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Sample records for butyric acid gaba

  1. Gamma-amino butyric acid (GABA) release in the ciliated protozoon Paramecium occurs by neuronal-like exocytosis.

    Science.gov (United States)

    Ramoino, P; Milanese, M; Candiani, S; Diaspro, A; Fato, M; Usai, C; Bonanno, G

    2010-04-01

    Paramecium primaurelia expresses a significant amount of gamma-amino butyric acid (GABA). Paramecia possess both glutamate decarboxylase (GAD)-like and vesicular GABA transporter (vGAT)-like proteins, indicating the ability to synthesize GABA from glutamate and to transport GABA into vesicles. Using antibodies raised against mammalian GAD and vGAT, bands with an apparent molecular weight of about 67 kDa and 57 kDa were detected. The presence of these bands indicated a similarity between the proteins in Paramecium and in mammals. VAMP, syntaxin and SNAP, putative proteins of the release machinery that form the so-called SNARE complex, are present in Paramecium. Most VAMP, syntaxin and SNAP fluorescence is localized in spots that vary in size and density and are primarily distributed near the plasma membrane. Antibodies raised against mammal VAMP-3, sintaxin-1 or SNAP-25 revealed protein immunoblot bands having molecular weights consistent with those observed in mammals. Moreover, P. primaurelia spontaneously releases GABA into the environment, and this neurotransmitter release significantly increases after membrane depolarization. The depolarization-induced GABA release was strongly reduced not only in the absence of extracellular Ca(2+) but also by pre-incubation with bafilomycin A1 or with botulinum toxin C1 serotype. It can be concluded that GABA occurs in Paramecium, where it is probably stored in vesicles capable of fusion with the cell membrane; accordingly, GABA can be released from Paramecium by stimulus-induced, neuronal-like exocytotic mechanisms.

  2. Gamma-amino butyric acid (GABA) synthesis of Lactobacillus in fermentation of defatted rice bran extract

    Science.gov (United States)

    Dat, Lai Quoc; Ngan, Tran Thi Kim; Nu, Nguyen Thi Xuan

    2017-09-01

    This research focused on the synthesis of GABA by Lactobacillus bacteria in fermentation of defatted rice bran extract without adding glutamate. Two strains of Lactobacillus were investigated into capacity of GABA synthesis. Result indicates that, Lactobacillus brevis VTCC - B - 454 exhibited the higher capacity of GABA synthesis in fermentation of defatted rice bran extract than that of Lactobacillus plantarum VTCC - B - 890. Total dissolved solid (TDS), free amino acids (AA) and reducing sugar (RS) contents in fermentation of defatted rice bran extract with two strains also significantly decreased. At pH 5 and 9 %w/w of TDS content in defatted rice bran extract, Lactobacillus brevis VTCC - B - 454 accumulated 2,952 ppm of GABA in 24 hours of fermentation. The result implies that fermentation with Lactobacillus brevis VTCC - B - 454 can be applied for GABA production from defatted rice bran extract.

  3. γ-amino butyric acid (GABA level as an overall survival risk factor in breast cancer

    Directory of Open Access Journals (Sweden)

    Anna Brzozowska

    2017-09-01

    GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

  4. Purification of gamma-amino butyric acid (GABA) from fermentation of defatted rice bran extract by using ion exchange resin

    Science.gov (United States)

    Tuan Nha, Vi; Phung, Le Thi Kim; Dat, Lai Quoc

    2017-09-01

    Rice bran is one of the significant byproducts of rice processing with 10 %w/w of constitution of whole rice grain. It is rich in nutrient compounds, including glutamic acid. Thus, it could be utilized for the fermentation with Lactobateria for synthesis of GABA, a valuable bioactive for antihypertensive effects. However, the concentration and purity of GABA in fermentation broth of defatted rice bran extract is low for production of GABA drug. This research focused on the purification of GABA from the fermentation broth of defatted rice bran extract by using cation exchange resin. The results indicate that, the adsorption isotherm of GABA by Purelite C100 showed the good agreement with Freundlich model, with high adsorption capacity. The effects of pH and concentration of NaCl in eluent on the elution were also investigated. The obtained results show that, at the operating conditions of elution as follows: pH 6.5, 0.8 M of NaCl in eluent, 0.43 of bed volume; concentration of GABA in accumulative eluent, the purity and recovery yield of GABA were 743.8 ppm, 44.0% and 84.2%, respectively. Results imply that, it is feasible to apply cation exchange resin for purification of GABA from fermentation broth of defatted rice bran extract.

  5. Effects of Chinese herbal medicine Ningdong granule on regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA) in patients with Tourette syndrome.

    Science.gov (United States)

    Wang, Shuzhen; Qi, Fanghua; Li, Jijun; Zhao, Lin; Li, Anyuan

    2012-08-01

    Many studies have indicated that a variety of neurotransmitters are implicated in the pathophysiology of Tourette syndrome (TS), including dopamine (DA), serotonin (5-TH), homovanillic acid (HVA), and gamma-amino butyric acid (GABA). Our previous studies found that Ningdong granule (NDG) is effective on a rat model with TS. NDG can regulate the metabolic disturbance of DA, 5-TH and HVA in the rat brain. However, the mechanisms of NDG in patients with TS are still not clear. To further evaluate the efficiency, safety, and possible mechanisms of NDG, a randomized and double-blind study was carried out. One hundred and twenty patients with TS were enrolled in this study, that were randomly divided into 4 groups (NDG group, Haloperidol (Hal) group, NDG + Hal group and Control group). First, the efficiency of NDG was assessed using the Yale Global Tic Severity Score (YGTSS). Second, the concentration of DA, HVA, 5-TH, 5-hydroxyindoleacetic acid (5-HIAA) and GABA in sera were tested by ELISA. In addition, the influence of NDG on liver and renal function was recorded. We found that NDG could ameliorate tics significantly according the YGTSS score. The concentration of HVA and GABA were increased after treatment with NDG. Furthermore, we found that there was no liver or renal damage in children treated with NDG. We also found that the NDG + Hal group was more effective and safe compared with other groups. In conclusion, the current study indicates that NDG might be effective on patients with TS by regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA).

  6. Production of γ-Amino Butyric Acid in Tea Leaves wit Treatment of Lactic Acid Bacteria

    Science.gov (United States)

    Watanabe, Yuko; Hayakawa, Kiyoshi; Ueno, Hiroshi

    Lactic acid bacteria was searched for producing termented tea that contained a lot of γ-amino butyric acid(GABA). Also examined were the growth condition, GABA production and changes in catechin contents in the tea leaves. Lactobacillus brevis L12 was found to be suitable for the production of fermented tea since it gave as much GABA as gabaron tea when tea leaves being suspended with water at 10% and incubated for 4 days at 25°C. The amount of GABA produced was more than calculated based upon the content of glutamic acid in tea leaves. It is probable to assume that glutamate derived from glutamine and theanine is converted into GABA.

  7. Method of extracting butyric acid from a fermented liquid and chemically converting butyric acid into biofuel

    OpenAIRE

    Ahn, Hyungwoong

    2014-01-01

    Disclosed is a method of converting butyric acid contained in a fermentation broth into biofuel. This chemical conversion method includes separating biohydrogen from gases generated in the course of production of butyric acid through fermentation of carbohydrate, extracting butyric acid from the broth using an insoluble solvent, esterifying butyric acid thus producing butylbutyrate, and hydrogenolyzing all or part of butylbutyrate, thus obtaining butanol. Thereby, biobutanol can be efficientl...

  8. The future of butyric acid in industry.

    Science.gov (United States)

    Dwidar, Mohammed; Park, Jae-Yeon; Mitchell, Robert J; Sang, Byoung-In

    2012-01-01

    In this paper, the different applications of butyric acid and its current and future production status are highlighted, with a particular emphasis on the biofuels industry. As such, this paper discusses different issues regarding butyric acid fermentations and provides suggestions for future improvements and their approaches.

  9. Biosynthesis of butyric acid by Clostridium tyrobutyricum.

    Science.gov (United States)

    Huang, Jin; Tang, Wan; Zhu, Shengquan; Du, Meini

    2018-03-21

    Butyric acid (C 3 H 7 COOH) is an important chemical that is widely used in foodstuffs along with in the chemical and pharmaceutical industries. The bioproduction of butyric acid via large-scale fermentation has the potential to be more economical and efficient than petrochemical synthesis. In this paper, the metabolic pathways involved in the production of butyric acid from Clostridium tyrobutyricum using hexose and pentose as substrates are investigated, and approaches to enhance butyric acid production via genetic modification are discussed. Finally, bioreactor modifications (including fibrous bed bioreactor, inner disc-shaped matrix bioreactor, fibrous matrix packed in porous levitated sphere carriers), low-cost feedstocks and special treatments (including continuous fermentation with cell recycling, extractive fermentation with solvent, using different artificial electron carriers) intended to improve the feasibility of commercial butyric acid bioproduction are summarized.

  10. Metabolic engineering of Clostridium acetobutylicum for butyric acid production with high butyric acid selectivity.

    Science.gov (United States)

    Jang, Yu-Sin; Im, Jung Ae; Choi, So Young; Lee, Jung Im; Lee, Sang Yup

    2014-05-01

    A typical characteristic of the butyric acid-producing Clostridium is coproduction of both butyric and acetic acids. Increasing the butyric acid selectivity important for economical butyric acid production has been rather difficult in clostridia due to their complex metabolic pathways. In this work, Clostridium acetobutylicum was metabolically engineered for highly selective butyric acid production. For this purpose, the second butyrate kinase of C. acetobutylicum encoded by the bukII gene instead of butyrate kinase I encoded by the buk gene was employed. Furthermore, metabolic pathways were engineered to further enhance the NADH-driving force. Batch fermentation of the metabolically engineered C. acetobutylicum strain HCBEKW (pta(-), buk(-), ctfB(-) and adhE1(-)) at pH 6.0 resulted in the production of 32.5g/L of butyric acid with a butyric-to-acetic acid ratio (BA/AA ratio) of 31.3g/g from 83.3g/L of glucose. By further knocking out the hydA gene (encoding hydrogenase) in the HCBEKW strain, the butyric acid titer was not further improved in batch fermentation. However, the BA/AA ratio (28.5g/g) obtained with the HYCBEKW strain (pta(-), buk(-), ctfB(-), adhE1(-) and hydA(-)) was 1.6 times higher than that (18.2g/g) obtained with the HCBEKW strain at pH 5.0, while no improvement was observed at pH 6.0. These results suggested that the buk gene knockout was essential to get a high butyric acid selectivity to acetic acid in C. acetobutylicum. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    International Nuclear Information System (INIS)

    Mo Qizhong; Gong Bin; Fang Jun

    1993-01-01

    3 H-QNB and 3 H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that R t of M receptor was decreased in cerebral cortex and hippocampus and R t of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (K D ) of M-receptor was decreased significantly in cerebral cortex and K D value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased R t of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin

  12. Metabolic engineering of Clostridium tyrobutyricum for enhanced butyric acid production with high butyrate/acetate ratio.

    Science.gov (United States)

    Suo, Yukai; Ren, Mengmeng; Yang, Xitong; Liao, Zhengping; Fu, Hongxin; Wang, Jufang

    2018-04-07

    Butyric acid fermentation by Clostridium couples with the synthesis of acetic acid. But the presence of acetic acid reduces butyric acid yield and increases separation and purification costs of butyric acid. Hence, enhancing the butyrate/acetate ratio is important for economical butyric acid production. This study indicated that enhancing the acetyl-CoA to butyrate flux by overexpression of both the butyryl-CoA/acetate CoA transferase (cat1) and crotonase (crt) genes in C. tyrobutyricum could significantly reduce acetic acid concentration. Fed-batch fermentation of ATCC 25755/cat1 + crt resulted in increased butyrate/acetate ratio of 15.76 g/g, which was 2.24-fold higher than that of the wild-type strain. Furthermore, in order to simultaneously increase the butyrate/acetate ratio, butyric acid concentration and productivity, the recombinant strain ATCC 25755/ppcc (co-expression of 6-phosphofructokinase (pfkA) gene, pyruvate kinase (pykA) gene, cat1, and crt) was constructed. Consequently, ATCC 25755/ppcc produced more butyric acid (46.8 vs. 35.0 g/L) with a higher productivity (0.83 vs. 0.49 g/L·h) and butyrate/acetate ratio (13.22 vs. 7.22 g/g) as compared with the wild-type strain in batch fermentation using high glucose concentration (120 g/L). This study demonstrates that enhancing the acetyl-CoA to butyrate flux is an effective way to reduce acetic acid production and increase butyrate/acetate ratio.

  13. Catalytic upgrading of butyric acid towards fine chemicals and biofuels.

    Science.gov (United States)

    Sjöblom, Magnus; Matsakas, Leonidas; Christakopoulos, Paul; Rova, Ulrika

    2016-04-01

    Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals. © FEMS 2016.

  14. Catalytic upgrading of butyric acid towards fine chemicals and biofuels

    OpenAIRE

    Sj?blom, Magnus; Matsakas, Leonidas; Christakopoulos, Paul; Rova, Ulrika

    2016-01-01

    Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the produc...

  15. Production of gaba (γ - aminobutyric acid by microorganisms: a review

    Directory of Open Access Journals (Sweden)

    Radhika Dhakal

    2012-12-01

    Full Text Available GABA (γ-aminobutyric acid is a four carbon non-protein amino acid that is widely distributed in plants, animals and microorganisms. As a metabolic product of plants and microorganisms produced by the decarboxylation of glutamic acid, GABA functions as an inhibitory neurotransmitter in the brain that directly affects the personality and the stress management. A wide range of traditional foods produced by microbial fermentation contain GABA, in which GABA is safe and eco-friendly, and also has the possibility of providing new health-benefited products enriched with GABA. Synthesis of GABA is catalyzed by glutamate decarboxylase, therefore, the optimal fermentation condition is mainly based on the biochemical properties of the enzyme. Major GABA producing microorganisms are lactic acid bacteria (LAB, which make food spoilage pathogens unable to grow and act as probiotics in the gastrointestinal tract. The major factors affecting the production of GABA by microbial fermentation are temperature, pH, fermentation time and different media additives, therefore, these factors are summarized to provide the most up-dated information for effective GABA synthesis. There has been a huge accumulation of knowledge on GABA application for human health accompanying with a demand on natural GABA supply. Only the GABA production by microorganisms can fulfill the demand with GABA-enriched health beneficial foods.

  16. Effects of glutamate decarboxylase and gamma-aminobutyric acid (GABA) transporter on the bioconversion of GABA in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Kim, Tae Wan; Hong, Soon Ho

    2012-05-01

    Gamma-aminobutyric acid (GABA) is a non-essential amino acid and a precursor of pyrrolidone, a monomer of nylon 4. GABA can be biosynthesized through the decarboxylation of L: -glutamate by glutamate decarboxylase. In this study, the effects of glutamate decarboxylase (gadA, gadB), glutamate/GABA antiporter (gadC) and GABA aminotransferase (gabT) on GABA production were investigated in Escherichia coli. Glutamate decarboxylase was overexpressed alone or with the glutamate/GABA antiporter to enhance GABA synthesis. GABA aminotransferase, which redirects GABA into the TCA cycle, was knock-out mutated. When gadB and gadC were co-overexpressed in the gabT mutant strain, a final GABA concentration of 5.46 g/l was obtained from 10 g/l of monosodium glutamate (MSG), which corresponded to a GABA yield of 89.5%.

  17. Fermentative production of butyric acid from wheat straw: Economic evaluation

    DEFF Research Database (Denmark)

    Baroi, G. N.; Gavala, Hariklia N.; Westermann, P.

    2017-01-01

    The economic feasibility of biochemical conversion of wheat straw to butyric acid was studied in this work. Basic process steps included physicochemical pretreatment, enzymatic hydrolysis and saccharification, fermentation with in-situ acids separation by electrodialysis and product purification....... Two scenarios (S1 and S2) were examined assuming a plant with an annual capacity of 10,000 tonnes of product installed in India (due to significantly lower feedstock prices). S1 resulted in a product of 89% butyric acid mixed with acetic acid and S2 produced butyric acid of 99% purity. Unit production...... cost was estimated at 2.75 and 3.31 $ per kg product for S1 and S2 respectively. The main part of production cost was attributed to steam for the purification step and electricity for the in-situ acids separation. This unit production cost combined with an estimated butyric acid selling price (year...

  18. Effects of dietary probiotic, prebiotic and butyric acid glycerides on ...

    African Journals Online (AJOL)

    Primalac), prebiotic (Fermacto) and butyric acid glycerides (Baby C4) on broiler performance and serum composition. Seven hundred and four day-old broilers were randomly distributed in a 222 factorial arrangement with two levels of probiotic ...

  19. Effects of dietary probiotic, prebiotic and butyric acid glycerides on ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    Primalac), prebiotic. (Fermacto) and butyric acid glycerides (Baby C4) on broiler performance and serum composition. Seven hundred and four day-old broilers were randomly distributed in a 2×2×2 factorial arrangement with ...

  20. Impact of butyric acid on butanol formation by Clostridium pasteurianum.

    Science.gov (United States)

    Regestein, Lars; Doerr, Eric Will; Staaden, Antje; Rehmann, Lars

    2015-11-01

    The butanol yield of the classic fermentative acetone-butanol-ethanol (ABE) process has been enhanced in the past decades through the development of better strains and advanced process design. Nevertheless, by-product formation and the incomplete conversion of intermediates still decrease the butanol yield. This study demonstrates the potential of increasing the butanol yield from glycerol though the addition of small amounts of butyric acid. The impact of butyric acid was investigated in a 7L stirred tank reactor. The results of this study show the positive impact of butyric acid on butanol yield under pH controlled conditions and the metabolic stages were monitored via online measurement of carbon dioxide formation, pH value and redox potential. Butyric acid could significantly increase the butanol yield at low pH values if sufficient quantities of primary carbon source (glycerol) were present. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Current progress on butyric acid production by fermentation.

    Science.gov (United States)

    Zhang, Chunhui; Yang, Hua; Yang, Fangxiao; Ma, Yujiu

    2009-12-01

    Several issues of butyric acid production with bacteria through fermentation are presented in this review. The current progress including the utilization of butyric acid, the production strains, the metabolic pathway, and regulation are presented in the paper. Process operation modes such as batch, fed-batch, and continuous fermentation are being discussed. Genetic engineering technologies for microbial strain improvement are also being discussed and fermentation systems have been recommended.

  2. Optimization of conditions to achieve high content of gamma amino butyric acid in germinated black rice, and changes in bioactivities

    Directory of Open Access Journals (Sweden)

    Chaiyavat CHAIYASUT

    Full Text Available Abstract The present study estimated the optimum germination conditions to achieve high content of Gamma-amino butyric acid (GABA and other phytochemicals in Thai black rice cultivar Kum Payao (BR. The Box–Behnken design of response surface methodology was employed to optimize the germination conditions. The changes in the GABA, phytochemical content, impact of salt, and temperature stress variation on phytochemical content, and stability of GABA were studied. The results showed that 12 h of soaking at pH 7, followed by 36 h of germination was the optimum condition to achieve maximum GABA content (0.2029 mg/g of germinated BR (GBR. The temperature (8 and 30 °C, and salt (50-200 mM NaCl content affected the phytochemicals of GBR, especially GABA, and anthocyanins. Obviously, the antioxidant capability, and enzyme (α-amylase and α-glucosidase inhibiting nature of BR was significantly (P < 0.001 increased after germination. The storage of GBR at 4 °C significantly, preserved the GABA content (∼80% for 45 days. Primarily, the current study revealed the changes in phytochemical content, and bioactivity of Thai black rice cr. Kum Payao during germination. More studies should be carried out on pharmacological benefits of GABA-rich GBR.

  3. Inhibitory effect of ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Wan, Wei; Wang, Jianlong [Laboratory of Environmental Technology, INET, Tsinghua University, Beijing 100084 (China)

    2008-12-15

    The inhibitory effect of added ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production by mixed cultures was investigated in batch tests using glucose as substrate. The experimental results showed that, at 35 C and initial pH 7.0, during the fermentative hydrogen production, the substrate degradation efficiency, hydrogen production potential, hydrogen yield and hydrogen production rate all trended to decrease with increasing added ethanol, acetic acid, propionic acid and butyric acid concentration from 0 to 300 mmol/L. The inhibitory effect of added ethanol on fermentative hydrogen production was smaller than those of added acetic acid, propionic acid and butyric acid. The modified Han-Levenspiel model could describe the inhibitory effects of added ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production rate in this study successfully. The modified Logistic model could describe the progress of cumulative hydrogen production. (author)

  4. Genetic differences in the modulation of accumbal glutamate and γ-amino butyric acid levels after cocaine-induced reinstatement.

    Science.gov (United States)

    Miguéns, Miguel; Botreau, Fanny; Olías, Oscar; Del Olmo, Nuria; Coria, Santiago M; Higuera-Matas, Alejandro; Ambrosio, Emilio

    2013-07-01

    The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine-induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self-administration and during cocaine-induced reinstatement (7.5mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self-administration or extinction behavior, although cocaine priming did induce a higher rate of lever pressing in LEW compared with F344 rats. After extinction, F344 rats that self-administered cocaine had less GABA than the saline controls, while the glutamate levels remained constant in both strains. There was more accumbal glutamate after cocaine priming in LEW rats that self-administered cocaine, while GABA levels were unaffected. By contrast, GABA increased transiently in F344 rats that self-administered cocaine, while glutamate levels were unaltered. In F344 saline controls, cocaine priming provoked contrasting effects in glutamate and GABA levels, inducing a delayed increase in glutamate and a delayed decrease in GABA levels. These amino acids were unaffected by cocaine priming in LEW saline rats. Together, these results suggest that genetic differences in cocaine-induced reinstatement reflect different responses of the accumbal GABA and glutamate systems to cocaine priming. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  5. Enhanced productivity of gamma-amino butyric acid by cascade modifications of a whole-cell biocatalyst.

    Science.gov (United States)

    Yang, Xinwei; Ke, Chongrong; Zhu, Jiangming; Wang, Yan; Zeng, Wenchao; Huang, Jianzhong

    2018-04-01

    We previously developed a gamma-amino butyric acid (GABA)-producing strain of Escherichia coli, leading to production of 614.15 g/L GABA at 45 °C from L-glutamic acid (L-Glu) with a productivity of 40.94 g/L/h by three successive whole-cell conversion cycles. However, the increase in pH caused by the accumulation of GABA resulted in inactivation of the biocatalyst and consequently led to relatively lower productivity. In this study, by overcoming the major problem associated with the increase in pH during the production process, a more efficient biocatalyst was obtained through cascade modifications of the previously reported E. coli strain. First, we introduced four amino acid mutations to the codon-optimized GadB protein from Lactococcus lactis to shift its decarboxylation activity toward a neutral pH, resulting in 306.65 g/L of GABA with 99.14 mol% conversion yield and 69.8% increase in GABA productivity. Second, we promoted transportation of L-Glu and GABA by removing the genomic region encoding the C-plug of GadC (a glutamate/GABA antiporter) to allow its transport path to remain open at a neutral pH, which improved the GABA productivity by 16.8% with 99.3 mol% conversion of 3 M L-Glu. Third, we enhanced the expression of soluble GadB by introducing the GroESL molecular chaperones, leading to 20.2% improvement in GABA productivity, with 307.40 g/L of GABA and a 61.48 g/L/h productivity obtained in one cycle. Finally, we inhibited the degradation of GABA by inactivation of gadA and gadB from the E. coli genome, which resulted in almost no GABA degradation after 40 h. After the cascade system modifications, the engineered recombinant E. coli strain achieved a 44.04 g/L/h productivity with a 99.6 mol% conversion of 3 M L-Glu in a 5-L bioreactor, about twofold increase in productivity compared to the starting strain. This increase represents the highest GABA productivity by whole-cell bioconversion using L-Glu as a substrate in one cycle observed

  6. Solid–liquid equilibria measurements for binary systems comprising (butyric acid + propionic or pentanoic acid) and (heptanoic acid + propionic or butyric or pentanoic or hexanoic acid)

    International Nuclear Information System (INIS)

    Tadie, Margreth; Bahadur, Indra; Reddy, Prashant; Ngema, Peterson Thokozani; Naidoo, Paramespri; Deenadayalu, Nirmala; Ramjugernath, Deresh

    2013-01-01

    Highlights: ► Binary SLE measurement for butyric acid + {propionic or pentanoic acid}. ► Binary SLE measurements for heptanoic acid + {propionic or butyric or pentanoic or hexanoic acid}. ► Measurements undertaken using a synthetic method using two new apparati. - Abstract: Solid–liquid equilibria (SLE) measurements have been undertaken for carboxylic acid systems comprising (butyric acid + propionic or pentanoic acid) and (heptanoic acid + propionic or butyric or pentanoic or hexanoic acid) via a synthetic method using two complementary pieces of equipment. The measurements have been obtained at atmospheric pressure and over the temperature range of (225.6 to 270.7) K. All the acid mixtures exhibit a eutectic point in their respective phase diagrams, which have been determined experimentally. The estimated maximum uncertainties in the reported temperatures and compositions are ±1 K and ±0.0006 mole fraction, respectively. The experimental data have been satisfactorily correlated with the Wilson and NRTL activity coefficient models.

  7. Gamma Amino Butyric Acid Attenuates Brain Oxidative Damage Associated with Insulin Alteration in Streptozotocin-Treated Rats.

    Science.gov (United States)

    Eltahawy, N A; Saada, H N; Hammad, A S

    2017-06-01

    The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in insulin disturbance and hyperglycemia associated with brain oxidative damage in streptozotocin-treated rats. Streptozotocin (STZ) was administered to male albino rats as a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to STZ-treated-rats. Male albino rats Sprague-Dawley (10 ± 2 weeks old; 120 ± 10 g body weight) were divided into 4 groups of 6 rats and treated in parallel. (1) Control group: received distilled water, (2) GABA group: received GABA, (3) STZ group: STZ-treated rats received distilled water, (4) STZ + GABA group: STZ-treated rats received GABA. Rats were sacrificed after a fasting period of 12 h next last dose of GABA. The results obtained showed that STZ-treatment produced hyperglycemia and insulin deficiency (similar to type1 Diabetes). These changes were associated with oxidative damage in brain tissue and notified by significant decreases of superoxide dismutase and catalase activities in parallel to significant increases of malondialdehyde and advanced oxidation protein products levels. The histopathology reports also revealed that STZ-treatment produced degeneration of pancreatic cells. The administration of GABA to STZ-treated rats preserved pancreatic tissue with improved insulin secretion, improved glucose level and minimized oxidative stress in brain tissues. It could be concluded that GABA might protect the brain from oxidative stress and preserve pancreas tissues with adjusting glucose and insulin levels in Diabetic rats and might decrease the risk of neurodegenerative disease in diabetes.

  8. Butyrate Suppresses The Severity Of Acetic Acid-Induced Ulcerative ...

    African Journals Online (AJOL)

    Short chain fatty acids are increasingly used as food additives due to the health benefits they have. Recently, they have been implicated in protecting patients against intestinal disorders but without a well-known mechanism. We explored the benefits of a major short chain fatty acid, butyrate on experimental ulcerative colitis ...

  9. (Liquid + liquid) equilibria of (water + butyric acid + esters) ternary systems

    International Nuclear Information System (INIS)

    Kirbaslar, S. Ismail; Sahin, Selin; Bilgin, Mehmet

    2007-01-01

    (Liquid + liquid) equilibrium (LLE) data of the solubility (binodal) curves and tie-line end compositions were examined for mixtures of {water (1) + butyric acid (2) + ethyl propionate or dimethyl phthalate or dibutyl phthalate (3)} at T = 298.15 K and (101.3 ± 0.7) kPa. The relative mutual solubility of the butyric acid is higher in the layers of esters than in the aqueous layer. The reliability of the experimental tie-line data was confirmed by using the Othmer-Tobias correlation. The LLE data of the ternary systems were predicted by UNIFAC method. Distribution coefficients and separation factors were evaluated for the immiscibility region

  10. Allosteric modulation of retinal GABA receptors by ascorbic acid

    Science.gov (United States)

    Calero, Cecilia I.; Vickers, Evan; Moraga Cid, Gustavo; Aguayo, Luis G.; von Gersdorff, Henrique; Calvo, Daniel J.

    2011-01-01

    Summary Ionotropic γ-aminobutyric acid receptors (GABAA and GABAC) belong to the cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA-puff evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereospecific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS. PMID:21715633

  11. Effect of indole butyric acid on micrografting of cactus | Moghadam ...

    African Journals Online (AJOL)

    Effect of indole butyric acid on micrografting of cactus. ARL Moghadam, ZO Ardebili, L Rezaie. Abstract. Grafting is a common technique to propagate cacti species. Gymnocalycium mihanovichii is an ornamental plant and they should be grafted to root stock containing chlorophyll. In this research, exogenous auxin ...

  12. Effects of acetic, propionic and butyric acids given intraruminally at ...

    African Journals Online (AJOL)

    USER

    2010-04-19

    Apr 19, 2010 ... gluconeogenesis (Bergman, 1990). However, the contri- bution of propionate to blood glucose via gluconeogenesis could probably be covered by the glucose infused into the abomasum. Effects of acetic, propionic and butyric acids given individually on rumen papillae size, and IGF-I, IGFBP-. 3, GH and ...

  13. Effects of Aqueous Extract of Saffron on Gamma-Amino Butyric Acid Content in Rat Hypothalami

    OpenAIRE

    Nikpour Moghaddam; Qujeq; Rastegari Efahani

    2016-01-01

    Background Preliminary studies revealed that 4-aminobutyric acid (GABA) is a key and major inhibitory neurotransmitter in the brain. Evidence from many animal studies and even some clinical studies indicate that GABA is responsible for regulating behavior and also plays an important role in brain functions. Previous studies presented Glutamic acid decarboxylase as a catalyst for the conversion of glutamic acid to GABA. Objectives ...

  14. (Liquid + liquid) equilibria of (water + butyric acid + esters) ternary systems

    Energy Technology Data Exchange (ETDEWEB)

    Kirbaslar, S. Ismail [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)], E-mail: krbaslar@istanbul.edu.tr; Sahin, Selin; Bilgin, Mehmet [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)

    2007-09-15

    (Liquid + liquid) equilibrium (LLE) data of the solubility (binodal) curves and tie-line end compositions were examined for mixtures of {l_brace}water (1) + butyric acid (2) + ethyl propionate or dimethyl phthalate or dibutyl phthalate (3){r_brace} at T = 298.15 K and (101.3 {+-} 0.7) kPa. The relative mutual solubility of the butyric acid is higher in the layers of esters than in the aqueous layer. The reliability of the experimental tie-line data was confirmed by using the Othmer-Tobias correlation. The LLE data of the ternary systems were predicted by UNIFAC method. Distribution coefficients and separation factors were evaluated for the immiscibility region.

  15. Continuous butyric acid fermentation coupled with REED technology for enhanced productivity

    DEFF Research Database (Denmark)

    Baroi, George Nabin; Skiadas, Ioannis; Westermann, Peter

    , today’s organic residues and wastes may become tomorrow’s platform for a variety of products for industrial use. Butyric acid fermentation has long been discussed in the last decade due to the wide application of butyric acid in chemical, pharmaceutical and food industries. Compared to other microbial...... strains, C.tyrobutyricum seems the most promising for biological production of butyric acid as it is characterised by higher selectivity and higher tolerance to butyric acid. However, studies on fermentative butyric production from lignocellulosic biomasses are scarce in the international literature....... The present study focuses on butyric acid fermentation of Pre-treated (by wet explosion) and enzymatically Hydrolysed Wheat Straw (PHWS) by an adapted C. tyrobutyricum strain. The strain could grow in up to 80% (v/v) PHWS in batch mode and it was capable of fermenting both glucose and xylose producing butyric...

  16. Cholesterylbutyrate Solid Lipid Nanoparticles as a Butyric Acid Prodrug

    Directory of Open Access Journals (Sweden)

    Alessandro Mauro

    2008-02-01

    Full Text Available Cholesterylbutyrate (Chol-but was chosen as a prodrug of butyric acid.Butyrate is not often used in vivo because its half-life is very short and therefore too largeamounts of the drug would be necessary for its efficacy. In the last few years butyric acid'santi-inflammatory properties and its inhibitory activity towards histone deacetylases havebeen widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs, whose lipid matrixis Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and totest its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsionmethod; their average diameter is on the order of 100-150 nm and their shape is spherical.The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer celllines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity wasevaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In thereview we will present data on Chol-but SLNs in vitro and in vivo experiments, discussingthe possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic andchronic inflammatory diseases.

  17. Modeling of Clostridium tyrobutyricum for Butyric Acid Selectivity in Continuous Fermentation

    OpenAIRE

    Du, Jianjun; McGraw, Amy; Hestekin, Jamie

    2014-01-01

    A mathematical model was developed to describe batch and continuous fermentation of glucose to organic acids with Clostridium tyrobutyricum. A modified Monod equation was used to describe cell growth, and a Luedeking-Piret equation was used to describe the production of butyric and acetic acids. Using the batch fermentation equations, models predicting butyric acid selectivity for continuous fermentation were also developed. The model showed that butyric acid production was a strong function ...

  18. Modeling of Clostridium t yrobutyricum for Butyric Acid Selectivity in Continuous Fermentation

    OpenAIRE

    Jianjun Du; Amy McGraw; Jamie A. Hestekin

    2014-01-01

    A mathematical model was developed to describe batch and continuous fermentation of glucose to organic acids with Clostridium tyrobutyricum . A modified Monod equation was used to describe cell growth, and a Luedeking-Piret equation was used to describe the production of butyric and acetic acids. Using the batch fermentation equations, models predicting butyric acid selectivity for continuous fermentation were also developed. The model showed that butyric acid production was a strong function...

  19. Butyric acid fermentation of sodium hydroxide pretreated rice straw with undefined mixed culture.

    Science.gov (United States)

    Ai, Binling; Li, Jianzheng; Chi, Xue; Meng, Jia; Liu, Chong; Shi, En

    2014-05-01

    This study describes an alternative mixed culture fermentation technology to anaerobically convert lignocellulosic biomass into butyric acid, a valuable product with wide application, without supplementary cellulolytic enzymes. Rice straw was soaked in 1% NaOH solution to increase digestibility. Among the tested pretreatment conditions, soaking rice straw at 50°C for 72 h removed ~66% of the lignin, but retained ~84% of the cellulose and ~71% of the hemicellulose. By using an undefined cellulose-degrading butyrate-producing microbial community as butyric acid producer in batch fermentation, about 6 g/l of butyric acid was produced from the pretreated rice straw, which accounted for ~76% of the total volatile fatty acids. In the repeated-batch operation, the butyric acid production declined batch by batch, which was most possibly caused by the shift of microbial community structure monitored by denaturing gradient gel electrophoresis. In this study, batch operation was observed to be more suitable for butyric acid production.

  20. Batch and fed-batch production of butyric acid by Clostridium butyricum ZJUCB

    OpenAIRE

    He, Guo-qing; Kong, Qing; Chen, Qi-he; Ruan, Hui

    2005-01-01

    The production of butyric acid by Clostridium butyricum ZJUCB at various pH values was investigated. In order to study the effect of pH on cell growth, butyric acid biosynthesis and reducing sugar consumption, different cultivation pH values ranging from 6.0 to 7.5 were evaluated in 5-L bioreactor. In controlled pH batch fermentation, the optimum pH for cell growth and butyric acid production was 6.5 with a cell yield of 3.65 g/L and butyric acid yield of 12.25 g/L. Based on these results, th...

  1. Butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1 with high butyric acid yield and selectivity.

    Science.gov (United States)

    Kim, Minsun; Kim, Ki-Yeon; Lee, Kyung Min; Youn, Sung Hun; Lee, Sun-Mi; Woo, Han Min; Oh, Min-Kyu; Um, Youngsoon

    2016-10-01

    The aim of this work was to study the butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1. Results showed that Clostridium sp. S1 produced butyric acid by simultaneously utilizing glucose and mannose in softwood hydrolysate and, more remarkably, it consumed acetic acid in hydrolysate. Clostridium sp. S1 utilized each of glucose, mannose, and xylose as well as mixed sugars simultaneously with partially repressed xylose utilization. When softwood (Japanese larch) hydrolysate containing glucose and mannose as the main sugars was used, Clostridium sp. S1 produced 21.17g/L butyric acid with the yield of 0.47g/g sugar and the selectivity of 1 (g butyric acid/g total acids) owing to the consumption of acetic acid in hydrolysate. The results demonstrate potential of Clostridium sp. S1 to produce butyric acid selectively and effectively from hydrolysate not only by utilizing mixed sugars simultaneously but also by converting acetic acid to butyric acid. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Modeling of Clostridium tyrobutyricum for Butyric Acid Selectivity in Continuous Fermentation

    Directory of Open Access Journals (Sweden)

    Jianjun Du

    2014-04-01

    Full Text Available A mathematical model was developed to describe batch and continuous fermentation of glucose to organic acids with Clostridium tyrobutyricum. A modified Monod equation was used to describe cell growth, and a Luedeking-Piret equation was used to describe the production of butyric and acetic acids. Using the batch fermentation equations, models predicting butyric acid selectivity for continuous fermentation were also developed. The model showed that butyric acid production was a strong function of cell mass, while acetic acid production was a function of cell growth rate. Further, it was found that at high acetic acid concentrations, acetic acid was metabolized to butyric acid and that this conversion could be modeled. In batch fermentation, high butyric acid selectivity occurred at high initial cell or glucose concentrations. In continuous fermentation, decreased dilution rate improved selectivity; at a dilution rate of 0.028 h−1, the selectivity reached 95.8%. The model and experimental data showed that at total cell recycle, the butyric acid selectivity could reach 97.3%. This model could be used to optimize butyric acid production using C. tyrobutyricum in a continuous fermentation scheme. This is the first study that mathematically describes batch, steady state, and dynamic behavior of C. tyrobutyricum for butyric acid production.

  3. Gamma-aminobutyric acid (GABA) and pentobarbital induce different conformational rearrangements in the GABA A receptor alpha1 and beta2 pre-M1 regions.

    Science.gov (United States)

    Mercado, Jose; Czajkowski, Cynthia

    2008-05-30

    Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and pentobarbital current activation are distinct. Moreover, pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of pentobarbital did not alter their modification rates, suggesting that the GABA- and pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.

  4. Continuous Fermentation of Clostridium tyrobutyricum with Partial Cell Recycle as a Long-Term Strategy for Butyric Acid Production

    OpenAIRE

    Jianjun Du; Amy McGraw; Nicole Lorenz; Robert R. Beitle; Edgar C. Clausen; Jamie A. Hestekin

    2012-01-01

    In making alternative fuels from biomass feedstocks, the production of butyric acid is a key intermediate in the two-step production of butanol. The fermentation of glucose via Clostridium tyrobutyricum to butyric acid produces undesirable byproducts, including lactic acid and acetic acid, which significantly affect the butyric acid yield and productivity. This paper focuses on the production of butyric acid using Clostridium tyrobutyricum in a partia...

  5. Butyric acid tolerance of rice mutant M4 families

    Directory of Open Access Journals (Sweden)

    Mauricio Marini Kopp

    2007-01-01

    Full Text Available Hydromorphic soils have a low drainage capacity and are used mainly for the cultivation of irrigated rice.This condition favors the development of anaerobic microorganisms that produce phytotoxic substances. The objective of thisstudy was to evaluate the response of rice mutants to the phytotoxicity caused by butyric acid under anaerobic conditions. Theexperiment consisted of four treatments arranged in a randomized block design. Plants of 40 families were grown in ahydroponic system and the measured variables were root length and length of aerial part (LAP, number of roots (NR androot dry matter (RDM and aerial part dry matter (DMAP. The analysis of variance was performed, the relative performancecalculated and linear regressions were fitted. Only the treatment effect for NR and effect of interaction for LAP were notsignificant. Root length was most affected by the acid and the regressions expressed positive as well as negative effects for acidtolerance in the mutant families.

  6. Butyric acid from anaerobic fermentation of lignocellulosic biomass hydrolysates by Clostridium sp. strain RPT-4213

    Science.gov (United States)

    A novel Clostridium sp. strain RPT-4213 was found producing butyrate under strict anaerobic conditions. This strain produced 9.47 g L-1 butyric acid from MRS media (0.48 g/g glucose). RPT-4213 was also used to ferment dilute acid pretreated hydrolysates including wheat straw (WSH), corn fiber (CFH...

  7. Recent advances and strategies in process and strain engineering for the production of butyric acid by microbial fermentation.

    Science.gov (United States)

    Luo, Hongzhen; Yang, Rongling; Zhao, Yuping; Wang, Zhaoyu; Liu, Zheng; Huang, Mengyu; Zeng, Qingwei

    2018-04-01

    Butyric acid is an important platform chemical, which is widely used in the fields of food, pharmaceutical, energy, etc. Microbial fermentation as an alternative approach for butyric acid production is attracting great attention as it is an environmentally friendly bioprocessing. However, traditional fermentative butyric acid production is still not economically competitive compared to chemical synthesis route, due to the low titer, low productivity, and high production cost. Therefore, reduction of butyric acid production cost by utilization of alternative inexpensive feedstock, and improvement of butyric acid production and productivity has become an important target. Recently, several advanced strategies have been developed for enhanced butyric acid production, including bioprocess techniques and metabolic engineering methods. This review provides an overview of advances and strategies in process and strain engineering for butyric acid production by microbial fermentation. Additionally, future perspectives on improvement of butyric acid production are also proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner

    OpenAIRE

    Rice, Teresa C.; Armocida, Stephanie M.; Kuethe, Joshua W.; Midura, Emily F.; Jain, Ayushi; Hildeman, David A.; Healy, Daniel P.; Gulbins, Erich; Caldwell, Charles C.

    2016-01-01

    Following burn injury, a key factor for patients susceptible to opportunistic infections is immune suppression. Butyrate levels are important in maintaining a functional immune system and these levels can be altered after injury. The acid sphingomyelinase (Asm) lipid signaling system has been implicated in a T cell actions with some evidence of being influenced by butyrate. Here, we hypothesized that burn-injury changes in butyrate levels would mediate Asm activity and, consequently, T cell h...

  9. Enhanced butyric acid tolerance and bioproduction by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor.

    Science.gov (United States)

    Jiang, Ling; Wang, Jufang; Liang, Shizhong; Cai, Jin; Xu, Zhinan; Cen, Peilin; Yang, Shangtian; Li, Shuang

    2011-01-01

    Repeated fed-batch fermentation of glucose by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor (FBB) was successfully employed to produce butyric acid at a high final concentration as well as to adapt a butyric-acid-tolerant strain. At the end of the eighth fed-batch fermentation, the butyric acid concentration reached 86.9 ± 2.17 g/L, which to our knowledge is the highest butyric acid concentration ever produced in the traditional fermentation process. To understand the mechanism and factors contributing to the improved butyric acid production and enhanced acid tolerance, adapted strains were harvested from the FBB and characterized for their physiological properties, including specific growth rate, acid-forming enzymes, intracellular pH, membrane-bound ATPase and cell morphology. Compared with the original culture used to seed the bioreactor, the adapted culture showed significantly reduced inhibition effects of butyric acid on specific growth rate, cellular activities of butyric-acid-forming enzyme phosphotransbutyrylase (PTB) and ATPase, together with elevated intracellular pH, and elongated rod morphology. © 2010 Wiley Periodicals, Inc.

  10. Circadian modulation of GABA function in the rat suprachiasmatic nucleus: excitatory effects during the night phase.

    NARCIS (Netherlands)

    De Jeu, M.T.G.; Pennartz, C.M.A.

    2002-01-01

    Gramicidin-perforated patch-clamp recordings were made from slices of the suprachiasmatic nucleus (SCN) of adult rats to characterize the role of gamma-amino butyric acid (GABA) in the circadian timing system. During the day, activation of GABA(A) receptors hyperpolarized the membrane of SCN

  11. Cloning and characterization of a functional human ¿-aminobutyric acid (GABA) transporter, human GAT-2

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Meinild, Anne-Kristine; Jensen, Anders A.

    2007-01-01

    Plasma membrane gamma-aminobutyric acid (GABA) transporters act to terminate GABA neurotransmission in the mammalian brain. Intriguingly four distinct GABA transporters have been cloned from rat and mouse, whereas only three functional homologs of these transporters have been cloned from human....... The aim of this study therefore was to search for this fourth missing human transporter. Using a bioinformatics approach, we successfully identified and cloned the full-length cDNA of a so far uncharacterized human GABA transporter (GAT). The predicted protein displays high sequence similarity to rat GAT...... in human. Furthermore the availability of human GAT-2 enables the use of all human clones of the GABA transporters in drug development programs and functional characterization of novel inhibitors of GABA transport....

  12. Batch and fed-batch production of butyric acid by Clostridium butyricum ZJUCB

    Science.gov (United States)

    He, Guo-qing; Kong, Qing; Chen, Qi-he; Ruan, Hui

    2005-01-01

    The production of butyric acid by Clostridium butyricum ZJUCB at various pH values was investigated. In order to study the effect of pH on cell growth, butyric acid biosynthesis and reducing sugar consumption, different cultivation pH values ranging from 6.0 to 7.5 were evaluated in 5-L bioreactor. In controlled pH batch fermentation, the optimum pH for cell growth and butyric acid production was 6.5 with a cell yield of 3.65 g/L and butyric acid yield of 12.25 g/L. Based on these results, this study then compared batch and fed-batch fermentation of butyric acid production at pH 6.5. Maximum value (16.74 g/L) of butyric acid concentration was obtained in fed-batch fermentation compared to 12.25 g/L in batch fermentation. It was concluded that cultivation under fed-batch fermentation mode could enhance butyric acid production significantly (P<0.01) by C. butyricum ZJUCB. PMID:16252341

  13. γ-aminobutyric acid (GABA) oral rinse reduces capsaicin-induced burning mouth pain sensation

    DEFF Research Database (Denmark)

    Zhang, Yang; Wang, Kelun; Arendt-Nielsen, Lars

    2018-01-01

    BACKGROUND: In burning mouth patients, analgesia after oral administration of clonazepam may result from modulation of peripheral γ-aminobutyric acid (GABA) receptors. METHODS: The effect of oral administration of test solutions (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated...

  14. A fluorescence-coupled assay for gamma aminobutyric acid (GABA reveals metabolic stress-induced modulation of GABA content in neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Joseph E Ippolito

    Full Text Available Pathways involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA have been implicated in the pathogenesis of high grade neuroendocrine (NE neoplasms as well as neoplasms from a non-NE lineage. Using The Cancer Genome Atlas, overexpression of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1, was found to be associated with decreased disease free-survival in prostate adenocarcinoma and decreased overall survival in clear cell renal cell carcinomas. Furthermore, GAD1 was found to be expressed in castrate-resistant prostate cancer cell lines, but not androgen-responsive cell lines. Using a novel fluorescence-coupled enzymatic microplate assay for GABA mediated through reduction of resazurin in a prostate neuroendocrine carcinoma (PNEC cell line, acid microenvironment-induced stress increased GABA levels while alkaline microenvironment-induced stress decreased GABA through modulation of GAD1 and glutamine synthetase (GLUL activities. Moreover, glutamine but not glucose deprivation decreased GABA through modulation of GLUL. Consistent with evidence in prokaryotic and eukaryotic organisms that GABA synthesis mediated through GAD1 may play a crucial role in surviving stress, GABA may be an important mediator of stress survival in neoplasms. These findings identify GABA synthesis and metabolism as a potentially important pathway for regulating cancer cell stress response as well as a potential target for therapeutic strategies.

  15. Butyric acid fermentation from pretreated and hydrolyzed wheat straw by C.tyrobutyricum

    DEFF Research Database (Denmark)

    Baroi, George Nabin; Westermann, Peter; Gavala, Hariklia N.

    ) and higher productivity. However, very few studies have focused on fermentation of sugars derived from lignocellulogic biomass. The present study investigates butyric acid fermentation from pretreated and enzymatically hydrolyzed wheat straw. The sugars derived from wheat straw consist mainly of glucose...... with C.tyrobutyricum showed that the strain was capable of producing butyric acid from hydrolyzed wheat straw by simultaneous uptake of glucose and xylose. Maximum yield of butyric acid (0,47g/g sugars, 96% of the theoretical yield) was obtained at a pH between 6 and 7 with higher selectivity (>90......%). However, the xylose uptake rate was much lower than that of glucose, implying that further process development is required. Moreover, reduced cell growth rate was observed at higher metal (K+) concentration added during pH control which could be overcome by in-situ separation of butyric acid....

  16. Structure activity relationship of selective GABA uptake inhibitors

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten K

    2015-01-01

    A series of β-amino acids with lipophilic diaromatic side chain was synthesized and characterized pharmacologically on mouse γ-amino butyric acid (GABA) transporter subtypes mGAT1-4 in order to investigate structure activity relationships (SAR) for mGAT2 (corresponding to hBGT-1). Variation...

  17. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation.

    Science.gov (United States)

    Zeng, Huawei; Claycombe, Kate J; Reindl, Katie M

    2015-10-01

    Consumption of a high-fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk, while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer-preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate (0.5-2 mmol/l) and DCA (0.05-0.3 mmol/l) on colon cell proliferation. We hypothesize that butyrate and DCA each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. In this study, we demonstrated that both butyrate and DCA inhibited cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, respectively. Cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only G1 fraction with a concomitant drop in the S-phase fraction when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species, genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated Rb protein level, and butyrate but not DCA increased p21 expression. Collectively, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways. Published by Elsevier Inc.

  18. Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.

    Science.gov (United States)

    Sheng, Lili; Jena, Prasant Kumar; Hu, Ying; Liu, Hui-Xin; Nagar, Nidhi; Kalanetra, Karen M; French, Samuel William; French, Samuel Wheeler; Mills, David A; Wan, Yu-Jui Yvonne

    2017-12-01

    Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild-type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate-generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD-fed FXR KO male mice had the highest concentration of hepatic β-muricholic acid (β-MCA) and bacteria-generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co-existed in both human liver cancers and WD-fed FXR KO mice. Microbiota transplantation using butyrate-deficient feces derived from 15-month-old WD-fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic β-MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic β-MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. Transfer of dietary fatty acids from butyric acid fortified canola oil into the meat of broilers

    Directory of Open Access Journals (Sweden)

    Stefano Rapaccini

    2010-01-01

    Full Text Available The literature reported positive beneficial effects of butyric acid and canola oil on production performance traits of broiler chickens. Three hundred hybrid Ross 708 (150 males and 150 females were randomly allotted to 10 pens per treatment with 5 males and 5 females per pen. Ten pens were administered a diet supplemented with soybean oil (control, ten pens the same basal diet but supplemented with a blend of mono-, di-, tri-glyceride of butyric acid added to soybean oil (T1 and ten pens the same basal diet supplemented with a mix of soybean and canola oil containing butyrate (T2. No differences in final body weight, dressing percentage, liver and thigh weight were found be- tween groups. The T2 birds showed the highest feed/gain ratio (P<0.05. The control group showed the highest value for breast weight while the highest quantity of abdominal fat was in T2 carcasses. Fatty acid profile was significantly influenced by the presence of oil supplements, not only quantitatively but also qualitatively.

  20. Effects of ptb knockout on butyric acid fermentation by Clostridium tyrobutyricum.

    Science.gov (United States)

    Zhang, Yali; Yu, Mingrui; Yang, Shang-Tian

    2012-01-01

    Clostridium tyrobutyricum ATCC 25755 is an anaerobic, rod-shaped, gram-positive bacterium that produces butyrate, acetate, hydrogen, and carbon dioxide from various saccharides, including glucose and xylose. Phosphotransbutyrylase (PTB) is a key enzyme in the butyric acid synthesis pathway. In this work, effects of ptb knockout by homologous recombination on metabolic flux and product distribution were investigated. When compared with the wild type, the activities of PTB and butyrate kinase in ptb knockout mutant decreased 76 and 42%, respectively; meanwhile, phosphotransacetylase and acetate kinase increased 7 and 29%, respectively. However, ptb knockout did not significantly reduce butyric acid production from glucose or xylose in batch fermentations. Instead, it increased acetic acid and hydrogen production 33.3-53.8% and ≈ 11%, respectively. Thus, the ptb knockout did increase the carbon flux toward acetate synthesis, resulting in a significant decrease (28-35% reduction) in the butyrate/acetate ratio in ptb mutant fermentations. In addition, the mutant displayed a higher specific growth rate (0.20 h(-1) vs. 0.15 h(-1) on glucose and 0.14 h(-1) vs. 0.10 h(-1) on xylose) and tolerance to butyric acid. Consequently, batch fermentation with the mutant gave higher fermentation rate and productivities (26-48% increase for butyrate, 81-100% increase for acetate, and 38-46% increase for hydrogen). This mutant thus can be used more efficiently than the parental strain in fermentations to produce butyrate, acetate, and hydrogen from glucose and xylose. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

  1. Identification of amino acids involved in histamine potentiation of GABA(A receptors

    Directory of Open Access Journals (Sweden)

    Ulrike eThiel

    2015-05-01

    Full Text Available Histamine is a neurotransmitter involved in a number of physiological and neuronal functions. In mammals, such as humans and rodents, the histaminergic neurons found in the tuberomamillary nucleus (TMN project widely throughout the central nervous system (CNS. Histamine acts as positive modulator of GABA(A receptors (GABA(ARs and, in high concentrations (10 mM, as negative modulator of the strychnine-sensitive glycine receptor. However, the exact molecular mechanisms by which histamine acts on GABA(ARs are unknown. In our study, we aimed to identify amino acids potentially involved in the modulatory effect of histamine on GABA(ARs. We expressed GABA(ARs with 12 different point mutations in Xenopus laevis oocytes and characterized the effect of histamine on GABA-induced currents using the two-electrode voltage clamp technique. Our data demonstrate that the amino acid residues ß2(N265 and ß2(M286, which are important for modulation by propofol, are not involved in the action of histamine. However, we found that histamine modulation is dependent on the amino acid residues alpha1(R120, ß2(Y157, ß3(D163, ß3(V175 and ß3(Q185. We showed that the amino acid residues ß2(Y157 and ß3(Q185 mediate the positive modulatory effect of histamine on GABA-induced currents, whereas alpha1(R120 and ß2(D163 form a potential histamine interaction site in GABA(ARs.

  2. Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

    2016-01-01

    Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

  3. Hyper-production of butyric acid from delignified rice straw by a novel consolidated bioprocess.

    Science.gov (United States)

    Chi, Xue; Li, Jianzheng; Wang, Xin; Zhang, Yafei; Antwi, Philip

    2018-04-01

    A novel consolidated bioprocess for hyper-production of butyric acid from delignified rice straw without exogenous enzymes involved was developed by co-fermentation of Clostridium thermocellum ATCC 27405 and C. thermobutyricum ATCC 49875. Feasibility of the consolidated bioprocess was approved by batch fermentations, with the optimum pH of 6.5. Fed-batch fermentation with a constant pH of 6.5 at 55 °C could enhance the butyric acid yield to a remarkable 33.9 g/L with a selectivity as high as 78%. Metabolic analysis of the co-culture indicated that sugars liberated by C. thermocellum ATCC 27405 were effectively converted to butyric acid by C. thermobutyricum ATCC 49875. Secondary metabolism of C. thermobutyricum ATCC 49875 also contributed to the hyper-production of butyric acid, resulting in the re-assimilation of by-products such as acetic acid and ethanol. This work provides a more effective fermentation process for butyric acid production from lignocellulosic biomass for future applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Butyric acid fermentation from pretreated and hydrolysed wheat straw by an adapted Clostridium tyrobutyricum strain.

    Science.gov (United States)

    Baroi, G N; Baumann, I; Westermann, P; Gavala, H N

    2015-09-01

    Butyric acid is a valuable building-block for the production of chemicals and materials and nowadays it is produced exclusively from petroleum. The aim of this study was to develop a suitable and robust strain of Clostridium tyrobutyricum that produces butyric acid at a high yield and selectivity from lignocellulosic biomasses. Pretreated (by wet explosion) and enzymatically hydrolysed wheat straw (PHWS), rich in C6 and C5 sugars (71.6 and 55.4 g l(-1) of glucose and xylose respectively), was used as substrate. After one year of serial selections, an adapted strain of C. tyrobutyricum was developed. The adapted strain was able to grow in 80% (v v(-1) ) PHWS without addition of yeast extract compared with an initial tolerance to less than 10% PHWS and was able to ferment both glucose and xylose. It is noticeable that the adapted C. tyrobutyricum strain was characterized by a high yield and selectivity to butyric acid. Specifically, the butyric acid yield at 60-80% PHWS lie between 0.37 and 0.46 g g(-1) of sugar, while the selectivity for butyric acid was as high as 0.9-1.0 g g(-1) of acid. Moreover, the strain exhibited a robust response in regards to growth and product profile at pH 6 and 7. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  5. Efficient production of butyric acid from Jerusalem artichoke by immobilized Clostridium tyrobutyricum in a fibrous-bed bioreactor.

    Science.gov (United States)

    Huang, Jin; Cai, Jin; Wang, Jin; Zhu, Xiangcheng; Huang, Lei; Yang, Shang-Tian; Xu, Zhinan

    2011-02-01

    Butyric acid is an important specialty chemical with wide industrial applications. The feasible large-scale fermentation for the economical production of butyric acid requires low-cost substrate and efficient process. In the present study, butyric acid production by immobilized Clostridium tyrobutyricum was successfully performed in a fibrous-bed bioreactor using Jerusalem artichoke as the substrate. Repeated-batch fermentation was carried out to produce butyric acid with a high butyrate yield (0.44 g/g), high productivity (2.75 g/L/h) and a butyrate concentration of 27.5 g/L. Furthermore, fed-batch fermentation using sulfuric acid pretreated Jerusalem artichoke hydrolysate resulted in a high butyric acid concentration of 60.4 g/L, with the yield of 0.38 g/g and the selectivity of ∼ 85.1 (85.1g butyric acid/g acetic acid). Thus, the production of butyric acid from Jerusalem artichoke on a commercial scale could be achieved based on the system developed in this work. Copyright © 2010. Published by Elsevier Ltd.

  6. Butyrate and retinoic acid imprint mucosal-like dendritic cell development synergistically from bone marrow cells.

    Science.gov (United States)

    Qiang, Y; Xu, J; Yan, C; Jin, H; Xiao, T; Yan, N; Zhou, L; An, H; Zhou, X; Shao, Q; Xia, S

    2017-09-01

    Accumulating data show that the phenotypes and functions of distinctive mucosal dendritic cells (DCs) in the gut are regulated by retinoic acid (RA). Unfortunately, the exact role of butyrate in RA-mediated mucosal DC differentiation has not been elucidated thoroughly to date. Mucosal-like dendritic cell differentiation was completed in vitro by culturing bone marrow cells with growth factors [granulocyte-macrophage colony-stimulating factor (GM-CSF/interleukin (IL)-4], RA and/or butyrate. The phenotypes, cytokine secretion, immune functions and levels of retinal dehydrogenase of different DCs were detected using quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The results showed that RA-induced DCs (RA-DCs) showed mucosal DC properties, including expression of CD103 and gut homing receptor α 4 β 7 , low proinflammatory cytokine secretion and low priming capability to antigen-specific CD4 + T cells. Butyrate-treated RA-DCs (Bu-RA-DCs) decreased CD11c, but increased CD103 and α 4 β 7 expression. Moreover, the CD4 + T priming capability and the levels of retinal dehydrogenase of RA-DCs were suppressed significantly by butyrate. Thus, butyrate and retinoic acid have different but synergistic regulatory functions on mucosal DC differentiation, indicating that immune homeostasis in the gut depends largely upon RA and butyrate to imprint different mucosal DC subsets, both individually and collectively. © 2017 British Society for Immunology.

  7. Consolidated bioprocessing for butyric acid production from rice straw with undefined mixed culture

    Directory of Open Access Journals (Sweden)

    Binling Ai

    2016-10-01

    Full Text Available Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L•d. In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41% and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

  8. Butyric acid from anaerobic fermentation of lignocellulosic biomass hydrolysates by Clostridium tyrobutyricum strain RPT-4213.

    Science.gov (United States)

    Liu, Siqing; Bischoff, Kenneth M; Leathers, Timothy D; Qureshi, Nasib; Rich, Joseph O; Hughes, Stephen R

    2013-09-01

    A novel Clostridium tyrobutyricum strain RPT-4213 was found producing butyrate under strict anaerobic conditions. This strain produced 9.47 g L(-1) butyric acid from MRS media (0.48 g/g glucose). RPT-4213 was also used to ferment dilute acid pretreated hydrolysates including wheat straw (WSH), corn fiber (CFH), corn stover (CSH), rice hull (RHH), and switchgrass (SGH). Results indicated that 50% WSH with a Clostridia medium (Ct) produced the most butyric acid (8.06 g L(-1), 0.46 g/g glucose), followed by 50% SGH with Ct (6.01 g L(-1), 0.44 g/g glucose), however, 50% CSH Ct showed growth inhibition. RPT-4213 was then used in pH-controlled bioreactor fermentations using 60% WSH and SGH, with a dilute (0.5×) Ct medium, resulting 9.87 g L(-1) butyric acid in WSH (yield 0.44 g/g) and 7.05 g L(-1) butyric acid in SGH (yield 0.42 g/g). The titer and productivity could be improved through process engineering. Published by Elsevier Ltd.

  9. Consolidated Bioprocessing for Butyric Acid Production from Rice Straw with Undefined Mixed Culture.

    Science.gov (United States)

    Ai, Binling; Chi, Xue; Meng, Jia; Sheng, Zhanwu; Zheng, Lili; Zheng, Xiaoyan; Li, Jianzheng

    2016-01-01

    Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L· d). In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41 and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

  10. The four human ¿-aminobutyric acid (GABA) transporters

    DEFF Research Database (Denmark)

    Kvist, Trine; Christiansen, Bolette; Jensen, Anders Asbjørn

    2009-01-01

    , we perform the first elaborate pharmacological characterization of all four human GAT subtypes. We conduct the experiments in parallel in a [3H]GABA uptake assay using 14 standard GAT substrates and inhibitors. This setup enables direct comparison of the absolute values of inhibitory activities...... at the four human GATs....

  11. Butyric acid fermentation from pre-treated wheat straw by a mutant clostridium tyrobutyricum strain

    DEFF Research Database (Denmark)

    Baroi, George Nabin; Baumann, Ivan; Westermann, Peter

    Only little research on butyric acid fermentation has been carried out in relationship to bio-refinery perspectives involving strain selection, development of adapted strains, physiological analyses for higher yield, productivity and selectivity. However, a major step towards the development......’s platform for a variety of products for industrial use. Butyric acid is considered as a potential chemical building-block for the production of chemicals for e.g. polymeric compounds and the aim of this work was to develop a suitable and robust strain of Clostridium tyrobutyricum that produces less acetic...... acid (higher selectivity), has a higher yield and a higher productivity of butyric acid from pre-treated lignocellulosic biomass. Pre-treated wheat straw was used as the main carbon source. After one year of serial adaptation and selection a mutant strain of C. tyrobutyricum was developed. This new...

  12. Metabolic engineering of Clostridium acetobutylicum for enhanced production of butyric acid.

    Science.gov (United States)

    Jang, Yu-Sin; Woo, Hee Moon; Im, Jung Ae; Kim, In Ho; Lee, Sang Yup

    2013-11-01

    Clostridium acetobutylicum has been considered as an attractive platform host for biorefinery due to its metabolic diversity. Considering its capability to overproduce butanol through butyrate, it was thought that butyric acid can also be efficiently produced by this bacterium through metabolic engineering. The pta-ctfB-deficient C. acetobutylicum CEKW, in which genes encoding phosphotransacetylase and CoA-transferase were knocked out, was assessed for its potential as a butyric acid producer in fermentations with four controlled pH values at 5.0, 5.5, 6.0, and 6.4. Butyric acid could be best produced by fermentation of the CEKW at pH 6.0, resulting in the highest titer of 26.6 g/l, which is 6.4 times higher than that obtained with the wild type. However, due to the remaining solventogenic ability of the CEKW, 3.6 g/l solvents were also produced. Thus, the CEKW was further engineered by knocking out the adhE1-encoding aldehyde/alcohol dehydrogenase to prevent solvent production. Batch fermentation of the resulting C. acetobutylicum HCEKW at pH 6.0 showed increased butyric acid production to 30.8 g/l with a ratio of butyric-to-acetic acid (BA/AA) of 6.6 g/g and a productivity of 0.72 g/l/h from 86.9 g/l glucose, while negligible solvent (0.8 g/l ethanol only) was produced. The butyric acid titer, BA/AA ratio, and productivity obtained in this study were the highest values reported for C. acetobutylicum, and the BA/AA ratio and productivity were also comparable to those of native butyric acid producer Clostridium tyrobutyricum. These results suggested that the simultaneous deletion of the pta-ctfB-adhE1 in C. acetobutylicum resulted in metabolic switch from biphasic to acidogenic fermentation, which enhanced butyric acid production.

  13. Comparative transcriptome analysis of Agrobacterium tumefaciens in response to plant signal salicylic acid, indole-3-acetic acid and gamma-amino butyric acid reveals signalling cross-talk and Agrobacterium--plant co-evolution.

    Science.gov (United States)

    Yuan, Ze-Chun; Haudecoeur, Elise; Faure, Denis; Kerr, Kathleen F; Nester, Eugene W

    2008-11-01

    Agrobacterium has evolved sophisticated strategies to perceive and transduce plant-derived cues. Recent studies have found that numerous plant signals, including salicylic acid (SA), indole-3-acetic acid (IAA) and gamma-amino butyric acid (GABA), profoundly affect Agrobacterium-plant interactions. Here we determine and compare the transcriptome profiles of Agrobacterium in response to these three plant signals. Collectively, the transcription of 103, 115 and 95 genes was significantly altered by SA, IAA and GABA respectively. Both distinct cellular responses and overlapping signalling pathways were elicited by these three plant signals. Interestingly, these three plant compounds function additively to shut off the Agrobacterium virulence programme and activate the quorum-quenching machinery. Moreover, the repression of the virulence programme by SA and IAA and the inactivation of quorum-sensing signals by SA and GABA are regulated through independent pathways. Our data indicate that these plant signals, while cross-talk in plant signalling networks, also act as cross-kingdom signals and play redundant roles in tailoring Agrobacterium regulatory pathways, resulting in intensive signalling cross-talk in Agrobacterium. Our results support the notion that Agrobacterium has evolved the ability to hijack plant signals for its own benefit. The complex signalling interplay between Agrobacterium and its plant hosts reflects an exquisite co-evolutionary balance.

  14. Effects of Aqueous Extract of Saffron on Gamma-Amino Butyric Acid Content in Rat Hypothalami

    Directory of Open Access Journals (Sweden)

    Nikpour Moghaddam

    2016-02-01

    Full Text Available Background Preliminary studies revealed that 4-aminobutyric acid (GABA is a key and major inhibitory neurotransmitter in the brain. Evidence from many animal studies and even some clinical studies indicate that GABA is responsible for regulating behavior and also plays an important role in brain functions. Previous studies presented Glutamic acid decarboxylase as a catalyst for the conversion of glutamic acid to GABA. Objectives The aim of this study was to evaluate the effects of saffron on GABA content in the hypothalamus of rats. Materials and Methods Male rats weighing 190 - 210 g were used. They were maintained in a temperature-controlled room with a 12-hour light/dark illumination cycle. The rats were fed standard pellet feed and had access to water ad libitum. The animals were divided into three groups: The first group received a 250 µL intraperitoneal injection of 0.05 g/mL saffron (Group I. The second group received a 250 µL intraperitoneal injection of 0.1 g/mL saffron (Group II. The third group acted as the control and received only water (Group III. The time intervals chosen for this experiment were 1, 2, 4, and 8 weeks following the administration of saffron. At least six animals were assigned to each experimental group. At each time interval, the animals were anaesthetized and brain tissue extracted, hypothalami separated and homogenized in PBS solution, rinsed with PBS, re-filtered, and centrifuged at 1200 g for 10 minutes. Results In this study, both doses of saffron (0.05 g/mL [Group I]; and 0.1 g/mL [Group II] caused significantly increased GABA content in each hypothalamus. GABA in Group I increased significantly compared to the control group (1.00 ± 0.05 [mean ± SD, n = 8] vs. 0.29 ± 0.05, mM. GABA in Group II also increased significantly compared to the control group (1.45 ± 0.07 [mean ± SD, n = 8] vs. 0.29 ± 0.05, mM. The effect of saffron on GABA was also dose dependent; the only exception occurring during the

  15. Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study.

    Science.gov (United States)

    Torii, Kazuhiro; Maeshige, Noriaki; Aoyama-Ishikawa, Michiko; Miyoshi, Makoto; Terashi, Hiroto; Usami, Makoto

    2017-01-01

    A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts. Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h. Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy. Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required. This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid.

  16. Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study*

    Science.gov (United States)

    Torii, Kazuhiro; Maeshige, Noriaki; Aoyama-Ishikawa, Michiko; Miyoshi, Makoto; Terashi, Hiroto; Usami, Makoto

    2017-01-01

    Background A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. Objective In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts. Methods Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h. Results Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy. Study limitations Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required. Conclusion This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid. PMID:28538876

  17. Efficient increase of ɣ-aminobutyric acid (GABA) content in tomato fruits by targeted mutagenesis.

    Science.gov (United States)

    Nonaka, Satoko; Arai, Chikako; Takayama, Mariko; Matsukura, Chiaki; Ezura, Hiroshi

    2017-08-01

    γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that has hypotensive effects. Tomato (Solanum lycopersicum L.) is among the most widely cultivated and consumed vegetables in the world and contains higher levels of GABA than other major crops. Increasing these levels can further enhance the blood pressure-lowering function of tomato fruit. Glutamate decarboxylase (GAD) is a key enzyme in GABA biosynthesis; it has a C-terminal autoinhibitory domain that regulates enzymatic function, and deleting this domain increases GAD activity. The tomato genome has five GAD genes (SlGAD1-5), of which two (SlGAD2 and SlGAD3) are expressed during tomato fruit development. To increase GABA content in tomato, we deleted the autoinhibitory domain of SlGAD2 and SlGAD3 using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 technology. Introducing a stop codon immediately before the autoinhibitory domain increased GABA accumulation by 7 to 15 fold while having variable effects on plant and fruit size and yield. This is the first study describing the application of the CRISPR/Cas9 system to increase GABA content in tomato fruits. Our findings provide a basis for the improvement of other types of crop by CRISPR/Cas9-based genetic modification.

  18. Properties of Kimchi Fermented with GABA-Producing Lactic Acid Bacteria as a Starter.

    Science.gov (United States)

    Lee, Kang Wook; Shim, Jae Min; Yao, Zhuang; Kim, Jeong A; Kim, Jeong Hwan

    2018-02-13

    Kimchi was prepared with a starter, Lactobacillus zymae GU240 producing γ-aminobutyric acid (GABA), and one precursor of GABA (glutamic acid, glutamic acid mono sodium salt (MSG), or kelp extract). L. zymae GU240, an isolate from kimchi, can grow at 7% NaCl and low temperature. Five different kimchi samples were fermented for 20 weeks at -1°C. Kimchi with starter alone could not produce GABA. GABA content was highest in kimchi with co-inoculation of starter and MSG (1%, w/w). Kimchi co-inoculated with a starter and kelp extract powder (3%, w/w) had the second highest GABA content. Addition of glutamic acid powder (1%, w/w) caused a reduction in the pH level of kimchi and growth inhibition of lactic acid bacteria (LAB) and yeasts. Kimchi samples with MSG or kelp extract showed improvement of sensory evaluation scores. The results demonstrate the possibility to produce kimchi with improved functionality and taste by using L. zymae GU240 as a starter along with a suitable precursor such as MSG or kelp extract.

  19. Hyperpolarized butyrate: a metabolic probe of short chain fatty acid metabolism in the heart.

    Science.gov (United States)

    Ball, Daniel R; Rowlands, Ben; Dodd, Michael S; Le Page, Lydia; Ball, Vicky; Carr, Carolyn A; Clarke, Kieran; Tyler, Damian J

    2014-05-01

    Butyrate, a short chain fatty acid, was studied as a novel hyperpolarized substrate for use in dynamic nuclear polarization enhanced magnetic resonance spectroscopy experiments, to define the pathways of short chain fatty acid and ketone body metabolism in real time. Butyrate was polarized via the dynamic nuclear polarization process and subsequently dissolved to generate an injectable metabolic substrate. Metabolism was initially assessed in the isolated perfused rat heart, followed by evaluation in the in vivo rat heart. Hyperpolarized butyrate was generated with a polarization level of 7% and was shown to have a T1 relaxation time of 20 s. These physical characteristics were sufficient to enable assessment of multiple steps in its metabolism, with the ketone body acetoacetate and several tricarboxylic acid cycle intermediates observed both in vitro and in vivo. Metabolite to butyrate ratios of 0.1-0.4% and 0.5-2% were observed in vitro and in vivo respectively, similar to levels previously observed with hyperpolarized [2-(13) C]pyruvate. In this study, butyrate has been demonstrated to be a suitable hyperpolarized substrate capable of revealing multi-step metabolism in dynamic nuclear polarization experiments and providing information on the metabolism of fatty acids not currently achievable with other hyperpolarized substrates. Copyright © 2013 Wiley Periodicals, Inc.

  20. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

    Science.gov (United States)

    Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of D...

  1. A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid composition.

    Science.gov (United States)

    Snowden, Christopher J; Thomas, Benjamin; Baxter, Charles J; Smith, J Andrew C; Sweetlove, Lee J

    2015-03-01

    Vacuolar accumulation of acidic metabolites is an important aspect of tomato fruit flavour and nutritional quality. The amino acids Asp and Glu accumulate to high concentrations during ripening, while γ-aminobutyrate (GABA) shows an approximately stoichiometric decline. Given that GABA can be catabolised to form Glu and subsequently Asp, and the requirement for the fruit to maintain osmotic homeostasis during ripening, we hypothesised the existence of a tonoplast transporter that exports GABA from the vacuole in exchange for import of either Asp or Glu. We show here that the tomato vacuolar membrane possesses such a transport property: transport of Glu across isolated tonoplast vesicle membranes was trans-stimulated in counterexchange mode by GABA, Glu and Asp. We identified SlCAT9 as a candidate protein for this exchanger using quantitative proteomics of a tonoplast-enriched membrane fraction. Transient expression of a SlCAT9-YFP fusion in tobacco confirmed a tonoplast localisation. The function of the protein was examined by overexpression of SlCAT9 in transgenic tomato plants. Tonoplast vesicles isolated from transgenic plants showed higher rates of Glu and GABA transport than wild-type (WT) only when assayed in counterexchange mode with Glu, Asp, or GABA. Moreover, there were substantial increases in the content of all three cognate amino acids in ripe fruit from the transgenic plants. We conclude that SlCAT9 is a tonoplast Glu/Asp/GABA exchanger that strongly influences the accumulation of these amino acids during fruit development. © 2015 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  2. Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria.

    Science.gov (United States)

    Imai, Kenichi; Yamada, Kiyoshi; Tamura, Muneaki; Ochiai, Kuniyasu; Okamoto, Takashi

    2012-08-01

    Latently infected cells harbor human immunodeficiency virus type 1 (HIV-1) proviral DNA copies integrated in heterochromatin, allowing persistence of transcriptionally silent proviruses. It is widely accepted that hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in maintaining the HIV-1 latency by repressing viral transcription. HIV-1 replication can be induced from latently infected cells by environmental factors, such as inflammation and co-infection with other microbes. It is known that a bacterial metabolite butyric acid inhibits catalytic action of HDAC and induces transcription of silenced genes including HIV-1 provirus. There are a number of such bacteria in gut, vaginal, and oral cavities that produce butyric acid during their anaerobic glycolysis. Since these organs are known to be the major site of HIV-1 transmission and its replication, we explored a possibility that explosive viral replication in these organs could be ascribable to butyric acid produced from anaerobic resident bacteria. In this study, we demonstrate that the culture supernatant of various bacteria producing butyric acid could greatly reactivate the latently-infected HIV-1. These bacteria include Fusobacterium nucleatum (commonly present in oral cavity, and gut), Clostridium cochlearium, Eubacterium multiforme (gut), and Anaerococcus tetradius (vagina). We also clarified that butyric acid in these culture supernatants could induce histone acetylation and HIV-1 replication by inhibiting HDAC. Our observations indicate that butyric acid-producing bacteria could be involved in AIDS progression by reactivating the latent HIV provirus and, subsequently, by eliminating such bacterial infection may contribute to the prevention of the AIDS development and transmission.

  3. Isolation of acetic, propionic and butyric acid-forming bacteria from biogas plants.

    Science.gov (United States)

    Cibis, Katharina Gabriela; Gneipel, Armin; König, Helmut

    2016-02-20

    In this study, acetic, propionic and butyric acid-forming bacteria were isolated from thermophilic and mesophilic biogas plants (BGP) located in Germany. The fermenters were fed with maize silage and cattle or swine manure. Furthermore, pressurized laboratory fermenters digesting maize silage were sampled. Enrichment cultures for the isolation of acid-forming bacteria were grown in minimal medium supplemented with one of the following carbon sources: Na(+)-dl-lactate, succinate, ethanol, glycerol, glucose or a mixture of amino acids. These substrates could be converted by the isolates to acetic, propionic or butyric acid. In total, 49 isolates were obtained, which belonged to the phyla Firmicutes, Tenericutes or Thermotogae. According to 16S rRNA gene sequences, most isolates were related to Clostridium sporosphaeroides, Defluviitoga tunisiensis and Dendrosporobacter quercicolus. Acetic, propionic or butyric acid were produced in cultures of isolates affiliated to Bacillus thermoamylovorans, Clostridium aminovalericum, Clostridium cochlearium/Clostridium tetani, C. sporosphaeroides, D. quercicolus, Proteiniborus ethanoligenes, Selenomonas bovis and Tepidanaerobacter sp. Isolates related to Thermoanaerobacterium thermosaccharolyticum produced acetic, butyric and lactic acid, and isolates related to D. tunisiensis formed acetic acid. Specific primer sets targeting 16S rRNA gene sequences were designed and used for real-time quantitative PCR (qPCR). The isolates were physiologically characterized and their role in BGP discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Production of Butyric Acid and Butanol from Biomass

    Energy Technology Data Exchange (ETDEWEB)

    Ramey, David E. [Environmental Energy Inc., Blacklick, OH (United States); Yang, Shang-Tian [The Ohio State Univ., Columbus, OH (United States). Dept. of Chemical and Biomolecular Engineering

    2005-08-25

    prices as a chemical are at $3.00 per gallon – wholesaling in 55 gallon drums for $6.80, with a worldwide market of 1.4 billion gallon per year. The market demand is expected to increase dramatically since butanol can now be produced economically from low-cost biomass. Butanol’s application as a replacement for gasoline will outpace ethanol, biodiesel and hydrogen when its safety and simplicity of use are seen. Butanol’s application for the Department of Defense as a clean-safe replacement for batteries when used in conjunction with fuel cell technology is seen as an application for the future. Disposable canisters made of PLA that carry butanol to be reformed and used to generate electricity for computers, night vision and stealth equipment can be easily disposed of. In a typical ABE fermentation, butyric, propionic and acetic acids are produced first by C. acetobutylicum; the culture then undergoes a metabolic shift and solvents (butanol, acetone, and ethanol) are formed (Fond et al., 1985). In conventional ABE fermentations, the butanol yield from glucose is low, typically at ~15% (w/w) and rarely exceeds 25% (0.77–1.3 gallons per bushel corn respectfully). The production of butanol is also limited by severe product inhibition. Butanol at a concentration of 10 g/L can significantly inhibit cell growth and the fermentation. Consequently, butanol titers in conventional ABE fermentations are usually lower than 13 g/L. The low butanol yield and butanol concentration made butanol production from glucose by ABE fermentation uneconomical.

  5. The role of GABA in the regulation of GnRH neurons

    Directory of Open Access Journals (Sweden)

    Miho eWatanabe

    2014-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

  6. Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA production

    Directory of Open Access Journals (Sweden)

    Qian Lin

    2013-01-01

    Full Text Available γ-Aminobutyric acid (GABA is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of y-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxylase activity, culture of Lb. rhamnosus YS9 in medium supplemented with 200 mM of monosodium glutamate and 200 µM of pyridoxal phosphate (PLP, produced 187 mM of GABA.

  7. Butyric acid fermentation in a fibrous bed bioreactor with immobilized Clostridium tyrobutyricum from cane molasses.

    Science.gov (United States)

    Jiang, Ling; Wang, Jufang; Liang, Shizhong; Wang, Xiaoning; Cen, Peilin; Xu, Zhinan

    2009-07-01

    Butyrate fermentation by immobilized Clostridium tyrobutyricum was successfully carried out in a fibrous bed bioreactor using cane molasses. Batch fermentations were conducted to investigate the influence of pH on the metabolism of the strain, and the results showed that the fermentation gave a highest butyrate production of 26.2 g l(-1) with yield of 0.47 g g(-1) and reactor productivity up to 4.13 g l(-1)h(-1) at pH 6.0. When repeated-batch fermentation was carried out, long-term operation with high butyrate yield, volumetric productivity was achieved. Several cane molasses pretreatment techniques were investigated, and it was found that sulfuric acid treatment gave better results regarding butyrate concentration (34.6+/-0.8 g l(-1)), yield (0.58+/-0.01 g g(-1)), and sugar utilization (90.8+/-0.9%). Also, fed-batch fermentation from cane molasses pretreated with sulfuric acid was performed to further increase the concentration of butyrate up to 55.2 g l(-1).

  8. Eicosanoid modulation by the short-chain fatty acid n-butyrate in human monocytes

    Science.gov (United States)

    Kovarik, Johannes J; Hölzl, Markus A; Hofer, Johannes; Waidhofer-Söllner, Petra; Sobanov, Yury; Koeffel, René; Saemann, Marcus D; Mechtcheriakova, Diana; Zlabinger, Gerhard J

    2013-01-01

    n-Butyrate deriving from bacterial fermentation in the mammalian intestine is a key determinant in gastrointestinal homeostasis. We examined the effects of this short-chain fatty acid and Toll-like receptor 2 (TLR) and TLR4 engagement on inflammatory/immunity-associated genes, cyclo-oxygenases (COXs), prostaglandins (PGs) and leukotrienes (LTs) in human monocytes. Before RNA isolation, freshly isolated human monocytes were co-incubated for different time-points with 1 mm n-butyrate alone or in combination with bacterial stimuli. Based on a knowledge-driven approach, a signature of 180 immunity/inflammation-associated genes was picked and real-time PCR analysis was performed. Pathway analysis was carried out using a web-based database analysing program. Based on these gene expression studies the findings were evaluated at the protein/mediator level by Western blot analysis, FACS and ELISA. Following co-incubation with n-butyrate and lipopolysaccharide, key enzymes of the eicosanoid pathway, like PTGS2 (COX-2), TXS, ALOX5, LTA4H and LTC4S, were significantly up-regulated compared with stimulation with lipopolysaccharide alone. Furthermore, release of the lipid mediators PGE2, 15d-PGJ2, LTB4 and thromboxane B2 was increased by n-butyrate. Regarding signalling, n-butyrate had no additional effect on mitogen-activated protein kinase and interfered differently with early and late phases of nuclear factor-κB signalling. Our results suggest that among many other mediators of eicosanoid signalling n-butyrate massively induces PGE2 production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR4 and TLR2 activation and induces secretion of LTB4 and thromboxane B2. This underscores the role of n-butyrate as a crucial mediator of gut-specific immunity. PMID:23398566

  9. Improving farm management by modeling the contamination of farm tank milk with butyric acid bacteria

    NARCIS (Netherlands)

    Vissers, M.M.M.; Driehuis, F.; Giffel, te M.C.; Jong, de P.; Lankveld, J.M.G.

    2006-01-01

    Control of contamination of farm tank milk (FTM) with the spore-forming butyric acid bacteria (BAB) is important to prevent the late-blowing defect in semi-hard cheeses. The risk of late blowing can be decreased via control of the contamination level of FTM with BAB. A modeling approach was applied

  10. Radiation induces acid tolerance of Clostridium tyrobutyricum and enhances bioproduction of butyric acid through a metabolic switch.

    Science.gov (United States)

    Zhou, Xiang; Lu, Xi-Hong; Li, Xue-Hu; Xin, Zhi-Jun; Xie, Jia-Rong; Zhao, Mei-Rong; Wang, Liang; Du, Wen-Yue; Liang, Jian-Ping

    2014-02-18

    Butyric acid as a renewable resource has become an increasingly attractive alternative to petroleum-based fuels. Clostridium tyrobutyricum ATCC 25755T is well documented as a fermentation strain for the production of acids. However, it has been reported that butyrate inhibits its growth, and the accumulation of acetate also inhibits biomass synthesis, making production of butyric acid from conventional fermentation processes economically challenging. The present study aimed to identify whether irradiation of C. tyrobutyricum cells makes them more tolerant to butyric acid inhibition and increases the production of butyrate compared with wild type. In this work, the fermentation kinetics of C. tyrobutyricum cultures after being classically adapted for growth at 3.6, 7.2 and 10.8 g·L-1 equivalents were studied. The results showed that, regardless of the irradiation used, there was a gradual inhibition of cell growth at butyric acid concentrations above 10.8 g·L-1, with no growth observed at butyric acid concentrations above 3.6 g·L-1 for the wild-type strain during the first 54 h of fermentation. The sodium dodecyl sulfate polyacrylamide gel electrophoresis also showed significantly different expression levels of proteins with molecular mass around the wild-type and irradiated strains. The results showed that the proportion of proteins with molecular weights of 85 and 106 kDa was much higher for the irradiated strains. The specific growth rate decreased by 50% (from 0.42 to 0.21 h-1) and the final concentration of butyrate increased by 68% (from 22.7 to 33.4 g·L-1) for the strain irradiated at 114 AMeV and 40 Gy compared with the wild-type strains. This study demonstrates that butyric acid production from glucose can be significantly improved and enhanced by using 12C6+ heavy ion-irradiated C. tyrobutyricum. The approach is economical, making it competitive compared with similar fermentation processes. It may prove useful as a first step in a combined

  11. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    Science.gov (United States)

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. Copyright © 2016 the American Physiological Society.

  12. Enhanced butyric acid tolerance and production by Class I heat shock protein-overproducing Clostridium tyrobutyricum ATCC 25755.

    Science.gov (United States)

    Suo, Yukai; Luo, Sheng; Zhang, Yanan; Liao, Zhengping; Wang, Jufang

    2017-08-01

    The response of Clostridium tyrobutyricum to butyric acid stress involves various stress-related genes, and therefore overexpression of stress-related genes can improve butyric acid tolerance and yield. Class I heat shock proteins (HSPs) play an important role in the process of protecting bacteria from sudden changes of extracellular stress by assisting protein folding correctly. The results of quantitative real-time PCR indicated that the Class I HSGs grpE, dnaK, dnaJ, groEL, groES, and htpG were significantly upregulated under butyric acid stress, especially the dnaK and groE operons. Overexpression of groESL and htpG could significantly improve the tolerance of C. tyrobutyricum to butyric acid, while overexpression of dnaK and dnaJ showed negative effects on butyric acid tolerance. Acid production was also significantly promoted by increased GroESL expression levels; the final butyric acid and acetic acid concentrations were 28.2 and 38% higher for C. tyrobutyricum ATCC 25755/groESL than for the wild-type strain. In addition, when fed-batch fermentation was carried out using cell immobilization in a fibrous-bed bioreactor, the butyric acid yield produced by C. tyrobutyricum ATCC 25755/groESL reached 52.2 g/L, much higher than that for the control. The improved butyric acid yield is probably attributable to the high GroES and GroEL levels, which can stabilize the biosynthetic machinery of C. tyrobutyricum under extracellular butyric acid stress.

  13. Co-culturing a novel Bacillus strain with Clostridium tyrobutyricum ATCC 25755 to produce butyric acid from sucrose

    Science.gov (United States)

    2013-01-01

    Background Currently, the most promising microorganism used for the bio-production of butyric acid is Clostridium tyrobutyricum ATCC 25755T; however, it is unable to use sucrose as a sole carbon source. Consequently, a newly isolated strain, Bacillus sp. SGP1, that was found to produce a levansucrase enzyme, which hydrolyzes sucrose into fructose and glucose, was used in a co-culture with this strain, permitting C. tyrobutyricum ATCC 25755T to ferment sucrose to butyric acid. Results B. sp. SGP1 alone did not show any butyric acid production and the main metabolite produced was lactic acid. This allowed C. tyrobutyricum ATCC 25755T to utilize the monosaccharides resulting from the activity of levansucrase together with the lactic acid produced by B. sp. SGP1 to generate butyric acid, which was the main fermentative product within the co-culture. Furthermore, the final acetic acid concentration in the co-culture was significantly lower when compared with pure C. tyrobutyricum ATCC 25755T cultures grown on glucose. In fed-batch fermentations, the optimum conditions for the production of butyric acid were around pH 5.50 and a temperature of 37°C. Under these conditions, the final butyrate concentration was 34.2±1.8 g/L with yields of 0.35±0.03 g butyrate/g sucrose and maximum productivity of 0.3±0.04 g/L/h. Conclusions Using this co-culture, sucrose can be utilized as a carbon source for butyric acid production at a relatively high yield. In addition, this co-culture offers also the benefit of a greater selectivity, with butyric acid constituting 92.8% of the acids when the fermentation was terminated. PMID:23452443

  14. Metabolic engineering of Clostridium tyrobutyricum for enhanced butyric acid production from glucose and xylose.

    Science.gov (United States)

    Fu, Hongxin; Yu, Le; Lin, Meng; Wang, Jufang; Xiu, Zhilong; Yang, Shang-Tian

    2017-03-01

    Clostridium tyrobutyricum is a promising microorganism for butyric acid production. However, its ability to utilize xylose, the second most abundant sugar found in lignocellulosic biomass, is severely impaired by glucose-mediated carbon catabolite repression (CCR). In this study, CCR in C. tyrobutyricum was eliminated by overexpressing three heterologous xylose catabolism genes (xylT, xylA and xlyB) cloned from C. acetobutylicum. Compared to the parental strain, the engineered strain Ct-pTBA produced more butyric acid (37.8g/L vs. 19.4g/L) from glucose and xylose simultaneously, at a higher xylose utilization rate (1.28g/L·h vs. 0.16g/L·h) and efficiency (94.3% vs. 13.8%), resulting in a higher butyrate productivity (0.53g/L·h vs. 0.26g/L·h) and yield (0.32g/g vs. 0.28g/g). When the initial total sugar concentration was ~120g/L, both glucose and xylose utilization rates increased with increasing their respective concentration or ratio in the co-substrates but the total sugar utilization rate remained almost unchanged in the fermentation at pH 6.0. Decreasing the pH to 5.0 significantly decreased sugar utilization rates and butyrate productivity, but the effect was more pronounced for xylose than glucose. The addition of benzyl viologen (BV) as an artificial electron carrier facilitated the re-assimilation of acetate and increased butyrate production to a final titer of 46.4g/L, yield of 0.43g/g sugar consumed, productivity of 0.87g/L·h, and acid purity of 98.3% in free-cell batch fermentation, which were the highest ever reported for butyric acid fermentation. The engineered strain with BV addition thus can provide an economical process for butyric acid production from lignocellulosic biomass. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  15. Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sean M. McNabney

    2017-12-01

    Full Text Available Increased dietary fiber consumption has been associated with many beneficial effects, including amelioration of obesity and insulin resistance. These effects may be due to the increased production of short chain fatty acids, including propionate, acetate and butyrate, during fermentation of the dietary fiber in the colon. Indeed, oral and dietary supplementation of butyrate alone has been shown to prevent high fat-diet induced obesity and insulin resistance. This review focuses on sources of short chain fatty acids, with emphasis on sources of butyrate, mechanisms of fiber and butyrate metabolism in the gut and its protective effects on colon cancer and the peripheral effects of butyrate supplementation in peripheral tissues in the prevention and reversal of obesity and insulin resistance.

  16. Fast detection of extrasynaptic GABA with a whole-cell sniffer

    DEFF Research Database (Denmark)

    Christensen, Rasmus K; Petersen, Anders V; Schmitt, Nicole

    2014-01-01

    Gamma-amino-butyric acid (GABA) is the main inhibitory transmitter of the brain. It operates by binding to specific receptors located both inside and outside synapses. The extrasynaptic receptors are activated by spillover from GABAergic synapses and by ambient GABA in the extracellular space....... Ambient GABA is essential for adjusting the excitability of neurons. However, due to the lack of suitable methods, little is known about its dynamics. Here we describe a new technique that allows detection of GABA transients and measurement of the steady state GABA concentration with high spatial...... and temporal resolution. We used a human embryonic kidney (HEK) cell line that stably expresses GABAA receptors composed of α1, β2, and γ2 subunits. We recorded from such a HEK cell with the whole-cell patch-clamp technique. The presence of GABA near the HEK cell generated a measurable electric current whose...

  17. Genetic manipulation of the γ-aminobutyric acid (GABA) shunt in rice: overexpression of truncated glutamate decarboxylase (GAD2) and knockdown of γ-aminobutyric acid transaminase (GABA-T) lead to sustained and high levels of GABA accumulation in rice kernels.

    Science.gov (United States)

    Shimajiri, Yasuka; Oonishi, Takayuki; Ozaki, Kae; Kainou, Kumiko; Akama, Kazuhito

    2013-06-01

    Gamma-aminobutyric acid (GABA) is a non-protein amino acid commonly present in all organisms. Because cellular levels of GABA in plants are mainly regulated by synthesis (glutamate decarboxylase, GAD) and catabolism (GABA-transaminase, GABA-T), we attempted seed-specific manipulation of the GABA shunt to achieve stable GABA accumulation in rice. A truncated GAD2 sequence, one of five GAD genes, controlled by the glutelin (GluB-1) or rice embryo globulin promoters (REG) and GABA-T-based trigger sequences in RNA interference (RNAi) cassettes controlled by one of these promoters as well, was introduced into rice (cv. Koshihikari) to establish stable transgenic lines under herbicide selection using pyriminobac. T₁ and T₂ generations of rice lines displayed high GABA concentrations (2-100 mg/100 g grain). In analyses of two selected lines from the T₃ generation, there was a strong correlation between GABA level and the expression of truncated GAD2, whereas the inhibitory effect of GABA-T expression was relatively weak. In these two lines both with two T-DNA copies, their starch, amylose, and protein levels were slightly lower than non-transformed cv. Koshihikari. Free amino acid analysis of mature kernels of these lines demonstrated elevated levels of GABA (75-350 mg/100 g polished rice) and also high levels of several amino acids, such as Ala, Ser, and Val. Because these lines of seeds could sustain their GABA content after harvest (up to 6 months), the strategy in this study could lead to the accumulation GABA and for these to be sustained in the edible parts. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Phase equilibria of liquid (water + butyric acid + oleyl alcohol) ternary system

    International Nuclear Information System (INIS)

    Bilgin, Mehmet

    2006-01-01

    (Liquid + liquid) equilibrium (LLE) data for the ternary system of (water + butyric acid + oleyl alcohol) at T = (298.15, 308.15, and 318.15) K are reported. Complete phase diagrams were obtained by determining solubility and the tie-line data. The reliability of the experimental tie lines was confirmed by using Othmer-Tobias correlation. The UNIFAC method was used to predict the phase equilibrium data. The phase diagrams for the ternary mixtures including both the experimental and correlated tie lines are presented. Distribution coefficients and separation factors were evaluated for the immiscibility region. A comparison of the solvent extracting capability was made with respect to distribution coefficients, separation factors, and solvent-free selectivity bases for T = (298.15, 308.15, and 318.15) K. It is concluded that oleyl alcohol may serve as an adequate solvent to extract butyric acid from its dilute aqueous solutions

  19. (Liquid + liquid) equilibria of (water + butyric acid + dibasic esters) ternary systems

    International Nuclear Information System (INIS)

    Kirbaslar, S. Ismail; Sahin, Selin; Bilgin, Mehmet

    2007-01-01

    (Liquid + liquid) equilibrium (LLE) data of the solubility (binodal) curves and tie-line end compositions were examined for mixtures of {water (1) + butyric acid (2) + dimethyl succinate or dimethyl glutarate or dimethyl adipate (3)} at T = 298.15 K and p = (101.3 ± 0.7) kPa. The relative mutual solubility of the butyric acid is higher in the dibasic esters layers than in the aqueous layer. The reliability of the experimental tie-line data was confirmed by using the Othmer-Tobias correlation. The LLE data of the ternary systems were predicted by UNIFAC method. Distribution coefficients and separation factors were evaluated for the immiscibility region

  20. Phase equilibria of liquid (water + butyric acid + oleyl alcohol) ternary system

    Energy Technology Data Exchange (ETDEWEB)

    Bilgin, Mehmet [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)]. E-mail: mbilgin@istanbul.edu.tr

    2006-12-15

    (Liquid + liquid) equilibrium (LLE) data for the ternary system of (water + butyric acid + oleyl alcohol) at T = (298.15, 308.15, and 318.15) K are reported. Complete phase diagrams were obtained by determining solubility and the tie-line data. The reliability of the experimental tie lines was confirmed by using Othmer-Tobias correlation. The UNIFAC method was used to predict the phase equilibrium data. The phase diagrams for the ternary mixtures including both the experimental and correlated tie lines are presented. Distribution coefficients and separation factors were evaluated for the immiscibility region. A comparison of the solvent extracting capability was made with respect to distribution coefficients, separation factors, and solvent-free selectivity bases for T = (298.15, 308.15, and 318.15) K. It is concluded that oleyl alcohol may serve as an adequate solvent to extract butyric acid from its dilute aqueous solutions.

  1. (Liquid + liquid) equilibria of (water + butyric acid + dibasic esters) ternary systems

    Energy Technology Data Exchange (ETDEWEB)

    Kirbaslar, S. Ismail [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)]. E-mail: krbaslar@istanbul.edu.tr; Sahin, Selin [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey); Bilgin, Mehmet [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)

    2007-02-15

    (Liquid + liquid) equilibrium (LLE) data of the solubility (binodal) curves and tie-line end compositions were examined for mixtures of {l_brace}water (1) + butyric acid (2) + dimethyl succinate or dimethyl glutarate or dimethyl adipate (3){r_brace} at T = 298.15 K and p = (101.3 {+-} 0.7) kPa. The relative mutual solubility of the butyric acid is higher in the dibasic esters layers than in the aqueous layer. The reliability of the experimental tie-line data was confirmed by using the Othmer-Tobias correlation. The LLE data of the ternary systems were predicted by UNIFAC method. Distribution coefficients and separation factors were evaluated for the immiscibility region.

  2. Effect of indole-3-butyric acid (IBA) on in vitro root induction in ...

    African Journals Online (AJOL)

    Root induction pre-developed in vitro plantlets of orchid was carried out using indole-3-butyric acid (IBA) (0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3 mM) on basal Murashige and Skoog (MS) medium. Among the concentrations of IBA, the number of roots per plantlet with 1 mM IBA was found to be the highest (2.25 roots per plantlet) ...

  3. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    OpenAIRE

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic ac...

  4. Proboscis conditioning experiments with honeybees, Apis mellifera caucasica, with butyric acid and DEET mixture as conditioned and unconditioned stimuli.

    Science.gov (United States)

    Abramson, Charles I; Giray, Tugrul; Mixson, T Andrew; Nolf, Sondra L; Wells, Harrington; Kence, Aykut; Kence, Meral

    2010-01-01

    Three experiments are described investigating whether olfactory repellents DEET and butyric acid can support the classical conditioning of proboscis extension in the honeybee, Apis mellifera caucasica (Hymenoptera: Apidae). In the first experiment DEET and butyric acid readily led to standard acquisition and extinction effects, which are comparable to the use of cinnamon as a conditioned stimulus. These results demonstrate that the odor of DEET or butyric acid is not intrinsically repellent to honey bees. In a second experiment, with DEET and butyric acid mixed with sucrose as an unconditioned stimulus, proboscis conditioning was not established. After several trials, few animals responded to the unconditioned stimulus. These results demonstrate that these chemicals are gustatory repellents when in direct contact. In the last experiment a conditioned suppression paradigm was used. Exposing animals to butyric acid or DEET when the proboscis was extended by direct sucrose stimulation or by learning revealed that retraction of the proboscis was similar to another novel odor, lavender, and in all cases greatest when the animal was not permitted to feed. These results again demonstrate that DEET or butyric acid are not olfactory repellents, and in addition, conditioned suppression is influenced by feeding state of the bee.

  5. Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD).

    Science.gov (United States)

    Russo, Anthony J; Pietsch, Stefanie C

    2013-01-01

    There is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD). Plasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations. In this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity. These results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

  6. Production of butyric acid from glucose and xylose with immobilized cells of Clostridium tyrobutyricum in a fibrous-bed bioreactor.

    Science.gov (United States)

    Jiang, Ling; Wang, Jufang; Liang, Shizhong; Wang, Xiaoning; Cen, Peilin; Xu, Zhinan

    2010-01-01

    Butyric acid has many applications in chemical, food, and pharmaceutical industries. In the present study, Clostridium tyrobutyricum ATCC 25755 was immobilized in a fibrous-bed bioreactor to evaluate the performance of butyrate production from glucose and xylose. The results showed that the final concentration and yield of butyric acid were 13.70 and 0.46 g g(-1), respectively, in batch fermentation when 30 g L(-1) glucose was introduced into the bioreactor. Furthermore, high concentration 10.10 g L(-1) and yield 0.40 g g(-1) of butyric acid were obtained with 25 g L(-1) xylose as the carbon source. The immobilized cells of C. tyrobutyricum ensured similar productivity and yield from repeated batch fermentation. In the fed-batch fermentation, the final concentration of butyric acid was further improved to 24.88 g L(-1) with one suitable glucose feeding in the fibrous-bed bioreactor. C. tyrobutyricum immobilized in the fibrous-bed bioreactor would provide an economically viable fermentation process to convert the reducing sugars derived from plant biomass into the final bulk chemical (butyric acid).

  7. Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds.

    Science.gov (United States)

    Lee, Na-Kyoung; Paik, Hyun-Dong

    2017-05-28

    Lactic acid bacteria (LAB) are used as fermentation starters in vegetable and dairy products and influence the pH and flavors of foods. For many centuries, LAB have been used to manufacture fermented foods; therefore, they are generally regarded as safe. LAB produce various substances, such as lactic acid, β-glucosidase, and β-galactosidase, making them useful as fermentation starters. Existing functional substances have been assessed as fermentation substrates for better component bioavailability or other functions. Representative materials that were bioconverted using LAB have been reported and include minor ginsenosides, γ-aminobutyric acid, equol, aglycones, bioactive isoflavones, genistein, and daidzein, among others. Fermentation mainly involves polyphenol and polysaccharide substrates and is conducted using bacterial strains such as Streptococcus thermophilus, Lactobacillus plantarum, and Bifidobacterium sp. In this review, we summarize recent studies of bioconversion using LAB and discuss future directions for this field.

  8. Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst.

    Science.gov (United States)

    Lee, Jong-Min; Upare, Pravin P; Chang, Jong-San; Hwang, Young Kyu; Lee, Jeong Ho; Hwang, Dong Won; Hong, Do-Young; Lee, Seung Hwan; Jeong, Myung-Geun; Kim, Young Dok; Kwon, Young-Uk

    2014-11-01

    Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Molecular Mechanisms Underlying γ-Aminobutyric Acid (GABA) Accumulation in Giant Embryo Rice Seeds.

    Science.gov (United States)

    Zhao, Guo-Chao; Xie, Mi-Xue; Wang, Ying-Cun; Li, Jian-Yue

    2017-06-21

    To uncover the molecular mechanisms underlying GABA accumulation in giant embryo rice seeds, we analyzed the expression levels of GABA metabolism genes and contents of GABA and GABA metabolic intermediates in developing grains and germinated brown rice of giant embryo rice 'Shangshida No. 5' and normal embryo rice 'Chao2-10' respectively. In developing grains, the higher GABA contents in 'Shangshida No. 5' were accompanied with upregulation of gene transcripts and intermediate contents in the polyamine pathway and downregulation of GABA catabolic gene transcripts, as compared with those in 'Chao2-10'. In germinated brown rice, the higher GABA contents in 'Shangshida No. 5' were parallel with upregulation of OsGAD and polyamine pathway gene transcripts and Glu and polyamine pathway intermediate contents and downregulation of GABA catabolic gene transcripts. These results are the first to indicate that polyamine pathway and GABA catabolic genes play a crucial role in GABA accumulation in giant embryo rice seeds.

  10. (Liquid + liquid) equilibria of the (water + butyric acid + dodecanol) ternary system

    Energy Technology Data Exchange (ETDEWEB)

    Kirbaslar, S. Ismail [Istanbul University, Engineering Faculty, Chemical Engineering Department, 34320 Avcilar, Istanbul (Turkey)]. E-mail: krbaslar@istanbul.edu.tr

    2006-06-15

    (Liquid + liquid) equilibrium (LLE) data for the (water + butyric acid + dodecanol) ternary system have been determined experimentally at T = (298.2, 308.2 and 318.2) K. Complete phase diagrams were obtained by determining binodal curves and tie lines. The reliability of the experimental tie lines was confirmed by using the Othmer-Tobias correlation. The UNIFAC method was used to predict the phase equilibrium in the ternary system using the interaction parameters determined from experimental data of CH{sub 3}, CH{sub 2}, COOH, OH and H{sub 2}O functional groups. Distribution coefficients and separation factors were evaluated for the immiscibility region.

  11. Liquid - liquid equilibria of the water + butyric acid + decanol ternary system

    Directory of Open Access Journals (Sweden)

    S.I. Kirbaslar

    2006-09-01

    Full Text Available Liquid-liquid equilibrium (LLE data for the water + butyric acid + decanol ternary system were determined experimentally at temperatures of 298.15, 308.15 and 318.15 K. Complete phase diagrams were obtained by determining the solubility curve and the tie lines. The reliability of the experimental tie line data was confirmed with the Othmer-Tobias correlation. The UNIFAC method was used to predict the phase equilibrium of the system using the interaction parameters for groups CH3, CH2, COOH, OH and H2O determined experimentally. Distribution coefficients and separation factors were evaluated for the immiscibility region.

  12. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

  13. Effects of NaCl Replacement with Gamma-Aminobutyric acid (GABA) on the Quality Characteristics and Sensorial Properties of Model Meat Products.

    Science.gov (United States)

    Chun, Ji-Yeon; Kim, Byeongsoo; Lee, Jung Gyu; Cho, Hyung-Yong; Min, Sang-Gi; Choi, Mi-Jung

    2014-01-01

    This study investigated the effects of γ-aminobutylic acid (GABA) on the quality and sensorial properties of both the GABA/NaCl complex and model meat products. GABA/NaCl complex was prepared by spray-drying, and the surface dimensions, morphology, rheology, and saltiness were characterized. For model meat products, pork patties were prepared by replacing NaCl with GABA. For characteristics of the complex, increasing GABA concentration increased the surface dimensions of the complex. However, GABA did not affect the rheological properties of solutions containing the complex. The addition of 2% GABA exhibited significantly higher saltiness than the control (no GABA treatment). In the case of pork patties, sensory testing indicated that the addition of GABA decreased the saltiness intensity. Both the intensity of juiciness and tenderness of patties containing GABA also scored lower than the control, based on the NaCl reduction. These results were consistent with the quality characteristics (cooking loss and texture profile analysis). Nevertheless, overall acceptability of the pork patties showed that up to 1.5%, patties containing GABA did not significantly differ from the control. Consequently, the results indicated that GABA has a potential application in meat products, but also manifested a deterioration of quality by the NaCl reduction, which warrants further exploration.

  14. Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet.

    Science.gov (United States)

    Xie, Z X; Xia, S F; Qiao, Y; Shi, Y H; Le, G W

    2015-06-01

    Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma-aminobutyric acid (GABA), a food additive, can reduce high-fat diet (HFD)-induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD-induced hyperglycaemia probably by repairing HFD-induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA-related decrease in the levels of pFAA and GABA as well as obesity. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  15. The structure and diffusion behaviour of the neurotransmitter γ-aminobutyric acid (GABA) in neutral aqueous solutions

    International Nuclear Information System (INIS)

    Rodrigo, M.M.; Esteso, M.A.; Barros, M.F.; Verissimo, L.M.P.; Romero, C.M.; Suarez, A.F.; Ramos, M.L.; Valente, A.J.M.; Burrows, H.D.; Ribeiro, A.C.F.

    2017-01-01

    Highlights: • Diffusion coefficients and densities of binary aqueous solutions of γ-aminobutyric acid (GABA). • Dependence on both shape and size of GABA on its diffusion. • Interactions intramolecular and the solute-water interactions in these systems. - Abstract: GABA (γ-aminobutyric acid) is a non-protein amino acid with important physiological properties, and with considerable relevance to the food and pharmaceutical industries. Particular interest has focused on its role as an inhibitory neurotransmitter in the mammalian cerebral cortex. In this paper, we report density and mutual diffusion coefficients of GABA in non-buffered aqueous solutions (0.001–0.100) mol·dm −3 at 298.15 K. Under these conditions, 1 H and 13 C NMR spectroscopy and pH measurements show that it is present predominantly as a monomeric zwitterionic species. Diffusion coefficients have been computed assuming that this behaves as the binary system GABA/water. From density and intermolecular diffusion coefficients measurements, the molar volume, hydrodynamic radii, R h , diffusion coefficients at infinitesimal concentration, D 0 , activity coefficients and the thermodynamic factors, F T , have been estimated. Within experimental error, the hydrodynamic volume calculated from this is identical to the molar volume obtained from density measurements. From the NMR spectra and literature data, it is suggested that this amino acid diffuses in aqueous solution as a curved, coil-like hydrated zwitterionic entity.

  16. Transplutonium elements separation on anionites by using aqueous-alcohol solutions of nitric acid and butyric acid mixtures

    International Nuclear Information System (INIS)

    Guseva, L.I.; Tikhomirova, G.S.

    1978-01-01

    The behaviour of 243 Am, 243 Cm, and 249 Cf isotopes has been investigated in aqueous-methanol solutions of butyric, isobutyric, α-oxybutyric and α-oxynisobutyric acids in a mixture with nitric acid during their sorption on strongly basic anionites. The coefficients of distribution of transplutonium elements have been determined depending on the concentration of various components of the solution. Under the optimum conditions, the factors of separation of Am-Cm and Cm-Cf pairs amount to about 6 and 4 respectively. The advantages of using macroporous anionites of the soviet production have been demonstrated for the separation of transplutonium elements in the systems under examination

  17. Continuous Fermentation of Clostridium tyrobutyricum with Partial Cell Recycle as a Long-Term Strategy for Butyric Acid Production

    Directory of Open Access Journals (Sweden)

    Edgar C. Clausen

    2012-08-01

    Full Text Available In making alternative fuels from biomass feedstocks, the production of butyric acid is a key intermediate in the two-step production of butanol. The fermentation of glucose via Clostridium tyrobutyricum to butyric acid produces undesirable byproducts, including lactic acid and acetic acid, which significantly affect the butyric acid yield and productivity. This paper focuses on the production of butyric acid using Clostridium tyrobutyricum in a partial cell recycle mode to improve fermenter yield and productivity. Experiments with fermentation in batch, continuous culture and continuous culture with partial cell recycle by ultrafiltration were conducted. The results show that a continuous fermentation can be sustained for more than 120 days, which is the first reported long-term production of butyric acid in a continuous operation. Further, the results also show that partial cell recycle via membrane ultrafiltration has a great influence on the selectivity and productivity of butyric acid, with an increase in selectivity from ≈9% to 95% butyric acid with productivities as high as 1.13 g/Lh. Continuous fermentation with low dilution rate and high cell recycle ratio has been found to be desirable for optimum productivity and selectivity toward butyric acid and a comprehensive model explaining this phenomenon is given.

  18. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L.

    Science.gov (United States)

    Appel, Kurt; Rose, Thorsten; Fiebich, Bernd; Kammler, Thomas; Hoffmann, Christine; Weiss, Gabriele

    2011-06-01

    Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for treating anxiety or nervousness, Generalized Anxiety Disorder (GAD), symptoms of opiate withdrawal, insomnia, neuralgia, convulsion, spasmodic asthma, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction and menopause. However, the mechanism of action is still under discussion. Despite gaps in our understanding of neurophysiological processes, it is increasingly being recognized that dysfunction of the GABA system is implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. Therefore, the in vitro effects of a dry extract of Passiflora incarnata (sole active ingredient in Pascoflair® 425 mg) on the GABA system were investigated. The extract inhibited [(3) H]-GABA uptake into rat cortical synaptosomes but had no effect on GABA release and GABA transaminase activity. Passiflora incarnata inhibited concentration dependently the binding of [(3) H]- SR95531 to GABA(A) -receptors and of [(3) H]-CGP 54626 to GABA(B) -receptors. Using the [(35) S]-GTPγS binding assay Passiflora could be classified as an antagonist of the GABA(B) receptor. In contrast, the ethanol- and the benzodiazepine-site of the GABA(A) -receptor were not affected by this extract. In conclusion, the first evidence was shown that numerous pharmacological effects of Passiflora incarnata are mediated via modulation of the GABA system including affinity to GABA(A) and GABA(B) receptors, and effects on GABA uptake. Copyright © 2010 John Wiley & Sons, Ltd.

  19. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could ......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

  20. The effect of fermented buckwheat on producing l-carnitine- and γ-aminobutyric acid (GABA)-enriched designer eggs.

    Science.gov (United States)

    Park, Namhyeon; Lee, Tae-Kyung; Nguyen, Thi Thanh Hanh; An, Eun-Bae; Kim, Nahyun M; You, Young-Hyun; Park, Tae-Sub; Kim, Doman

    2017-07-01

    The potential of fermented buckwheat as a feed additive was studied to increase l-carnitine and γ-aminobutyric acid (GABA) in designer eggs. Buckwheat contains high levels of lysine, methionine and glutamate, which are precursors for the synthesis of l-carnitine and GABA. Rhizopus oligosporus was used for the fermentation of buckwheat to produce l-carnitine and GABA that exert positive effects such as enhanced metabolism, antioxidant activities, immunity and blood pressure control. A novel analytical method for simultaneously detecting l-carnitine and GABA was developed using liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS. The fermented buckwheat extract contained 4 and 34 times more l-carnitine and GABA respectively compared with normal buckwheat. Compared with the control, the fermented buckwheat extract-fed group showed enriched l-carnitine (13.6%) and GABA (8.4%) in the yolk, though only l-carnitine was significantly different (P superfood production and supplement industries. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  1. Exogenous γ-aminobutyric Acid (GABA) Application Improved Early Growth, Net Photosynthesis, and Associated Physio-Biochemical Events in Maize.

    Science.gov (United States)

    Li, Wu; Liu, Jianhua; Ashraf, Umair; Li, Gaoke; Li, Yuliang; Lu, Wenjia; Gao, Lei; Han, Fuguang; Hu, Jianguang

    2016-01-01

    γ-aminobutyric acid (GABA) is an endogenous signaling molecule and involved in growth regulations and plant development, however, a little information is available on the consequences of exogenous GABA application on growth, development, and associated physio-biochemical processes in maize. The present study examined the GABA-induced regulations in early growth, net photosynthetic rate, gas exchange, osmoregulation, and enzymatic activities in three maize cultivars, i.e., Yuecainuo 6, Zhengtian 68, and Yuecainuo 2. Two levels of GABA, i.e., 0 mg L(-1) and 50 mg L(-1), in solution form, with total application volume of 100 ml per pot containing 15 maize seedlings were exogenously applied. Results revealed that exogenous GABA application improved seedling growth in terms of seedling length and biomass accumulation in all maize cultivars at both 3 and 7 days after treatment (DAT). It also promoted net photosynthesis and variably affected gas exchange attributes, i.e., stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), as well as leaves SPAD value. Furthermore, lipid peroxidation [in terms of malondialdehyde (MDA)] under GABA treated maize seedlings were also remained variable; however, osmolyte accumulation (protein and proline) and activities of anti-oxidants enzymes, i.e., super-oxide dismutase and peroxidase were also affected differently at both 3 and 7 DAT in all maize cultivars. Furthermore, enzymes involved in nitrogen metabolism, e.g., nitrate reductase and glutamine synthetase were improved. These results suggest the involvement of GABA in various physio-metablical mechanisms which might lead to improvement in morphological growth of maize. In future, research is still needed at molecular and genetic levels to unravel the involvement of GABA-mediated regulations in growth and its associated physio-biochemical mechanisms.

  2. Quantification of γ-aminobutyric acid (GABA) in1H MRS volumes composed heterogeneously of grey and white matter.

    Science.gov (United States)

    Mikkelsen, Mark; Singh, Krish D; Brealy, Jennifer A; Linden, David E J; Evans, C John

    2016-11-01

    The quantification of γ-aminobutyric acid (GABA) concentration using localised MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey (GM) and white (WM) matter. These differences can be represented as a ratio between intrinsic GABA in GM and WM: r M . Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has been described previously. Partial volume effects attributed to r M can be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of r M weighted by the proportion of GM and WM within tissue-segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of r M taken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of r M . It was shown that incorrect assumptions of r M can lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to r M successfully removed this dependence. With an appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between-participant variance, increased power in statistical tests and better discriminability of true effects. Copyright © 2016 John

  3. [Simultaneous determination of clevidipine butyrate and its metabolite clevidipine acid in dog blood by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Wei, Hui-hui; Gu, Yuan; Liu, Yan-ping; Wei, Guang-li; Chen, Yong; Liu, Chang-xiao; Si, Duan-yun

    2015-10-01

    A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 µm) with a gradient mobile phase consisting of methanol and 5 mmol · L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng · mL and 1-200 ng · mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng · mL(-1) and 1 ng · mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg · h(-1) for 0.5 h.

  4. Construction and characterization of pta gene-deleted mutant of Clostridium tyrobutyricum for enhanced butyric acid fermentation.

    Science.gov (United States)

    Zhu, Ying; Liu, Xiaoguang; Yang, Shang-Tian

    2005-04-20

    Clostridium tyrobutyricum ATCC 25755 is an acidogenic bacterium, producing butyrate and acetate as its main fermentation products. In order to decrease acetate and increase butyrate production, integrational mutagenesis was used to disrupt the gene associated with the acetate formation pathway in C. tyrobutyricum. A nonreplicative integrational plasmid containing the phosphotransacetylase gene (pta) fragment cloned from C. tyrobutyricum by using degenerate primers and an erythromycin resistance cassette were constructed and introduced into C. tyrobutyricum by electroporation. Integration of the plasmid into the homologous region on the chromosome inactivated the target pta gene and produced the pta-deleted mutant (PTA-Em), which was confirmed by Southern hybridization. SDS-PAGE and two-dimensional protein electrophoresis results indicated that protein expression was changed in the mutant. Enzyme activity assays using the cell lysate showed that the activities of PTA and acetate kinase (AK) in the mutant were reduced by more than 60% for PTA and 80% for AK. The mutant grew more slowly in batch fermentation with glucose as the substrate but produced 15% more butyrate and 14% less acetate as compared to the wild-type strain. Its butyrate productivity was approximately 2-fold higher than the wild-type strain. Moreover, the mutant showed much higher tolerance to butyrate inhibition, and the final butyrate concentration was improved by 68%. However, inactivation of pta gene did not completely eliminate acetate production in the fermentation, suggesting the existence of other enzymes (or pathways) also leading to acetate formation. This is the first-reported genetic engineering study demonstrating the feasibility of using a gene-inactivation technique to manipulate the acetic acid formation pathway in C. tyrobutyricum in order to improve butyric acid production from glucose. Copyright 2005 Wiley Periodicals, Inc.

  5. Profile of preoperative fecal organic acids closely predicts the incidence of postoperative infectious complications after major hepatectomy with extrahepatic bile duct resection: Importance of fecal acetic acid plus butyric acid minus lactic acid gap.

    Science.gov (United States)

    Yokoyama, Yukihiro; Mizuno, Takashi; Sugawara, Gen; Asahara, Takashi; Nomoto, Koji; Igami, Tsuyoshi; Ebata, Tomoki; Nagino, Masato

    2017-10-01

    To investigate the association between preoperative fecal organic acid concentrations and the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection for biliary malignancies. The fecal samples of 44 patients were collected before undergoing hepatectomy with bile duct resection for biliary malignancies. The concentrations of fecal organic acids, including acetic acid, butyric acid, and lactic acid, and representative fecal bacteria were measured. The perioperative clinical characteristics and the concentrations of fecal organic acids were compared between patients with and without postoperative infectious complications. Among 44 patients, 13 (30%) developed postoperative infectious complications. Patient age and intraoperative bleeding were significantly greater in patients with postoperative infectious complications compared with those without postoperative infectious complications. The concentrations of fecal acetic acid and butyric acid were significantly less, whereas the concentration of fecal lactic acid tended to be greater in the patients with postoperative infectious complications. The calculated gap between the concentrations of fecal acetic acid plus butyric acid minus lactic acid gap was less in the patients with postoperative infectious complications (median 43.5 vs 76.1 μmol/g of feces, P = .011). Multivariate analysis revealed that an acetic acid plus butyric acid minus lactic acid gap acid profile (especially low acetic acid, low butyric acid, and high lactic acid) had a clinically important impact on the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection. Copyright © 2017. Published by Elsevier Inc.

  6. Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, G H; Elster, L

    1998-01-01

    ; that is, GABA acts as a trophic signal. Accordingly, activating preexisting GABA receptors, a trophic GABA signal enhances the growth rate of neuronal processes, facilitates synapse formation, and promotes synthesis of specific proteins. Transcription and de novo synthesis are initiated by the GABA signal......, this ability to target the induced GABAA receptors is probably coupled to the maturation of neurons and not to the action of GABA per se. The induced GABAA receptors apparently mediate a pronounced inhibition of neurotransmitter release, whereas other subtypes of GABAA receptors may be modulatory rather than...

  7. Efficient gamma-aminobutyric acid bioconversion by employing synthetic complex between glutamate decarboxylase and glutamate/GABA antiporter in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Ko, Ji-seun; Park, Si Jae; Lee, Seung Hwan; Hong, Soon Ho

    2013-08-01

    Gamma-aminobutyric acid (GABA) is a precursor of one of the most promising heat-resistant biopolymers, Nylon-4, and can be produced by the decarboxylation of monosodium glutamate (MSG). In this study, a synthetic protein complex was applied to improve the GABA conversion in engineered Escherichia coli. Complexes were constructed by assembling a single protein-protein interaction domain SH3 to the glutamate decarboxylase (GadA and GadB) and attaching a cognate peptide ligand to the glutamate/GABA antiporter (GadC) at the N-terminus, C-terminus, and the 233rd amino acid residue. When GadA and GadC were co-overexpressed via the C-terminus complex, a GABA concentration of 5.65 g/l was obtained from 10 g/l MSG, which corresponds to a GABA yield of 93 %. A significant increase of the GABA productivity was also observed where the GABA productivity increased 2.5-fold in the early culture period due to the introduction of the synthetic protein complex. The GABA pathway efficiency and GABA productivity were enhanced by the introduction of the complex between Gad and glutamate/GABA antiporter.

  8. Diet structure, butyric acid, and fermentable carbohydrates influence growth performance, gut morphology, and cecal fermentation characteristics in broilers

    NARCIS (Netherlands)

    Qaisrani, S.N.; Krimpen, van M.M.; Kwakkel, R.P.; Verstegen, M.W.A.; Hendriks, W.H.

    2015-01-01

    An experiment with 288 male (Ross 308) 1-d-old broilers was conducted to test the hypothesis that a coarse diet supplemented with butyric acid (BA) and fermentable carbohydrates (FC) improves performance of broilers with a poorly digestible protein source. The interaction effects of diet structure

  9. Lipase in biphasic alginate beads as a biocatalyst for esterification of butyric acid and butanol in aqueous media.

    Science.gov (United States)

    Ng, Choong Hey; Yang, Kun-Lin

    2016-01-01

    Esterification of organic acids and alcohols in aqueous media is very inefficient due to thermodynamic constraints. However, fermentation processes used to produce organic acids and alcohols are often conducted in aqueous media. To produce esters in aqueous media, biphasic alginate beads with immobilized lipase are developed for in situ esterification of butanol and butyric acid. The biphasic beads contain a solid matrix of calcium alginate and hexadecane together with 5 mg/mL of lipase as the biocatalyst. Hexadecane in the biphasic beads serves as an organic phase to facilitate the esterification reaction. Under optimized conditions, the beads are able to catalyze the production of 0.16 mmol of butyl butyrate from 0.5 mmol of butyric acid and 1.5 mmol of butanol. In contrast, when monophasic beads (without hexadecane) are used, only trace amount of butyl butyrate is produced. One main application of biphasic beads is in simultaneous fermentation and esterification (SFE) because the organic phase inside the beads is very stable and does not leach out into the culture medium. SFE is successfully conducted with an esterification yield of 6.32% using biphasic beads containing iso-octane even though the solvent is proven toxic to the butanol-producing Clostridium spp. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. (Liquid + liquid) equilibria of (water + butyric acid + isoamyl alcohol) ternary system

    Energy Technology Data Exchange (ETDEWEB)

    Bilgin, Mehmet [Engineering Faculty, Chemical Engineering Department, Istanbul University, Avcilar-Campus, 34320 Istanbul (Turkey); Ismail Kirbaslar, S. [Engineering Faculty, Chemical Engineering Department, Istanbul University, Avcilar-Campus, 34320 Istanbul (Turkey)]. E-mail: krbaslar@istanbul.edu.tr; Oezcan, Oender [Mustafa Nevzat Ilac San. AS., 34530 Yenibosna, Istanbul (Turkey); Dramur, Umur [Engineering Faculty, Chemical Engineering Department, Istanbul University, Avcilar-Campus, 34320 Istanbul (Turkey)

    2005-04-15

    (Liquid + liquid) equilibrium (LLE) data for the ternary system (water + butyric acid + isoamyl alcohol) have been determined experimentally at T (298.15, 308.15 and 318.15) K. Complete phase diagrams were obtained by determining solubility and the tie-line data. Tie-line compositions were correlated by Othmer-Tobias method. The UNIFAC method was used to predict the phase equilibrium in the system using the interaction parameters determined from experimental data between groups CH{sub 3}, CH{sub 2}, CH, COOH, OH and H{sub 2}O. It is found that UNIFAC group interaction parameters used for LLE could not provide a good prediction. Distribution coefficients and separation factors were evaluated for the immiscibility region.

  11. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    Science.gov (United States)

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Hepatic metabolism of anaesthetized growing pigs during acute portal infusion of volatile fatty acids and hydroxy-methyl butyrate

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Larsen, Uffe Krogh; Bjerre-Harpøth, Vibeke

    2016-01-01

    intervals and analyzed for contents of paraamino- hippuric acid (PAH; blood flow marker) and plasma metabolites. Total VFA was infused at a rate of 0 mmol/h (background; Inf1, Inf6), 60 mmol/h (Inf2) or 120 mmol/h (Inf3 to Inf5). Infused VFA contained 70, 20, and 5% of acetate, propionate, and butyrate......, respectively, for Inf2 and Inf3, or 65%, 20%, and 10% of acetate, propionate, and butyrate, respectively, for Inf4 and Inf5. In addition, for Inf5, HMB was infused at 2 mmol/h. Statistical analysis included fixed effects of infusion and interaction between infusion and samplings within infusion while...... accounting for repeated measurements. A net hepatic uptake of propionate, butyrate, and lactate was observed, whereas the liver released acetate, glucose, and urea. The portal lactate absorption could not account for the net hepatic uptake of lactate, suggesting lactate originated from partial oxidation...

  13. p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo.

    Science.gov (United States)

    Scheepens, Arjan; Bisson, Jean-Francois; Skinner, Margot

    2014-02-01

    The increasing prevalence and social burden of subclinical anxiety in the western world represents a significant psychosocial and financial cost. Consumers are favouring a more natural and nonpharmacological approach for alleviating the effects of everyday stress and anxiety. The gamma-aminobutyric acid (GABA) receptor is the primary mediator of central inhibitory neurotransmission, and GABA-receptor agonists are well known to convey anxiolytic effects. Using an in vitro screening approach to identify naturally occurring phytochemical GABA agonists, we discovered the plant secondary metabolite p-coumaric acid to have significant GABAergic activity, an effect that could be blocked by co-administration of the specific GABA-receptor antagonist, picrotoxin. Oral administration of p-coumaric acid to rodents induced a significant anxiolytic effect in vivo as measured using the elevated plus paradigm, in line with the effects of oral diazepam. Given that p-coumaric acid is reasonably well absorbed following oral consumption in man and is relatively nontoxic, it may be suitable for the formulation of a safe and effective anxiolytic functional food. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Deuterium kinetic isotope effect in the oxidation of deuteriated butyric acid-D7 with chromium trioxide in 85% orthophosphoric acid

    International Nuclear Information System (INIS)

    Zielinska, A.; Zielinski, M.

    2001-01-01

    A comparative study of the deuterium kinetic isotope effect in the oxidation of the deuteriated butyric acid-D 7 with Cr(VI) in 85% orthophosphoric acid has been carried out. The (k HH /k DD ) KIE values between 5.7 and 7.0 indicate that the tunnelling is not involved in oxidation of deuteriated aliphatic carboxylic acids with chromium trioxide in acidic media and the oxidation KIE is determined by the zero point energy difference corresponding to the C-H/C-D stretching vibrations lost in the transition state. The results were compared with the large D-KIE observed in the oxidation of butyrate-D 7 with alkaline manganate caused by the simultaneous operation of zeropoint energy effect and tunnelling. (author)

  15. β-Amino-n-butyric Acid Regulates Seedling Growth and Disease Resistance of Kimchi Cabbage.

    Science.gov (United States)

    Kim, Yeong Chae; Kim, Yeon Hwa; Lee, Young Hee; Lee, Sang Woo; Chae, Yun-Soek; Kang, Hyun-Kyung; Yun, Byung-Wook; Hong, Jeum Kyu

    2013-09-01

    Non-protein amino acid, β-amino-n-butyric acid (BABA), has been involved in diverse physiological processes including seedling growth, stress tolerance and disease resistance of many plant species. In the current study, treatment of kimchi cabbage seedlings with BABA significantly reduced primary root elongation and cotyledon development in a dose-dependent manner, which adverse effects were similar to the plant response to exogenous abscisic acid (ABA) application. BABA was synergistically contributing ABA-induced growth arrest during the early seedling development. Kimchi cabbage leaves were highly damaged and seedling growth was delayed by foliar spraying with high concentrations of BABA (10 to 20 mM). BABA played roles differentially in in vitro fungal conidial germination, mycelial growth and conidation of necrotroph Alternaria brassicicola causing black spot disease and hemibiotroph Colletotrichum higginsianum causing anthracnose. Pretreatment with BABA conferred induced resistance of the kimchi cabbage against challenges by the two different classes of fungal pathogens in a dose-dependent manner. These results suggest that BABA is involved in plant development, fungal development as well as induced fungal disease resistance of kimchi cabbage plant.

  16. β-Amino-n-butyric Acid Regulates Seedling Growth and Disease Resistance of Kimchi Cabbage

    Directory of Open Access Journals (Sweden)

    Yeong Chae Kim

    2013-09-01

    Full Text Available Non-protein amino acid, β-amino-n-butyric acid (BABA, has been involved in diverse physiological processes including seedling growth, stress tolerance and disease resistance of many plant species. In the current study, treatment of kimchi cabbage seedlings with BABA significantly reduced primary root elongation and cotyledon development in a dose-dependent manner, which adverse effects were similar to the plant response to exogenous abscisic acid (ABA application. BABA was synergistically contributing ABA-induced growth arrest during the early seedling development. Kimchi cabbage leaves were highly damaged and seedling growth was delayed by foliar spraying with high concentrations of BABA (10 to 20 mM. BABA played roles differentially in in vitro fungal conidial germination, mycelial growth and conidation of necrotroph Alternaria brassicicola causing black spot disease and hemibiotroph Colletotrichum higginsianum causing anthracnose. Pretreatment with BABA conferred induced resistance of the kimchi cabbage against challenges by the two different classes of fungal pathogens in a dose-dependent manner. These results suggest that BABA is involved in plant development, fungal development as well as induced fungal disease resistance of kimchi cabbage plant.

  17. Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia.

    Science.gov (United States)

    Morland, Cecilie; Frøland, Anne-Sofie; Pettersen, Mi Nguyen; Storm-Mathisen, Jon; Gundersen, Vidar; Rise, Frode; Hassel, Bjørnar

    2018-02-16

    Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here, we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in the striatum and neocortex. Propionate caused an increase in GABA (γ-amino butyric acid) levels in the brain, suggesting inhibition of GABA breakdown. In vitro propionate inhibited GABA transaminase with a K i of ∼1 mmol/l. In isolated nerve endings, propionate caused increased release of GABA to the extracellular fluid. In vivo , propionate reduced cerebral glucose metabolism in both striatum and neocortex. We conclude that propionate-induced inhibition of GABA transaminase causes accumulation of GABA in the brain, leading to increased extracellular GABA concentration, which inhibits neuronal activity and causes lethargy. Propionate-mediated inhibition of neuronal GABA transaminase, an enzyme of the inner mitochondrial membrane, indicates entry of propionate into neuronal mitochondria. However, previous work has shown that neurons are unable to metabolize propionate oxidatively, leading us to conclude that propionyl-CoA synthetase is probably absent from neuronal mitochondria. Propionate-induced inhibition of energy metabolism in GABAergic neurons may render the striatum, in which >90% of the neurons are GABAergic, particularly vulnerable to degeneration in propionic acidemia. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  18. Effects of propionate and methylmalonate on conversions of acetate, butyrate, and D(-)-3-hydroxybutyrate to fatty acids and carbon dioxide by mammary tissue slices of goats

    International Nuclear Information System (INIS)

    Emmanuel, B.; Kennelly, J.J.

    1985-01-01

    Incorporations of [1-carbon-14] acetate, [1-carbon-14] propionate, n-[1-carbon-14] butyrate, and D(-)-3-hydroxy[3-carbon-14] butyrate into individual milk fatty acids and their conversion to carbon dioxide were studied in vitro with caprine mammary tissue slices in the presence and absence of propionate and methylmalonate. Neither propionate nor methylmalonate affected incorporation of these substances into fatty acids. In a decreasing order butyrate, acetate, propionate, and D(-)-3-hydroxybutyrate were converted to carbon dioxide. Acetate had the highest incorporation rate into fatty acids followed by D(-)-3-hydroxybutyrate, butyrate, and propionate. Labeled propionate was incorporated mainly into odd-numbered fatty acids. Results do not support the theory that either propionate or its metabolite, methylmalonate, inhibit de novo synthesis of fatty acids in the mammary gland in relation to the etiology of low milk fat syndrome

  19. Sensitization of colon cancer cell lines to butyrate-mediated proliferation inhibition by combined application of indomethacin and nordihydroguaiaretic acid.

    Science.gov (United States)

    Galfi, Peter; Neogrady, Zsuzsa; Amberger, Albert; Margreiter, Raimund; Csordas, Adam

    2005-01-01

    The aim of the study was to investigate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on histone deacetylase-mediated proliferation inhibition. In the colon cancer cell line HT29 butyrate-mediated proliferation inhibition was enhanced by the additional presence of indomethacin (IM) and/or nordihydroguaiaretic acid (NDGA). Sensitisation to butyrate-mediated proliferation inhibition was abolished by the general caspase inhibitor Z-VAD-fmk, however, only IM-induced cell detachment was prevented by the caspase inhibitor but not that induced by NDGA or NDGA plus IM. In contrast to the parental cell line HT29, in the methotrexate-resistant sub-lines HT29-12 and HT29-21, IM counteracted butyrate-mediated proliferation inhibition, which was abrogated by NDGA. In all the investigated cell lines, proliferation inhibition was most effectively achieved under the combined application of butyrate with IM and NDGA, suggesting that inhibition of both cyclooxygenase (COX) and lipoxygenase (LOX) isoenzymes is needed for proliferation inhibition by NSAIDs in tumour cells.

  20. Subclinical Ketosis on Dairy Cows in Transition Period in Farms with Contrasting Butyric Acid Contents in Silages

    Directory of Open Access Journals (Sweden)

    Fernando Vicente

    2014-01-01

    Full Text Available This study examines the relationship between subclinical ketosis (SCK in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05. As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake.

  1. Subclinical ketosis on dairy cows in transition period in farms with contrasting butyric acid contents in silages.

    Science.gov (United States)

    Vicente, Fernando; Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

    2014-01-01

    This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).

  2. Moessbauer spectroscopic evidence for iron(III) complexation and reduction in acidic aqueous solutions of indole-3-butyric acid

    International Nuclear Information System (INIS)

    Kovacs, K.; Kuzmann, E.; Vertes, A.; Kamnev, A.A.; Shchelochkov, A.G.; Medzihradszky-Schweiger, H.; Mink, J.; Hungarian Academy of Sciences, Budapest

    2004-01-01

    Moessbauer spectroscopic studies were carried out in acidic (pH 2.3) 57 Fe III nitrate containing aqueous solutions of indole-3-butyric acid (IBA), rapidly frozen in liquid nitrogen at various periods of time after mixing the reagents. The data obtained show that in solution in the presence of IBA, iron(III) forms a complex with a dimeric structure characterised by a quadrupole doublet, whereas without IBA under similar conditions iron(III) exhibits a broad spectral feature due to a slow paramagnetic spin relaxation which, at liquid nitrogen temperature, results in a large anomalous line broadening (or, at T = 4.2 K, in a hyperfine magnetic splitting). The spectra of 57 Fe III +IBA solutions, kept at ambient temperature under aerobic conditions for increasing periods of time before freezing, contained a gradually increasing contribution of a component with a higher quadrupole splitting. The Moessbauer parameters for that component are typical for iron(II) aquo complexes, thus showing that under these conditions gradual reduction of iron(III) occurs, so that the majority (85%) of dissolved iron(III) is reduced within 2 days. The Moessbauer parameters for the iron(III)-IBA complex in aqueous solution and in the solid state (separated from the solution by filtration) were found to be similar, which may indicate that the dissolved and solid complexes have the same composition and/or iron(III) coordination environment. For the solid complex, the data of elemental analysis suggest the following composition of the dimer: [L 2 Fe-(OH) 2 -FeL 2 ] (where L is indole-3-butyrate). This structure is also in agreement with the data of infrared spectroscopic study of the complex reported earlier, with the side-chain carboxylic group in indole-3-butyrate as a bidentate ligand. The Moessbauer parameters for the solid 57 Fe III -IBA complex at T = 80 K and its acetone solution rapidly frozen in liquid nitrogen were virtually identical, which indicates that the complex retains its

  3. Colon cancer cell apoptosis is induced by combined exposure to the n-3 fatty acid docosahexaenoic acid and butyrate through promoter methylation.

    Science.gov (United States)

    Cho, Youngmi; Turner, Nancy D; Davidson, Laurie A; Chapkin, Robert S; Carroll, Raymond J; Lupton, Joanne R

    2014-03-01

    DNA methylation and histone acetylation contribute to the transcriptional regulation of genes involved in apoptosis. We have demonstrated that docosahexaenoic acid (DHA, 22:6 n-3) and butyrate enhance colonocyte apoptosis. To determine if DHA and/or butyrate elevate apoptosis through epigenetic mechanisms thereby restoring the transcription of apoptosis-related genes, we examined global methylation; gene-specific promoter methylation of 24 apoptosis-related genes; transcription levels of Cideb, Dapk1, and Tnfrsf25; and global histone acetylation in the HCT-116 colon cancer cell line. Cells were treated with combinations of (50 µM) DHA or linoleic acid (18:2 n-6), (5 mM) butyrate or an inhibitor of DNA methyltransferases, and 5-aza-2'-deoxycytidine (5-Aza-dC, 2 µM). Among highly methylated genes, the combination of DHA and butyrate significantly reduced methylation of the proapoptotic Bcl2l11, Cideb, Dapk1, Ltbr, and Tnfrsf25 genes compared to untreated control cells. DHA treatment reduced the methylation of Cideb, Dapk1, and Tnfrsf25. These data suggest that the induction of apoptosis by DHA and butyrate is mediated, in part, through changes in the methylation state of apoptosis-related genes.

  4. The effect of butyric acid with autogenous omental graft on healing of experimental Achilles tendon injury in rabbits.

    Science.gov (United States)

    Jahani, S; Moslemi, H R; Dehghan, M M; Sedaghat, R; Mazaheri Nezhad, R; Rezaee Moghaddam, D

    2015-01-01

    In this study, the role of local injection of butyric acid (BA) with autogenous omental graft was evaluated in healing of experimental Achilles tendon injury in rabbits. Nine adult male New Zealand rabbits were anesthetized and a partial thickness tenotomy was created on both hindlimbs. In treated group, omental graft was secured in place using BA soaked polygalactin 910 suture. In control group, the graft was sutured without BA. Butyric acid and normal saline were injected daily to treatment and control groups for three days, respectively. Based on the findings, on day 15 after injury, the tendon sections showed that healing rate in BA treated group was higher than that in control group. Furthermore, at days 28 and 45, comparison between BA treated and control groups demonstrated that BA increased the healing rate but with no significance. In summary, results of this study show that application of BA with autogenous omental graft can improve healing process of damaged Achilles tendon.

  5. A comparison of three pH control methods for revealing effects of undissociated butyric acid on specific butanol production rate in batch fermentation of Clostridium acetobutylicum.

    Science.gov (United States)

    Yang, Xuepeng; Tu, Maobing; Xie, Rui; Adhikari, Sushil; Tong, Zhaohui

    2013-01-07

    pH control has been essential for butanol production with Clostridium acetobutylicum. However, it is not very clear at what pH level the acid crash will occur, at what pH level butanol production will be dominant, and at what pH level butyric acid production will be prevailing. Furthermore, contradictory results have been reported about required acidic conditions for initiation of solventogenesis. In this study, with the aim of further understanding the role of undissociated butyric acid in butanol production, we investigated the correlation between undissociated butyric acid concentration and specific butanol production rate in batch fermentation of Clostridium acetobutylicum by comparing three pH control approaches: NaOH neutralization (at 12, 24 or 36 h), CaCO3 supplementation (2, 5, or 8 g/l) and NaOAc buffering (pH 4.6, 5.0 or 5.6). By neutralizing the fermentation pH to ~5.0 at different time, we observed that neutralization should take place at the beginning of exponential phase (12 h), and otherwise resulting in lower concentrations of undissociated butyric acid, cell biomass and final butanol. CaCO3 supplementation extended cell growth to 36 h and resulted in higher butyrate yield under 8 g/L of CaCO3. In the NaOAc buffering, the highest specific butanol rate (0.58 h-1) was associated with the highest undissociated butyric acid (1.92 g/L). The linear correlation of the undissociated butyric acid with the specific butanol production rates suggested the undissociated butyric acid could be the major driving force for butanol production.

  6. Synthesis and biological evaluation of bis-CNB-GABA, a photoactivatable neurotransmitter with low receptor interference and chemical two-photon uncaging properties.

    Science.gov (United States)

    Shi, Diana D; Trigo, Federico F; Semmelhack, Martin F; Wang, Samuel S-H

    2014-02-05

    Photoactivatable "caged" neurotransmitters allow optical control of neural tissue with high spatial and temporal precision. However, the development of caged versions of the chief vertebrate inhibitory neurotransmitter, γ-amino butyric acid (GABA), has been limited by the propensity of caged GABAs to interact with GABA receptors. We describe herein the synthesis and application of a practically useful doubly caged GABA analog, termed bis-α-carboxy-2-nitrobenzyl-GABA (bis-CNB-GABA). Uncaging of bis-CNB-GABA evokes inward GABAergic currents in cerebellar molecular layer interneurons with rise times of 2 ms, comparable to flash duration. Response amplitudes depend on the square of flash intensity, as expected for a chemical two-photon uncaging effect. Importantly, prior to uncaging, bis-CNB-GABA is inactive at the GABAA receptor, evoking no changes in holding current in voltage-clamped neurons and showing an IC50 of at least 2.5 mM as measured using spontaneous GABAergic synaptic currents. Bis-CNB-GABA is stable in solution, with an estimated half-life of 98 days in the light. We expect that bis-CNB-GABA will prove to be an effective tool for high-resolution chemical control of brain circuits.

  7. Lipid alterations in human colon epithelial cells induced to differentiation and/or apoptosis by butyrate and polyunsaturated fatty acids

    Czech Academy of Sciences Publication Activity Database

    Hofmanová, Jiřina; Ciganek, M.; Slavík, J.; Kozubík, Alois; Stixová, Lenka; Vaculová, Alena; Dušek, L.; Machala, M.

    2012-01-01

    Roč. 23, č. 6 (2012), s. 539-548 ISSN 0955-2863 R&D Projects: GA ČR(CZ) GA524/07/1178; GA ČR(CZ) GAP301/11/1730 Institutional research plan: CEZ:AV0Z50040507 Institutional support: RVO:68081707 Keywords : Colon cancer * Polyunsaturated fatty acids * Butyrate Subject RIV: BO - Biophysics Impact factor: 4.552, year: 2012

  8. Negative polarity of phenyl-C61 butyric acid methyl ester adjacent to donor macromolecule domains

    International Nuclear Information System (INIS)

    Alley, Olivia J.; Dawidczyk, Thomas J.; Hardigree, Josué F. Martínez; Katz, Howard E.; Wu, Meng-Yin; Johns, Gary L.; Markovic, Nina; Arnold, Michael S.

    2015-01-01

    Interfacial fields within organic photovoltaics influence the movement of free charge carriers, including exciton dissociation and recombination. Open circuit voltage (V oc ) can also be dependent on the interfacial fields, in the event that they modulate the energy gap between donor HOMO and acceptor LUMO. A rise in the vacuum level of the acceptor will increase the gap and the V oc , which can be beneficial for device efficiency. Here, we measure the interfacial potential differences at donor-acceptor junctions using Scanning Kelvin Probe Microscopy, and quantify how much of the potential difference originates from physical contact between the donor and acceptor. We see a statistically significant and pervasive negative polarity on the phenyl-C 61 butyric acid methyl ester (PCBM) side of PCBM/donor junctions, which should also be present at the complex interfaces in bulk heterojunctions. This potential difference may originate from molecular dipoles, interfacial interactions with donor materials, and/or equilibrium charge transfer due to the higher work function and electron affinity of PCBM. We show that the contact between PCBM and poly(3-hexylthiophene) doubles the interfacial potential difference, a statistically significant difference. Control experiments determined that this potential difference was not due to charges trapped in the underlying substrate. The direction of the observed potential difference would lead to increased V oc , but would also pose a barrier to electrons being injected into the PCBM and make recombination more favorable. Our method may allow unique information to be obtained in new donor-acceptor junctions

  9. Augmentation of tendon healing with butyric acid-impregnated sutures: biomechanical evaluation in a rabbit model.

    Science.gov (United States)

    Leek, Bryan T; Tasto, James P; Tibor, Lisa M; Healey, Robert M; Freemont, Anthony; Linn, Michael S; Chase, Derek E; Amiel, David

    2012-08-01

    Butyric acid (BA) has been shown to be angiogenic and to enhance transcriptional activity in tissue. These properties of BA have the potential to augment biological healing of a repaired tendon. To evaluate this possibility both biomechanically and histologically in an animal tendon repair model. Controlled laboratory study. A rabbit Achilles tendon healing model was used to evaluate the biomechanical strength and histological properties at 6 and 12 weeks after repair. Unilateral tendon defects were created in the middle bundle of the Achilles tendon of each rabbit, which were repaired equivalently with either Ultrabraid BA-impregnated sutures or control Ultrabraid sutures. After 6 weeks, BA-impregnated suture repairs had a significantly increased (P Tendons repaired with BA-impregnated sutures demonstrated improved biomechanical properties at 6 weeks relative to control sutures, suggesting a neoangiogenic mechanism of enhanced healing through an increased myofibroblast presence. These findings demonstrate that a relatively simple alteration of suture material may augment early tendon healing to create a stronger repair construct during this time.

  10. Indole butyric acid and substrates influence on multiplication of blackberry 'Xavante'

    Directory of Open Access Journals (Sweden)

    Ibrar Hussain

    2014-10-01

    Full Text Available Blackberry is a shrubby plant specie which has a high economic importance among agriculture crops. Brazil is the major country of Latin America with the highest future scope for blackberries. For availability of good quality and maximum quantity of seedlings, the present study was carried out at the Universidade Estadual de Londrina,PR from January to March in 2013. The aim of the study was to evaluate the multiplication of blackberry 'Xavante' cuttings under different type of substrates treated with different levels of indole butyric acid (IBA. The experiment was laid out in randomized complete block design with 2 factors, i.e., substrate (rice husk, vermiculite and coconut fiber and IBA (0; 1,000; 2,000 and 3,000mg L-1, with 5 replications. Each replicate consisted of 10 cuttings. The variables studied were: cutting rooting, cutting survival, leaf retention, cuttings with new leaves, number of major roots, length of major roots and roots dry weight. Most of the variables were significantly affected by both substrate and IBA. Rice husk and vermiculite performed better than coconut fiber and provided the same results for most of the variables, while coconut fiber showed lower performance for all of the variables studied. IBA significantly affected the rooting and the number of major roots. It is concluded that for multiplication of blackberry 'Xavante', both rice husk and vermiculite can be used along 2,000mg L-1 of IBA

  11. Electronic Structures and Optical Properties of Phenyl C71 Butyric Acid Methyl Esters

    Directory of Open Access Journals (Sweden)

    Cai-Rong Zhang

    2013-01-01

    Full Text Available Phenyl C71 butyric acid methyl ester (PC71BM has been adopted as electron acceptor materials in bulk heterojunction solar cells with relatively higher power conversion efficiency. The understanding of the mechanism and performance for the devices based upon PC71BM requires the information of conformations, electronic structures, optical properties, and so forth. Here, the geometries, IR and Raman, electronic structures, polarizabilities, and hyperpolarizabilities of PC71BM isomers are studied by using density functional theory (DFT; the absorption and excitation properties are investigated via time-dependent DFT with B3LYP, PBE0, and CAM-B3LYP functionals. The calculated results show that [6,6]PC71BM is more stable than [5,6]PC71BM due to the lower total energy. The vibrational modes of the isomers at IR and Raman peaks are quite similar. As to absorption properties, CAM-B3LYP functional is the suitable functional for describing the excitations of PC71BM because the calculated results with CAM-B3LYP functional agree well with that of the experiment. The analysis of transition configurations and molecular orbitals demonstrated that the transitions at the absorption maxima in UV/Vis region are localized π-π* transitions in fullerenes cages. Furthermore, the larger isotropic polarizability of PC71BM indicates that the response of PC71BM to applied external electric field is stronger than that of PC61BM, and therefore resulting into better nonlinear optical properties.

  12. Rhizogenic behavior of black pepper cultivars to indole-3-butyric acid

    Directory of Open Access Journals (Sweden)

    Welington Secundino

    2014-07-01

    Full Text Available Little information is available regarding vegetative propagation of the species Piper nigrum L. to generate technical recommendations for the production of seedlings on a commercial scale. The purpose of this study was to investigate the rhizogenic behavior of cultivars of this species regarding indol-3-butyric acid (IBA. The experiment was performed at a vegetation house equipped with an intermittent nebulization irrigation system. The experimental site was located in the University Center of Northern Espírito Santo (CEUNES of the Federal University of Espírito Santo (UFES, Brazil. The experimental design consisted of randomized blocks arranged in a 3 x 5 factorial scheme: three cultivars (Bragantina, Iaçará and Guajarina x five IBA concentrations (0; 1,500; 3,000; 4,500 and 6,000 mg kg-1, with four repetitions of 16 cuttings each. Total immersion of the cuttings in IBA is recommended for the Iaçará and Guajarina cultivars, and immersion of only the basal region is recommended for cv. Bragantina. The recommended IBA concentration for these cultivars is 4,000 mg kg-1.

  13. Butyric acid production from lignocellulosic biomass hydrolysates by engineered Clostridium tyrobutyricum overexpressing Class I heat shock protein GroESL.

    Science.gov (United States)

    Suo, Yukai; Fu, Hongxin; Ren, Mengmeng; Yang, Xitong; Liao, Zhengping; Wang, Jufang

    2018-02-01

    Lignocellulosic biomass is the most abundant and renewable substrate for biological fermentation, but the inhibitors present in the lignocellulosic hydrolysates could severely inhibit the cell growth and productivity of industrial strains. This study confirmed that overexpressing of native groESL in Clostridium tyrobutyricum could significantly improve its tolerance to lignocellulosic hydrolysate-derived inhibitors, especially for phenolic compounds. Consequently, ATCC 25755/groESL showed a better performance in butyric acid fermentation with hydrolysates of corn cob, corn straw, rice straw, wheat straw, soybean hull and soybean straw, respectively. When corn straw and rice straw hydrolysates, which showed strong toxicity to C. tyrobutyricum, were used as the substrates, 29.6 g/L and 30.1 g/L butyric acid were obtained in batch fermentation, increased by 26.5% and 19.4% as compared with the wild-type strain, respectively. And more importantly, the butyric acid productivity reached 0.31 g/L·h (vs. 0.20-0.21 g/L·h for the wild-type strain) due to the shortened lag phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Diastereoselective Three-Component Reactions of Chiral Nickel(II Glycinate for Convenient Synthesis of Novel α-Amino-β-Substituted-γ,γ-Disubstituted Butyric Acids

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    2014-01-01

    Full Text Available The convenient, high yielding and diastereoselective synthesis of α-amino-β-substituted-γ,γ-disubstituted butyric acid derivatives was carried out by a three-component tandem reaction of a chiral equivalent of nucleophilic glycine. The reaction was performed smoothly under mild conditions and enabled the construction of two or three adjacent chiral centers in one step, thus affording a novel and convenient route to α-amino-β-substituted-γ,γ-disubstituted butyric acid derivatives.

  15. Study on flavour volatiles of γ-aminobutyric acid (GABA) green tea ...

    African Journals Online (AJOL)

    It was shown by the sensory evaluation that the color of the soup and the extracted leaves of GABA tea were similar to that of the oolong tea, and the smell was similar to the aroma of cooked sweet red dates mixed with some of sour. In GABA tea, the contents of 2,6-bis(1,1-dimethylethyl)-4-methyl phenol, methyl myristate, ...

  16. Allosteric ligands and their binding sites define γ-aminobutyric acid (GABA) type A receptor subtypes.

    Science.gov (United States)

    Olsen, Richard W

    2015-01-01

    GABAA receptors (GABA(A)Rs) mediate rapid inhibitory transmission in the brain. GABA(A)Rs are ligand-gated chloride ion channel proteins and exist in about a dozen or more heteropentameric subtypes exhibiting variable age and brain regional localization and thus participation in differing brain functions and diseases. GABA(A)Rs are also subject to modulation by several chemotypes of allosteric ligands that help define structure and function, including subtype definition. The channel blocker picrotoxin identified a noncompetitive channel blocker site in GABA(A)Rs. This ligand site is located in the transmembrane channel pore, whereas the GABA agonist site is in the extracellular domain at subunit interfaces, a site useful for low energy coupled conformational changes of the functional channel domain. Two classes of pharmacologically important allosteric modulatory ligand binding sites reside in the extracellular domain at modified agonist sites at other subunit interfaces: the benzodiazepine site and the high-affinity, relevant to intoxication, ethanol site. The benzodiazepine site is specific for certain GABA(A)R subtypes, mainly synaptic, while the ethanol site is found at a modified benzodiazepine site on different, extrasynaptic, subtypes. In the transmembrane domain are allosteric modulatory ligand sites for diverse chemotypes of general anesthetics: the volatile and intravenous agents, barbiturates, etomidate, propofol, long-chain alcohols, and neurosteroids. The last are endogenous positive allosteric modulators. X-ray crystal structures of prokaryotic and invertebrate pentameric ligand-gated ion channels, and the mammalian GABA(A)R protein, allow homology modeling of GABA(A)R subtypes with the various ligand sites located to suggest the structure and function of these proteins and their pharmacological modulation. © 2015 Elsevier Inc. All rights reserved.

  17. Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

    2002-01-01

    The rat gamma-aminobutyric acid transporter-1 (GAT-1) was expressed in Xenopus laevis oocytes and the substrate-independent Li(+)-induced leak current was examined using two-electrode voltage clamp. The leak current was not affected by the addition of GABA and was not due to H(+) permeation. The Li......(+)-bound conformation of the protein displayed a lower passive water permeability than that of the Na(+)- and choline (Ch(+))-bound conformations and the leak current did not saturate with increasing amounts of Li(+) in the test solution. The mechanism that gives rise to the leak current did not support active water...... millimolar concentrations of Na(+) (the apparent affinity constant, K'(0.5) = 3 mM). In addition, it was found that the GABA transport current was sustained at correspondingly low Na(+) concentrations if Li(+) was present instead of choline. This is consistent with a model in which Li(+) can bind...

  18. Effects of Feeding Methylthio Butyric Acid Isopropyl Ester on Postpartum Performance and Metabolism in Dairy Cows

    Directory of Open Access Journals (Sweden)

    K. Xia

    2012-05-01

    Full Text Available The present experiment aimed to evaluate the effect of HMBi on the production performance and metabolism in dairy cows. Thirty multiparous Holstein dairy cows under similar conditions were randomly assigned to three dietary treatments; i Control, a basal diet; ii T1, a basal diet plus HMBi (0 g prepartum and 18 g postpartum; and iii T2, a basal diet plus HMBi (10 g prepartum and 18 g postpartum. Treatments were initiated 21 d before expected calving and continued through 91 d postpartum. HMBi was top-dressed onto the total mixed ration of each cow. Treatments did not affect dry matter intake, plasma urea nitrogen, peak milk yield, days to peak milk yield, nonesterified fatty acid, glutamate pyruvate transaminase, glutamic oxalaetic transaminase, milk fat content, milk protein content, milk lactose content, and milk solid non-fat content. The milk composition yields were increased by the HMBi-supplemented treatment. The T1 and T2 treatments increased the yields of 4% fat-corrected milk yield, milk fat, milk protein, and milk lactose compared with the control. Although there was no difference in the milk composition of the control and T2-treated cows, the T2-treated cows exhibited higher milk fat yield (increased by 74 g/d, lower milk urea nitrogen (reduced by 3.41%, and plasma β-hydroxy butyrate than the control cows. The results indicate that HMBi supplementation to diet has beneficial effects, and that there is no difference between supplementation at prepartum and starting only at parturition.

  19. Comparative photocatalytic study of two selected pesticide derivatives, indole-3-acetic acid and indole-3-butyric acid in aqueous suspensions of titanium dioxide

    International Nuclear Information System (INIS)

    Qamar, M.; Muneer, M.

    2005-01-01

    Heterogeneous photocatalysed degradation of two selected pesticide derivatives such as indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) has been investigated in aqueous suspensions of titanium dioxide by monitoring the change in substrate concentration employing UV spectroscopic analysis technique and depletion in total organic carbon (TOC) content as a function of irradiation time. The degradation kinetics was studied under different conditions such as pH, types of TiO 2, substrate and catalyst concentration, and in the presence of electron acceptor such as hydrogen peroxide (H 2 O 2 ) besides molecular oxygen. The degradation rates were found to be strongly influenced by all the above parameters. The photocatalyst Degussa P25 showed comparatively highest photocatalytics. The pesticide derivative, indole-3-acetic acid was found to degrade slightly faster than indole-3-butyric acid

  20. Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.

    Science.gov (United States)

    Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nabekura, J; Noguchi, K; Akaike, N; Witt, M R; Nielsen, M

    1997-06-25

    Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induces a marked decrease in agonist GABA(A) receptor ligand sensitivity. The potency of muscimol and GABA to inhibit the binding of the GABA(A) receptor antagonist [3H]SR 95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide) was higher in receptor complexes of alpha1(ile 121) beta2gamma2 than in those of alpha1(val 121) beta2gamma2 (IC50 values were 32-fold and 26-fold lower for muscimol and GABA, respectively). The apparent affinity of the GABA(A) receptor antagonist bicuculline methiodide to inhibit the binding of [3H]SR 95531 did not differ between the two receptor complex variants. Electrophysiological measurements of GABA induced whole-cell Cl- currents showed a ten-fold decrease in the GABA(A) receptor sensitivity of alpha1 (val 121) beta2gamma2 as compared to alpha1(ile 121) beta2gamma2 receptor complexes. Thus, a relatively small change in the primary structure of the alpha1 subunit leads to a decrease selective for GABA(A) receptor sensitivity to agonist ligands, since no changes were observed in a GABA(A) receptor antagonist affinity and benzodiazepine receptor binding.

  1. Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum.

    Science.gov (United States)

    Jakobsdottir, Greta; Jädert, Cecilia; Holm, Lena; Nyman, Margareta E

    2013-11-14

    SCFA are important end products formed during colonic fermentation of dietary fibre (DF). It has been suggested that propionic and butyric acids affect metabolic parameters, low-grade systemic inflammation, insulin resistance and obesity. The aim of the present study was to investigate whether the various SCFA profiles observed after fermentation in the caecum of rats fed pectin, guar gum and fructo-oligosaccharides (FOS) were also represented in hepatic portal and aortic serum. The SCFA in serum were extracted using hollow fibre-supported liquid membrane extraction before GLC analysis. The concentrations of acetic, propionic and butyric acids in caecal content correlated well with those in portal serum (Pbutyric acids between the caecal content and aortic serum (PButyric acid concentration in caecal content was also reflected in the aortic serum (P= 0·019) of rats fed FOS. FOS gave rather low amounts of the SCFA, especially butyric acid, but caecal tissue weight was higher with FOS than with the other two diets. This may be explained by rapid fermentation and quick utilisation/absorption of the SCFA. The present study also showed that propionic acid was metabolised/utilised to a higher extent than butyric acid by colonocytes before reaching the liver. We conclude that the formation of propionic and butyric acids in the caecum is reflected by increased concentrations in the aortic blood. This approach may therefore simplify the evaluation and study of SCFA from DF in human subjects.

  2. Transport of the Two Natural Auxins, Indole-3-Butyric Acid and Indole-3-Acetic Acid, in Arabidopsis1

    Science.gov (United States)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins. PMID:14526119

  3. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    Science.gov (United States)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  4. GABA predicts visual intelligence.

    Science.gov (United States)

    Cook, Emily; Hammett, Stephen T; Larsson, Jonas

    2016-10-06

    Early psychological researchers proposed a link between intelligence and low-level perceptual performance. It was recently suggested that this link is driven by individual variations in the ability to suppress irrelevant information, evidenced by the observation of strong correlations between perceptual surround suppression and cognitive performance. However, the neural mechanisms underlying such a link remain unclear. A candidate mechanism is neural inhibition by gamma-aminobutyric acid (GABA), but direct experimental support for GABA-mediated inhibition underlying suppression is inconsistent. Here we report evidence consistent with a global suppressive mechanism involving GABA underlying the link between sensory performance and intelligence. We measured visual cortical GABA concentration, visuo-spatial intelligence and visual surround suppression in a group of healthy adults. Levels of GABA were strongly predictive of both intelligence and surround suppression, with higher levels of intelligence associated with higher levels of GABA and stronger surround suppression. These results indicate that GABA-mediated neural inhibition may be a key factor determining cognitive performance and suggests a physiological mechanism linking surround suppression and intelligence. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. Does gamma-aminobutyric acid (GABA influence the development of chronic inflammation in rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    Bridges S Louis

    2008-01-01

    Full Text Available Abstract Background Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA. Genetic studies have also associated RA with members of the p38 MAPK pathway. Hypothesis We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.

  6. Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1

    DEFF Research Database (Denmark)

    Larsen, Mie; Larsen, Birger Brodin; Frølund, Bente

    2008-01-01

    The objective of this study was to investigate transepithelial amino acid transport as a function of Caco-2 cell culture time. Furthermore, the objective was to investigate apical uptake characteristics of hPAT1-mediated transport under various experimental conditions. Apical amino acid uptake...... and transport studies were conducted in Caco-2 monolayers cultured for 4-28 days. Transepithelial transport of the prototypic hPAT1 (SLC36A1) substrates l-proline and glycine were maximal after 21-28 days in culture. Based on proton-dependency and substrate kinetics the major apical uptake and transport of Gly...... and Pro in Caco-2 cell monolayers is hPAT1-mediated. The apical uptake of Pro is decreased at apical hyperosmolarity conditions. Furthermore we identified the two GABA-analogues, muscimol and THPO as novel hPAT1 substrates. THPO had an affinity for hPAT1 of 11.3mM, whereas muscimol had one of the highest...

  7. The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T

    International Nuclear Information System (INIS)

    Hatayama, Hajime; Iwashita, Jun; Kuwajima, Akiko; Abe, Tatsuya

    2007-01-01

    The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells

  8. Effects of adding butyric acid to PN on gut-associated lymphoid tissue and mucosal immunoglobulin A levels.

    Science.gov (United States)

    Murakoshi, Satoshi; Fukatsu, Kazuhiko; Omata, Jiro; Moriya, Tomoyuki; Noguchi, Midori; Saitoh, Daizoh; Koyama, Isamu

    2011-07-01

    Parenteral nutrition (PN) causes intestinal mucosal atrophy, gut-associated lymphoid tissue (GALT) atrophy and dysfunction, leading to impaired mucosal immunity and increased susceptibility to infectious complications. Therefore, new PN formulations are needed to maintain mucosal immunity. Short-chain fatty acids have been demonstrated to exert beneficial effects on the intestinal mucosa. We examined the effects of adding butyric acid to PN on GALT lymphocyte numbers, phenotypes, mucosal immunoglobulin A (IgA) levels, and intestinal morphology in mice. Male Institute of Cancer Research mice (n = 103) were randomized to receive either standard PN (S-PN), butyric acid-supplemented PN (Bu-PN), or ad libitum chow (control) groups. The mice were fed these respective diets for 5 days. In experiment 1, cells were isolated from Peyer's patches (PPs) to determine lymphocyte numbers and phenotypes (αβTCR(+), γδTCR(+), CD4(+), CD8(+), B220(+) cells). IgA levels in small intestinal washings were also measured. In experiment 2, IgA levels in respiratory tract (bronchoalveolar and nasal) washings were measured. In experiment 3, small intestinal morphology was evaluated. Lymphocyte yields from PPs and small intestinal, bronchoalveolar, and nasal washing IgA levels were all significantly lower in the S-PN group than in the control group. Bu-PN moderately, but significantly, restored PP lymphocyte numbers, as well as intestinal and bronchoalveolar IgA levels, as compared with S-PN. Villous height and crypt depth in the small intestine were significantly decreased in the S-PN group vs the control group, however Bu-PN restored intestinal morphology. A new PN formula containing butyric acid is feasible and would ameliorate PN-induced impairment of mucosal immunity.

  9. A comparison of three pH control methods for revealing effects of undissociated butyric acid on specific butanol production rate in batch fermentation of Clostridium acetobutylicum

    OpenAIRE

    Yang, Xuepeng; Tu, Maobing; Xie, Rui; Adhikari, Sushil; Tong, Zhaohui

    2013-01-01

    pH control has been essential for butanol production with Clostridium acetobutylicum. However, it is not very clear at what pH level the acid crash will occur, at what pH level butanol production will be dominant, and at what pH level butyric acid production will be prevailing. Furthermore, contradictory results have been reported about required acidic conditions for initiation of solventogenesis. In this study, with the aim of further understanding the role of undissociated butyric acid in b...

  10. Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and Decreases pH Values in Mouse Colon.

    Science.gov (United States)

    Xie, Min; Chen, Hai-Hong; Nie, Shao-Ping; Yin, Jun-Yi; Xie, Ming-Yong

    2017-04-20

    Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the gastrointestinal tract. The present study aimed to investigate the effect of GABA on colon health in mice. The female Kunming mice were given GABA at doses of 5, 10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids (SCFAs) concentrations, pH values, colon index, colon length and weight of colonic and cecal contents were determined to evaluate the effects of GABA on colon health. The results showed that intake of GABA could increase the concentrations of acetate, propionate, butyrate and total SCFAs in colonic and cecal contents, as well as the weight of colonic and cecal contents. The colon index and length of the 40 mg/kg/d GABA-treated group were significantly higher than those of the control group ( p colonic and cecal contents was also observed. These results suggest that GABA may improve colon health.

  11. Upregulation of genes related to bone formation by γ-amino butyric acid and γ-oryzanol in germinated brown rice is via the activation of GABAB-receptors and reduction of serum IL-6 in rats.

    Science.gov (United States)

    Muhammad, Sani Ismaila; Maznah, Ismail; Mahmud, Rozi; Zuki, Abu Bakar Zakaria; Imam, Mustapha Umar

    2013-01-01

    Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects. In this study, we investigated the effects of gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2), secreted protein acidic and rich in cysteine (SPARC), runt-related transcription factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx), periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6) and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg), compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the bone tissue was determined using the Genetic Analysis System (Beckman Coulter Inc., Brea, CA, USA). The results indicate that groups treated with GABA (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200 mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels increased significantly (P < 0.05) in the treated groups as compared to ovariectomized non-treated groups. GABA and ORZ from

  12. Kinetic study of the electroreduction of Cd2+ and Zn2+ cations in the presence of n-butyric acid

    International Nuclear Information System (INIS)

    Afanas'ev, B.N.; Skobochkina, Yu.P.; Serdyukova, G.G.

    1988-01-01

    Consideration is being given to electrochemical reactions which proceed both in 'pores' inside the surface layer, composed of surfactant molecules, and on the surface covered by adsorbate molecules. It is shown that in the course of n-butyric acid adsorption electroreduction of Cd 2+ and Zn 2+ takes place in 'pores' and on the surface of electrode due to formation of electroactive surface complexes. Values of constants characterizing process rates in the case of complete occupation of electrode surface by surfactant molecules have been determined

  13. Continuous fermentation and in-situ reed separation of butyric acid for higher sugar consumption rate and productivity

    DEFF Research Database (Denmark)

    Baroi, George Nabin; Skiadas, Ioannis; Westermann, Peter

    that disconnection of the REED system resulted to much lower (48 and 83% for glucose and xylose, respectively) sugars consumption rates and consequently lower butyric acid production rates. It was also noticeable that continuous operation, even without the REED system, resulted to higher glucose consumption rates...... than batch operation (0.85 compared to 0.31 g/L/h). Similar conclusions were drawn from the experiments with increasing concentrations of PHWS. It should also be emphasized that fermentation of 100% PHWS proceeded unhindered with just urea and K2HPO4 added (to making up for nutrient deficiency...

  14. Comparison of the effects of high energy carbon heavy ion irradiation and Eucommia ulmoides Oliv. on biosynthesis butyric acid efficiency in Clostridium tyrobutyricum.

    Science.gov (United States)

    Zhou, Xiang; Wang, Shu-Yang; Lu, Xi-Hong; Liang, Jian-Ping

    2014-06-01

    Clostridium tyrobutyricum is well documented as a fermentation strain for the production of butyric acid. In this work, using high-energy carbon heavy ion irradiated C. tyrobutyricum, then butyric acid fermentation using glucose or alkali and acid pretreatments of Eucommia ulmoides Oliv. as a carbon source was carried out. Initially, the modes at pH 5.7-6.5 and 37°C were compared using a model medium containing glucose as a carbon source. When the 72gL(-1) glucose concentration was found to be the highest yield, the maximum butyric acid production from glucose increased significantly, from 24gL(-1) for the wild type strains to 37gL(-1) for the strain irradiated at 126AMeV and a dose of 35Gy and a 10(7)ions/pulse. By feeding 100gL(-1) acid pretreatments of E. ulmoides Oliv. into the fermentations, butyrate yields (5.8gL(-1)) and butyrate/acetate (B/A) ratio (4.32) were achieved. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Activating glutamate decarboxylase activity by removing the autoinhibitory domain leads to hyper γ-aminobutyric acid (GABA) accumulation in tomato fruit.

    Science.gov (United States)

    Takayama, Mariko; Matsukura, Chiaki; Ariizumi, Tohru; Ezura, Hiroshi

    2017-01-01

    The C-terminal extension region of SlGAD3 is likely involved in autoinhibition, and removing this domain increases GABA levels in tomato fruits. γ-Aminobutyric acid (GABA) is a ubiquitous non-protein amino acid with several health-promoting benefits. In many plants including tomato, GABA is synthesized via decarboxylation of glutamate in a reaction catalyzed by glutamate decarboxylase (GAD), which generally contains a C-terminal autoinhibitory domain. We previously generated transgenic tomato plants in which tomato GAD3 (SlGAD3) was expressed using the 35S promoter/NOS terminator expression cassette (35S-SlGAD3-NOS), yielding a four- to fivefold increase in GABA levels in red-ripe fruits compared to the control. In this study, to further increase GABA accumulation in tomato fruits, we expressed SlGAD3 with (SlGAD3 OX ) or without (SlGAD3ΔC OX ) a putative autoinhibitory domain in tomato using the fruit ripening-specific E8 promoter and the Arabidopsis heat shock protein 18.2 (HSP) terminator. Although the GABA levels in SlGAD3 OX fruits were equivalent to those in 35S-SlGAD3-NOS fruits, GABA levels in SlGAD3ΔC OX fruits increased by 11- to 18-fold compared to control plants, indicating that removing the autoinhibitory domain increases GABA biosynthesis activity. Furthermore, the increased GABA levels were accompanied by a drastic reduction in glutamate and aspartate levels, indicating that enhanced GABA biosynthesis affects amino acid metabolism in ripe-fruits. Moreover, SlGAD3ΔC OX fruits exhibited an orange-ripe phenotype, which was associated with reduced levels of both carotenoid and mRNA transcripts of ethylene-responsive carotenogenic genes, suggesting that over activation of GAD influences ethylene sensitivity. Our strategy utilizing the E8 promoter and HSP terminator expression cassette, together with SlGAD3 C-terminal deletion, would facilitate the production of tomato fruits with increased GABA levels.

  16. Tie line data for the (water + butyric acid + n-butyl alcohol or amyl alcohol) at T = (298.2, 308.2, and 318.2) K and (water + butyric acid + isoamyl alcohol) at T = 298.2 K

    International Nuclear Information System (INIS)

    Ghanadzadeh Gilani, A.; Ghanadzadeh Gilani, H.; Amouzadeh, F.

    2014-01-01

    Highlights: • Liquid equilibrium data of (water + BA + alcohols) systems were measured. • Experimental LLE data were correlated with NRTL and UNIQUAC models. • Distribution coefficients and separation factors were evaluated. -- Abstract: In this study, solubility and tie-line data of the (water + butyric acid + n-butyl alcohol or amyl alcohol) ternary systems were determined at T = (298.2, 308.2, and 318.2) K and p = 101.3 kPa for the first time. Due to the structural similarity, the tie-line data for (water + butyric acid + isoamyl alcohol) system were also measured and correlated at T = 298.2 K. The ternary systems investigated display type-1 behaviour of LLE. The cloud point method was used to measure the solubility data and the Karl-Fischer, acidimetric titration, and refractive index methods were used to determine the tie-line data. For each system, the experimental tie-line data were correlated using the UNIQUAC and NRTL models. The Othmer–Tobias and Hand correlations equations were used to establish the quality of the LLE data. Experimental distribution coefficients and separation factors were evaluated over the immiscibility regions

  17. Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors

    Science.gov (United States)

    Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

    2015-01-01

    This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23–0.99 U mg−1 protein), butyrate kinase (Buk, biogas reactor content from three different biogas reactors. Furthermore, the detection of Ack was successful via Western blot analysis. Quantification of corresponding functional genes encoding Buk (buk) and But (but) was not feasible, although an amplification was possible. Thus, phylogenetic trees were constructed based on respective gene fragments. Four new clades of possible butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH3 and NH4+-N), and a negative dependency can be postulated. Thus, high concentrations of NH3 and NH4+-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities. PMID:26086956

  18. Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors.

    Science.gov (United States)

    Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

    2015-09-01

    This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23-0.99 U mg(-1) protein), butyrate kinase (Buk, butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH₃ and NH₄(+)-N), and a negative dependency can be postulated. Thus, high concentrations of NH₃ and NH₄(+)-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  19. Improvement of Chia Seeds with Antioxidant Activity, GABA, Essential Amino Acids, and Dietary Fiber by Controlled Germination Bioprocess.

    Science.gov (United States)

    Gómez-Favela, Mario Armando; Gutiérrez-Dorado, Roberto; Cuevas-Rodríguez, Edith Oliva; Canizalez-Román, Vicente Adrián; Del Rosario León-Sicairos, Claudia; Milán-Carrillo, Jorge; Reyes-Moreno, Cuauhtémoc

    2017-12-01

    Chia (Salvia hispanica L.) plant is native from southern Mexico and northern Guatemala. Their seeds are a rich source of bioactive compounds which protect consumers against chronic diseases. Germination improves functionality of the seeds due to the increase in the bioactive compounds and associated antioxidant activity. The purpose of this study was to obtain functional flour from germinated chia seeds under optimized conditions with increased antioxidant activity, phenolic compounds, GABA, essential amino acids, and dietary fiber with respect to un-germinated chia seeds. The effect of germination temperature and time (GT = 20-35 °C, Gt = 10-300 h) on protein, lipid, and total phenolic contents (PC, LC, TPC, respectively), and antioxidant activity (AoxA) was analyzed by response surface methodology as optimization tool. Chia seeds were germinated inside plastic trays with absorbent paper moisturized with 50 mL of 100 ppm sodium hypochlorite dissolution. The sprouts were dried (50 °C/8 h) and ground to obtain germinated chia flours (GCF). The prediction models developed for PC, LC, TPC, and AoxA showed high coefficients of determination, demonstrating their adequacy to explain the variations in experimental data. The highest values of PC, LC, TPC, and AoxA were obtained at two different optimal conditions (GT = 21 °C/Gt = 157 h; GT = 33 °C/Gt = 126 h). Optimized germinated chia flours (OGCF) had higher PC, TPC, AoxA, GABA, essential amino acids, calculated protein efficiency ratio (C-PER), and total dietary fiber (TDF) than un-germinated chia seed flour. The OGCF could be utilized as a natural source of proteins, dietary fiber, GABA, and antioxidants in the development of new functional beverages and foods.

  20. (Liquid + liquid) equilibria of aqueous solutions of butyric acid with n-heptane and toluene at T = (298.2, 308.2, and 318.2) K

    International Nuclear Information System (INIS)

    Ghanadzadeh Gilani, H.; Ghanadzadeh Gilani, A.; Janbaz, M.

    2013-01-01

    Highlights: ► Liquid equilibrium data of (water + butyric acid + n-heptane) were obtained. ► LLE data were correlated with NRTL and UNIQUAC models. ► Distribution coefficients and separation factors were evaluated. - Abstract: Solubility and tie line data for the (water + butyric acid + n-heptane) and (water + butyric acid + toluene) ternary systems were determined at T = (298.2, 308.2, and 318.2) K and atmospheric pressure. Solubility data were obtained by the cloud-point titration method. The concentration of each phase was determined by acidimetric titration, the Karl-Fischer technique, and refractive index measurements. The experimental tie-line data were correlated using the UNIQUAC and NRTL thermodynamic models. The reliability of the experimental data was determined through the Othmer–Tobias and Hand plots. Distribution coefficients and separation factors were evaluated for each system over the immiscibility regions.

  1. Stable isotope dilution HILIC-MS/MS method for accurate quantification of glutamic acid, glutamine, pyroglutamic acid, GABA and theanine in mouse brain tissues.

    Science.gov (United States)

    Inoue, Koichi; Miyazaki, Yasuto; Unno, Keiko; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2016-01-01

    In this study, we developed the stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS) technique for the accurate, reasonable and simultaneous quantification of glutamic acid (Glu), glutamine (Gln), pyroglutamic acid (pGlu), γ-aminobutyric acid (GABA) and theanine in mouse brain tissues. The quantification of these analytes was accomplished using stable isotope internal standards and the HILIC separating mode to fully correct the intramolecular cyclization during the electrospray ionization. It was shown that linear calibrations were available with high coefficients of correlation (r(2)  > 0.999, range from 10 pmol/mL to 50 mol/mL). For application of the theanine intake, the determination of Glu, Gln, pGlu, GABA and theanine in the hippocampus and central cortex tissues was performed based on our developed method. In the region of the hippocampus, the concentration levels of Glu and pGlu were significantly reduced during reality-based theanine intake. Conversely, the concentration level of GABA increased. This result showed that transited theanine has an effect on the metabolic balance of Glu analogs in the hippocampus. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Amelioration of bleomycin-induced lung fibrosis in rats by valproic acid and butyrate: Role of nuclear factor kappa-B, proinflammatory cytokines and oxidative stress.

    Science.gov (United States)

    Kabel, Ahmed M; Omar, Mohamed S; Elmaaboud, Maaly A Abd

    2016-10-01

    Bleomycin is one of the anticancer agents used frequently in management of various types of tumors. Pulmonary fibrosis is the major limiting factor for the use of bleomycin. Mechanisms of fibrosis may include disordered wound healing, infiltration with inflammatory cells and fibroblasts and release of reactive oxygen species and growth factors. The aim of this study was to investigate the effect of valproic acid and butyrate on lung fibrosis induced by bleomycin, and to clarify their mechanisms of action. Fifty male Wistar rats were divided into 5 equal groups as follows: control group; bleomycin group; bleomycin+valproic acid group; bleomycin+butyrate group and bleomycin+valproic acid+butyrate group. Weight of rats, lung tissue hydroxyproline, malondialdehyde, superoxide dismutase and catalase were measured. Also, bronchoalveolar lavage (BAL) was analyzed for total and differential leukocytic count, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1). Lung tissue was examined histopathologically and immunostained for nuclear factor kappa B (NF-κB). Valproic acid and/or butyrate resulted in significant improvement of the body weight gain, oxidative stress, TGF-β1, IL-6, TNF-α, hydroxyproline and BAL cellularity together with significant improvement of the histopathological and immunohistochemical picture. The use of valproic acid/butyrate combination was better than the use of each of these drugs alone in bleomycin-induced pulmonary fibrosis. In conclusion, valproic acid/butyrate combination may be used prophylactically for amelioration of bleomycin-induced pulmonary fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Driving carbon flux through exogenous butyryl-CoA: Acetate CoA-transferase to produce butyric acid at high titer in Thermobifida fusca.

    Science.gov (United States)

    Deng, Yu; Mao, Yin; Zhang, Xiaojuan

    2015-12-20

    Butyric acid, a 4-carbon short chain fatty acid, is widely used in chemical, food, and pharmaceutical industries. The low activity of butyryl-CoA: acetate CoA-transferase in Thermobifida fusca muS, a thermophilic actinobacterium whose optimal temperature was 55°C, was found to hinder the accumulation of high yield of butyric acid. In order to solve this problem, an exogenous butyryl-CoA: acetate CoA-transferase gene (actA) from Thermoanaerobacterium thermosaccharolyticum DSM571 was integrated into the chromosome of T. fusca muS by replacing celR gene, forming T. fusca muS-1. We demonstrated that on 5g/L cellulose, the yield of butyric acid by the engineered muS-1 strain was increased by 42.9 % compared to the muS strain. On 100g/L of cellulose, the muS-1 strain could consume 90.5% of total cellulose in 144h, with 33.2g/L butyric acid produced. Furthermore, on the mix substrates including the major components of biomass: cellulose, xylose, mannose and galactose, 70.4g/L butyric acid was produced in 168h by fed-batch fermentation. To validate the ability of fermenting biomass, the muS-1 strain was grown on the milled corn stover ranging from 200 to 250μm. The muS-1 strain had the highest butyrate titer 17.1g/L on 90g/L corn stover. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Synthesis of neurotransmitter GABA via the neuronal tricarboxylic acid cycle is elevated in rats with liver cirrhosis consistent with a high GABAergic tone in chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Leke, Renata; Bak, Lasse Kristoffer; Iversen, Peter

    2011-01-01

    the neuronal tricarboxylic acid cycle, an energy-generating pathway, prior to being employed for GABA synthesis (the indirect pathway). We have previously shown that ammonia induces an elevation of the neuronal tricarboxylic acid cycle activity. Thus, the aims of the present study were to determine...

  5. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A.

    Science.gov (United States)

    Nakamura, H; Takishima, T; Kometani, T; Yokogoshi, H

    2009-01-01

    We studied the psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA), on stress induced by an arithmetic task using changes of heart rate variability (HRV) and salivary chromogranin A (CgA). Subjects ingested 10 g chocolate enriched with 28 mg GABA (GABA chocolate); 15 min after the ingestion, subjects were assigned an arithmetic task for 15 min. After the task, an electrocardiogram was recorded and saliva samples were collected. HRV was determined from the electrocardiogram, and the activity of the autonomic nervous system was estimated through HRV. The CgA concentration of all saliva samples, an index for acute psychological stress, was measured. From HRV, those taking GABA chocolate made a quick recovery to the normal state from the stressful state. The CgA value after the task in those taking GABA chocolate did not increased in comparison with that before ingestion. From these results, GABA chocolate was considered to have a psychological stress-reducing effect.

  6. Enhancing Contents of γ-Aminobutyric Acid (GABA) and Other Micronutrients in Dehulled Rice during Germination under Normoxic and Hypoxic Conditions.

    Science.gov (United States)

    Ding, Junzhou; Yang, Tewu; Feng, Hao; Dong, Mengyi; Slavin, Margaret; Xiong, Shanbai; Zhao, Siming

    2016-02-10

    Biofortification of staple grains with high contents of essential micronutrients is an important strategy to overcome micronutrient malnutrition. However, few attempts have targeted at γ-aminobutyric acid (GABA), a functional nutrient for aging populations. In this study, two rice cultivars, Heinuo and Xianhui 207, were used to investigate changes in GABA and other nutritional compounds of dehulled rice after germination under normoxic and hypoxic conditions. Forty-one metabolites were identified in both cultivars treated by normoxic germination, whereas the germinated dehulled rice of Heinuo and Xianhui 207 under hypoxic treatment had 43 and 41 metabolites identified, respectively. GABA increased in dehulled rice after germination, especially under hypoxia. Meanwhile, a number of other health-beneficial and/or flavor-related compounds such as lysine and d-mannose increased after the hypoxic treatment. The accumulation of GABA exhibited genotype-specific modes in both normoxic and hypoxic treatments. With regard to GABA production, Xianhui 207 was more responsive to the germination process than Heinuo, whereas Heinuo was more responsive to hypoxia than Xianhui 207. This study provides a promising approach to biofortify dehulled rice with increased GABA and other nutrients through metabolomic-based regulation.

  7. Continuous fermentation and kinetic experiments for the conversion of crude glycerol derived from second-generation biodiesel into 1,3 propanediol and butyric acid

    DEFF Research Database (Denmark)

    Varrone, Cristiano; Floriotis, Georgis; Heggeset, Tonje M. B.

    2017-01-01

    This study investigated the performance of different mixed microbial cultures (MMC) able to ferment crude glycerol generated from animal fat-based biodiesel to produce 1,3 propanediol (1,3 PDO) and butyric acid, under non-sterile conditions. Eight different continuous flow stirred-tank reactors...... communities were monitored by means of Next Generation Sequencing (NGS). Maximum substrate degradation rate reached approximately 110 g/L/d of glycerol (with a productivity of 38 g/L/d and 11 g/L/d for 1,3 PDO and butyric acid, respectively), obtained with an hydraulic retention time of 12 h and 60 g/L feed...

  8. Phase diagrams for the system water/butyric acid/propylene carbonate at T = 293.2-313.2 K and p = 101.3 kPa

    Science.gov (United States)

    Shekarsaraee, Sina; Nahzomi, Hossein Taherpour; Nasiri-Touli, Elham

    2017-11-01

    Phase diagrams for the system water/butyric acid/propylene carbonate were plotted at T = 293.2, 303.2, 313.2 K and p = 101.3 kPa. Acidimetric titration and refractive index methods were used to determine tie-line data. Solubility data revealed that the studied system exhibits type-1 behavior of liquid-liquid equilibrium. The experimental data were regressed and acceptably correlated using the UNIQUAC and NRTL models. As a result, propylene carbonate is a suitable separating agent for aqueous mixture of butyric acid.

  9. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    International Nuclear Information System (INIS)

    Bartlett, S.E.; Smith, M.T.; Dood, P.R.

    1994-01-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of 3 H-MK801 (non-competitive antagonist) and 125 I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of 3 H-muscimol (GABA receptor agonist), 3 H-diazepam and 3 H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA A receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of 3 H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.)

  10. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  11. Effects of malting conditions on the amino acid compositions of final ...

    African Journals Online (AJOL)

    Administrator

    2010-12-27

    Dec 27, 2010 ... leucine; Ile, isoleucine; Val, valine; Phe, phenylalanine; Gly, glycine; Ala, alanine; Tyr, tyrosine; Asp, aspartic acid; Asn, asparagine; Glu, glutamic acid; Gln, glutamine; Thr, threonine;. Ser, serine; Met, methionine; Pro, proline; Trp, tryptophan;. GABA, γ-amino butyric acid; TP, total protein; SP, soluble protein ...

  12. Natural and Synthetic Variants of the Tricarboxylic Acid Cycle in Cyanobacteria: Introduction of the GABA Shunt into Synechococcus sp. PCC 7002.

    Science.gov (United States)

    Zhang, Shuyi; Qian, Xiao; Chang, Shannon; Dismukes, G C; Bryant, Donald A

    2016-01-01

    For nearly half a century, it was believed that cyanobacteria had an incomplete tricarboxylic acid (TCA) cycle, because 2-oxoglutarate dehydrogenase (2-OGDH) was missing. Recently, a bypass route via succinic semialdehyde (SSA), which utilizes 2-oxoglutarate decarboxylase (OgdA) and succinic semialdehyde dehydrogenase (SsaD) to convert 2-oxoglutarate (2-OG) into succinate, was identified, thus completing the TCA cycle in most cyanobacteria. In addition to the recently characterized glyoxylate shunt that occurs in a few of cyanobacteria, the existence of a third variant of the TCA cycle connecting these metabolites, the γ-aminobutyric acid (GABA) shunt, was considered to be ambiguous because the GABA aminotransferase is missing in many cyanobacteria. In this study we isolated and biochemically characterized the enzymes of the GABA shunt. We show that N -acetylornithine aminotransferase (ArgD) can function as a GABA aminotransferase and that, together with glutamate decarboxylase (GadA), it can complete a functional GABA shunt. To prove the connectivity between the OgdA/SsaD bypass and the GABA shunt, the gadA gene from Synechocystis sp. PCC 6803 was heterologously expressed in Synechococcus sp. PCC 7002, which naturally lacks this enzyme. Metabolite profiling of seven Synechococcus sp. PCC 7002 mutant strains related to these two routes to succinate were investigated and proved the functional connectivity. Metabolite profiling also indicated that, compared to the OgdA/SsaD shunt, the GABA shunt was less efficient in converting 2-OG to SSA in Synechococcus sp. PCC 7002. The metabolic profiling study of these two TCA cycle variants provides new insights into carbon metabolism as well as evolution of the TCA cycle in cyanobacteria.

  13. Fermentation of sweet sorghum derived sugars to butyric acid at high titer and productivity by a moderate thermophile Clostridium thermobutyricum at 50°C.

    Science.gov (United States)

    Wang, Liang; Ou, Mark S; Nieves, Ismael; Erickson, John E; Vermerris, Wilfred; Ingram, L O; Shanmugam, K T

    2015-12-01

    In this study, a moderate thermophile Clostridium thermobutyricum is shown to ferment the sugars in sweet sorghum juice treated with invertase and supplemented with tryptone (10 g L(-1)) and yeast extract (10 g L(-1)) at 50°C to 44 g L(-1) butyrate at a calculated highest volumetric productivity of 1.45 g L(-1)h(-1) (molar butyrate yield of 0.85 based on sugars fermented). This volumetric productivity is among the highest reported for batch fermentations. Sugars from acid and enzyme-treated sweet sorghum bagasse were also fermented to butyrate by this organism with a molar yield of 0.81 (based on the amount of cellulose and hemicellulose). By combining the results from juice and bagasse, the calculated yield of butyric acid is approximately 90 kg per tonne of fresh sweet sorghum stalk. This study demonstrates that C. thermobutyricum can be an effective microbial biocatalyst for production of bio-based butyrate from renewable feedstocks at 50°C. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The amino acid transporters of the glutamate/GABA-glutamine cycle and their impact on insulin and glucagon secretion

    Directory of Open Access Journals (Sweden)

    Monica eJenstad

    2013-12-01

    Full Text Available Intercellular communication is pivotal in optimising and synchronising cellular responses to keep internal homeostasis and to respond adequately to external stimuli. In the central nervous system (CNS, glutamatergic and GABAergic signals are postulated to be dependent on the glutamate/GABA-glutamine (GGG cycle for vesicular loading of neurotransmitters, for inactivating the signal and for the replenishment of the neurotransmitters. Islets of Langerhans release the hormones insulin and glucagon, but share similarities with CNS cells in for example transcriptional control of development and differentiation, and chromatin methylation. Interestingly, proteins involved in the CNS in secretion of the neurotransmitters and emitting their responses as well as the regulation of these processes, are also found in islet cells. Moreover, high levels of glutamate, GABA and glutamine and their respective vesicular and plasma membrane transporters have been shown in the islet cells and there is emerging support for these amino acids and their transporters playing important roles in the maturation and secretion of insulin and glucagon. In this review, we will discuss the feasibility of recent data in the field in relation to the biophysical properties of the transporters (Slc1, Slc17, Slc32 and Slc38 and physiology of hormone secretion in islets of Langerhans.

  15. Hyper-thermal acid hydrolysis and adsorption treatment of red seaweed, Gelidium amansii for butyric acid production with pH control.

    Science.gov (United States)

    Ra, Chae Hun; Jeong, Gwi-Taek; Kim, Sung-Koo

    2017-03-01

    Optimal hyper-thermal (HT) acid hydrolysis conditions for Gelidium amansii were determined to be 12% (w/v) seaweed slurry content and 144 mM H 2 SO 4 at 150 °C for 10 min. HT acid hydrolysis-treated G. amansii hydrolysates produced low concentrations of inhibitory compounds and adsorption treatment using 3% activated carbon. An adsorption time of 5 min was subsequently used to remove the inhibitory 5-hydroxymethylfurfural from the medium. A final maximum monosaccharide concentration of 44.6 g/L and 79.1% conversion from 56.4 g/L total fermentable monosaccharides with 120 g dw/L G. amansii slurry was obtained from HT acid hydrolysis, enzymatic saccharification, and adsorption treatment. This study demonstrates the potential for butyric acid production from G. amansii hydrolysates under non-pH-controlled as well as pH-controlled fermentation using Clostridium acetobutylicum KCTC 1790. The activated carbon treatment and pH-controlled fermentation showed synergistic effects and produced butyric acid at a concentration of 11.2 g/L after 9 days of fermentation.

  16. Localisation of 3H-GABA in the rat olfactory bulb: An in vivo and in vitro autoradiographic study

    International Nuclear Information System (INIS)

    Jaffe, E.H.; Cuello, A.C.; Priestley, J.V.

    1983-01-01

    In an attempt to further clarify the localisation of GABAergic elements in the olfactory bulb we have performed, in vivo and in vitro, autoradiographic studies with 3 H-GABA (#betta#-amino butyric acid) and 3 H-DABA (L-2,4 diamino butyric acid). The results have shown a strong labelling with 3 H-GABA of the glial cells in all the layers of the olfactory bulb. A high concentration of grains was observed in the periglomerular region. The labelling in the external plexiform layer was uniformly distributed in the neuropile with the strongest activity at the level of the dendritic processes of the granule cells, leaving the mitral cell dendrites and cell bodies almost free of grains. 3 H-DABA showed a very similar pattern to 3 H-GABA. When olfactory bulb slices were preincubated with #betta#-alanine the labelling of the glial elements almost disappeared especially at the level of the olfactory nerve layer. The labelling pattern of the other layers of the bulb remained mostly unchanged. This supports the view that a population of periglomerular and granule cells are GABAergic and that #betta#-alanine competes with GABA uptake sites only in glial cells. (orig.)

  17. The response of Culex quinquefasciatus (Diptera: Culicidae)to traps baited with carbon dioxide, 1-octen-3-ol, acetone, butyric acid and human foot odour in Tanzania

    NARCIS (Netherlands)

    Mboera, L.E.G.; Takken, W.; Sambu, E.Z.

    2000-01-01

    The responses of Culex quinquefasciatus Say to traps baited with carbon dioxide, 1-octen-3-ol, acetone, butyric acid and human foot odour were studied in the field in Muheza, north-east Tanzania using Counterflow Geometry (CFG) and Centers for Disease Control (CDC) traps. It was found that

  18. Bioprotective carnitinoids: lipoic acid, butyrate, and mitochondria-targeting to treat radiation injury: mitochondrial drugs come of age.

    Science.gov (United States)

    Steliou, Kosta; Faller, Douglas V; Pinkert, Carl A; Irwin, Michael H; Moos, Walter H

    2015-06-01

    Preclinical Research Given nuclear-power-plant incidents such as the 2011 Japanese Fukushima-Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic-driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds described herein reveal the potential-although further research and development is required to prove the effectiveness of this approach-to provide field-ready radiation-protective drugs. © 2015 Wiley Periodicals, Inc.

  19. Morphology characterization of phenyl-C61-butyric acid methyl ester films via an electrohydrodynamic spraying route

    International Nuclear Information System (INIS)

    Park, Sung-Eun; Park, Ji-Woon; Hwang, Jungho

    2014-01-01

    In this study, we fabricated a thin film layer of phenyl-C61-butyric acid methyl ester (PCBM) fine particles using electrohydrodynamic (EHD) spray and evaluated the effects of the process parameters on the film morphology. After the PCBM was dissolved in dichloromethane, the solution was sprayed onto a substrate using the stable cone-jet mode of EHD spraying at various flow rates ranging from 5 to 15 μl/min and electric potentials ranging from 3 to 5 kV. The effects of the liquid flow rate, nozzle-plate distance, solute fraction, and electrical conductivity on the spray characteristics were investigated. The sizes of the PCBM particles deposited on the substrate were calculated using a scaling law and a mass balance equation, the results of which were in agreement with those obtained by scanning electron microscopy. A thin film was obtained with the structure of PCBM particles deposited without any void or agglomeration from the EHD spraying technique. The electrical conductivity of the PCBM solution was the dominant parameter in controlling the size of the PCBM particles. As the conductivity was increased to 2.4 × 10 −3 S/m from 4.3 × 10 −9 S/m, the particle size decreased from 6.7 μm to 320 nm. The size distribution measured using a scanning mobility particle sizer also supported the generation of nano-scale PCBM particles. The decrease of the particle size with increasing electrical conductivity may lead to a better morphology of PCBM films. - Highlights: • The phenyl-C61-butyric acid methyl ester thin film was obtained by electrospray. • The morphology of film consisting of microparticles was investigated. • The particle size was controlled by adjusting experimental parameters. • The nanoparticle was obtained by increasing the solution conductivity. • The particle size distribution was studied using a scanning mobility particle sizer

  20. Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

    Directory of Open Access Journals (Sweden)

    Ju-Ri Sim

    2018-01-01

    Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

  1. Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate.

    Science.gov (United States)

    Sim, Ju-Ri; Kang, Seok-Seong; Lee, Daesang; Yun, Cheol-Heui; Han, Seung Hyun

    2018-01-01

    Short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC) inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP). Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

  2. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.

    Directory of Open Access Journals (Sweden)

    Shien Hu

    Full Text Available Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3' UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3'UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs.

  3. Demonstration of in situ product recovery of butyric acid via CO2 -facilitated pH swings and medium development in two-phase partitioning bioreactors.

    Science.gov (United States)

    Peterson, Eric C; Daugulis, Andrew J

    2014-03-01

    Production of organic acids in solid-liquid two-phase partitioning bioreactors (TPPBs) is challenging, and highly pH-dependent, as cell growth occurs near neutral pH, while acid sorption occurs only at low pH conditions. CO2 sparging was used to achieve acidic pH swings, facilitating undissociated organic acid uptake without generating osmotic stress inherent in traditional acid/base pH control. A modified cultivation medium was formulated to permit greater pH reduction by CO2 sparging (pH 4.8) compared to typical media (pH 5.3), while still possessing adequate nutrients for extensive cell growth. In situ product recovery (ISPR) of butyric acid (pKa = 4.8) produced by Clostridium tyrobutyricum was achieved through intermittent CO2 sparging while recycling reactor contents through a column packed with absorptive polymer Hytrel® 3078. This polymer was selected on the basis of its composition as a polyether copolymer, and the use of solubility parameters for predicting solute polymer affinity, and was found to have a partition coefficient for butyric acid of 3. Total polymeric extraction of 3.2 g butyric acid with no CO2 mediated pH swings was increased to 4.5 g via CO2 -facilitated pH shifting, despite the buffering capacity of butyric acid, which resists pH shifting. This work shows that CO2 -mediated pH swings have an observable positive effect on organic acid extraction, with improvements well over 150% under optimal conditions in early stage fermentation compared to CO2 -free controls, and this technique can be applied other organic acid fermentations to achieve or improve ISPR. © 2013 Wiley Periodicals, Inc.

  4. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  5. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  6. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET

    International Nuclear Information System (INIS)

    Kim, Sung Won; Hooker, Jacob M.; Otto, Nicola; Win, Khaing; Muench, Lisa; Shea, Colleen; Carter, Pauline; King, Payton; Reid, Alicia E.; Volkow, Nora D.; Fowler, Joanna S.

    2013-01-01

    The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using 11 CO 2 and the appropriate Grignard reagents. [ 11 C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity were the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low ( VPA > PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [ 11 C]BA showed relatively high uptake in spleen and pancreas whereas [ 11 C]PBA showed high uptake in liver and heart. Notably, [ 11 C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects

  7. Butyric acid production from lignocellulosic biomass hydrolysates by engineered Clostridium tyrobutyricum overexpressing xylose catabolism genes for glucose and xylose co-utilization.

    Science.gov (United States)

    Fu, Hongxin; Yang, Shang-Tian; Wang, Minqi; Wang, Jufang; Tang, I-Ching

    2017-06-01

    Clostridium tyrobutyricum can utilize glucose and xylose as carbon source for butyric acid production. However, xylose catabolism is inhibited by glucose, hampering butyric acid production from lignocellulosic biomass hydrolysates containing both glucose and xylose. In this study, an engineered strain of C. tyrobutyricum Ct-pTBA overexpressing heterologous xylose catabolism genes (xylT, xylA, and xylB) was investigated for co-utilizing glucose and xylose present in hydrolysates of plant biomass, including soybean hull, corn fiber, wheat straw, rice straw, and sugarcane bagasse. Compared to the wild-type strain, Ct-pTBA showed higher xylose utilization without significant glucose catabolite repression, achieving near 100% utilization of glucose and xylose present in lignocellulosic biomass hydrolysates in bioreactor at pH 6. About 42.6g/L butyrate at a productivity of 0.56g/L·h and yield of 0.36g/g was obtained in batch fermentation, demonstrating the potential of C. tyrobutyricum Ct-pTBA for butyric acid production from lignocellulosic biomass hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Vegetative propagation of Plukenetia polyadenia by cuttings: effects of leaf area and indole-3-butyric acid concentration

    Directory of Open Access Journals (Sweden)

    R. Solis

    Full Text Available Abstract The seeds of Plukenetia polyadenia have high levels of unsaturated fatty acids and are used as medicine and food for native people in the Peruvian and Brazilian Amazon. The objective of this study was to develop a method for vegetative propagation of Plukenetia polyadenia by rooting of cuttings. The experiment was laid out in a randomized complete block design with 12 treatments and 3 replications of 8 cuttings, in a 3 × 4 factorial arrangement. The factors were: 3 levels of leaf area (25, 50 and 75% and 3 indole-3-butyric acid - IBA concentrations (9.84, 19.68 and 29.52mM and a control without IBA. Data were submitted to analysis of variance and means were compared by Tukey test at 5% probability. Our results show that the use of cuttings with 50% of leaf area and treatment with 29.52mM of IBA induced high percentages of rooting (93% and the best root formation. Vegetative propagation of Plukenetia polyadenia by cuttings will be used as a tool to conserve and propagate germplasm in breeding programs.

  9. Vegetative propagation of Plukenetia polyadenia by cuttings: effects of leaf area and indole-3-butyric acid concentration.

    Science.gov (United States)

    Solis, R; Pezo, M; Diaz, G; Arévalo, L; Cachique, D

    2017-01-01

    The seeds of Plukenetia polyadenia have high levels of unsaturated fatty acids and are used as medicine and food for native people in the Peruvian and Brazilian Amazon. The objective of this study was to develop a method for vegetative propagation of Plukenetia polyadenia by rooting of cuttings. The experiment was laid out in a randomized complete block design with 12 treatments and 3 replications of 8 cuttings, in a 3 × 4 factorial arrangement. The factors were: 3 levels of leaf area (25, 50 and 75%) and 3 indole-3-butyric acid - IBA concentrations (9.84, 19.68 and 29.52mM) and a control without IBA. Data were submitted to analysis of variance and means were compared by Tukey test at 5% probability. Our results show that the use of cuttings with 50% of leaf area and treatment with 29.52mM of IBA induced high percentages of rooting (93%) and the best root formation. Vegetative propagation of Plukenetia polyadenia by cuttings will be used as a tool to conserve and propagate germplasm in breeding programs.

  10. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC

    NARCIS (Netherlands)

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R.; Lambers, Tim T.; van Tol, Eric A.; de Jonge, Wouter J.

    2016-01-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory

  11. Upregulation of genes related to bone formation by γ-amino butyric acid and γ-oryzanol in germinated brown rice is via the activation of GABAB-receptors and reduction of serum IL-6 in rats

    Directory of Open Access Journals (Sweden)

    Muhammad SI

    2013-09-01

    Full Text Available Sani Ismaila Muhammad,1,2 Ismail Maznah,1,3 Rozi Mahmud,4 Abu Bakar Zakaria Zuki,5 Mustapha Umar Imam1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 4Department of Radiology, Faculty of Medicine and Health Sciences, 5Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia Background: Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects. Methods: In this study, we investigated the effects of gamma-amino butyric acid (GABA, gamma-oryzanol (ORZ, acylated steryl glucosides (ASG, and phenolic extracts from germinated brown rice (GBR on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2, secreted protein acidic and rich in cysteine (SPARC, runt-related transcription factor 2 (RUNX-2, osteoblast-specific transcription factor osterix (Osx, periostin, osteoblast specific factor (Postn, collagen 1&2 (Col1&2, calcitonin receptor gene (CGRP; body weight measurement and also serum interleukin-6 (IL-6 and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg; estrogen (0.2 mg/kg, or remifemin (10 and 20 mg/kg, compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the

  12. A case of relapsing encephalitis positive for gamma aminobutyric acid (GABA)A receptor antibody associated with Type B3 thymoma.

    Science.gov (United States)

    Kitano, Takaya; Kinoshita, Makoto; Shimazu, Kohki; Fushimi, Hiroaki; Omori, Kenichi; Hazama, Takanori

    2016-11-29

    A 87-year-old female presented with subacute progression of cognitive decline. Fluid-attenuated inversion recovery images of brain MRI showed multifocal high-intensity lesions. Thoracic CT image revealed the presence of thymoma, and serum autoantibody screening showed positivity for anti-gamma aminobutyric acid (GABA) A receptor antibody. Histopathological analysis confirmed type B3 thymoma after thymectomy. The patient received both plasmapheresis and intravenous methylprednisolone therapy, and showed remarkable amelioration of clinical symptoms and MRI abnormal high intensity. However, after 2 month from the clinical recovery, the patient showed recurrence of brain lesions and intravenous methylprednisolone monotherapy was performed. Continuation of oral steroid therapy was required to maintain the quienscent state of inflammation within the central nervous system. Anti-GABA A receptor antibody is a recently discovered novel autoantibody associated with autoimmue encephalitis. Due to the limited number of literature reported, clinical course and therapeutic response of GABA A receptor antibody encephalitis remains elusive. Here we reported a rare case of GABA A receptor antibody encephalitis with type B3 thymoma. Clinical, radiological and therapeutic courses described in our report highlight the importance of immunotherapy for treatment of the disease.

  13. Molecular structure of the 1:2 complex of 2-quinuclidinium-butyrate with p-hydroxybenzoic acid

    Science.gov (United States)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2011-05-01

    The structure of the 1:2 complex of 2-quinuclidinium-butyrate, QNBu, with p-hydroxybenzoic acid, HBA, ( 1) has been determined by X-ray diffraction, DFT calculations, and the complex was characterized by FTIR and NMR spectroscopy. The crystals are triclinic, space group P1¯. The QNBu and HBA molecules are linked by medium-strong O sbnd H···O hydrogen bonds into a double strand related by two types of inversion centers, each inside different H-bonded rings. The O···O distances vary between 2.652(3) and 2.720(2) Å. The FTIR spectrum of the solid complex is consistent with the X-ray results. The second-derivative IR spectrum and calculated frequencies for the optimized structure of QNBu·2HBA were used to explain the FTIR spectrum in the carbonyl-carboxylate region. The interpretation of 1H and 13C NMR spectra has been based on 2D experiments and calculated GIAO/B3LYP/6-31G( d, p) magnetic isotropic shielding constants.

  14. Diet structure, butyric acid, and fermentable carbohydrates influence growth performance, gut morphology, and cecal fermentation characteristics in broilers.

    Science.gov (United States)

    Qaisrani, S N; van Krimpen, M M; Kwakkel, R P; Verstegen, M W A; Hendriks, W H

    2015-09-01

    An experiment with 288 male (Ross 308) 1-d-old broilers was conducted to test the hypothesis that a coarse diet supplemented with butyric acid (BA) and fermentable carbohydrates (FC) improves performance of broilers with a poorly digestible protein source. The interaction effects of diet structure (fine or coarse), FC supplementation (with or without), and BA supplementation (with or without) in a poorly digestible diet based on rapeseed meal (RSM) were tested in a factorial arrangement of 8 (2×2×2) dietary treatments. The coarseness of the diet affected feed intake (FI) (PFermentable carbohydrate supplementation did not influence growth performance, gut development, or contents of total BCFA and total biogenic amines in the cecal digesta (P>0.05). Supplementation with FC, however, decreased the cecal concentration of spermine by approximately 31% compared with broilers fed diets without FC (P=0.002). In conclusion, feeding a coarse diet supplemented with BA improved performance of broilers fed a diet containing a poorly digestible protein source. The negative effects of a poorly digestible protein source can thus be partly counterbalanced by coarse grinding and BA supplementation in the diet. © The Author 2015. Published by Oxford University Press on behalf of Poultry Science Association.

  15. Butyrate presence in distinct gastrointestinal tract segments modifies differentially digestive processes and amino acid bioavailability in young broiler chickens

    NARCIS (Netherlands)

    Moquet, P.C.A.; Salami, S.A.; Onrust, L.; Hendriks, W.H.; Kwakkel, R.P.

    2018-01-01

    The hypothesis was tested that butyrate presence in the digesta of distinct gastrointestinal tract (GIT) segments of broilers leads to differential effects on digesta retention time, gut morphology, and proteolytic enzymatic activities, ultimately resulting in differences in protein digestibility. A

  16. The use of high pressure CO2 -facilitated pH swings to enhance in situ product recovery of butyric acid in a two-phase partitioning bioreactor.

    Science.gov (United States)

    Peterson, Eric C; Daugulis, Andrew J

    2014-11-01

    Through the use of high partial pressures of CO2 (pCO2 ) to facilitate temporary pH reductions in two-phase partitioning bioreactors (TPPBs), improved pH dependent partitioning of butyric acid was observed which achieved in situ product recovery (ISPR), alleviating end-product inhibition (EPI) during the production of butyric acid by Clostridium tyrobutyricum (ATCC 25755). Through high pressure pCO2 studies, media buffering effects were shown to be substantially overcome at 60 bar pCO2 , resulting in effective extraction of the organic acid by the absorptive polymer Pebax® 2533, yielding a distribution coefficient (D) of 2.4 ± 0.1 after 1 h of contact at this pressure. Importantly, it was also found that C. tyrobutyricum cultures were able to withstand 60 bar pCO2 for 1 h with no decrease in growth ability when returned to atmospheric pressure in batch reactors after several extraction cycles. A fed-batch reactor with cyclic high pCO2 polymer extraction recovered 92 g of butyric acid to produce a total of 213 g compared to 121 g generated in a control reactor. This recovery reduced EPI in the TPPB, resulting in both higher productivity (0.65 vs. 0.33 g L(-1)  h(-1) ) and yield (0.54 vs. 0.40). Fortuitously, it was also found that repeated high pCO2 -facilitated polymer extractions of butyric acid during batch growth of C. tyrobutyricum lessened the need for pH control, and reduced base requirements by approximately 50%. Thus, high pCO2 -mediated absorptive polymer extraction presents a novel method for improving process performance in butyric acid fermentation, and this technique could be applied to the bioproduction of other organic acids as well. © 2014 Wiley Periodicals, Inc.

  17. Enhancement of gama-aminobutyric acid (GABA) and other health-related metabolites in germinated red rice (Oryza sativa L.) by ultrasonication.

    Science.gov (United States)

    Ding, Junzhou; Ulanov, Alexander V; Dong, Mengyi; Yang, Tewu; Nemzer, Boris V; Xiong, Shanbai; Zhao, Siming; Feng, Hao

    2018-01-01

    Red rice (Oryza sativa L.) that has a red (reddish brown) bran layer in de-hulled rice is known to contain rich biofunctional components. Germination is an effective technique to improve the nutritional quality, digestibility, and flavor of de-hulled rice. Ultrasonication, a form of physical stimulation, has been documented as a novel approach to improve the nutritional quality of plant-based food. This study was undertaken to test the use of ultrasound to enhance the nutritional value of red rice. Ultrasonication (5min, 16W/L) was applied to rice during soaking or after 66h germination. Changes of metabolites (amino acids, sugars, and organic acids) in red rice treated by ultrasonication were determined using a GC/MS plant primary metabolomics analysis platform. Differential expressed metabolites were identified through multivariate statistical analysis. Results showed that γ-aminobutyric acid (GABA) and riboflavin (vitamin B 2 ) in red rice significantly increased after germination for 72h, and then experienced a further increase after treatment by ultrasound at different stages during germination. The metabolomics analysis showed that some plant metabolites, i.e. GABA, O-phosphoethanolamine, and glucose-6-phosphate were significantly increased after the ultrasonic treatment (VIP>1.5) in comparison with the untreated germinated rice. The findings of this study showed that controlled germination with ultrasonic stress is an effective method to enhance GABA and other health-promoted components in de-hulled rice. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Interaction of polyunsaturated fatty acids and sodium butyrate in human colon adenocarcinoma cells in vitro

    Czech Academy of Sciences Publication Activity Database

    Hofmanová, Jiřina; Vaculová, Alena; Kovaříková, Martina; Zadák, Z.; Kozubík, Alois

    Suppl. 11 (2002), s. 77 ISSN 0196-4763. [Congress of the International Society for Analytical Cytology /21./. 04.05.2002-09.05.2002, San Diego] R&D Projects: GA MZd NC6171; GA ČR GA525/01/0419; GA AV ČR IBS5004009 Keywords : polyunsaturated fatty acids * colon cancer Subject RIV: BO - Biophysics

  19. Butyrate and other short-chain fatty acids as modulators of immunity : what relevance for health?

    NARCIS (Netherlands)

    Meijer, Kees; de Vos, Paul; Priebe, Marion G.

    2010-01-01

    Purpose of review High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune

  20. Role of indole-3-butyric acid or/and putrescine in improving productivity of chickpea (Cicer arientinum L.) plants.

    Science.gov (United States)

    Amin, A A; Gharib, F A; Abouziena, H F; Dawood, Mona G

    2013-12-15

    The response of chickpea (Cicer arientinum L. cv. Giza 3) to treatment with two plant growth regulators putrescine (Put) and Indole-3-butyric acid (IBA) at 25, 50 and 100 mg L(-1) applied either alone or in combinations was studied. Spraying of Put and IBA either individually or in combination significantly increased the plant height, number and dry weight of branches, leaves and pods/plant and leaf area/plant at the two growth stages. Total photosynthetic pigments in fresh leaves were significantly promoted as a result of application of Put or IBA. Generally, application of Put and/or IBA at 100 mg L(-1) produced the highest numbers of pods which resulted in substantially the highest seed yield. Put and IBA increased the seed yield by 21.3 and 19.2%, respectively, while the combination of Put at 100 mgL(-1) and IBA at 50 mgL(-1) increased it by 27.4%. Greatest increases in straw and biological yield/fed (38.3 and 30.4%, respectively) were noted with the combination treatment of IBA 100 mg L(-1) plus Put at 100 mg L(-1). Put and IBA significantly increased the nitrogen, phosphorus, potassium, total soluble sugars and total free amino acids in chickpea seeds over control, but the effects were less marked than those of their combination. This response was greater following treatment with IBA than with Put. It could be conclude that spraying Put or/and IBA on chickpea plants have promotion effects on the seeds yield criteria which have promising potential as sources of low-cost protein and minerals for possible use as food/feed supplements.

  1. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

    Directory of Open Access Journals (Sweden)

    Mathew Jobin

    2012-02-01

    Full Text Available Abstact Background Gamma amino butyric acid (GABA, the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P Aά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

  2. Autoradiographic analysis of 3H-glutamate, 3H-dopamine, and 3H-GABA accumulation in rabbit retina after kainic acid treatment

    International Nuclear Information System (INIS)

    Hampton, C.K.; Redburn, D.A.

    1983-01-01

    We have previously reported that exposure of isolated rabbit retina to 10(-3) M kainic acid produces profound morphological changes in specific retinal neurons (Hampton et al, 1981). We noted specific swelling of horizontal cell bodies and neurites, necrosis of cell bodies in the amacrine and ganglion cell layers, and swelling of elements in the inner plexiform layer. We now report a differential sensitivity to kainic acid of specific subclasses of amacrine cells autoradiographically labeled with 3H-glutamate, 3H-GABA, or 3H-dopamine. Three different effects were observed: (1) Labeling of neurons after incubation in 3H-glutamate was uniformly reduced while labeling of glia was much less affected. (2) The accumulation of 3H-dopamine was also decreased by kainic acid in two of the three labeled bands of the inner plexiform layer. The outermost labeled band was insensitive to kainic acid at the highest concentration tested (10(-2) M). These findings provide a basis for the subclassification of dopaminergic amacrine cells into at least two subclasses based on their sensitivity to kainic acid. (3) Kainic acid caused a dramatic increase in the labeling of GABAergic amacrine cell bodies and their terminals. This increased intensity may reflect a compensatory increase in uptake activity in response to kainic acid-induced depletion of endogenous GABA stores. These results confirm the highly toxic nature of kainic acid and demonstrate a high degree of specificity and complexity in its action in the retina

  3. Contributions of GABA to alcohol responsivity during adolescence: Insights from preclinical and clinical studies

    Science.gov (United States)

    Silveri, Marisa M.

    2015-01-01

    There is a considerable body of literature demonstrating that adolescence is a unique age period, which includes rapid and dramatic maturation of behavioral, cognitive, hormonal and neurobiological systems. Most notably, adolescence is also a period of unique responsiveness to alcohol effects, with both hyposensitivity and hypersensitivity observed to the various effects of alcohol. Multiple neurotransmitter systems are undergoing fine-tuning during this critical period of brain development, including those that contribute to the rewarding effects of drugs of abuse. The role of developmental maturation of the γ-amino-butyric acid (GABA) system, however, has received less attention in contributing to age-specific alcohol sensitivities. This review integrates GABA findings from human magnetic resonance spectroscopy studies as they may translate to understanding adolescent-specific responsiveness to alcohol effects. Better understanding of the vulnerability of the GABA system both during adolescent development, and in psychiatric conditions that include alcohol dependence, could point to a putative mechanism, boosting brain GABA, that may have increased effectiveness for treating alcohol abuse disorders. PMID:24631274

  4. Plasmonic-based colorimetric and spectroscopic discrimination of acetic and butyric acids produced by different types of Escherichia coli through the different assembly structures formation of gold nanoparticles.

    Science.gov (United States)

    La, Ju A; Lim, Sora; Park, Hyo Jeong; Heo, Min-Ji; Sang, Byoung-In; Oh, Min-Kyu; Cho, Eun Chul

    2016-08-24

    We present a plasmonic-based strategy for the colourimetric and spectroscopic differentiation of various organic acids produced by bacteria. The strategy is based on our discovery that particular concentrations of dl-lactic, acetic, and butyric acids induce different assembly structures, colours, and optical spectra of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically-engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce acetic and butyric acid, respectively. Different assembly structures and optical properties of gold nanoparticles were observed when different organic acids, obtained after the removal of acid-producing bacteria, were mixed with gold nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli, which produce sufficient amounts of acetic acid to induce the assembly of gold nanoparticles, a direct estimate of the number of bacteria was possible based on time-course colour change observations of gold nanoparticle aqueous suspensions. The plasmonic-based colourimetric and spectroscopic methods described here may enable onsite testing for the identification of organic acids produced by bacteria and the estimation of bacterial numbers, which have applications in health and environmental sciences. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. GABA Levels Are Decreased After Stroke and GABA Changes During Rehabilitation Correlate With Motor Improvement

    Science.gov (United States)

    Blicher, Jakob Udby; Near, Jamie; Næss-Schmidt, Erhard; Stagg, Charlotte J.; Johansen-Berg, Heidi; Nielsen, Jørgen Feldbæk; Østergaard, Leif; Ho, Yi-Ching Lynn

    2017-01-01

    Background and Objective γ-Aminobutyric acid (GABA) is the dominant inhibitory neurotransmitter in the brain and is important in motor learning. We aimed to measure GABA content in primary motor cortex poststroke (using GABA-edited magnetic resonance spectroscopy [MRS]) and in relation to motor recovery during 2 weeks of constraint-induced movement therapy (CIMT). Methods Twenty-one patients (3-12 months poststroke) and 20 healthy subjects were recruited. Magnetic resonance imaging structural T1 and GABA-edited MRS were performed at baseline and after CIMT, and once in healthy subjects. GABA:creatine (GABA:Cr) ratio was measured by GABA-edited MRS. Motor function was measured using Wolf Motor Function Test (WMFT). Results Baseline comparison between stroke patients (n = 19) and healthy subjects showed a significantly lower GABA:Cr ratio in stroke patients (P < .001) even after correcting for gray matter content in the voxel (P < .01) and when expressing GABA relative to N-acetylaspartic acid (NAA; P = .03). After 2 weeks of CIMT patients improved significantly on WMFT, but no consistent change across the group was observed for the GABA:Cr ratio (n = 17). However, the extent of improvement on WMFT correlated significantly with the magnitude of GABA:Cr changes (P < .01), with decreases in GABA:Cr ratio being associated with better improvements in motor function. Conclusions In patients 3 to 12 months poststroke, GABA levels are lower in the primary motor cortex than in healthy subjects. The observed association between GABA and recovery warrants further studies on the potential use of GABA MRS as a biomarker in poststroke recovery. PMID:25055837

  6. Assembly of the outer retina in the absence of GABA synthesis in horizontal cells

    Directory of Open Access Journals (Sweden)

    Parker Edward

    2010-06-01

    Full Text Available Abstract Background The inhibitory neurotransmitter gamma-amino-butyric acid (GABA not only modulates excitability in the mature nervous system but also regulates neuronal differentiation and circuit development. Horizontal cells, a subset of interneurons in the outer retina, are transiently GABAergic during the period of cone photoreceptor synaptogenesis. In rodents, both horizontal cells and cone axonal terminals express GABAA receptors. To explore the possibility that transient GABA expression in mouse neonatal horizontal cells influences the structural development of synaptic connectivity in the outer retina, we examined a mutant in which expression of GAD67, the major synthesizing enzyme for GABA, is selectively knocked out in the retina. Results Immunocytochemistry and electron microscopy revealed that the assembly of triad synapses involving cone axonal pedicles and the dendrites of horizontal and bipolar cells is unaffected in the mutant retina. Moreover, loss of GABA synthesis in the outer retina did not perturb the spatial distributions and cell densities of cones and horizontal cells. However, there were some structural alterations at the cellular level: the average size of horizontal cell dendritic clusters was larger in the mutant, and there was also a small but significant increase in cone photoreceptor pedicle area. Moreover, metabotropic glutamate receptor 6 (mGluR6 receptors on the dendrites of ON bipolar cells occupied a slightly larger proportion of the cone pedicle in the mutant. Conclusions Together, our analysis shows that transient GABA synthesis in horizontal cells is not critical for synapse assembly and axonal and dendritic lamination in the outer retina. However, pre- and postsynaptic structures are somewhat enlarged in the absence of GABA in the developing outer retina, providing for a modest increase in potential contact area between cone photoreceptors and their targets. These findings differ from previous results

  7. The endogenous GABA analogue gamma-hydroxybutyric acid: Tritium labeling at high specific activity

    International Nuclear Information System (INIS)

    Egan, J.A.; Filer, C.N.

    2004-01-01

    [2,3,4- 3 H] Gamma-hydroxybutyric acid (GHB, 4) was prepared by means of a catalytic tritium reduction of 2(5H)-furanone (2) followed by hydrolysis. It has proven useful as a tool to study the GHB receptor. (author)

  8. GABA interaction with lipids in organic medium

    International Nuclear Information System (INIS)

    Beltramo, D.; Kivatinitz, S.; Lassaga, E.; Arce, A.

    1987-01-01

    The interaction of 3 H-GABA and 14 C-glutamate with lipids in an aqueous organic partition system was studied. With this partition system 3 H-GABA and 14 C-glutamate were able to interact with sphingomyelin, sulfatide, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid but not with cholesterol or ceramide. In an homogeneous aqueous medium the authors could not demonstrate any interaction between 3 H-GABA-lipids. The apparent dissociation constants (K/sub d/) for 3 H-GABA-lipids or 14 C-glutamate-lipids interactions inorganic medium were in the millimolar range and maximal charge between 3 and 7 moles of GABA or glutamate by mole of lipid. Amino acids such as glutamic acid, β-alanine and glycine displaced 3 H-GABA with the same potency as GABA itself; thus these results show that the interaction lacks pharmacological specificity. To detect this interaction lipid concentrations higher than 2 μM were required and in the partition system 3 H-GABA and lipid phosphorus were both concentrated at the interface. Therefore, lipids tested with a biphasic partition system do not fulfill the classical criteria for a neurotransmitter receptor at least not for GABA and glutamate. 15 references, 1 figure, 3 tables

  9. Use of sourdough fermentation and pseudo-cereals and leguminous flours for the making of a functional bread enriched of gamma-aminobutyric acid (GABA).

    Science.gov (United States)

    Coda, Rossana; Rizzello, Carlo Giuseppe; Gobbetti, Marco

    2010-02-28

    Lactobacillus plantarum C48 and Lactococcus lactis subsp. lactis PU1, previously selected for the biosynthesis of gamma-aminobutyric acid (GABA), were used for sourdough fermentation of cereal, pseudo-cereal and leguminous flours. Chickpea, amaranth, quinoa and buckwheat were the flours most suitable to be enriched of GABA. The parameters of sourdough fermentation were optimized. Addition of 0.1mM pyridoxal phosphate, dough yield of 160, inoculum of 5 x 10(7)CFU/g of starter bacteria and fermentation for 24h at 30 degrees C were found to be the optimal conditions. A blend of buckwheat, amaranth, chickpea and quinoa flours (ratio 1:1:5.3:1) was selected and fermented with baker's yeast (non-conventional flour bread, NCB) or with Lb. plantarum C48 sourdough (non-conventional flour sourdough bread, NCSB) and compared to baker's yeast started wheat flour bread (WFB). NCSB had the highest concentration of free amino acids and GABA (ca. 4467 and 504 mg/kg, respectively). The concentration of phenolic compounds and antioxidant activity of NCSB bread was the highest, as well as the rate of in vitro starch hydrolysis was the lowest. Texture analysis showed that sourdough fermentation enhances several characteristics of NCSB with respect to NCB, thus approaching the features of WFB. Sensory analysis showed that sourdough fermentation allowed to get good palatability and overall taste appreciation. (c) 2009 Elsevier B.V. All rights reserved.

  10. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

    Science.gov (United States)

    Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

    2014-10-01

    Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

  11. GABA signalling during development: new data and old questions.

    Science.gov (United States)

    Varju, P; Katarova, Z; Madarász, E; Szabó, G

    2001-08-01

    In addition to being the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is thought to play a morphogenetic role in embryonic development. During the last decade, considerable progress has been made in elucidating the molecular mechanisms involved in GABA synthesis and biological action. The present review is an attempt to summarise recent results on the ontogeny of the different components of embryonic GABA signalling with an emphasis on the synthesis of GABA by different molecular forms of glutamic acid decarboxylase (GAD).

  12. Biochemical changes in barberries during adventitious root formation: the role of indole-3-butyric acid and hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Ali Tehranifar

    2014-03-01

    Full Text Available Peroxidase, polyphenol oxidase (PPO, phenolic compounds and total sugars (TS were investigated during root formation in cuttings of Berberis vulgaris var. asperma (BVA and Berberis thunbergii var. atropurpurea (BTA treated with indole-3-butyric acid (IBA and IBA+H2O2. Rooting was observed on BTA cuttings but not on BVA cuttings. The BTA cuttings treated with IBA and IBA+H2O2 showed higher rooting percentages, number of roots, and root length over the control. Those treated with IBA+H2O2 recorded the lowest peroxidase activity after planting. BTA cuttings treated with IBA+H2O2 showed the highest peroxidase activity at 50 d after planting; BVA cuttings under different treatments showed no significant difference for peroxidase activity at planting time or up to 80 d after planting. PPO activity for the BTA cuttings in the control treatment was lower than for other treatments during root formation. The cuttings in the IBA and IBA+H2O2 treatments showed increased PPO activity from 0 to 50 d after planting and a slight decrease in PPO activity from 60 to 80 d after planting. PPO activity for the BVA cuttings was significantly lower than for BTA during root formation. The BTA cuttings treated with IBA and IBA+H2O2 showed the highest phenolic compound content during root formation. The BVA cuttings displayed higher TS than BTA during the initial stage of root formation. A comparison of the anatomical structure of easy-to-root and difficult-to-root cuttings indicated that physical inhibitors did not affect the rooting capacity of BVA.

  13. Revealing charge carrier dynamics in squaraine:[6, 6]-phenyl-C 71-butyric acid methyl ester based organic solar cells

    Science.gov (United States)

    Rana, Aniket; Sharma, Chhavi; Prabhu, Deepak D.; Kumar, Mahesh; Karuvath, Yoosaf; Das, Suresh; Chand, Suresh; Singh, Rajiv K.

    2018-04-01

    Ultrafast charge carrier dynamics as well as the generation of polaron pair in squaraine (SQ) and squaraine:[6,6]-phenyl-C 71-butyric acid methyl ester (SQ:PCBM71) have been studied using ultrafast transient absorption spectroscopy (UTAS). The current study reveals that the pure SQ exhibits the creation of singlet and triplet states; however, incorporation of PCBM71 in SQ results in the formation of polaron pairs with ˜550ps lifetime, which in turn leads to the creation of free electrons in the device. We show that the considerable increment in monomolecular and bimolecular recombination in SQ:PCBM71 compared to pure SQ which describes the interfacial compatibility of SQ and PCBMC71 molecules. The present work not only provides the information about the carrier generation in SQ and SQ:PCBM71 but also gives the facts relating to the effect of PCBM71 mixing into the SQ which is very significant because the SQ has donor-acceptor-donor (D-A-D) structure and mixing one more acceptor can introduce more complex recombinations in the blend. These findings have been complimented by the charge transport study in the device using impedance spectroscopy. The various important transport parameters are transit time (τt), diffusion constant (Dn), global mobility (μ) and carrier lifetime (τr). The values of these parameters are 26.38 μs, 4.64x10-6 cm2s-1, 6.12x10-6 cm2V-1s-1 and 399 μs, respectively. To the best of our knowledge such study related to SQ is not present in the literature comprehensively.

  14. Effect of indole-3-butyric acid and Trichoderma harzianum Rifai on asexual cape gooseberry propagation (Physalis peruviana L.

    Directory of Open Access Journals (Sweden)

    Oscar Humberto Alvarado-Sanabria

    2014-12-01

    Full Text Available The growth and development of cape gooseberry plants obtained from cuttings is affected by microorganisms in the substrate and by the concentration of plant growth regulators applied during planting. Using a factorial design, the effect of four concentrations of indole-3-butyric acid (IBA (0, 800, 1,200, and 1,600 mg L-1 and four suspensions of Trichoderma harzianum (0, 2·10(6, 3·10(6, and 4·10(6 cfu/mL on the growth of cape gooseberry cuttings was evaluated. Apical cuttings were used, 20 cm long, from 20-month-old plants of the Colombian ecotype, which were planted in pots (2 L using peat moss with burned rice husks as the substrate at a 3:1 ratio (v/v. The 800 mg L-1 of IBA application showed the highest accumulation of total dry mass (DM and root DM. Moreover, 800 mg L-1 of IBA resulted in the highest leaf chlorophyll content, showing significant differences from 1,600 mg L-1, which had the lowest value. The 3·10(6 cfu/mL suspension of T. harzianum caused a greater accumulation of root DM and total DM and a higher leaf area in the plants. The most favorable interaction between the factors, which favors the growth of cape gooseberry plants obtained from cuttings, was observed with the application of 800 mg L-1 of IBA and 3·10(6 cfu/mL of T. harzianum.

  15. Effect of sodium caproate on the volumetric and viscometric properties of glycine, DL-α-alanine, and DL-α-amino-n-butyric acid in aqueous solutions

    International Nuclear Information System (INIS)

    Wang Jianji; Yan Zhenning; Lu Jinsuo

    2004-01-01

    The apparent molar volumes (V m,2 ) and relative viscosities (η r ) at T=(298.15 and 308.15) K have been obtained for glycine, DL-α-alanine, and DL-α-amino-butyric acid in aqueous sodium caproate solutions from measurements of density and the flow time. The standard partial molar volumes (V 0 m,2 ), standard volumes of transfer (Δ t V 0 ), the viscosity B-coefficients, and the activation thermodynamic quantities (Δμ 2 0≠ and ΔS 2 0≠ ) of viscous flow have been calculated for the amino acids. It is shown that the standard partial molar volumes, viscosity B-coefficients, and activation free energies for viscous flow increase with increasing number of carbon atoms in the alkyl chain of the amino acids. An increase in V 0 m,2 and Δ t V 0 with increasing electrolyte concentrations have been explained due to the interactions of sodium caproate with the charged center of zwitterions for the amino acids. A comparison of the V 0 m,2 values for glycine, DL-α-alanine, and DL-α-aminon-n-butyric acid in different aqueous salts solutions showed that carboxylate ions have stronger interactions with amino acid than chloride, thiocyanate, and nitrate ions. Results of viscosity are discussed in terms of changes in solvent structure

  16. Effects of ruminal ammonia and butyrate concentrations on reticuloruminal epithelial blood flow and volatile fatty acid absorption kinetics under washed reticulorumen conditions in lactating dairy cows.

    Science.gov (United States)

    Storm, A C; Hanigan, M D; Kristensen, N B

    2011-08-01

    The effect of reticuloruminal epithelial blood flow on the absorption of propionate as a volatile fatty acid (VFA) marker in 8 lactating Holstein cows was studied under washed rumen conditions. The cows were surgically prepared with ruminal cannulas and permanent catheters in an artery and mesenteric, right ruminal, and hepatic portal veins. The experiment was designed with 2 groups of cows: 4 cows adapted to high crude protein (CP) and 4 to low CP. All cows were subjected to 3 buffers: butyric, ammonia, and control in a randomized replicated 3 × 3 incomplete Latin square design. The buffers (30 kg) were maintained in a temporarily emptied and washed rumen for 40 min. The initial concentration of VFA was 84.2 mmol/L. Butyrate was increased from 4 to 36 mmol/L in butyric buffer by replacement of acetate, and ammonia (NH(3)) was increased from 2.5 to 22.5 mmol/L in ammonia buffer by replacement of NaCl. Increasing amounts of deuterium oxide (D(2)O) were added to the buffers as the order of buffer sequence increased (6, 12, and 18 g of D(2)O). Ruminal clearance of D(2)O was used to estimate epithelial blood flow. To increase accuracy of the epithelial blood flow estimates, data of ruminal liquid marker (Cr-EDTA), and initial and final buffer volumes were fitted to a dynamic simulation model. The model was used to estimate ruminal liquid passages, residual liquid, and water influx (saliva and epithelia water) for each combination of cow and buffer (n=24). Epithelial blood flow increased 49±11% for butyric buffer compared with control. The ruminal disappearance of propionate (marker VFA) was affected by buffer and followed the same pattern as for epithelial blood flow. The correlation between ruminal disappearance of propionate and epithelial blood flow (r=0.56) indicates that the removal of propionate can be limited by epithelial blood flow. The ruminal disappearance of propionate increased 30±12% for the butyric compared with ammonia buffer and 12.5±8% when

  17. Effect of indole-butyric acid on the rooting of ficus cuttings

    Directory of Open Access Journals (Sweden)

    Đukić Matilda

    2013-01-01

    Full Text Available Propagation by cuttings is one of the most successful methods of vegetative propagation of floral crops. In addition to applications in interior decoration, ficuses belong to the group of plants that will potentially be used in green spaces of Belgrade due to global climate changes. In this paper, the possibility of rooting stimulated by adding different concentrations of the indolbytric acid phytohormone was investigated in the commonly cultivated species Ficus benjamina L. and Ficus elastica Roxb.. This is the most commonly used phytohormone in the propagation of ornamental plants due to its stability and stimulation of the rooting process, i.e. its favourable impact on the formation of adventitious roots, their size, number and weight. In this research, the rooting percent of cuttings was 100 % in F. benjamina and 77.66 % in F. elastica. It was found that the highest dose (2 % of the phytohormone significantly increased all indicators of rooting success in F. benjamina and that the application of weaker concentrations also showed good success. The rooting of F. elastica cuttings was not successful without phytohormones, and the best results were achieved at the phytohormone concentration of 2 %, which increased the dry weight of the roots of this ficus about 4 times. It would be useful to examine higher concentrations of this phytohormone and also some combinations with other rooting stimulators, to be able to make sound recommendations on the optimal dose for the mass production of these ficuses. [Projekat Ministarstva nauke Republike Srbije, br. 43007

  18. The effect of amino acid backbone length on molecular packing: crystalline tartrates of glycine, β-alanine, γ-aminobutyric acid (GABA) and DL-α-aminobutyric acid (AABA).

    Science.gov (United States)

    Losev, Evgeniy; Boldyreva, Elena

    2018-02-01

    We report a novel 1:1 cocrystal of β-alanine with DL-tartaric acid, C 3 H 7 NO 2 ·C 4 H 6 O 6 , (II), and three new molecular salts of DL-tartaric acid with β-alanine {3-azaniumylpropanoic acid-3-azaniumylpropanoate DL-tartaric acid-DL-tartrate, [H(C 3 H 7 NO 2 ) 2 ] + ·[H(C 4 H 5 O 6 ) 2 ] - , (III)}, γ-aminobutyric acid [3-carboxypropanaminium DL-tartrate, C 4 H 10 NO 2 + ·C 4 H 5 O 6 - , (IV)] and DL-α-aminobutyric acid {DL-2-azaniumylbutanoic acid-DL-2-azaniumylbutanoate DL-tartaric acid-DL-tartrate, [H(C 4 H 9 NO 2 ) 2 ] + ·[H(C 4 H 5 O 6 ) 2 ] - , (V)}. The crystal structures of binary crystals of DL-tartaric acid with glycine, (I), β-alanine, (II) and (III), GABA, (IV), and DL-AABA, (V), have similar molecular packing and crystallographic motifs. The shortest amino acid (i.e. glycine) forms a cocrystal, (I), with DL-tartaric acid, whereas the larger amino acids form molecular salts, viz. (IV) and (V). β-Alanine is the only amino acid capable of forming both a cocrystal [i.e. (II)] and a molecular salt [i.e. (III)] with DL-tartaric acid. The cocrystals of glycine and β-alanine with DL-tartaric acid, i.e. (I) and (II), respectively, contain chains of amino acid zwitterions, similar to the structure of pure glycine. In the structures of the molecular salts of amino acids, the amino acid cations form isolated dimers [of β-alanine in (III), GABA in (IV) and DL-AABA in (V)], which are linked by strong O-H...O hydrogen bonds. Moreover, the three crystal structures comprise different types of dimeric cations, i.e. (A...A) + in (III) and (V), and A + ...A + in (IV). Molecular salts (IV) and (V) are the first examples of molecular salts of GABA and DL-AABA that contain dimers of amino acid cations. The geometry of each investigated amino acid (except DL-AABA) correlates with the melting point of its mixed crystal.

  19. Continuous hydrogen and butyric acid fermentation by immobilized Clostridium tyrobutyricum ATCC 25755: effects of the glucose concentration and hydraulic retention time.

    Science.gov (United States)

    Mitchell, Robert J; Kim, Ji-Seong; Jeon, Byung-Seung; Sang, Byoung-In

    2009-11-01

    The effects of the hydraulic retention time (HRT=8, 10, 12 or 16.7 h) and glucose concentration (30, 40 or 50 g/L) on the production of hydrogen and butyrate by an immobilized Clostridium tyrobutyricum culture, grown under continuous culturing conditions, were evaluated. With 30 g/L glucose, the higher HRTs tested led to greater butyrate concentrations in the culture, i.e., 9.3 g/L versus 12.9 g/L with HRTs of 8 h and 16.7 h, respectively. In contrast, higher biogas and hydrogen production rates were generally seen when the HRT was lower. Experiments with different glucose concentrations saw a significant amount of glucose washed out when 50 g/L was used, the highest being 22.7 g/L when the HRT was 16.7 h. This study found the best conditions for the continuous production of hydrogen and butyric acid by C. tyrobutyricum to be with an HRT of 12 h and a glucose concentration of 50 g/L, respectively.

  20. Interaction of polyunsaturated fatty acids and sodium butyrate during apoptosis in HT-29 human colon adenocarcinoma cells

    Czech Academy of Sciences Publication Activity Database

    Hofmanová, Jiřina; Vaculová, Alena; Lojek, Antonín; Kozubík, Alois

    2005-01-01

    Roč. 44, č. 1 (2005), s. 40-51 ISSN 1436-6207 R&D Projects: GA ČR(CZ) GA525/01/0419 Institutional research plan: CEZ:AV0Z50040507 Keywords : colon cancer * diet * butyrate Subject RIV: BO - Biophysics Impact factor: 2.257, year: 2005

  1. Detection and molecular characterization of butyrate-producing ...

    African Journals Online (AJOL)

    Butyrate-producing gut microflora synthesizes and secretes butyrate which serves as source of energy and stimulates rumen development in young animals. The present study was undertaken to characterize and screen butyrate-producing lactic acid bacteria (LAB) for probiotic use in animals in order to manipulate their gut ...

  2. Butyrate-induced transcriptional changes in human colonic mucosa

    NARCIS (Netherlands)

    Vanhoutvin, S.A.L.W.; Troost, F.J.; Hamer, H.M.; Lindsey, P.J.; Koek, G.H.; Jonkers, D.M.A.E.; Kodde, A.; Venema, K.; Brummer, R.J.M.

    2009-01-01

    Background: Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on

  3. Brain γ-aminobutyric acid (GABA) detection in vivo with the J-editing (1) H MRS technique: a comprehensive methodological evaluation of sensitivity enhancement, macromolecule contamination and test-retest reliability.

    Science.gov (United States)

    Shungu, Dikoma C; Mao, Xiangling; Gonzales, Robyn; Soones, Tacara N; Dyke, Jonathan P; van der Veen, Jan Willem; Kegeles, Lawrence S

    2016-07-01

    Abnormalities in brain γ-aminobutyric acid (GABA) have been implicated in various neuropsychiatric and neurological disorders. However, in vivo GABA detection by (1) H MRS presents significant challenges arising from the low brain concentration, overlap by much stronger resonances and contamination by mobile macromolecule (MM) signals. This study addresses these impediments to reliable brain GABA detection with the J-editing difference technique on a 3-T MR system in healthy human subjects by: (i) assessing the sensitivity gains attainable with an eight-channel phased-array head coil; (ii) determining the magnitude and anatomic variation of the contamination of GABA by MM; and (iii) estimating the test-retest reliability of the measurement of GABA with this method. Sensitivity gains and test-retest reliability were examined in the dorsolateral prefrontal cortex (DLPFC), whereas MM levels were compared across three cortical regions: DLPFC, the medial prefrontal cortex (MPFC) and the occipital cortex (OCC). A three-fold higher GABA detection sensitivity was attained with the eight-channel head coil compared with the standard single-channel head coil in DLPFC. Despite significant anatomical variation in GABA + MM and MM across the three brain regions (p test-retest reliability of GABA measurement, expressed as either the ratio to voxel tissue water (W) or to total creatine, was found to be very high for both the single-channel coil and the eight-channel phased-array coil. For the eight-channel coil, for example, Pearson's correlation coefficient of test vs. retest for GABA/W was 0.98 (R(2)  = 0.96, p = 0.0007), the percentage coefficient of variation (CV) was 1.25% and the intraclass correlation coefficient (ICC) was 0.98. Similar reliability was also found for the co-edited resonance of combined glutamate and glutamine (Glx) for both coils. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Molecular modeling study of agglomeration of [6,6]-phenyl-C61-butyric acid methyl ester in solvents.

    Science.gov (United States)

    Mortuza, S M; Banerjee, Soumik

    2012-12-28

    The molecular interactions between solvent and nanoparticles during photoactive layer formation in organic photovoltaic (OPV) cells influence the morphology of the photoactive layer and hence determine the power conversion efficiency. Prediction of optimal synthesis parameters in OPVs, such as choice of solvent, processing temperature, and nanoparticle concentration, requires fundamental understanding of the mechanisms that govern the agglomeration of nanoparticles in solvents. In this study, we used molecular dynamics simulations to simulate a commonly used organic nanoparticle, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), in various solvents to correlate solvent-nanoparticle interactions with the size of the agglomerate structure of PCBM. We analyzed the effects of concentration of PCBM and operating temperature on the molecular rearrangement and agglomeration of PCBM in three solvents: (i) toluene, (ii) indane, and (iii) toluene-indane mixture. We evaluated the agglomeration behavior of PCBM by determining sizes of the largest clusters of PCBM and the corresponding size distributions. To obtain further insight into the agglomerate structure of PCBMs, we evaluated radial distribution functions (RDFs) and coordination numbers of the various moieties of PCBMs with respect to solvent atoms as well as with respect to that of other PCBMs. Our simulations demonstrate that PCBMs form larger clusters in toluene while they are relatively dispersed in indane, which indicates the greater solubility of PCBM in indane than in toluene. In toluene-indane mixture, PCBMs are clustered to a greater extent than in indane and less than that in toluene. To correlate agglomerate size to nanoparticle-solvent interactions, we also evaluated the potential of mean force (PMF) of the fullerene moiety of PCBM in toluene and indane. Our results also show that the cluster size of PCBM molecules increases with the increase of concentration of PCBM and the processing temperature. To

  5. Reduced parahippocampal and lateral temporal GABA{sub A}-[{sup 11}C]flumazenil binding in major depression: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Klumpers, Ursula M.H. [VU University Medical Center, Department of Psychiatry, Amsterdam (Netherlands); GGZ inGeest, partner of VUmc, Department of Psychiatry, Amsterdam (Netherlands); VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Veltman, Dick J. [VU University Medical Center, Department of Psychiatry, Amsterdam (Netherlands); VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Drent, Madeleine L. [VU University Medical Center, Department of Endocrinology, Amsterdam (Netherlands); Boellaard, Ronald; Lammertsma, Adriaan A. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Comans, Emile F.I. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Meynen, Gerben [VU University Medical Center, Department of Psychiatry, Amsterdam (Netherlands); Hoogendijk, Witte J.G. [VU University Medical Center, Department of Psychiatry, Amsterdam (Netherlands); VU University Medical Center, Center for Neurogenomics and Cognitive Research, Amsterdam (Netherlands); VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands)

    2010-03-15

    Major depressive disorder (MDD) has been related to both a dysfunctional {gamma}-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABA{sub A}-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment. Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer [{sup 11}C]flumazenil ([{sup 11}C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (V{sub T}) and binding potential (BP{sub ND}) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed. In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [{sup 11}C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (p uncorrected {<=}0.001). In the temporal area, [{sup 11}C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [{sup 11}C]FMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex. The bilateral reduction in limbic parahippocampal and right temporal [{sup 11}C]FMZ binding found in MDD indicates decreased GABA{sub A}-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABA{sub A} binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition. (orig.)

  6. The radioautographical localization in the vertebrate retina of [3H]-(+-)-Cis-aminocyclohexane carboxylic acid (ACHC); a selective inhibitor of neuronal GABA transport

    International Nuclear Information System (INIS)

    Cunningham, J.; Neal, M.J.; Marshall, J.

    1981-01-01

    The cellular sites of uptake of [ 3 H]ACHC in the retinae of rat, guinea pig and rabbit have been examined by radioautography. The uptake of [ 3 H]ACHC occurred predominantly in the Muller cells in the retinae of the guinea pig, rabbit and rat. L-2,4-Diaminobutyric acid (DABA), another compound which inhibits neuronal GABA uptake, was also taken up mainly by glial cells in frog and rat retinae although some of the analogue was accumulated by photoreceptor cells. (author)

  7. Transport of Indole-3-Butyric Acid and Indole-3-Acetic Acid in Arabidopsis Hypocotyls Using Stable Isotope Labeling1[C][W][OA

    Science.gov (United States)

    Liu, Xing; Barkawi, Lana; Gardner, Gary; Cohen, Jerry D.

    2012-01-01

    The polar transport of the natural auxins indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) has been described in Arabidopsis (Arabidopsis thaliana) hypocotyls using radioactive tracers. Because radioactive assays alone cannot distinguish IBA from its metabolites, the detected transport from applied [3H]IBA may have resulted from the transport of IBA metabolites, including IAA. To test this hypothesis, we used a mass spectrometry-based method to quantify the transport of IBA in Arabidopsis hypocotyls by following the movement of [13C1]IBA and the [13C1]IAA derived from [13C1]IBA. We also assayed [13C6]IAA transport in a parallel control experiment. We found that the amount of transported [13C1]IBA was dramatically lower than [13C6]IAA, and the IBA transport was not reduced by the auxin transport inhibitor N-1-naphthylphthalamic acid. Significant amounts of the applied [13C1]IBA were converted to [13C1]IAA during transport, but [13C1]IBA transport was independent of IBA-to-IAA conversion. We also found that most of the [13C1]IBA was converted to ester-linked [13C1]IBA at the apical end of hypocotyls, and ester-linked [13C1]IBA was also found in the basal end at a level higher than free [13C1]IBA. In contrast, most of the [13C6]IAA was converted to amide-linked [13C6]IAA at the apical end of hypocotyls, but very little conjugated [13C6]IAA was found in the basal end. Our results demonstrate that the polar transport of IBA is much lower than IAA in Arabidopsis hypocotyls, and the transport mechanism is distinct from IAA transport. These experiments also establish a method for quantifying the movement of small molecules in plants using stable isotope labeling. PMID:22323783

  8. Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain.

    Science.gov (United States)

    Vazquez-DeRose, Jacqueline; Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Gulati, Srishti; Mathew, Thomas K; Neylan, Thomas C; Kilduff, Thomas S

    2016-03-01

    Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.

  9. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S

    1999-01-01

    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GABA...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  10. GABA(A) receptor- and GABA transporter polymorphisms and risk for essential tremor

    DEFF Research Database (Denmark)

    Thier, S; Kuhlenbäumer, G; Lorenz, D

    2011-01-01

    Background:  Clinical features and animal models of essential tremor (ET) suggest gamma-aminobutyric acid A receptor (GABA(A) R) subunits and GABA transporters as putative candidate genes. Methods:  A total of 503 ET cases and 818 controls were investigated for an association between polymorphisms...... in 15 GABA(A) R and four GABA transporter genes and ET. Results:  Nine nominally significant tagging SNPs (P values from 4.9 × 10(-2) to 5.2 × 10(-4) ) were found in the hypothesis generation stage. Five SNPs were followed up in a second verification stage but failed to reach significance. (P values...... from 0.30 to 0.77). Discussion:  In our samples, no evidence of association between GABA(A) R and GABA transporter genes with ET was detected. Further studies are necessary to clarify the role of these genes in ET....

  11. GABA-A stimulation in normal volunteers and during temporal epilepsy measured by 18FDG with positron emission tomography

    International Nuclear Information System (INIS)

    Cinotti, L.; Le Bars, D.; Garcia-Larrea, L.; Peyron, R.; Gregoire, M.C.; Lavenne, F.; Comar, D.; Mauguiere, F.; Krogsgaard-Larsen, P.

    1996-01-01

    The γ-amino butyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and it has been evoked in epilepto-genesis. Using a GABA analog, the THIP, we tried to establish if the gabaergic neurotransmission was modified in the epileptic focus. For this purpose, we measured the effects of this specific GABA agonist on the cerebral glucose consumption (CMRGlu) as measured by 18F-fluoro-deoxyglucose ( 18 FDG) with positron emission tomography (PET). Eight patients presenting temporal epilepsy and three normal volunteers received two 18 FDG PET studies, after placebo and THIP injection, in random order. Clinical symptoms and electroencephalographic data demonstrated a trend towards sleepiness and a diminution of alpha waves after THIP injection. CMRGlu was globally increased with THIP in cortical regions, cerebellum and caudate nuclei. The average increase was 17% in grey matter while it did not reach significancy in white matter. Under the placebo condition, the asymmetry between the focus and the controlateral internal temporal zone was 18% as an average, and reduced significantly to 11% after THIP injection. In the external temporal zones, the asymmetry decreased from 28% to 14%. These results suggest that gabaergic inhibition requires energy in the normal brain tissue and in this with temporal epilepsy. Since the asymmetry of glucose consumption tends to diminish, the inhibitory GABA system appears preserved in temporal epilepsy with an enhanced sensitivity in the focus. (Authors). 6 refs., 4 figs

  12. HPLC conditions are critical for the detection of GABA by microdialysis

    NARCIS (Netherlands)

    Rea, Kieran; Cremers, T.I.F.H.; Westerink, B.H.C.

    In microdialysis studies, neither exocytotic release of gamma-aminobutyric acid (GABA), nor the presence of GABA type B (GABA(B)) autoreceptors, have been clearly established. It was investigated whether the chromatographic separation of GABA may have contributed to discrepancies in the literature.

  13. The role of genetic sex in affect regulation and expression of GABA-related genes across species

    Directory of Open Access Journals (Sweden)

    Marianne eSeney

    2013-09-01

    Full Text Available Although circulating hormones and inhibitory gamma-amino butyric acid (GABA-related factors are known to affect mood, considerable knowledge gaps persist for biological mechanisms underlying the female bias in mood disorders. Here, we combine human and mouse studies to investigate sexual dimorphism in the GABA system in the context of major depressive disorder (MDD and then use a genetic model to dissect the role of sex-related factors in GABA-related gene expression and anxiety-/depressive-like behaviors in mice. First, using meta-analysis of gene array data in human postmortem brain (N = 51 MDD subjects, 50 controls, we show that the previously-reported down-regulation in MDD of somatostatin (SST, a marker of a GABA neuron subtype, is significantly greater in women with MDD. Second, using gene co-expression network analysis in control human subjects (N = 214; 2 frontal cortex regions and expression quantitative trait loci mapping (N = 170 subjects, we show that expression of SST and the GABA-synthesizing enzymes glutamate decarboxylase 67 (GAD67 and GAD65 are tightly co-regulated and influenced by X-chromosome genetic polymorphisms. Third, using a rodent genetic model (Four Core Genotypes (FCG mice, in which genetic and gonadal sex are artificially dissociated (N ≥ 12/group, we show that genetic sex (i.e. X/Y chromosome influences both gene expression (lower Sst, Gad67, Gad65 in XY mice and anxiety-like behaviors (higher in XY mice. This suggests that in an intact male animal, the observed behavior represents the outcomes of male genetic sex increasing and male-like testosterone decreasing anxiety-like behaviors. Gonadal sex was the only factor influencing depressive-like behavior (gonadal males < gonadal females. Collectively, these combined human and mouse studies provide mechanistic insight into sexual dimorphism in mood disorders, and specifically demonstrate an unexpected role for XY genetic sex on GABA-related genes and anxiety

  14. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  15. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  16. Further evidence for involvement of the dorsal hippocampus serotonergic and γ-aminobutyric acid (GABA)ergic pathways in the expression of contextual fear conditioning in rats.

    Science.gov (United States)

    Almada, Rafael C; Albrechet-Souza, Lucas; Brandão, Marcus L

    2013-12-01

    Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning. However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred. Thus, the purpose of the present study was to investigate the role of DH serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior. The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity. Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response. Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol. The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.

  17. Indole-3-butyric acid promotes adventitious rooting in Arabidopsis thaliana thin cell layers by conversion into indole-3-acetic acid and stimulation of anthranilate synthase activity.

    Science.gov (United States)

    Fattorini, L; Veloccia, A; Della Rovere, F; D'Angeli, S; Falasca, G; Altamura, M M

    2017-07-11

    Indole-3-acetic acid (IAA), and its precursor indole-3-butyric acid (IBA), control adventitious root (AR) formation in planta. Adventitious roots are also crucial for propagation via cuttings. However, IBA role(s) is/are still far to be elucidated. In Arabidopsis thaliana stem cuttings, 10 μM IBA is more AR-inductive than 10 μM IAA, and, in thin cell layers (TCLs), IBA induces ARs when combined with 0.1 μM kinetin (Kin). It is unknown whether arabidopsis TCLs produce ARs under IBA alone (10 μM) or IAA alone (10 μM), and whether they contain endogenous IAA/IBA at culture onset, possibly interfering with the exogenous IBA/IAA input. Moreover, it is unknown whether an IBA-to-IAA conversion is active in TCLs, and positively affects AR formation, possibly through the activity of the nitric oxide (NO) deriving from the conversion process. Revealed undetectable levels of both auxins at culture onset, showing that arabidopsis TCLs were optimal for investigating AR-formation under the total control of exogenous auxins. The AR-response of TCLs from various ecotypes, transgenic lines and knockout mutants was analyzed under different treatments. It was shown that ARs are better induced by IBA than IAA and IBA + Kin. IBA induced IAA-efflux (PIN1) and IAA-influx (AUX1/LAX3) genes, IAA-influx carriers activities, and expression of ANTHRANILATE SYNTHASE -alpha1 (ASA1), a gene involved in IAA-biosynthesis. ASA1 and ANTHRANILATE SYNTHASE -beta1 (ASB1), the other subunit of the same enzyme, positively affected AR-formation in the presence of exogenous IBA, because the AR-response in the TCLs of their mutant wei2wei7 was highly reduced. The AR-response of IBA-treated TCLs from ech2ibr10 mutant, blocked into IBA-to-IAA-conversion, was also strongly reduced. Nitric oxide, an IAA downstream signal and a by-product of IBA-to-IAA conversion, was early detected in IAA- and IBA-treated TCLs, but at higher levels in the latter explants. Altogether, results showed that IBA induced

  18. Synthesis of L-2,4-diamino[4-11C]butyric acid and its use in some in vitro and in vivo tumour models

    International Nuclear Information System (INIS)

    Antoni, G.; Omura, H.; Bergstroem, M.; Furuya, Y.; Moulder, R.; Roberto, A.; Sundin, A.; Watanabe, Y.; Laangstroem, B.

    1997-01-01

    L-2,4-Diamino[4- 11 C]butyric acid (DAB) was synthesized by an enzyme catalysed carrier added (0.1 μmol KCN) reaction of hydrogen [ 11 C]cyanide with O-acetyl-L-serine followed by reduction. L-[ 11 C]DAB was obtained with a radiochemical purity higher than 96% and with a decay corrected radiochemical yield of 30-40% within a 32 min reaction time. The enantiomeric excess was 98%. The uptake of L-[ 11 C]DAB was investigated in multicellular aggregates of six different cell lines and animal tumour models. L-[ 11 C]DAB is potentially useful for the assessment of pharmacokinetics of L-DAB in vivo for part of its evaluation as an antitumoural agent, although its use for diagnostic purposes seems limited

  19. 4,4,4-trifluoro-3-(indole-3-)butyric acid promotes root elongation in Lactuca sativa independent of ethylene synthesis and pH

    Science.gov (United States)

    Zhang, Nenggang; Hasenstein, Karl H.

    2002-01-01

    We studied the mode of action of 4,4,4-trifluoro-3- (indole-3-) butyric acid (TFIBA), a recently described root growth stimulator, on primary root growth of Lactuca sativa L. seedlings. TFIBA (100 micromoles) promoted elongation of primary roots by 40% in 72 h but inhibited hypocotyl growth by 35%. TFIBA induced root growth was independent of pH. TFIBA did not affect ethylene production, but reduced the inhibitory effect of ethylene on root elongation. TFIBA promoted root growth even in the presence of the ethylene biosynthesis inhibitor L-alpha-(2-aminoethoxyvinyl)glycine. TFIBA and the ethylene-binding inhibitor silver thiosulphate (STS) had a similar effect on root elongation. The results indicate that TFIBA-stimulated root elongation was neither pH-dependent nor related to inhibition of ethylene synthesis, but was possibly related to ethylene action.

  20. Metabolism of γ-hydroxyl-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids

    International Nuclear Information System (INIS)

    Doherty, J.D.; Roth, R.H.

    1978-01-01

    Ninhydrin decarboxylation experiments were carried out on the labelled amino acids produced following intraventricular injection of either γ-hydroxy-[1- 14 C] butyric acid (GHB) or [1- 14 C] succinate. The loss of isotope (as 14 CO 2 ) was similar for both substances. The [1- 14 C] GHB metabolites lost 75% of the label and the [1- 14 C] succinate metabolites lost 68%. This observation gives support to the hypothesis that the rat brain has the enzymatic capacity to metabolize [1- 14 C] GHB to succinate and to amino acids that have the isotope in the carboxylic acid group adjacent to the α-amino group. These results also indicate that the label from [1- 14 C] GHB does not enter the Krebs cycle as acetate. The specific activity ratio of radio-labelled glutamine to glutamic acid was determined in order to evaluate which of the two major metabolic compartments prefentially metabolize GHB. It was found that for [1- 14 C] GHB the ratio was 4.20 +- 0.18 (S.E. for n = 7) and for [1- 14 C] succinate the ratio was 7.71 (average of two trials, 7.74 and 7.69). These results suggest that the compartment thought to be associated with glial cells and synaptosomal structures is largely responsible for the metabolism of GHB. Metabolism as it might relate to the neuropharmacological action of GHB is discussed. (author)

  1. Impact of pH and butyric acid on butanol production during batch fermentation using a new local isolate of Clostridium acetobutylicum YM1.

    Science.gov (United States)

    Al-Shorgani, Najeeb Kaid Nasser; Kalil, Mohd Sahaid; Yusoff, Wan Mohtar Wan; Hamid, Aidil Abdul

    2018-02-01

    The effect of pH and butyric acid supplementation on the production of butanol by a new local isolate of Clostridium acetobutylicum YM1 during batch culture fermentation was investigated. The results showed that pH had a significant effect on bacterial growth and butanol yield and productivity. The optimal initial pH that maximized butanol production was pH 6.0 ± 0.2. Controlled pH was found to be unsuitable for butanol production in strain YM1, while the uncontrolled pH condition with an initial pH of 6.0 ± 0.2 was suitable for bacterial growth, butanol yield and productivity. The maximum butanol concentration of 13.5 ± 1.42 g/L was obtained from cultures grown under the uncontrolled pH condition, resulting in a butanol yield ( Y P / S ) and productivity of 0.27 g/g and 0.188 g/L h, respectively. Supplementation of the pH-controlled cultures with 4.0 g/L butyric acid did not improve butanol production; however, supplementation of the uncontrolled pH cultures resulted in high butanol concentrations, yield and productivity (16.50 ± 0.8 g/L, 0.345 g/g and 0.163 g/L h, respectively). pH influenced the activity of NADH-dependent butanol dehydrogenase, with the highest activity obtained under the uncontrolled pH condition. This study revealed that pH is a very important factor in butanol fermentation by C. acetobutylicum YM1.

  2. Impact of pH and butyric acid on butanol production during batch fermentation using a new local isolate of Clostridium acetobutylicum YM1

    Directory of Open Access Journals (Sweden)

    Najeeb Kaid Nasser Al-Shorgani

    2018-02-01

    Full Text Available The effect of pH and butyric acid supplementation on the production of butanol by a new local isolate of Clostridium acetobutylicum YM1 during batch culture fermentation was investigated. The results showed that pH had a significant effect on bacterial growth and butanol yield and productivity. The optimal initial pH that maximized butanol production was pH 6.0 ± 0.2. Controlled pH was found to be unsuitable for butanol production in strain YM1, while the uncontrolled pH condition with an initial pH of 6.0 ± 0.2 was suitable for bacterial growth, butanol yield and productivity. The maximum butanol concentration of 13.5 ± 1.42 g/L was obtained from cultures grown under the uncontrolled pH condition, resulting in a butanol yield (YP/S and productivity of 0.27 g/g and 0.188 g/L h, respectively. Supplementation of the pH-controlled cultures with 4.0 g/L butyric acid did not improve butanol production; however, supplementation of the uncontrolled pH cultures resulted in high butanol concentrations, yield and productivity (16.50 ± 0.8 g/L, 0.345 g/g and 0.163 g/L h, respectively. pH influenced the activity of NADH-dependent butanol dehydrogenase, with the highest activity obtained under the uncontrolled pH condition. This study revealed that pH is a very important factor in butanol fermentation by C. acetobutylicum YM1.

  3. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action

    DEFF Research Database (Denmark)

    Lehmann, Anders; Antonsson, Madeleine; Holmberg, Ann Aurell

    2009-01-01

    recombinant human GABA transporters. AR-H061719 [(R/S)-(3-amino-2-fluoropropyl)phosphinic acid], (the racemate of AZD3355) inhibited the response of ferret mechanoreceptors to gastric distension, further supporting its peripheral site of action on TLESR. In summary, AZD3355 probably inhibits TLESR through...

  4. Gaba /SUB a/ vs gaba /SUB b/ modulation of septal-hippocampal interconnections

    International Nuclear Information System (INIS)

    Blaker, W.D.; Cheney, D.L.; Costa, E.

    1986-01-01

    The authors perform studies to correlate pharmacologically induced decreases in the hippocampal TR /SUB ACh/ with changes in extinction of a foodreinforced lever press response. The authors differentiate the behavioral effects elicited by GABAergic vs. non-GABAergic inhibition of hippocampal cholinergic activity as well as show that GABA /SUB A/ receptor activation in the septum produces a behavioral-biochemical profile different from that elicited by GABA /SUB B/ receptor activation. To characterize GABA receptors tritium-GABA binding was performed in rats injected bilaterally with 1 ug kainic acid into the ventral and dorsal hippocampi. Representative cumulative recorder tracings showing the effect of varius intraseptal doses of the GABA /SUB A/ agonist muscimol on extinction after CRF training are show for one experiment. The most marked differences between muscimol and saline treated rats were seen in the extinction response patterns

  5. A Co-Drug of Butyric Acid Derived from Fermentation Metabolites of the Human Skin Microbiome Stimulates Adipogenic Differentiation of Adipose-Derived Stem Cells: Implications in Tissue Augmentation.

    Science.gov (United States)

    Wang, Yanhan; Zhang, Lingjuan; Yu, Jinghua; Huang, Stephen; Wang, Zhenping; Chun, Kimberly Ann; Lee, Tammy Ling; Chen, Ying-Tung; Gallo, Richard L; Huang, Chun-Ming

    2017-01-01

    We show that Staphylococcus epidermidis, a commensal bacterium in the human skin microbiome, produces short-chain fatty acids by glycerol fermentation that can induce adipogenesis. Although the antimicrobial and anti-inflammatory activities of short-chain fatty acids have been previously well characterized, little is known about the contribution of short-chain fatty acids to the adipogenic differentiation of adipose-derived stem cells (ADSCs). We show that ADSCs differentiated into adipocytes and accumulated lipids in the cytoplasm when cultured with butyric acid, a principal short-chain fatty acid in the fermentation metabolites of S. epidermidis. Additionally, a co-drug, butyric acid 2-(2-butyryloxyethoxy) ethyl ester (BA-DEG-BA), released active butyric acid when it was intradermally injected into mouse ears and induced ADSC differentiation, characterized by an increased expression of cytoplasmic lipids and perilipin A. The BA-DEG-BA-induced adipogenic differentiation was mediated via peroxisome proliferator-activated receptor gamma. Furthermore, intradermal injection of ADSCs along with BA-DEG-BA into mouse ears markedly enhanced the adipogenic differentiation of ADSCs, leading to dermal augmentation. Our study introduces BA-DEG-BA as an enhancer of ADSC adipogenesis and suggests an integral interaction between the human skin microbiome and ADSCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Measurement of release of endogenous GABA and catabolites of [3H]GABA from synaptosomal preparations using ion-exchange chromatography

    International Nuclear Information System (INIS)

    Grove, J.; Gardner, C.R.; Richards, M.H.

    1982-01-01

    Picomole quantities of endogenous GABA in acidified superfusates of synaptosomal preparations have been measured using micro-bore ion-exchange chromatography and post-column formation of the fluorescent iso-indole derivative. Using this technique superfusates have been analyzed directly, without further manipulations, to investigate the release of endogenous GABA. Spontaneous release of GABA was 2-5 pmol/200 microliters superfusate increasing to 20 pmol/200 microliters with potassium stimulation. When gamma-vinyl GABA (RMI 71754), an inhibitor of GABA-T was injected into rats (750 mg/kg) and synaptosomes prepared the potassium-evoked release of GABA was increased 3-fold compared to controls. Chromatographic separations and measurement of release of endogenous and radiolabeled GABA allowed the real specific activity of released GABA to be calculated. Only when 500 microM amino-oxyacetic acid was added during isolation of synaptosomes was the specific activity of released GABA the same as the initial specific activity

  7. Novel agents acting on GABA2 receptors: potential cognitive enhancers

    International Nuclear Information System (INIS)

    Chebib, M.

    2001-01-01

    γ- Aminobutyric acid (GABA) is a low molecular weight ammo acid found throughout the central and peripheral nervous systems. It is a very flexible molecule and thus can attain a number of low-energy conformations which are recognised by a series of enzymes, receptors and transporter systems. This article will concentrate on the effects of GABA C as the major inhibitory neurotransmitter in the brain. GABA C receptors belong to the superfamily of ligand-gated ion channels that include nicotinic acetylcholine, GABA A , strychnine-sensitive glycine, and serotonin type 3 receptors. The compound outlined in this article provide us with novel leads for the design and development of compounds that may be selective for GABA receptors. Such compounds will help in the study of GABA C receptors both in vitro and in vivo, providing an insight into the role these receptors play in the brain

  8. Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

    Science.gov (United States)

    Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

    2016-05-01

    Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

  9. An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells

    Directory of Open Access Journals (Sweden)

    Baraldi O

    2017-09-01

    Full Text Available Olga Baraldi,1 Francesca Bianchi,2,3 Viola Menghi,1 Andrea Angeletti,1 Anna Laura Croci Chiocchini,1 Maria Cappuccilli,1 Valeria Aiello,1 Giorgia Comai,1 Gaetano La Manna1 1Department of Experimental, Diagnostic and Specialty Medicine, Nephrology, Dialysis and Renal Transplant Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, 2Stem Wave Institute for Tissue Healing, Gruppo Villa Maria Care & Research – Ettore Sansavini Health Science Foundation, Lugo, Ravenna, 3National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Background: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress.Materials and methods: Lactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9 and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using

  10. GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: a pilot study.

    Science.gov (United States)

    Tian, Yingfang; Gunther, Joan R; Liao, Isaac H; Liu, Dazhi; Ander, Bradley P; Stamova, Boryana S; Lit, Lisa; Jickling, Glen C; Xu, Huichun; Zhan, Xinhua; Sharp, Frank R

    2011-03-24

    Tourette syndrome (TS) is a complex childhood neurodevelopmental disorder characterized by motor and vocal tics. Recently, altered numbers of GABAergic-parvalbumin (PV) and cholinergic interneurons were observed in the basal ganglia of individuals with TS. Thus, we postulated that gamma-amino butyric acid (GABA)- and acetylcholine (ACh)-related genes might be associated with the pathophysiology of TS. Total RNA isolated from whole blood of 26 un-medicated TS subjects and 23 healthy controls (HC) was processed on Affymetrix Human Exon 1.0 ST arrays. Data were analyzed to identify genes whose expression correlated with tic severity in TS, and to identify genes differentially spliced in TS compared to HC subjects. Many genes (3627) correlated with tic severity in TS (p genes were significantly over-represented. Moreover, several GABA and ACh-related genes were predicted to be alternatively spliced in TS compared to HC including GABA receptors GABRA4 and GABRG1, the nicotinic ACh receptor CHRNA4 and cholinergic differentiation factor (CDF). This pilot study suggests that at least some of these GABA- and ACh-related genes observed in blood that correlate with tics or are alternatively spliced are involved in the pathophysiology of TS and tics. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Acute desensitization of presynaptic GABA(B)-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus

    NARCIS (Netherlands)

    Tosetti, P; Bakels, R; Colin-Le Brun, [No Value; Ferrand, N; Gaiarsa, JL; Caillard, O

    The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release

  12. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring

    Directory of Open Access Journals (Sweden)

    Hadiza Altine Adamu

    2016-02-01

    Full Text Available Background: Evidence suggests perinatal environments influence the risk of developing insulin resistance. Objective: The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR and GBR-derived gamma (γ aminobutyric acid (GABA extract on epigenetically mediated high fat diet–induced insulin resistance. Design: Pregnant Sprague Dawley rats were fed high-fat diet (HFD, HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4 were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Results: Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. Conclusions: These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis.

  13. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring.

    Science.gov (United States)

    Adamu, Hadiza Altine; Imam, Mustapha Umar; Ooi, Der-Jiun; Esa, Norhaizan Mohd; Rosli, Rozita; Ismail, Maznah

    2016-01-01

    Evidence suggests perinatal environments influence the risk of developing insulin resistance. The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR) and GBR-derived gamma (γ) aminobutyric acid (GABA) extract on epigenetically mediated high fat diet-induced insulin resistance. Pregnant Sprague Dawley rats were fed high-fat diet (HFD), HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4) were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis.

  14. Growth and development of moringa (Moringa oleifera L. stem cuttings as affected by diameter magnitude, growth media, and indole-3-butyric acid

    Directory of Open Access Journals (Sweden)

    Shamsuddeen Rufai

    2016-12-01

    Full Text Available The acknowledged status of Moringa oleifera L. in sub-Saharan Africa, especially western Africa, has of recent accorded it the significance of being a good source of income to a large segment of many of its populace. Intensification of research into the realization of its full economic potential will be of utmost value to impoverished societies globally. One way to achieve this is the full exploration of all possible means that will facilitate its successful growth, propagation, and domestication. Even though it can be successfully raised through seeds, the high level outcrossing (64.3% observed is a hindrance to realization of true to type trees. Vegetative propagation can be employed as an option to tackle the noted limitation, ease the cultivation process, and achieve the required realization of its economic potential. Our trial was carried out to study the influence of two growth media and three levels of indole 3-butyric acid (IBA on root and shoot development in cuttings taken from a coppiced moringa tree existent in Universiti Putra Malaysia. Semi-hardwood cuttings of moringa, of between 20 and 30 mm diameter, cut into 25 cm length, were obtained, rinsed with a fungicide, then dipped, through their basal portion, inside varying levels (0, 1000, 2000, and 3000 ppm of indole-3-butyric acid (IBA for between 7 and 10 seconds. The treated cuttings were then transplanted into a polyethylene bags (23 cm × 36 cm, containing two growth media - a munchong series soil (M and a combination of a munchong series soil thoroughly mixed with biochar (MB in a 3:1 ratio sequence. The trial was conducted inside a shade house where the humidity of the experimental area was manipulated through a regular daily manual hand sprinkling. Plant height, percentage of primary branch produced, leaf area, and dry matter (DM were found to be significantly (P<0.05 influenced by variation in stem diameter magnitude, while the diameter of the primary branch and spad

  15. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

    Science.gov (United States)

    Canani, Roberto Berni; Costanzo, Margherita Di; Leone, Ludovica; Pedata, Monica; Meli, Rosaria; Calignano, Antonio

    2011-01-01

    The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine. PMID:21472114

  16. GABA Shunt in Durum Wheat

    Directory of Open Access Journals (Sweden)

    Petronia Carillo

    2018-02-01

    Full Text Available Plant responses to salinity are complex, especially when combined with other stresses, and involve many changes in gene expression and metabolic fluxes. Until now, plant stress studies have been mainly dealt only with a single stress approach. However, plants exposed to multiple stresses at the same time, a combinatorial approach reflecting real-world scenarios, show tailored responses completely different from the response to the individual stresses, due to the stress-related plasticity of plant genome and to specific metabolic modifications. In this view, recently it has been found that γ-aminobutyric acid (GABA but not glycine betaine (GB is accumulated in durum wheat plants under salinity only when it is combined with high nitrate and high light. In these conditions, plants show lower reactive oxygen species levels and higher photosynthetic efficiency than plants under salinity at low light. This is certainly relevant because the most of drought or salinity studies performed on cereal seedlings have been done in growth chambers under controlled culture conditions and artificial lighting set at low light. However, it is very difficult to interpret these data. To unravel the reason of GABA accumulation and its possible mode of action, in this review, all possible roles for GABA shunt under stress are considered, and an additional mechanism of action triggered by salinity and high light suggested.

  17. GABA Shunt in Durum Wheat.

    Science.gov (United States)

    Carillo, Petronia

    2018-01-01

    Plant responses to salinity are complex, especially when combined with other stresses, and involve many changes in gene expression and metabolic fluxes. Until now, plant stress studies have been mainly dealt only with a single stress approach. However, plants exposed to multiple stresses at the same time, a combinatorial approach reflecting real-world scenarios, show tailored responses completely different from the response to the individual stresses, due to the stress-related plasticity of plant genome and to specific metabolic modifications. In this view, recently it has been found that γ-aminobutyric acid (GABA) but not glycine betaine (GB) is accumulated in durum wheat plants under salinity only when it is combined with high nitrate and high light. In these conditions, plants show lower reactive oxygen species levels and higher photosynthetic efficiency than plants under salinity at low light. This is certainly relevant because the most of drought or salinity studies performed on cereal seedlings have been done in growth chambers under controlled culture conditions and artificial lighting set at low light. However, it is very difficult to interpret these data. To unravel the reason of GABA accumulation and its possible mode of action, in this review, all possible roles for GABA shunt under stress are considered, and an additional mechanism of action triggered by salinity and high light suggested.

  18. GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-hours Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Priyanka eChanana

    2016-03-01

    Full Text Available ABSTRACTRationale- Panax quinquefolius (American Ginseng is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid plays an important role in sleep wake cycle homeostasis. Thus there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems.Objective- The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-hours sleep deprivation induced anxiety like behaviour, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation.Materials and Methods- Male laca mice were sleep deprived for 72-hours by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100 and 200 mg/kg was administered alone and in combination with GABA modulators (GABA Cl- channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist for 8 days, starting five days prior to 72-hours sleep deprivation period. Various behavioural (locomotor activity, mirror chamber test, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels, mitochondrial complexes, neuroinflammation marker (Tumour Necrosis Factor, TNF-alpha, serum corticosterone, and histopathological sections of brains were assessed. Results- 72-hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behaviour, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg treatment restored the behavioural, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of

  19. GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, P; Frølund, B; Frydenvang, Karla Andrea

    2000-01-01

    GABAA receptor agonists. The availability of these compounds made it possible to study the pharmacology of the GABA uptake systems and the GABAA receptors separately. Based on extensive cellular and molecular pharmacological studies using 23, 24, and a number of mono- and bicyclic analogues, it has been...... demonstrated that neuronal and glial GABA transport mechanisms have dissimilar substrate specificities. With GABA transport mechanisms as pharmacological targets, strategies for pharmacological interventions with the purpose of stimulating GABA neurotransmission seem to be (1) effective blockade of neuronal...... recently been reported as the most selective glial GABA uptake inhibitor so far known and may be a useful tool for further elucidation of the pharmacology of GABA transporters. In recent years, a variety of lipophilic analogues of the amino acids 23 and 24 have been developed, and one of these compounds...

  20. Review article: the role of butyrate on colonic function

    NARCIS (Netherlands)

    Hamer, H.M.; Jonkers, D.; Venema, K.; Vanhoutvin, S.; Troost, F.J.; Brummer, R.J.

    2008-01-01

    Background: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. Aim: To provide an overview on the

  1. GABA-A stimulation in normal volunteers and during temporal epilepsy measured by {sup 18}FDG with positron emission tomography; Stimulation GABA-A chez le volontaire sain et au cours des epilepsies temporales etudiee par le {sup 18}FDG en tomographie d`emission de positons

    Energy Technology Data Exchange (ETDEWEB)

    Cinotti, L.; Le Bars, D.; Garcia-Larrea, L.; Peyron, R.; Gregoire, M.C.; Lavenne, F.; Comar, D.; Mauguiere, F. [CERMEP, 69 - Lyon (France); Krogsgaard-Larsen, P. [Royal Danish School of Pharmacy, Copenhague (Denmark)

    1996-01-01

    The {gamma}-amino butyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and it has been evoked in epilepto-genesis. Using a GABA analog, the THIP, we tried to establish if the gabaergic neurotransmission was modified in the epileptic focus. For this purpose, we measured the effects of this specific GABA agonist on the cerebral glucose consumption (CMRGlu) as measured by 18F-fluoro-deoxyglucose ({sup 18}FDG) with positron emission tomography (PET). Eight patients presenting temporal epilepsy and three normal volunteers received two {sup 18}FDG PET studies, after placebo and THIP injection, in random order. Clinical symptoms and electroencephalographic data demonstrated a trend towards sleepiness and a diminution of alpha waves after THIP injection. CMRGlu was globally increased with THIP in cortical regions, cerebellum and caudate nuclei. The average increase was 17% in grey matter while it did not reach significancy in white matter. Under the placebo condition, the asymmetry between the focus and the controlateral internal temporal zone was 18% as an average, and reduced significantly to 11% after THIP injection. In the external temporal zones, the asymmetry decreased from 28% to 14%. These results suggest that gabaergic inhibition requires energy in the normal brain tissue and in this with temporal epilepsy. Since the asymmetry of glucose consumption tends to diminish, the inhibitory GABA system appears preserved in temporal epilepsy with an enhanced sensitivity in the focus. (Authors). 6 refs., 4 figs.

  2. Levels of glutamate, aspartate, GABA, and taurine in different regions of the cerebellum after x-irradiation-induced neuronal loss

    International Nuclear Information System (INIS)

    Rea, M.A.; McBride, W.J.; Rohde, B.H.

    1981-01-01

    The levels of glutamate (Glu), aspartate (Asp), gamma-amino-n-butyric acid (GABA), and taurine (Tau) were determined in the cortex, molecular layer, and deep nuclei of cerebella of adult rats exposed to X-irradiation at 12-15 days following birth (to prevent the acquisition of late-forming granule cells; 12-15x group) and 8-15 days following birth (to prevent the acquisition of granule and stellate cells; 8-15x group). Also, the levels of the four amino acids were measured in the crude synaptosomal fraction (P2) isolated from the whole cerebella of the control, 12-15x, and 8-15x groups. The level of Glu was significantly decreased by (1) 6-20% in the cerebellar cortex; (2) 15-20% in the molecular layer; and (3) 25-50% in the P2 fraction of the X-irradiated groups relative to control values. The content of Glu in the deep nuclei was not changed by X-irradiation treatment. Regional levels of Asp were unchanged by X-irradiation, while its level in P2 decreased by 15-30% after treatment. The levels of GABA and Tau in the molecular layer, deep nuclei, or P2 were not changed in the experimental groups. However, there was a 15% increase in the levels of GABA and Tau in the cerebellar cortex of the 8-15x group relative to control values. The data support the proposed role of glutamate as the excitatory transmitter released from the cerebellar granule cells but are inconclusive regarding a transmitter role for either Tau or GABA from cerebellar stellate cells

  3. Temporal- and Location-Specific Alterations of the GABA Recycling System in Mecp2 KO Mouse Brains

    Directory of Open Access Journals (Sweden)

    Seok K. Kang

    2014-01-01

    Full Text Available Rett syndrome (RTT, associated with mutations in methyl-CpG-binding protein 2 (Mecp2, is linked to diverse neurological symptoms such as seizures, motor disabilities, and cognitive impairments. An altered GABAergic system has been proposed as one of many underlying pathologies of progressive neurodegeneration in several RTT studies. This study for the first time investigated the temporal- and location-specific alterations in the expression of γ-amino butyric acid (GABA transporter 1 (GAT-1, vesicular GABA transporter (vGAT, and glutamic acid decarboxylase 67kD (GAD67 in wild type (WT and knockout (KO mice in the Mecp2 m1.1Bird/y mouse model of RTT. Immunohistochemistry (IHC co-labeling of GAT-1 with vGAT identified GABAergic synapses that were quantitated for mid-sagittal sections in the frontal cortex (FC, hippocampal dentate gyrus (DG, and striatum (Str. An age-dependent increase in the expression of synaptic GABA transporters, GAT-1, and vGAT, was observed in the FC and DG in WT brains. Mecp2 KO mice showed a significant alteration in this temporal profile that was location-specific, only in the FC. GAD67-positive cell densities also showed an age-dependent increase in the FC, but a decrease in the DG in WT mice. However, these densities were not significantly altered in the KO mice in the regions examined in this study. Therefore, the significant location-specific downregulation of synaptic GABA transporters in Mecp2 KO brains with unaltered densities of GAD67-positive interneurons may highlight the location-specific synaptic pathophysiology in this model of RTT.

  4. Side chain effect on electronic structure of spin-coated films of [6,6]-phenyl-C61-butyric acid methyl ester and its bis-adduct

    International Nuclear Information System (INIS)

    Akaike, Kouki; Kanai, Kaname; Ouchi, Yukio; Seki, Kazuhiko

    2013-01-01

    Highlights: ► Electronic structure of spin-coated films of PCBM and bis-PCBM was investigated. ► Ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. ► Electron donation from the side chain to C 60 -backbone raises the HOMO and LUMO. ► Open circuit voltages of PCBM-based solar cells relates to electron affinities. - Abstract: We investigated the electronic structure of spin-coated films of two soluble fullerenes; [6,6]-phenyl-C 61 -butyric acid methyl ester (PCBM) and its bis-adduct (bis-PCBM) using ultraviolet photoelectron spectroscopy, inverse photoemission spectroscopy and molecular orbital calculations. The ionization energy and electron affinity of spin-coated films of bis-PCBM were determined to be 6.01 eV and 3.4 eV, respectively. Analysis of electron density suggested the stronger electron donation from the two side chains to fullerene-backbone in a bis-PCBM molecule, compared with PCBM. The electron donation raises the energies of the frontier orbitals of bis-PCBM, which mainly consist of π-orbitals of fullerene-backbone. As a result, the ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. Moreover, we also concluded that the larger open circuit voltage observed for bis-PCBM based organic photovoltaics was explained by the higher-lying unoccupied molecular orbital of bis-PCBM

  5. Ultraviolet photoelectron spectroscopy and inverse photoemission spectroscopy of [6,6]-phenyl-C61-butyric acid methyl ester in gas and solid phases

    International Nuclear Information System (INIS)

    Akaike, Kouki; Nishi, Toshio; Ouchi, Yukio; Seki, Kazuhiko; Kanai, Kaname; Yoshida, Hiroyuki; Tsutsumi, Jun'ya; Sato, Naoki

    2008-01-01

    The electronic structure of [6,6]-phenyl-C 61 -butyric acid methyl ester (PCBM) was studied using ultraviolet photoelectron spectroscopy of vapor and thin film and inverse photoemission spectroscopy of thin film. The threshold ionization energy of PCBM was found to be 7.17±0.04 eV in gas phase and 5.96±0.02 eV in solid phase. The threshold electron affinity was 3.9±0.1 eV in solid phase. These values are 0.4-0.6 eV smaller than C 60 . The density functional theory calculations gave consistent results with these trends and suggested that the electron donation from the side chain to C 60 backbone raised the C 60 -backbone-derived π orbitals of PCBM. The polarization energy of PCBM is 1.21 eV, which is almost the same as C 60 but is about 0.5 eV smaller than the value of typical aromatic hydrocarbons

  6. Enhanced performance of poly(3-hexylthiophene-2,5-diyl):[6,6]-phenyl-C61-butyric acid methyl ester solar cells by UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Wenjin; Song, Guoxin; Li, Yonghua; Yuan, Chunqiu; Fan, Tianju; Tang, Wei; Wang, Jin; Zhao, Chunyan; Lai, Wenyong [Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023 (China); Zhang, Hongmei, E-mail: iamhmzhang@njupt.edu.cn [Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023 (China); Min, Yong, E-mail: iamygmin@njupt.edu.cn [Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023 (China); Huang, Wei, E-mail: wei-huang@njtech.edu.cn [Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023 (China); Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials - SICAM, Nanjing Tech University - NanjingTech, 30 South Puzhu Road, Nanjing 211816 (China)

    2016-02-01

    This study was undertaken to investigate the effect of ultraviolet (UV) irradiation on poly(3-hexylthiophene-2,5-diyl):[6,6]-phenyl-C61-butyric acid methyl (P3HT:PCBM) solar cells before the thermal annealing of its active layer. Aggregation size of the active layer was observed to increase after UV irradiation, according to the transmission electron microscopy images. Characterization of X-ray diffraction and atomic force microscopy demonstrated that UV irradiation can improve the crystallinity of P3HT phase and optimize the roughness of the active layer. Simulation results indicated that UV irradiation of appropriate time can improve physics parameters of the devices. As a result, the maximum power conversion efficiency of the devices was increased from 3.5% to 4.5%. - Highlights: • High efficiency of 4.5% was achieved based on P3HT:PCBM system. • UV irradiation of 365 nm significantly influenced aggregate morphology of PCBM. • Physical parameters were calculated to evaluate the variation quantitatively.

  7. Efficient and stable, structurally inverted poly(3-hexylthiopen): [6,6]-phenyl-C61-butyric acid methyl ester heterojunction solar cells with fibrous like poly(3-hexylthiopen)

    International Nuclear Information System (INIS)

    Bandara, Jayasundera; Shankar, Karthik; Grimes, Craig A.; Thelakkat, Mukundan

    2011-01-01

    We investigated an inverted organic photovoltaic device structure in which a densely packed ∼ 100 nm thin TiO 2 layer on fluorine doped conducting glass serves as anode and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate)/Au layer on top of the active layer serves as cathode. The active layer is comprised of a blend of poly(3-hexylthiopene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). The rectification behavior of such a device is improved significantly and injection losses are minimized compared to devices without any compact TiO 2 layer. Moreover, nanostructured P3HT active layer was achieved in-situ by spin coating concentrated pure P3HT and P3HT:PCBM blend and solar cell performances on thickness of the active layer were also investigated. For the inverted solar cells constructed with different concentrations of P3HT and PCBM keeping the P3HT:PCBM ratio 1:0.8 (wt.%), the highest short circuit current and efficiency was observed when the P3HT and PCBM concentration was equal to 1.5 (wt.%) and 1.2 (wt.%) respectively. This leads to highly stable and reproducible power conversion efficiency above 3.7% at 100 mW/cm 2 light intensity under AM 1.5 conditions.

  8. Dependence of protein binding capacity of dimethylamino-γ-butyric-acid (DMGABA)-immobilized porous membrane on composition of solvent used for DMGABA immobilization

    International Nuclear Information System (INIS)

    Iwanade, Akio; Umeno, Daisuke; Saito, Kyoichi; Sugo, Takanobu

    2013-01-01

    Dimethylamino-γ-butyric acid (DMGABA) as an ampholite was reacted with the epoxy group of the poly-glycidyl methacrylate chain grafted onto the pore surface of a porous hollow-fiber polyethylene membrane by radiation-induced graft polymerization. DMGABA was dissolved in a mixture of dioxane and water at various dioxane volume fractions, defined by dividing the dioxane volume by the total volume. The equilibrium binding capacity (EBC) of the DMGABA-immobilized porous hollow-fiber membrane for lysozyme was evaluated in the permeation mode. The EBC was varied from a 1/50-fold monolayer binding capacity to a 10-fold monolayer binding capacity by controlling the composition of the solvent used for DMGABA immobilization and the molar conversion of the epoxy group into the DMGABA group. - Highlights: ► A DMGABA membrane was immobilized by irradiation induced graft polymerization. ► The DMGABA was immobilized in a mixture of dioxane and water of various compositions. ► Lysozyme adsorptivity of DMGABA-immobilized membranes evaluated in the permeation mode. ► The composition of the DMGABA immobilized solvent can control adsorptivity

  9. Influence of indole-butyric acid and electro-pulse on in vitro rooting and development of olive (Olea europea L.) microshoots.

    Science.gov (United States)

    Padilla, Isabel Maria Gonzalez; Vidoy, I; Encina, C L

    2009-09-01

    The effects of indole-butyric acid (IBA) and electro-pulses on rooting and shoot growth were studied in vitro, using olive shoot cultures. Tested shoots were obtained from seedlings belonging to three Spanish cultivars, 'Arbequina', 'Manzanilla de Sevilla' and 'Gordal Sevillana', which have easy-, medium- and difficult-to-root rooting abilities, respectively. The standard two-step rooting method (SRM), consisting of root induction in olive rooting medium supplemented with 0, 0.1 or 1 mg/l IBA followed by root elongation in the same rooting medium without IBA, was compared with a novel one-step method consisting of shoot electro-pulses of 250, 1,250 or 2,500 V in a solution of IBA (0, 0.1 or 1 mg/l) and direct transferral to root elongation medium. The rooting percentage of the seedling-derived shoots obtained with the SRM was 76% for 'Arbequina' and 'Gordal Sevillana' cultivars and 100% for 'Manzanilla de Sevilla' cultivar, whereas with the electro-pulse method, the rooting percentages were 68, 64 and 88%, respectively. IBA dipping without pulse produced 0% rooting in 'Arbequina' seedling-derived shoots. The electroporation in IBA not only had an effect on shoot rooting but also on shoot growth and development, with longer shoots and higher axillary shoot sprouting and growth after some of the treatments. These effects were cultivar-dependent. The electro-pulse per se could explain some of these effects on shoot development.

  10. Electrical and optical modeling of poly(3-hexylthiophene):[6,6]-phenyl-C61 butyric acid methyl ester P3HT-PCBM bulk heterojunction solar cells

    Science.gov (United States)

    Brioua, Fathi; Remram, Mohamed; Nechache, Riad; Bourouina, Hicham

    2017-11-01

    In this work, we investigate a two-dimensional theoretical model for the photon conversion through an integration of the optical and electrical part of multilayer system in a bulk heterojunction solar cell based on poly(3-hexylthiophene) (P3HT)/6,6-phenyl C61-butyric acid methyl ester (PCBM) blend. The optical properties of the studied structure ITO/PEDOT:PSS/P3HT:PCBM/Ca/Al, such as the exciton generation rate and the electrical field distribution, are predicted at vicinity of the active layer and have been used to solve Poisson and continuity, drift-diffusion equations of the electrical model which characterize the electrical behavior of semiconductor device using finite element method (FEM). The electrical parameters such as power conversion efficiency (PCE), open voltage circuit ( V oc), short-circuit current density ( J sc) and fill factor (FF) are extracted from the current-voltage (J-V) characteristics under illumination and in dark conditions. Highest external quantum efficiency (IPCE), up to 60%, is obtained around 520 nm, while a power conversion efficiency (PCE) value of 3.62% is found to be in good agreement with the literature results. Integration of such theoretical approach into technological applications dealing with optoelectrical material performance will rapidly provide to the user accurate data outputs required for efficient validation of proof-of-concepts.

  11. Succinic semialdehyde dehydrogenase deficiency: Decrease in 4-OH-butyric acid levels with low doses of vigabatrin

    NARCIS (Netherlands)

    Escalera, G.I.; Ferrer, I.; Marina, L.C.; Sala, P.R.; Salomons, G.S.; Jakobs, C.; Perez-Cerda, C.

    2010-01-01

    Succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disease caused by a deficiency in gamma-aminobutyric degradation, resulting in an increase in gamma-hydroxybutyric acid in biological fluids. The clinical spectrum is heterogeneous, including a

  12. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Bistra B Nankova

    Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

  13. Role of proline and GABA in sexual reproduction of angiosperms

    OpenAIRE

    Biancucci, Marco; Mattioli, Roberto; Forlani, Giuseppe; Funck, Dietmar; Costantino, Paolo; Trovato, Maurizio

    2015-01-01

    Two glutamate derivatives, proline and γ-aminobutyric acid (GABA), appear to play pivotal roles in different aspects of sexual reproduction in angiosperms, although their precise function in plant reproduction and the molecular basis of their action are not yet fully understood. Proline and GABA have long been regarded as pivotal amino acids in pollen vitality and fertility. Proline may constitute up to 70% of the free amino acid pool in pollen grains and it has been recently shown that Arabi...

  14. Distribution of 3H-GABA uptake sites in the nematode Ascaris

    Energy Technology Data Exchange (ETDEWEB)

    Guastella, J.; Stretton, A.O. (University of Wisconsin, Madison (USA))

    1991-05-22

    The distribution of uptake sites for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, located at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations. Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously, these results define three classes of GABA-associated neurons in Ascaris: (1) neurons that contain endogenous GABA and possess a GABA uptake system; (2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; (3) neurons that possess a GABA uptake system, but that lack endogenous GABA.

  15. Distribution of 3H-GABA uptake sites in the nematode Ascaris

    International Nuclear Information System (INIS)

    Guastella, J.; Stretton, A.O.

    1991-01-01

    The distribution of uptake sites for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, located at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations. Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously, these results define three classes of GABA-associated neurons in Ascaris: (1) neurons that contain endogenous GABA and possess a GABA uptake system; (2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; (3) neurons that possess a GABA uptake system, but that lack endogenous GABA

  16. Vegetative propagation of Plukenetia polyadenia by cuttings: effects of leaf area and indole-3-butyric acid concentration

    OpenAIRE

    Solis, R.; Pezo, M.; Diaz, G.; Arévalo, L.; Cachique, D.

    2016-01-01

    Abstract The seeds of Plukenetia polyadenia have high levels of unsaturated fatty acids and are used as medicine and food for native people in the Peruvian and Brazilian Amazon. The objective of this study was to develop a method for vegetative propagation of Plukenetia polyadenia by rooting of cuttings. The experiment was laid out in a randomized complete block design with 12 treatments and 3 replications of 8 cuttings, in a 3 × 4 factorial arrangement. The factors were: 3 levels of leaf are...

  17. Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease.

    Science.gov (United States)

    Nishihara, Masaaki; Takesue, Ko; Hirooka, Yoshitaka

    2017-05-01

    Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Effect of butyrate and Lactobacillus GG on a butyrate receptor and transporter during Campylobacter jejuni exposure.

    Science.gov (United States)

    Cresci, Gail A M; Mayor, Paul C; Thompson, Stuart A

    2017-03-01

    Campylobacter jejuni frequently infects humans causing many gastrointestinal symptoms, fever, fatigue and several long-term debilitating diseases. Current treatment for campylobacteriosis includes rehydration and in some cases, antibiotic therapy. Probiotics are used to treat several gastrointestinal diseases. Butyrate is a short-chain fatty acid known to promote intestinal health. Interaction of butyrate with its respective receptor (HCAR2) and transporter (SLC5A8), both expressed in the intestine, is associated with water and electrolyte absorption as well as providing defense against colon cancer and inflammation. Alterations in gut microbiota influence the presence of HCAR2 and SLC5A8 in the intestine. We hypothesized that adherence and/or invasion of C. jejuni and alterations in HCAR2 and SLC5A8 expression would be minimized with butyrate or Lactobacillus GG (LGG) pretreatment of Caco-2 cells. We found that both C. jejuni adhesion but not invasion was reduced with butyrate pretreatment. While LGG pretreatment did not prevent C. jejuni adhesion, it did result in reduced invasion which was associated with altered cell supernate pH. Both butyrate and LGG protected HCAR2 and SLC5A8 protein expression following C. jejuni infection. These results suggest that the first stages of C. jejuni infection of Caco-2 cells may be minimized by LGG and butyrate pretreatment. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. α4βδ GABA receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)

    DEFF Research Database (Denmark)

    Absalom, N.; Karim, N.; Eghorn, L.F.

    2012-01-01

    γ-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both physiological and pharmacological actions. However, the mechanistic links between these lines of data are unknown. To identify molecular targets for specific GHB high-affinit...... and physiology. This finding will aid in elucidating the molecular mechanisms behind the proposed function of GHB as a neurotransmitter and its unique therapeutic effects in narcolepsy and alcoholism....

  20. Osmotic stress- and indole-3-butyric acid-induced NO generation are partially distinct processes in root growth and development in Pisum sativum.

    Science.gov (United States)

    Kolbert, Zsuzsanna; Bartha, Bernadett; Erdei, László

    2008-06-01

    In this work, the effects of osmotic stress and exogenous auxin (indole-3-butyric acid, IBA) on root morphology and nitric oxide (NO) generation in roots were compared in pea plants. Five-day-old plants were treated with 0, 10(-3), 10(-4), 10(-5), 10(-6), 10(-7), 10(-8) or 10(-9) M IBA or with PEG 6000 at concentrations that determined 0, 50, 100, 200 or 400 mOsm in the medium, during 5 days. NO generation was examined by in situ and in vivo fluorescence method. Increasing concentrations of PEG as well as IBA resulted in shortening of primary root (PR), enhancement of lateral root (LR) number and significant increase of NO generation. Time-dependent investigations revealed that in the case of IBA treatments, the LR number increased in parallel with an intensified NO generation, while elongation of PR was not followed by changes in NO levels. Under osmotic stress, the time curve of NO development was distinct compared with that of IBA-treated roots, because significantly, the appearance of lateral initials was preceded by a transient burst of NO. This early phase of NO generation under osmotic stress was clearly distinguishable from that which accompanied LR initiation. It is concluded that osmotic stress and the presence of exogenous auxin resulted in partly similar root architecture but different time courses of NO synthesis. We suppose that the early phase of NO generation may fulfill a role in the osmotic stress-induced signalization process leading to the modification of root morphology.

  1. Seed priming with BABA (β-amino butyric acid): a cost-effective method of abiotic stress tolerance in Vigna radiata (L.) Wilczek.

    Science.gov (United States)

    Jisha, K C; Puthur, Jos T

    2016-03-01

    The effects of β-amino butyric acid (BABA) on abiotic stress tolerance potential of three Vigna radiata varieties were studied. The reduction in the growth of seedlings subjected to NaCl/polyethylene glycol (PEG) stress is alleviated by BABA seed priming, which also enhanced photosynthetic pigment content and photosynthetic and mitochondrial activities, and also modified the chlorophyll a fluorescence-related parameters. Moreover, BABA seed priming reduced malondialdehyde content in the seedlings and enhanced the accumulation of proline, total protein, total carbohydrate, nitrate reductase activity, and activities of antioxidant enzymes like guaiacol peroxidase and superoxide dismutase. Most of these positive features of BABA priming were predominantly exhibited when the plants were encountered with stress (NaCl/PEG). The BABA content in the BABA-treated green gram seeds and seedlings was also detected and quantified with high-performance thin layer chromatography (HPTLC), and it revealed that the priming effect of BABA initiated in seeds and further gets carried over to the seedlings. It was concluded that BABA seed priming improved the drought and salinity stress tolerance potential of all the three green gram varieties, and it was evident in the NaCl-tolerant variety Pusa Vishal as compared to Pusa Ratna (abiotic stress sensitive) and Pusa 9531(drought tolerant). Dual mode in cost effectiveness of BABA priming is evident from: (1) the positive features of priming are being exhibited more during the exposure of plants to stress, and (2) priming of seedlings can be carried out by BABA application to seeds at very low concentration and volume.

  2. Gaseous CO2 signal initiates growth of butyric-acid-producing Clostridium butyricum in both pure culture and mixed cultures with Lactobacillus brevis.

    Science.gov (United States)

    Hakalehto, Elias; Hänninen, Osmo

    2012-07-01

    Microbial strains produce numerous volatile substances in the anaerobic conditions of the human intestines. The availability of CO(2) is known to be a prerequisite for bacterial growth in general. In experiments with anaerobic Lactobacillus brevis and Clostridium butyricum bacteria in the Portable Microbial Enrichment Unit (PMEU) it was shown that these strains interact; this interaction being mediated by CO(2) emission. CO(2) promoted clostridial growth in pure cultures and mixed cultures with lactobacilli. The growth of C. butyricum in pure cultures was much delayed or did not start at all without CO(2) from outside. Conversely, the onset of growth was provoked by a short (15 min) CO(2) burst. In mixed cultures the presence of lactobacilli in equal numbers speeded up the onset of clostridial growth by 10 h. If C. butyricum cultures designated as PMEU 1, 2, and 3 in cultivation syringes were chained by connecting the gas flow thereby allowing the volatiles of the preceding syringe culture to bubble to the next one, the growth started in 20, 10, or 6 h, respectively. This effect of gaseous emissions from other cultures speeding up the bacterial growth initiation was abolished if the gas was passed through sodium hydroxide to remove the CO(2). The positive contribution of lactobacilli to the growth of butyric-acid-producing clostridia documented in this simulation experiment with PMEU has in vivo implications and indicates molecular communication between the species. CO(2) is a necessary signal for the growth of clostridia, and lactobacilli can promote clostridial growth in mixed cultures where both bacteria grow well with mutual benefit.

  3. Quantum confinement-tunable ultrafast charge transfer at the PbS quantum dot and phenyl-C61-butyric acid methyl ester interface

    KAUST Repository

    El-Ballouli, AlA'A O.

    2014-05-14

    Quantum dot (QD) solar cells have emerged as promising low-cost alternatives to existing photovoltaic technologies. Here, we investigate charge transfer and separation at PbS QDs and phenyl-C61-butyric acid methyl ester (PCBM) interfaces using a combination of femtosecond broadband transient absorption (TA) spectroscopy and steady-state photoluminescence quenching measurements. We analyzed ultrafast electron injection and charge separation at PbS QD/PCBM interfaces for four different QD sizes and as a function of PCBM concentration. The results reveal that the energy band alignment, tuned by the quantum size effect, is the key element for efficient electron injection and charge separation processes. More specifically, the steady-state and time-resolved data demonstrate that only small-sized PbS QDs with a bandgap larger than 1 eV can transfer electrons to PCBM upon light absorption. We show that these trends result from the formation of a type-II interface band alignment, as a consequence of the size distribution of the QDs. Transient absorption data indicate that electron injection from photoexcited PbS QDs to PCBM occurs within our temporal resolution of 120 fs for QDs with bandgaps that achieve type-II alignment, while virtually all signals observed in smaller bandgap QD samples result from large bandgap outliers in the size distribution. Taken together, our results clearly demonstrate that charge transfer rates at QD interfaces can be tuned by several orders of magnitude by engineering the QD size distribution. The work presented here will advance both the design and the understanding of QD interfaces for solar energy conversion. © 2014 American Chemical Society.

  4. Effects of ruminal ammonia and butyrate concentrations on reticuloruminal epithelial blood flow and volatile fatty acid absorption kinetics under washed reticulorumen conditions in lactating dairy cows

    DEFF Research Database (Denmark)

    Storm, Adam Christian; Hanigan, M.D.; Kristensen, Niels Bastian

    2011-01-01

    and mesenteric, right ruminal, and hepatic portal veins. The experiment was designed with 2 groups of cows: 4 cows adapted to high crude protein (CP) and 4 to low CP. All cows were subjected to 3 buffers: butyric, ammonia, and control in a randomized replicated 3 × 3 incomplete Latin square design. The buffers...... liquid marker (Cr-EDTA), and initial and final buffer volumes were fitted to a dynamic simulation model. The model was used to estimate ruminal liquid passages, residual liquid, and water influx (saliva and epithelia water) for each combination of cow and buffer (n = 24). Epithelial blood flow increased...... that the removal of propionate can be limited by epithelial blood flow. The ruminal disappearance of propionate increased 30 ± 12% for the butyric compared with ammonia buffer and 12.5 ± 8% when compared with control. The net portal flux of propionate increased 32 ± 6% in butyric compared with control...

  5. Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

    Science.gov (United States)

    Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

    2015-08-01

    Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  6. Effects of non-protein amino acids on survival and locomotion of Osmia bicornis.

    Science.gov (United States)

    Felicioli, Antonio; Sagona, Simona; Galloni, Marta; Bortolotti, Laura; Bogo, Gherardo; Guarnieri, Massimo; Nepi, Massimo

    2018-04-17

    To investigate the effects of two non-protein amino acids, β-alanine and γ-amino butyric acid (GABA), on Osmia bicornis survival and locomotion, two groups of caged bees were fed with sugar syrup enriched with β-alanine and GABA, respectively. A further control group was fed with sugar syrup. Five behavioural categories were chosen according to the principle of parsimony and intrinsic unitary consistency from start to end, and recorded by scan sampling: two states (remaining under paper or in tubes) and three events (walking on net, feeding from flower and flying). We also analysed the amino acid content of haemolymph sampled from an additional 45 bees fed the same diets (15 per diet type). Bees fed with ß-alanine had a significantly shorter survival than those fed with control and GABA diets. The GABA diet induced higher locomotion than β-alanine. The former non-protein amino acid was only detected in the haemolymph of bees fed GABA. The results suggest that insects consuming non-protein amino-acid-rich diets absorb and transfer these substances to the haemolymph and that non-protein amino acids affect survival and locomotion. Ecological consequences are discussed in the framework of plant reproductive biology. This article is protected by copyright. All rights reserved. © 2018 The Royal Entomological Society.

  7. (photoautotrophic, photomixotrophic) and the auxin indole-butyric ...

    African Journals Online (AJOL)

    Effects of different culture conditions (photoautotrophic, photomixotrophic) and the auxin indole-butyric acid on the in vitro acclimatization of papaya ( Carica papaya L. var. Red Maradol) plants using zeolite as support.

  8. Neurotoxins from Snake Venoms and α-Conotoxin ImI Inhibit Functionally Active Ionotropic γ-Aminobutyric Acid (GABA) Receptors*

    Science.gov (United States)

    Kudryavtsev, Denis S.; Shelukhina, Irina V.; Son, Lina V.; Ojomoko, Lucy O.; Kryukova, Elena V.; Lyukmanova, Ekaterina N.; Zhmak, Maxim N.; Dolgikh, Dmitry A.; Ivanov, Igor A.; Kasheverov, Igor E.; Starkov, Vladislav G.; Ramerstorfer, Joachim; Sieghart, Werner; Tsetlin, Victor I.; Utkin, Yuri N.

    2015-01-01

    Ionotropic receptors of γ-aminobutyric acid (GABAAR) regulate neuronal inhibition and are targeted by benzodiazepines and general anesthetics. We show that a fluorescent derivative of α-cobratoxin (α-Ctx), belonging to the family of three-finger toxins from snake venoms, specifically stained the α1β3γ2 receptor; and at 10 μm α-Ctx completely blocked GABA-induced currents in this receptor expressed in Xenopus oocytes (IC50 = 236 nm) and less potently inhibited α1β2γ2 ≈ α2β2γ2 > α5β2γ2 > α2β3γ2 and α1β3δ GABAARs. The α1β3γ2 receptor was also inhibited by some other three-finger toxins, long α-neurotoxin Ls III and nonconventional toxin WTX. α-Conotoxin ImI displayed inhibitory activity as well. Electrophysiology experiments showed mixed competitive and noncompetitive α-Ctx action. Fluorescent α-Ctx, however, could be displaced by muscimol indicating that most of the α-Ctx-binding sites overlap with the orthosteric sites at the β/α subunit interface. Modeling and molecular dynamic studies indicated that α-Ctx or α-bungarotoxin seem to interact with GABAAR in a way similar to their interaction with the acetylcholine-binding protein or the ligand-binding domain of nicotinic receptors. This was supported by mutagenesis studies and experiments with α-conotoxin ImI and a chimeric Naja oxiana α-neurotoxin indicating that the major role in α-Ctx binding to GABAAR is played by the tip of its central loop II accommodating under loop C of the receptors. PMID:26221036

  9. Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors.

    Science.gov (United States)

    Kudryavtsev, Denis S; Shelukhina, Irina V; Son, Lina V; Ojomoko, Lucy O; Kryukova, Elena V; Lyukmanova, Ekaterina N; Zhmak, Maxim N; Dolgikh, Dmitry A; Ivanov, Igor A; Kasheverov, Igor E; Starkov, Vladislav G; Ramerstorfer, Joachim; Sieghart, Werner; Tsetlin, Victor I; Utkin, Yuri N

    2015-09-11

    Ionotropic receptors of γ-aminobutyric acid (GABAAR) regulate neuronal inhibition and are targeted by benzodiazepines and general anesthetics. We show that a fluorescent derivative of α-cobratoxin (α-Ctx), belonging to the family of three-finger toxins from snake venoms, specifically stained the α1β3γ2 receptor; and at 10 μm α-Ctx completely blocked GABA-induced currents in this receptor expressed in Xenopus oocytes (IC50 = 236 nm) and less potently inhibited α1β2γ2 ≈ α2β2γ2 > α5β2γ2 > α2β3γ2 and α1β3δ GABAARs. The α1β3γ2 receptor was also inhibited by some other three-finger toxins, long α-neurotoxin Ls III and nonconventional toxin WTX. α-Conotoxin ImI displayed inhibitory activity as well. Electrophysiology experiments showed mixed competitive and noncompetitive α-Ctx action. Fluorescent α-Ctx, however, could be displaced by muscimol indicating that most of the α-Ctx-binding sites overlap with the orthosteric sites at the β/α subunit interface. Modeling and molecular dynamic studies indicated that α-Ctx or α-bungarotoxin seem to interact with GABAAR in a way similar to their interaction with the acetylcholine-binding protein or the ligand-binding domain of nicotinic receptors. This was supported by mutagenesis studies and experiments with α-conotoxin ImI and a chimeric Naja oxiana α-neurotoxin indicating that the major role in α-Ctx binding to GABAAR is played by the tip of its central loop II accommodating under loop C of the receptors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Sløk, F A; Skjaerbaek, N

    1996-01-01

    , however, shown to be a specific and rather potent agonist at mGlu6, approximately 4 times weaker than the nonselective excitatory amino acid receptor agonist (S)-glutamic acid. 2-Aminoadipic acid (3), which shows a complex excitatory amino acid synaptic pharmacology, was an agonist at mGlu6 as well as m......The homologous series of acidic amino acids, ranging from aspartic acid (1) to 2-aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5......-methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N...

  11. Microbial degradation products influence colon cancer risk: the butyrate controversy.

    Science.gov (United States)

    Lupton, Joanne R

    2004-02-01

    All dietary fiber, by definition, escapes digestion in the small intestine and thus arrives relatively intact in the large intestine. Its fate in the large intestine depends upon the type of fiber and the colonic microflora. Highly fermentable fibers result in short chain fatty acids including butyrate, which is thought by some to be protective against colon cancer. However, not all studies support a chemopreventive effect for butyrate and the lack of agreement (particularly between in vivo and in vitro studies) on butyrate and colon cancer has been termed the "butyrate paradox." There are a number of reasons for this discrepant effect including differences between the in vitro and in vivo environments, the timing of butyrate administration, the amount of butyrate administered, the source of butyrate (usually dietary fiber) as a potential confounder, and an interaction with dietary fat. Collectively, the studies suggest that the chemopreventive benefits of butyrate depend in part on amount, time of exposure with respect to the tumorigenic process, and the type of fat in the diet.

  12. Astrocytic GABA Transporters

    DEFF Research Database (Denmark)

    Schousboe, Arne; Wellendorph, Petrine; Frølund, Bente

    2017-01-01

    , and several of these compounds have been shown to exhibit pronounced anticonvulsant activity in a variety of animal seizure models. As proof of concept of the validity of this drug development approach, one GABA-transport inhibitor, tiagabine, has been developed as a clinically active antiepileptic drug...

  13. Effects of β-hydroxy β-methyl butyrate supplementation to sows in late gestation on absorption and hepatic metabolism of glucose and amino acids during transition

    DEFF Research Database (Denmark)

    Flummer, Christine; Lyby, H; Storli, K S

    2012-01-01

    A multicatheter sow model was established to study the effects of dietary β-hydroxy β-methyl butyrate (HMB) supplementation on net portal flux (NPF) and net hepatic flux (NHF) of HMB, glucose, and the AA Ala, Gly, Ile, Leu, Phe, Tyr, and Val. Eight second parity sows were fitted with permanent...

  14. A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism.

    Science.gov (United States)

    Michaeli, Simon; Fait, Aaron; Lagor, Kelly; Nunes-Nesi, Adriano; Grillich, Nicole; Yellin, Ayelet; Bar, Dana; Khan, Munziba; Fernie, Alisdair R; Turano, Frank J; Fromm, Hillel

    2011-08-01

    In plants, γ-aminobutyric acid (GABA) accumulates in the cytosol in response to a variety of stresses. GABA is transported into mitochondria, where it is catabolized into TCA cycle or other intermediates. Although there is circumstantial evidence for mitochondrial GABA transporters in eukaryotes, none have yet been identified. Described here is an Arabidopsis protein similar in sequence and topology to unicellular GABA transporters. The expression of this protein complements a GABA-transport-deficient yeast mutant. Thus the protein was termed AtGABP to indicate GABA-permease activity. In vivo localization of GABP fused to GFP and immunobloting of subcellular fractions demonstrate its mitochondrial localization. Direct [(3) H]GABA uptake measurements into isolated mitochondria revealed impaired uptake into mitochondria of a gabp mutant compared with wild-type (WT) mitochondria, implicating AtGABP as a major mitochondrial GABA carrier. Measurements of CO(2) release, derived from radiolabeled substrates in whole seedlings and in isolated mitochondria, demonstrate impaired GABA-derived input into the TCA cycle, and a compensatory increase in TCA cycle activity in gabp mutants. Finally, growth abnormalities of gabp mutants under limited carbon availability on artificial media, and in soil under low light intensity, combined with their metabolite profiles, suggest an important role for AtGABP in primary carbon metabolism and plant growth. Thus, AtGABP-mediated transport of GABA from the cytosol into mitochondria is important to ensure proper GABA-mediated respiration and carbon metabolism. This function is particularly essential for plant growth under conditions of limited carbon. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  15. The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: a pilot [(11)C]Ro15-4513 positron emission tomography study.

    Science.gov (United States)

    Mendez, Maria Andreina; Horder, Jamie; Myers, Jim; Coghlan, Suzanne; Stokes, Paul; Erritzoe, David; Howes, Oliver; Lingford-Hughes, Anne; Murphy, Declan; Nutt, David

    2013-05-01

    GABA (gamma-amino-butyric-acid) is the primary inhibitory neurotransmitter in the human brain. It has been proposed that the symptoms of autism spectrum disorders (ASDs) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABAA receptors. However, this hypothesis has not been directly tested in living adults with ASD. In this preliminary investigation, we used Positron Emission Tomography (PET) with the benzodiazepine receptor PET ligand [(11)C]Ro15-4513 to measure α1 and α5 subtypes of the GABAA receptor levels in the brain of three adult males with well-characterized high-functioning ASD compared with three healthy matched volunteers. We found significantly lower [(11)C]Ro15-4513 binding throughout the brain of participants with ASD (p < 0.0001) compared with controls. Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally. Further analysis suggested that these results were driven by lower levels of the GABAA α5 subtype. These results provide initial evidence of a GABAA α5 deficit in ASD and support further investigations of the GABA system in this disorder. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans.

    Science.gov (United States)

    van der Beek, Christina M; Bloemen, Johanne G; van den Broek, Maartje A; Lenaerts, Kaatje; Venema, Koen; Buurman, Wim A; Dejong, Cornelis H

    2015-09-01

    Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration. The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange. Twelve patients (7 men; age: 66.4 ± 2.0 y; BMI 24.5 ± 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period. Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 ± 27.0 μmol/L vs. 14.3 ± 3.4 μmol/L, respectively; P butyrate-treated group, iAUCs of gut release (282.8 ± 133.8 μmol/kg BW · 0.5 h) and liver uptake (-293.7 ± 136.0 μmol/kg BW · 0.5 h) of butyrate were greater than in the placebo group [-16.6 ± 13.4 μmol/kg BW · 0.5 h (gut release) and 16.0 ± 13.8 μmol/kg BW · 0.5 h (liver uptake); P = 0.01 and P butyrate release did not differ between groups. After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802. © 2015 American Society for Nutrition.

  17. Endogenous synthesis of taurine and GABA in rat ocular tissues

    International Nuclear Information System (INIS)

    Heinaemaeki, A.A.

    1988-01-01

    The endogenous production of taurine and γ-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye. (author)

  18. Nanofibrillar self-organization of regioregular poly(3-hexylthiophene) and [6,6]-phenyl C61-butyric acid methyl ester by dip-coating: a simple method to obtain efficient bulk heterojunction solar cells

    International Nuclear Information System (INIS)

    Valentini, L; Bagnis, D; Kenny, J M

    2009-01-01

    In this paper the dip-coating technique has been investigated as a method for the production of regioregular poly(3-hexylthiophene) (RR-P3HT):[6,6]-phenyl C 61 -butyric acid methyl ester (PCBM)-based solar cells. We found that the utilization of the dip-coating technique for the RR-P3HT:PCBM system can facilitate its self-assembly into a nanofibrillar lamellar structure after evaporation of the solvent. The condition for the formation of the nanofibrillar structures leads to a power conversion efficiency of 3.6% by using only this approach without thermal treatment.

  19. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    Science.gov (United States)

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. γ-aminobutyric acid (GABA) mediated transmembrane chloride flux with membrane vesicles from rat brain measured by quench flow technique: kinetic homogeneity of ion flux and receptor desensitization

    International Nuclear Information System (INIS)

    Cash, D.J.; Subbarao, K.

    1987-01-01

    Transmembrane chloride flux mediated by the GABA/sub A/ receptor and the desensitization of the receptor were followed using quench flow technique with 36 Cl - and a membrane preparation from rat cerebral cortex. Measurements in short times allowed these two processes to be resolved. In general the ion-flux activity was desensitized in two phases. A fast phase took place in circa 200 ms (100 μM GABA) followed by a slower phase in several seconds. A minority of the membrane preparations did not display the fast phase. It is desirable to be able to separate these two phases of desensitization to facilitate analysis of the responses of the receptor. A short preincubation with GABA removed the fast phase from a subsequent measurement. In the absence of the fast phase the whole ion-flux equilibrium was seen as a single phase. The measurements presented covering a time range of 0.01 seconds to 10 seconds show a single phase of ion flux which can be described by a first order ion influx process and a single first order desensitization process with a halt time of circa 1 s (100 μM GABA). The results imply a single population of vesicles containing a single population of GABA receptor (remaining active) with a single phase of desensitization. An understanding of this homogeneity, and how to ensure it, gives a basis for quantitatively testing the effects of drugs on these responses. Ion flux measurements with quench flow technique are a suitable tool for investigation of the mechanism of action of neurotransmitter receptors from brain. 37 references, 3 figures

  1. Butyrate increases IL-23 production by stimulated dendritic cells

    Science.gov (United States)

    Berndt, Bradford E.; Zhang, Min; Owyang, Stephanie Y.; Cole, Tyler S.; Wang, Teresa W.; Luther, Jay; Veniaminova, Natalia A.; Merchant, Juanita L.; Chen, Chun-Chia; Huffnagle, Gary B.

    2012-01-01

    The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrow-derived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration. PMID:23086919

  2. In vitro effects of hydrochloric acid and various concentrations of acetic, propionic, butyric, or valeric acids on bioelectric properties of equine gastric squamous mucosa.

    Science.gov (United States)

    Andrews, Frank M; Buchanan, Benjamin R; Smith, Sionagh H; Elliott, Sarah B; Saxton, Arnold M

    2006-11-01

    To compare the effects of hydrochloric acid (HCl) and various concentrations of volatile fatty acids (VFAs) on tissue bioelectric properties of equine stomach nonglandular (NG) mucosa. Gastric tissues obtained from 48 adult horses. NG gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured and electrical resistance (R) and conductance calculated for tissues after addition of HCl and VFAs (5, 10, 20, and 40 mM) in normal Ringer's solution (NRS). Mucosa exposed to HCl in NRS (pH of 1.5 and, to a lesser extent, 4.0) had a significant decrease in Isc, PD, and R, whereas tissues exposed to acetic acid at a pH of acids at a pH of acid at a pH of acid at a pH of acid, in the presence of HCl at a pH of

  3. Strategies for production of butanol and butyl-butyrate through lipase-catalyzed esterification.

    Science.gov (United States)

    Xin, Fengxue; Basu, Anindya; Yang, Kun-Lin; He, Jianzhong

    2016-02-01

    In this study, a fermentation process for production of butanol and butyl-butyrate by using Clostridium sp. strain BOH3 is developed. This strain is able to produce butyric acid and butanol when it ferments 60 g/L xylose. Meanwhile, it also excreted indigenous lipases (induced by olive oil) which naturally convert butyric acid and butanol into 1.2 g/L of butyl-butyrate. When Bio-OSR was used as both an inducer for lipase and extractant for butyl-butyrate, the butyl-butyrate concentration can reach 6.3 g/L. To further increase the yield, additional lipases and butyric acid are added to the fermentation system. Moreover, kerosene was used as an extractant to remove butyl-butyrate in situ. When all strategies are combined, 22.4 g/L butyl-butyrate can be produced in a fed-batch reactor spiked with 70 g/L xylose and 7.9 g/L butyric acid, which is 4.5-fold of that in a similar system (5 g/L) with hexadecane as the extractant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Glutamate and GABA in appetite regulation

    Directory of Open Access Journals (Sweden)

    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  5. Accumulation, selection and covariation of amino acids in sieve tube sap of tansy (Tanacetum vulgare) and castor bean (Ricinus communis): evidence for the function of a basic amino acid transporter and the absence of a γ-amino butyric acid transporter.

    Science.gov (United States)

    Bauer, Susanne N; Nowak, Heike; Keller, Frank; Kallarackal, Jose; Hajirezaei, Mohamad-Reza; Komor, Ewald

    2014-09-01

    Sieve tube sap was obtained from Tanacetum by aphid stylectomy and from Ricinus after apical bud decapitation. The amino acids in sieve tube sap were analyzed and compared with those from leaves. Arginine and lysine accumulated in the sieve tube sap of Tanacetum more than 10-fold compared to the leaf extracts and they were, together with asparagine and serine, preferably selected into the sieve tube sap, whereas glycine, methionine/tryptophan and γ-amino butyric acid were partially or completely excluded. The two basic amino acids also showed a close covariation in sieve tube sap. The acidic amino acids also grouped together, but antagonistic to the other amino acids. The accumulation ratios between sieve tube sap and leaf extracts were smaller in Ricinus than in Tanacetum. Arginine, histidine, lysine and glutamine were enriched and preferentially loaded into the phloem, together with isoleucine and valine. In contrast, glycine and methionine/tryptophan were partially and γ-amino butyric acid almost completely excluded from sieve tube sap. The covariation analysis grouped arginine together with several neutral amino acids. The acidic amino acids were loaded under competition with neutral amino acids. It is concluded from comparison with the substrate specificities of already characterized plant amino acid transporters, that an AtCAT1-like transporter functions in phloem loading of basic amino acids, whereas a transporter like AtGAT1 is absent in phloem. Although Tanacetum and Ricinus have different minor vein architecture, their phloem loading specificities for amino acids are relatively similar. © 2014 Scandinavian Plant Physiology Society.

  6. In vitro and in vivo study of transcriptome alternation induced by butyrate in cattle using deep RNA-seq

    Science.gov (United States)

    Short-chain fatty acids (SCFAs,), especially butyrate, affect cell differentiation, proliferation, and motility. Furthermore, butyrate induces cell cycle arrest and apoptosis through its inhibition on histone deacetylases (HDACs). Butyrate is a potent inducer of histone hyper-acetylation in cells a...

  7. THE SIGNIFICANCE OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA OF THE RAT DURING SEIZURES AND ANTICONVULSANT TREATMENTS

    NARCIS (Netherlands)

    SAYIN, U; TIMMERMAN, W; WESTERINK, BHC

    1995-01-01

    The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold

  8. The Glutamine-Glutamate/GABA Cycle

    DEFF Research Database (Denmark)

    Walls, Anne B; Waagepetersen, Helle S; Bak, Lasse Kristoffer

    2015-01-01

    The operation of a glutamine-glutamate/GABA cycle in the brain consisting of the transfer of glutamine from astrocytes to neurons and neurotransmitter glutamate or GABA from neurons to astrocytes is a well-known concept. In neurons, glutamine is not only used for energy production and protein...... synthesis, as in other cells, but is also an essential precursor for biosynthesis of amino acid neurotransmitters. An excellent tool for the study of glutamine transfer from astrocytes to neurons is [(14)C]acetate or [(13)C]acetate and the glial specific enzyme inhibitors, i.e. the glutamine synthetase...... inhibitor methionine sulfoximine and the tricarboxylic acid cycle (aconitase) inhibitors fluoro-acetate and -citrate. Acetate is metabolized exclusively by glial cells, and [(13)C]acetate is thus capable when used in combination with magnetic resonance spectroscopy or mass spectrometry, to provide...

  9. An Electrostatic Funnel in the GABA-Binding Pathway.

    Directory of Open Access Journals (Sweden)

    Timothy S Carpenter

    2016-04-01

    Full Text Available The γ-aminobutyric acid type A receptor (GABAA-R is a major inhibitory neuroreceptor that is activated by the binding of GABA. The structure of the GABAA-R is well characterized, and many of the binding site residues have been identified. However, most of these residues are obscured behind the C-loop that acts as a cover to the binding site. Thus, the mechanism by which the GABA molecule recognizes the binding site, and the pathway it takes to enter the binding site are both unclear. Through the completion and detailed analysis of 100 short, unbiased, independent molecular dynamics simulations, we have investigated this phenomenon of GABA entering the binding site. In each system, GABA was placed quasi-randomly near the binding site of a GABAA-R homology model, and atomistic simulations were carried out to observe the behavior of the GABA molecules. GABA fully entered the binding site in 19 of the 100 simulations. The pathway taken by these molecules was consistent and non-random; the GABA molecules approach the binding site from below, before passing up behind the C-loop and into the binding site. This binding pathway is driven by long-range electrostatic interactions, whereby the electrostatic field acts as a 'funnel' that sweeps the GABA molecules towards the binding site, at which point more specific atomic interactions take over. These findings define a nuanced mechanism whereby the GABAA-R uses the general zwitterionic features of the GABA molecule to identify a potential ligand some 2 nm away from the binding site.

  10. Butyrate influences intracellular levels of adenine and adenine derivatives in the fungus Penicillium restrictum.

    Science.gov (United States)

    Zutz, Christoph; Chiang, Yi Ming; Faehnrich, Bettina; Bacher, Markus; Hellinger, Roland; Kluger, Bernhard; Wagner, Martin; Strauss, Joseph; Rychli, Kathrin

    2017-04-01

    Butyrate, a small fatty acid, has an important role in the colon of ruminants and mammalians including the inhibition of inflammation and the regulation of cell proliferation. There is also growing evidence that butyrate is influencing the histone structure in mammalian cells by inhibition of histone deacetylation. Butyrate shows furthermore an antimicrobial activity against fungi, yeast and bacteria, which is linked to its toxicity at a high concentration. In fungi there are indications that butyrate induces the production of secondary metabolites potentially via inhibition of histone deacetylases. However, information about the influence of butyrate on growth, primary metabolite production and metabolism, besides lipid catabolism, in fungi is scarce. We have identified the filamentous fungus Penicillium (P.) restrictum as a susceptible target for butyrate treatment in an antimicrobial activity screen. The antimicrobial activity was detected only in the mycelium of the butyrate treated culture. We investigated the effect of butyrate ranging from low (0.001mM) to high (30mM), potentially toxic, concentrations on biomass and antimicrobial activity. Butyrate at high concentrations (3 and 30mM) significantly reduced the fungal biomass. In contrast P. restrictum treated with 0.03mM of butyrate showed the highest antimicrobial activity. We isolated three antimicrobial active compounds, active against Staphylococcus aureus, from P. restrictum cellular extracts treated with butyrate: adenine, its derivate hypoxanthine and the nucleoside derivate adenosine. Production of all three compounds was increased at low butyrate concentrations. Furthermore we found that butyrate influences the intracellular level of the adenine nucleoside derivate cAMP, an important signalling molecule in fungi and various organisms. In conclusion butyrate treatment increases the intracellular levels of adenine and its respective derivatives. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Butyrate Specifically Down-Regulates Salmonella Pathogenicity Island 1 Gene Expression

    OpenAIRE

    Gantois, I.; Ducatelle, R.; Pasmans, F.; Haesebrouck, F.; Hautefort, I.; Thompson, A.; Hinton, J. C.; Van Immerseel, F.

    2006-01-01

    Invasion of intestinal epithelial cells by Salmonella enterica is decreased after exposure to butyric acid. To understand the molecular mechanisms of this phenomenon, a comparative transcriptomic analysis of Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium grown in medium supplemented with butyrate was performed. We found that butyrate down-regulated the expression of 19 genes common to both serovars by a factor of twofold or more, and 17 of these genes loca...

  12. Spatial distributions of GABA receptors and local inhibition of Ca2+ transients studied with GABA uncaging in the dendrites of CA1 pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yuya Kanemoto

    Full Text Available GABA (γ-amino-butylic acid-mediated inhibition in the dendrites of CA1 pyramidal neurons was characterized by two-photon uncaging of a caged-GABA compound, BCMACM-GABA, and one-photon uncaging of RuBi-GABA in rat hippocampal slice preparations. Although we found that GABA(A-mediated currents were diffusely distributed along the dendrites, currents elicited at the branch points of the apical dendritic trunk were approximately two times larger than those elsewhere in the dendrite. We examined the inhibitory action of the GABA-induced currents on Ca(2+ transients evoked with a single back-propagating action potential (bAP in oblique dendrites. We found that GABA uncaging selectively inhibited the Ca(2+ transients in the region adjacent (20 µm. Our data indicate that GABA inhibition results in spatially confined inhibition of Ca(2+ transients shortly after bAP, and suggest that this effect is particularly potent at the dendritic branch points where GABA receptors cluster.

  13. Immunocytochemical mapping of an RDL-like GABA receptor subunit and of GABA in brain structures related to learning and memory in the cricket Acheta domesticus.

    Science.gov (United States)

    Strambi, C; Cayre, M; Sattelle, D B; Augier, R; Charpin, P; Strambi, A

    1998-01-01

    The distribution of putative RDL-like GABA receptors and of gamma-aminobutyric acid (GABA) in the brain of the adult house cricket Acheta domesticus was studied using specific antisera. Special attention was given to brain structures known to be related to learning and memory. The main immunostaining for the RDL-like GABA receptor was observed in mushroom bodies, in particular the upper part of mushroom body peduncle and the two arms of the posterior calyx. Weaker immunostaining was detected in the distal part of the peduncle and in the alpha and beta lobes. The dorso- and ventrolateral protocerebrum neuropils appeared rich in RDL-like GABA receptors. Staining was also detected in the glomeruli of the antennal lobe, as well as in the ellipsoid body of the central complex. Many neurons clustered in groups exhibit GABA-like immunoreactivity. Tracts that were strongly immunostained innervated both the calyces and the lobes of mushroom bodies. The glomeruli of the antennal lobe, the ellipsoid body, as well as neuropils of the dorso- and ventrolateral protocerebrum were also rich in GABA-like immunoreactivity. The data demonstrated a good correlation between the distribution of the GABA-like and of the RDL-like GABA receptor immunoreactivity. The prominent distribution of RDL-like GABA receptor subunits, in particular areas of mushroom bodies and antennal lobes, underlines the importance of inhibitory signals in information processing in these major integrative centers of the insect brain.

  14. Liquid-liquid equilibrium data in aqueous solutions of propionic and butyric acids with 1-heptanol at T=(298.15, 308.15, and 318.15) K

    International Nuclear Information System (INIS)

    Gilani, Ali Ghanadzadeh; Gilani, Hossein Ghanadzadeh; Saadat, Seyedeh Laleh Seyed; Nasiri-Touli, Elham; Peer, Mahrokh

    2016-01-01

    Liquid-liquid phase equilibrium (LLE) data were determined for the (water+propionic or butyric acid+1- heptanol) ternary systems at T=(298.15, 308.15, and 318.15) K and p=101.3 kPa. For both systems, a type-1 LLE phase diagram was obtained. The quality of the experimental LLE data was determined through the Othmer-Tobias and Bancroft equations. The experimental tie-lines were fitted using the UNIQUAC and NRTL correlation models. For the studied systems, a comparison was made between the experimental and correlated distribution coefficients and separation factors. The LSER model of Katritzky was applied to obtain the contributions of intermolecular interactions in these systems.

  15. Selective agonists at group II metabotropic glutamate receptors: synthesis, stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Bräuner-Osborne, Hans; Greenwood, Jeremy R

    2002-01-01

    )-form of the 1,2,5-thiadiazol-3-ol Glu analogue, 2-amino-3-(4-hydroxy[1,2,5]thiadiazol-3-yl)propionic acid (TDPA, 6), is an 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, which in addition stereospecifically activates group I mGluRs. We have now synthesized the (S)- and (R......Homologation of analogues of the central excitatory neurotransmitter glutamic acid (Glu), in which the distal carboxy group has been bioisosterically replaced by acidic heterocyclic units, has previously provided subtype selective ligands for metabotropic Glu receptors (mGluRs). The (S......)-forms of 2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid (homo-TDPA, 7) and shown that whereas neither enantiomer interacts with AMPA receptors, (S)- and (R)-7 appear to be selective and equipotent agonists at group II mGluRs as represented by the mGluR2 subtype. The activities of (S)- and (R)-7...

  16. Synchronization by Food Access Modifies the Daily Variations in Expression and Activity of Liver GABA Transaminase

    Directory of Open Access Journals (Sweden)

    Dalia De Ita-Pérez

    2014-01-01

    Full Text Available Daytime restricted feeding (DRF is an experimental protocol that influences the circadian timing system and underlies the expression of a biological clock known as the food entrained oscillator (FEO. Liver is the organ that reacts most rapidly to food restriction by adjusting the functional relationship between the molecular circadian clock and the metabolic networks. γ-Aminobutyric acid (GABA is a signaling molecule in the liver, and able to modulate the cell cycle and apoptosis. This study was aimed at characterizing the expression and activity of the mostly mitochondrial enzyme GABA transaminase (GABA-T during DRF/FEO expression. We found that DRF promotes a sustained increase of GABA-T in the liver homogenate and mitochondrial fraction throughout the entire day-night cycle. The higher amount of GABA-T promoted by DRF was not associated to changes in GABA-T mRNA or GABA-T activity. The GABA-T activity in the mitochondrial fraction even tended to decrease during the light period. We concluded that DRF influences the daily variations of GABA-T mRNA levels, stability, and catalytic activity of GABA-T. These data suggest that the liver GABAergic system responds to a metabolic challenge such as DRF and the concomitant appearance of the FEO.

  17. Mechanisms involved in enhancement of apoptosis by radiation or hyperthermia in combination with sodium butyrate

    International Nuclear Information System (INIS)

    Wei, Z.L.; Zhao, Q.L.; Hassan, M.A.; Kondo, Takashi

    2010-01-01

    Sodium butyrate is a four-carbon fatty acid and natural component of the colonic milieu. Butyrate has been shown to induce apoptosis in numerous types of cancer cells, and received much attention as a potential chemopreventive agent for colorectal cancer. However, during initial clinical trials, its efficacy was limited. X-irradiation or hyperthermia as an adjuvant significantly enhanced the cell growth arrest, alteration of the cell cycle, and cell death caused by butyrate. The balance between anti-apoptotic and pro-apoptotic Bcl-2 family proteins was lost and a mitochondrial pathway was activated. In this review, the interactions of butyrate with X-irradiation and hyperthermia are discussed. (author)

  18. GABA shapes the dynamics of bistable perception.

    Science.gov (United States)

    van Loon, Anouk M; Knapen, Tomas; Scholte, H Steven; St John-Saaltink, Elexa; Donner, Tobias H; Lamme, Victor A F

    2013-05-06

    Sometimes, perception fluctuates spontaneously between two distinct interpretations of a constant sensory input. These bistable perceptual phenomena provide a unique window into the neural mechanisms that create the contents of conscious perception. Models of bistable perception posit that mutual inhibition between stimulus-selective neural populations in visual cortex plays a key role in these spontaneous perceptual fluctuations. However, a direct link between neural inhibition and bistable perception has not yet been established experimentally. Here, we link perceptual dynamics in three distinct bistable visual illusions (binocular rivalry, motion-induced blindness, and structure from motion) to measurements of gamma-aminobutyric acid (GABA) concentrations in human visual cortex (as measured with magnetic resonance spectroscopy) and to pharmacological stimulation of the GABAA receptor by means of lorazepam. As predicted by a model of neural interactions underlying bistability, both higher GABA concentrations in visual cortex and lorazepam administration induced slower perceptual dynamics, as reflected in a reduced number of perceptual switches and a lengthening of percept durations. Thus, we show that GABA, the main inhibitory neurotransmitter, shapes the dynamics of bistable perception. These results pave the way for future studies into the competitive neural interactions across the visual cortical hierarchy that elicit conscious perception. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Measuring the longitudinal relaxation time of GABA in vivo at 3 Tesla.

    Science.gov (United States)

    Puts, Nicolaas A J; Barker, Peter B; Edden, Richard A E

    2013-04-01

    To measure the in vivo longitudinal relaxation time T1 of GABA at 3 Tesla (T). J-difference edited single-voxel MR spectroscopy was used to isolate γ-aminobutyric acid (GABA) signals. An increased echo time (80 ms) acquisition was used, accommodating the longer, more selective editing pulses required for symmetric editing-based suppression of co-edited macromolecular signal. Acquiring edited GABA measurements at a range of relaxation times in 10 healthy participants, a saturation-recovery equation was used to model the integrated data. The longitudinal relaxation time of GABA was measured as T(1,GABA) = 1.31 ± 0.16 s. The method described has been successfully applied to measure the T1 of GABA in vivo at 3T. Copyright © 2012 Wiley Periodicals, Inc.

  20. Contribution of the GABA shunt to hypoxia-induced alanine accumulation in roots of Arabidopsis thaliana.

    Science.gov (United States)

    Miyashita, Yo; Good, Allen G

    2008-01-01

    When subjected to low oxygen stress, plants accumulate alanine and gamma-aminobutyric acid (GABA). To investigate the function of GABA metabolism under hypoxia and its contribution to alanine accumulation, we studied the genes that encode the two key enzymes of the GABA shunt, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T). Among the five homologous GAD genes found in Arabidopsis thaliana, GAD1 expression was predominantly found in roots, while GAD2 expression was evident in all organs. Expression of the other three GAD genes was generally weak. In response to hypoxia, transcriptional induction was observed for GAD4 only. For GABA-T1, its expression was detected in all organs, but there was no significant transcriptional change under hypoxic conditions. Moreover, we have isolated and characterized Arabidopsis mutants defective in GAD1 and GABA-T1. In gad1 mutants, GAD activity was significantly reduced in roots but was not affected in shoots. In the gaba-t1 mutant, GABA-T activity was decreased to negligible levels in both shoots and roots. These mutants were phenotypically normal under normal growth conditions except for the reduced seed production of the pop2 mutants as described previously. However, metabolite analysis revealed significant changes in GABA content in gad1 and gaba-t1 mutants. The levels of alanine under hypoxic conditions were also affected in the roots of gad1 and gaba-t1 mutants. The partial inhibition of the hypoxia-induced alanine accumulation in roots of these mutants suggests that the GABA shunt is, in part, responsible for the alanine accumulation under hypoxia.

  1. Glutamate modulation of GABA transport in retinal horizontal cells of the skate

    Science.gov (United States)

    Kreitzer, Matthew A; Andersen, Kristen A; Malchow, Robert Paul

    2003-01-01

    Transport of the amino acid GABA into neurons and glia plays a key role in regulating the effects of GABA in the vertebrate retina. We have examined the modulation of GABA-elicited transport currents of retinal horizontal cells by glutamate, the likely neurotransmitter of vertebrate photoreceptors. Enzymatically isolated external horizontal cells of skate were examined using whole-cell voltage-clamp techniques. GABA (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors tiagabine (10 μm) and SKF89976-A (100 μm), but was unaffected by 100 μm picrotoxin. Prior application of 100 μm glutamate significantly reduced the GABA-elicited current. Glutamate depressed the GABA dose-response curve without shifting the curve laterally or altering the voltage dependence of the current. The ionotropic glutamate receptor agonists kainate and AMPA also reduced the GABA-elicited current, and the effects of glutamate and kainate were abolished by the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline. NMDA neither elicited a current nor modified the GABA-induced current, and metabotropic glutamate analogues were also without effect. Inhibition of the GABA-elicited current by glutamate and kainate was reduced when extracellular calcium was removed and when recording pipettes contained high concentrations of the calcium chelator BAPTA. Caffeine (5 mm) and thapsigargin (2 nm), agents known to alter intracellular calcium levels, also reduced the GABA-elicited current, but increases in calcium induced by depolarization alone did not. Our data suggest that glutamate regulates GABA transport in retinal horizontal cells through a calcium-dependent process, and imply a close physical relationship between calcium-permeable glutamate receptors and GABA transporters in these cells. PMID:12562999

  2. Sodium-independent, bicuculline-sensitive [3H]GABA binding to isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Minuk, G.Y.; Bear, C.E.; Sarjeant, E.J.

    1987-01-01

    To determine whether hepatocytes possess specific receptor sites for gamma-aminobutyric acid (GABA), a potent amino acid neurotransmitter, [ 3 H]GABA, was added to sodium-free suspensions of Percoll-purified hepatocytes derived from collagenase-perfused rat livers under various experimental conditions and in the presence or absence of specific GABA receptor agonists (muscimol) and antagonists (bicuculline). The effects of GABA, muscimol, and bicuculline on hepatocyte resting membrane potentials were also determined. Specific binding of [ 3 H]GABA to hepatocytes was a consistent finding. GABA-hepatocyte interactions were reversible and temperature dependent. Muscimol and bicuculline inhibited binding in a dose-dependent manner (IC50, 30 nM and 50 microM, respectively), whereas strychnine (1.0-100 microM), a nonspecific central nervous system stimulant, had no appreciable effect. Both GABA and muscimol (100 microM) caused significant hyperpolarization of hepatocyte resting membrane potential (delta PD 5.4 +/- 3.1 and 22.2 +/- 16.2 mV, respectively, means +/- SD, P less than 0.0005). Bicuculline (100 microM) inhibited the effect of muscimol (P less than 0.05). The results of this study suggest that specific GABA receptor sites exist on the surface of isolated rat hepatocytes. The presence of such sites raises the possibility that, in addition to adrenergic and cholinergic innervation, hepatic function may be influenced by GABA-ergic neurotransmitter mechanisms

  3. A study on quality components and sleep-promoting effects of GABA black tea.

    Science.gov (United States)

    Zhao, Wenfang; Li, Yun; Ma, William; Ge, Yazhong; Huang, Yahui

    2015-10-01

    The aims of this study were to analyze the changes in quality components of gamma (γ)-aminobutyric acid (GABA) black tea during processing, and to investigate the effect of three dosages of GABA black tea on sleep improvement. The results showed that the GABA content was increased significantly up to 2.70 mg g(-1) after vacuum anaerobic and aerobic treatment. In addition, the content of GABA after drying reached 2.34 mg g(-1), which achieved the standard of GABA tea. During the entire processing of GABA black tea, the contents of tea polyphenols, caffeine and total catechins displayed a gradually descending trend, while the contents of free amino acids and GABA were firstly increased, and then reduced. The GABA black tea had significant effects on prolonging the sleeping time with sodium pentobarbital (P sleeping rate induced by sodium pentobarbital at a sub-threshold dose (P sleeping latency period induced by sodium barbital was not significant (P > 0.05). It had no effect on directly inducing sleep and the mouse body weight. The extract of GABA black tea improved the sleeping quality of mice to extend with an optimal effect being found in the high dose-treated mice.

  4. Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard

    2013-01-01

    β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

  5. The effects of butyrate enemas on visceral perception in healthy volunteers

    NARCIS (Netherlands)

    Vanhoutvin, S.A.L.W.; Troost, F.J.; Kilkens, T.O.C.; Lindsey, P.J.; Hamer, H.M.; Jonkers, D.M.A.E.; Venema, K.; Brummer, R.-J.M.

    2009-01-01

    Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and

  6. GABA receptors and benzodiazepine binding sites modulate hippocampal acetylcholine release in vivo

    NARCIS (Netherlands)

    Moor, E; de Boer, P; Westerink, B.H.C.

    1998-01-01

    In the present study, the regulation of acetylcholine release from the ventral hippocampus by gamma-aminobutyric acid (GABA) was investigated in vivo. GABA receptor agonists and antagonists were administered locally in the medial septum and the adjacent vertical limb of the diagonal band of Broca,

  7. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    DEFF Research Database (Denmark)

    Carvill, Gemma L; McMahon, Jacinta M; Schneider, Amy

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutatio...

  8. Molecular basis of the alternative recruitment of GABA(A) versus glycine receptors through gephyrin

    DEFF Research Database (Denmark)

    Maric, Hans-Michael; Kasaragod, Vikram Babu; Hausrat, Torben Johann

    2014-01-01

    γ-Aminobutyric acid type A and glycine receptors (GABA(A)Rs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABA(A)Rs are important drug targets regulated by direct interactions with the scaffolding protein ge...

  9. CHARACTERIZATION OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA-RETICULATA BY MEANS OF BRAIN MICRODIALYSIS

    NARCIS (Netherlands)

    TIMMERMAN, W; ZWAVELING, J; WESTERINK, BHC

    Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4-8 h after surgery; day 1) and chronically implanted probes

  10. Regulation of gaba neurotransmisson in the nigrostiatal stystem of the rat brain.

    NARCIS (Netherlands)

    Heyden, Johannes Antonius Maria van der

    1980-01-01

    The aminoacid γ-aminobutyric acid (GABA) occurs throughout the brain and spinal cord and its role as a major inhibitory neurotransmitter is generally accepted. Though several human disease states are claimed to involve a deranged GABA rnetabolism, the causal relationship between such a dysfunction

  11. Restoration of GABA production machinery in Lactobacillus brevis by accessible carbohydrates, anaerobiosis and early acidification.

    Science.gov (United States)

    Wu, Qinglong; Shah, Nagendra P

    2018-02-01

    Lactobacillus brevis is an efficient cell factory for producing bioactive γ-aminobutyric acid (GABA) by its gad operon-encoded glutamic acid decarboxylase (GAD) system. However, little mechanistic insights have been reported on the effects of carbohydrate, oxygen and early acidification on GABA production machinery in Lb. brevis. In the present study, GABA production from Lb. brevis was enhanced by accessible carbohydrates. Fast growth of this organism was stimulated by maltose and xylose. However, its GABA production was highly suppressed by oxygen exposure, but was fully restored by anaerobiosis that up-regulated the expression of gad operon in Lb. brevis cells. Although the level of cytosolic acidity was suitable for the functioning of GadA and GadB, early acidification of the medium (ipH 5 and ipH 4) restored GABA synthesis strictly in aerated cells of Lb. brevis because the expression of gad operon was not up-regulated in them. We conclude that GABA production machinery in Lb. brevis could be restored by accessible carbohydrates, anaerobiosis and early acidification. This will be of interest for controlling fermentation for synthesis of GABA and manufacturing GABA-rich fermented vegetables. Copyright © 2017. Published by Elsevier Ltd.

  12. Biosynthesis of heparin. Effects of n-butyrate on cultured mast cells

    International Nuclear Information System (INIS)

    Jacobsson, K.G.; Riesenfeld, J.; Lindahl, U.

    1985-01-01

    Murine mastocytoma cells were incubated in vitro with inorganic [ 35 S]sulfate, in the absence or presence of 2.5 mM n-butyrate, and labeled heparin was isolated. The polysaccharide produced in the presence of butyrate showed a lower charge density on anion exchange chromatography than did the control material and a 3-fold increased proportion of components with high affinity for antithrombin. Structural analysis of heparin labeled with [ 3 H] glucosamine in the presence of butyrate showed that approximately 35% of the glucosamine units were N-acetylated, as compared to approximately 10% in the control material; the nonacetylated glucosamine residues were N-sulfated. The presence of butyrate thus leads to an inhibition of the N-deacetylation/N-sulfation process in heparin biosynthesis, along with an augmented formation of molecules with high affinity for antithrombin. Preincubation of the mastocytoma cells with butyrate was required for manifestation of either effect; when the preincubation period was reduced from 24 to 10 h the effects of butyrate were no longer observed. A polysaccharide formed on incubating mastocytoma microsomal fraction with UDP-[ 3 H]glucuronic acid, UDP-N-acetylglucosamine, and 3'-phosphoadenylylsulfate in the presence of 5 mM butyrate showed the same N-acetyl/N-sulfate ratio as did the corresponding control polysaccharide, produced in the absence of butyrate. These findings suggest that the effect of butyrate on heparin biosynthesis depends on the integrity of the cell

  13. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats.

    Science.gov (United States)

    Zhang, Mingming; Zhou, Qian; Dorfman, Robert G; Huang, Xiaoli; Fan, Tingting; Zhang, Hao; Zhang, Jun; Yu, Chenggong

    2016-07-30

    Butyrate is an energy source for colonocytes that is formed by bacterial fermentation of dietary fiber in the colon and that exerts broad anti-inflammatory activities. Although the administration of butyrate improves homeostasis in patients and ameliorates IBD (Inflammatory Bowel Disease)-related lesions and symptoms, the anti-inflammatory mechanisms of butyrate still remain unclear. To explore the impact of butyrate on Treg (Regulatory T cell)/Th17 (T helper 17 cell) differentiation and colitis in rats. The effect of butyrate on the expression of markers related to both Tregs and Th17 cells were determined in human monocytes as well as a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Rats were treated with butyrate in vivo, whereas the rat splenocytes and human monocytes were treated in vitro. We found that butyrate administration increased peripheral blood Treg cell levels as well as plasma levels of anti-Th17 cytokines (IL-10 and IL-12). Butyrate administration further suppressed IL-17 levels in both plasma and colonic mucosa, and ameliorated colonic colitis lesions in rats. This promotion of Treg activity and inhibition of IL-17 release was also observed in human venous monocytes and rat splenocytes in vitro. Our results suggest that butyrate plays a key role in regulating the Treg/Th17 balance and ultimately protects the colon mucosa against the development of IBD.

  14. Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3

    Science.gov (United States)

    Li, Huating; Gao, Zhanguo; Zhang, Jin; Ye, Xin; Xu, Aimin; Ye, Jianping; Jia, Weiping

    2012-01-01

    Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator–activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3. PMID:22338096

  15. Comparative Mapping of GABA-Immunoreactive Neurons in the Buccal Ganglia of Nudipleura Molluscs.

    Science.gov (United States)

    Gunaratne, Charuni A; Katz, Paul S

    2016-04-15

    Phylogenetic comparisons of neurotransmitter distribution are important for understanding the ground plan organization of nervous systems. This study describes the γ-aminobutyric acid (GABA)-immunoreactive (GABA-ir) neurons in the buccal ganglia of six sea slug species (Mollusca, Gastropoda, Euthyneura, Nudipleura). In the nudibranch species, Hermissenda crassicornis, Tritonia diomedea, Tochuina tetraquetra, and Dendronotus iris, the number of GABA-ir neurons was highly consistent. Another nudibranch, Melibe leonina, however, contained approximately half the number of GABA-ir neurons. This may relate to its loss of a radula and its unique feeding behavior. The GABA immunoreactivity in a sister group to the nudibranchs, Pleurobranchaea californica, differed drastically from that of the nudibranchs. Not only did it have significantly more GABA-ir neurons but it also had a unique GABA distribution pattern. Furthermore, unlike the nudibranchs, the Pleurobranchaea GABA distribution was also different from that of other, more distantly related, euopisthobranch and panpulmonate snails and slugs. This suggests that the Pleurobranchaea GABA distribution may be a derived feature, unique to this lineage. The majority of GABA-ir axons and neuropil in the Nudipleura were restricted to the buccal ganglia, commissures, and connectives. However, in Tritonia and Pleurobranchaea, we detected a few GABA-ir fibers in buccal nerves that innervate feeding muscles. Although the specific functions of the GABA-ir neurons in the species in this study are not known, the innervation pattern suggests these neurons may play an integrative or regulatory role in bilaterally coordinated behaviors in the Nudipleura. © 2015 Wiley Periodicals, Inc.

  16. Stimulation of butyrate absorption in the human rectum in vivo

    DEFF Research Database (Denmark)

    Holtug, K; Hove, H; Mortensen, P B

    1995-01-01

    the change in fluid composition. RESULTS: Sodium absorption was highest (24 +/- 8 mumol/cm2 h) in the presence of chloride and lowest (16 +/- 2 mumol/cm2 h) in the presence of bicarbonate and butyrate. Butyrate (70 mmol/l) was absorbed at a high rate of 7.1 +/- 2.2 mumol/cm2 h, independent on the presence...... of chloride, and was accompanied by increased bicarbonate secretion. Butyrate absorption increased to 9.6 +/- 1.8 mumol/cm2 h in sodium-free high-potassium media containing bicarbonate. CONCLUSION: The results show that it is possible to increase butyrate uptake by manipulation of the electrolyte composition......BACKGROUND: Models of short-chain fatty acid absorption have focused on the stimulation of sodium absorption, an effect mainly located in the proximal colon of man. With the present efforts to utilize butyrate enemas as a treatment of ulcerative colitis, it seemed important to assess the transport...

  17. Big GABA : Edited MR spectroscopy at 24 research sites

    NARCIS (Netherlands)

    Mikkelsen, Mark; Barker, Peter B; Bhattacharyya, Pallab K; Brix, Maiken K; Buur, Pieter F; Cecil, Kim M; Chan, Kimberly L; Chen, David Y-T; Craven, Alexander R; Cuypers, Koen; Dacko, Michael; Duncan, Niall W; Dydak, Ulrike; Edmondson, David A; Ende, Gabriele; Ersland, Lars; Gao, Fei; Greenhouse, Ian; Harris, Ashley D; He, Naying; Heba, Stefanie; Hoggard, Nigel; Hsu, Tun-Wei; Jansen, Jacobus F A; Kangarlu, Alayar; Lange, Thomas; Lebel, R Marc; Li, Yan-Mei; Lin, Chien-Yuan E; Liou, Jy-Kang; Lirng, Jiing-Feng; Liu, Feng; Ma, Ruoyun; Maes, Celine; Moreno-Ortega, Marta; Murray, Scott O; Noah, Sean; Noeske, Ralph; Noseworthy, Michael D; Oeltzschner, Georg; Prisciandaro, James J; Puts, Nicolaas A J; Roberts, Timothy P L; Sack, Markus; Sailasuta, Napapon; Saleh, Muhammad G; Schallmo, Michael-Paul; Simard, Nicholas; Swinnen, Stephan P; Tegenthoff, Martin; Truong, Peter; Wang, Guangbin; Wilkinson, Iain D; Wittsack, Hans-Jörg; Xu, Hongmin; Yan, Fuhua; Zhang, Chencheng; Zipunnikov, Vadim; Zöllner, Helge J; Edden, Richard A E

    Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition

  18. Role of proline and GABA in sexual reproduction of angiosperms

    Directory of Open Access Journals (Sweden)

    Marco eBiancucci

    2015-09-01

    Full Text Available Two glutamate derivatives, proline and γ-aminobutyric acid (GABA, appear to play pivotal roles in different aspects of sexual reproduction in angiosperms, although their precise function in plant reproduction and the molecular basis of their action are not yet fully understood. Proline and GABA have long been regarded as pivotal amino acids in pollen vitality and fertility. Proline may constitute up to 70% of the free amino acid pool in pollen grains and it has been recently shown that Arabidopsis mutants affected in the first and rate-limiting step in proline synthesis produce aberrant and infertile pollen grains, indicating that proline synthesis is required for pollen development and fertility. Concerning GABA, a large body of evidence points to this glutamate derivative as a key determinant of post-pollination fertilization. Intriguingly, proline has also been associated with pollination, another aspect of sexual reproduction, since honeybees were reported to show a strong preference for proline-enriched nectars. In this review, we survey current knowledge on the roles of proline and GABA in plant fertility, and discuss future perspectives potentially capable to improve our understanding on the functions of these amino acids in pollen development, pollination, and pollen tube guidance.

  19. Actions of insecticides on the insect GABA receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J. (School of Biological and Molecular Sciences, Oxford Polytechnic, Headington, Oxford (England))

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using (35S)t-butylbicyclophosphorothionate (( 35S)TBPS) binding and voltage-clamp techniques. Specific binding of (35S)TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 {plus minus} 2.9 nM and a Bmax value of 1770 {plus minus} 40 fmol/mg protein. (35S)TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of (35S)TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on (35S)TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current.

  20. Actions of insecticides on the insect GABA receptor complex

    International Nuclear Information System (INIS)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J.

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 ± 2.9 nM and a Bmax value of 1770 ± 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current

  1. p300 Knockout Promotes Butyrate Resistance

    OpenAIRE

    Lazarova, Darina L.; Bordonaro, Michael

    2017-01-01

    Dietary fiber is linked to a reduced risk of colorectal cancer (CRC), and this protective activity is likely due to its fermentation product, butyrate. Dependent upon the hyperactivation of Wnt signaling, butyrate represses CRC cell growth and induces apoptosis. However, resistance to butyrate activity may allow for CRC development even in the context of relatively high fiber intake. We have previously determined that CRC cells resistant to butyrate are deficient in p300 expression. The histo...

  2. Quality components and antidepressant-like effects of GABA green tea.

    Science.gov (United States)

    Teng, Jie; Zhou, Wen; Zeng, Zhen; Zhao, Wenfang; Huang, Yahui; Zhang, Xu

    2017-09-20

    Gamma (γ)-aminobutyric acid (GABA) green tea, with high GABA content, is a kind of special green tea. The goals of this study are to analyze the changes in quality components of green tea during anaerobic treatment, and to investigate whether or not the extract of GABA present in green tea can prevent depression or improve the depressive state of animals. Results showed that GABA content in green tea had increased significantly after anaerobic treatment. The contents of tea polysaccharides, total free amino acids, and water extracts were also increased whereas tea polyphenols were reduced. More importantly, the extract of GABA green tea could alleviate mouse depression and stress from desperate environments through the forced swim test (FST), tail suspension test (TST), mRNA and protein expression levels of GABA A receptors. Therefore, these results indicate that GABA green tea may have a health effect on prevention and alleviation of depression, and it works on the GABAergic neurotransmission of mouse cerebral cortex via up-regulating expression of the GABA A receptor α1 subunit, thus ameliorating depression.

  3. Models construction for acetone-butanol-ethanol fermentations with acetate/butyrate consecutively feeding by graph theory.

    Science.gov (United States)

    Li, Zhigang; Shi, Zhongping; Li, Xin

    2014-05-01

    Several fermentations with consecutively feeding of acetate/butyrate were conducted in a 7 L fermentor and the results indicated that exogenous acetate/butyrate enhanced solvents productivities by 47.1% and 39.2% respectively, and changed butyrate/acetate ratios greatly. Then extracellular butyrate/acetate ratios were utilized for calculation of acids rates and the results revealed that acetate and butyrate formation pathways were almost blocked by corresponding acids feeding. In addition, models for acetate/butyrate feeding fermentations were constructed by graph theory based on calculation results and relevant reports. Solvents concentrations and butanol/acetone ratios of these fermentations were also calculated and the results of models calculation matched fermentation data accurately which demonstrated that models were constructed in a reasonable way. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Restricted Distribution of the Butyrate Kinase Pathway among Butyrate-Producing Bacteria from the Human Colon

    OpenAIRE

    Louis, Petra; Duncan, Sylvia H.; McCrae, Sheila I.; Millar, Jacqueline; Jackson, Michelle S.; Flint, Harry J.

    2004-01-01

    The final steps in butyrate synthesis by anaerobic bacteria can occur via butyrate kinase and phosphotransbutyrylase or via butyryl-coenzyme A (CoA):acetate CoA-transferase. Degenerate PCR and enzymatic assays were used to assess the presence of butyrate kinase among 38 anaerobic butyrate-producing bacterial isolates from human feces that represent three different clostridial clusters (IV, XIVa, and XVI). Only four strains were found to possess detectable butyrate kinase activity. These were ...

  5. A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder.

    Science.gov (United States)

    Yin, Honglei; Pantazatos, Spiro P; Galfalvy, Hanga; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, John J

    2016-04-01

    Gamma-amino butyric acid (GABA) and glutamate are the major inhibitory and excitatory neurotransmitters in the mammalian central nervous system, respectively, and have been associated with suicidal behavior and major depressive disorder (MDD). We examined the relationship between genotype, brain transcriptome, and MDD/suicide for 24 genes involved in GABAergic and glutamatergic signaling. In part 1 of the study, 119 candidate SNPs in 24 genes (4 transporters, 4 enzymes, and 16 receptors) were tested for associations with MDD and suicidal behavior in 276 live participants (86 nonfatal suicide attempters with MDD and 190 non-attempters of whom 70% had MDD) and 209 postmortem cases (121 suicide deaths of whom 62% had MDD and 88 sudden death from other causes of whom 11% had MDD) using logistic regression adjusting for sex and age. In part 2, RNA-seq was used to assay isoform-level expression in dorsolateral prefrontal cortex of 59 postmortem samples (21 with MDD and suicide, 9 MDD without suicide, and 29 sudden death non-suicides and no psychiatric illness) using robust regression adjusting for sex, age, and RIN score. In part 3, SNPs with subthreshold (uncorrected) significance levels below 0.05 for an association with suicidal behavior and/or MDD in part 1 were tested for eQTL effects in prefrontal cortex using the Brain eQTL Almanac (www.braineac.org). No SNPs or transcripts were significant after adjustment for multiple comparisons. However, a protein coding transcript (ENST00000414552) of the GABA A receptor, gamma 2 (GABRG2) had lower brain expression postmortem in suicide (P = 0.01) and evidence for association with suicide death (P = 0.03) in a SNP that may be an eQTL in prefrontal cortex (rs424740, P = 0.02). These preliminary results implicate GABRG2 in suicide and warrant further investigation and replication in larger samples. © 2016 Wiley Periodicals, Inc.

  6. Oncosecretomics coupled to bioenergetics identifies α-amino adipic acid, isoleucine and GABA as potential biomarkers of cancer: Differential expression of c-Myc, Oct1 and KLF4 coordinates metabolic changes.

    Science.gov (United States)

    Bellance, Nadège; Pabst, Lisa; Allen, Genevara; Rossignol, Rodrigue; Nagrath, Deepak

    2012-11-01

    Bioenergetic profiling of tumors is a new challenge of cancer research and medicine as therapies are currently being developed. Meanwhile, methodological means must be proposed to gather information on tumor metabolism in order to adapt these potential therapies to the bioenergetic specificities of tumors. Studies performed on tumors and cancer cell lines have shown that cancer cells bioenergetics is highly variable. This profile changes with microenvironmental conditions (eg. substrate availability), the oncogenes activated (and the tumor suppressors inactivated) and the interaction with the stroma (i.e. reverse Warburg effect). Here, we assessed the power of metabolic footprinting (MFP) to unravel the bioenergetics and associated anabolic changes induced by three oncogenes, c-Myc, KLF4 and Oct1. The MFP approach provides a quantitative analysis of the metabolites secreted and consumed by cancer cells. We used ultra performance liquid chromatography for quantifying the amino acid uptake and secretion. To investigate the potential oncogene-mediated alterations in mitochondrial metabolism, we measured oxygen consumption rate and ATP production as well as the glucose uptake and lactate release. Our findings show that c-Myc deficiency initiates the Warburg effect along with a reduction of mitochondrial respiration. KLF4 deficiency also stimulated glycolysis, albeit without cellular respiration impairment. In contrast, Oct1 deficiency reduced glycolysis and enhanced oxidative phosphorylation efficiency. MFP revealed that c-Myc, KLF4 and Oct1 altered amino acid metabolism with specific patterns. We identified isoleucine, α-aminoadipic acid and GABA (γ-aminoisobutyric acid) as biomarkers related. Our findings establish the impact of Oct1, KLF4 and c-Myc on cancer bioenergetics and evidence a link between oncosecretomics and cellular bioenergetics profile. © 2012 Elsevier B.V. All rights reserved.

  7. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages.

    Science.gov (United States)

    Fernando, Maria R; Saxena, Alpana; Reyes, José-Luis; McKay, Derek M

    2016-05-15

    The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4)s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4)s and M(IL-4 + butyrate)s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4)s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis. Copyright © 2016 the American Physiological Society.

  8. Acetylcarnitine potentiates the anticarcinogenic effects of butyrate on SW480 colon cancer cells.

    Science.gov (United States)

    Elimrani, Ihsan; Dionne, Serge; Saragosti, Dan; Qureshi, Ijaz; Levy, Emile; Delvin, Edgar; Seidman, Ernest G

    2015-08-01

    Butyrate is a potent anticarcinogenic compound against colon cancer cells in vitro. However, its rapid metabolism is hypothesized to limit its anticancer benefits in colonic epithelial cells. Carnitine, a potent antioxidant, is essential to fatty acid oxidation. The aims of this study were to identify a colon cancer cell line capable of transporting carnitine. We evaluated the effect of carnitine and acetylcarnitine (ALCAR) on the response of colon carcinoma cells to butyrate. We explored the mechanisms underlying the anticarcinogenic benefit. SW480 cells were incubated with butyrate ± carnitine or ALCAR. Carnitine uptake was assessed using [3H]-carnitine. Apoptosis and cell viability were assessed using an ELISA kit and flow cytometry, respectively. Modulation of proteins implicated in carnitine transport, cell death and proliferation were assessed by western blotting. SW480 cells were found to transport carnitine primarily via the OCTN2 transporter. Butyrate induced SW480 cell death occurred at concentrations of 2 mM and higher. Cells treated with the combination of butyrate (3 mM) with ALCAR exhibited increased mortality. The addition of carnitine or ALCAR also increased butyrate-induced apoptosis. Butyrate increased levels of cyclin D1, p21 and PARP p86, but decreased Bcl-XL and survivin levels. Butyrate also downregulated dephospho-β-catenin and increased acetylated histone H4 levels. Butyrate and carnitine decreased survivin levels by ≥25%. ALCAR independently induced a 20% decrease in p21. These results demonstrate that butyrate and ALCAR are potentially beneficial anticarcinogenic nutrients that inhibit colon cancer cell survival in vitro. The combination of both agents may have superior anticarcinogenic properties than butyrate alone.

  9. Does extracellular calcium determine what pool of GABA is the target for alpha-latrotoxin?

    Science.gov (United States)

    Storchak, L G; Linetska, M V; Himmelreich, N H

    2002-04-01

    Presynaptic neurotoxin alpha-latrotoxin, from the venom of Latrodectus mactans tredecimguttatus, causes massive [(3)H]GABA release from rat brain synaptosomes, irrespective of calcium presence in the extracellular medium. Whether the binding of alpha-latrotoxin to Ca(2+)-dependent (neurexin 1 alpha) or to Ca(2+)-independent (latrophilin) receptor triggers [(3)H]GABA release by the same mechanisms or different ones, inducing either exocytotic process or outflow by mobile membrane GABA transporter, is unknown. We examined alpha-latrotoxin-evoked [(3)H]GABA release from synaptosomes which cytosolic [(3)H]GABA pool was depleted either by applying competitive inhibitors of the GABA transporter, nipecotic acid and 2,4-diaminobutyric acid, or by permeation with digitonin. We also compared the effect of the GABA transporter inhibitors on depolarisation-evoked and alpha-latrotoxin-evoked [(3)H]GABA release using as depolarising agents 4-aminopyridine and high KCl in the Ca(2+)-containing and in Ca(2+)-free medium, respectively. Incubation of synaptosomes with nipecotic acid induced the essential acceleration of unstimulated [(3)H]GABA release and deep inhibition of high KCl-evoked Ca(2+)-independent [(3)H]GABA release. In contrast, at the similar conditions the effect of alpha-latrotoxin was greatly augmented with respect to the control response. Another way to assay what GABA pool was involved in alpha-latrotoxin-induced release lays in an analysis of the effects of depolarisation and alpha-latrotoxin in consecutive order. The preliminary 4-aminopyridine-stimulated [(3)H]GABA release attenuated the toxin effect. But when depolarisation occurred in Ca(2+)-free medium, no influence on alpha-latrotoxin effect was revealed. Employing digitonin-permeated synaptosomes, we have shown that alpha-latrotoxin could stimulate [3H]GABA release in the medium with 1mM EGTA, this effect of the toxin was blocked by concanavalin A and was ATP-dependent. The latter suggests that alpha

  10. Homology Modelling of the GABA Transporter and Analysis of Tiagabine Binding

    DEFF Research Database (Denmark)

    Skovstrup, S.; Taboureau, Olivier; Bräuner-Osborne, H.

    2010-01-01

    A homology model of the human GABA transporter (GAT-1) based on the recently reported crystal structures of the bacterial leucine transporter from Aquifex aeolicus (LeuT) was developed. The stability of the resulting model embedded in a membrane environment was analyzed by extensive molecular...... dynamics (MD) simulations. Based on docking studies and subsequent MD simulations of three compounds, the endogenous ligand GABA and two potent inhibitors, (R)-nipecotic acid and the anti-epilepsy drug tiagabine, various binding modes were identified and are discussed. Whereas GABA and (R)-nipecotic acid...

  11. Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen.

    Science.gov (United States)

    El-Ansary, Afaf; Al-Salem, Huda S; Asma, Alqahtani; Al-Dbass, Abeer

    2017-05-22

    Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups. The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent. In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.

  12. Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?

    Science.gov (United States)

    Brahe, L K; Astrup, A; Larsen, L H

    2013-12-01

    It is increasingly recognized that there is a connection between diet, intestinal microbiota, intestinal barrier function and the low-grade inflammation that characterizes the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment relevant. In this context, the ability of some Gram-positive anaerobic bacteria to produce the short-chain fatty acid butyrate is interesting. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans, and recent studies suggest that butyrate might have an anti-inflammatory potential that can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Here, we review and discuss the potential of butyrate as an anti-inflammatory mediator in metabolic diseases, and the potential for dietary interventions increasing the intestinal availability of butyrate. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  13. Knockout of GAD65 has major impact on synaptic GABA synthesized from astrocyte-derived glutamine

    DEFF Research Database (Denmark)

    Walls, Anne Byriel; Eyjolfsson, Elvar M.; Smeland, Olav B.

    2011-01-01

    γ-Aminobutyric acid (GABA) synthesis from glutamate is catalyzed by glutamate decarboxylase (GAD) of which two isoforms, GAD65 and GAD67, have been identified. The GAD65 has repeatedly been shown to be important during intensified synaptic activity. To specifically elucidate the significance of GAD......65 for maintenance of the highly compartmentalized intracellular and intercellular GABA homeostasis, GAD65 knockout and corresponding wild-type mice were injected with [1-(13)C]glucose and the astrocyte-specific substrate [1,2-(13)C]acetate. Synthesis of GABA from glutamine in the GABAergic synapses...... was further investigated in GAD65 knockout and wild-type mice using [1,2-(13)C]acetate and in some cases γ-vinylGABA (GVG, Vigabatrin), an inhibitor of GABA degradation. A detailed metabolic mapping was obtained by nuclear magnetic resonance (NMR) spectroscopic analysis of tissue extracts of cerebral cortex...

  14. Synergetic Enhancement of Device Efficiency in Poly(3-hexylthiophene-2,5-diyl/[6,6]-phenyl C61 Butyric Acid Methyl Ester Bulk Heterojunction Solar Cells by Glycerol Addition in the Active Layer

    Directory of Open Access Journals (Sweden)

    Bobins Augustine

    2015-01-01

    Full Text Available Poly(3-hexylthiophene-2,5-diyl(P3HT:[6,6]-phenyl-C61-butyric acid methyl ester (PC60BM is the widely used active layer for the bulk heterojunction solar cells. Annealing is essential for P3HT:PC60BM active layer, since it facilitates the creation of better network for the transfer of the charge carriers. However, the PC60BM in the active layer can crystallize excessively during annealing treatments and disrupt the favorable morphology by forming crystallites in micrometer ranges, thus reducing device efficiency. In this paper we used glycerol as an additive in the active layer. Due to high boiling point of glycerol, it makes slow drying of the active layer possible during the annealing. It thus gives enough time to both electron donor (P3HT and electron acceptor (PC60BM components of the active layer to self-organize and also restrict the crystal overgrowth of PC60BM. Further, the glycerol additive makes the active layer smoother, which may also improve adhesion between the electrode and the active layer. The devices with the pristine active layer showed a power conversion efficiency (PCE of about 2.1% and, with the addition of 30 vol% of glycerol in the active layer, the PCE value increased to 3%.

  15. The efficient n-doping of [6,6]-phenyl C61-butyric acid methyl ester by leuco-crystal violet to enhance the performance of inverted organic solar cells

    Science.gov (United States)

    Chen, Li; Zhao, Wei; Cao, Huan; Shi, Zhihua; Zhang, Jidong; Qin, Dashan

    2018-02-01

    Inverted organic solar cells (OSCs) have been fabricated using the photoactive blend thin films based on regioregular poly(3-hexylthiophene) (P3HT), [6,6]-phenyl C61-butyric acid methyl ester (PCBM), and leuco-crystal violet (LCV). It was found that the LCV as an efficient n-dopant could significantly increase intrinsic electron concentration of PCBM zone. The electron mobility of P3HT:PCBM:LCV blend thin film was measured 1.75 times as high as that of P3HT:PCBM blend thin film, as a result of LCV-induced trap filling in the bandgap of PCBM. The power conversion efficiency for the inverted device using the photoactive layer of P3HT:PCBM:LCV could be 1.22 times as high as that for the inverted device using the conventional photoactive layer of P3HT:PCBM, mostly because (1) the higher electron mobility could enhance the exciton dissociation and thereby short-circuit current density in the former relative to the latter; (2) the increase in the electron concentration of PCBM zone in P3HT:PCBM:LCV blend thin film may help blocking holes diffusion towards cathode, improving the hole collection efficiency and thereby fill factor of device. We provide a new insight on optimizing the electron-conducting property of bulk-heterojunction photoactive thin film, useful for pushing forward inverted OSCs towards the cost-effective commercialization.

  16. Supplemental butyrate does not enhance the absorptive or barrier functions of the isolated ovine ruminal epithelia.

    Science.gov (United States)

    Wilson, D J; Mutsvangwa, T; Penner, G B

    2012-09-01

    Our objective was to determine if increasing the ruminal butyrate concentration would improve the selective permeability of ruminal epithelia. Suffolk wether lambs (n = 18) with an initial BW of 47.4 ±1.4 kg were housed in individual pens (1.5 × 1.5 m) with rubber mats on the floor. Lambs were blocked by initial BW into 6 blocks and, within block, were randomly assigned to either the control (CON) or 1 of 2 butyrate supplementation amounts (i.e., 1.25% or 2.50% butyrate as a proportion of DMI). With the exception of butyrate supplementation, all lambs were fed a common diet (90% concentrate and 10% barley silage). After a 14-d feeding period, lambs were killed, and ruminal epithelia from the ventral sac were mounted in Ussing chambers. To facilitate the Ussing chamber measurements, only 1 lamb was killed on an individual day. Thus, the starting date was staggered so that all lambs were exposed to the same experimental protocol. In Ussing chambers, epithelia were incubated using separate mucosal (pH 6.2) and serosal (pH 7.4) bathing solutions. Then 1-14C-butyrate (74 kBq/10 mL) was added to the mucosal side and was used to measure the mucosal-to-serosal flux (J(ms-butyrate)) in 2 consecutive 60-min flux periods with simultaneous measurement of transepithelial conductance (G(t)). During the first (challenge) flux period, the mucosal buffer solution was either acidified to pH 5.2 (ACID) or used as a control (pH 6.2; SHAM). Buffer solutions bathing the epithelia were replaced before the second flux period (recovery). Total ruminal short-chain fatty acid and butyrate concentrations were greater (P = 0.001) in lambs fed 2.50% compared with those fed 0% or 1.25% butyrate. The J(ms-butyrate) was less for lambs fed 1.25% and 2.50% butyrate [3.00 and 3.12 μmol/(cm2·h), respectively] than for CON [3.91 μmol/(cm2· h)]. However, no difference (P = 0.13)was observed for G(t). An ex vivo treatment × flux period interaction was detected (P = 0.003) for J(ms-butyrate), where

  17. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells.

    Directory of Open Access Journals (Sweden)

    Hui Yan

    Full Text Available Short chain fatty acids (SCFA, products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity.

  18. Butyrate as preferred substrate for polyhydroxybutyrate production.

    Science.gov (United States)

    Marang, Leonie; Jiang, Yang; van Loosdrecht, Mark C M; Kleerebezem, Robbert

    2013-08-01

    In this study, the suitability of butyrate as substrate for polyhydroxyalkanoate (PHA) production by microbial enrichment cultures was assessed. Two sequencing batch reactors were operated under feast-famine conditions: one fed with butyrate, and another with mixed acetate and butyrate. The obtained results were compared to previous results with acetate as sole substrate. In all three reactors Plasticicumulans acidivorans dominated the enrichment culture. The carbon uptake rate and PHA yield were significantly higher on butyrate than on acetate, resulting in a higher PHA production rate. When both substrates were available the bacteria strongly preferred the uptake of butyrate. Only after butyrate depletion acetate was taken up at a high rate. The molar substrate uptake rate remained the same, suggesting that substrate uptake is the rate-limiting step. The results show that for optimized waste-based PHA production the pre-fermentation process should be directed towards butyrate production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Segregation of acetylcholine and GABA in the rat superior cervical ganglia: functional correlation.

    Directory of Open Access Journals (Sweden)

    Diana eElinos

    2016-04-01

    Full Text Available Sympathetic neurons have the capability to segregate their neurotransmitters (NTs and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh and other classical NTs such as gamma aminobutyric acid (GABA. Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX. We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region show larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons.

  20. Insulin reduces neuronal excitability by turning on GABA(A channels that generate tonic current.

    Directory of Open Access Journals (Sweden)

    Zhe Jin

    Full Text Available Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid decreases neuronal excitability by activating GABA(A channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM "turns on" new extrasynaptic GABA(A channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50 in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

  1. Neurotransmitters as food supplements: the effects of GABA on brain and behavior

    Directory of Open Access Journals (Sweden)

    Evert eBoonstra

    2015-10-01

    Full Text Available The food supplement version of gamma-aminobutyric acid (GABA is widely available online. Although many consumers claim that they experience benefits from the use of these products, it is unclear whether these supplements confer benefits beyond a placebo effect. Currently, the mechanism of action behind these products is unknown. It has long been thought that GABA is unable to cross the blood brain barrier (BBB, but the studies that have assessed this issue are often contradictory and range widely in their employed methods. Accordingly, future research needs to establish the effects of oral GABA administration on GABA levels in the human brain, for example using magnetic resonance spectroscopy. There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest. We suggest that any veridical effects of GABA food supplements on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system. We conclude that the mechanism of action of GABA food supplements is far from clear, and that further work is needed to establish the behavioral effects of GABA.

  2. Development of a high-affinity GABA uptake system in embryonic amphibian spinal neurons.

    Science.gov (United States)

    Lamborghini, J E; Iles, A

    1985-11-01

    High-affinity uptake systems for amino acid neurotransmitter precursors have been highly correlated with the use of the particular amino acid or its derivative as a transmitter. We have found interneurons in the Xenopus embryo spinal cord which accumulate GABA by a high-affinity uptake system. They originate near the end of gastrulation and their ability to accumulate GABA first appears at the early tail bud stage. By position and appearance they are comparable to some of the embryonic interneurons described by A. Roberts and J. D. W. Clarke (1982, Phil. Trans. R. Soc. London Ser. B 296, 195-212). GABA-accumulating neurons also develop in dissociated cell cultures made from the presumptive spinal cord of neural plate stage Xenopus embryos. GABA accumulation in cultured neurons, as in cells in vivo, occurs via a high-affinity uptake system; GABA-accumulating cells have the same time of origin as the cells in vivo, and the ability to accumulate GABA in the population of cultured neurons appears at a time equivalent to that observed in intact sibling embryos. Thus it seems likely that the population of GABA-accumulating neurons developing in cell culture corresponds to the GABA-accumulating interneurons in vivo. The development of these neurons in dissociated cell cultures permits perturbation experiments that would be difficult to perform in vivo. We have examined the development of high-affinity GABA uptake in conditions that permit no electrical impulse activity in the cultures. The onset and extent of development of GABA accumulation in the neuronal population are normal under these conditions.

  3. The effect of GABA receptor ligands in experimental spina bifida occulta.

    Science.gov (United States)

    Briner, W

    2001-01-01

    The pathophysiology behind spina bifida and other neural tube defects (NTDs) is unclear. Folic acid is one variable, but other factors remain. Studies suggest that substances active at the GABA receptor may produce NTDs. To test this hypothesis pregnant rats were exposed to either the GABA a agonist muscimol (1, 2 or 4 mg/kg), the GABA a antagonist bicuculline (.5, 1, or 2 mg/kg), the GABA b agonist baclofen (15, 30, 60 mg/kg), or the GABA b antagonist hydroxysaclofen (1, 3, or 5 mg/kg) during neural tube formation. Normal saline was used as a control and valproic acid (600 mg/kg) as a positive control. The embryos were analyzed for the presence of a spina bifida like NTD. After drug administration the pregnancies were allowed to proceed to the 21st day of gestation. Then embryos were removed and skeletons staining and cleared. Vertebral arch closure was measured. Results indicate that the GABAa receptor agonist muscimol, the GABAa receptor antagonist bicuculline, and the GABAb agonist baclofen produced NTDs characterized by widening of the vertebral arch. Oppositely the GABAb antagonist hydroxysaclofen produced narrowing of the vertebral arches. The findings indicate that GABA a or b ligands are capable of altering neural formation. GABA may play a greater than appreciated role in neural tube formation and may be important in NTDs. The narrowing of the vertebral arch produced by the GABA b antagonist hydroxysalcofen suggests that GABA b receptor may play an undefined role in neural tube closure that differs from the GABA a receptor.

  4. Characterization of GABA/sub A/ receptor-mediated 36chloride uptake in rat brain synaptoneurosomes

    International Nuclear Information System (INIS)

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-01-01

    γ-Aminobutyric acid (GABA) receptor-mediated 36 chloride ( 36 Cl - ) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36 Cl - uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36 Cl - uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36 Cl - uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br - >Cl - ≥NO 3 - >I - ≥SCN - >>C 3 H 5 OO - ≥ClO 4 - >F - , consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl - channel. 43 references, 4 figures, 3 tables

  5. A synergistic effect of GABA tea and copper(II) on DNA breakage in human peripheral lymphocytes.

    Science.gov (United States)

    Wang, Hsueh-Fang; Chuang, Show-Mei; Hsiao, Ching-Chuan; Cherng, Shur-Hueih

    2011-04-01

    GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). The oxidant and antioxidant roles of GABA tea in DNA damage were investigated in this study. DNA cleavage was observed by GABA-tea extract in the presence of copper ions. Comet assay revealed that combination of GABA-tea extract, but not pure GABA, and Cu(2+) is capable of oxidatively degrading cellular DNA in human peripheral lymphocytes. Using various reactive oxygen scavengers, we found that catalase and sodium azide effectively inhibited GABA-tea extract/Cu(II)-induced DNA degradation, suggesting the essential role of singlet oxygen and H(2)O(2) in the reaction. In addition, neocuproine inhibited the DNA degradation, confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Therefore, we speculate that GABA-tea extract/Cu(II)-induced DNA damage is probably mediated through the formation of H(2)O(2) and the reduction of copper. Furthermore, our data showed that GABA-tea extract was more genotoxic and pro-oxidant than its major catechin constituent, (-)-epigallocatechin-3-gallate (EGCG), leading to DNA cleavage in the presence of Cu(2+). These findings will provide implications for the potential of GABA-tea extract in anticancer property, which may involve copper ions and the consequent pro-oxidant action. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. GABA-shunt enzymes activity in GH3 cells with reduced level of PMCA2 or PMCA3 isoform

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Antoni, E-mail: antoni.kowalski@umed.lodz.pl [Department of Molecular Neurochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz (Poland); Zylinska, Ludmila, E-mail: ludmila.zylinska@umed.lodz.pl [Department of Molecular Neurochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz (Poland); Boczek, Tomasz, E-mail: tomasz.boczek@umed.lodz.pl [Department of Molecular Neurochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz (Poland); Rebas, Elzbieta, E-mail: elzbieta.rebas@umed.lodz.pl [Department of Molecular Neurochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz (Poland)

    2011-08-12

    Highlights: {yields} Suppression of PMCA2 or PMCA3 slows down proliferation of GH3 cells. {yields} PMCA2 suppression lowers the activity of GABA-shunt enzymes. {yields} PMCA3 suppression increases the expression of glutamate decarboxylase 65. {yields} PMCA2 and PMCA3 function appears to be linked to regulation of GABA metabolism. -- Abstract: GABA ({gamma}-aminobutyric acid) is important neurotransmitter and regulator of endocrine functions. Its metabolism involves three enzymes: glutamate decarboxylase (GAD65 and GAD67), GABA aminotransferase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). As many cellular processes GABA turnover can depend on calcium homeostasis, which is maintained by plasma membrane calcium ATPases (PMCAs). In excitable cells PMCA2 and PMCA3 isoforms are particularly important. In this study we focused on GABA-metabolizing enzymes expression and activity in rat anterior pituitary GH3 cells with suppressed expression of PMCA2 or PMCA3. We observed that PMCA3-reduced cells have increased GAD65 expression. Suppression of PMCA2 caused a decrease in total GAD and GABA-T activity. These results indicate that PMCA2 and PMCA3 presence may be an important regulatory factor in GABA metabolism. Results suggest that PMCA2 and PMCA3 function is rather related to regulation of GABA synthesis and degradation than supplying cells with metabolites, which can be potentially energetic source.

  7. In vivo quantification of intracerebral GABA by single-voxel {sup 1}H-MRS-How reproducible are the results?

    Energy Technology Data Exchange (ETDEWEB)

    Bogner, W. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: wolfgang@nmr.at; Gruber, S. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: stephan@nmr.at; Doelken, M. [Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: marc.doelken@uk-erlangen.de; Stadlbauer, A. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: andi@nmr.at; Ganslandt, O. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: oliver.ganslandt@uk-erlangen.de; Boettcher, U. [Siemens Medical Solution, Karl-Schall Str. 6, D-91052 Erlangen (Germany)], E-mail: uwe.boettcher@siemens.com; Trattnig, S. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: siegfried.trattnig@meduniwien.ac.at; Doerfler, A. [Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: a.doerfler@nrad.imed.uni-erlangen.de; Stefan, H. [Center Epilepsy Erlangen (ZEE), Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany)], E-mail: Hermann.Stefan@uk-erlangen.de; Hammen, T. [Center Epilepsy Erlangen (ZEE), Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany)], E-mail: thilo.hammen@uk-erlangen.de

    2010-03-15

    Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H{sub 2}O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H{sub 2}O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H{sub 2}O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr {approx}10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

  8. In vivo quantification of intracerebral GABA by single-voxel 1H-MRS-How reproducible are the results?

    International Nuclear Information System (INIS)

    Bogner, W.; Gruber, S.; Doelken, M.; Stadlbauer, A.; Ganslandt, O.; Boettcher, U.; Trattnig, S.; Doerfler, A.; Stefan, H.; Hammen, T.

    2010-01-01

    Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H 2 O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H 2 O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H 2 O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr ∼10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

  9. Differential responses to isoprenoid, N-6-substituted aromatic cytokinins and indole-3-butyric acid in direct plant regeneration of Eriocephalus africanus

    Czech Academy of Sciences Publication Activity Database

    Madzikane-Mlungwana, O.; Moyo, M.; Aremu, A.O.; Plíhalová, Lucie; Doležal, Karel; Van Staden, J.; Finnie, J.F.

    2017-01-01

    Roč. 82, č. 1 (2017), s. 103-110 ISSN 0167-6903 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : in-vitro cultures * auxin transport * meta-topolin * antioxidant activity * biological-activity * arabidopsis roots * phenolic-acids * l. asteraceae * south-africa * flavonoids * Auxins * Cytokinins * Flavonoids * Plant regeneration * Phenolics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 2.646, year: 2016

  10. Effect of thidiazuron and indole-butyric acid in the in vitro propagation of two varieties of strawberry (Oso Grande and Sweet Charlie from foliar sections

    Directory of Open Access Journals (Sweden)

    Pillco-Tancara Hilda Corina

    2017-08-01

    Full Text Available Strawberry farmers indicate that yields are low compared to other countries. This effect is due to the fact that they plant seedlings that come from stolons since the strawberries are propagated asexual. This con-ventional form of reproduction has disadvantages such as: decreased yield, loss of fruit quality. An alter-native to solve this problem is micropropagation. The present research evaluated the in vitro behavior of two varieties of strawberry (Oso Grande and Sweet Charlie from leaf segments with different degrees of maturation (juvenile and adult in two periods of introduction. To induce in vitro propagation, the culture media were supplemented with growth regulators, using two concentrations 4.54 and 9.08 μM of thidiazuron with the combination of three concentrations of 0, 0.98 and 2.5 μM of acid Indolebutyric acid. Explants of leaf segments showing juvenile tissues (May came to form buds. The same did not occur with those that came from adult tissue (June, so it can be noted that those that came from juvenile tissue had a better response in vitro. It was determined that the combination of 9.08 μM thidiazuron and 0.98 μM indolbutyric acid was the most suitable for the in vitro propagation of leaf sections of strawberry leaves in both varieties, since in this medium more formation was obtained Of cell aggregates, for the formation of outbreaks compared to the other treatments.

  11. Selective GABA transporter inhibitors tiagabine and EF1502 exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABA(A) receptor agonist gaboxadol

    DEFF Research Database (Denmark)

    Madsen, Karsten Kirkegaard; Ebert, Bjarke; Clausen, Rasmus Prætorius

    2011-01-01

    Modulation of the extracellular levels of GABA via inhibition of the synaptic GABA transporter GAT1 by the clinically effective and selective GAT1 inhibitor tiagabine [(R)-N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid; Gabitril] has proven to be an effective treatment strategy for focal...

  12. Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis.

    Science.gov (United States)

    Pulliam, Stephanie R; Pellom, Samuel T; Shanker, Anil; Adunyah, Samuel E

    2016-08-01

    Butyrate is a histone deacetylase inhibitor implicated in many studies as a potential therapy for various forms of cancer. High concentrations of butyrate (>1.5mM) have been shown to activate apoptosis in several cancer cell lines including prostate, breast, and leukemia. Butyrate is also known to influence multiple signaling pathways that are mediators of cytokine production. The purpose of this study was to evaluate the impact of high concentrations of butyrate on the cancer microenvironment vis-à-vis apoptosis, cellular migration, and capacity to modulate cytokine expression in cancer cells. The results indicate that high concentrations of butyrate induced a 2-fold activation of caspase-3 and reduced cell viability by 60% in U937 leukemia cells. Within 24h, butyrate significantly decreased the levels of chemokines CCL2 and CCL5 in HL-60 and U937 cells, and decreased CCL5 in THP-1 leukemia cells. Differential effects were observed in treatments with valproic acid for CCL2 and CCL5 indicating butyrate-specificity. Many of the biological effects examined in this study are linked to activation of the AKT and MAPK signaling pathways; therefore, we investigated whether butyrate alters the levels of phosphorylated forms of these signaling proteins and how it correlated with the expression of chemokines. The results show that butyrate may partially regulate CCL5 production via p38 MAPK. The decrease in p-ERK1/2 and p-AKT levels correlated with the decrease in CCL2 production. These data suggest that while promoting apoptosis, butyrate has the potential to influence the cancer microenvironment by inducing differential expression of cytokines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Focal Uncaging of GABA Reveals a Temporally Defined Role for GABAergic Inhibition during Appetitive Associative Olfactory Conditioning in Honeybees

    Science.gov (United States)

    Raccuglia, Davide; Mueller, Uli

    2013-01-01

    Throughout the animal kingdom, the inhibitory neurotransmitter ?-aminobutyric acid (GABA) is a key modulator of physiological processes including learning. With respect to associative learning, the exact time in which GABA interferes with the molecular events of learning has not yet been clearly defined. To address this issue, we used two…

  14. Edited Magnetic Resonance Spectroscopy Detects an Age-related Decline in Brain GABA Levels

    OpenAIRE

    Gao, Fei; Edden, Richard A.E.; Li, Muwei; Puts, Nicolaas A.J.; Wang, Guangbin; Liu, Cheng; Zhao, Bin; Wang, Huiquan; Bai, Xue; Zhao, Chen; Wang, Xin; Barker, Peter B.

    2013-01-01

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy (1H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3 Tesl...

  15. Anion transport and GABA signaling

    Directory of Open Access Journals (Sweden)

    Christian Andreas Huebner

    2013-10-01

    Full Text Available Whereas activation of GABAA receptors by GABA usually results in a hyperpolarizing influx of chloride into the neuron, the reversed chloride driving force in the immature nervous system results in a depolarizing efflux of chloride. This GABAergic depolarization is deemed to be important for the maturation of the neuronal network. The concept of a developmental GABA switch has mainly been derived from in vitro experiments and reliable in vivo evidence is still missing. As GABAA receptors are permeable for both chloride and bicarbonate, the net effect of GABA also critically depends on the distribution of bicarbonate. Whereas chloride can either mediate depolarizing or hyperpolarizing currents, bicarbonate invariably mediates a depolarizing current under physiological conditions. Intracellular bicarbonate is quickly replenished by cytosolic carbonic anhydrases. Intracellular bicarbonate levels also depend on different bicarbonate transporters expressed by neurons. The expression of these proteins is not only developmentally regulated but also differs between cell types and even subcellular regions. In this review we will summarize current knowledge about the role of some of these transporters for brain development and brain function.

  16. Morphological and spectroscopic characterizations of inkjet-printed poly(3-hexylthiophene-2,5-diyl): Phenyl-C61-butyric acid methyl ester blends for organic solar cell applications

    International Nuclear Information System (INIS)

    Bruno, A.; Villani, F.; Grimaldi, I.A.; Loffredo, F.; Morvillo, P.; Diana, R.; Haque, S.; Minarini, C.

    2014-01-01

    The most exploited active material for photovoltaic devices is the regioregular poly(3-hexylthiophene) (P3HT), p-type conjugated polymer, blended with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), n-type material. The deposition methods and the induced morphology strongly influence the functionality of the active material and in turn the final charge generation performances of a photoactive layer. In the present work, we studied the influence of PCBM concentration on the morphological and spectroscopic properties of the inkjet printed P3HT:PCBM blends through atomic force microscopy (AFM), Raman spectroscopy and transient absorption spectroscopy. The aim is to value the charge formation yield in the blends, prepared by inkjet technology, as function of the acceptor concentrations in correlation with morphology and intermixing of the two components. For the inkjet printed samples the blends composition that corresponds to the best intermixing between P3HT and PCBM and the higher charges formation yield should be between 20% and 45% in weight (wt)., differently for what has been found previously for spin-coated samples. Indeed, for inkjet prepared film, the 45 wt.% blend ratio leads to much bigger domains with respect to the spin-coated samples as shown from the AFM measurements. - Highlights: • Inkjet-printed P3HT:PCBM blends for organic solar cell applications • Coarser morphology of inkjet P3HT:PCBM films with respect to the spin-coated film • Inkjet P3HT:PCBM films showed charge formation maximum for PCBM wt.% lower than 45

  17. A novel approach for the characterization of a bilayer of phenyl-c71-butyric-acid-methyl ester and pentacene using ultraviolet photoemission spectroscopy and argon gas cluster ion beam sputtering process

    International Nuclear Information System (INIS)

    Yun, Dong-Jin; Chung, JaeGwan; Jung, Changhoon; Chung, Yeonji; Kim, SeongHeon; Lee, Seunghyup; Kim, Ki-Hong; Han, Hyouksoo; Park, Gyeong-Su; Park, SungHoon

    2013-01-01

    The material arrangement and energy level alignment of an organic bilayer comprising of phenyl-c71-butyric-acid-methyl ester (PCBM-71) and pentacene were studied using ultraviolet photoelectron spectroscopy (UPS) and the argon gas cluster ion beam (GCIB) sputtering process. Although there is a small difference in the full width at half maximum of the carbon C 1s core level peaks and differences in the oxygen O 1s core levels of an X-ray photoemission spectroscopy spectra, these differences are insufficient to clearly distinguish between PCBM-71 and pentacene layers and to classify the interface and bulk regions. On the other hand, the valence band structures in the UPS spectra contain completely distinct configurations for the PCBM-71 and pentacene layers, even when they have similar atomic compositions. According to the valence band structures of the PCBM-71/pentacene/electrodes, the highest unoccupied molecular orbital (HOMO) region of pentacene is at least 0.8 eV closer to the Fermi level than that of PCBM-71 and it does not overlap with any of the chemical states in the valence band structure of PCBM-71. Therefore, by just following the variations in the area of the HOMO region of pentacene, the interface/bulk regions of the PCBM/pentacene layers were distinctly categorized. Besides, the variation of valence band structures as a function of the Ar GCIB sputtering time fully corroborated with the surface morphologies observed in the atomic force microscope images. In summary, we believe that the novel approach, which involves UPS analysis in conjunction with Ar GCIB sputtering, can be one of the best methods to characterize the material distribution and energy level alignments of stacks of organic layers

  18. Spray deposition of poly(3-hexylthiophene) and [6,6]-phenyl-C{sub 61}-butyric acid methyl ester blend under electric field for improved interface and organic solar cell characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Neha, E-mail: nchaturvedi9@gmail.com; Swami, Sanjay Kumar; Dutta, Viresh

    2016-01-01

    Spray process is used for the deposition of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) blend film under different voltages (0 V, 300 V, 500 V and 700 V) applied to the nozzle. The presence of the electric field during the spray process makes the P3HT:PCBM film smoother, uniform and more crystalline with well aligned domains. X-ray photoelectron spectroscopy study shows that PCBM rich surface is formed by application of the DC voltage (700 V) which improves the electron transport at the active layer and cathode interface. The application of electric field reduces the recombination at interfaces. The increased charge carrier separation between donor and acceptor at the interface and the crystallinity enhancement result in improved short circuit current density–voltage characteristics of Indium tin oxide/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS) /P3HT:PCBM/Aluminum solar cell. The organic bulk-heterojunction solar cell using the electric field assisted spray deposited PEDOT:PSS and P3HT:PCBM layers exhibited 84% and 154% increment in the short circuit current density and power conversion efficiency, respectively in comparison to the solar cell having spray deposited PEDOT:PSS and P3HT:PCBM layers in the absence of the electric field. - Highlights: • Spray deposition of P3HT:PCBM is carried out. • Spray deposition under electric field is done. • Electric field application enhanced the crystallinity of the layers. • P3HT:PCBM film arranged in more ordered form with electric field • Efficiency of organic solar cell is enhanced with application of electric field.

  19. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

    Science.gov (United States)

    Stilling, Roman M; van de Wouw, Marcel; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2016-10-01

    Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication. Copyright © 2016 Elsevier Ltd. All

  20. Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models.

    Science.gov (United States)

    Hong, Ki-Bae; Park, Yooheon; Suh, Hyung Joo

    2016-09-01

    The aim of this study was to investigate the sleep-promoting effect of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) on sleep quality and quantity in vertebrate models. Pentobarbital-induced sleep test and electroencephalogram (EEG) analysis were applied to investigate sleep latency, duration, total sleeping time and sleep quality of two amino acids and GABA/5-HTP mixture. In addition, real-time PCR and HPLC analysis were applied to analyze the signaling pathway. The GABA/5-HTP mixture significantly regulated the sleep latency, duration (pHTP mixture modulates both GABAergic and serotonergic signaling. Moreover, the sleep architecture can be controlled by the regulation of GABAA receptor and GABA content with 5-HTP. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    International Nuclear Information System (INIS)

    Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

    2011-01-01

    Highlights: →We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. → Deletion of the UGA1 or GAD1 genes extends replicative lifespan. → Addition of GABA to wild-type cultures has no effect on lifespan. → Intracellular GABA levels do not differ in longevity mutants and wild-type cells. → Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for γ-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The Δuga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for Δuga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of 1 H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan extension. These results strongly suggest

  2. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

    2011-04-01

    Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

  3. Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA

    OpenAIRE

    Schousboe, Arne; Bak, Lasse K.; Waagepetersen, Helle S.

    2013-01-01

    Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of t...

  4. Glutamate and GABA uptake by cerebellar granule and glial cell enriched populations

    International Nuclear Information System (INIS)

    Campbell, G.L.; Shank, R.P.

    1978-01-01

    The results of a study on the uptake of glutamate and GABA by the granule and glial cell enriched populations are reported. They demonstrate that the granule cells vigorously accumulate glutamate but not GABA, whereas the glial cell enriched fraction takes up both amino acids quite rapidly. An unexpected and significant finding is that both cell populations take up glutamate by two distinct high-affinity transport systems as well as a low-affinity system. (Auth.)

  5. Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.

    Science.gov (United States)

    Liu, Bin; Qian, Jianmin; Wang, Qingbao; Wang, Fangrui; Ma, Zhenyu; Qiao, Yingli

    2014-01-01

    Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

  6. Dietary fibres modulate the composition and activity of butyrate-producing bacteria in the large intestine of suckling piglets.

    Science.gov (United States)

    Mu, Chunlong; Zhang, Lingli; He, Xiangyu; Smidt, Hauke; Zhu, Weiyun

    2017-05-01

    Dietary fibres have been shown to affect early-life microbiota colonization in the large intestine of suckling piglets, however, much less is known as to whether they also modulate the composition and activity of butyrate-producing bacteria. Here, we investigated the effect of dietary fibres on the abundance, composition, and activity of butyrate-producing bacteria in suckling piglets. Piglets were fed a control diet or creep feeds containing alfalfa, wheat bran, or pure cellulose, respectively, from postnatal day 7 to 22. Large intestinal digesta and mucosa samples were collected for quantitative analysis of bacterial group-specific 16S ribosomal RNA- and butyrate production-related genes, and digesta samples for quantification of short-chain fatty acids. The alfalfa diet increased (P butyrate production (butyryl-CoA:acetate CoA-transferase, butyrate kinase), and butyrate concentration compared to the wheat bran diet in the digesta of the proximal colon. In the distal colonic digesta, animals fed the alfalfa diet had the highest number of butyryl-CoA:acetate CoA-transferase gene copies (P butyrate concentration, albeit not significant (P > 0.05), compared to other groups. In the distal colonic mucosa, the cellulose diet increased (P butyrate-producing bacteria in the large intestine of suckling piglets, and that a moderate supplementation of alfalfa and cellulose may benefit early-life gut health through the delivery of butyrate to the mucosa.

  7. Characterization of a Clostridium beijerinckii spo0A mutant and its application for butyl butyrate production.

    Science.gov (United States)

    Seo, Seung-Oh; Wang, Yi; Lu, Ting; Jin, Yong-Su; Blaschek, Hans P

    2017-01-01

    Spo0A is a master regulator that governs the metabolic shift of solventogenic Clostridium species such as Clostridium beijerinckii. Its disruption can thus potentially cause a significant alteration of cellular physiology as well as metabolic patterns. To investigate the specific effect of spo0A disruption in C. beijerinckii, a spo0A mutant of C. beijerinckii was characterized in this study. In a batch fermentation with pH control at 6.5, the spo0A mutant accumulated butyrate and butanol up to 8.96 g/L and 3.32 g/L, respectively from 60 g/L glucose. Noticing the unique phenotype of the spo0A mutant accumulating both butyrate and butanol at significant concentrations, we decided to use the spo0A mutant for the production of butyl butyrate that can be formed by the condensation of butyrate and butanol during the ABE fermentation in the presence of the enzyme lipase. Butyl butyrate is a value-added chemical that has numerous uses in the food and fragrance industry. Moreover, butyl butyrate as a biofuel is compatible with Jet A-1 aviation kerosene and used for biodiesel enrichment. In an initial trial of small-scale extractive batch fermentation using hexadecane as the extractant with supplementation of lipase CalB, the spo0A mutant was subjected to acid crash due to the butyrate accumulation, and thus produced only 98 mg/L butyl butyrate. To alleviate the butyrate toxicity, the biphasic medium was supplemented with 10 g/L CaCO 3 and 5 g/L butanol. The butyl butyrate production was then increased up to 2.73 g/L in the hexadecane layer. When continuous agitation was performed to enhance the esterification and extraction of butyl butyrate, 3.32 g/L butyl butyrate was obtained in the hexadecane layer. In this study, we successfully demonstrated the use of the C. beijerinckii spo0A mutant for the butyl butyrate production through the simultaneous ABE fermentation, condensation, and extraction. Biotechnol. Bioeng. 2017;114: 106-112. © 2016 Wiley Periodicals

  8. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks.

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABA A mediated signaling.

  9. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  10. Regulation of (/sup 3/H)GABA release from strips of guinea pig urinary bladder

    Energy Technology Data Exchange (ETDEWEB)

    Shirakawa, J.; Taniyama, K.; Iwai, S.; Tanaka, C.

    1988-12-01

    The presence of receptors that regulate the release of gamma-aminobutyric acid (GABA) was studied in strips of the guinea pig urinary bladder. GABA (10(-8)-10(-5) M) and muscimol (10(-8)-10(-5) M), but not baclofen (10(-5) M), reduced the Ca2+-dependent, tetrodotoxin-resistant release of (/sup 3/H)GABA evoked by high K+ from the urinary bladder strips preloaded with (/sup 3/H)GABA. The inhibitory effect of muscimol was antagonized by bicuculline and potentiated by diazepam, clonazepam, and pentobarbital sodium. The potentiating effect of clonazepam was antagonized by Ro 15-1788. Acetylcholine (ACh) inhibited the high K+-evoked release of (/sup 3/H)GABA. The inhibitory effect of ACh was antagonized by atropine sulfate and pirenzepine but not by hexamethonium. Norepinephrine (NE) inhibited the evoked release of (/sup 3/H)GABA. The inhibitory effect of NE was mimicked by clonidine, but not by phenylephrine, and was antagonized by yohimbine but not by prazosin. These results provide evidence that the release of GABA from strips of guinea pig urinary bladder is regulated via the bicuculline-sensitive GABAA receptor, M1-muscarinic, and alpha 2-adrenergic receptors.

  11. Prevention of GABA reduction during dough fermentation using a baker's yeast dal81 mutant.

    Science.gov (United States)

    Ando, Akira; Nakamura, Toshihide

    2016-10-01

    γ-Aminobutyric acid (GABA) is consumed by yeasts during fermentation. To prevent GABA reduction in bread dough, a baker's yeast mutant AY77 deficient in GABA assimilation was characterized and utilized for wheat dough fermentation. An amber mutation in the DAL81 gene, which codes for a positive regulator of multiple nitrogen degradation pathways, was found in the AY77 strain. The qPCR analyses of genes involved in nitrogen utilization showed that transcriptional levels of the UGA1 and DUR3 genes encoding GABA transaminase and urea transporter, respectively, are severely decreased in the AY77 cells. The AY77 strain cultivated by fed-batch culture using cane molasses exhibited inferior gas production during dough fermentation compared to that of wild-type strain AY13. However, when fed with molasses containing 0.5% ammonium sulfate, the mutant strain exhibited gas production comparable to that of the AY13 strain. In contrast to the AY13 strain, which completely consumed GABA in dough within 5 h, the AY77 strain consumed no GABA under either culture condition. Dough fermentation with the dal81 mutant strain should be useful for suppression of GABA reduction in breads. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  12. Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

    Science.gov (United States)

    Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

    2013-04-01

    The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

  13. A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods

    Directory of Open Access Journals (Sweden)

    Bita Forghani

    2012-05-01

    Full Text Available L-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218 were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA as a bioactive compound.

  14. A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods

    Science.gov (United States)

    Zareian, Mohsen; Ebrahimpour, Afshin; Bakar, Fatimah Abu; Mohamed, Abdul Karim Sabo; Forghani, Bita; Ab-Kadir, Mohd Safuan B.; Saari, Nazamid

    2012-01-01

    l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. PMID:22754309

  15. Butyrate induces reactive oxygen species production and affects cell cycle progression in human gingival fibroblasts.

    Science.gov (United States)

    Chang, M-C; Tsai, Y-L; Chen, Y-W; Chan, C-P; Huang, C-F; Lan, W-C; Lin, C-C; Lan, W-H; Jeng, J-H

    2013-02-01

    Short-chain fatty acids, such as butyric acid and propionic acid, are metabolic by-products generated by periodontal microflora such as Porphyromonas gingivalis, and contribute to the pathogenesis of periodontitis. However, the effects of butyrate on the biological activities of gingival fibroblasts (GFs) are not well elucidated. Human GFs were exposed to various concentrations of butyrate (0.5-16 mm) for 24 h. Viable cells that excluded trypan blue were counted. Cell cycle distribution of GFs was analyzed by propidium iodide-staining flow cytometry. Cellular reactive oxygen species (ROS) production was measured by flow cytometry using 2',7'-dichlorofluorescein (DCF). Total RNA and protein lysates were isolated and subjected to RT-PCR using specific primers or to western blotting using specific antibodies, respectively. Butyrate inhibited the growth of GFs, as indicated by a decrease in the number of viable cells. This event was associated with an induction of G0/G1 and G2/M cell cycle arrest by butyrate (4-16 mm) in GFs. However, no marked apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT-PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS. These results suggest that butyrate generated by periodontal pathogens may be involved in the pathogenesis of periodontal diseases via the induction of ROS production and the impairment of cell growth, cell cycle progression and expression of cell cycle-related genes in GFs. These events are important in the initiation and prolongation of inflammatory processes in periodontal diseases. © 2012 John Wiley & Sons A/S.

  16. Effect of butyrate on immune response of a chicken macrophage cell line.

    Science.gov (United States)

    Zhou, Z Y; Packialakshmi, B; Makkar, S K; Dridi, S; Rath, N C

    2014-11-15

    Butyric acid is a major short chain fatty acid (SCFA), produced in the gastrointestinal tract by anaerobic bacterial fermentation, that has beneficial health effects in many species including poultry. To understand the immunomodulating effects of butyrate on avian macrophage, we treated a naturally transformed line of chicken macrophage cells named HTC with Na-butyrate in the absence or presence of Salmonella typhimurium lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA), a metabolic activator, evaluating its various functional parameters. The results demonstrate that, butyrate by itself had no significant effect on variables such as nitric oxide (NO) production and the expression of genes associated with various inflammatory cytokines but it inhibited NO production, and reduced the expression of cytokines such as IL-1β, IL-6, IFN-γ, and IL-10 in LPS-stimulated cells. Butyrate decreased the expression of TGF-β3 in the presence or absence of LPS, while it had no effect on IL-4, Tβ4, and MMP2 gene expression. In addition, butyrate augmented PMA induced oxidative burst indicated by DCF-DA oxidation and restored LPS induced attenuation of tartrate resistant acid phosphatase (TRAP) activity. Although butyrate had no significant effect on phagocytosis or matrix metalloproteinase (MMP) activities of resting macrophages, it significantly suppressed the effects induced by their respective stimulants such as LPS induced phagocytosis and PMA induced MMP expression. These results suggest that butyrate has immunomodulatory property in the presence of agents that incite the cells thus, has potential to control inflammation and restore immune homeostasis. Published by Elsevier B.V.

  17. Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

    Directory of Open Access Journals (Sweden)

    Guillaume Dalmasso

    Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. RESULTS: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1 promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. CONCLUSIONS: Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.

  18. Metabotropic GABAB receptors mediate GABA inhibition of acetylcholine release in the rat neuromuscular junction.

    Science.gov (United States)

    Malomouzh, Artem I; Petrov, Konstantin A; Nurullin, Leniz F; Nikolsky, Evgeny E

    2015-12-01

    Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. GABA's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GABAA receptor blocker, but was attenuated following application of the GABAB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the GABA-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GABAB receptor (GABAB R1 and GABAB R2) in the neuromuscular junction. These findings suggest that metabotropic GABAB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (GABA) on neuromuscular transmission. GABA reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GABAB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GABAB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release. © 2015 International Society for Neurochemistry.

  19. Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract.

    Science.gov (United States)

    Mei, Lin; Zhang, Jing; Mifflin, Steve

    2003-12-01

    Previous studies have demonstrated that microinjection of baclofen, a GABA(B) receptor agonist, into the nucleus of the solitary tract (NTS) results in an enhanced pressor response in hypertensive (HT) rats compared with normotensive (NT) rats, suggesting a possible alteration in the responses of neurons in this area to activation of GABA(B) receptors. The following studies were designed to determine whether HT alters the sensitivity of neurons in the NTS to GABA receptor agonists. Sham-operated NT and unilateral nephrectomized, renal-wrap HT Sprague-Dawley rats were anesthetized, and the responses of NTS neurons receiving aortic nerve (AN) afferent inputs to iontophoretic application of GABA, the GABA(A) receptor agonist muscimol, and the GABA(B) agonist baclofen were examined. The AN input was classified as monosynaptic (MSN) if the cell responded to each of two stimuli separated by 5 ms with an action potential. If the cell did not respond, the input was considered polysynaptic (PSN). In MSNs, inhibition of AN-evoked discharge by GABA was not altered in 1 wk of HT but was reduced in 4 wk of HT, whereas in PSNs, sensitivity to GABA was reduced at 1 and 4 wk of HT. In HT rats, inhibition of AN-evoked discharge by baclofen was enhanced in MSNs, but not in PSNs, after 1 and 4 wk of HT, whereas inhibition by muscimol was reduced in MSNs and PSNs at 1 and 4 wk of HT. Changes in sensitivity to muscimol and baclofen within MSNs were the same whether the MSN received a slowly or a rapidly conducted AN afferent input. The results demonstrate that early in HT the sensitivity of NTS neurons to inhibitory amino acids is altered and that these changes are maintained for > or =4 wk. The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono- or polysynaptic baroreceptor afferent input.

  20. Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner.

    Science.gov (United States)

    Li, Qingran; Ding, Chujie; Meng, Tuo; Lu, Wenjie; Liu, Wenyue; Hao, Haiping; Cao, Lijuan

    2017-12-01

    Butyrate is a typical short chain fatty acid produced by gut microbiota of which the dysmetabolism has been consistently associated with colorectal diseases. However, whether butyrate affects metastatic colorectal cancer is not clear. In this study we investigated in vitro the effect of butyrate on motility, a significant metastatic factor of colorectal cancer cells and explored the potential mechanism. By using wound healing and transwell-based invasion models, we demonstrated that pretreatment of butyrate significantly inhibited motility of HCT116, HT29, LOVO and HCT8 cells, this activity was further attributed to deactivation of Akt1 and ERK1/2. Suberanilohydroxamic acid (SAHA), another HDAC inhibitor, mimicked the inhibitory effect of butyrate on cell motility and deactivation of Akt/ERK. Furthermore, by silencing of HDAC3 with siRNA, we confirmed dependence of butyrate's effect on HDAC3, the similar reduced cell motility observed under HDAC3 silencing also indicates the significance of HDAC itself in cell motility. In conclusion, we confirmed the HDAC3-relied activity of butyrate on inhibiting motility of colorectal cancer cells via deactivating Akt/ERK signaling. Our data indicate that modulating butyrate metabolism is an effective therapeutic strategy of metastatic colorectal cancer; and HDAC3 might be a novel target for management of colorectal cancer metastasis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. The Transporter GAT1 Plays an Important Role in GABA-mediated Carbon-Nitrogen Interactions in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Albert eBatushansky

    2015-09-01

    Full Text Available Glutamate derived γ-aminobutyric acid (GABA is synthetized in the cytosol prior to delivery to the mitochondria where it is catabolized via the TCA cycle. GABA accumulates under various environmental conditions, but an increasing number of studies show its involvement at the crossroad between C and N metabolism. To assess the role of GABA in modulating cellular metabolism, we exposed seedlings of A. thaliana GABA transporter gat1 mutant to full nutrition medium and media deficient in C and N combined with feeding of different concentrations (0.5 mM and 1mM of exogenous GABA. GC-MS based metabolite profiling showed an expected effect of medium composition on the seedlings metabolism of mutant and wild type alike. That being said, a significant interaction between GAT1 deficiency and medium composition was determined with respect to magnitude of change in relative amino acid levels. The effect of exogenous GABA treatment on metabolism was contingent on both the medium and the genotype, leading for instance to a drop in asparagine under full nutrition and low C conditions and glucose under all tested media, but not to changes in GABA content. We additionally assessed the effect of GAT1 deficiency on the expression of glutamate metabolism related genes and genes involved in abiotic stress responses. These results suggest a role for GAT1 in GABA-mediated metabolic alterations in the context of the C-N equilibrium of plant cells.

  2. The role of butyrate, a histone deacetylase inhibitor in diabetes mellitus: experimental evidence for therapeutic intervention.

    Science.gov (United States)

    Khan, Sabbir; Jena, Gopabandhu

    2015-01-01

    The contribution of epigenetic mechanisms in diabetes mellitus (DM), β-cell reprogramming and its complications is an emerging concept. Recent evidence suggests that there is a link between DM and histone deacetylases (HDACs), because HDAC inhibitors promote β-cell differentiation, proliferation, function and improve insulin resistance. Moreover, gut microbes and diet-derived products can alter the host epigenome. Furthermore, butyrate and butyrate-producing microbes are decreased in DM. Butyrate is a short-chain fatty acid produced from the fermentation of dietary fibers by microbiota and has been proven as an HDAC inhibitor. The present review provides a pragmatic interpretation of chromatin-dependent and independent complex signaling/mechanisms of butyrate for the treatment of Type 1 and Type 2 DM, with an emphasis on the promising strategies for its drugability and therapeutic implication.

  3. n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells

    International Nuclear Information System (INIS)

    Diakos, Christos; Prieschl, Eva E.; Saeemann, Marcus D.; Boehmig, Georg A.; Csonga, Robert; Sobanov, Yury; Baumruker, Thomas; Zlabinger, Gerhard J.

    2006-01-01

    Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-α transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling

  4. n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells.

    Science.gov (United States)

    Diakos, Christos; Prieschl, Eva E; Säemann, Marcus D; Böhmig, Georg A; Csonga, Robert; Sobanov, Yury; Baumruker, Thomas; Zlabinger, Gerhard J

    2006-10-20

    Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-alpha transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling.

  5. GABA localization in the nematode Ascaris

    Energy Technology Data Exchange (ETDEWEB)

    Guastella, J.

    1988-01-01

    A histochemical approach was used to examine the distribution of GABA-associated neurons in the nematode Ascaris, an organism whose small number of morphologically simple neurons make it an excellent preparation for analyzing neuronal phenotypes. Two GABAergic markers were examined: GABA-like immunoreactivity (GLIR), a marker for endogenous stores of GABA; and ({sup 3}H)-GABA uptake, a marker for GABA uptake sites. Strong GLIR was present in the cell bodies, neurites and commissures of dorsal and ventral inhibitory motorneurons present in this region. Strong GLIR was also present in the cell bodies and processes of the four RME neurons in the nerve ring and in several other ganglionic neurons. Staining was absent in excitatory motorneurons, in ventral cord interneurons and in muscle cells and hypodermis. GABA uptake sites were found in single neural processes in both the ventral and dorsal nerve cords. ({sup 3}H)-GABA labeling was also observed in the other two RME cells and several other cephalic neurons. Four putative cholinergic excitatory motorneurons in the retrovesicular ganglion (RVG) were heavily labeled. Ventral and dorsal nerve cord inhibitory motorneurons did not take up ({sup 3}H)-GABA. Labeling of the ventral cord excitatory motorneuron somata and cell bodies was at or slightly above background. Heavy labeling of muscle cells was also observed.

  6. Photic release of radioactivity from rabbit retina preloaded with [3H]GABA

    International Nuclear Information System (INIS)

    Bauer, B.

    1978-01-01

    The in vitro release of radioactivity by light from rabbit retina was studied after intravitreal injection of [ 3 H]GABA (γ-aminobutyric acid). The site of uptake of [ 3 H]GABA into the retina after intravitreal injection was checked by autoradiography and was localized at 2 h after the injection mainly in glia but at 4 h in amacrine cells and some ganglion cells. If the retina loaded with [ 3 H]GABA was stimulated by light flashes the efflux of radioactivity increased significantly. Chromatographic analysis of the superfusate demonstrated that [ 3 H]GABA was released by light stimulation. However, the efflux was not elicited by constant light, and was abolished in a medium containing 20 mM Mg ++ and 0.2 mM ++ ). When the metabolism of GABA was inhibited by amino-oxyacetic acid, light flashes no longer increased the efflux of radioactivity significantly. No light-evoked release of radioactivity could be demonstrated from glia. Pentobarbitone inhibited the spontaneous efflux and prior anaesthetization with pentobarbitone abolished the light-evoked release. These results support the view that GABA is a retinal neurotransmitter in the rabbit. (author)

  7. Indol-butyric acid levels on cashew cloning by air-layering process Níveis de ácido indolbutírico na clonagem do cajueiro pelo processo de mergulhia aérea

    Directory of Open Access Journals (Sweden)

    Rodrigo Luiz Lopes

    2005-12-01

    Full Text Available A study was conducted to determine the possibility of cashew (Anacardium occidentale cloning by air-layering and influence of IBA (indol-butyric acid on this process. It was adopted a completely randomized design with 4 treatments, 10 air layers each and 4 replications, reaching 160 air layers. The IBA levels on the treatments were, as follow: 0, 1000, 3000 and 5000 mg.kg-1. It was evaluated: survival, callus and rooting percentage, average number and length of roots. The highest survival rate (67.5% was registered with no growth regulator and IBA at 1000 mg.kg-1, while the best rooting percentage (82% referred to 1000 mg.kg-1. In spite of average number and length of roots, the highest results were observed with IBA at 5000 mg.kg-1. IBA concentrations had no influence on cashew air-layering formation.Um estudo foi conduzido com a finalidade de determinar a possibilidade de clonagem do cajueiro (Anacardium occidentale por alporquia e a influência do AIB (ácido indolbutírico nesse processo. Adotou-se delineamento experimental inteiramente casualizado, com 4 tratamentos, 10 alporques por parcela, repetidos por 4 vezes, num total de 160 alporques. Os tratamentos constaram das concentrações de AIB: 0 (testemunha, 1.000, 3.000 e 5.000 mg.kg-1. Foram avaliadas as percentagens de sobrevivência, calejamento e enraizamento, bem como número e comprimento médio de raízes. A maior percentagem de sobrevivência (67,5% foi observada para a testemunha e concentração de 1.000 mg.kg-1, enquanto a melhor percentagem de enraizamento (82% foi relacionada com o nível de 1.000 mg.kg-1. Para o número e comprimento médio de raízes, os melhores resultados foram concernentes à dose de 5.000 mg.kg-1. Não houve influência do AIB na clonagem do cajueiro por alporquia.

  8. Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression.

    Science.gov (United States)

    Seki, Keisuke; Cueno, Marni E; Kamio, Noriaki; Saito, Yuko; Kamimoto, Atsushi; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2016-06-01

    Neuropathic pain is absent from the early stages of periodontal disease possibly due to neurite retraction. Butyric acid (BA) is a periodontopathic metabolite that activates several stress-related signals and, likewise, induce neurite retraction. Neuronal cell death is associated to neurite retraction which would suggest that BA-induced neurite retraction is ascribable to neuronal cell death. However, the underlying mechanism of BA-related cell death signaling remains unknown. In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress-related (H2O2, glutathione reductase, calcium (Ca(2+)), plasma membrane Ca(2+) ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF-α, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodontal disease-level BA concentration (5 mM), we observed that only FasL amounts were affected and occurred concurrently with chromatin condensation insinuating that cells have fully committed to neurodegeneration. Thus, we believe that both stress and cell death signaling in NGF-treated PC12 cells are affected differently depending on BA concentration. In a periodontal disease scenario, we hypothesize that during the early stages, low BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurite non-proliferation, whereas, during the later stages, high BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurodegeneration. More importantly, we propose that neuropathic pain absence at any stage of periodontal disease progression is ascribable to BA accumulation regardless of amount.

  9. Bicarbonate-dependent transport of acetate and butyrate across the basolateral membrane of sheep rumen epithelium.

    Science.gov (United States)

    Dengler, F; Rackwitz, R; Benesch, F; Pfannkuche, H; Gäbel, G

    2014-02-01

    This study aimed to assess the role of HCO₃⁻ in the transport of acetate and butyrate across the basolateral membrane of rumen epithelium and to identify transport proteins involved. The effects of basolateral variation in HCO₃⁻ concentrations on acetate and butyrate efflux out of the epithelium and the transepithelial flux of these short-chain fatty acids were tested in Ussing chamber experiments using (14)C-labelled substrates. HCO₃⁻-dependent transport mechanisms were characterized by adding specific inhibitors of candidate proteins to the serosal side. Effluxes of acetate and butyrate out of the epithelium were higher to the serosal side than to the mucosal side. Acetate and butyrate effluxes to both sides of rumen epithelium consisted of HCO₃⁻-independent and -dependent parts. HCO₃⁻-dependent transport across the basolateral membrane was confirmed in studies of transepithelial fluxes. Mucosal to serosal fluxes of acetate and butyrate decreased with lowering serosal HCO₃⁻ concentrations. In the presence of 25 mm HCO₃⁻, transepithelial flux of acetate was inhibited effectively by p-hydroxymercuribenzoic acid or α-cyano-4-hydroxycinnamic acid, while butyrate flux was unaffected by the blockers. Fluxes of both acetate and butyrate from the serosal to the mucosal side were diminished largely by the addition of NO₃⁻ to the serosal side, with this effect being more pronounced for acetate. Our results indicate the existence of a basolateral short-chain fatty acid/HCO₃⁻ exchanger, with monocarboxylate transporter 1 as a primary candidate for acetate transfer. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Avaliação de genótipos de arroz sob efeito do ácido butírico Rice genotype evaluation under butyric acid effect

    Directory of Open Access Journals (Sweden)

    Mauricio Marini Kopp

    2010-06-01

    Full Text Available Solos do tipo hidromórfico apresentam uma reduzida capacidade de drenagem, sendo utilizados principalmente para cultivo de arroz irrigado. Esta condição favorece o desenvolvimento de microrganismos anaeróbios que produzem substâncias fitotóxicas. O objetivo do trabalho foi avaliar a resposta de 25 genótipos de arroz ao ácido butírico, um composto produzido em solos de deficiente drenagem e alto teor de matéria orgânica. O trabalho foi executado em sistema de hidroponia com 4 doses do ácido e o delineamento utilizado foi blocos casualizados com 3 repetições em um esquema fatorial. As variáveis mensuradas foram comprimento de raízes (CR e de parte aérea (CPA, número de raízes (NR e matéria seca de raízes (MSR e parte aérea (MSPA. Foram procedidas análise de variância, desempenho relativo e ajuste de regressões. Os efeitos para genótipos e doses de ácido butírico foram todos significativos. Apenas os efeitos de interação entre doses x genótipos para as variáveis CR e MSR revelaram significância. A variável CR foi a mais afetada pelo ácido e as regressões estabelecidas para essa variável revelaram 9 genótipos tolerantes e 16 sensíveis ao efeito fitototoxico do ácido butírico. Genótipos desenvolvidos para sistema de irrigação por inundação se mostraram mais tolerantes ao ácido.Hydromorphic soils have low drainage capacity and are used mainly for growing irrigated rice.. This condition favors the development of anaerobic microorganisms that produce phytotoxic substances. The objective of this work was to evaluate the response of 25 rice genotypes to butyric acid, a phytotoxic compound produced in low-drainage soils with high organic matter content. This work was performed by hydroponics with four acid doses as treatments using a random block design with three replications. The variables measured were root (CR and shoot (CPA length, number of roots (NR and root (MSR and shoot (MSPA dry matter. Analysis of

  11. Dorsolateral Prefrontal Cortex GABA Concentration in Humans Predicts Working Memory Load Processing Capacity.

    Science.gov (United States)

    Yoon, Jong H; Grandelis, Anthony; Maddock, Richard J

    2016-11-16

    The discovery of neural mechanisms of working memory (WM) would significantly enhance our understanding of complex human behaviors and guide treatment development for WM-related impairments found in neuropsychiatric conditions and aging. Although the dorsolateral prefrontal cortex (DLPFC) has long been considered critical for WM, we still know little about the neural elements and pathways within the DLPFC that support WM in humans. In this study, we tested whether an individual's DLPFC gamma-aminobutryic acid (GABA) content predicts individual differences in WM task performance using a novel behavioral approach. Twenty-three healthy adults completed a task that measured the unique contribution of major WM components (memory load, maintenance, and distraction resistance) to performance. This was done to address the possibility that components have differing GABA dependencies and the failure to parse WM into components would lead to missing true associations with GABA. The subjects then had their DLPFC GABA content measured by single-voxel proton magnetic spectroscopy. We found that individuals with lower DLPFC GABA showed greater performance degradation with higher load, accounting for 31% of variance, p (corrected) = 0.015. This relationship was component, neurochemical, and brain region specific. DLPFC GABA content did not predict performance sensitivity to other components tested; DLPFC glutamate + glutamine and visual cortical GABA content did not predict load sensitivity. These results confirm the involvement of DLPFC GABA in WM load processing in humans and implicate factors controlling DLPFC GABA content in the neural mechanisms of WM and its impairments. This study demonstrated for the first time that the amount of gamma-aminobutryic acid (GABA), the major inhibitory neurotransmitter of the brain, in an individual's prefrontal cortex predicts working memory (WM) task performance. Given that WM is required for many of the most characteristic cognitive and

  12. Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocan expression by MAPK signaling pathway.

    Science.gov (United States)

    Zuo, Li; Lu, Man; Zhou, Qing; Wei, Wei; Wang, Yuan

    2013-12-01

    Butyrate is a short-chain fatty acid produced by colonic bacterial fermentation. In colon cancer cells butyrate is able to suppress cell growth, induce apoptosis. It also inhibits tumor growth in vivo. However, the underlying mechanism is still not fully understood. We hypothesize that butyrate regulates the growth and migration of colon cancer cells by altering endocan expression. To test this hypothesis, we performed quantitative real time RT–PCR and Western blots, and found that butyrate increased endocan expression of colon cancer cell RKO. Moreover, endocan over-expression inhibited RKO proliferation, migration and colony formation. Functionally, butyrate significantly suppressed RKO proliferation, migration, and colony formation, as well as induced apoptosis. Knocking down endogenous endocan was able to attenuate the inhibitory role of butyrate in RKO migration and proliferation. Since our results showed that butyrate inhibited MAPK/ERK2 phosphorylation. To determine whether ERK2 signaling is associated with endocan expression, we knocked down endogenous ERK2 expression. Our results showed that knocking down ERK2 expression up-regulated endocan expression. Taken together, these results suggested that butyrate suppressed RKO proliferation, colony formation, migration through up-regulating endocan expression via ERK2/MAPK signaling pathway.

  13. Transcriptome Characterization by RNA-seq Unravels the Mechanisms of Butyrate-Induced Epigenomic Regulation in Bovine Cells

    Science.gov (United States)

    Wu, Sitao; Li, Robert W.; Li, Weizhong; Li, Cong-jun

    2012-01-01

    Short-chain fatty acids (SCFAs), especially butyrate, affect cell differentiation, proliferation, and motility. Butyrate also induces cell cycle arrest and apoptosis through its inhibition of histone deacetylases (HDACs). In addition, butyrate is a potent inducer of histone hyper-acetylation in cells. Therefore, this SCFA provides an excellent in vitro model for studying the epigenomic regulation of gene expression induced by histone acetylation. In this study, we analyzed the differential in vitro expression of genes induced by butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA-seq). The number of sequences read, ranging from 57,303,693 to 78,933,744, were generated per sample. Approximately 11,408 genes were significantly impacted by butyrate, with a false discovery rate (FDR) butyrate included cell morphological changes, cell cycle arrest, and apoptosis. Our results provided insight into the transcriptome alterations induced by butyrate, which will undoubtedly facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells. PMID:22615851

  14. Transcriptome characterization by RNA-seq unravels the mechanisms of butyrate-induced epigenomic regulation in bovine cells.

    Directory of Open Access Journals (Sweden)

    Sitao Wu

    Full Text Available Short-chain fatty acids (SCFAs, especially butyrate, affect cell differentiation, proliferation, and motility. Butyrate also induces cell cycle arrest and apoptosis through its inhibition of histone deacetylases (HDACs. In addition, butyrate is a potent inducer of histone hyper-acetylation in cells. Therefore, this SCFA provides an excellent in vitro model for studying the epigenomic regulation of gene expression induced by histone acetylation. In this study, we analyzed the differential in vitro expression of genes induced by butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA-seq. The number of sequences read, ranging from 57,303,693 to 78,933,744, were generated per sample. Approximately 11,408 genes were significantly impacted by butyrate, with a false discovery rate (FDR <0.05. The predominant cellular processes affected by butyrate included cell morphological changes, cell cycle arrest, and apoptosis. Our results provided insight into the transcriptome alterations induced by butyrate, which will undoubtedly facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells.

  15. Pathway of butyrate catabolism by Desulfobacterium cetonicum

    OpenAIRE

    Janssen, Peter H.; Schink, Bernhard

    1995-01-01

    Desulfobacterium cetonicum 480 oxidized butyrate to 1 mol of acetate and 2 mol of CO2; this reaction was coupled to reduction of sulfate to sulfide. Butyrate was activated by coenzyme A (CoA) transfer from acetyl-CoA, and butyryl-CoA was oxidized to acetyl-CoA by a classical beta-oxidation pathway. Acetyl-CoA was oxidized through the acetyl-CoA/carbon monoxide dehydrogenase pathway. There was a rapid exchange of 14CO2 into the intermediate CoA esters and into acetate and butyrate, showing tha...

  16. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

  17. GABA(B) receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats.

    Science.gov (United States)

    McQuail, Joseph A; Bañuelos, Cristina; LaSarge, Candi L; Nicolle, Michelle M; Bizon, Jennifer L

    2012-06-01

    Gamma aminobutyric acid (GABA)(B) receptors (GABA(B)Rs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABA(B)R expression and signaling. Thus, we investigated GABA(B)R expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABA(B)R1 and GABA(B)R2 proteins were reduced in the prefrontal cortex of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABA(B)R1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABA(B)R complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Directory of Open Access Journals (Sweden)

    Meeri Eeva-Liisa Mäkinen

    2018-03-01

    Full Text Available The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging and temporal resolution microelectrode array (MEA. We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling.

  19. GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2014-04-01

    Full Text Available Aims: γ-aminobutyric acid (GABA, the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs. Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.

  20. Butyrate: A dietary inhibitor of histone deacetylases and an epigenetic regulator

    Science.gov (United States)

    The short-chain fatty acids (SCFAs) acetate, propionate and butyrate, also known as volatile fatty acids (VFA), are produced in the gastrointestinal tract by microbial fermentation. Consumption of dietary fibers has been shown to have positive metabolic health effects, such as increasing satiety, an...

  1. Detection of amino acid neurotransmitters by surface enhanced Raman scattering and hollow core photonic crystal fiber

    Science.gov (United States)

    Tiwari, Vidhu S.; Khetani, Altaf; Monfared, Ali Momenpour T.; Smith, Brett; Anis, Hanan; Trudeau, Vance L.

    2012-03-01

    The present work explores the feasibility of using surface enhanced Raman scattering (SERS) for detecting the neurotransmitters such as glutamate (GLU) and gamma-amino butyric acid (GABA). These amino acid neurotransmitters that respectively mediate fast excitatory and inhibitory neurotransmission in the brain, are important for neuroendocrine control, and upsets in their synthesis are also linked to epilepsy. Our SERS-based detection scheme enabled the detection of low amounts of GLU (10-7 M) and GABA (10-4 M). It may complement existing techniques for characterizing such kinds of neurotransmitters that include high-performance liquid chromatography (HPLC) or mass spectrography (MS). This is mainly because SERS has other advantages such as ease of sample preparation, molecular specificity and sensitivity, thus making it potentially applicable to characterization of experimental brain extracts or clinical diagnostic samples of cerebrospinal fluid and saliva. Using hollow core photonic crystal fiber (HC-PCF) further enhanced the Raman signal relative to that in a standard cuvette providing sensitive detection of GLU and GABA in micro-litre volume of aqueous solutions.

  2. Maternal butyrate supplementation induces insulin resistance associated with enhanced intramuscular fat deposition in the offspring.

    Science.gov (United States)

    Huang, Yanping; Gao, Shixing; Chen, Jinglong; Albrecht, Elke; Zhao, Ruqian; Yang, Xiaojing

    2017-02-21

    Maternal nutrition is important for the risk of the offspring to develop insulin resistance and adiposity later in life. The study was undertaken to determine effects of maternal butyrate supplementation on lipid metabolism and insulin sensitivity in the offspring skeletal muscle. The offspring of rats, fed a control diet or a butyrate diet (1% sodium butyrate) throughout gestation and lactation, was studied at weaning and at 60 days of age. The offspring of dams fed a butyrate diet had higher HOMA-insulin resistance and impaired glucose tolerance. This was associated with elevated mRNA and protein expressions of lipogenic genes and decreased amounts of lipolytic enzyme. Simultaneously, enhanced acetylation of histone H3 lysine 9 and histone H3 lysine 27 modification on the lipogenic genes in skeletal muscle of adult offspring was observed. Higher concentration of serum insulin and intramuscular triglyceride in skeletal muscle of offspring from the butyrate group at weaning were accompanied by increasing levels of lipogenic genes and enrichment of acetylation of histone H3 lysine 27. Maternal butyrate supplementation leads to insulin resistance and ectopic lipid accumulation in skeletal muscle of offspring, indicating the importance of short chain fatty acids in the maternal diet on lipid metabolism.

  3. Perturbation Dynamics of the Rumen Microbiota in Response to Exogenous Butyrate

    Science.gov (United States)

    Li, Robert W.; Wu, Sitao; Baldwin, Ransom L.; Li, Weizhong; Li, Congjun

    2012-01-01

    The capacity of the rumen microbiota to produce volatile fatty acids (VFAs) has important implications in animal well-being and production. We investigated temporal changes of the rumen microbiota in response to butyrate infusion using pyrosequencing of the 16S rRNA gene. Twenty one phyla were identified in the rumen microbiota of dairy cows. The rumen microbiota harbored 54.5±6.1 genera (mean ± SD) and 127.3±4.4 operational taxonomic units (OTUs), respectively. However, the core microbiome comprised of 26 genera and 82 OTUs. Butyrate infusion altered molar percentages of 3 major VFAs. Butyrate perturbation had a profound impact on the rumen microbial composition. A 72 h-infusion led to a significant change in the numbers of sequence reads derived from 4 phyla, including 2 most abundant phyla, Bacteroidetes and Firmicutes. As many as 19 genera and 43 OTUs were significantly impacted by butyrate infusion. Elevated butyrate levels in the rumen seemingly had a stimulating effect on butyrate-producing bacteria populations. The resilience of the rumen microbial ecosystem was evident as the abundance of the microorganisms returned to their pre-disturbed status after infusion withdrawal. Our findings provide insight into perturbation dynamics of the rumen microbial ecosystem and should guide efforts in formulating optimal uses of probiotic bacteria treating human diseases. PMID:22253719

  4. Characterization of butyrate transport across the luminal membranes of equine large intestine.

    Science.gov (United States)

    Nedjadi, Taoufik; Moran, Andrew W; Al-Rammahi, Miran A; Shirazi-Beechey, Soraya P

    2014-10-01

    The diet of the horse, pasture forage (grass), is fermented by the equine colonic microbiota to short-chain fatty acids, notably acetate, propionate and butyrate. Short-chain fatty acids provide a major source of energy for the horse and contribute to many vital physiological processes. We aimed to determine both the mechanism of butyrate uptake across the luminal membrane of equine colon and the nature of the protein involved. To this end, we isolated equine colonic luminal membrane vesicles. The abundance and activity of cysteine-sensitive alkaline phosphatase and villin, intestinal luminal membrane markers, were significantly enriched in membrane vesicles compared with the original homogenates. In contrast, the abundance of GLUT2 protein and the activity of Na(+)-K(+)-ATPase, known markers of the intestinal basolateral membrane, were hardly detectable. We demonstrated, by immunohistochemistry, that monocarboxylate transporter 1 (MCT1) protein is expressed on the luminal membrane of equine colonocytes. We showed that butyrate transport into luminal membrane vesicles is energized by a pH gradient (out butyrate uptake is time and concentration dependent, with a Michaelis-Menten constant of 5.6 ± 0.45 mm and maximal velocity of 614 ± 55 pmol s(-1) (mg protein)(-1). Butyrate transport is significantly inhibited by p-chloromercuribenzoate, phloretin and α-cyano-4-hydroxycinnamic acid, all potent inhibitors of MCT1. Moreover, acetate and propionate, as well as the monocarboxylates pyruvate and lactate, also inhibit butyrate uptake. Data presented here support the conclusion that transport of butyrate across the equine colonic luminal membrane is predominantly accomplished by MCT1. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  5. Unusual aggregation of bis(2-quinuclidinium-butyrate) hydrobromides

    Science.gov (United States)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2010-12-01

    The molecular structure of di-[bis(2-quinuclidinium-butyrate) hydrobromide], [(QNBu) 2HBr] 2 ( 1), has been characterized by single-crystal X-ray diffraction, infrared spectroscopy and DFT calculations. The crystals ( 1) are monoclinic, space group P2 1/c with [(QNBu) 2HBr] 2 symmetry-independent units. The complex 1 consists of two independent homoconjugated cations, in which two ( S) QNBu semications, and ( S) and ( R) QNBu semications are joined by short, symmetrical O⋯H⋯O hydrogen bonds of 2.418(12) and 2.411(13) Å, respectively. The bromide anions interact electrostatically with the one positively charged nitrogen atom of each cation. The presence of short OHO hydrogen bonds is confirmed by the broad absorption in the 1500-400 cm -1 region, with the center of gravity, νH, at ca. 900 cm -1, in the solid-state FTIR spectrum. In the structure of [(QNBu) 2HBr] 2 ( 2) optimized at the B3LYP/6-31G(d,p) level of theory, the 2-quinuclidinium-butyrate units are non-equivalent. In each homoconjugated cation the 2-quinuclidinium-butyric acid interacts with the QNBu inner salt by the short, asymmetric O-H···O hydrogen bonds of 2.440 and 2.446 Å, respectively. Each bromide anion interacts electrostatically with the positively charged nitrogen atoms from both homoconjugated cations, which fold into a globular supramolecular aggregate.

  6. Genome Sequence of Lactococcus lactis subsp. lactis NCDO 2118, a GABA-Producing Strain

    DEFF Research Database (Denmark)

    Oliveira, Letícia C; Saraiva, Tessália D L; Soares, Siomar C

    2014-01-01

    Lactococcus lactis subsp. lactis NCDO 2118 is a nondairy lactic acid bacterium, a xylose fermenter, and a gamma-aminobutyric acid (GABA) producer isolated from frozen peas. Here, we report the complete genome sequence of L. lactis NCDO 2118, a strain with probiotic potential activity....

  7. Sustained Induction of Fetal Hemoglobin by Pulse Butyrate Therapy in Sickle Cell Disease

    Science.gov (United States)

    Atweh, George F.; Sutton, Millicent; Nassif, Imad; Boosalis, Vassiliki; Dover, George J.; Wallenstein, Sylvan; Wright, Elizabeth; McMahon, Lillian; Stamatoyannopoulos, George; Faller, Douglas V.; Perrine, Susan P.

    2014-01-01

    High levels of fetal hemoglobin (Hb F) protect from many of the complications of sickle cell disease and lead to improved survival. Butyrate and other short chain fatty acids were previously shown to increase Hb F production in erythroid cells in vitro and in animal models in vivo. However, butyrates are also known to inhibit the proliferation of many cell types, including erythroid cells. Experience with the use of butyrate in animal models and in early clinical trials demonstrated that the Hb F response may be lost after prolonged administration of high doses of butyrate. We hypothesized that this loss of response may be a result of the antiproliferative effects of butyrate. We designed a regimen consisting of intermittent or pulse therapy in which butyrate was administered for 4 days followed by 10 to 24 days with no drug exposure. This pulse regimen induced fetal globin gene expression in 9 of 11 patients. The mean Hb F in this group increased from 7.2% to 21.0% (P butyrate therapy for a mean duration of 29.9 weeks. This was associated with a parallel increase in the number of F cells and F reticulocytes. The total hemoglobin levels also increased from a mean of 7.8 g/dL to a mean of 8.8 g/dL (P butyrate therapy for more than 28 months. This regimen, which resulted in a marked and sustained increase in Hb F levels in more than two thirds of the adult sickle cell patients enrolled in this study, was well tolerated without adverse side effects. These encouraging results require confirmation along with an appropriate evaluation of clinical outcomes in a larger number of patients with sickle cell disease. PMID:10068649

  8. Butyrate-mediated acquisition of chemoresistance by human colon cancer cells.

    Science.gov (United States)

    Kang, Hyang Ri; Choi, Hyeon Gyeom; Jeon, Chae Kyung; Lim, Soo-Jeong; Kim, So Hee

    2016-08-01

    Butyrate is a short-chain fatty acid produced by the intestinal microflora and it not only induces apoptosis but also inhibits the proliferation of cancer cells. Recently, it has been reported that butyrate may cause resistance in colon cancer cells. Therefore, we investigated the effects of increased resistance to butyrate in HCT116 colon cancer cells. We established HCT116 cells resistant to butyrate (HCT116/BR) by treating HCT116 parental cells (HCT116/PT) with increasing concentrations of butyrate to a maximum of 1.6 mM for 3 months. The butyrate concentrations that inhibited cell growth by 50% (IC50) were 0.508 and 5.50 mM in HCT116/PT and HCT116/BR cells. The values after treatment with paclitaxel, 5-fluorouracil (5-FU), doxorubicin and trichostatin A (TSA) were 2.42, 2.36, 4.31 and 11.3-fold higher, respectively, in HCT116/BR cells compared with HCT116/PT cells. The protein expression of drug efflux pumps, such as P-glycoprotein (P-gp), breast cancer-resistant protein (BCRP) and the multidrug resistance associated protein 1 (MRP1), did not differ between HCT116/PT and HCT116/BR cells. The expression level of the anti-apoptotic Bcl-xL protein was increased while those of pro-apoptotic Bax and Bim proteins were reduced in HCT116/BR cells. There were no significant differences in cell motility and invasion. This study suggests that exposure of colon cancer cells to butyrate results in development of resistance to butyrate, which may play a role in the acquisition of chemoresistance in colon cancer.

  9. GABA expression and regulation by sensory experience in the developing visual system.

    Directory of Open Access Journals (Sweden)

    Loïs S Miraucourt

    Full Text Available The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function.

  10. The role of GABA in the hypoxia tolerance of the epaulette shark

    International Nuclear Information System (INIS)

    Wise, G.; Mulvey, J.; Renshaw, G.M.C.; Dodd, P.R.

    1998-01-01

    Full text: The epaulette shark responds to hypoxia with brain hypometabolism which is correlated with increased levels of gamma-aminobutyric acid (GABA). We examined GABA-like immunoreactivity (GABA-IR) and the density and binding characteristics of GABA A receptors in the Epaulette shark brainstem. These studies were conducted to investigate changes in response to hypoxia. Experimental animals were exposed to eight cycles of an extreme hypoxic regimen (5% of normoxia). Animals were anaesthetised with 80mg/L of MS222 and the brain was dissected and processed either for immunohistochemistry or receptor ligand binding. Membranes were prepared at 4 deg C according to a previously reported protocol and the binding characteristics of [ 3 H]flunitrazeparn ([ 3 H]FNZ) were examined using an in vitro centrifugation assay. We report on the effect of hypoxia on specific [ 3 H]FNZ binding characteristics. GABA-IR was detected using a primary antibody dilution of 1:15 000 and the Vector ABC method. We report that an overall increase in the optical density of GABA-IR occurs with significant increases in three out of the four brainstem nuclei examined in experimental animals. The results of these studies are discussed in conjunction with the hypoxia-tolerance .of the epaulette shark. Copyright (1998) Australian Neuroscience Society

  11. Prefrontal Cortical GABA Transmission Modulates Discrimination and Latent Inhibition of Conditioned Fear: Relevance for Schizophrenia

    Science.gov (United States)

    Piantadosi, Patrick T; Floresco, Stan B

    2014-01-01

    Inhibitory gamma-aminobutyric acid (GABA) transmission within the prefrontal cortex (PFC) regulates numerous functions, and perturbations in GABAergic transmission within this region have been proposed to contribute to some of the cognitive and behavioral abnormalities associated with disorders such as schizophrenia. These abnormalities include deficits in emotional regulation and aberrant attributions of affective salience. Yet, how PFC GABA regulates these types of emotional processes are unclear. To address this issue, we investigated the contribution of PFC GABA transmission to different aspects of Pavlovian emotional learning in rats using translational discriminative fear conditioning and latent inhibition (LI) assays. Reducing prelimbic PFC GABAA transmission via infusions of the antagonist bicuculline before the acquisition or expression of fear conditioning eliminated the ability to discriminate between an aversive conditioned stimulus (CS+) paired with footshock vs a neutral CS–, resembling similar deficits observed in schizophrenic patients. In a separate experiment, blockade of PFC GABAA receptors before CS preexposure (PE) and conditioning did not affect subsequent expression of LI, but did enhance fear in rats that were not preexposed to the CS. In contrast, PFC GABA-blockade before a fear expression test disrupted the recall of learned irrelevance and abolished LI. These data suggest that normal PFC GABA transmission is critical for regulating and mitigating multiple aspects of aversive learning, including discrimination between fear vs safety signals and recall of information about the irrelevance of stimuli. Furthermore, they suggest that similar deficits in emotional regulation observed in schizophrenia may be driven in part by deficient PFC GABA activity. PMID:24784549

  12. Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: A direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (1H-MRS

    Directory of Open Access Journals (Sweden)

    Thomas J Brozoski

    2012-02-01

    Full Text Available Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA, and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu. Because central processing systems are integrated and well regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high-resolution point resolved proton magnetic-resonance spectroscopy (1H-MRS was used to quantify their levels in the dorsal cochlear nucleus (DCN, inferior colliculus (IC, medial geniculate body( (MGB, and primary auditory cortex (A1 of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective

  13. Temperature dependence and GABA modulation of [3H]triazolam binding in the rat brain

    International Nuclear Information System (INIS)

    Earle, M.E.; Concas, A.; Wamsley, J.K.; Yamamura, H.I.

    1987-01-01

    The hypnotic triazolam (TZ), a triazolobenzodiazepine displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. The authors major objectives were the direct measurement of the temperature dependence and the gamma-aminobutyric acid (GABA) effect of [ 3 H]TZ binding in the rat brain. Saturation studies showed a shift to lower affinity with increasing temperatures (K/sub d/ = 0.27 +/- 08 nM at 0 0 C; K/sub d/ = 1.96 +/- 0.85 nM at 37 0 C) while the B/sub max/ values remained unchanged (1220 +/- 176 fmoles/mg protein at 0 0 C and 1160 +/- 383 fmoles/mg protein at 37 0 C). Saturation studies of [ 3 H]TZ binding in the presence or absence of GABA (100μM) showed a GABA-shift. At 0 0 C the K/sub d/ values were (K/sub d/ = 0.24 +/- 0.03 nM/-GABA; K/sub d/ = 0.16 +/- 0.04/+GABA) and at 37 0 C the K/sub d/ values were (K/sub d/ = 1.84 +/- 0.44 nM/-GABA; K/sub d/ = 0.95 +/- 0.29 nM/+GABA). In contrast to reported literature, the authors findings show that TZ interacts with benzodiazepine receptors with a temperature dependence and GABA-shift consistent with predicted behavior for benzodiazepine agonists. 20 references, 3 tables

  14. Turnover and release of GABA in rat cortical slices: effect of a GABA-T inhibitor, gabaculine

    International Nuclear Information System (INIS)

    Szerb, J.C.

    1982-01-01

    The turnover and release of endogenous and labeled GABA were followed in rat cortical slices after incubation with [ 3 H]GABA. High performance liquid chromatography was used to measure endogenous GABA and to separate [ 3 H]GABA from its metabolites. During superfusion with 3 mM K + the slices rapidly lost their [ 3 H]GABA content while maintaining constant GABA levels. Exposure to 50 mM K + for 25 min caused an initial rapid rise in the release of both endogenous and [ 3 H]GABA followed by a more rapid decline in the release of the latter. The specific activity of released GABA was two to four times higher than that in the slices. Depolarization lead to a net synthesis of GABA. The GABA -T inhibitor, gabaculine, (5 micrometers) in vitro arrested the metabolism of [ 3 H]GABA and rapidly doubled the GABA content but did not significantly increase the high K + evoked release of endogenous GABA. In vivo pretreatment with 0.5 mM/kg gabaculine quadrupled GABA content and increased both the spontaneous and evoked release of endogenous GABA but while its Ca 2 + -dependent release increased by 50%, the Ca 2 + -independent release was enhanced sevenfold. This large Ca 2 + -independent release of GABA is likely to have different functional significance from the normal Ca 2 + -dependent release

  15. The changes in drug binding activity of GABA receptor and animal neural-behavior after gamma irradiation

    International Nuclear Information System (INIS)

    Zheng Hui; Zhen Rong; Zhao Naikun; Xue Hong; Wang Zihui

    2004-01-01

    Objective: The purpose of this study was to investigate the effect of irradiation on gamma-aminobutyric-acid receptor (GABA-R) as well as behavioral changes after brain 60 Co γ-irradiation. Methods: The mice were irradiated with gamma rays (20 Gy; 10 Gy and 5 Gy) . The drug binding activity of GABA receptor in brain receptor was measured by fluorescence anisotropy (FA) and equilibrium dissociation constants. The behavioral changes were observed by the locomotor activity test, elevated plus-maze test and hole-board test at 1, 10, 24 and 48 hr after irradiation. Results: 1. The drug binding activity of the GABA receptor was decreased and the equilibrium dissociation constant (K d ) was significantly increased compared with the negative control group 2 hr after irradiation, and a spike value appeared at 24 hr. It showed that the irradiation might damage or decrease the binding activity and the bio-activity of GABA receptor. 2. The animal experiment confirmed that the irradiated animal model showed neural-behavioral changes of anxiety or depression. 3. The decreased binding activity of GABA receptor and changes in behavior of irradiated animal were dependent on radiation intensity. 4. The changes of behavior was similar to the blocked GABA receptor group. It suggests the relationship of radiation and GABA receptor. Conclusion: These results suggest that GABA receptor may be involved in radiation injury. The functional changes of GABA receptor may be an induction factor of behavioral disorder. The article also discussed the effect of anxiety and results obtained from the point of view of GABA receptor system involvement in the changes observed after irradiation. (authors)

  16. Fat coating of Ca butyrate results in extended butyrate release in the gastrointestinal tract of broilers

    NARCIS (Netherlands)

    Borne, van den J.J.G.C.; Heetkamp, M.J.W.; Buyse, J.; Niewold, T.A.

    2015-01-01

    Based on its described beneficial effects on small and large intestinal epithelium, butyrate can be a very good alternative to antimicrobial growth promoters. Effective dietary application requires coating because the majority of uncoated butyrate is purportedly absorbed before reaching the proximal

  17. Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice.

    Science.gov (United States)

    Mollica, Maria Pina; Mattace Raso, Giuseppina; Cavaliere, Gina; Trinchese, Giovanna; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Pirozzi, Claudio; Di Guida, Francesca; Lama, Adriano; Crispino, Marianna; Tronino, Diana; Di Vaio, Paola; Berni Canani, Roberto; Calignano, Antonio; Meli, Rosaria

    2017-05-01

    Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver. Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet-induced obese mice. In particular, butyrate and FBA improved respiratory capacity and fatty acid oxidation, activated the AMPK-acetyl-CoA carboxylase pathway, and promoted inefficient metabolism, as shown by the increase in proton leak. Both treatments consistently increased utilization of substrates, especially fatty acids, leading to the reduction of intracellular lipid accumulation and oxidative stress. Finally, the shift of the mitochondrial dynamic toward fusion by butyrate and FBA resulted in the improvement not only of mitochondrial cell energy metabolism but also of glucose homeostasis. In conclusion, butyrate and its more palatable synthetic derivative, FBA, modulating mitochondrial function, efficiency, and dynamics, can be considered a new therapeutic strategy to counteract obesity and insulin resistance. © 2017 by the American Diabetes Association.

  18. [Effect of dietary fiber in the quantitative expression of butyrate receptor GPR43 in rats colon].

    Science.gov (United States)

    Corte Osorio, L Y; Martínez Flores, H E; Ortiz Alvarado, R

    2011-01-01

    Short chain fatty acids (SCFA) acetate, propionate and butyrate are the major anions produced by the bacterial fermentation of dietary fiber (DF) in colon. Recently, butyrate has been recently studied because is important to maintain colonic functions and because it has been related with a protective effect in colorectal cancer, which is mainly, explained by its potential to regulate gene expression by inhibiting enzyme histonedeacetylase (HDAC). Several investigationsshown that SCFAreceptor GPR43 is involved insignal transduction mechanisms once they bind to ligands such as butyrate to generate different physiological effects in colonocytes. Determine if dietary fiber consumption from nopal (Opuntia ficus I.) containing a ratio of soluble-insoluble fiber 40/60, has a direct influence on the quantitative expression of butyrate-specific receptor GPR43. Wistar rats were fed with four different diets formulated at different concentrations of dietary fiber of 0, 5, 15 and 25% of dietary fiber from opuntia, respectively. The results shown an increase in the expression of GPR43 (93.1%) when rats was fed with a 5% fiber diet, using β-actin as a reference gene. The results of this investigation will contribute to determinate the relation of diet with intestinal health for the purpose of expanding the knowledge of butyric acid on colonic functions.

  19. Oxidative stress plays a key role in butyrate-mediated autophagy via Akt/mTOR pathway in hepatoma cells.

    Science.gov (United States)

    Pant, Kishor; Saraya, Anoop; Venugopal, Senthil K

    2017-08-01

    Hepatocellular Carcinoma (HCC) is one of the most aggressive forms of cancer, responsible for a number of deaths in humans. Butyrate, one of the short chain fatty acids produced by the gut microbiota during anaerobic fermentation, was shown to be beneficial for inhibiting cancer growth. In this study, we showed that sodium butyrate induced autophagy via reactive oxygen species (ROS) in hepatoma cells. Butyrate (0-6 mM) incubation significantly increased intracellular ROS levels (45.2% compared to control), which in turn inhibited phosphorylation of akt and mTOR, leading to the upregulation of autophagic proteins, such as beclin 1, ATG 5, LC3-II, followed by the increased autophagosome formation (34.4% compared to control cells). Addition of a known antioxidant, N-acetyl cysteine (NAC), reversed these butyrate-induced ROS and autophagy. It was also found that butyrate-induced ROS enhanced MAPK activation, which was inhibited by NAC. In conclusion, our data showed that butyrate induced ROS, which in turn induced autophagy via inhibition of akt/mTOR pathway. Hence, butyrate could be considered as a potential candidate for HCC treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sodium Butyrate Reduces Colitogenic Immunoglobulin A-Coated Bacteria and Modifies the Composition of Microbiota in IL-10 Deficient Mice.

    Science.gov (United States)

    Zhang, Tenghui; Ding, Chao; Zhao, Mingli; Dai, Xujie; Yang, Jianbo; Li, Yi; Gu, Lili; Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Li, Ning; Li, Jieshou

    2016-11-24

    High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving inflammatory bowel disease (IBD). We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL)-10 -/- mice. At 8 weeks of age, mice were allocated into three groups ( n = 4/group): normal (C57BL/6), IL-10 -/- , and IL-10 -/- treated with sodium butyrate (100 mM). Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF)-α and IL-6 in IL-10 -/- mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10 -/- mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10 -/- mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10 -/- mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10 -/- mice.

  1. Butyrate down regulates BCL-XL and sensitizes human fibroblasts to radiation and chemotherapy induced apoptosis

    International Nuclear Information System (INIS)

    Chung, Diana H.; Ljungman, Mats; Zhang Fenfen; Chen Feng; McLaughlin, William P.

    1997-01-01

    Purpose/Objective: Butyrate is a short chain fatty acid that has been implicated in the induction of cell cycle arrest, cell differentiation and apoptosis. The purpose of this study was to determine if butyrate treatment sensitizes cells to radiation or chemotherapy induced apoptosis. Materials and Methods: Normal neonatal human diploid fibroblasts were used throughout this study. Apoptosis was scored and quantified using three different methods. First, cell morphology using propidium iodide and fluorescence microscopy was used to qualitatively determine apoptosis and to quantify the percentage of cells undergoing apoptosis. Second, apoptosis induced DNA degradation was scored by quantifying the amount of cells appearing in a sub-G1 peak using fixed and PI-stained cells and flow cytometry. Third, apoptosis-induced DNA degradation was examined by using an assay involving direct lysis of cells in the wells of agarose gels followed by conventional gel electrophoresis. Western blotting was used to quantify the cellular levels of the apoptosis regulators, Bcl-2, Bcl-XL and Bax. Results: Human diploid fibroblasts, which were resistant to radiation induced apoptosis, were found to undergo massive apoptosis when radiation was combined with butyrate treatment. Sensitization was obtained when butyrate was added before or after radiation although the combination of both pre and post-treatment was the most effective. Butyrate was also found to enhance UV light and cisplatin-induced apoptosis. These findings correlated with a reduction of the apoptosis antagonist Bcl-XL. Bcl-XL levels significantly dropped in a time and dose dependent manner. In addition, butyrate effectively blocked UV-induced accumulation of p53. Conclusion: Our results suggest that butyrate may be an attractive agent to use in combination with radiation or chemotherapy to lower the apoptotic threshold of tumor cells, regardless of the p53 status of the tumor cells

  2. Effects of a whole body gamma irradiation on GABA repartition in infant rats cerebellum and hippocampal formation

    International Nuclear Information System (INIS)

    Menetrier, F.; Vernois, Y.; Court, L.

    1992-01-01

    'Full-Text:' Thirteen-day-old rats were exposed to a single dose of 4 or 0,5 Gy of gamma at a dose rate of 0,25 Gy/min and were killed about 5h after. Fixation was achieved in situ using glutaraldehyde. For GABA immunocytochemistry transversal sections were incubated with antiserum against GABA, then with PAP and revealed with diaminobenzidine. Proliferative layers are still observed in the infant rat cerebellum (external granular layer) and hippocampal formation (subgranular layer of the dentate gyrus). When irradiation occurs a high percent of these two layers cells are pycnotic. In the normal cerebellum, no immunostaining is observed in external granular layer cell bodies. The only labelled structures are few cytoplasmic expansions coming from subjacent layers. When irradiated, a strong GABA staining appears around pycnotic cells as a network with labelled meshes. GABA staining and pycnotic cells were more especially important when the irradiation increases. Further studies are needed to specify the nature of labelled meshes. In the normal hippocampal formation, subgranular cells are not GABA stained. Staining occurs in cells which are not granule cells. They are scattered throughout cell layers of the dentate gyrus with predominance in the hilus. After irradiation, GABA repartition is not modified. After a 4 Gy whole body gamma irradiation, the inhibitory GABA system is not injured. Other amino-acid neurotransmitters such as Glutamate could be modified. (author)

  3. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  4. Comparative mapping of GABA-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

    Science.gov (United States)

    Gunaratne, Charuni A; Sakurai, Akira; Katz, Paul S

    2014-03-01

    The relative simplicity of certain invertebrate nervous systems, such as those of gastropod molluscs, allows behaviors to be dissected at the level of small neural circuits composed of individually identifiable neurons. Elucidating the neurotransmitter phenotype of neurons in neural circuits is important for understanding how those neural circuits function. In this study, we examined the distribution of γ-aminobutyric-acid;-immunoreactive (GABA-ir) neurons in four species of sea slugs (Mollusca, Gastropoda, Opisthobranchia, Nudibranchia): Tritonia diomedea, Melibe leonina, Dendronotus iris, and Hermissenda crassicornis. We found consistent patterns of GABA immunoreactivity in the pedal and cerebral-pleural ganglia across species. In particular, there were bilateral clusters in the lateral and medial regions of the dorsal surface of the cerebral ganglia as well as a cluster on the ventral surface of the pedal ganglia. There were also individual GABA-ir neurons that were recognizable across species. The invariant presence of these individual neurons and clusters suggests that they are homologous, although there were interspecies differences in the numbers of neurons in the clusters. The GABAergic system was largely restricted to the central nervous system, with the majority of axons confined to ganglionic connectives and commissures, suggesting a central, integrative role for GABA. GABA was a candidate inhibitory neurotransmitter for neurons in central pattern generator (CPG) circuits underlying swimming behaviors in these species, however none of the known swim CPG neurons were GABA-ir. Although the functions of these GABA-ir neurons are not known, it is clear that their presence has been strongly conserved across nudibranchs. Copyright © 2013 Wiley Periodicals, Inc.

  5. Comparative genomics and physiology of the butyrate-producing bacterium Intestinimonas butyriciproducens

    NARCIS (Netherlands)

    Bui, Thi Phuong Nam; Shetty, Sudarshan Anand; Lagkouvardos, Ilias; Ritari, Jarmo; Chamlagain, Bhawani; Douillard, François P.; Paulin, Lars; Piironen, Vieno; Clavel, Thomas; Plugge, Caroline M.; Vos, de Willem M.

    2016-01-01

    Intestinimonas is a newly described bacterial genus with representative strains present in the intestinal tract of human and other animals. Despite unique metabolic features including the production of butyrate from both sugars and amino acids, there is to date no data on their diversity,

  6. Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons

    DEFF Research Database (Denmark)

    Kanaani, Jamil; Cianciaruso, Chiara; Phelps, Edward A

    2015-01-01

    The inhibitory neurotransmitter GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD) in neurons and in pancreatic β-cells in islets of Langerhans where it functions as a paracrine and autocrine signaling molecule regulating the function of islet endocrine cells. The localization...

  7. Divergent influences of anterior cingulate cortex GABA concentrations on the emotion circuitry

    NARCIS (Netherlands)

    Levar, Nina; van Leeuwen, Judith M C; Denys, Damiaan; Van Wingen, G.

    2017-01-01

    Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA)

  8. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA

    DEFF Research Database (Denmark)

    Schousboe, Arne; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2013-01-01

    . Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA...... that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed. This review is intended to delineate the above mentioned...

  9. Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis.

    Science.gov (United States)

    Dewei, Song; Min, Chen; Haiming, Cheng

    2016-11-01

    Candida rugosa lipases were immobilized onto collagen fibers through glutaraldehyde cross-linking method. The immobilization process has been optimized. Under the optimal immobilization conditions, the activity of the collagen-immobilized lipase reached 340 U/g. The activity was recovered of 28.3 % by immobilization. The operational stability of the obtained collagen-immobilized lipase for hydrolysis of olive oil emulsion was determined. The collagen-immobilized lipase showed good tolerance to temperature and pH variations in comparison to free lipase. The collagen-immobilized lipase was also applied as biocatalyst for synthesis of butyl butyrate from butyric acid and 1-butanol in n-hexane. The conversion yield was 94 % at the optimal conditions. Of its initial activity, 64 % was retained after 5 cycles for synthesizing butyl butyrate in n-hexane.

  10. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway.

    Science.gov (United States)

    De Preter, Vicky; Arijs, Ingrid; Windey, Karen; Vanhove, Wiebe; Vermeire, Severine; Schuit, Frans; Rutgeerts, Paul; Verbeke, Kristin

    2012-06-01

    In ulcerative colitis (UC) butyrate metabolism is impaired due to a defect in the butyrate oxidation pathway and/or transport. In the present study we correlated butyrate uptake and oxidation to the gene expression of the butyrate transporter SLC16A1 and the enzymes involved in butyrate oxidation (ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2) in UC and controls. Colonic mucosal biopsies were collected during endoscopy of 88 UC patients and 20 controls with normal colonoscopy. Butyrate uptake and oxidation was measured by incubating biopsies with (14) C-labeled Na-butyrate. To asses