (LAPWI) on the complex fractionated atrial electrogram (CFAE) is unknown.

Methods: CFAE mapping was performed before and after LAPWI in 46 patients with persistent atrial fibrillation (AF).

Results: LAPWI decreased both the variable (fractionated index ≤ 120 ms; from 60 ± 4 cm to 50 ± 4 cm,  < 0.001) and continuous (fractionated index ≤ 50 ms; from 4.2 ± 1.0 cm to 3.5 ± 0.9 cm,  = 0.036) CFAE areas. Especially, the CFAE areas on the bottom and roof walls of the left atrium and on the posterior and bottom walls of the right atrium significantly decreased after LAPWI. The distribution of variable CFAE areas was not different between the AF-recurrence (n = 9) and AF-free (n = 37) groups before LAPWI; however, it was larger in the anterior and septal walls of the right atrium in the AF-recurrence group than in the AF-free group after LAPWI (anterior wall, 8% ± 2% vs 5% ± 1%,  = 0.048; septal wall, 23% ± 4% vs 16% ± 1%,  = 0.043). The distribution of continuous CFAE areas on the bottom wall of the right atrium was larger in the AF-recurrence group than in the AF-free group both before LAPWI (30% ± 20% vs 4% ± 2%,  = 0.008) and after LAPWI (25% ± 25% vs 3% ± 1%,  = 0.027).

Conclusions: LAPWI decreased the CFAE areas and affected their distribution, which contributed to AF recurrence.
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http://dx.doi.org/10.1002/joa3.12182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595290PMC
June 2019

Comparing the catheter delivery system and the stylet delivery system for ventricular lead placement in pacemaker implantation-The CATS delivery system randomized controlled trial.

J Arrhythm 2019 Jun 29;35(3):524-527. Epub 2019 Mar 29.

Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan.

Background: Right ventricular lead placement is one of the fundamental procedures during pacemaker implantation through the subclavian vein. Currently, there are two techniques to deliver the lead to the right ventricle: the catheter and stylet delivery systems. Surgeons, especially trainees in the early stage of training, are known to face difficulty while delivering the lead to the right ventricle. The objective of this study is to investigate and compare the two techniques of lead delivery by trainees in patients who are scheduled to undergo pacemaker implantation.

Methods: This is a prospective, single-center, randomized controlled clinical trial. One-hundred patients who were scheduled to undergo pacemaker implantation with a right ventricular lead will be randomized such that the pacemaker can be implanted via either the catheter delivery system or the stylet delivery system at a 1:1 ratio. The primary endpoint is the total number of attempts needed to place the lead in the ideal position. Secondary endpoints are the efficacy and safety of the implantation procedure. All implantation procedures will be performed by trainees under the supervision of expert cardiologists.

Results: The results of this study are currently under investigation.

Conclusion: This will be the first clinical trial to compare the efficacy and safety of the catheter delivery system and the stylet delivery system during the implantation of the ventricular lead in pacemaker implantation. Our findings are expected to improve the lead implantation procedure by providing information about which delivery system to choose in which situation.
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http://dx.doi.org/10.1002/joa3.12179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595325PMC
June 2019

Clinical Differences in Japanese Patients Between Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy With Long-Term Follow-Up.

Am J Cardiol 2019 09 12;124(5):715-722. Epub 2019 Jun 12.

Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Some Brugada syndrome (BrS) patients have been suspected of being in the initial state of arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aimed to clarify the electrocardiographic (ECG) and clinical differences between BrS and ARVC in long-term follow-up (mean 11.9 ± 6.3 years). A total of 50 BrS and 65 ARVC patients with fatal ventricular tachyarrhythmia (VTA) were evaluated according to the revised Task Force Criteria for ARVC. Based on the current diagnostic criteria concerning electrocardiographic, repolarization abnormality was positive in 2.0% and 2.6% of BrS patients at baseline and follow-up, and depolarization abnormality was positive in 6.0% and 12.8% of BrS patients at baseline and follow-up, respectively. At baseline, none of the BrS patients were definitively diagnosed with ARVC. Considering patients' lives since birth, Kaplan-Meier analysis revealed that age at first VTA attack showed the same tendency between the groups (BrS: mean 42.2 ± 12.5 years old vs ARVC: mean 44.8 ± 13.7 years old, log-rank p = 0.123). Moreover, the incidence of VTA recurrence was similar between the groups during follow-up (log-rank p = 0.906). Incidence of sustained monomorphic ventricular tachycardia was significantly higher in ARVC than in BrS whereas the opposite was true for ventricular fibrillation (log-rank p <0.001 and p <0.001, respectively). None of the diagnoses of BrS patients were changed to ARVC during follow-up. During long-term follow-up, although age at first VTA attack and VTA recurrence were similar, BrS consistently exhibited features that differed from those of ARVC.
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http://dx.doi.org/10.1016/j.amjcard.2019.05.067DOI Listing
September 2019

The effect of reactive oxygen species (ROS) and ROS-scavenging enzymes, superoxide dismutase and catalase, on the thermotolerant ability of Corynebacterium glutamicum.

Appl Microbiol Biotechnol 2019 Jul 30;103(13):5355-5366. Epub 2019 Apr 30.

Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, 753-8515, Japan.

The function of two reactive oxygen species (ROS) scavenging enzymes, superoxide dismutase (SOD) and catalase, on the thermotolerant ability of Corynebacterium glutamicum was investigated. In this study, the elevation of the growth temperature was shown to lead an increased intracellular ROS for two strains of Corynebacterium glutamicum, the wild-type (KY9002) and the temperature-sensitive mutant (KY9714). In order to examine the effects of ROS-scavenging enzymes on cell growth, either the SOD or the catalase gene was disrupted or overexpressed in KY9002 and KY9714. In the case of the KY9714 strain, it was shown that the disruption of SOD and catalase disturbs cell growth, while the over-productions of both the enzymes enhances cell growth with a growth temperature of 30 °C and 33 °C. Whereas, in the relatively thermotolerant KY9002 strain, the disruption of both enzymes exhibited growth defects more intensively at higher growth temperatures (37 °C or 39 °C), while the overexpression of at least SOD enhanced the cell growth at higher temperatures. Based on the correlation between the cell growth and ROS level, it was suggested that impairment of cell growth in SOD or catalase-disrupted strains could be a result of an increased ROS level. In contrast, the improvement in cell growth for strains with overexpressed SOD or catalase resulted from a decrease in the ROS level, especially at higher growth temperatures. Thus, SOD and catalase might play a crucial role in the thermotolerant ability of C. glutamicum by reducing ROS-induced temperature stress from higher growth temperatures.
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http://dx.doi.org/10.1007/s00253-019-09848-2DOI Listing
July 2019

CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.

FASEB J 2019 07 27;33(7):8069-8082. Epub 2019 Mar 27.

Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan.

Increased formation of brown and beige adipocytes is critical for adaptive thermogenesis to maintain homeothermy in cold or to circumvent diet-induced obesity (DIO). Cellular repressor of adenovirus early region 1A-stimulated genes 1 (CREG1) exhibits the ability to stimulate brown adipogenesis, including the induction of uncoupling protein 1 (UCP1), . Thus, we aimed to clarify whether CREG1 promotes brown adipocyte formation and inhibits DIO at the whole-animal level. In mouse brown adipose tissue (BAT), CREG1 expression was markedly increased in cold but was decreased under thermoneutrality, suggesting CREG1 involvement in BAT thermogenesis. Moreover, in BAT and white adipose tissue, expression of UCP1 and fibroblast growth factor-21 and browning were both significantly higher in adipocyte P2-Creg1-transgenic (Tg) mice than in wild-type (WT) littermates. Following stimulation with a β3-adrenergic agonist, energy consumption was elevated in the Tg mice, which showed increased resistance to DIO and improvement of obesity-associated complications including fatty liver relative to WT mice. The CREG1 stimulatory effect on brown adipogenesis was confirmed in Tg-BAT primary cultures. It was also found that CREG1 binds to retinoid X receptor α, which interacts with thyroid hormone receptor for brown adipogenesis. Our findings demonstrate that CREG1 stimulates brown adipocyte formation and browning, ameliorating obesity and its related pathology .-Hashimoto, M., Kusudo, T., Takeuchi, T., Kataoka, N., Mukai, T., Yamashita, H. CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.
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http://dx.doi.org/10.1096/fj.201802147RRDOI Listing
July 2019

P-wave vector magnitude predicts recurrence of atrial fibrillation after catheter ablation in patients with persistent atrial fibrillation.

Ann Noninvasive Electrocardiol 2019 09 21;24(5):e12646. Epub 2019 Mar 21.

Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

Background: The predictive efficacies of parameters related to P-wave amplitude (PWA) for atrial fibrillation (AF) recurrence after catheter ablation are unclear.

Methods: We measured multiple PWA parameters using an automated system in 126 consecutive patients with persistent and long-standing persistent AF who underwent catheter ablation. The relationships between AF recurrence and various PWA parameters were examined, including the association with P-wave vector magnitude (calculated as the square root of the sum of lead II PWA squared, lead V6 PWA squared, and a one-half lead V2 PWA squared).

Results: Atrial fibrillation did not recur in 87 patients (69%) during 32 ± 15 months of follow-up. The maximum PWA, mean PWA, and P-wave vector magnitude were lower in patients with AF recurrence than those without (maximum PWA, 0.14 ± 0.05 mV vs. 0.16 ± 0.05 mV, p = 0.017; mean PWA, 0.05 ± 0.02 mV vs. 0.06 ± 0.02 mV, p = 0.003; P-wave vector magnitude, 0.09 ± 0.03 mV vs. 0.13 ± 0.04 mV, p < 0.001). A multivariate Cox regression analysis revealed that the predictive ability of P-wave vector magnitude for AF recurrence was independent of other clinical properties (hazard ratio: 0.153, 95% confidence interval: 0.046-0.507, p = 0.002). Atrial fibrillation freedom rates of patients with P-wave vector magnitude higher and lower than 0.13 mV were 93% and 57%, respectively. P-wave vector magnitude weakly correlated with left atrial dimension (R = -0.280, p = 0.004).

Conclusions: P-wave vector magnitude can predict AF recurrence after catheter ablation in patients with persistent AF.
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http://dx.doi.org/10.1111/anec.12646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931428PMC
September 2019