Publications by authors named "Noriko Hayashi"

63 Publications

Complete sequencing of expanded SAMD12 repeats by long-read sequencing and Cas9-mediated enrichment.

Brain 2021 Apr 1. Epub 2021 Apr 1.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

A pentanucleotide TTTCA repeat insertion into a polymorphic TTTTA repeat element in SAMD12 causes benign adult familial myoclonic epilepsy. Although the precise determination of the entire SAMD12 repeat sequence is important for molecular diagnosis and research, obtaining this sequence remains challenging when using conventional genomic/genetic methods, and even short-read and long-read next-generation sequencing technologies have been insufficient. Incomplete information regarding expanded repeat sequences may hamper our understanding of the pathogenic roles played by varying numbers of repeat units, genotype-phenotype correlations, and mutational mechanisms. Here, we report a new approach for the precise determination of the entire expanded repeat sequence and present a workflow designed to improve the diagnostic rates in various repeat expansion diseases.
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http://dx.doi.org/10.1093/brain/awab021DOI Listing
April 2021

Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study.

BMJ Open Diabetes Res Care 2021 Feb;9(1)

Department of Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.

Introduction: Current dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.

Research Design And Methods: This was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7-14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.

Results: D-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).

Conclusions: This is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.

Trial Registration Number: NCT02714413.
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http://dx.doi.org/10.1136/bmjdrc-2020-001939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919569PMC
February 2021

Changes in the Dimensions of Lignocellulose Nanofibrils with Different Lignin Contents by Enzymatic Hydrolysis.

Polymers (Basel) 2020 Sep 25;12(10). Epub 2020 Sep 25.

Department of Forest Biomaterials and Engineering, College of Forest and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea.

Changes in the dimensions of lignocellulose nanofibrils (LCNFs) with different lignin contents from betung bamboo () by enzymatic hydrolysis using endoglucanase (EG) were investigated. Lignin contents were adjusted from 3% to 27% by NaClO/acetic acid treatment, and LCNFs were prepared using a wet disk-mill (WDM). The dimensions of the LCNFs significantly decreased with decreasing lignin content and increasing EG addition. With increasing EG content, the average diameter of the LCNFs significantly decreased, even though they contained parts of hemicellulose and lignin. The crystal structure showed the typical cellulose I structure in all samples, but the intensity of the diffraction peak slightly changed depending on the lignin and EG contents. The crystallinity index (CrI) values of the LCNFs increased a maximum of 23.8% (LCNF-L27) under increasing EG addition, regardless of the lignin content. With the EG addition of three times the LCNF amount, LCNF-L3 showed the highest CrI value (59.1%). By controlling the composition and structure of LCNFs, it is expected that the wide range of properties of these materials can extend the property range available for existing materials.
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http://dx.doi.org/10.3390/polym12102201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600893PMC
September 2020

Localization of (+)-Catechin in Phloem: Responses to Wounding and Fungal Inoculation.

Molecules 2020 Jun 26;25(12). Epub 2020 Jun 26.

Nagoya University, Department of Forest and Environmental Resources Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

To understand the positional and temporal defense mechanisms of coniferous tree bark at the tissue and cellular levels, the phloem topochemistry and structural properties were examined after artificially induced bark defense reactions. Wounding and fungal inoculation with of spruce bark were carried out, and phloem tissues were frequently collected to follow the temporal and spatial progress of chemical and structural responses. The changes in (+)-catechin, (-)-epicatechin, stilbene glucoside, and resin acid distribution, and accumulation patterns within the phloem, were mapped using time-of-flight secondary ion mass spectrometry (cryo-ToF-SIMS), alongside detailed structural (LM, TEM, SEM) and quantitative chemical microanalyses of the tissues. Our results show that axial phloem parenchyma cells of Norway spruce contain (+)-catechins, the amount of which locally increases in response to fungal inoculation. The preformed, constitutive distribution and accumulation patterns of (+)-catechins closely follow those of stilbene glucosides. Phloem phenolics are not translocated but form a layered defense barrier with oleoresin compounds in response to pathogen attack. Our results suggest that axial phloem parenchyma cells are the primary location for (+)-catechin storage and synthesis in Norway spruce phloem. Chemical mapping of bark defensive metabolites by cryo-ToF-SIMS, in addition to structural and chemical microanalyses of the defense reactions, can provide novel information on the local amplitudes and localizations of chemical and structural defense mechanisms and pathogen-host interactions of trees.
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http://dx.doi.org/10.3390/molecules25122952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356009PMC
June 2020

Eucommia Leaf Extract Induces BDNF Production in Rat Hypothalamus and Enhances Lipid Metabolism and Aerobic Glycolysis in Rat Liver.

Curr Mol Pharmacol 2021 ;14(2):234-244

Department of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Mie513-8670, Japan.

Background: Mutations in the brain-derived neurotrophic factor (BDNF) gene and its receptor, tyrosine receptor kinase B (TrkB), have been reported to cause severe obesity in rodents. Our previous study demonstrated that the oral administration of 5% Eucommia leaf extract (ELE) or ELE aroma treatment (ELE aroma) produced anti-obesity effects.

Objective: In this study, we investigated the effects of ELE on glycolysis and lipid metabolism in male Sprague-Dawley rats, as well as the effects of ELE on BDNF in rat hypothalamus.

Methods And Results: A significant reduction and a reduction tendency in the respiratory quotient were observed in association with 5% ELE and ELE aroma treatment, respectively. Furthermore, RT-qPCR results showed significant increases in Cpt2, Acad, Complex II, and Complex V mRNA levels in the liver with both treatments. In addition, in rat hypothalamus, significant elevations in BDNF, Akt, PLCγ proteins and CREB phosphorylation were observed in the 5% ELE group and the ELE aroma group. Furthermore, the Ras protein was significantly increased in the ELE aroma group. On the other hand, significant dephosphorylation of ERK1/2 was observed by the western blotting in the 5% ELE group and the ELE aroma group.

Conclusion: These findings suggest that the ELE treatment enhances the lipid metabolism and increases the aerobic glycolytic pathway, while ELE-induced BDNF may affect such energy regulation. Therefore, ELE has the possibility to control metabolic syndrome.
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http://dx.doi.org/10.2174/1874467213666200505094631DOI Listing
January 2021

Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients.

Neurosci Res 2020 Nov 24;160:43-49. Epub 2019 Oct 24.

Department of Neurology and Stroke Medicine, Yokohama, Japan. Electronic address:

Exosomes contain many proteins associated with neurodegenerative diseases. To identify new candidate biomarkers and proteins associated with amyotrophic lateral sclerosis (ALS), we performed liquid chromatography-tandem mass spectrometry proteomic analysis of exosome-enriched fractions isolated from cerebrospinal fluid (CSF) of sporadic ALS patients using gel filtration chromatography. Proteomic data revealed that three proteins were increased and 11 proteins were decreased in ALS patients. The protein with the greatest increase in exosome-enriched fractions of CSF derived from ALS was novel INHAT repressor (NIR), which is closely associated with nucleolar function. By immunohistochemical analysis, we found that NIR was reduced in the nucleus of motor neurons in ALS patients. Our results demonstrate the potential utility of our methodology for proteomic analysis of CSF exosomes and suggest that nucleolar stress might play a role in sporadic ALS pathogenesis through the dysfunction of NIR.
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http://dx.doi.org/10.1016/j.neures.2019.10.010DOI Listing
November 2020

Ataxic phenotype with altered Ca3.1 channel property in a mouse model for spinocerebellar ataxia 42.

Neurobiol Dis 2019 10 20;130:104516. Epub 2019 Jun 20.

Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Spinocerebellar ataxia 42 (SCA42) is a neurodegenerative disorder recently shown to be caused by c.5144G > A (p.Arg1715His) mutation in CACNA1G, which encodes the T-type voltage-gated calcium channel Ca3.1. Here, we describe a large Japanese family with SCA42. Postmortem pathological examination revealed severe cerebellar degeneration with prominent Purkinje cell loss without ubiquitin accumulation in an SCA42 patient. To determine whether this mutation causes ataxic symptoms and neurodegeneration, we generated knock-in mice harboring c.5168G > A (p.Arg1723His) mutation in Cacna1g, corresponding to the mutation identified in the SCA42 family. Both heterozygous and homozygous mutants developed an ataxic phenotype from the age of 11-20 weeks and showed Purkinje cell loss at 50 weeks old. Degenerative change of Purkinje cells and atrophic thinning of the molecular layer were conspicuous in homozygous knock-in mice. Electrophysiological analysis of Purkinje cells using acute cerebellar slices from young mice showed that the point mutation altered the voltage dependence of Ca3.1 channel activation and reduced the rebound action potentials after hyperpolarization, although it did not significantly affect the basic properties of synaptic transmission onto Purkinje cells. Finally, we revealed that the resonance of membrane potential of neurons in the inferior olivary nucleus was decreased in knock-in mice, which indicates that p.Arg1723His Ca3.1 mutation affects climbing fiber signaling to Purkinje cells. Altogether, our study shows not only that a point mutation in CACNA1G causes an ataxic phenotype and Purkinje cell degeneration in a mouse model, but also that the electrophysiological abnormalities at an early stage of SCA42 precede Purkinje cell loss.
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http://dx.doi.org/10.1016/j.nbd.2019.104516DOI Listing
October 2019

Long-term outcomes after sustained unresponsiveness in patients who underwent oral immunotherapy for egg, cow's milk, or wheat allergy.

Allergol Int 2019 Oct 29;68(4):527-528. Epub 2019 Mar 29.

Department of Allergy, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.alit.2019.02.012DOI Listing
October 2019

Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.

Food Funct 2018 Dec;9(12):6279-6286

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.

Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1-3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4-10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6'-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the corresponding amino acid residues at the binding site of P-gp. In addition, we investigated the cytotoxicity of these compounds towards cell lines overexpressing other ABC transporters (BCRP, ABCB5), cell lines with a knocked out tumor suppressor gene TP53 or cell lines overexpressing a deletion-activated EGFR oncogene. These cell lines were sensitive or only minimally cross-resistant to these compounds compared with their corresponding wild-type cell lines.
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http://dx.doi.org/10.1039/c8fo01804aDOI Listing
December 2018

Brain activity in response to the touch of a hand on the center of the back.

PLoS One 2018 29;13(10):e0206451. Epub 2018 Oct 29.

Nagoya University of Arts and Sciences, Nisshin, Aichi, Japan.

The aim of this study was to validate the possibility of using functional Near-Infrared Spectroscopy (fNIRS) to measure changes in cerebral blood flow in response to a hand being placed on a participant's back, and to identify the areas of enhanced activity in the brain. Nineteen female adult volunteers participated in the study. An experienced school nurse touched the center of the participant's back between the shoulder blades with the palm of her hand. Cerebral blood volume dynamics were measured with a 52-channel fNIRS system. Significantly higher oxygenated hemoglobin (oxy-Hb) concentration levels were recorded by channels 11, 14, 21, 22, 24, 32, 35, 45, 46, and 49 during the touching period than during the resting period. These channels indicated enhanced activity in the supramarginal gyrus, the middle frontal gyrus, the superior temporal gyrus, and the inferior frontal gyrus. The ability to detect changes in cerebral blood flow using this method indicates the possibility of measuring changes in cerebral blood flow using fNIRS when a person is touched on the back. fNIRS has been shown to be useful for studying the effects of touch.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206451PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205618PMC
April 2019

Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.

J Hum Genet 2018 Apr 5;63(4):417-423. Epub 2018 Feb 5.

Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous neurological disorders. Through whole-exome sequencing of Japanese ARCA patients, we identified three index patients from unrelated families who had biallelic mutations in ERCC4. ERCC4 mutations have been known to cause xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anemia phenotypes. All of the patients described here showed very slowly progressive cerebellar ataxia and cognitive decline with choreiform involuntary movement, with young adolescent or midlife onset. Brain MRI demonstrated atrophy that included the cerebellum and brainstem. Of note, cutaneous symptoms were very mild: there was normal to very mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn. However, an unscheduled DNA synthesis assay of fibroblasts from the patient revealed impairment of nucleotide excision repair. A similar phenotype was very recently recognized through genetic analysis of Caucasian cerebellar ataxia patients. Our results confirm that biallelic ERCC4 mutations cause a cerebellar ataxia-dominant phenotype with mild cutaneous symptoms, possibly accounting for a high proportion of the genetic causes of ARCA in Japan, where XP-F is prevalent.
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http://dx.doi.org/10.1038/s10038-017-0408-5DOI Listing
April 2018

Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis.

Am J Pathol 2018 02 9;188(2):507-514. Epub 2017 Nov 9.

Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address:

Mutations in the MATR3 gene have been identified as a cause of familial amyotrophic lateral sclerosis, but involvement of the matrin 3 (MATR3) protein in sporadic amyotrophic lateral sclerosis (SALS) pathology has not been fully assessed. We immunohistochemically analyzed MATR3 pathology in the spinal cords of SALS and control autopsy specimens. MATR3 immunostaining of the motor neuron nuclei revealed two distinct patterns: mild and strong staining. There were no differences in the ratio of mild versus strong nuclear staining between the SALS and control cases. MATR3-containing neuronal cytoplasmic inclusions (NCIs) were observed in 60% of SALS cases. Most motor neurons with MATR3-positive NCIs exhibited a mild nuclear staining pattern. Although 16.8% of NCIs positive for transactivating response region DNA-binding protein 43 (TDP-43) were estimated as double-labeled by MATR3, no MATR3-positive or TDP-43-negative NCIs were observed. Although a previous study found that MATR3-positive NCIs are present only in cases with C9orf72 hexanucleotide repeat expansion, ubiquitin-positive granular NCIs were not observed in the cerebellum, which have been reported as specific to C9orf72-related ALS. Six ALS cases were confirmed to be negative for the GGGGCC hexanucleotide. Our results reveal that MATR3 is a component of TDP-43-positive NCIs in motor neurons, even in SALS, and indicate the broader involvement of MATR3 in ALS pathology and the heterogeneity of TDP-43-positive NCIs.
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http://dx.doi.org/10.1016/j.ajpath.2017.10.007DOI Listing
February 2018

Promoter-level transcriptome in primary lesions of endometrial cancer identified biomarkers associated with lymph node metastasis.

Sci Rep 2017 10 26;7(1):14160. Epub 2017 Oct 26.

Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.

For endometrial cancer patients, lymphadenectomy is recommended to exclude rarely metastasized cancer cells. This procedure is performed even in patients with low risk of recurrence despite the risk of complications such as lymphedema. A method to accurately identify cases with no lymph node metastases (LN-) before lymphadenectomy is therefore highly required. We approached this clinical problem by examining primary lesions of endometrial cancers with CAGE (Cap Analysis Gene Expression), which quantifies promoter-level expression across the genome. Fourteen profiles delineated distinct transcriptional networks between LN + and LN- cases, within those classified as having the low or intermediate risk of recurrence. Subsequent quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses of 115 primary tumors showed SEMA3D mRNA and TACC2 isoforms expressed through a novel promoter as promising biomarkers with high accuracy (area under the receiver operating characteristic curve, 0.929) when used in combination. Our high-resolution transcriptome provided evidence of distinct molecular profiles underlying LN + /LN- status in endometrial cancers, raising the possibility of preoperative diagnosis to reduce unnecessary operations in patients with minimum recurrence risk.
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http://dx.doi.org/10.1038/s41598-017-14418-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658375PMC
October 2017

Atomic and nanoscale imaging of a cellulose nanofiber and Pd nanoparticles composite using lower-voltage high-resolution TEM.

Microscopy (Oxf) 2017 Oct;66(5):348-355

Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan.

We have examined the advanced application of transmission electron microscopy (TEM) for the structural characterization of a composite of cellulose nanofiber (CNF) and palladium (Pd) nanoparticles. In the present study, we focused on electron-irradiation damage and optimization of high-resolution TEM imaging of the composite. The investigation indicates that the CNF breaks even under low-electron-dose conditions at an acceleration voltage of 200 kV. We then applied lower-voltage TEM at 60 kV using a spherical aberration corrector and a monochromator, in order to reduce electron-irradiation damage and improve the spatial resolution. The TEM observation achieved high-resolution imaging and revealed the existence of small Pd nanoparticles, around 2 nm in diameter, supported on the CNF. It is considered that the use of a monochromator in combination with spherical aberration correction contributed to the atomic and nanoscale imaging of the composite, owing to the improvement of the information limit under a lower-acceleration voltage.
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http://dx.doi.org/10.1093/jmicro/dfx021DOI Listing
October 2017

d-Allulose enhances postprandial fat oxidation in healthy humans.

Nutrition 2017 Nov - Dec;43-44:16-20. Epub 2017 Jul 6.

Research and Development Department, Matsutani Chemical Industry Co., Ltd., Hyogo, Japan.

Objective: d-Allulose, a C-3 epimer of d-fructose, has been reported to decrease body weight and adipose tissue weight in animal studies and is expected to be a potent antiobese sweetener. Our animal study suggested that one of the mechanisms of d-allulose's antiobesity function is an increase in energy expenditure. However, a few studies have thus far explored the underlying mechanism in humans. The aim of this study was to examine the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy participants.

Methods: Thirteen healthy men and women (mean age of 35.7 ± 2.1 y and body mass index 20.9 ± 0.7 kg/m) were studied. The study was a randomized, single-blind crossover design with a 1-wk washout period. At 30 min after taking 5 g of d-allulose or 10 mg of aspartame without any sugar as a control, overnight-fasted participants ingested a standardized meal, and energy metabolism was evaluated by a breath-by-breath method. During the experiment, blood was collected and biochemical parameters such as plasma glucose were analyzed.

Results: In the d-allulose-treated group, the area under the curve of fat oxidation was significantly higher than in the control group (10.5 ± 0.4 versus 9.6 ± 0.3 kJ·4 h·kg body weight [BW]; P < 0.05), whereas that of carbohydrate oxidation was significantly lower (8.1 ± 0.5 versus 9.2 ± 0.5 kJ·4 h·kg BW; P < 0.05). Furthermore, plasma glucose levels were significantly lower, and free fatty acid levels were significantly higher in the d-allulose group than in the control group. No other parameters such as insulin, total cholesterol, or triacylglycerol were modified.

Conclusion: d-Allulose enhances postprandial fat oxidation in healthy humans, indicating that it could be a novel sweetener to control and maintain healthy body weight, probably through enhanced energy metabolism.
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http://dx.doi.org/10.1016/j.nut.2017.06.007DOI Listing
May 2018

Induced accumulation of tyramine, serotonin, and related amines in response to Bipolaris sorokiniana infection in barley.

Biosci Biotechnol Biochem 2017 Jun 13;81(6):1090-1098. Epub 2017 Feb 13.

a Faculty of Agriculture , Tottori University , Tottori , Japan.

The inducible metabolites were analyzed in barley leaves inoculated with Bipolaris sorokiniana, the causal agent of spot blotch of barley. HPLC analysis revealed that B. sorokiniana-infected leaves accumulated 4 hydrophilic compounds. They were purified by ODS column chromatography and preparative HPLC. Spectroscopic analyses revealed that they were tyramine (1), 3-(2-aminoethyl)-3-hydroxyindolin-2-one (2), serotonin (3), and 5,5'-dihydroxy-2,4'-bitryptamine (4). Among these, 2 and 4 have not been reported as natural products. They showed antifungal activity in an assay of inhibition of B. sorokiniana conidia germination, suggesting that they play a role in the chemical defense of barley as phytoalexins. The accumulation of 1-4 was examined also in the leaves of rice and foxtail millet. Rice leaves accumulated 2, 3, and 4, whereas foxtail millet leaves accumulated 3 and 4 in response to pathogen attack, suggesting the generality of accumulation of 3 and 4 in the Poaceae species.
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http://dx.doi.org/10.1080/09168451.2017.1290520DOI Listing
June 2017

Rare Sugar Syrup Containing d-Allulose but Not High-Fructose Corn Syrup Maintains Glucose Tolerance and Insulin Sensitivity Partly via Hepatic Glucokinase Translocation in Wistar Rats.

J Agric Food Chem 2017 Apr 9;65(13):2888-2894. Epub 2017 Mar 9.

Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University , 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi468-8503, Japan.

Ingestion of high-fructose corn syrup (HFCS) is associated with the risk of both diabetes and obesity. Rare sugar syrup (RSS) has been developed by alkaline isomerization of HFCS and has anti-obesity and anti-diabetic effects. However, the influence of RSS on glucose metabolism has not been explored. We investigated whether long-term administration of RSS maintains glucose tolerance and whether the underlying mechanism involves hepatic glucokinase translocation. Wistar rats were administered water, RSS, or HFCS in drinking water for 10 weeks and then evaluated for glucose tolerance, insulin tolerance, liver glycogen content, and subcellular distribution of liver glucokinase. RSS significantly suppressed body weight gain and abdominal fat mass (p < 0.05). The glucose tolerance test revealed significantly higher blood glucose levels in the HFCS group compared to the water group, whereas the RSS group had significantly lower blood glucose levels from 90 to 180 min (p < 0.05). At 30, 60, and 90 min, the levels of insulin in the RSS group were significantly lower than those in the water group (p < 0.05). The amount of hepatic glycogen was more than 3 times higher in the RSS group than that in the other groups. After glucose loading, the nuclear export of glucokinase was significantly increased in the RSS group compared to the water group. These results imply that RSS maintains glucose tolerance and insulin sensitivity, at least partly, by enhancing nuclear export of hepatic glucokinase.
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http://dx.doi.org/10.1021/acs.jafc.6b05627DOI Listing
April 2017

Tunicamycin-induced inhibition of protein secretion into culture medium of Arabidopsis T87 suspension cells through mRNA degradation on the endoplasmic reticulum.

Biosci Biotechnol Biochem 2016 Jun 29;80(6):1168-71. Epub 2016 Feb 29.

a Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Osaka , Japan.

The N-glycosylation inhibitor tunicamycin triggers endoplasmic reticulum stress response and inhibits efficient protein secretion in eukaryotes. Using Arabidopsis suspension cells, we showed that the reduced secretion of mannose-binding lectin 1 (MBL1) protein by tunicamycin is accompanied by a significant decrease in MBL1 mRNA, suggesting that mRNA destabilization is the major cause of the inhibition of protein secretion in plants.
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http://dx.doi.org/10.1080/09168451.2016.1151340DOI Listing
June 2016

Synthesis of Polyaniline (PANI) in Nano-Reaction Field of Cellulose Nanofiber (CNF), and Carbonization.

Polymers (Basel) 2016 Feb 2;8(2). Epub 2016 Feb 2.

Division of Materials Science, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba Ibaraki 305-8573, Japan.

Polymerization of aniline in the presence of cellulose nano-fiber (CNF) is carried out. We used dried CNF, CNF suspension, and CNF treated by enzyme and ultra-sonification to obtain polyaniline (PANI)/CNF as a synthetic polymer/natural nano-polymer composite. The polymerization proceeds on the surface of CNF as a nano-reaction field. Resultant composites show extended effective π-conjugation length because CNF as a reaction field in molecular level produced polymer with expanded coil structure with an aid of orientation effect of CNF. Possibility of PANI β-pleats structure in molecular level of PANI on the CNF is also discussed. SEM observation showed that fine structure is easily obtained by combining PANI with CNF. Carbonization of PANI/CNF allows production of nano-fine form with shape preserved carbonization (SPC).
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http://dx.doi.org/10.3390/polym8020040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432580PMC
February 2016

[Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

Shokuhin Eiseigaku Zasshi 2015 ;56(5):211-6

Matsutani Chemical Industry Co., Ltd., Research & Development.

The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.
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http://dx.doi.org/10.3358/shokueishi.56.211DOI Listing
June 2016

Wheat oral immunotherapy for wheat-induced anaphylaxis.

J Allergy Clin Immunol 2015 Oct 28;136(4):1131-3.e7. Epub 2015 Aug 28.

Department of Allergy, Clinical Research Center for Allergology and Rheumatology, Sagamihara National Hospital, Kanagawa, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2015.07.019DOI Listing
October 2015

Dietary D-sorbose decreases serum insulin levels in growing Sprague-Dawley rats.

J Nutr Sci Vitaminol (Tokyo) 2014 ;60(4):297-9

Research and Development, Matsutani Chemical Industry Co., Ltd.

D-Sorbose is naturally occurring rare sugar. In this study, we examined the effects of dietary D-sorbose in rats. Four-week-old male Sprague-Dawley rats were fed either an AIN-93G-based control diet or a 3% D-sorbose diet for 28 d. Body weight and body fat accumulation were not different between the two diet groups. Dietary supplementation of D-sorbose lowered the serum insulin level (*p<0.05) significantly compared to the control, although the glucose was not changed. In addition, the relative weight of the cecum increased significantly in the D-sorbose group (**p<0.01). These findings suggest that intake of D-sorbose may improve the glucose metabolism by reducing insulin secretion, and D-sorbose can be used as a food ingredient.
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http://dx.doi.org/10.3177/jnsv.60.297DOI Listing
June 2015

Defects in IRE1 enhance cell death and fail to degrade mRNAs encoding secretory pathway proteins in the Arabidopsis unfolded protein response.

Proc Natl Acad Sci U S A 2013 Apr 18;110(14):5713-8. Epub 2013 Mar 18.

Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Nakaku, Sakai, Osaka 599-8531, Japan.

The unfolded protein response (UPR) is a cellular response highly conserved in eukaryotes to obviate accumulation of misfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) catalyzes the cytoplasmic splicing of mRNA encoding bZIP transcription factors to activate the UPR signaling pathway. Arabidopsis IRE1 was recently shown to be involved in the cytoplasmic splicing of bZIP60 mRNA. In the present study, we demonstrated that an Arabidopsis mutant with defects in two IRE1 paralogs showed enhanced cell death upon ER stress compared with a mutant with defects in bZIP60 and wild type, suggesting an alternative function of IRE1 in the UPR. Analysis of our previous microarray data and subsequent quantitative PCR indicated degradation of mRNAs encoding secretory pathway proteins by tunicamycin, DTT, and heat in an IRE1-dependent manner. The degradation of mRNAs localized to the ER during the UPR was considered analogous to a molecular mechanism referred to as the regulated IRE1-dependent decay of mRNAs reported in metazoans. Another microarray analysis conducted in the condition repressing transcription with actinomycin D and a subsequent Gene Set Enrichment Analysis revealed the regulated IRE1-dependent decay of mRNAs-mediated degradation of a significant portion of mRNAs encoding the secretory pathway proteins. In the mutant with defects in IRE1, genes involved in the cytosolic protein response such as heat shock factor A2 were up-regulated by tunicamycin, indicating the connection between the UPR and the cytosolic protein response.
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http://dx.doi.org/10.1073/pnas.1219047110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619347PMC
April 2013

Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup.

Food Chem 2013 Jun 17;138(2-3):781-5. Epub 2012 Nov 17.

Research Institute, Matsutani Chemical Industry Co., Ltd., 5-3, Kita-Itami, Itami, Hyogo 664-8508, Japan.

Many studies have shown that ingestion of high-fructose corn syrup (HFCS) may cause an increase in body weight and abdominal fat. We recently developed a new sweetener containing rare sugars (rare sugar syrup; RSS) by slight isomerization of HFCS. Here, the functional effects of RSS on body weight and abdominal fat, and biochemical parameters in Wistar rats were examined. Rats (n=30) were randomly divided into three groups and maintained for 8-weeks on starch, starch+HFCS (50:50), and starch+RSS (50:50) diets. Rats in the Starch and HFCS groups gained significantly more body weight and abdominal fat than the RSS group. Fasting serum insulin in the RSS group was significantly lower than in the Starch and HFCS groups, although serum glucose in the HFCS and RSS groups was significantly lower than that in the Starch group. Thus, the substitution of HFCS with RSS prevents obesity induced by the consumption of HFCS.
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http://dx.doi.org/10.1016/j.foodchem.2012.11.017DOI Listing
June 2013

Energy value evaluation of hydrogenated resistant maltodextrin.

Biosci Biotechnol Biochem 2012 7;76(10):1828-34. Epub 2012 Oct 7.

Research Laboratory, Matsutani Chemical Industry Co., Ltd., Kita-Itami, Itami, Japan.

Hydrogenated resistant maltodextrin (H-RMD) is a dietary fiber whose energy value has not previously been reported. We evaluated the energy value of H-RMD. We conducted an in vitro digestion test, in vivo blood glucose measurement after ingestion, in vitro fermentability test, excretion test by rats and indirect calorimetry combined with breath hydrogen measurement for humans. H-RMD was hydrolyzed in vitro in a very small amount by human salivary amylase and by the rat small intestinal mucosal enzyme. Ingestion of H-RMD did not increase the blood glucose level of human subjects. An examination of in vitro fermentability suggested that H-RMD was fermented by several enterobacteria. Oral administration of H-RMD showed a saccharide excretion ratio of 42% by rats. A combination of indirect calorimetry and breath hydrogen measurement evaluated the metabolizable energy of H-RMD as 1.1 kcal/g in humans. We concluded from these results that H-RMD was not digested or absorbed in the upper gastrointestinal tract and was fermented in the colon to produce short-chain fatty acids which provided a lower amount of energy than that of resistant maltodextrin.
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http://dx.doi.org/10.1271/bbb.120106DOI Listing
April 2013

Degradation of microcrystalline cellulose and non-pretreated plant biomass by a cell-free extracellular cellulase/hemicellulase system from the extreme thermophilic bacterium Caldicellulosiruptor bescii.

J Biosci Bioeng 2013 Jan 23;115(1):64-70. Epub 2012 Aug 23.

Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.

Caldicellulosiruptor bescii is a cellulolytic/hemicellulolytic anaerobe, which extracellularly secretes various proteins, including multidomain cellulases with two-catalytic domains, for plant biomass degradation. Degradation by C. bescii cells has been well characterized, but degradation by the cell-free extracellular cellulase/hemicellulase system (CEC) of C. bescii has not been as well studied. In the present study, C. bescii CEC was prepared from cell-free culture supernatant, and the degradation properties for defined substrates and non-pretreated plant biomass were characterized. Four multidomain cellulases (Cbes_1857, Cbes_1859, Cbes_1865, and Cbes_1867), composed of the glycoside hydrolase families 5, 9, 10, 44, and 48, were the major enzymes identified in the CEC by mass spectrometry. The CEC degraded xylan, mannose-based substrates, β-1,4-linked glucans, including microcrystalline cellulose (Avicel), and non-pretreated timothy grass and rice straw. However, degradation of chitin, pectin, dextran, and wheat starch was not observed. The optimum temperatures for degradation activities were 75°C for timothy grass and Avicel, 85°C for carboxylmethyl cellulose, and >85°C for xylan. The optimum pH for these substrates was 5-6. The degradation activities were compared with a CEC derived from the fungus Trichoderma reesei, the most common enzyme used for plant biomass saccharification. The amounts of degraded Avicel, timothy grass, and rice straw by C. bescii CEC were 2.2-2.4-fold larger than those of T. reesei CEC. The high hydrolytic activity of C. bescii CEC might be attributed to the two-catalytic domain architecture of the cellulases.
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http://dx.doi.org/10.1016/j.jbiosc.2012.07.019DOI Listing
January 2013

[Case report; typical MR image findings in Japanese encephalitis; a case report].

Nihon Naika Gakkai Zasshi 2011 Aug;100(8):2256-8

Department of Neurology, Osaka City General Hospital, Japan.

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http://dx.doi.org/10.2169/naika.100.2256DOI Listing
August 2011

Down-regulation of UDP-arabinopyranose mutase reduces the proportion of arabinofuranose present in rice cell walls.

Phytochemistry 2011 Nov 6;72(16):1962-8. Epub 2011 Aug 6.

Forestry and Forest Products Research Institute, Tsukuba, Ibaraki 305-8687, Japan.

Arabinoxylans may account for up to 25% of the mass of grass cell walls. The interactions of these polysaccharides with themselves and with cellulose and lignin is believed to affect the walls physical properties and increase the walls resistance to biochemical conversion to fermentable sugars. Arabinoxylans have a backbone composed of 1,4-linked β-D-xylosyl residues, some of which are substituted at O-2 or O-3 with single arabinofuranosyl (Araf) residues. The Araf residues are likely transferred from UDP-Araf to the xylan backbone by arabinofuranosyltransferases. UDP-Araf is itself formed from UDP-arabinopyranose (UDP-Arap) by UDP-arabinopyranose mutase (UAM). In this study, RNA interference (RNAi) was used to suppress UAM expression in rice plants and thereby reduce the amounts of UDP-Araf available for cell wall synthesis. Several of the transgenic plants had reduced proportions of Araf in their walls together with a decrease in the extent of substitution of the xylan backbone, and a reduction of between 25% and 80% in ferulic acid and p-coumaric acid contents of the cell walls. Those transgenic plants with >25% reduction in the amounts of Araf were dwarfed and infertile.
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http://dx.doi.org/10.1016/j.phytochem.2011.07.012DOI Listing
November 2011

[Formed visual hallucination after excision of the right temporo parietal cystic meningioma--a case report].

Brain Nerve 2010 Aug;62(8):893-7

Department of Neurosurgery, Osaka City General Hospital, Miyakojima-ku, Osaka, Japan.

We report the case of a 64-year-old woman with cystic meningioma; this patients was otherwise healthy and experienced formed visual hallucinations after excision of the tumor. She experienced diplopia associated with metamorphopsia, which had persisted for 5 years only when she laid down and turned on her left side. After the excision of the convexity meningioma located in the right temporoparietal lobe, she experienced several types of formed visual hallucinations such as closet-like pictures, flowers sketched on stones, falling maple-like leaves, and moving or wriggling dwarves. She was alert and her visual field was normal; further, she did not experience delirium or seizures. She experienced these hallucinations only when she closed her eyes; these hallucinations persisted for 3 days after the operation. The patient illustrated her observations with beautiful sketches, and the mechanism of visual hallucinations was studied.
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August 2010

Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects.

Biosci Biotechnol Biochem 2010 7;74(3):510-9. Epub 2010 Mar 7.

Research and Development, Matsutani Chemical Industry Co., Ltd., Itami, Hyogo, Japan.

This clinical study was conducted to investigate the safety and effect of D-psicose on postprandial blood glucose levels in adult men and women, including borderline diabetes patients. A randomized double-blind placebo-controlled crossover experiment of single ingestion was conducted on 26 subjects who consumed zero or 5 g of D-psicose in tea with a standard meal. The blood glucose levels at fasting and 30, 60, 90, and 120 min after the meal were compared. The blood glucose level was significantly lower 30 and 60 min after the meal with D-psicose (p<0.01, p<0.05), and a significant decrease was also shown in the area under the curve (p<0.01). The results suggest that D-psicose had an effect to suppress the postprandial blood glucose elevation mainly in borderline diabetes cases. A randomized double-blind placebo-controlled parallel-group experiment of long-term ingestion was conducted on 17 normal subjects who took 5 g of D-psicose or D-glucose with meals three times a day for 12 continuous weeks. Neither any abnormal effects nor clinical problems caused by the continuous ingestion of D-psicose were found.
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http://dx.doi.org/10.1271/bbb.90707DOI Listing
July 2010