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Sample records for crotoxin potentiates l-type

  1. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical

    International Nuclear Information System (INIS)

    Silveira, Marina Bicalho

    2010-01-01

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ( 125 I-Crotoxin) and iodine-131 ( 131 I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL 50 in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. 125 I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K d =24.98 nmol/L and B max =16,570 sites/cell for low affinity binding sites and K d =0.06 nmol/L and B max =210 sites/cell high affinity binding sites

  2. Obtainment of crotoxin/phema-g-LDPE and crotoxin/PCL systems

    International Nuclear Information System (INIS)

    Lorenzetti, Solange Gubbelini

    2006-01-01

    crotoxin had visible loss of weight higher than the other groups. It was concluded that, potentially the immobilized crotoxin could be used by its catalytic phospholipase action, possibly for the hydrolysis of phospholipids present in human serum low density lipoproteins (LDL). By the other side, the entrapped crotoxin in the microspheres of epsilon-polycaprolactone could be employed in the managed drug delivered system for the tumoral therapy. (author)

  3. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical; Estudo do mecanismo de acao da crotoxina em tumores mamarios e avaliacao do seu potenctial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina Bicalho

    2010-07-01

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ({sup 125}I-Crotoxin) and iodine-131 ({sup 131}I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL{sub 50} in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. {sup 125}I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K{sub d}=24.98 nmol/L and B{sub max}=16,570 sites/cell for low affinity binding sites and K{sub d}=0.06 nmol/L and B{sub max}=210 sites

  4. Study of crotoxin on the induction of paralysis in extraocular muscle in animal model

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    Geraldo de Barros Ribeiro

    2012-10-01

    Full Text Available PURPOSE: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A. METHODS: The crotoxin, with LD50 of 1.5 µg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 µg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. RESULTS: The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 µg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 µg. CONCLUSION: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 µg was able to induce similar effects as botulinum toxin type A.

  5. Obtainment of crotoxin/phema-g-LDPE and crotoxin/PCL systems;Obtencao dos sistemas bioconjugados crotoxina/PEBD-g-phema e crotoxina/PCL

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    Lorenzetti, Solange Gubbelini

    2006-07-01

    injected with crotoxin had visible loss of weight higher than the other groups. It was concluded that, potentially the immobilized crotoxin could be used by its catalytic phospholipase action, possibly for the hydrolysis of phospholipids present in human serum low density lipoproteins (LDL). By the other side, the entrapped crotoxin in the microspheres of epsilon-polycaprolactone could be employed in the managed drug delivered system for the tumoral therapy. (author)

  6. Effect of gamma irradiation on the behavioral properties of crotoxin

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    E.G. Moreira

    1997-02-01

    Full Text Available Crotoxin has been detoxified with gamma radiation in order to improve crotalic antiserum production. Nevertheless, present knowledge of the biological characteristics of irradiated crotoxin is insufficient to propose it as an immunizing agent. Crotoxin is known to increase the emotional state of rats and to decrease their exploratory behavior (Moreira EG, Nascimento N, Rosa GJM, Rogero JR and Vassilieff VS (1996 Brazilian Journal of Medical and Biological Research, 29: 629-632. Therefore, we decided 1 to evaluate the effects of crotoxin in the social interaction test, which has been widely used for the evaluation of anxiogenic drugs, and 2 to determine if irradiated crotoxin induces behavioral alterations similar to those of crotoxin in the social interaction, open-field and hole-board tests. Male Wistar rats (180-220 g were used. Crotoxin (100, 250, and 500 µg/kg was injected intraperitoneally 2 h before the social interaction test. Similarly, irradiated crotoxin (2000 Gy gamma radiation from a 60Co source was administered at the doses of 100, 250, and 500 µg/kg for the hole-board test, and at the doses of 1000 and 2500 µg/kg for the open-field and social interaction tests. ANOVA complemented with the Dunnett test was used for statistical analysis (P<0.05. Crotoxin decreased the social interaction time (s at the doses of 100, 250 and 500 µg/kg (means ± SEM from 51.6 ± 4.4 to 32.6 ± 3.7, 28.0 ± 3.6 and 31.6 ± 4.4, respectively. Irradiated crotoxin did not induce behavioral alterations. These results indicate that 1 crotoxin may be an anxiogenic compound, and 2 in contrast to crotoxin, irradiated crotoxin was unable to induce behavioral alterations, which makes it a promising compound for the production of crotalic antiserum

  7. Comparative study of native and irradiated crotoxin. Biochemical and pharmacological effects

    International Nuclear Information System (INIS)

    Nascimento, N. do.

    1991-01-01

    Ionizing radiation is able to detoxify several venoms, including snake venom, without affecting significantly their antigenic and immunogenic properties. In order to elucidate this phenomena, we conceived a comparative biochemical and pharmacological study between native and gamma irradiated (2000Gy) crotoxin, main toxin of south american rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified from crude venom by molecular exclusion chromatography, pI precipitation and then irradiated. Immunodiffusion, electrophoresis and gel filtration showed that the molecular integrity was preserved after irradiation with some higher molecular weight aggregate formation and maintenance of its antigenic capacity. The antibodies induced by irradiated toxin had a similar titer to the antibodies induced by native crotoxin; however with higher protective effects in mice. Crotoxin toxicity became 15 times lower after irradiation, as determined by LD sub(50) in mice. Native and irradiated crotoxin biodistribution occurred with a similar general pattern, with renal elimination. In contrast to irradiated crotoxin, the native crotoxin is initially retained in kidneys. A later concentration (2-3hs) occurs in phagocyticmononuclear cells rich organs (liver and spleen) and neural junctions rich organs (muscle and brain). (author)

  8. Crotoxin in humans: analysis of the effects on extraocular and facial muscles

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    Geraldo de Barros Ribeiro

    2012-12-01

    Full Text Available PURPOSE: Crotoxin is the main neurotoxin of South American rattlesnake Crotalus durissus terrificus. The neurotoxic action is characterized by a presynaptic blockade. The purpose of this research is to assess the ability of crotoxin to induce temporary paralysis of extraocular and facial muscles in humans. METHODS: Doses of crotoxin used ranged from 2 to 5 units (U, each unit corresponding to one LD50. We first applied 2U of crotoxin in one of the extraocular muscles of 3 amaurotic individuals to be submitted to ocular evisceration. In the second stage, we applied crotoxin in 12 extraocular muscles of 9 patients with strabismic amblyopia. In the last stage, crotoxin was used in the treatment of blepharospasm in another 3 patients. RESULTS: No patient showed any systemic side effect or change in vision or any eye structure problem after the procedure. The only local side effects observed were slight conjunctival hyperemia, which recovered spontaneously. In 2 patients there was no change in ocular deviation after 2U crotoxin application. Limitation of the muscle action was observed in 8 of the 12 applications. The change in ocular deviation after application of 2U of crotoxin (9 injections was in average 15.7 prism diopters (PD. When the dose was 4U (2 applications the change was in average 37.5 PD and a single application of 5U produced a change of 16 PD in ocular deviation. This effect lasted from 1 to 3 months. Two of the 3 patients with blepharospasm had the hemifacial spasm improved with crotoxin, which returned after 2 months. CONCLUSIONS: This study provides data suggesting that crotoxin may be a useful new therapeutic option for the treatment of strabismus and blepharospasm. We expect that with further studies crotoxin could be an option for many other medical areas.

  9. Crotoxin in humans: analysis of the effects on extraocular and facial muscles.

    Science.gov (United States)

    Ribeiro, Geraldo de Barros; Almeida, Henderson Celestino de; Velarde, David Toledo

    2012-01-01

    Crotoxin is the main neurotoxin of South American rattlesnake Crotalus durissus terrificus. The neurotoxic action is characterized by a presynaptic blockade. The purpose of this research is to assess the ability of crotoxin to induce temporary paralysis of extraocular and facial muscles in humans. Doses of crotoxin used ranged from 2 to 5 units (U), each unit corresponding to one LD50. We first applied 2U of crotoxin in one of the extraocular muscles of 3 amaurotic individuals to be submitted to ocular evisceration. In the second stage, we applied crotoxin in 12 extraocular muscles of 9 patients with strabismic amblyopia. In the last stage, crotoxin was used in the treatment of blepharospasm in another 3 patients. No patient showed any systemic side effect or change in vision or any eye structure problem after the procedure. The only local side effects observed were slight conjunctival hyperemia, which recovered spontaneously. In 2 patients there was no change in ocular deviation after 2U crotoxin application. Limitation of the muscle action was observed in 8 of the 12 applications. The change in ocular deviation after application of 2U of crotoxin (9 injections) was in average 15.7 prism diopters (PD). When the dose was 4U (2 applications) the change was in average 37.5 PD and a single application of 5U produced a change of 16 PD in ocular deviation. This effect lasted from 1 to 3 months. Two of the 3 patients with blepharospasm had the hemifacial spasm improved with crotoxin, which returned after 2 months. This study provides data suggesting that crotoxin may be a useful new therapeutic option for the treatment of strabismus and blepharospasm. We expect that with further studies crotoxin could be an option for many other medical areas.

  10. Structural analysis of irradiated crotoxin by spectroscopic techniques

    International Nuclear Information System (INIS)

    Oliveira, Karina C. de; Fucase, Tamara M.; Silva, Ed Carlos S. e; Chagas, Bruno B.; Buchi, Alisson T.; Viala, Vincent L.; Spencer, Patrick J.; Nascimento, Nanci do

    2013-01-01

    Snake bites are a serious public health problem, especially in subtropical countries. In Brazil, the serum, the only effective treatment in case of snake bites, is produced in horses which, despite of their large size, have a reduced lifespan due to the high toxicity of the antigen. Ionizing radiation has been successfully employed to attenuate the biological activity of animal toxins. Crotoxin, the main toxic compound from Crotalus durissus terrificus (Cdt), is a heterodimeric protein composed of two subunits: crotapotin and phospholipase A 2 . Previous data indicated that this protein, following irradiation process, undergoes unfolding and/or aggregation, resulting in a much lower toxic antigen. The exact mechanisms and structural modifications involved in aggregation process are not clear yet. This work investigates the effects of ionizing radiation on crotoxin employing Infrared Spectroscopy, Circular Dichroism and Dynamic Light Scattering techniques. The infrared spectrum of lyophilized crotoxin showed peaks corresponding to the vibrational spectra of the secondary structure of crotoxin, including β-sheet, random coil, α-helix and β-turns. We calculated the area of these spectral regions after adjusting for baseline and normalization using the amide I band (1590-1700 cm -1 ), obtaining the variation of secondary structures of the toxin following irradiation. The Circular Dichroism spectra of native and irradiated crotoxin suggests a conformational change within the molecule after the irradiation process. This data indicates structural changes between the samples, apparently from ordered conformation towards a random coil. The analyses by light scattering indicated that the irradiated crotoxin formed multimers with an average molecular radius 100 folds higher than the native toxin. (author)

  11. Biochemical and immunological characterization of the main products of crotoxin irradiation

    International Nuclear Information System (INIS)

    Nascimento, Nanci do

    1995-01-01

    Irradiation of crotoxin and its subunits with 2,000 Gy of γ-rays from 60 Co source leads to aggregation and generation of lower molecular wight breakdown products. Aggregates separated by gel filtration retain at least part of their higher-ordered structure, based on their reactivity with monoclonal antibodies known to react with conformation epitopes in native crotoxin. These same aggregates can serve as antigens to raise antisera that cross-reacts and neutralizes crotoxin. Compared with native crotoxin, aggregates appears less myotoxic, are largely devoid of phospholipase activity, and are virtually non-toxic in mice. These results indicate that irradiation of toxic proteins can promote significant detoxification, but still retain many of the original antigenic and immunological properties of native crotoxin. (author)

  12. Structural analysis of irradiated crotoxin by spectroscopic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Karina C. de; Fucase, Tamara M.; Silva, Ed Carlos S. e; Chagas, Bruno B.; Buchi, Alisson T.; Viala, Vincent L.; Spencer, Patrick J.; Nascimento, Nanci do, E-mail: kcorleto@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia

    2013-07-01

    Snake bites are a serious public health problem, especially in subtropical countries. In Brazil, the serum, the only effective treatment in case of snake bites, is produced in horses which, despite of their large size, have a reduced lifespan due to the high toxicity of the antigen. Ionizing radiation has been successfully employed to attenuate the biological activity of animal toxins. Crotoxin, the main toxic compound from Crotalus durissus terrificus (Cdt), is a heterodimeric protein composed of two subunits: crotapotin and phospholipase A{sub 2}. Previous data indicated that this protein, following irradiation process, undergoes unfolding and/or aggregation, resulting in a much lower toxic antigen. The exact mechanisms and structural modifications involved in aggregation process are not clear yet. This work investigates the effects of ionizing radiation on crotoxin employing Infrared Spectroscopy, Circular Dichroism and Dynamic Light Scattering techniques. The infrared spectrum of lyophilized crotoxin showed peaks corresponding to the vibrational spectra of the secondary structure of crotoxin, including β-sheet, random coil, α-helix and β-turns. We calculated the area of these spectral regions after adjusting for baseline and normalization using the amide I band (1590-1700 cm{sup -1}), obtaining the variation of secondary structures of the toxin following irradiation. The Circular Dichroism spectra of native and irradiated crotoxin suggests a conformational change within the molecule after the irradiation process. This data indicates structural changes between the samples, apparently from ordered conformation towards a random coil. The analyses by light scattering indicated that the irradiated crotoxin formed multimers with an average molecular radius 100 folds higher than the native toxin. (author)

  13. Biochemical and immunological characterization of the main products of crotoxin irradiation

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    Nascimento, M. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Dept. de Bioengenharia

    1996-07-01

    Irradiation of crotoxin and its subunits with 2,000 Gy of gamma-rays from {sup 60} Co source leads to aggregation and generation of lower molecular weight breakdown products. Aggregates separated by gel filtration retain at least part of their higher-ordered structure, based on their reactivity with monoclonal antibodies, known to react with conformational epitopes in native crotoxin. Linear epitopes are also preserved, as demonstrated by peptide mapping of the aggregates. These same aggregates can function as antigens to raise antisera which cross-react and neutralize crotoxin. Compared with crotoxin, the aggregates appear to be less myotoxic, largely devoid of phospholipase activity and virtually non-toxic in mice. These results indicate that the irradiation of toxic proteins can promote significant detoxification, but still retain many of the original antigenic and immunological properties of native crotoxin. (author)

  14. Biochemical and immunological characterization of the main products of crotoxin irradiation

    International Nuclear Information System (INIS)

    Nascimento, M.

    1996-01-01

    Irradiation of crotoxin and its subunits with 2,000 Gy of gamma-rays from 60 Co source leads to aggregation and generation of lower molecular weight breakdown products. Aggregates separated by gel filtration retain at least part of their higher-ordered structure, based on their reactivity with monoclonal antibodies, known to react with conformational epitopes in native crotoxin. Linear epitopes are also preserved, as demonstrated by peptide mapping of the aggregates. These same aggregates can function as antigens to raise antisera which cross-react and neutralize crotoxin. Compared with crotoxin, the aggregates appear to be less myotoxic, largely devoid of phospholipase activity and virtually non-toxic in mice. These results indicate that the irradiation of toxic proteins can promote significant detoxification, but still retain many of the original antigenic and immunological properties of native crotoxin. (author)

  15. Structural aspects of crotoxin modified by ionizing radiation; Aspectos estruturais da crotoxina modificada pela radiacao ionizante

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Karina Corleto de; Albero, Felipe Guimaraes; Zezell, Denise Maria; Spencer, Patrick Jack; Nascimento, Nanci do, E-mail: kcorleto@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2010-03-15

    Ionizing radiation has proven to be an excellent tool for reducing the toxicity of venoms and isolated toxins, resulting in better immunogens for serum production, the only effective treatment in case of snake bites, and contributing to the welfare of serum-producing animals. Since the action of gamma radiation of venoms and toxins has not been yet fully clarified from the structural point of view, we proposed in this paper, to characterize the crotoxin, a venom protein of the species Crotalus durissus terrificus by Circular Dichroism (CD) and Infrared Spectroscopy (FTIR) techniques. After chromatographic techniques, crotoxin was irradiated with 2.0 kGy ({sup 60}Co source). The CD spectra obtained of native and irradiated crotoxin solutions showed changes between the samples in characteristic regions of -sheet and-helix . The Infrared analyse showed expressive changes in the spectra of the native and irradiated crotoxin (amide I band region). These tests showed that crotoxin when subjected to gamma radiation, showed changes in their structural conformation compared with the samples in the native state. Such changes probably occur in the secondary structure and may explain its neurotoxic activity loss. (author)

  16. Comparative nephrotoxicity of native or Co-60 gamma rays irradiated crotoxin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Andre Moreira; Alves, Glaucie J.; Aires, Raquel da Silva; Turibio, Thompson O.; Thomazi, Gabriela O. Coelho; Spencer, Patrick J.; Nascimento, Nanci do, E-mail: andrerocha@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Nascimento-Rocha, Josefa M.; Magalhaes Filho, Asterio Souza, E-mail: 0304@prof.itpacporto.com.br [Instituto Tocantinense Presidente Antonio Carlos Porto (ITPAC), Porto Nacional, TO (Brazil)

    2015-07-01

    Snake venoms are complex mixtures of proteins and peptides with a wide spectrum of physiological targets such as the blood coagulation and cardiovascular systems and the motor end plate among others. Acute renal failure is a common complication in accidents with the South American rattlesnake. The toxin involved in this pathology is the crotoxin, a major component of the venom in terms of concentration and toxicity. Snake venoms, when irradiated with {sup 60}Co gamma rays present a significant decrease in toxicity while the immunogenic properties of its components are preserved. The use of irradiated venom is an attractive alternative for antisera production since it might reduce the appearance of renal lesions improving the welfare and lifespan of those animals employed on antivenom production. At the present work, we have compared the effects of native and irradiated crotoxin on the mice renal function. Tubular lesions were observed in all the samples from the animal group injected with native crotoxin. Animals injected with the irradiated toxin presented alteration only after 30 minutes and 1 hour after injection. These data suggest that the onset of the renal lesions is delayed and that the severity of the lesions might be lower when using irradiated crotoxin. (author)

  17. Comparative nephrotoxicity of native or Co-60 gamma rays irradiated crotoxin in mice

    International Nuclear Information System (INIS)

    Rocha, Andre Moreira; Alves, Glaucie J.; Aires, Raquel da Silva; Turibio, Thompson O.; Thomazi, Gabriela O. Coelho; Spencer, Patrick J.; Nascimento, Nanci do; Nascimento-Rocha, Josefa M.; Magalhaes Filho, Asterio Souza

    2015-01-01

    Snake venoms are complex mixtures of proteins and peptides with a wide spectrum of physiological targets such as the blood coagulation and cardiovascular systems and the motor end plate among others. Acute renal failure is a common complication in accidents with the South American rattlesnake. The toxin involved in this pathology is the crotoxin, a major component of the venom in terms of concentration and toxicity. Snake venoms, when irradiated with 60 Co gamma rays present a significant decrease in toxicity while the immunogenic properties of its components are preserved. The use of irradiated venom is an attractive alternative for antisera production since it might reduce the appearance of renal lesions improving the welfare and lifespan of those animals employed on antivenom production. At the present work, we have compared the effects of native and irradiated crotoxin on the mice renal function. Tubular lesions were observed in all the samples from the animal group injected with native crotoxin. Animals injected with the irradiated toxin presented alteration only after 30 minutes and 1 hour after injection. These data suggest that the onset of the renal lesions is delayed and that the severity of the lesions might be lower when using irradiated crotoxin. (author)

  18. Structural studies of the oligomeric formation crotoxin and their complexes; Estudos estruturais da formacao oligomerica da crotoxina e seus complexos

    Energy Technology Data Exchange (ETDEWEB)

    Morelli, Humberto A.S.; Fernandes, Carlos A.H.; Magro, Angelo J.; Fontes, Marcos R.M.; Fernandez, Roberto M., E-mail: rmorato@ibb.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Inst. de Biociencias. Dept. de Fisica e Biofisica; Bicev, Renata N.; Oliveira, Cristiano L.P. de [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Inst. de Fisica. Dept. de Fisica Experimental; Barioni, Marina B.; Ito, Amando S. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Fac. de Filosofia, Ciencias e Letras. Dept. de Fisica

    2013-08-15

    The crotoxin is a phospholipase A{sub 2} that is the mainly responsible for the neurotoxic effect of the snakes' venom of the species Crotalus durissus, popularly known as rattlesnakes. In the crotoxin there are two subunits: an acidic, non-toxic and devoid of enzymatic action, (called crotoxin A or CA); and a basic, toxic with enzymatic activity (called crotoxin B or CB). The main objective of this work is to study the CA, CB and the complex CA + CB using the Small-Angle X-ray Scattering (SAXS), Optical absorption spectrometry and static fluorescence techniques. (author)

  19. Crotoxin, the major toxin from the rattlesnake Crotalus durissus terrificus, inhibits ³H-choline uptake in guinea pig ileum

    Directory of Open Access Journals (Sweden)

    L.S. Kattah

    2000-09-01

    Full Text Available We examined the effect of crotoxin, the neurotoxic complex from the venom of the South American rattlesnake Crotalus durissus terrificus, on the uptake of ³H-choline in minces of smooth muscle myenteric plexus from guinea pig ileum. In the concentration range used (0.03-1 µM and up to 10 min of treatment, crotoxin decreased ³H-choline uptake by 50-75% compared to control. This inhibition was time dependent and did not seem to be associated with the disruption of the neuronal membrane, because at least for the first 20 min of tissue exposure to the toxin (up to 1 µM the levels of lactate dehydrogenase (LDH released into the supernatant were similar to those of controls. Higher concentrations of crotoxin or more extensive incubation times with this toxin resulted in elevation of LDH activity detected in the assay supernatant. The inhibitory effect of crotoxin on ³H-choline uptake seems to be associated with its phospholipase activity since the equimolar substitution of Sr2+ for Ca2+ in the incubation medium or the modification of the toxin with p-bromophenacyl bromide substantially decreased this effect. Our results show that crotoxin inhibits ³H-choline uptake with high affinity (EC25 = 10 ± 5 nM. We suggest that this inhibition could explain, at least in part, the blocking effect of crotoxin on neurotransmission.

  20. Biochemical and immunological characterization of the main products of crotoxin irradiation; Caracterizacao bioquimica e imunologica dos principais produtos gerados pela irradiacao de crotoxina

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Nanci do

    1995-07-01

    Irradiation of crotoxin and its subunits with 2,000 Gy of {gamma}-rays from {sup 60} Co source leads to aggregation and generation of lower molecular wight breakdown products. Aggregates separated by gel filtration retain at least part of their higher-ordered structure, based on their reactivity with monoclonal antibodies known to react with conformation epitopes in native crotoxin. These same aggregates can serve as antigens to raise antisera that cross-reacts and neutralizes crotoxin. Compared with native crotoxin, aggregates appears less myotoxic, are largely devoid of phospholipase activity, and are virtually non-toxic in mice. These results indicate that irradiation of toxic proteins can promote significant detoxification, but still retain many of the original antigenic and immunological properties of native crotoxin. (author)

  1. Study of crotoxin on the induction of paralysis in extraocular muscle in animal model Estudo da crotoxina na indução de paralisia da musculatura extraocular em modelo animal

    Directory of Open Access Journals (Sweden)

    Geraldo de Barros Ribeiro

    2012-10-01

    Full Text Available PURPOSE: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A. METHODS: The crotoxin, with LD50 of 1.5 µg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 µg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. RESULTS: The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 µg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 µg. CONCLUSION: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 µg was able to induce similar effects as botulinum toxin type A.OBJETIVO: A

  2. Obtained and evaluation of antisera raised against irradiated crotalic whole venom or crotoxin in 60 Co source

    International Nuclear Information System (INIS)

    Paula, Regina A. de.

    1995-01-01

    Snake bite is a great Public Health problem in our country. The accidents with snakes from Crotalus genus are the most severe. About 1% of the victims die without seratherapy. The antivenons are obtained from hyper immune horse plasma. During the production these animals present signs of envenoming that result in a decrease of organic resistance besides the horses maintenance is very expensive and the producers are fewer, so the sera production is restrict. Many techniques which could reduce the venoms toxicity and increase the sera production using chemical and physical agents have been studied. The gamma rays are excellent tool to detoxify venoms and toxins. It is able to modify protein structures that decrease lethally, toxic and enzymatic activities without modifying the immunogenicity. So, it is important evaluate the sera production in rabbits using gamma rays detoxified venom and crotoxin as immunogen and their power as reagents in immuno assays. In order to obtain the antisera, Crotalus durissus terrificus whole venom or isolated crotoxin was irradiated with 2.000 Gy in 60 Co source, in a 150 mM NaCl solution, and inoculated in rabbits. The sera production were screened by immunoprecipitation, immuno enzymatic (ELISA) and immunoradiometric (IRMA) assays. The specificity was studied by immuno-electrophoresis, ELISA and western blot techniques. The neutralizing power was evaluated by neutralization of phospholipase A 2 activity of toxin in vitro. The antisera were used as reagents in antigen capture assays ELISA and IRMA immuno assays to detect circulant antigens in sera of mice experimentally inoculated with crotalic venom or crotoxin. The results showed that both detoxified venom or crotoxin were good immunogens, and they were able to induce antibodies that could recognize non-irradiated venom or isolated crotoxin. The data suggest that those antibodies present more specificity and higher in vitro neutralizing power, when compared with commercial

  3. Crotoxin: Structural Studies, Mechanism of Action and Cloning of Its Gene

    Science.gov (United States)

    1987-03-01

    with these same antisera, while cross-reactivity with B3-bungarotoxin was very slight. Neurophysin and phospholipase A2 from N. n. atra and honey bee ...toxin from Cror alus viridis concolor, and monoclonal antibodies to czotoxin. We have used these to search for cross-reactive, homologoiis proteins in...concolor, and monoclonal antibodies to crotoxin. We have used these to search for cross-reactive, homclogous proteins in other venoms and examine their

  4. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Santos, Raquel G. dos; Dias, Consuelo L. Fortes; Cassali, Geovanni D.

    2009-01-01

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  5. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)], e-mail: consuelo@pq.cnpq.br; Cassali, Geovanni D. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada], e-mail: cassalig@icb.ufmg.br

    2009-07-01

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  6. Crotoxin in humans: analysis of the effects on extraocular and facial muscles Crotoxina em humanos: estudo da ação em músculos extraoculares e faciais

    Directory of Open Access Journals (Sweden)

    Geraldo de Barros Ribeiro

    2012-12-01

    Full Text Available PURPOSE: Crotoxin is the main neurotoxin of South American rattlesnake Crotalus durissus terrificus. The neurotoxic action is characterized by a presynaptic blockade. The purpose of this research is to assess the ability of crotoxin to induce temporary paralysis of extraocular and facial muscles in humans. METHODS: Doses of crotoxin used ranged from 2 to 5 units (U, each unit corresponding to one LD50. We first applied 2U of crotoxin in one of the extraocular muscles of 3 amaurotic individuals to be submitted to ocular evisceration. In the second stage, we applied crotoxin in 12 extraocular muscles of 9 patients with strabismic amblyopia. In the last stage, crotoxin was used in the treatment of blepharospasm in another 3 patients. RESULTS: No patient showed any systemic side effect or change in vision or any eye structure problem after the procedure. The only local side effects observed were slight conjunctival hyperemia, which recovered spontaneously. In 2 patients there was no change in ocular deviation after 2U crotoxin application. Limitation of the muscle action was observed in 8 of the 12 applications. The change in ocular deviation after application of 2U of crotoxin (9 injections was in average 15.7 prism diopters (PD. When the dose was 4U (2 applications the change was in average 37.5 PD and a single application of 5U produced a change of 16 PD in ocular deviation. This effect lasted from 1 to 3 months. Two of the 3 patients with blepharospasm had the hemifacial spasm improved with crotoxin, which returned after 2 months. CONCLUSIONS: This study provides data suggesting that crotoxin may be a useful new therapeutic option for the treatment of strabismus and blepharospasm. We expect that with further studies crotoxin could be an option for many other medical areas.OBJETIVO: A crotoxina é a principal neurotoxina da cascavel sul-americana Crotalus durissus terrificus e sua ação neurotóxica caracteriza-se por um bloqueio pr

  7. Gamma radiation effects on crotoxin (toxin of crotalus durissus terrificus venom)

    International Nuclear Information System (INIS)

    Souza Filho, J.N.; Rogero, J.R.

    1988-01-01

    The crotoxin is a great neurotoxin found on Crotalus durissus terrificus venom. This protein was isolated using molecular exclusion cromatography with Sephadex G-75 and irradiated in a source of 60 Co GAMMA-CELL in the concentration of 2 mg/ml 0.85% NaCl with dose rate of 1.19 x 10 3 Gy/hr. The doses used were 250, 500, 1000 and 2000 Gy. It was determinated for this samples, the proteic concentration, the diffusion immunoassay using crotalic antiserum and eletrophoresis (SDS-PAGE). The results showed some changes on the irradiated toxin. Preliminary results with doses of radiation of 100, 250, 500 and 1000 Gy showed that the letal dose 50% (LD50) in mice increase greatly with the increase of radiation's dose. (author) [pt

  8. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

    Science.gov (United States)

    Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

    2017-09-01

    American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

  9. Biodistribution and SPECT imaging of 125/131I-crotoxin on mice bearing Ehrlich solid tumour

    International Nuclear Information System (INIS)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos; Silveira, Marina B.; Simal, Carlos

    2009-01-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with 125/131 I using lactoperoxidase method and radiochemical analysis was performed by chromatography. 125 I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while 131 I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T 1/2 = 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). 131 I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  10. Effects of gamma radiation on crotoxin (toxin of Crotalus durissus terrificus venom)

    International Nuclear Information System (INIS)

    Souza Filho, J.N.; Rogero, J.R.

    1988-07-01

    The crotoxin in a great neurotoxin found on Crotalus durissus terrificus venom. This protein was isolated using molecular exclusion cromatrography with Sephadex G-75 and irradiated in a source of 60 Co GAMMACELL in the concentration of 2 mg/ml 0.85% NaCl with dose rate of 1.19 x 10 3 Gy/hr. The doses used were 250, 500, 1000 and 2000 Gy. It was determinated for this samples, the proteic concentration, the diffusion immunoassay using crotalic antiserum and eletrophoresis (SDS-PAGE). The results showed some changes on the irradiated toxin. Preliminary results with doses of radiation of 100, 250, 500 and 1000 Gy showed that the letal dose 50% (LD50) in mice increase greatly with the increase of radiation's dose. (author) [pt

  11. Study of uptake and endocytosis of gamma rays-irradiated crotoxin by mice peritoneal macrophages

    International Nuclear Information System (INIS)

    Cardi, Bruno Andrade

    1999-01-01

    The purpose was to investigate the uptake and endocytosis of 2000 Gy 60 Co irradiated crotoxin through mouse peritoneal macrophages, correlating with native one and another non related protein, the ovalbumin. Native (CTXN) or 2000 Gy 60 Co γ-rays (dose rate 540 Gy/hour) irradiated crotoxin (CTXI) or ovalbumin processed of same manner (OVAN - OVAI) were offered to mouse peritoneal macrophages and their uptake was evaluated by immunohistochemistry and quantitative in situ ELISA. The involvement of scavenger receptors (ScvR) was evaluated by using blockers drugs (Probuco-PBC or Dextran Sulfate - SD) or with nonspecific blocking using fetal calf serum (FBS). The morphology and viability of macrophages were preserved during the experiments. CTXI showed irradiation-induced aggregates and formation of oxidative changing were observed on this protein after gamma rays treatment. By immunohistochemistry we could observe heavy stained phagocytic vacuole on macrophages incubated with CTXI, as compared with CTXN. Quantitatively by in situ ELISA, the sema pattern was observed, displaying a 2-fold CTXI incorporation. In presence of PBC or SD we could find a significant decrease of CTXI uptake but not of CTXN. However the CTXN uptake was depressed by FBS, not observed with CTXI. OVA, after gamma rays treatment, underwent a high degradation suffering a potent incorporation and metabolism by macrophages, with a major uptake of OVAI in longer incubation (120 minutes). Gamma rays ( 60 Co) produced oxidative changes on CTX molecule, leading to a uptake by ScvR-mice peritoneal macrophages, suggesting that the relation antigen-presenting cells and gamma rays-modified proteins are responsible for the better immune response presented by irradiated antigens. (author)

  12. Biodistribution and SPECT imaging of {sup 125/131}I-crotoxin on mice bearing Ehrlich solid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: marcellaaraugio@yahoo.com.br, e-mail: santosr@cdtn.br; Silveira, Marina B.; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)

    2009-07-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with {sup 125/131}I using lactoperoxidase method and radiochemical analysis was performed by chromatography. {sup 125}I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while {sup 131}I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T{sub 1/2}= 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). {sup 131}I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  13. Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study

    Directory of Open Access Journals (Sweden)

    Jacques Medioni

    2017-09-01

    Full Text Available Introduction: Crotoxin has a broad antitumor activity but has shown frequent neurotoxic toxicity. To induce tolerance and limit this toxicity, we propose a new design with intra-patient dose escalation. Methods: A new Dose Limiting Toxicity definition was used. The concept of Target Ceiling Dose was introduced. Results: Dose Limiting Toxicity was the inability to dose escalate twice. Target Ceiling Dose was the highest planned dose to be administered to a patient and could change for patients along time. Recommended Dose was defined similarly as in a (3 + 3 conventional design. Conclusion: This innovant design was used and the clinical trial is now closed for inclusions. Results will be presented later. Keywords: Clinical trial, Phase 1, Intra-patient dose escalation, Cancer

  14. Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies.

    Science.gov (United States)

    Castro, Edgar Neri; Lomonte, Bruno; del Carmen Gutiérrez, María; Alagón, Alejandro; Gutiérrez, José María

    2013-07-11

    The composition and toxicological profile of the venom of the rattlesnake Crotalus simus in Mexico was analyzed at the subspecies and individual levels. Venoms of the subspecies C. s. simus, C. s. culminatus and C. s. tzabcan greatly differ in the expression of the heterodimeric neurotoxin complex 'crotoxin', with highest concentrations in C. s. simus, followed by C. s. tzabcan, whereas the venom of C. s. culminatus is almost devoid of this neurotoxic PLA2. This explains the large variation in lethality (highest in C. s. simus, which also exerts higher myotoxicity). Coagulant activity on plasma and fibrinogen occurs with the venoms of C. s. simus and C. s. tzabcan, being absent in C. s. culminatus which, in turn, presents higher crotamine-like activity. Proteomic analysis closely correlates with toxicological profiles, since the venom of C. s. simus has high amounts of crotoxin and of serine proteinases, whereas the venom of C. s. culminatus presents higher amounts of metalloproteinases and crotamine. This complex pattern of intraspecies venom variation provides valuable information for the diagnosis and clinical management of envenoming by this species in Mexico, as well as for the preparation of venom pools for the production and quality control of antivenoms. This study describes the variation in venom composition and activities of the three subspecies of Crotalus simus from Mexico. Results demonstrate that there is a notorious difference in these venoms, particularly regarding the content of the potent neurotoxic phospholipase A2 complex 'crotoxin'. In addition, other differences were observed regarding myotoxic and coagulant activities, and expression of the myotoxin 'crotamine'. These findings have implications in, at least, three levels: (a) the adaptive role of variations in venom composition; (b) the possible differences in the clinical manifestations of envenomings by these subspecies in Mexico; and (c) the design of venom mixtures for the preparation of

  15. 12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

    Science.gov (United States)

    DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

    2010-01-01

    Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

  16. Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells.

    Science.gov (United States)

    Liu, F; Weng, S-J; Yang, X-L; Zhong, Y-M

    2015-10-01

    Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-β-S/GPAnt-2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Gö6976. Neither adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. Copyright

  17. Crotamine and crotoxin interact with tumor cells and trigger cell death

    International Nuclear Information System (INIS)

    Soares, Marcella Araugio; Pujatti, Priscilla Brunelli; Santos, Raquel Gouvea dos; Dias, Consuelo Latorre Fortes; Chavez Olortegui, Carlos Delfin; Santos, Wagner Gouvea dos

    2007-01-01

    Crotoxin (Crtx) and Crotamine (Crota) are polypeptides isolated from Crotalus durissus terrificus snake venom (CV). Previous reports have been shown therapeutic effects of Crotalus durissus terrificus venom and Crtx on skin, breast and lung tumours, although, the mechanisms of this antitumoral effect are still unknown. The aim of this work was to investigate the antitumoral effect of Crtx and Crota on brain tumours cells (GH3 and RT2) in vitro and their capacity of interaction with these tumour cells membranes. Cell survival after Crtx and Crota treatment was evaluated by MTT assay in different times post-treatment and apoptosis was evaluated by DAPI staining. In order to evaluate the specific interaction of Crtx and Crota, these polypeptides were radiolabelled, using 125 I as radiotracer and binding assays were performed. The results were compared with the binding in nontumoral brain tissue. Crtx and Crota induced apoptosis on both tumour cells lineages but, Crota was more powerful than Crtx 90% and 20% cell death for RT2 cells; 80% and 20% cell death for GH3 cells, respectively). Both 125 I-Crtx and 125 I-Crota bound specifically in glioblastoma membranes. Nonetheless, CV polypeptides recognised glioblastoma cells with higher specificity than normal brain tissue. These results suggest that the Crtx and Crota interactions with the plasmatic membrane of tumour cells may be the first step of the cascade of signalling that trigger their antitumoral effect. (author)

  18. CO, Pb++ and SO2 effects on L-type calcium channel and action potential in human atrial myocytes. In silico study

    Directory of Open Access Journals (Sweden)

    Diana C. Pachajoa

    2017-09-01

    Full Text Available Exposure to air pollutants like carbon monoxide (CO, lead (Pb++ and sulfur dioxide (SO2 promotes the occurrence of cardiovascular diseases. Experimental studies have shown that CO, Pb++ and SO2 block L-type calcium channels, reducing the calcium current (ICaL and the action potential duration (APD, which favors the initiation of atrial arrhythmias. The goal is to study the effects of CO, Pb++ and SO2 at different concentrations on ICaL and action potential using computational simulation. For this purpose, models of the effects of the air pollutants on the atrial L-type calcium channel were developed and were incorporated into a mathematical model of a human atrial cell. The results suggest that CO, Pb++ and SO2 block the ICaL current in a fraction that increases along with the concentration, generating an APD shortening. These results are consistent with experimental studies. The combined effect of the three air pollutants produced an APD shortening, which is considered to be a pro-arrhythmic effect.

  19. Effective Kratzer and Coulomb potentials as limit cases of a multiparameter exponential-type potential

    Energy Technology Data Exchange (ETDEWEB)

    García-Ravelo, J., E-mail: g.ravelo@hotmail.com [Departamento de Física, Escuela Superior de Física y Matemáticas, Instituto Politécnico Nacional, Edificio 9, Unidad Profesional Adolfo López Mateos, México D.F., 07738 (Mexico); Menéndez, A.; García-Martínez, J. [Departamento de Física, Escuela Superior de Física y Matemáticas, Instituto Politécnico Nacional, Edificio 9, Unidad Profesional Adolfo López Mateos, México D.F., 07738 (Mexico); Schulze-Halberg, A. [Department of Mathematics and Actuarial Science and Department of Physics, Indiana University Northwest, 3400 Broadway, Gary, IN 46408 (United States)

    2014-06-13

    We show that the effective Kratzer and Coulomb potentials can be obtained by taking particular limits of a multiparameter exponential potential that was studied recently. Moreover, we demonstrate that the bound state solutions of the exponential potential reduce correctly to their well-known counterparts associated with the Kratzer and Coulomb potentials. As a byproduct, we obtain a new limit relation for the hypergeometric function. - Highlights: • Kratzer and Coulomb potentials are limit cases of an exponential-type potential. • From exact s-waves, approximate solutions for l-waves are obtained. • l-waves of the potential tend to the solutions of the Kratzer and Coulomb potentials. • A non-evident identity between hypergeometric functions is demonstrated.

  20. Effective Kratzer and Coulomb potentials as limit cases of a multiparameter exponential-type potential

    International Nuclear Information System (INIS)

    García-Ravelo, J.; Menéndez, A.; García-Martínez, J.; Schulze-Halberg, A.

    2014-01-01

    We show that the effective Kratzer and Coulomb potentials can be obtained by taking particular limits of a multiparameter exponential potential that was studied recently. Moreover, we demonstrate that the bound state solutions of the exponential potential reduce correctly to their well-known counterparts associated with the Kratzer and Coulomb potentials. As a byproduct, we obtain a new limit relation for the hypergeometric function. - Highlights: • Kratzer and Coulomb potentials are limit cases of an exponential-type potential. • From exact s-waves, approximate solutions for l-waves are obtained. • l-waves of the potential tend to the solutions of the Kratzer and Coulomb potentials. • A non-evident identity between hypergeometric functions is demonstrated

  1. Effects of ionizing radiation on crotoxin (toxin of Crotalus durissus terrificus venom): molecular studies

    International Nuclear Information System (INIS)

    Souza Filho, J.N. de.

    1988-01-01

    It is know that the ionizing radiation is able to change significantly the biological and antigenic response of a toxin depending of the dose and irradiation's conditions, probable by structural alterations caused by radiation. In this work, the crotoxin, principal neurotoxin of the South American rattlesnake venom, was isolated using molecular exclusion chromatography with Sephadex G-75 and follwed by precipitation on the isoelectric point. Fractions in the concentration of 2 mg of protein/m1 0.85% NaCl were irradiated in a source of sup(60)Co GAMMACELL with dose rate of 1100 Gy/h using doses of 250, 500, 1000, 1500 and 2000 Gy. It was determinated for these samples, the proteic concentration (Lowry's method), the content sulphydryl (Ellman's method), the profile electrophoretic (SDS-PAGE), the toxicity by lethal dose 50% in mice and the antigenic response using crotalic antiserum by the diffusion imunoassay (Ouchterlony's method). The results showed the formation of aggregates and loss of protein in solution by precipitation. In the dose of 1000 Gy and higher it was possible to observe the presence of sulphydryl groups indicating the breakage of S-S bridges. The lethal dose 50% increased 2 times for the dose of 1000 Gy and 3.5 times for 1500 Gy shoding a detoxication. By the other hand, the antigenic response seems to be still intact at doses up to 1000 Gy. (author)

  2. Potential Biomarker of L type Amino Acid Transporter 1 in Breast Cancer Progression

    International Nuclear Information System (INIS)

    Liang, Zhongxing; Cho, Heidi T.; Williams, Larry; Zhu, Aizhi; Liang, Ke; Huang, Ke; Wu, Hui; Jiang, Chunsu; Hong, Samuel; Crowe, Ronald; Goodman, Mark M.; Shim, Hyunsuk

    2011-01-01

    L type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with 1 amino 3 [ 18F ]fluorocyclo butane 1 carboxylic acid ([ 18F ]FACBC) PET was assessed for its diagnostic biomarker potential. Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced stage breast cancer. Furtermore, the blockade of LAT1 with its inhibitor, 2 amino bicyclo[2.2.1]heptane 2 carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, [ 18F ]FACBC, has been demonstrated to be an excellent PET tracer for the non invasive imaging og malignant breast cancer using an orthotopic animal model. The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. [ 18F ]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging

  3. L-Type Calcium Channels Modulation by Estradiol.

    Science.gov (United States)

    Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

    2017-09-01

    Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

  4. Reduction of low potential electron acceptors requires the CbcL inner membrane cytochrome of Geobacter sulfurreducens.

    Science.gov (United States)

    Zacharoff, Lori; Chan, Chi Ho; Bond, Daniel R

    2016-02-01

    The respiration of metals by the bacterium Geobacter sulfurreducens requires electrons generated by metabolism to pass from the interior of the cell to electron acceptors beyond the cell membranes. The G. sulfurreducens inner membrane multiheme c-type cytochrome ImcH is required for respiration to extracellular electron acceptors with redox potentials greater than -0.1 V vs. SHE, but ImcH is not essential for electron transfer to lower potential acceptors. In contrast, deletion of cbcL, encoding an inner membrane protein consisting of b-type and multiheme c-type cytochrome domains, severely affected reduction of low potential electron acceptors such as Fe(III)-oxides and electrodes poised at -0.1 V vs. SHE. Catalytic cyclic voltammetry of a ΔcbcL strain growing on poised electrodes revealed a 50 mV positive shift in driving force required for electron transfer out of the cell. In non-catalytic conditions, low-potential peaks present in wild type biofilms were absent in ∆cbcL mutants. Expression of cbcL in trans increased growth at low redox potential and restored features to cyclic voltammetry. This evidence supports a model where CbcL is a component of a second electron transfer pathway out of the G. sulfurreducens inner membrane that dominates when redox potential is at or below -0.1 V vs. SHE. Copyright © 2015. Published by Elsevier B.V.

  5. Neuromuscular paralysis by the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage.

    Science.gov (United States)

    Cavalcante, Walter L G; Noronha-Matos, José B; Timóteo, Maria A; Fontes, Marcos R M; Gallacci, Márcia; Correia-de-Sá, Paulo

    2017-11-01

    Crotoxin (CTX), a heterodimeric phospholipase A 2 (PLA 2 ) neurotoxin from Crotalus durissus terrificus snake venom, promotes irreversible blockade of neuromuscular transmission. Indirect electrophysiological evidence suggests that CTX exerts a primary inhibitory action on transmitter exocytosis, yet contribution of a postsynaptic action of the toxin resulting from nicotinic receptor desensitization cannot be excluded. Here, we examined the blocking effect of CTX on nerve-evoked transmitter release measured directly using radioisotope neurochemistry and video microscopy with the FM4-64 fluorescent dye. Experiments were conducted using mice phrenic-diaphragm preparations. Real-time fluorescence video microscopy and liquid scintillation spectrometry techniques were used to detect transmitter exocytosis and nerve-evoked [ 3 H]-acetylcholine ([ 3 H]ACh) release, respectively. Nerve-evoked myographic recordings were also carried out for comparison purposes. Both CTX (5μg/mL) and its basic PLA 2 subunit (CB, 20μg/mL) had biphasic effects on nerve-evoked transmitter exocytosis characterized by a transient initial facilitation followed by a sustained decay. CTX and CB reduced nerve-evoked [ 3 H]ACh release by 60% and 69%, respectively, but only the heterodimer, CTX, decreased the amplitude of nerve-evoked muscle twitches. Data show that CTX exerts a presynaptic inhibitory action on ACh release that is highly dependent on its intrinsic PLA 2 activity. Given the high safety margin of the neuromuscular transmission, one may argue that the presynaptic block caused by the toxin is not enough to produce muscle paralysis unless a concurrent postsynaptic inhibitory action is also exerted by the CTX heterodimer. Copyright © 2017. Published by Elsevier Inc.

  6. Study of uptake and endocytosis of gamma rays-irradiated crotoxin by mice peritoneal macrophages; Avaliacao do mecanismo de captacao e endocitose de crotoxina submetida a acao da radiacao, por macrofagos peritoneais de camundongos

    Energy Technology Data Exchange (ETDEWEB)

    Cardi, Bruno Andrade

    1999-07-01

    The purpose was to investigate the uptake and endocytosis of 2000 Gy {sup 60}Co irradiated crotoxin through mouse peritoneal macrophages, correlating with native one and another non related protein, the ovalbumin. Native (CTXN) or 2000 Gy {sup 60} Co {gamma}-rays (dose rate 540 Gy/hour) irradiated crotoxin (CTXI) or ovalbumin processed of same manner (OVAN - OVAI) were offered to mouse peritoneal macrophages and their uptake was evaluated by immunohistochemistry and quantitative in situ ELISA. The involvement of scavenger receptors (ScvR) was evaluated by using blockers drugs (Probuco-PBC or Dextran Sulfate - SD) or with nonspecific blocking using fetal calf serum (FBS). The morphology and viability of macrophages were preserved during the experiments. CTXI showed irradiation-induced aggregates and formation of oxidative changing were observed on this protein after gamma rays treatment. By immunohistochemistry we could observe heavy stained phagocytic vacuole on macrophages incubated with CTXI, as compared with CTXN. Quantitatively by in situ ELISA, the sema pattern was observed, displaying a 2-fold CTXI incorporation. In presence of PBC or SD we could find a significant decrease of CTXI uptake but not of CTXN. However the CTXN uptake was depressed by FBS, not observed with CTXI. OVA, after gamma rays treatment, underwent a high degradation suffering a potent incorporation and metabolism by macrophages, with a major uptake of OVAI in longer incubation (120 minutes). Gamma rays ({sup 60} Co) produced oxidative changes on CTX molecule, leading to a uptake by ScvR-mice peritoneal macrophages, suggesting that the relation antigen-presenting cells and gamma rays-modified proteins are responsible for the better immune response presented by irradiated antigens. (author)

  7. Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2

    International Nuclear Information System (INIS)

    Ullrich, Nina D.; Koschak, Alexandra; MacLeod, Kenneth T.

    2007-01-01

    Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca 2+ channel (Ca v 1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca 2+ current, I CaL . The effect of oestrogen on I CaL was measured in Ca v 1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I CaL . Oestrogen (50 μM) rapidly reduced I CaL by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca 2+ channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I CaL through direct interaction of the steroid with the channel protein

  8. Effects of gamma radiation on snake venoms

    International Nuclear Information System (INIS)

    Nascimento, N.; Spencer, P.J.; Andrade, H.F.; Guarnieri, M.C.; Rogero, J.R.

    1998-01-01

    Ionizing radiation is able to detoxify several venoms, including snake venoms, without affecting significantly their immunogenic properties. In order to elucidate this phenomena, we conceived a comparative pharmacological study between native and irradiated (2,000 Gy) crotoxin, the main toxin of the South American rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified by molecular exclusion chromatography, pI precipitation and, subsequently submitted to irradiation. Gel filtration of the irradiated toxin resulted in some high molecular weight aggregates formation. Crotoxin toxicity decreased two folds after irradiation, as determined by LD 50 in mice. Native and irradiated crotoxin biodistribution ocurred in the same general manner, with renal elimination. However, in contrast to irradiated crotoxin, the native form was initially retained in kidneys. A later concentration (2-3 hr) appeared in phagocytic mononuclear cells rich organs (liver and spleen) and neural junction rich organs (muscle and brain)

  9. Impaired Inactivation of L-Type Ca2+ Current as a Potential Mechanism for Variable Arrhythmogenic Liability of HERG K+ Channel Blocking Drugs.

    Directory of Open Access Journals (Sweden)

    Jae Gon Kim

    Full Text Available The proarrhythmic effects of new drugs have been assessed by measuring rapidly activating delayed-rectifier K+ current (IKr antagonist potency. However, recent data suggest that even drugs thought to be highly specific IKr blockers can be arrhythmogenic via a separate, time-dependent pathway such as late Na+ current augmentation. Here, we report a mechanism for a quinolone antibiotic, sparfloxacin-induced action potential duration (APD prolongation that involves increase in late L-type Ca2+ current (ICaL caused by a decrease in Ca2+-dependent inactivation (CDI. Acute exposure to sparfloxacin, an IKr blocker with prolongation of QT interval and torsades de pointes (TdP produced a significant APD prolongation in rat ventricular myocytes, which lack IKr due to E4031 pretreatment. Sparfloxacin reduced peak ICaL but increased late ICaL by slowing its inactivation. In contrast, ketoconazole, an IKr blocker without prolongation of QT interval and TdP produced reduction of both peak and late ICaL, suggesting the role of increased late ICaL in arrhythmogenic effect. Further analysis showed that sparfloxacin reduced CDI. Consistently, replacement of extracellular Ca2+ with Ba2+ abolished the sparfloxacin effects on ICaL. In addition, sparfloxacin modulated ICaL in a use-dependent manner. Cardiomyocytes from adult mouse, which is lack of native IKr, demonstrated similar increase in late ICaL and afterdepolarizations. The present findings show that sparfloxacin can prolong APD by augmenting late ICaL. Thus, drugs that cause delayed ICaL inactivation and IKr blockage may have more adverse effects than those that selectively block IKr. This mechanism may explain the reason for discrepancies between clinically reported proarrhythmic effects and IKr antagonist potencies.

  10. The Ultracool Typing Kit - An Open-Source, Qualitative Spectral Typing GUI for L Dwarfs

    Science.gov (United States)

    Schwab, Ellianna; Cruz, Kelle; Núñez, Alejandro; Burgasser, Adam J.; Rice, Emily; Reid, Neill; Faherty, Jacqueline K.; BDNYC

    2018-01-01

    The Ultracool Typing Kit (UTK) is an open-source graphical user interface for classifying the NIR spectral types of L dwarfs, including field and low-gravity dwarfs spanning L0-L9. The user is able to input an NIR spectrum and qualitatively compare the input spectrum to a full suite of spectral templates, including low-gravity beta and gamma templates. The user can choose to view the input spectrum as both a band-by-band comparison with the templates and a full bandwidth comparison with NIR spectral standards. Once an optimal qualitative comparison is selected, the user can save their spectral type selection both graphically and to a database. Using UTK to classify 78 previously typed L dwarfs, we show that a band-by-band classification method more accurately agrees with optical spectral typing systems than previous L dwarf NIR classification schemes. UTK is written in python, released on Zenodo with a BSD-3 clause license and publicly available on the BDNYC Github page.

  11. Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

    Science.gov (United States)

    Mahmoudi, Leila; Kissner, Reinhard; Nauser, Thomas; Koppenol, Willem H

    2016-05-24

    Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

  12. Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Caroline de Souza Almeida

    Full Text Available Inflammatory bowel diseases (IBD is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS. The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI, macroscopic tissue damage, histopathological score and myeloperoxidase (MPO activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3 and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2 and lipoxin A4 (LXA4 was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the

  13. New type shift operators for circular well potential in two dimensions

    International Nuclear Information System (INIS)

    Sun Guohua; Dong Shihai

    2010-01-01

    New type shift operators for circular well potential in two dimensions are identified. These so-called shift operators connect those quantum systems with the different potentials but with same energy spectrum. It should be noted that these operators depend on both the radial circular and angular variables r and φ. We find that the operators P ± =P x ±P y play the role of the shift operators. The radial linear momentum P r =-ih(∂)/(∂r) , the angular momentum L z =-ih(∂)/(∂φ) and the Hamiltonian form a complete set of commuting operators with the SO(2) symmetry.

  14. Relation of Different Type Love-Shida Numbers Determined with the Use of Time-Varying Incremental Gravitational Potential

    Science.gov (United States)

    Varga, Peter; Grafarend, Erik; Engels, Johannes

    2017-03-01

    There are different equations to describe relations between different classes of Love-Shida numbers. In this study with the use of the time-varying gravitational potential an integral relation was obtained which connects tidal Love-Shida numbers (h, l, k), load numbers (h', l', k'), potential free Love-Shida numbers generated by normal (h″, l″, k″) and horizontal (h‴, l‴, k‴) stresses. The equations obtained in frame of present study is the only one which - holds for every type of Love-Shida numbers, - describes a relationship not between different, but the same type of Love-Shida numbers, - does not follow from the sixth-order differential equation system of motion usually applied to calculate the Love-Shida numbers.

  15. Effect of the L499M mutation of the ascomycetous Botrytis aclada laccase on redox potential and catalytic properties

    International Nuclear Information System (INIS)

    Osipov, Evgeny; Polyakov, Konstantin; Kittl, Roman; Shleev, Sergey; Dorovatovsky, Pavel; Tikhonova, Tamara; Hann, Stephan; Ludwig, Roland; Popov, Vladimir

    2014-01-01

    The structures of the ascomycetous B. aclada laccase and its L499M T1-site mutant have been solved at 1.7 Å resolution. The mutant enzyme shows a 140 mV lower redox potential of the type 1 copper and altered kinetic behaviour. The wild type and the mutant have very similar structures, which makes it possible to relate the changes in the redox potential to the L499M mutation Laccases are members of a large family of multicopper oxidases that catalyze the oxidation of a wide range of organic and inorganic substrates accompanied by the reduction of dioxygen to water. These enzymes contain four Cu atoms per molecule organized into three sites: T1, T2 and T3. In all laccases, the T1 copper ion is coordinated by two histidines and one cysteine in the equatorial plane and is covered by the side chains of hydrophobic residues in the axial positions. The redox potential of the T1 copper ion influences the enzymatic reaction and is determined by the nature of the axial ligands and the structure of the second coordination sphere. In this work, the laccase from the ascomycete Botrytis aclada was studied, which contains conserved Ile491 and nonconserved Leu499 residues in the axial positions. The three-dimensional structures of the wild-type enzyme and the L499M mutant were determined by X-ray crystallography at 1.7 Å resolution. Crystals suitable for X-ray analysis could only be grown after deglycosylation. Both structures did not contain the T2 copper ion. The catalytic properties of the enzyme were characterized and the redox potentials of both enzyme forms were determined: E 0 = 720 and 580 mV for the wild-type enzyme and the mutant, respectively. Since the structures of the wild-type and mutant forms are very similar, the change in the redox potential can be related to the L499M mutation in the T1 site of the enzyme

  16. A 2MASS/AllWISE Search for Extremely Red L Dwarfs: The Discovery of Several Likely L Type Members of β Pic, AB Dor, Tuc-Hor, Argus, and the Hyades

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Adam C.; Shkolnik, Evgenya L. [School of Earth and Space Exploration, Arizona State University, Tempe, AZ, 85282 (United States); Windsor, James; Cushing, Michael C. [Department of Physics and Astronomy, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606 (United States); Kirkpatrick, J. Davy, E-mail: aschneid10@gmail.com [IPAC, Mail Code 100-22, Caltech, 1200 E. California Boulevard, Pasadena, CA 91125 (United States)

    2017-04-01

    Young brown dwarfs share many properties with directly imaged giant extrasolar planets. They therefore provide unique laboratories for investigating the full range of temperature and mass encompassed by the growing collection of planets discovered outside our Solar System. Furthermore, if they can be tied to a particular group of coeval stars, they also provide vital anchor points for low-mass empirical isochrones. We have developed a novel procedure for identifying such objects based on their unique 2MASS and AllWISE colors. Using our search criteria, we have identified 50 new, late-type L dwarf candidates, 47 of which are spectroscopically confirmed as L dwarfs with follow-up near-infrared spectroscopy. We evaluate the potential membership of these objects in nearby, young moving groups using their proper motions, photometric distance estimates, and spectroscopic indicators of youth, and find seven likely L-type members belonging to the β Pictoris moving group, the AB Doradus moving group, the Tucana-Horologium association, or the Argus association, in addition to several lower probability members. Also found are two late-type (L5 and L6) potential members of the nearby Hyades cluster (WISEA J043642.75+190134.8 and WISEA J044105.56+213001.5).

  17. Role of L-Type Ca[superscript 2+] Channel Isoforms in the Extinction of Conditioned Fear

    Science.gov (United States)

    Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J.; Striessnig, Jorg; Singewald, Nicolas

    2008-01-01

    Dihydropyridine (DHP) L-type Ca[superscript 2+] channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the…

  18. L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites

    Directory of Open Access Journals (Sweden)

    Brian G. Hiester

    2017-11-01

    Full Text Available The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion.

  19. Type III-L Solar Radio Bursts and Solar Energetic Particle Events

    Science.gov (United States)

    Duffin, R. T.; White, S. M.; Ray, P. S.; Kaiser, M. L.

    2015-09-01

    A radio-selected sample of fast drift radio bursts with complex structure occurring after the impulsive phase of the associated flare (“Type III-L bursts”) is identified by inspection of radio dynamic spectra from 1 to 180 MHz for over 300 large flares in 2001. An operational definition that takes into account previous work on these radio bursts starting from samples of solar energetic particle (SEP) events is applied to the data, and 66 Type III-L bursts are found in the sample. In order to determine whether the presence of these radio bursts can be used to predict the occurrence of SEP events, we also develop a catalog of all SEP proton events in 2001 using data from the ERNE detector on the SOHO satellite. 68 SEP events are found, for 48 of which we can identify a solar source and hence look for associated Type III-L emission. We confirm previous work that found that most (76% in our sample) of the solar sources of SEP events exhibit radio emission of this type. However, the correlation in the opposite direction is not as strong: starting from a radio-selected sample of Type III-L events, around 64% of the bursts that occur at longitudes magnetically well-connected to the Earth, and hence favorable for detection of SEPs, are associated with SEP events. The degree of association increases when the events have durations over 10 minutes at 1 MHz, but in general Type III-L bursts do not perform any better than Type II bursts in our sample as predictors of SEP events. A comparison of Type III-L timing with the arrival of near-relativistic electrons at the ACE spacecraft is not inconsistent with a common source for the accelerated electrons in both phenomena.

  20. Type III-L Solar Radio Bursts and Solar Energetic Particle Events

    International Nuclear Information System (INIS)

    Duffin, R T; White, S M; Ray, P S; Kaiser, M L

    2015-01-01

    A radio-selected sample of fast drift radio bursts with complex structure occurring after the impulsive phase of the associated flare (“Type III-L bursts”) is identified by inspection of radio dynamic spectra from 1 to 180 MHz for over 300 large flares in 2001. An operational definition that takes into account previous work on these radio bursts starting from samples of solar energetic particle (SEP) events is applied to the data, and 66 Type III-L bursts are found in the sample. In order to determine whether the presence of these radio bursts can be used to predict the occurrence of SEP events, we also develop a catalog of all SEP proton events in 2001 using data from the ERNE detector on the SOHO satellite. 68 SEP events are found, for 48 of which we can identify a solar source and hence look for associated Type III-L emission. We confirm previous work that found that most (76% in our sample) of the solar sources of SEP events exhibit radio emission of this type. However, the correlation in the opposite direction is not as strong: starting from a radio-selected sample of Type III-L events, around 64% of the bursts that occur at longitudes magnetically well-connected to the Earth, and hence favorable for detection of SEPs, are associated with SEP events. The degree of association increases when the events have durations over 10 minutes at 1 MHz, but in general Type III-L bursts do not perform any better than Type II bursts in our sample as predictors of SEP events. A comparison of Type III-L timing with the arrival of near-relativistic electrons at the ACE spacecraft is not inconsistent with a common source for the accelerated electrons in both phenomena. (paper)

  1. Martensitic transformation in 304L and 316L types stainless steels cathodically hydrogen charged

    International Nuclear Information System (INIS)

    Minkovitz, E.; Eliezer, D.

    1984-01-01

    This paper reports a TEM study on the role of phase transitions at the crack tip in 304L and 316L types stainless steels cathodically hydrogen charged in the absence of any eternally applied forces. The possible role of α prime and epsilon martensite phases in the fracture mechanism is discussed

  2. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  3. Localization of Rod Bipolar Cells in the Mammalian Retina Using an Antibody Against the α1c L-type Ca2+ Channel

    International Nuclear Information System (INIS)

    Huh, Yu-Jin; Choi, Jae-Sik; Jeon, Chang-Jin

    2015-01-01

    Bipolar cells transmit stimuli via graded changes in membrane potential and neurotransmitter release is modulated by Ca 2+ influx through L-type Ca 2+ channels. The purpose of this study was to determine whether the α 1 c subunit of L-type voltage-gated Ca 2+ channel (α 1 c L-type Ca 2+ channel) colocalizes with protein kinase C alpha (PKC-α), which labels rod bipolar cells. Retinal whole mounts and vertical sections from mouse, hamster, rabbit, and dog were immunolabeled with antibodies against PKC-α and α 1 c L-type Ca 2+ channel, using fluorescein isothiocyanate (FITC) and Cy5 as visualizing agents. PKC-α-immunoreactive cells were morphologically identical to rod bipolar cells as previously reported. Their cell bodies were located within the inner nuclear layer, dendritic processes branched into the outer plexiform layer, and axons extended into the inner plexiform layer. Immunostaining showed that α 1 c L-type Ca 2+ channel colocalized with PKC-α in rod bipolar cells. The identical expression of PKC-α and α 1 c L-type Ca 2+ channel indicates that the α 1 c L-type Ca 2+ channel has a specific role in rod bipolar cells, and the antibody against the α 1 c L-type Ca 2+ channel may be a useful marker for studying the distribution of rod bipolar cells in mouse, hamster, rabbit, and dog retinas

  4. Corrosion studies on type AISI 316L stainless steel and other materials in lithium-salt solutions

    International Nuclear Information System (INIS)

    Zheng, J.H.; Bogaerts, W.F.; Agema, K.; Phlippo, K.; Bruggeman, A.; Lorenzetto, P.; Embrechts, M.J.

    1991-01-01

    A possible concept for the blanket for next generation fusion devices is the lithium salt blanket, where lithium salt is dissolved in an aqueous coolant in order to provide for tritium. Type AISI 316L stainless steel has been considered as a structural material for such a blanket for NET (Next European Torus), and a systematic study of the corrosion behaviour of 316L stainless steel has been carried out in a number of lithium salt solutions. The experiments include cyclic potentiodynamic polarization measurement, crevice corrosion fatigue and stress corrosion cracking (SCC) tests. This paper presents a part of novel corrosion results concerning the compatibility of 316L steel and a series of other materials relevant to a fusion blanket environment. No major uniform corrosion problem has been observed, but localized corrosion, particularly corrosion fatigue and SCC, of 316L stainless steel have been found so far in a lithium hydroxide solution under some specific potential conditions. The critical electrochemical potential zones for SCC have been identified in the present study. (orig.)

  5. Immunochemical aspects of crotoxim and its subunits

    International Nuclear Information System (INIS)

    Nakazone, A.K.

    1979-01-01

    Crotamine and crotoxin with the subunits - phospholipase A and crotapotin - were obtained by purification from Crotalus durissus terrificus venom. Interaction studies of the subunits using crotalic antiserum, indicated that: crotoxin is formed of crotapotin and phospholipase A with the molar ratio of 1 to 1; using crotapotin 125 I the presence of a soluble complex was shown with the same antiserum. Immunological precipitation reactions demonstrated that crotapotin is antigenic: crotapotin and phospholipase A presented similar antigenic determinants; crotoxin antiserum reacted with each one of the submits; when the subunits are mixed to form synthetic crotoxin some antigenic determinants are masked in the process of interaction. Crotamine, interacted with crotapotin 1:1, without hidden antigenic determinants crotapotin antigenic site seems to be formed by, at least, one lysine. Enzimatical activity of phospholipase A apreared to be dependent on some reaction conditions when its arginine residues are blocked. Tyrosines of phospholipase A are more susceptible to labelling with 131 I than crotapotin. Gama irradiation of aqueous solutions of the subunits produced modifications in the ultraviolet spectra. A decrease of the enzymatic activity occured as a function of radiation dosis. Immunological activities of crotapotin and phospholipase A were not altered [pt

  6. An allosteric gating model recapitulates the biophysical properties of IK,L expressed in mouse vestibular type I hair cells.

    Science.gov (United States)

    Spaiardi, Paolo; Tavazzani, Elisa; Manca, Marco; Milesi, Veronica; Russo, Giancarlo; Prigioni, Ivo; Marcotti, Walter; Magistretti, Jacopo; Masetto, Sergio

    2017-11-01

    Vestibular type I and type II hair cells and their afferent fibres send information to the brain regarding the position and movement of the head. The characteristic feature of type I hair cells is the expression of a low-voltage-activated outward rectifying K + current, I K,L , whose biophysical properties and molecular identity are still largely unknown. In vitro, the afferent nerve calyx surrounding type I hair cells causes unstable intercellular K + concentrations, altering the biophysical properties of I K,L . We found that in the absence of the calyx, I K,L in type I hair cells exhibited unique biophysical activation properties, which were faithfully reproduced by an allosteric channel gating scheme. These results form the basis for a molecular and pharmacological identification of I K,L . Type I and type II hair cells are the sensory receptors of the mammalian vestibular epithelia. Type I hair cells are characterized by their basolateral membrane being enveloped in a single large afferent nerve terminal, named the calyx, and by the expression of a low-voltage-activated outward rectifying K + current, I K,L . The biophysical properties and molecular profile of I K,L are still largely unknown. By using the patch-clamp whole-cell technique, we examined the voltage- and time-dependent properties of I K,L in type I hair cells of the mouse semicircular canal. We found that the biophysical properties of I K,L were affected by an unstable K + equilibrium potential (V eq K + ). Both the outward and inward K + currents shifted V eq K + consistent with K + accumulation or depletion, respectively, in the extracellular space, which we attributed to a residual calyx attached to the basolateral membrane of the hair cells. We therefore optimized the hair cell dissociation protocol in order to isolate mature type I hair cells without their calyx. In these cells, the uncontaminated I K,L showed a half-activation at -79.6 mV and a steep voltage dependence (2.8 mV). I K,L also

  7. Allelopathic Potential of Switchgrass ( Panicum virgatum L.) on Perennial Ryegrass ( Lolium perenne L.) and Alfalfa ( Medicago sativa L.)

    Science.gov (United States)

    Shui, Junfeng; An, Yu; Ma, Yongqing; Ichizen, Nobumasa

    2010-10-01

    This study investigated allelopathy and its chemical basis in nine switchgrass ( Panicum virgatum L.) accessions. Perennial ryegrass ( Lolium perenne L.) and alfalfa ( Medicago sativa L.) were used as test species. Undiluted aqueous extracts (5 g plant tissue in 50 ml water) from the shoots and roots of most of the switchgrass accessions inhibited the germination and growth of the test species. However, the allelopathic effect of switchgrass declined when extracts were diluted 5- or 50-fold. Seedling growth was more sensitive than seed germination as an indicator of allelopathic effect. Allelopathic effect was related to switchgrass ecotype but not related to ploidy level. Upland accessions displayed stronger allelopathic potential than lowland accessions. The aqueous extract from one switchgrass accession was separated into phenols, organic acids, neutral chemicals, and alkaloids, and then these fractions were bioassayed to test for allelopathic potential. Alkaloids had the strongest allelopathic effect among the four chemical fractions. In summary, the results indicated that switchgrass has allelopathic potential; however, there is not enough evidence to conclude that allelopathic advantage is the main factor that has contributed to the successful establishment of switchgrass on China’s Loess Plateau.

  8. Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure.

    Science.gov (United States)

    Bond, Richard C; Bryant, Simon M; Watson, Judy J; Hancox, Jules C; Orchard, Clive H; James, Andrew F

    2017-03-01

    Constitutive regulation by PKA has recently been shown to contribute to L-type Ca 2+ current ( I CaL ) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I CaL in heart failure. The hypothesis that downregulation of atrial I CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N =10) or equivalent sham-operation (Sham, N =12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). I CaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal I CaL conductance ( G max ) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P 50% more effectively in CAL than in Sham so that differences in I CaL density were abolished. Differences between CAL and Sham G max were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for I CaL downregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I CaL Expression of the L-type α 1C -subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial I CaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca 2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit

  9. Wegner estimate and localization for alloy-type models with sign-changing exponentially decaying single-site potentials

    Science.gov (United States)

    Leonhardt, Karsten; Peyerimhoff, Norbert; Tautenhahn, Martin; Veselić, Ivan

    2015-05-01

    We study Schrödinger operators on L2(ℝd) and ℓ2(ℤd) with a random potential of alloy-type. The single-site potential is assumed to be exponentially decaying but not necessarily of fixed sign. In the continuum setting, we require a generalized step-function shape. Wegner estimates are bounds on the average number of eigenvalues in an energy interval of finite box restrictions of these types of operators. In the described situation, a Wegner estimate, which is polynomial in the volume of the box and linear in the size of the energy interval, holds. We apply the established Wegner estimate as an ingredient for a localization proof via multiscale analysis.

  10. Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

    Science.gov (United States)

    Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

    2017-10-01

    Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

  11. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    International Nuclear Information System (INIS)

    Bevilacqua, M.; Vago, T.; Norbiato, G.

    1991-01-01

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [ 3 H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca 2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca 2+ -containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca 2+ to the medium. This result was consistent with a competition between Ca 2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca 2+

  12. A Renewable and Ultrasensitive Electrochemiluminescence Immunosenor Based on Magnetic RuL@SiO2-Au~RuL-Ab2 Sandwich-Type Nano-Immunocomplexes

    Directory of Open Access Journals (Sweden)

    Ning Gan

    2011-08-01

    Full Text Available An ultrasensitive and renewable electrochemiluminescence (ECL immunosensor was developed for the detection of tumor markers by combining a newly designed trace tag and streptavidin-coated magnetic particles (SCMPs. The trace tag (RuL@SiO2-Au~RuL-Ab2 was prepared by loading Ru(bpy32+(RuL-conjuged secondary antibodies (RuL-Ab2 on RuL@SiO2 (RuL-doped SiO2 doped Au (RuL@SiO2-Au. To fabricate the immunosensor, SCMPs were mixed with biotinylated AFP primary antibody (Biotin-Ab1, AFP, and RuL@SiO2-Au~RuL-Ab2 complexes, then the resulting SCMP/Biotin-Ab1/AFP/RuL@SiO2-Au~RuL-Ab2 (SBAR sandwich-type immunocomplexes were absorbed on screen printed carbon electrode (SPCE for detection. The immunocomplexes can be easily washed away from the surface of the SPCE when the magnetic field was removed, which made the immunosensor reusable. The present immunosensor showed a wide linear range of 0.05–100 ng mL–1 for detecting AFP, with a low detection limit of 0.02 ng mL–1 (defined as S/N = 3. The method takes advantage of three properties of the immunosensor: firstly, the RuL@SiO2-Au~RuL-Ab2 composite exhibited dual amplification since SiO2 could load large amount of reporter molecules (RuL for signal amplification. Gold particles could provide a large active surface to load more reporter molecules (RuL-Ab2. Accordingly, through the ECL response of RuL and tripropylamine (TPA, a strong ECL signal was obtained and an amplification analysis of protein interaction was achieved. Secondly, the sensor is renewable because the sandwich-type immunocomplexes can be readily absorbed or removed on the SPCE’s surface in a magnetic field. Thirdly, the SCMP modified probes can perform the rapid separation and purification of signal antibodies in a magnetic field. Thus, the present immunosensor can simultaneously realize separation, enrichment and determination. It showed potential application for the detection of AFP in human sera.

  13. Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.

    Science.gov (United States)

    Choisy, Stéphanie C; Cheng, Hongwei; Orchard, Clive H; James, Andrew F; Hancox, Jules C

    2015-11-01

    The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35-37°C. Hyperpolarizing voltage commands from -40 mV elicited a Ba(2+)-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from -40 mV L-type Ca(2+) current, IC a,L, was elicited with a half maximal activation voltage (V0.5) of -7.6 ± 1.2 mV (n = 24). IC a,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IK r) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to -40 mV, with an activation V0.5 of -10.7 ± 4.7 mV (n = 8). The IK r magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (-40 mV). Spontaneous APs (5.2 ± 0.5 sec(-1); n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca(2+) release by 1 μmol/L ryanodine, implicating intracellular Ca(2+) cycling in murine AVN cell electrogenesis. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Stability at Potential Maxima: The L-4 and L-5 Points of the Restricted Three-Body Problem.

    Science.gov (United States)

    Greenberg, Richard; Davis, Donald R.

    1978-01-01

    Describes a dynamical system which is stable at potential maxima. The maxima, called L-4 and L-5, are stable locations of the restricted three-body problem. Energy loss from the system will tend to drive it away from stability. (GA)

  15. Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Morisawa, T; Hasegawa, J; Hama, R; Kitano, M; Kishimoto, Y; Kawasaki, H

    1999-01-01

    The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

  16. Potentially toxic elements in foodcrops: Triticum aestivum L., Zea mays L.

    Science.gov (United States)

    Bini, Claudio; Fontana, Silvia; Squizzato, Stefania; Minello, Fabiola; Fornasier, Flavio; Wahsha, Mohammad

    2013-04-01

    Soil is the basis of the ecosystems and of our system of food production. Crops can uptake heavy metals and potentially toxic elements from the soil and store them in the roots or translocate them to the aerial parts. Excessive content of these elements in edible parts can produce toxic effects and, through the food chain and food consumption, result in a potential hazard for human health. In this study soils and plants (spring wheat, Triticum aestivum L. and maize, Zea mays L.) from a tannery district in North-East Italy were analyzed to determine pedological characters, soil microbial indicators and the content of some major and micro-nutrients and potentially toxic elements (Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Ni, P, Pb, S, Zn, V). The soils of the area are moderately polluted; Cr is the most important inorganic contaminant, followed by Ni, Cu and V. Factor analysis evidenced that the contaminants are in part anthropogenic and in part geogenic. Major anthropogenic origin was detected for Cr, Ni (from industrial activities), Zn, Cu, Cd (from agriculture practices). Biological Absorption Coefficient (BAC) from soil to plant roots and Translocation factor (TF) within the plant were calculated; major nutrients (K, P, S) and some micronutrients (Cu, Zn, Mg, Mn) are easily absorbed and translocated, whilst other nutrients (Ca, Fe) and potentially toxic elements or micronutrients (Al, Cd, Cr, Ni, Pb, V) are not accumulated in the seeds of the two considered species. However, the two edible species proved differently able to absorb and translocate elements, and this suggests to consider separately every species as potential PHEs transporter to the food chain and to humans. Cr concentrations in seeds and other aerial parts (stem and leaves) of the examined plants are higher than the values found for the same species and for other cereals grown on unpolluted soils. Comparing the Cr levels in edible parts with recommended dietary intake, besides other possible Cr sources

  17. Comparative study of displacement cascades simulated with ‘magnetic’ potentials and Mendelev-type potential in α-Fe

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Chan, E-mail: gaochan@caep.cn [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China); School of Graduate, China Academy of Engineering Physics, Mianyang 621900 (China); Tian, Dongfeng [China Academy of Engineering Physics, Mianyang 621900 (China); Li, Maosheng [Institute of Applied Physics and Computational Mathematics, Beijing 100088 (China); Qian, Dazhi [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China)

    2017-04-15

    Different interatomic potentials produce displacement cascades with different features, and hence they significantly influence the results obtained from the displacement cascade simulations. The displacement cascade simulations in α-Fe have been carried out by molecular dynamics with three ‘magnetic’ potentials (MP) and Mendelev-type potential in this paper. Prior to the cascade simulations, the ‘magnetic’ potentials are hardened to suit for cascade simulations. We find that the peak time, maximum of defects, cascade volume and cascade density with ‘magnetic’ potentials are smaller than those with Mendelev-type potential. There is no significant difference within statistical uncertainty in the defect production efficiency with Mendelev-type potential and the second ‘magnetic’ potential at the same cascade energy, but remarkably smaller than those with the first and third ‘magnetic’ potential. Self interstitial atom (SIA) clustered fractions with ‘magnetic’ potentials are smaller than that with Mendelev-type potential, especially at the higher energy, due to the larger interstitial formation energies which result from the ‘magnetic’ potentials. The defect clustered fractions, which are input data for radiation damage accumulation models, may influence the prediction of microstructural evolution under radiation.

  18. Predictive Potential of Twenty-Two Biochemical Biomarkers for Coronary Artery Disease in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Edimar Cristiano Pereira

    2015-01-01

    Full Text Available We investigated the potential of a panel of 22 biomarkers to predict the presence of coronary artery disease (CAD in type 2 diabetes mellitus (DM2 patients. The study enrolled 96 DM2 patients with (n = 75 and without (n = 21 evidence of CAD. We assessed a biochemical profile that included 22 biomarkers: total cholesterol, LDL, HDL, LDL/HDL, triglycerides, glucose, glycated hemoglobin, fructosamine, homocysteine, cysteine, methionine, reduced glutathione, oxidized glutathione, reduced glutathione/oxidized glutathione, L-arginine, asymmetric dimethyl-L-arginine, symmetric dimethyl-L-arginine, asymmetric dimethyl-L-arginine/L-arginine, nitrate plus nitrite, S-nitrosothiols, nitrotyrosine, and n-acetyl-β-glucosaminidase. Prediction models were built using logistic regression models. We found that eight biomarkers (methionine, nitratate plus nitrite, n-acetyl-β-glucosaminidase, BMI, LDL, HDL, reduced glutathione, and L-arginine/asymmetric dimethyl-L-arginine along with gender and BMI were significantly associated with the odds of CAD in DM2. These preliminary findings support the notion that emerging biochemical markers might be used for CAD prediction in patients with DM2. Our findings warrant further investigation with large, well-designed studies.

  19. Cold rolled texture and microstructure in types 304 and 316L austenitic stainless steels

    International Nuclear Information System (INIS)

    Wasnik, D.N.; Samajdar, I.; Gopalakrishnan, I.K.; Yakhmi, J.V.; Kain, V.

    2003-01-01

    Two grades of austenitic stainless steel (ASS), types 304 (UNS S 30400) and 316L (UNS S 31603), were cold rolled to different reductions by unidirectional and by cross-rolling. The steels had reasonable difference in stacking fault energy (estimated respectively as 15 and 61 mJ/m 2 in types 304 and 316L) and also in starting (or pre-deformation) crystallographic texture-being relatively weak and reasonably strong in types 304 and 316L respectively. The cold rolling increased texturing in type 304, but not in type 316L ASS. The more significant effect of cold rolled texture development was in the relative increase of Brass ({011} ) against Copper ({112} ) and S ({231} ) orientations. In type 304 the increase in Brass was significant, while in type 316L the increase in Copper and S was stronger. This effect could be captured by Taylor type deformation texture simulations considering stronger twinning contributions in type 304 - for example the respective 'best-fits' (in terms of matching the changes in the volume fractions of Brass against Copper and S) were obtained by full constraint Taylor model with 1:100 and 1:10 slip:twin activities in types 304 and 316L ASS respectively. Microstructural developments during cold rolling were generalized as strain induced martensite formation and developments of dislocation substructure. The former, as estimated by vibrating sample magnetometer (VSM), increased with cold reduction, being significantly more in type 304 and was also noticeably stronger in both grades under cross-rolling. The most significant aspect of substructural developments was the formation of strain localizations. These were observed as dense dislocation walls (DDWs), micro-bands (MBs) and twin lamellar structures (TLS). The TLS contribution gained significance at higher reductions and during cross-rolling, especially in type 304. Large misorientation development and the accompanying grain splittings were always associated with such strain localizations

  20. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential.

    Science.gov (United States)

    Chen, Ying-Bei; Aon, Miguel A; Hsu, Yi-Te; Soane, Lucian; Teng, Xinchen; McCaffery, J Michael; Cheng, Wen-Chih; Qi, Bing; Li, Hongmei; Alavian, Kambiz N; Dayhoff-Brannigan, Margaret; Zou, Shifa; Pineda, Fernando J; O'Rourke, Brian; Ko, Young H; Pedersen, Peter L; Kaczmarek, Leonard K; Jonas, Elizabeth A; Hardwick, J Marie

    2011-10-17

    Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-x(L) was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-x(L) reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F(1)F(O)-ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase β subunit in a screen for Bcl-x(L)-binding partners, we tested and found that Bcl-x(L) failed to protect β subunit-deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins.

  1. Stac gets the skeletal L-type calcium channel unstuck

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert

    2015-01-01

    Roč. 34, č. 2 (2015), s. 101-103 ISSN 0231-5882 Institutional support: RVO:61388963 Keywords : calcium channel * L-type calcium channel * Ca(v)1.1 channel * Stac adaptor protein * excitation- contraction coupling * trafficking Subject RIV: CE - Biochemistry Impact factor: 0.892, year: 2015

  2. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

    Science.gov (United States)

    Saung, Wint Thu; Foskett, J. Kevin

    2017-01-01

    Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

  3. Arguments for fundamental emission by the parametric process L yields T + S in interplanetary type III bursts. [langmuir, electromagnetic, ion acoustic waves (L, T, S)

    Science.gov (United States)

    Cairns, I. H.

    1984-01-01

    Observations of low frequency ion acoustic-like waves associated with Langmuir waves present during interplanetary Type 3 bursts are used to study plasma emission mechanisms and wave processes involving ion acoustic waves. It is shown that the observed wave frequency characteristics are consistent with the processes L yields T + S (where L = Langmuir waves, T = electromagnetic waves, S = ion acoustic waves) and L yields L' + S proceeding. The usual incoherent (random phase) version of the process L yields T + S cannot explain the observed wave production time scale. The clumpy nature of the observed Langmuir waves is vital to the theory of IP Type 3 bursts. The incoherent process L yields T + S may encounter difficulties explaining the observed Type 3 brightness temperatures when Langmuir wave clumps are incorporated into the theory. The parametric process L yields T + S may be the important emission process for the fundamental radiation of interplanetary Type 3 bursts.

  4. SCC growth behavior of stainless steel weld metals in high-temperature water. Influence of corrosion potential, weld type, thermal aging, cold-work and temperature

    International Nuclear Information System (INIS)

    Yamada, Takuyo; Terachi, Takumi; Miyamoto, Tomoki; Arioka, Koji

    2009-01-01

    Recent studies on crack growth rate measurement in oxygenated high-temperature pure water conditions, such as normal water chemistry in boiling water reactors, using compact tension type specimens have shown that weld stainless steels are susceptible to stress corrosion cracking. However, to our knowledge, there is no crack growth data of weld stainless steels in pressurized water reactor primary water. The principal purpose of this study was to examine the SCC growth behavior of stainless steel weld metals in simulated PWR primary water. A second objective was to examine the effect of (1) corrosion potential, (2) thermal-aging, (3) Mo in alloy and (4) cold-working on SCC growth in hydrogenated and oxygenated water environments at 320degC. In addition, the temperature dependence of SCC growth in simulated PWR primary water was also studied. The results were as follows: (1) No significant SCC growth was observed on all types of stainless steel weld metals: as-welded, aged (400degC x 10 kh) 308L and 316L, in 2.7 ppm-hydrogenated (low-potential) water at 320degC. (2) 20% cold-working markedly accelerated the SCC growth of weld metals in high-potential water at 320degC, but no significant SCC growth was observed in the hydrogenated water, even after 20% cold-working. (3) No significant SCC growth was observed on stainless steel weld metals in low-potential water at 250degC and 340degC. Thus, stainless steel weld metals have excellent SCC resistance in PWR primary water. On the other hand, (4) significant SCC growth was observed on all types of stainless steel weld metals: as-weld, aged (400degC x 10 kh) and 20% cold-worked 308L and 316L, in 8 ppm-oxygenated (high-potential) water at 320degC. (5) No large difference in SCC growth was observed between 316L (Mo) and 308L. (6) No large effect on SCC growth was observed between before and after aging up to 400degC for 10 kh. (7) 20% cold-working markedly accelerated the SCC growth of stainless steel weld metals. (author)

  5. L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

    Science.gov (United States)

    Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

    2018-03-01

    The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of

  6. Cytoskeleton, L-type Ca2+ and stretch activated channels in injured skeletal muscle

    Directory of Open Access Journals (Sweden)

    Fabio Francini

    2013-07-01

    Full Text Available The extra-sarcomeric cytoskeleton (actin microfilaments and anchoring proteins is involved in maintaining the sarco-membrane stiffness and integrity and in turn the mechanical stability and function of the intra- and sub-sarcoplasmic proteins. Accordingly, it regulates Ca2+ entry through the L-type Ca2+ channels and the mechano-sensitivity of the stretch activated channels (SACs. Moreover, being intra-sarcomeric cytoskeleton bound to costameric proteins and other proteins of the sarcoplasma by intermediate filaments, as desmin, it integrates the properties of the sarcolemma with the skeletal muscle fibres contraction. The aim of this research was to compare the cytoskeleton, SACs and the ECC alterations in two different types of injured skeletal muscle fibres: by muscle denervation and mechanical overload (eccentric contraction. Experiments on denervation were made in isolated Soleus muscle of male Wistar rats; forced eccentric-contraction (EC injury was achieved in Extensor Digitorum Longus muscles of Swiss mice. The method employed conventional intracellular recording with microelectrodes inserted in a single fibre of an isolated skeletal muscle bundle. The state of cytoskeleton was evaluated by recording SAC currents and by evaluating the resting membrane potential (RMP value determined in current-clamp mode. The results demonstrated that in both injured skeletal muscle conditions the functionality of L-type Ca2+ current, ICa, was affected. In parallel, muscle fibres showed an increase of the resting membrane permeability and of the SAC current. These issues, together with a more depolarized RMP are an index of altered cytoskeleton. In conclusion, we found a symilar alteration of ICa, SAC and cytoskeleton in both injured skeletal muscle conditions.

  7. CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through upregulating L-type calcium channel activity.

    Science.gov (United States)

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-09-01

    A specialized culture medium termed ciliary neurotrophic factor-treated astrocyte-conditioned medium (CNTF-ACM) allows investigators to assess the peripheral effects of CNTF-induced activated astrocytes upon cultured neurons. CNTF-ACM has been shown to upregulate neuronal L-type calcium channel current activity, which has been previously linked to changes in mitochondrial respiration and oxidative stress. Therefore, the aim of this study was to evaluate CNTF-ACM's effects upon mitochondrial respiration and oxidative stress in rat cortical neurons. Cortical neurons, CNTF-ACM, and untreated control astrocyte-conditioned medium (UC-ACM) were prepared from neonatal Sprague-Dawley rat cortical tissue. Neurons were cultured in either CNTF-ACM or UC-ACM for a 48-h period. Changes in the following parameters before and after treatment with the L-type calcium channel blocker isradipine were assessed: (i) intracellular calcium levels, (ii) mitochondrial membrane potential (ΔΨm), (iii) oxygen consumption rate (OCR) and adenosine triphosphate (ATP) formation, (iv) intracellular nitric oxide (NO) levels, (v) mitochondrial reactive oxygen species (ROS) production, and (vi) susceptibility to the mitochondrial complex I toxin rotenone. CNTF-ACM neurons displayed the following significant changes relative to UC-ACM neurons: (i) increased intracellular calcium levels (p ACM (p ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through elevating L-type calcium channel activity.

  8. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Holst, Jens Juul; McGill, Maria A

    2012-01-01

    Type 2 diabetes mellitus is associated with a progressive decline in insulin-producing pancreatic ß-cells, an increase in hepatic glucose production, and a decrease in insulin sensitivity. The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1....... The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. However, they may be unable to halt the progression of type 2...... diabetes, perhaps because they do not increase secretion of endogenous GLP-1. Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. Potential new approaches...

  9. Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

    Science.gov (United States)

    Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

    2016-08-15

    In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Enteroendocrine K and L cells in healthy and type 2 diabetic individuals

    DEFF Research Database (Denmark)

    Jorsal, Tina; Rhee, Nicolai A.; Pedersen, Jens

    2018-01-01

    Aims/hypothesis: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells...... and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. Methods: In this cross-sectional study, 12 individuals with type 2...... diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Results: Significantly different densities...

  11. TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes.

    Science.gov (United States)

    Redondo, Maria J; Geyer, Susan; Steck, Andrea K; Sosenko, Jay; Anderson, Mark; Antinozzi, Peter; Michels, Aaron; Wentworth, John; Xu, Ping; Pugliese, Alberto

    2018-02-01

    The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 ( TCF7L2 ) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data ( n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old ( n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones ( n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) ( P = 0.008) and lower mean glucose AUC ( P = 0.0127). The results were similar for the rs7901695 SNP. In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. © 2017 by the American Diabetes Association.

  12. Climate change and the potential distribution of an invasive shrub, Lantana camara L.

    Directory of Open Access Journals (Sweden)

    Subhashni Taylor

    Full Text Available The threat posed by invasive species, in particular weeds, to biodiversity may be exacerbated by climate change. Lantana camara L. (lantana is a woody shrub that is highly invasive in many countries of the world. It has a profound economic and environmental impact worldwide, including Australia. Knowledge of the likely potential distribution of this invasive species under current and future climate will be useful in planning better strategies to manage the invasion. A process-oriented niche model of L. camara was developed using CLIMEX to estimate its potential distribution under current and future climate scenarios. The model was calibrated using data from several knowledge domains, including phenological observations and geographic distribution records. The potential distribution of lantana under historical climate exceeded the current distribution in some areas of the world, notably Africa and Asia. Under future scenarios, the climatically suitable areas for L. camara globally were projected to contract. However, some areas were identified in North Africa, Europe and Australia that may become climatically suitable under future climates. In South Africa and China, its potential distribution could expand further inland. These results can inform strategic planning by biosecurity agencies, identifying areas to target for eradication or containment. Distribution maps of risk of potential invasion can be useful tools in public awareness campaigns, especially in countries that have been identified as becoming climatically suitable for L. camara under the future climate scenarios.

  13. Effect of epoxy resin on bending momentum in L type corner joins

    Directory of Open Access Journals (Sweden)

    Mehmet Nuri Yıldırım

    2017-11-01

    Full Text Available In the furniture industry, the joining points of frame and box construction furniture according to the loads to be affected by the use place is important for the security of the user and service life of the furniture element. In this direction, it is aimed to determine the diagonal compression and diagonal tensile moment values of "L" type corner joints of box framed construction furniture prepared from solid wood materials. The Pinus Nigra, Fagus Orientalis L and Populus Nigra were used as solid wood materials. Wood-based biscuit joining elements were used in corner joints of the test construction and epoxy resin was used as glue for materials. The static loads were applied to construction according to ASTM-D1037. The results show that, the highest tensile and compression values were obtained from Fagus Orientalis L and the lowest values were obtained from Populus Nigra specimens. In the statistical study, the difference between the tensile and compressive bending moment values of the biscuit connection element was found to be statistically significant. This study indicates that, it is suggested to use of L type joints prepared from Fagus Orientalis L by using epoxy resin and wood based biscuit joining element in frame constructions.

  14. L-Type Calcium Channel Inhibition Contributes to the Proarrhythmic Effects of Aconitine in Human Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Jianjun Wu

    Full Text Available Aconitine (ACO is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na+ channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs. ACO concentration-dependently (0.3 ~ 3.0 μM shortened the action potentials (AP durations (APD in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization. Laser-scanning confocal calcium imaging analysis showed that ACO decreased the duration and amplitude of [Ca2+]i transients and increased in the beating frequencies by over 60%. Moreover, ACO was found to markedly reduce the L-type calcium channel (LTCC currents (ICa,L in hiPSC-CMs associated with a positive-shift of activation and a negative shift of inactivation. ACO failed to alter the peak and late Na+ currents (INa in hiPSC-CMs while it drastically increased the late INa in Guinea-pig ventricular myocytes associated with enhanced activation/delayed inactivation of INa at -55 mV~ -85 mV. Further, the effects of ACO on ICa,L, INa and the rapid delayed rectifier potassium current (Ikr were validated in heterologous expression systems by automated voltage-clamping assays and a moderate suppression of Ikr was observed in addition to concentration-dependent ICa,L inhibition. Lastly, increased beating frequency, decreased Ca2+ wave and shortened field potential duration were recorded from hiPSC-CMs by microelectrode arrays assay. In summary, our data demonstrated that LTCC inhibition could play a main role in the proarrhythmic action of ACO in human cardiomyocytes.

  15. The arbitrary l continuum states of the hyperbolic molecular potential

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Gao-Feng, E-mail: fgwei_2000@163.com [School of Physics and Mechatronics Engineering, Xi' an University of Arts and Science, Xi' an 710065 (China); Chen, Wen-Li, E-mail: physwlchen@163.com [Department of Basic Science, Xi' an Peihua University, Xi' an 710065 (China); Dong, Shi-Hai, E-mail: dongsh2@yahoo.com [Escuela Superior de Física y Matemáticas, Instituto Politécnico Nacional, Edificio 9, Unidad Profesional Adolfo López Mateos, Mexico D.F. 07738 (Mexico); Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803-4001 (United States)

    2014-06-27

    Within the framework of partial-wave method, we study in this Letter the arbitrary l continuum states of the Schrödinger equation with the hyperbolic molecular potential in terms of an improved approximation to the centrifugal term. We present the normalized radial wave functions and obtain analytical formula of phase shifts. In addition, the corresponding bound states are also discussed by studying the analytical properties of the scattering amplitude. We calculate the energy spectra and scattering phase shifts by the improved, previous approximations and the accurate methods, respectively and find that the improved approximation is better than the previous one since the present results are in better agreement with the accurate ones. - Highlights: • The hyperbolic potential with arbitrary l state is solved. • Improved approximation to centrifugal term is used. • Phase shift formula is derived analytically. • Accurate results are compared with the present results.

  16. Membrane potential and ion transport in lung epithelial type II cells

    International Nuclear Information System (INIS)

    Gallo, R.L.

    1986-01-01

    The alveolar type II pneumocyte is critically important to the function and maintenance of pulmonary epithelium. To investigate the nature of the response of type II cells to membrane injury, and describe a possible mechanism by which these cells regulate surfactant secretion, the membrane potential of isolated rabbit type II cells was characterized. This evaluation was accomplished by measurements of the accumulation of the membrane potential probes: [ 3 H]triphenylmethylphosphonium ([ 3 H]TPMP + ), rubidium 86, and the fluorescent dye DiOC 5 . A compartmental analysis of probe uptake into mitochondrial, cytoplasmic, and non-membrane potential dependent stores was made through the use of selective membrane depolarizations with carbonycyanide M-chlorophenylhydrazone (CCCP), and lysophosphatidylcholine (LPC). These techniques and population analysis with flow cytometry, permitted the accurate evaluation of type II cell membrane potential under control conditions and under conditions which stimulated cell activity. Further analysis of ion transport by cells exposed to radiation or adrenergic stimulation revealed a common increase in Na + /K + ATPase activity, and an increase in sodium influx across the plasma membrane. This sodium influx was found to be a critical step in the initiation of surfactant secretion. It is concluded that radiation exposure as well as other pulmonary toxicants can directly affect the membrane potential and ionic regulation of type II cells. Ion transport, particularly of sodium, plays an important role in the regulation of type II cell function

  17. Accelerated inactivation of the L-type calcium current due to a mutation in CACNB2b underlies Brugada syndrome

    DEFF Research Database (Denmark)

    Cordeiro, Jonathan M; Marieb, Mark; Pfeiffer, Ryan

    2009-01-01

    S in which loss of function is caused by accelerated inactivation of I(Ca). The proband, a 32 year old male, displayed a Type I ST segment elevation in two right precordial ECG leads following a procainamide challenge. EP study was positive with induction of polymorphic VT/VF. Interrogation of implanted ICD...... significantly faster in mutant channels between 0 and + 20 mV. Action potential voltage clamp experiments showed that total charge was reduced by almost half compared to WT. We report the first BrS mutation in CaCNB2b resulting in accelerated inactivation of L-type calcium channel current. Our results suggest...

  18. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    Science.gov (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Task type and incidental L2 vocabulary learning: Repetition versus ...

    African Journals Online (AJOL)

    This study investigated the effect of task type on incidental L2 vocabulary learning. The different tasks investigated in this study differed in terms of repetition of encounters and task involvement load. In a within-subjects design, 72 Iranian learners of English practised 18 target words in three exercise conditions: three ...

  20. Turtle Flexion Reflex Motor Patterns Show Windup, Mediated Partly by L-type Calcium Channels

    Directory of Open Access Journals (Sweden)

    Keith P. Johnson

    2017-10-01

    Full Text Available Windup is a form of multisecond temporal summation in which identical stimuli, delivered seconds apart, trigger increasingly strong neuronal responses. L-type Ca2+ channels have been shown to play an important role in the production of windup of spinal cord neuronal responses, initially in studies of turtle spinal cord and later in studies of mammalian spinal cord. L-type Ca2+ channels have also been shown to contribute to windup of limb withdrawal reflex (flexion reflex in rats, but flexion reflex windup has not previously been described in turtles and its cellular mechanisms have not been studied. We studied windup of flexion reflex motor patterns, evoked with weak mechanical and electrical stimulation of the dorsal hindlimb foot skin and assessed via a hip flexor (HF nerve recording, in spinal cord-transected and immobilized turtles in vivo. We found that an L-type Ca2+ channel antagonist, nifedipine, applied at concentrations of 50 μM or 100 μM to the hindlimb enlargement spinal cord, significantly reduced windup of flexion reflex motor patterns, while lower concentrations of nifedipine had no such effect. Nifedipine similarly reduced the amplitude of an individual flexion reflex motor pattern evoked by a stronger mechanical stimulus, in a dose-dependent manner, suggesting that L-type Ca2+ channels contribute to each flexion reflex as well as to multisecond summation of flexion reflex responses in turtles. We also found that we could elicit flexion reflex windup consistently using a 4-g von Frey filament, which is not usually considered a nociceptive stimulus. Thus, it may be that windup can be evoked by a wide range of tactile stimuli and that L-type calcium channels contribute to multisecond temporal summation of diverse tactile stimuli across vertebrates.

  1. Chemical composition and nutritive potential of Cichorium intybus L. leaves from Montenegro

    Directory of Open Access Journals (Sweden)

    Jančić Dejan

    2016-01-01

    Full Text Available The leaves of chicory (Cichorium intybus L. plant have been used for centuries in Montenegro and other Mediterranean countries as a vegetable in salads, sauces and other types of appetizers and meals. The wild and cultivated chicory leaves from different location in Montenegro were analysed regarding several nutrients, major and trace element and vitamin composition using standard methods of analysis. The results of the study indicated that chicory leaves were rich in total dietary fiber and mineral content and had low energy value. Also, they were potential sources of useful nutrients such as potassium, calcium, manganese, iron, and vitamin A, with the average content of 391.9, 164.7, 0.55, 2.33 and 0.47 mg / 100 g in fresh leaves, respectively. Wild plants were superior to the cultivated ones regarding carbohydrate, calcium and manganese content. Origin of the chicory leaves significantly influenced most of the analyzed parameters.

  2. Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.

    Science.gov (United States)

    Baidya, Sunanda; Das, Rasel; Kabir, Md Golam; Arifuzzaman, Md

    2017-01-01

    Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through "reverse vaccinology" approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.

  3. Zeta-potential and flotability of the scheelite mineral in different type of waters, Part 1: Zeta-potential

    Directory of Open Access Journals (Sweden)

    Milanović Dragan B.

    2009-01-01

    Full Text Available The aim of this work is the investigation of zeta-potential of the mineral scheelite from mine 'Rudnik', located in central Serbia. Electrophoresis measurements using zeta-meter were carried out on four different types of water, namely: tap water, distilled water, rain water and spring water. All types of water had different hardness and conductivity as well as natural pH values. It was found that the zeta-potential of mineral scheelite depends on the hardness and electro-conductivity of the chosen type of water as well as on Ca2+ content. The results obtained reveal the importance of proper choice of water as well as the type of reagents for flotation processes.

  4. Generators with interior degeneracy on spaces of L^2 type

    Directory of Open Access Journals (Sweden)

    Genni Fragnelli

    2012-10-01

    Full Text Available We consider operators in divergence and in nondivergence form with degeneracy at the interior of the space domain. Characterizing the domain of the operators, we prove that they generate positive analytic semigroups on spaces of L^2 type. Finally, some applications to linear and semilinear parabolic evolution problems and to linear hyperbolic ones are presented.

  5. Electric potential behaviour in segmented Faraday-type MHD generators

    International Nuclear Information System (INIS)

    James, M.I.; Mittal, M.L.; Gupta, G.P.; Rohatgi, V.K.

    1985-01-01

    The potential distribution in the transverse cross-section of a segmented Faraday-type MHD generator is studied. The governing elliptic equation, derived with allowance for the finite electrode segmentation effect and nonuniformity of the gas in the channel, is solved numerically using the Alternating Direction Implicit method in the finite difference scheme, instead of the successive over-relaxation method. The computed potential distribution and the potential drops are found to compare well with experimental results. The potential drops at the electrodes are found to increase with increasing current density. (author)

  6. THE POSSIBLE IMPACT OF L5 MAGNETOGRAMS ON NON-POTENTIAL SOLAR CORONAL MAGNETIC FIELD SIMULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Weinzierl, Marion; Yeates, Anthony R. [Department of Mathematical Sciences, Durham University South Road, Durham DH1 3LE (United Kingdom); Mackay, Duncan H. [School of Mathematics and Statistics, University of St. Andrews North Haugh, St. Andrews, Fife KY16 9SS (United Kingdom); Pevtsov, Alexei A., E-mail: marion.weinzierl@durham.ac.uk [National Solar Observatory 3010 Coronal Loop, sunspot NM 88349 (United States)

    2016-09-10

    The proposed Carrington-L5 mission would bring instruments to the L5 Lagrange point to provide us with crucial data for space weather prediction. To assess the importance of including a magnetograph, we consider the possible differences in non-potential solar coronal magnetic field simulations when magnetograph observations are available from the L5 point, compared with an L1-based field of view (FOV). A timeseries of synoptic radial magnetic field maps is constructed to capture the emergence of two active regions from the L5 FOV. These regions are initially absent in the L1 magnetic field maps, but are included once they rotate into the L1 FOV. Non-potential simulations for these two sets of input data are compared in detail. Within the bipolar active regions themselves, differences in the magnetic field structure can exist between the two simulations once the active regions are included in both. These differences tend to reduce within 5 days of the active region being included in L1. The delayed emergence in L1 can, however, lead to significant persistent differences in long-range connectivity between the active regions and the surrounding fields, and also in the global magnetic energy. In particular, the open magnetic flux and the location of open magnetic footpoints, are sensitive to capturing the real-time of emergence. These results suggest that a magnetograph at L5 could significantly improve predictions of the non-potential corona, the interplanetary magnetic field, and of solar wind source regions on the Sun.

  7. Comparisons of phaseolin type and α-amylase inhibitor in common bean(Phaseolus vulgaris L.)in China

    Institute of Scientific and Technical Information of China (English)

    Yang Yao; Yibo Hu; Yingying Zhu; Yue Gao; Guixing Ren

    2016-01-01

    The objective of this study was to characterize the phaseolin type and a-amylase(αAI) level in common bean(Phaseolus vidgaris L.) accessions deposited in the Chinese National Genebank.The 40 accessions sampled were common varieties originating in Asia,North America,South America,Europe,and Africa.No Inca(I-) phaseolin was observed in the accessions.Only four accessions contained Tendergreen(T-) phaseolin and the remaining36 contained Sanilac(S-) phaseolin.aAI proteins extracted from nine accessions showed higher a-amylase inhibitory activity than the control(Phase 2,IC50 = 0.65 μg).These common bean accessions have potential use as nutraceutical ingredients.

  8. The potential of halophilic and halotolerant bacteria for the production of antineoplastic enzymes: L-asparaginase and L-glutaminase.

    Science.gov (United States)

    Shirazian, Pejman; Asad, Sedigheh; Amoozegar, Mohammad Ali

    2016-01-01

    L-asparaginase and L-glutaminase can be effectively used for the treatment of patients who suffer from accute lymphoblastic leukemia and tumor cells. Microbial sources are the best source for the bulk production of these enzymes. However, their long-term administration may cause immunological responses, so screening for new enzymes with novel properties is required. Halophilic and halotolerant bacteria with novel enzymatic characteristics can be considered as a potential source for production of enzymes with different immunological properties. In this study, L-asparaginase and L-glutaminase production by halophilic bacteria isolated from Urmia salt lake was studied. Out of the 85 isolated halophilic and halotolerant bacterial strains, 16 (19 %) showed L-asparaginase activity and 3 strains (3.5 %) showed L-glutaminase activity. Strains with the highest activities were selected for further studies. Based on 16S rDNA sequence analysis, it was shown that the selected isolates for L-asparaginase and L-glutaminase production belong to the genus Bacillus and Salicola, respectively. Both enzymes were produced extracellularly. The strain with the most L-asparaginase production did not show L-glutaminase production which is medically important. The effects of key parameters including temperature, initial pH of the solution, and concentrations of glucose, asparagine or glutamine, and sodium chloride were evaluated by means of response surface methodology (RSM) to optimize enzymes production. Under the obtained optimal conditions, L-asparaginase and L-glutaminase production was increased up to 1.5 (61.7 unit/mL) and 2.6 fold (46.4 unit/mL), respectively.

  9. Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.

    Science.gov (United States)

    Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula

    2014-03-01

    Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

  10. Polymorphic New World monkeys with more than three M/L cone types

    Science.gov (United States)

    Jacobs, Gerald H.; Deegan, Jess F.

    2005-10-01

    Most New World (platyrrhine) monkeys have M/L cone photopigment polymorphisms that map directly into individual variations in visual sensitivity and color vision. We used electroretinogram flicker photometry to examine M/L cone photopigments in the New World monkey Callicebus moloch (the dusky Titi). Like other New World monkeys, this species has an M/L cone photopigment polymorphism that reflects the presence of X-chromosome opsin gene alleles. However, unlike other platyrrhines in which three M/L photopigments are typical, Callicebus has a total of five M/L cone photopigments. The peak sensitivity values for these pigments extend across the range from 530 to 562 nm. The result is an enhanced array of potential color vision phenotypes in this species.

  11. Direct organogenesis of Mandevilla illustris (Vell) Woodson and effects of its aqueous extract on the enzymatic and toxic activities of Crotalus durissus terrificus snake venom.

    Science.gov (United States)

    Biondo, R; Soares, A M; Bertoni, B W; França, S C; Pereira, A M S

    2004-03-01

    In order to produce explants of Mandevilla illustris (Vell) Woodson for the "Cerrado in vitro", the Germplasm Bank of UNAERP, we carried out a micropropagation protocol using MS or MS/3 medium supplemented with different concentrations of 6-benzyladeninepurine (BA), Zeatin or 2-isopentenyladenine for nodal segment growth, and alpha-naphthaleneacetic acid, indole-3-butyric acid (IBA) or 1,4 dithiothreitol for rooting. For nodal segments, all the cytokinins tested yielded similar results. However, 2.22 micro M BA is more economical to use. MS/3 medium supplemented with 0.49 micro M IBA was the most appropriate medium for rooting, resulting in 29% rooted explants. The crude aqueous extract from the subterranean system (SS) of M. illustris was assayed for its inhibitory action on the enzymatic activity of Crotalus durissus terrificus snake venom, isolated basic phospholipase A2 (CB) and crotoxin. It totally inhibited the phospholipase activity of crude Cdt venom and CB toxin and inhibited the phospholipase activity of crotoxin by 49%. The toxic action of both the crude venom and crotoxin was partially inhibited-there was a prolonged survival time and a 40.0% decrease in lethality.

  12. Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France

    Directory of Open Access Journals (Sweden)

    Sala Carole

    2012-05-01

    Full Text Available Abstract Background Cattle with L-type (L-BSE and H-type (H-BSE atypical Bovine Spongiform encephalopathy (BSE were identified in 2003 in Italy and France respectively before being identified in other countries worldwide. As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, with over one third in France. While the epidemiology of classical BSE (C-BSE has been widely described, atypical BSEs are still poorly documented, but appear to differ from C-BSE. We analysed the epidemiological characteristics of the 12 cases of L-BSE and 11 cases of H-BSE detected in France from January 2001 to late 2009 and looked for individual risk factors. As L-BSE cases did not appear to be homogeneously distributed throughout the country, two complementary methods were used: spatial analysis and regression modelling. L-BSE and H-BSE were studied separately as both the biochemical properties of their pathological prion protein and their features differ in animal models. Results The median age at detection for L-BSE and H-BSE cases was 12.4 (range 8.4-18.7 and 12.5 (8.3-18.2 years respectively, with no significant difference between the two distributions. However, this median age differed significantly from that of classical BSE (7.0 (range 3.5-15.4 years. A significant geographical cluster was detected for L-BSE. Among animals over eight years of age, we showed that the risk of being detected as a L-BSE case increased with age at death. This was not the case for H-BSE. Conclusion To the best of our knowledge this is the first study to describe the epidemiology of the two types of atypical BSE. The geographical cluster detected for L-BSE could be partly due to the age structure of the background-tested bovine population. Our regression analyses, which adjusted for the effect of age and birth cohort showed an age effect for L-BSE and the descriptive analysis showed a particular age structure in the area where the cluster was

  13. Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Gapsys, Vytautas; Ucurum, Zöhre; de Groot, Bert L; Fotiadis, Dimitrios

    2016-09-13

    Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

  14. Conservation properties and potential systems of vorticity-type equations

    International Nuclear Information System (INIS)

    Cheviakov, Alexei F.

    2014-01-01

    Partial differential equations of the form divN=0, N t +curl M=0 involving two vector functions in R 3 depending on t, x, y, z appear in different physical contexts, including the vorticity formulation of fluid dynamics, magnetohydrodynamics (MHD) equations, and Maxwell's equations. It is shown that these equations possess an infinite family of local divergence-type conservation laws involving arbitrary functions of space and time. Moreover, it is demonstrated that the equations of interest have a rather special structure of a lower-degree (degree two) conservation law in R 4 (t,x,y,z). The corresponding potential system has a clear physical meaning. For the Maxwell's equations, it gives rise to the scalar electric and the vector magnetic potentials; for the vorticity equations of fluid dynamics, the potentialization inverts the curl operator to yield the fluid dynamics equations in primitive variables; for MHD equations, the potential equations yield a generalization of the Galas-Bogoyavlenskij potential that describes magnetic surfaces of ideal MHD equilibria. The lower-degree conservation law is further shown to yield curl-type conservation laws and determined potential equations in certain lower-dimensional settings. Examples of new nonlocal conservation laws, including an infinite family of nonlocal material conservation laws of ideal time-dependent MHD equations in 2+1 dimensions, are presented

  15. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    International Nuclear Information System (INIS)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2015-01-01

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells

  16. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  17. Twinflower (Linnaea borealis L. – plant species of potential medicinal properties

    Directory of Open Access Journals (Sweden)

    Thiem Barbara

    2017-09-01

    Full Text Available Twinflower (Linnaea borealis L. is a widespread circumboreal plant species belonging to Linnaeaceae family (previously Caprifoliaceae. L. borealis commonly grows in taiga and tundra. In some countries in Europe, including Poland, twinflower is protected as a glacial relict. Chemical composition of this species is not well known, however in folk medicine of Scandinavian countries, L. borealis has a long tradition as a cure for skin diseases and rheumatism. It is suggested that twinflower has potential medicinal properties. The new study on lead secondary metabolites responsible for biological activity are necessary. This short review summarizes very sparse knowledge on twinflower: its biology, distribution, conservation status, chemical constituents, and describes the role of this plant in folk tradition of Scandinavian countries.

  18. The erosive potential of jawbreakers, a type of hard candy

    NARCIS (Netherlands)

    Brand, H.S.; Gambon, D.L.; van Dop, L.F.; van Liere, L.E.; Veerman, E.C.I.

    2010-01-01

    Objectives:  To explore the consumption pattern of a specific type of acidic solid candy, the so-called jawbreakers, by primary school children and determine the erosive potential of this type of candy in vivo. Methods:  A questionnaire about jawbreaker consumption was distributed among 10-12

  19. Formation historique et genese des types canoniques de l'habitation domestique du Hodna oriental

    Directory of Open Access Journals (Sweden)

    BOUTABBA HYNDA

    2012-01-01

    Full Text Available Le présent papier se focalise sur l'étude de la for mation historique et l'analyse architecturale des types canoniques d'habitat domes tique dans la région du Hodna oriental en Algérie. Cette recherche diachronique prend en charg e l’évolution de l’habitation depuis le début du 19 ème siècle avec les Guitounes (premières tentes nomade s jusqu’au début du 21 ème siècle et la consécration des Diar charpenti (habitations en cha rpente, modernes et ostentatoires. Par l'étude de ces différents types, l'objectif n'est p as seulement de rendre compte de l'évolution de chacun de ces savoirs spécifiques, mais plutôt de r enseigner sur la façon dont ces derniers pourraient éventuellement s'articuler dans sa produ ction. Autrement dit voire si la logique d'un niveau pourrait avoir une influence sur un autre, d e détecter les traits caractéristiques d'un niveau qui pourraient rester pertinents à un autre. L'approche utilisée est la typologie analytico-historique qui analyse l'espace architectural en mettant l'acc ent sur les facteurs intrinsèques et extrinsèques qui ont contribué à sa formation

  20. l-dependent potential barriers and superdeformed states

    International Nuclear Information System (INIS)

    Gherghescu, R.A.; Royer, G.

    1999-01-01

    The macroscopic-microscopic energy of rotating nuclei moving in the fusion-like deformation valley has been determined within a generalized liquid drop model including the nuclear proximity energy, the two-center shell model and the Strutinsky method. The l-dependent potential barriers of the 84 Zr, 132 Ce, 152 Dy and 192 Hg nuclei have been determined. A first minimum having a pure microscopic origin and lodging the normally deformed states, progressively disappears with increasing angular momenta. The microscopic and macroscopic energies contribute to generate a second minimum where superdeformed states may survive. It becomes progressively the lowest one at intermediate spins. At still higher angular momenta, the minimum moves towards the foot of the external fission barrier leading to macroscopic hyper-deformed quasi-molecular states. (authors)

  1. Role of voltage-gated L-type Ca2+ channel isoforms for brain function.

    Science.gov (United States)

    Striessnig, J; Koschak, A; Sinnegger-Brauns, M J; Hetzenauer, A; Nguyen, N K; Busquet, P; Pelster, G; Singewald, N

    2006-11-01

    Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1 .2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

  2. Effect of nitrogen and water deficit type on the yield gap between the potential and attainable wheat yield

    Directory of Open Access Journals (Sweden)

    Jiangang Liu

    2015-12-01

    Full Text Available Water deficit and N fertilizer are the two primary limiting factors for wheat yield in the North China plain, the most important winter wheat (Triticum aestivum L. production area in China. Analyzing the yield gap between the potential yield and the attainable yield can quantify the potential for increasing wheat production and exploring the limiting factors to yield gap in the high-yielding farming region of North China Plain. The Decision Support System for Agrotechnology Transfer (DSSAT model was used to identify methods to increase the grain yield and decrease the gap. In order to explore the impact of N and cultivars on wheat yield in the different drought types, the climate conditions during 1981 to 2011 growing seasons was categorized into low, moderate, and severe water deficit classes according to the anomaly percentage of the water deficit rate during the entire wheat growing season. There are differences (P < 0.0001 in the variations of the potential yields among three cultivars over 30 yr. For all three water deficit types, the more recent cultivars Jimai22 and Shijiazhuang8 had higher yields compared to the older 'Jinan17'. As the N fertilizer rate increased, the yield gap decreased more substantially during the low water deficit years because of the significant increase in attainable yield. Overall, the yield gaps were smaller with less water stress. Replacement of cultivars and appropriate N fertilizer application based on the forecasted drought types can narrow the yield gap effectively.

  3. Nonlinear parabolic problems with Neumann-type boundary conditions and L^1-data

    Directory of Open Access Journals (Sweden)

    Abderrahmane El Hachimi

    2007-11-01

    $$ \\frac{\\partial u}{\\partial t}-\\triangle_{p}u+\\alpha(u=f \\quad \\text{in } ]0,\\ T[\\times\\Omega, $$ with Neumann-type boundary conditions and initial data in $L^1$. Our approach is based essentially on the time discretization technique by Euler forward scheme.

  4. A special correcting winding for the l = 2 torsatron with split-type helical coils

    International Nuclear Information System (INIS)

    Kotenko, V.G.

    2012-01-01

    A split-type special correcting winding (split-type SCW) for the l = 2 torsatron toroidal magnetic system with split-type helical coils is considered. The split-type SCW gives the possibility of controlling the position of the magnetic surface configuration in the direction perpendicular to the torus equatorial plane. Numerical simulations were carried out to investigate the influence of the split-type SCW magnetic field on centered and distant relative to the torus surface magnetic surface configuration with a plane magnetic axis, being promising for the fusion reactor. The configuration is realized in the l = 2 torsatron with split-type helical coils and with the coils of an additional toroidal magnetic field. The calculations show that the split-type SCW magnetic field influence on the initial magnetic surface configuration leads mainly to the magnetic surface configuration displacement along the straight z axis of torus rotation. The displacement of ∼0.1a, a is the minor radius of the torus, has no critical effect on the magnetic surface parameters. An idea on the split-type SCW magnetic field structure is obtained by numerical simulations of the effect of this field as a minority magnetic field imposed on the magnetic field of a well-known configuration. The split-type SCW magnetic field is directed, predominantly along the major radius of the torus within its volume. The displacement range of the closed magnetic surface configuration depends on the split-type SCW magnetic field value.

  5. Development of an interatomic EAM type potential for Zr

    International Nuclear Information System (INIS)

    Pasianot, R.C.; Monti, A.M.

    1996-01-01

    In the present work are developed interatomic potentials of the embedded atom type (EAM) adequate for computer simulation of microstructural defects in the Zr lattice. It is observed that the less repulsive potential agrees better with the experimental data of the self-interstitial relaxation volume and predicts the basal crowdion as the stable configuration, the basal dumbbell having a formation energy slightly higher (0.01 eV). (author). 9 refs., 1 fig., 3 tabs

  6. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...... mimics IPC. 2. Rat hearts were studied in a Langendorff preparation perfused with Krebs'-Henseleit solution and subjected to 40 min global no-flow ischaemia, followed by 120 min reperfusion. L-Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non-diabetic...

  7. The direct l-type resonance spectrum of CF3CCH in the vibrational state ν 10 = 2

    International Nuclear Information System (INIS)

    Woetzel, Ulf; Maeder, Heinrich; Harder, Hauke; Pracna, Petr; Sarka, Kamil

    2005-01-01

    The direct l-type resonance spectrum of CF 3 CCH in the vibrational state ν 10 = 2 has been measured by means of waveguide microwave Fourier transform spectroscopy in the range 8-26 GHz. Two types of direct l-type resonance transitions induced by the (Δk = ±2, Δl = ±2) interaction could be observed: 262 transitions following the ΔJ = 0, Δk = Δl = 2 selection rule covering values of J = 17-64 and G vertical bar k - l vertical bar from 2 to 15, and 75 transitions following the ΔJ = 0, Δk = Δl = 4 selection rule covering values of J = 44-70 and G up to 3. The strong (2, 2) resonance furthermore allowed the observation of A 1 -A 2 splittings of the k = l = ±2 states from J = 63-70. The transitions with G = 3 showed splittings due to the (4, -2) and (0, 6) interactions. The corresponding energy level systems and part of the Hamiltonian matrix are discussed. Strong perturbations due to Δ(k - l) = 3 interactions coupling the states k = ±1, l = ±2 and k = ±4, l ±2 made possible the observation of perturbation-allowed transitions with selection rule k = ±1, l =± 2 ↔ k = 0, l = ±2. Additionally, the J = 2-1 and 3-2 rotational transitions have been measured. A multiple fitting analysis has been performed in which the experimental data have been fitted using five reduced forms of the effective Hamiltonian as proposed by Sarka and Harder [J. Mol. Spectrosc. 197 (1999) 254]. Parameters up to sixth order have been determined including the axial rotational constant A for both values of vertical bar l vertical bar and the unitary equivalence of the determined parameter sets has been demonstrated

  8. Acoustic emission from hydrogen saturated Type 304L stainless steel

    International Nuclear Information System (INIS)

    Caskey, G.R. Jr.

    1978-01-01

    Acoustic emission is attributed to energy release within a material body by localized plastic deformation or failure processes. The elastic stress waves may come from slip band formation, mechanical twinning, martensite transformation, or crack propagation. Each of these processes has slightly different acoustic characteristics allowing for easy identification. Acoustic emission was monitored during tensile tests of Type 304L austenitic stainless steel to explore the applicability of the technique to hydrogen-assisted fracture

  9. Structural Characterization and Oligomerization of the TssL Protein, a Component Shared by Bacterial Type VI and Type IVb Secretion Systems*

    Science.gov (United States)

    Durand, Eric; Zoued, Abdelrahim; Spinelli, Silvia; Watson, Paul J. H.; Aschtgen, Marie-Stéphanie; Journet, Laure; Cambillau, Christian; Cascales, Eric

    2012-01-01

    The Type VI secretion system (T6SS) is a macromolecular system distributed in Gram-negative bacteria, responsible for the secretion of effector proteins into target cells. The T6SS has a broad versatility as it can target both eukaryotic and prokaryotic cells. It is therefore involved in host pathogenesis or killing neighboring bacterial cells to colonize a new niche. At the architecture level, the T6SS core apparatus is composed of 13 proteins, which assemble in two subcomplexes. One of these subcomplexes, composed of subunits that share structural similarities with bacteriophage tail and baseplate components, is anchored to the cell envelope by the membrane subcomplex. This latter is constituted of at least three proteins, TssL, TssM, and TssJ. The crystal structure of the TssJ outer membrane lipoprotein and its interaction with the inner membrane TssM protein have been recently reported. TssL and TssM share sequence homology and characteristics with two components of the Type IVb secretion system (T4bSS), IcmH/DotU and IcmF, respectively. In this study, we report the crystal structure of the cytoplasmic domain of the TssL inner membrane protein from the enteroaggregative Escherichia coli Sci-1 T6SS. It folds as a hook-like structure composed of two three-helix bundles. Two TssL molecules associate to form a functional complex. Although the TssL trans-membrane segment is the main determinant of self-interaction, contacts between the cytoplasmic domains are required for TssL function. Based on sequence homology and secondary structure prediction, we propose that the TssL structure is the prototype for the members of the TssL and IcmH/DotU families. PMID:22371492

  10. Antioxidant potential of chestnut (Castanea sativa L.) and almond (Prunus dulcis L.) by-products.

    Science.gov (United States)

    Barreira, J C M; Ferreira, I C F R; Oliveira, M B P P; Pereira, J A

    2010-06-01

    The antioxidant properties of almond green husks (Cvs. Duro Italiano, Ferraduel, Ferranhês, Ferrastar and Orelha de Mula), chestnut skins and chestnut leaves (Cvs. Aveleira, Boa Ventura, Judia and Longal) were evaluated through several chemical and biochemical assays in order to provide a novel strategy to stimulate the application of waste products as new suppliers of useful bioactive compounds, namely antioxidants. All the assayed by-products revealed good antioxidant properties, with very low EC(50) values (lower than 380 μg/mL), particularly for lipid peroxidation inhibition (lower than 140 μg/mL). The total phenols and flavonoids contents were also determined. The correlation between these bioactive compounds and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of β-carotene bleaching and inhibition of lipid peroxidation in pig brain tissue through formation of thiobarbituric acid reactive substances, was also obtained. Although, all the assayed by-products proved to have a high potential of application in new antioxidants formulations, chestnut skins and leaves demonstrated better results.

  11. High production of D-tagatose, a potential sugar substitute, using immobilized L-arabinose isomerase.

    Science.gov (United States)

    Kim, P; Yoon, S H; Roh, H J; Choi, J H

    2001-01-01

    An L-arabinose isomerase of Escherichia coli was immobilized using covalent binding to agarose to produce D-tagatose, a bulking sweetener that can be economically used as a sugar substitute. The immobilized L-arabinose isomerase stably produced an average of 7.5 g-tagatose/L.day for 7 days with a productivity exceeding that of the free enzyme (0.47 vs 0.30 mg/U.day). Using a scaled-up immobilized enzyme system, 99.9 g-tagatose/L was produced from galactose with 20% equilibrium in 48 h. The process was repeated two more times with production of 104.1 and 103.5 g-tagatose/L. D-Tagatose production using an immobilized L-arabinose isomerase has a high potential for commercial application.

  12. Single-channel L-type Ca2+ currents in chicken embryo semicircular canal type I and type II hair cells.

    Science.gov (United States)

    Zampini, Valeria; Valli, Paolo; Zucca, Giampiero; Masetto, Sergio

    2006-08-01

    Few data are available concerning single Ca channel properties in inner ear hair cells and particularly none in vestibular type I hair cells. By using the cell-attached configuration of the patch-clamp technique in combination with the semicircular canal crista slice preparation, we determined the elementary properties of voltage-dependent Ca channels in chicken embryo type I and type II hair cells. The pipette solutions included Bay K 8644. With 70 mM Ba(2+) in the patch pipette, Ca channel activity appeared as very brief openings at -60 mV. Ca channel properties were found to be similar in type I and type II hair cells; therefore data were pooled. The mean inward current amplitude was -1.3 +/- 0.1 (SD) pA at - 30 mV (n = 16). The average slope conductance was 21 pS (n = 20). With 5 mM Ba(2+) in the patch pipette, very brief openings were already detectable at -80 mV. The mean inward current amplitude was -0.7 +/- 0.2 pA at -40 mV (n = 9). The average slope conductance was 11 pS (n = 9). The mean open time and the open probability increased significantly with depolarization. Ca channel activity was still present and unaffected when omega-agatoxin IVA (2 microM) and omega-conotoxin GVIA (3.2 microM) were added to the pipette solution. Our results show that types I and II hair cells express L-type Ca channels with similar properties. Moreover, they suggest that in vivo Ca(2+) influx might occur at membrane voltages more negative than -60 mV.

  13. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

  14. Mercury exposure on potential plant Ludwigia octovalvis L. - Preliminary toxicological testing

    Science.gov (United States)

    Alrawiq, Huda S. M.; Mushrifah, I.

    2013-11-01

    The preliminary test in phytoremediation is necessaryto determine the ability of plant to survive in media with different concentrations of contaminant. It was conducted to determine the maximum concentration of the contaminant that isharmful to the plant and suppress the plant growth. This study showed the ability of Ludwigia octovalvisto resist mercury (Hg) contaminant in sand containing different concentrations of Hg (0, 0.5, 1, 2, 4, 6 and 8 mg/L). The experimental work wasperformed under greenhouse conditions for an observation period of 4 weeks. Throughout the 4 weeks duration, the resultsshowed that 66.66% of the plants withered for on exposure to Hg concentration of 4 mg/L and 100% withered at higher concentrations of 6 and 8 mg/L. The results of this study may serve as a basis for research that aims to study uptake and accumulation of Hg using potential phytoremediation plants.

  15. Direct Interaction of CaVβ with Actin Up-regulates L-type Calcium Currents in HL-1 Cardiomyocytes*

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E.; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-01-01

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. PMID:25533460

  16. Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability.

    Science.gov (United States)

    Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K; Morales, Cyndi R; Contreras-Ferrat, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J; Somlo, Stefan; Rothermel, Beverly A; Gillette, Thomas G; Lavandero, Sergio; Hill, Joseph A

    2015-06-16

    L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. © 2015 American Heart Association, Inc.

  17. Sequencing type material resolves the identity and distribution of the generitype Lithophyllum incrustans, and related European species L. hibernicum and L. bathyporum (Corallinales, Rhodophyta).

    Science.gov (United States)

    Hernandez-Kantun, Jazmin J; Rindi, Fabio; Adey, Walter H; Heesch, Svenja; Peña, Viviana; Le Gall, Line; Gabrielson, Paul W

    2015-08-01

    DNA sequences from type material in the nongeniculate coralline genus Lithophyllum were used to unambiguously link some European species names to field-collected specimens, thus providing a great advance over morpho-anatomical identifi-cation. In particular, sequence comparisons of rbcL, COI and psbA genes from field-collected specimens allowed the following conclusion: the generitype species, L. incrustans, occurs mostly as subtidal rhodoliths and crusts on both Atlantic and Mediterranean coasts, and not as the common, NE Atlantic, epilithic, intertidal crust reported in the literature. The heterotypic type material of L. hibernicum was narrowed to one rhodolith belonging in Lithophyllum. As well as occurring as a subtidal rhodolith, L. hibernicum is a common, epilithic and epizoic crust in the intertidal zone from Ireland south to Mediterranean France. A set of four features distinguished L. incrustans from L. hibernicum, including epithallial cell diameter, pore canal shape of sporangial conceptacles and sporangium height and diameter. An rbcL sequence of the lectotype of Lithophyllum bathyporum, which was recently proposed to accommodate Atlantic intertidal collections of L. incrustans, corresponded to a distinct taxon hitherto known only from Brittany as the subtidal, bisporangial, lectotype, but also occurs intertidally in Atlantic Spain. Specimens from Ireland and France morpho-anatomically identified as L. fasciculatum and a specimen from Cornwall likewise identified as L. duckerae were resolved as L. incrustans and L. hibernicum, respectively. © 2015 Phycological Society of America.

  18. Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes.

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-02-20

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

    Directory of Open Access Journals (Sweden)

    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  20. Antimicrobial Potential of Momordica charantia L. against Multiresistant Standard Species and Clinical Isolates.

    Science.gov (United States)

    Lucena Filho, José Hardman Sátiro de; Lima, Rennaly de Freitas; Medeiros, Ana Claudia Dantas de; Pereira, Jozinete Vieira; Granville-Garcia, Ana Flávia; Costa, Edja Maria Melo de Brito

    2015-11-01

    The aim of the present study was to evaluate the antibacterial and antifungal potential in vitro of Momordica charantia L. against the microorganisms of clinical interest (standard strains and multiresistant isolates) in order to aggregate scientific information in relation to its use as a therapeutic product. M. charantia L. plant material was acquired in municipality of Malta, Paraiba, Brazil. The extract was obtained through maceration, filtration and then concentrated under reduced pressure in a rotary evaporator, resulting in a dough, and was then dried in an oven for 72 hours at 40°C. Antimicrobial action of ethanolic extract of seed M. charantia L. was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) against standard strains of bacteria, isolates multiresistant bacteria and Candida species, by microdilution in broth method. All organisms were sensitive to the extract, being considered strong antimicrobial activity (MIC and MBC/MFC charantia L. showed strong antimicrobial potential, with bactericidal and fungicidal profile, there is the prospect to constitute a new therapeutic strategy for the control of infections, particularly in multiresistant strains. The use of medicinal plants in treatment of infectious processes have an important function nowadays, due to the limitations of the use of synthetic antibiotics available, related specifically to the microbial resistance emergence.

  1. Citalopram inhibits L-type calcium channel current in rat cardiomyocytes in culture

    Czech Academy of Sciences Publication Activity Database

    Hamplová-Peichlová, J.; Krůšek, Jan; Paclt, I.; Slavíček, J.; Lisá, Věra; Vyskočil, František

    2002-01-01

    Roč. 51, č. 3 (2002), s. 317-321 ISSN 0862-8408 R&D Projects: GA AV ČR IAA7011902; GA ČR GA305/02/1333 Institutional research plan: CEZ:AV0Z5011922 Keywords : citalopram * amitriptyline * L-type calcium channel current Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

  2. SOMATOSENSORY EVOKED POTENTIALS IN DIABETES MELLITUS TYPE - 2

    Directory of Open Access Journals (Sweden)

    Rekha

    2015-10-01

    Full Text Available Diabetes mellitus is the most common metabolic disorder affecting majority of population. It is estimated that over 400 million people throughout the world have diabetes. It has progressed to be a pandemic from an epidemic causing morbidity and mortality in the population. Among the many complications of diabetes, diabetic neuropathies contribute majorly to the morbidity associated with the disease. Axonal conduction is affected by elevated levels of protein kinase c causing neuronal ischemia; decreased ce llular myoinositol affecting sodium potassium ATPase pump leads to decreased nerve conduction; Somatosensory E voked P otentials (SSEPs reflect the activity of somatosensory pathways mediated through the dorsal columns of the spinal cord and the specific so matosensory cortex. Recording of Somatosensory Evoked Potentials in diabetics is done to assess the sensory involvement of spinal cord. Presence of SEPs provides clear evidence for axonal continuity and by using different stimulation sites, the rate of reg eneration can be determined. Both onset and peak latencies of all SEP components are prolonged in patients with diabetes. Present study is done to compare somatosensory evoked potentials in diabetics and normal subjects. MATERIALS AND METHOD S: The present study was undertaken at the Upgraded Department of Physiology, Osmania Medical College, Koti, Hyderabad. The study was conducted on subjects, both male and female in the age group of 45 to 55 years, suffering from type II diabetes excluding other neurologi cal disorders. Non - invasive method of estimation of nerve conduction studies using SFEMG/EP — Electromyography or evoked potential system (Nicolet systems — USA using surface electrodes with automated computerized monitor attached with printer is used. RESUL TS : ANOVA showed statistically significant N9 latency (right & left sides. Latencies of all the components of SSEPs were more significant than amplitudes in Diabetic

  3. [Influence of a variation potential on photosynthesis in pumpkin seedlings (Cucurbita pepo L.)].

    Science.gov (United States)

    Sukhov, V S; Shesterneva, O N; Surova, L M; Rumiantsev, E A; Vodeneev, V A

    2013-01-01

    The influence of a variation potential on photosynthesis in pumpkin seedlings (Cucurbita pepo L.) was investigated in our work. It was shown that the variation potential induced by cotyledon burning propagates into a leaf. It decreases CO2 assimilation and transpiration as well as increases nonphotochemical quenching. Investigation of isolated chloroplasts showed that lowering of the pH in incubation medium from 6.9-7.2 to 6.5 increases nonphotochemical quenching. It was proposed that lowering of the cytoplasmic pH induced by the variation potential takes place in the photosynthetic response development.

  4. Method of renormalization potential for one model of Hartree-Fock-Slater type

    CERN Document Server

    Zasorin, Y V

    2002-01-01

    A new method of the potential renormalization for the quasiclassical model of the Hartree-Fock-Slater real potential is proposed. The method makes it possible to easily construct the wave functions and contrary to the majority od similar methods it does not require the knowledge of the real-type potential

  5. Allelopathic potential of Robinia pseudo-acacia L.

    Science.gov (United States)

    Nasir, Habib; Iqbal, Zahida; Hiradate, Syuntaro; Fujii, Yoshiharu

    2005-09-01

    Robinia pseudo-acacia L. (black locust) is a nonindigenous species currently invading the central part of Japanese grasslands. Several allelochemicals were identified and characterized from the leaf tissue. The growth of both radicle and hypocotyl in the tested species (barnyard grass, white clover, lettuce, and Chinese cabbage) was reduced when grown in soil mixed with the leaves of R. pseudo-acacia at various concentrations. Aqueous leaf extracts, when bioassayed, exhibited a significant suppression of radicle growth. Chromatographic separation of an ethanolic extract of R. pseudo-acacia leaves resulted in isolation of three compounds, identified as robinetin (1), myricetin (2), and quercetin (3) by nuclear magnetic resonance and mass spectroscopy. All inhibited root and shoot growth of lettuce. Robinetin, found in a large amount, caused 50% suppression of the root and shoot growth of lettuce at 100 ppm. The presence of these bioactive substances in leaf tissue suggests a potential role for flavonoids in R. pseudo-acacia invasion in introduced habitats.

  6. Comparison of ribotyping, randomly amplified polymorphic DNA analysis, and pulsed-field gel electrophoresis in typing of Lactobacillus rhamnosus and L. casei strains.

    Science.gov (United States)

    Tynkkynen, S; Satokari, R; Saarela, M; Mattila-Sandholm, T; Saxelin, M

    1999-09-01

    A total of 24 strains, biochemically identified as members of the Lactobacillus casei group, were identified by PCR with species-specific primers. The same set of strains was typed by randomly amplified polymorphic DNA (RAPD) analysis, ribotyping, and pulsed-field gel electrophoresis (PFGE) in order to compare the discriminatory power of the methods. Species-specific primers for L. rhamnosus and L. casei identified the type strain L. rhamnosus ATCC 7469 and the neotype strain L. casei ATCC 334, respectively, but did not give any signal with the recently revived species L. zeae, which contains the type strain ATCC 15820 and the strain ATCC 393, which was previously classified as L. casei. Our results are in accordance with the suggested new classification of the L. casei group. Altogether, 21 of the 24 strains studied were identified with the species-specific primers. In strain typing, PFGE was the most discriminatory method, revealing 17 genotypes for the 24 strains studied. Ribotyping and RAPD analysis yielded 15 and 12 genotypes, respectively.

  7. Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

    Science.gov (United States)

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-01-01

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

  8. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    Directory of Open Access Journals (Sweden)

    Laurent Nottale

    2013-12-01

    Full Text Available We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided.

  9. Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Williams, Carlyn; Kim, Seong Man; Garcea, Robert L; Sapp, Martin

    2012-09-01

    Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.

  10. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

    DEFF Research Database (Denmark)

    Helgason, Agnar; Pálsson, Snaebjörn; Thorleifsson, Gudmar

    2007-01-01

    diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East......We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2...

  11. Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

    Science.gov (United States)

    Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

    2015-01-01

    SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

  12. L-type calcium channels refine the neural population code of sound level

    Science.gov (United States)

    Grimsley, Calum Alex; Green, David Brian

    2016-01-01

    The coding of sound level by ensembles of neurons improves the accuracy with which listeners identify how loud a sound is. In the auditory system, the rate at which neurons fire in response to changes in sound level is shaped by local networks. Voltage-gated conductances alter local output by regulating neuronal firing, but their role in modulating responses to sound level is unclear. We tested the effects of L-type calcium channels (CaL: CaV1.1–1.4) on sound-level coding in the central nucleus of the inferior colliculus (ICC) in the auditory midbrain. We characterized the contribution of CaL to the total calcium current in brain slices and then examined its effects on rate-level functions (RLFs) in vivo using single-unit recordings in awake mice. CaL is a high-threshold current and comprises ∼50% of the total calcium current in ICC neurons. In vivo, CaL activates at sound levels that evoke high firing rates. In RLFs that increase monotonically with sound level, CaL boosts spike rates at high sound levels and increases the maximum firing rate achieved. In different populations of RLFs that change nonmonotonically with sound level, CaL either suppresses or enhances firing at sound levels that evoke maximum firing. CaL multiplies the gain of monotonic RLFs with dynamic range and divides the gain of nonmonotonic RLFs with the width of the RLF. These results suggest that a single broad class of calcium channels activates enhancing and suppressing local circuits to regulate the sensitivity of neuronal populations to sound level. PMID:27605536

  13. Relativistic bound states in the presence of spherically ring-shaped q-deformed Woods–Saxon potential with arbitrary l-states

    International Nuclear Information System (INIS)

    Ikhdair, S.M.; Hamzavi, M.; Rajabi, A.A.

    2013-01-01

    Approximate bound-state solutions of the Dirac equation with q-deformed Woods–Saxon (WS) plus a new generalized ring-shaped (RS) potential are obtained for any arbitrary l-state. The energy eigenvalue equation and corresponding two-component wave functions are calculated by solving the radial and angular wave equations within a shortcut of the Nikiforov–Uvarov (NU) method. The solutions of the radial and polar angular parts of the wave function are expressed in terms of the Jacobi polynomials. A new approximation being expressed in terms of the potential parameters is carried out to deal with the strong singular centrifugal potential term l(l+1)r -2 . Under some limitations, we can obtain solution for the RS Hulthen potential and the standard usual spherical WS potential (q = 1). (author)

  14. Tetrahymena thermophila acidic ribosomal protein L37 contains an archaebacterial type of C-terminus.

    Science.gov (United States)

    Hansen, T S; Andreasen, P H; Dreisig, H; Højrup, P; Nielsen, H; Engberg, J; Kristiansen, K

    1991-09-15

    We have cloned and characterized a Tetrahymena thermophila macronuclear gene (L37) encoding the acidic ribosomal protein (A-protein) L37. The gene contains a single intron located in the 3'-part of the coding region. Two major and three minor transcription start points (tsp) were mapped 39 to 63 nucleotides upstream from the translational start codon. The uppermost tsp mapped to the first T in a putative T. thermophila RNA polymerase II initiator element, TATAA. The coding region of L37 predicts a protein of 109 amino acid (aa) residues. A substantial part of the deduced aa sequence was verified by protein sequencing. The T. thermophila L37 clearly belongs to the P1-type family of eukaryotic A-proteins, but the C-terminal region has the hallmarks of archaebacterial A-proteins.

  15. Effect of plantain (Musa paradisiaca L. cv. Dominico Harton peel flour as binder in frankfurter-type sausage

    Directory of Open Access Journals (Sweden)

    Gilver Rosero Chasoy

    2017-07-01

    Full Text Available Agroindustrial residues such as plantain (Musa paradisiaca L. cv. Dominico Harton peel have functional properties, which made them suitable for use as a food ingredient. The aim of this research was to evaluate plantain peel flour (PPF as a binder in the production of frankfurter- type sausage. Five formulations were prepared in which wheat flour (WF was replaced by PPF as follows: 25%, 50%, 70% and 100%, respectively. Once the sausages are obtained, the water retention capacity (WRC, emulsifying stability (ES, and pH, were evaluated. When comparing treatments with the control sample, it was found that replacing up to 50% of WF by PPF, significantly increased WRC by 7.5%. When replacing 25%, Es, there were no statistically significant changes among treatments. When replacing 100%, the product pH, was significantly decreased. The results indicated, the sausages made with 50% of PPF, retain the formulation water, which is why the PPF has potential for this type of sausage manufacture. PPF could replace WF up to 25% in the frankfurter formulation, without affecting ES and pH and favoring WRC.

  16. Mutagenic Potential ofBos taurus Papillomavirus Type 1 E6 Recombinant Protein: First Description

    Directory of Open Access Journals (Sweden)

    Rodrigo Pinheiro Araldi

    2015-01-01

    Full Text Available Bovine papillomavirus (BPV is considered a useful model to study HPV oncogenic process. BPV interacts with the host chromatin, resulting in DNA damage, which is attributed to E5, E6, and E7 viral oncoproteins activity. However, the oncogenic mechanisms of BPV E6 oncoprotein per se remain unknown. This study aimed to evaluate the mutagenic potential of Bos taurus papillomavirus type 1 (BPV-1 E6 recombinant oncoprotein by the cytokinesis-block micronucleus assay (CBMNA and comet assay (CA. Peripheral blood samples of five calves were collected. Samples were subjected to molecular diagnosis, which did not reveal presence of BPV sequences. Samples were treated with 1 μg/mL of BPV-1 E6 oncoprotein and 50 μg/mL of cyclophosphamide (positive control. Negative controls were not submitted to any treatment. The samples were submitted to the CBMNA and CA. The results showed that BPV E6 oncoprotein induces clastogenesis per se, which is indicative of genomic instability. These results allowed better understanding the mechanism of cancer promotion associated with the BPV E6 oncoprotein and revealed that this oncoprotein can induce carcinogenesis per se. E6 recombinant oncoprotein has been suggested as a possible vaccine candidate. Results pointed out that BPV E6 recombinant oncoprotein modifications are required to use it as vaccine.

  17. First evidence of a potential antibacterial activity involving a laccase-type enzyme of the phenoloxidase system in Pacific oyster Crassostrea gigas haemocytes.

    Science.gov (United States)

    Luna-Acosta, Andrea; Saulnier, Denis; Pommier, Mylène; Haffner, Philippe; De Decker, Sophie; Renault, Tristan; Thomas-Guyon, Hélène

    2011-12-01

    Phenoloxidases (POs) are a group of copper proteins including tyrosinase, catecholase and laccase. In several insects and crustaceans, antibacterial substances are produced through the PO cascade, participating in the direct killing of invading microorganisms. However, although POs are widely recognised as an integral part of the invertebrate immune defence system, experimental evidence is lacking that these properties are conserved in molluscs, and more particularly in the Pacific oyster Crassostrea gigas. In the present study, Vibrio splendidus LGP32 and Vibrio aestuarianus 02/041 growths were affected, after being treated with C. gigas haemocyte lysate supernatant (HLS), and either a common substrate of POs, l-3,4-dihydroxyphenylalanine (L-DOPA), to detect catecholase-type PO activity, or a specific substrate of laccase, p-phenylenediamine (PPD), to detect laccase-type PO activity. Interestingly, a higher bacterial growth inhibition was observed in the presence of PPD than in the presence of L-DOPA. These effects were suppressed when the specific PO inhibitor, phenylthiourea (PTU), was added to the medium. Results of the present study suggest, for the first time in a mollusc species, that antibacterial activities of HLS from C. gigas potentially involve POs, and more particularly laccase catalysed reactions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Linking child maltreatment history with child abuse potential: Relative roles of maltreatment types

    Directory of Open Access Journals (Sweden)

    Mitkovic-Voncina Marija

    2014-01-01

    Full Text Available The independent roles of each childhood maltreatment type on child abuse potential in adults have been insufficiently explored and are inconsistent, with dissociation as one of the possible suggested mediators of intergenerational child abuse. We investigated these effects among 164 non-clinical adult parents, who filled in general questionnaires: Childhood Trauma Questionnaire (CTQ, Child Abuse Potential Inventory (CAPI and Dissociative Experience Scale (DES. Among all maltreatment types (emotional, physical and sexual abuse, emotional and physical neglect, emotional abuse was the only independent predictor in the regression model of child abuse potential. The relationship between emotional abuse history and child abuse potential was partially mediated by dissociation. The findings could speak in favor of the potentially unique detrimental role of emotional abuse in intergenerational maltreatment, with dissociation as one of the possible mechanisms.

  19. Overexpression of wild-type aspartokinase increases L-lysine production in the thermotolerant methylotrophic bacterium Bacillus methanolicus.

    Science.gov (United States)

    Jakobsen, Oyvind M; Brautaset, Trygve; Degnes, Kristin F; Heggeset, Tonje M B; Balzer, Simone; Flickinger, Michael C; Valla, Svein; Ellingsen, Trond E

    2009-02-01

    Aspartokinase (AK) controls the carbon flow into the aspartate pathway for the biosynthesis of the amino acids l-methionine, l-threonine, l-isoleucine, and l-lysine. We report here the cloning of four genes (asd, encoding aspartate semialdehyde dehydrogenase; dapA, encoding dihydrodipicolinate synthase; dapG, encoding AKI; and yclM, encoding AKIII) of the aspartate pathway in Bacillus methanolicus MGA3. Together with the known AKII gene lysC, dapG and yclM form a set of three AK genes in this organism. Overexpression of dapG, lysC, and yclM increased l-lysine production in wild-type B. methanolicus strain MGA3 2-, 10-, and 60-fold (corresponding to 11 g/liter), respectively, without negatively affecting the specific growth rate. The production levels of l-methionine (less than 0.5 g/liter) and l-threonine (less than 0.1 g/liter) were low in all recombinant strains. The AK proteins were purified, and biochemical analyses demonstrated that they have similar V(max) values (between 47 and 58 micromol/min/mg protein) and K(m) values for l-aspartate (between 1.9 and 5.0 mM). AKI and AKII were allosterically inhibited by meso-diaminopimelate (50% inhibitory concentration [IC(50)], 0.1 mM) and by l-lysine (IC(50), 0.3 mM), respectively. AKIII was inhibited by l-threonine (IC(50), 4 mM) and by l-lysine (IC(50), 5 mM), and this enzyme was synergistically inhibited in the presence of both of these amino acids at low concentrations. The correlation between the impact on l-lysine production in vivo and the biochemical properties in vitro of the individual AK proteins is discussed. This is the first example of improving l-lysine production by metabolic engineering of B. methanolicus and also the first documentation of considerably increasing l-lysine production by overexpression of a wild-type AK.

  20. Evaluation of insulin expression and secretion in genetically engineered gut K and L-cells

    Directory of Open Access Journals (Sweden)

    Ahmad Zalinah

    2012-09-01

    Full Text Available Abstract Background Gene therapy could provide an effective treatment of diabetes. Previous studies have investigated the potential for several cell and tissue types to produce mature and active insulin. Gut K and L-cells could be potential candidate hosts for gene therapy because of their special features. Results In this study, we isolated gut K and L-cells to compare the potential of both cell types to produce insulin when exposed to similar conditions. The isolated pure K and L-cells were transfected with recombinant plasmids encoding insulin and with specific promoters for K or L-cells. Insulin expression was studied in response to glucose or meat hydrolysate. We found that glucose and meat hydrolysate efficiently induced insulin secretion from K and L-cells. However, the effects of meat hydrolysate on insulin secretion were more potent in both cells compared with glucose. Results of enzyme-linked immunosorbent assays showed that L-cells secreted more insulin compared with K-cells regardless of the stimulator, although this difference was not statistically significant. Conclusion The responses of K and L-cells to stimulation with glucose or meat hydrolysate were generally comparable. Therefore, both K and L-cells show similar potential to be used as surrogate cells for insulin gene expression in vitro. The potential use of these cells for diabetic gene therapy warrants further investigation.

  1. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons.

    Science.gov (United States)

    Qian, Hai; Patriarchi, Tommaso; Price, Jennifer L; Matt, Lucas; Lee, Boram; Nieves-Cintrón, Madeline; Buonarati, Olivia R; Chowdhury, Dhrubajyoti; Nanou, Evanthia; Nystoriak, Matthew A; Catterall, William A; Poomvanicha, Montatip; Hofmann, Franz; Navedo, Manuel F; Hell, Johannes W

    2017-01-24

    The L-type Ca 2+ channel Ca v 1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving β-adrenergic receptors (βARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser 1928 in Ca v 1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser 1928 is not required for regulation of cardiac Ca v 1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Ca v 1.2 and enhancement of its activity by the β 2 -adrenergic receptor (β 2 AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Ca v 1.2 by PKA in cardiomyocytes and hippocampal neurons. Copyright © 2017, American Association for the Advancement of Science.

  2. Construction of the landscape for multi-stable systems: Potential landscape, quasi-potential, A-type integral and beyond

    Science.gov (United States)

    Zhou, Peijie; Li, Tiejun

    2016-03-01

    Motivated by the famous Waddington's epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct the landscape for multi-stable complex systems. We aim to summarize and elucidate the relationships among these theories from a mathematical point of view. We systematically investigate and compare three different but closely related realizations in the recent literature: the Wang's potential landscape theory from steady state distribution of stochastic differential equations (SDEs), the Freidlin-Wentzell quasi-potential from the large deviation theory, and the construction through SDE decomposition and A-type integral. We revisit that the quasi-potential is the zero noise limit of the potential landscape, and the potential function in the third proposal coincides with the quasi-potential. We compare the difference between local and global quasi-potential through the viewpoint of exchange of limit order for time and noise amplitude. We argue that local quasi-potentials are responsible for getting transition rates between neighboring stable states, while the global quasi-potential mainly characterizes the residence time of the states as the system reaches stationarity. The difference between these two is prominent when the transitivity property is broken. The most probable transition path by minimizing the Onsager-Machlup or Freidlin-Wentzell action functional is also discussed. As a consequence of the established connections among different proposals, we arrive at the novel result which guarantees the existence of SDE decomposition while denies its uniqueness in general cases. It is, therefore, clarified that the A-type integral is more appropriate to be applied to the decomposed SDEs rather than its primitive form as believed by previous researchers. Our results contribute to a deeper understanding of landscape theories for biological systems.

  3. Construction of the landscape for multi-stable systems: Potential landscape, quasi-potential, A-type integral and beyond

    International Nuclear Information System (INIS)

    Zhou, Peijie; Li, Tiejun

    2016-01-01

    Motivated by the famous Waddington’s epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct the landscape for multi-stable complex systems. We aim to summarize and elucidate the relationships among these theories from a mathematical point of view. We systematically investigate and compare three different but closely related realizations in the recent literature: the Wang’s potential landscape theory from steady state distribution of stochastic differential equations (SDEs), the Freidlin-Wentzell quasi-potential from the large deviation theory, and the construction through SDE decomposition and A-type integral. We revisit that the quasi-potential is the zero noise limit of the potential landscape, and the potential function in the third proposal coincides with the quasi-potential. We compare the difference between local and global quasi-potential through the viewpoint of exchange of limit order for time and noise amplitude. We argue that local quasi-potentials are responsible for getting transition rates between neighboring stable states, while the global quasi-potential mainly characterizes the residence time of the states as the system reaches stationarity. The difference between these two is prominent when the transitivity property is broken. The most probable transition path by minimizing the Onsager-Machlup or Freidlin-Wentzell action functional is also discussed. As a consequence of the established connections among different proposals, we arrive at the novel result which guarantees the existence of SDE decomposition while denies its uniqueness in general cases. It is, therefore, clarified that the A-type integral is more appropriate to be applied to the decomposed SDEs rather than its primitive form as believed by previous researchers. Our results contribute to a deeper understanding of landscape theories for biological systems.

  4. Construction of the landscape for multi-stable systems: Potential landscape, quasi-potential, A-type integral and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Peijie, E-mail: cliffzhou@pku.edu.cn; Li, Tiejun, E-mail: tieli@pku.edu.cn [LMAM and School of Mathematical Sciences, Peking University, Beijing 100871 (China)

    2016-03-07

    Motivated by the famous Waddington’s epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct the landscape for multi-stable complex systems. We aim to summarize and elucidate the relationships among these theories from a mathematical point of view. We systematically investigate and compare three different but closely related realizations in the recent literature: the Wang’s potential landscape theory from steady state distribution of stochastic differential equations (SDEs), the Freidlin-Wentzell quasi-potential from the large deviation theory, and the construction through SDE decomposition and A-type integral. We revisit that the quasi-potential is the zero noise limit of the potential landscape, and the potential function in the third proposal coincides with the quasi-potential. We compare the difference between local and global quasi-potential through the viewpoint of exchange of limit order for time and noise amplitude. We argue that local quasi-potentials are responsible for getting transition rates between neighboring stable states, while the global quasi-potential mainly characterizes the residence time of the states as the system reaches stationarity. The difference between these two is prominent when the transitivity property is broken. The most probable transition path by minimizing the Onsager-Machlup or Freidlin-Wentzell action functional is also discussed. As a consequence of the established connections among different proposals, we arrive at the novel result which guarantees the existence of SDE decomposition while denies its uniqueness in general cases. It is, therefore, clarified that the A-type integral is more appropriate to be applied to the decomposed SDEs rather than its primitive form as believed by previous researchers. Our results contribute to a deeper understanding of landscape theories for biological systems.

  5. Fabrication of Well-Ordered Three-Phase Boundary with Nanostructure Pore Array for Mixed Potential-Type Zirconia-Based NO2 Sensor.

    Science.gov (United States)

    Wang, Bin; Liu, Fangmeng; Yang, Xue; Guan, Yehui; Ma, Ce; Hao, Xidong; Liang, Xishuang; Liu, Fengmin; Sun, Peng; Zhang, Tong; Lu, Geyu

    2016-07-06

    A well-ordered porous three-phase boundary (TPB) was prepared with a polystyrene sphere as template and examined to improve the sensitivity of yttria-stabilized zirconia (YSZ)-based mixed-potential-type NO2 sensor due to the increase of the electrochemical reaction active sites. The shape of pore array on the YSZ substrate surface can be controlled through changing the concentration of the precursor solution (Zr(4+)/Y(3+) = 23 mol/L/4 mol/L) and treatment conditions. An ordered hemispherical array was obtained when CZr(4+) = 0.2 mol/L. The processed YSZ substrates were used to fabricate the sensors, and different sensitivities caused by different morphologies were tested. The sensor with well-ordered porous TPB exhibited the highest sensitivity to NO2 with a response value of 105 mV to 100 ppm of NO2, which is approximately twice as much as the smooth one. In addition, the sensor also showed good stability and speedy response kinetics. All these enhanced sensing properties might be due to the structure and morphology of the enlarged TPB.

  6. Constant extension rate testing of Type 304L stainless steel in simulated waste tank environments

    International Nuclear Information System (INIS)

    Wiersma, B.J.

    1992-01-01

    New tanks for storage of low level radioactive wastes will be constructed at the Savannah River Site (SRS) of AISI Type 304L stainless steel (304L). The presence of chlorides and fluorides in the wastes may induce Stress Corrosion Cracking (SCC) in 304L. Constant Extension Rate Tests (CERT) were performed to determine the susceptibility of 304L to SCC in simulated wastes. In five of the six tests conducted thus far 304L was not susceptible to SCC in the simulated waste environments. Conflicting results were obtained in the final test and will be resolved by further tests. For comparison purposes the CERT tests were also performed with A537 carbon steel, a material similar to that utilized for the existing nuclear waste storage tanks at SRS

  7. Tetrahymena thermophila acidic ribosomal protein L37 contains an archaebacterial type of C-terminus

    DEFF Research Database (Denmark)

    Hansen, T S; Andreasen, P H; Dreisig, H

    1991-01-01

    We have cloned and characterized a Tetrahymena thermophila macronuclear gene (L37) encoding the acidic ribosomal protein (A-protein) L37. The gene contains a single intron located in the 3'-part of the coding region. Two major and three minor transcription start points (tsp) were mapped 39 to 63 ...... by protein sequencing. The T. thermophila L37 clearly belongs to the P1-type family of eukaryotic A-proteins, but the C-terminal region has the hallmarks of archaebacterial A-proteins.......We have cloned and characterized a Tetrahymena thermophila macronuclear gene (L37) encoding the acidic ribosomal protein (A-protein) L37. The gene contains a single intron located in the 3'-part of the coding region. Two major and three minor transcription start points (tsp) were mapped 39 to 63...... nucleotides upstream from the translational start codon. The uppermost tsp mapped to the first T in a putative T. thermophila RNA polymerase II initiator element, TATAA. The coding region of L37 predicts a protein of 109 amino acid (aa) residues. A substantial part of the deduced aa sequence was verified...

  8. Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis

    Science.gov (United States)

    Lian, Yu-Ling; Cheng, Ming-Jun; Zhang, Xian-Xia; Wang, Li

    2017-01-01

    Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto-transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail-flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene-related peptide (CGRP) in L1-L6 DRG was measured via immunohistochemistry, western blotting and RT-qPCR. The results indicated that the Model group exhibited a significant decrease in tail flick latency compared to pre-surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1-L6 DRG significantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1-L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain. PMID:28627595

  9. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Structural characterization of a rhamnogalacturonan I-arabinan-type I arabinogalactan macromolecule from starfruit (Averrhoa carambola L.).

    Science.gov (United States)

    Leivas, Carolina Lopes; Iacomini, Marcello; Cordeiro, Lucimara M C

    2015-05-05

    A structural characterization of polysaccharides obtained from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. After fractionation by freeze-thaw and Fehling precipitation, a pectic polysaccharide was obtained. It was composed of rhamnose, arabinose, galactose and uronic acid in the 5.0:72.5:12.1:10.4 molar ratios, respectively. A combination of monosaccharide, GPC, methylation and NMR analysis and enzymatic hydrolysis with endo-β-(1→4)-D-galactanase showed the presence of a rhamnogalacturonan I to which a branched arabinan and a type I arabinogalactan are attached. The arabinan moiety was formed by (1→5)-linked α-L-Araf units in the backbone, branched only at O-3 by (1→2)- and (1→3)-linked α-L-Araf units, while the type I arabinogalactan was formed by (1→4)- and (1→4,6)-linked β-D-Galp units in the backbone with (1→5)-, (1→3,5)- and (1→3)-linked α-L-Araf units as side chains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Evaluation of an Epitypified Ophiocordyceps formosana (Cordyceps s.l.) for Its Pharmacological Potential

    Science.gov (United States)

    Wang, Yen-Wen; Hong, Tzu-Wen; Tai, Yu-Ling; Wang, Ying-Jing; Tsai, Sheng-Hong; Lien, Pham Thi Kim; Chou, Tzu-Ho; Lai, Jui-Ya; Chu, Richard; Ding, Shih-Torng; Irie, Kenji; Li, Tsai-Kun; Tzean, Shean-Shong; Shen, Tang-Long

    2015-01-01

    The substantial merit of Cordyceps s.l. spp. in terms of medicinal benefits is largely appreciated. Nevertheless, only few studies have characterized and examined the clinical complications of the use of health tonics containing these species. Here, we epitypified C. formosana isolates that were collected and characterized as Ophiocordyceps formosana based on morphological characteristics, molecular phylogenetic analyses, and metabolite profiling. Thus, we renamed and transferred C. formosana to the new protologue Ophiocordyceps formosana (Kobayasi & Shimizu) Wang, Tsai, Tzean & Shen comb. nov. Additionally, the pharmacological potential of O. formosana was evaluated based on the hot-water extract from its mycelium. The relative amounts of the known bioactive ingredients that are unique to Cordyceps s.l. species in O. formosana were found to be similar to the amounts in O. sinensis and C. militaris, indicating the potential applicability of O. formosana for pharmacological uses. Additionally, we found that O. formosana exhibited antioxidation activities in vitro and in vivo that were similar to those of O. sinensis and C. militaris. Furthermore, O. formosana also displayed conspicuously effective antitumor activity compared with the tested Cordyceps s.l. species. Intrinsically, O. formosana exhibited less toxicity than the other Cordyceps species. Together, our data suggest that the metabolites of O. formosana may play active roles in complementary medicine. PMID:26451152

  12. The potential of white-rot fungi to degrade phorbol esters of Jatropha curcas L. seed cake

    NARCIS (Netherlands)

    Barros, de C.R.M.; Ferreira, L.M.M.; Nunes, F.M.; Bezerra, R.M.F.; Dias, A.A.; Guedes, C.; Cone, J.W.; Marques, G.S.M.; Rodrigues, M.A.M.

    2011-01-01

    The potential of solid-state cultivation, with three white-rot fungi (Bjerkandera adusta, Ganoderma resinaceum and Phlebia rufa), to decrease phorbol esters concentration of Jatropha curcas L. was evaluated in this study. Incubation was conducted in 250¿mL Erlenmeyer flasks without agitation at 28°C

  13. Optical potential study of positron scattering by hydrogenic-type atoms

    International Nuclear Information System (INIS)

    Kuru Ratnavelu; Nithyanandan Natchimuthu; Kalai Kumar Rajgopal

    1999-01-01

    An optical potential method based on the close-coupling formalism has been implemented to study positron scattering by hydrogenic-type atoms. The present work will be reviewed in the context of other theories. Preliminary results will be presented and compared with experimental results. (author)

  14. Structural characterization of copia-type retrotransposons leads to insights into the marker development in a biofuel crop, Jatropha curcas L.

    Science.gov (United States)

    2013-01-01

    Background Recently, Jatropha curcas L. has attracted worldwide attention for its potential as a source of biodiesel. However, most DNA markers have demonstrated high levels of genetic similarity among and within jatropha populations around the globe. Despite promising features of copia-type retrotransposons as ideal genetic tools for gene tagging, mutagenesis, and marker-assisted selection, they have not been characterized in the jatropha genome yet. Here, we examined the diversity, evolution, and genome-wide organization of copia-type retrotransposons in the Asian, African, and Mesoamerican accessions of jatropha, then introduced a retrotransposon-based marker for this biofuel crop. Results In total, 157 PCR fragments that were amplified using the degenerate primers for the reverse transcriptase (RT) domain of copia-type retroelements were sequenced and aligned to construct the neighbor-joining tree. Phylogenetic analysis demonstrated that isolated copia RT sequences were classified into ten families, which were then grouped into three lineages. An in-depth study of the jatropha genome for the RT sequences of each family led to the characterization of full consensus sequences of the jatropha copia-type families. Estimated copy numbers of target sequences were largely different among families, as was presence of genes within 5 kb flanking regions for each family. Five copia-type families were as appealing candidates for the development of DNA marker systems. A candidate marker from family Jc7 was particularly capable of detecting genetic variation among different jatropha accessions. Fluorescence in situ hybridization (FISH) to metaphase chromosomes reveals that copia-type retrotransposons are scattered across chromosomes mainly located in the distal part regions. Conclusion This is the first report on genome-wide analysis and the cytogenetic mapping of copia-type retrotransposons of jatropha, leading to the discovery of families bearing high potential as DNA

  15. Potential for Drug Abuse: the Predictive Role of Parenting Styles, Stress and Type D Personality

    Directory of Open Access Journals (Sweden)

    mahin soheili

    2015-06-01

    Full Text Available Objective: This study was an attempt to predict potential for drug abuse on the basis of three predictors of parenting style, stress and type D personality. Method: In this descriptive-correlational study, 200 students (100 males and 100 females of Islamic Azad University of Karaj were selected by convenience sampling. For data collection, perceived parenting styles questionnaire, perceived stress scale, type D personality scale, and addiction potential scale were used. Results: The results showed that rejecting/neglecting parenting style and emotional warmth were positively and negatively correlated with addiction potential, respectively. Conclusion: The child-parent relationship and also the relationship between stress and type D personality can be considered as predictive factors in addiction potential.

  16. A chimeric 18L1-45RG1 virus-like particle vaccine cross-protects against oncogenic alpha-7 human papillomavirus types.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Persistent infection with oncogenic human papillomaviruses (HPV types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC, a subset of cervical cancer (CxC. Although the incidence of cervical squamous cell carcinoma (SCC has dramatically decreased following introduction of Papanicolaou (PAP screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent HPV vaccines comprise virus-like particles (VLP of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7 includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18 targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1 of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1. Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent

  17. Rock Tea extract (Jasonia glutinosa) relaxes rat aortic smooth muscle by inhibition of L-type Ca(2+) channels.

    Science.gov (United States)

    Valero, Marta Sofía; Oliván-Viguera, Aida; Garrido, Irene; Langa, Elisa; Berzosa, César; López, Víctor; Gómez-Rincón, Carlota; Murillo, María Divina; Köhler, Ralf

    2015-12-01

    In traditional herbal medicine, Rock Tea (Jasonia glutinosa) is known for its prophylactic and therapeutic value in various disorders including arterial hypertension. However, the mechanism by which Rock Tea exerts blood pressure-lowering actions has not been elucidated yet. Our aim was to demonstrate vasorelaxing effects of Rock Tea extract and to reveal its possible action mechanism. Isometric myography was conducted on high-K+-precontracted rings from rat thoracic aorta and tested extracts at concentrations of 0.5-5 mg/ml. Whole-cell patch-clamp experiments were performed in rat aortic vascular smooth muscle cells (line A7r5) to determine blocking effects on L-type Ca(2+) channels. Rock Tea extract relaxed the aorta contracted by high [K+] concentration dependently with an EC50 of ≈2.4 mg/ml and produced ≈75 % relaxation at the highest concentration tested. The L-type Ca(2+) channel blocker, verapamil (10(-6) M), had similar effects. Rock Tea extract had no effect in nominally Ca(2+)-free high-K(+) buffer but significantly inhibited contractions to re-addition of Ca(2+). Rock Tea extract inhibited the contractions induced by the L-type Ca(2+) channel activator Bay K 8644 (10(-5) M) and by phenylephrine (10(-6) M). Rock Tea extract and Y-27632 (10(-6) M), Rho-kinase inhibitor, had similar effects and the respective effects were not additive. Patch-clamp experiments demonstrated that Rock Tea extract (2.5 mg/ml) virtually abolished L-type Ca(2+) currents in A7r5. We conclude that Rock Tea extract produced vasorelaxation of rat aorta and that this relaxant effect is mediated by inhibition of L-type Ca(2+) channels. Rock Tea extracts may be of phytomedicinal value for prevention and adjuvant treatment of hypertension and other cardiovascular diseases.

  18. Arbitrary l-wave solutions of the Schroedinger equation for the screen Coulomb potential

    International Nuclear Information System (INIS)

    Dong, Shishan; Sun, Guohua; Dong, Shihai

    2013-01-01

    Using improved approximate schemes for centrifugal term and the singular factor 1/r appearing in potential itself, we solve the Schroedinger equation with the screen Coulomb potential for arbitrary angular momentum state l. The bound state energy levels are obtained. A closed form of normalization constant of the wave functions is also found. The numerical results show that our results are in good agreement with those obtained by other methods. The key issue is how to treat two singular points in this quantum system. (author)

  19. Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    Bermúdez-Humarán Luis G

    2009-08-01

    Full Text Available Abstract Background The expression of vaccine antigens in lactic acid bacteria (LAB is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i the expression of Human papillomavirus type 16 (HPV-16 L1 major capsid protein in the model LAB Lactococcus lactis and ii the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs. Results and conclusion HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L. lactis, respectively. The capacity of L. lactis harboring either pCYT:L1 or pSEC:L1 plasmid to accumulate L1 in the cytoplasm and supernatant samples was confirmed by Western blot assays. Electron microscopy analysis suggests that, L1 protein produced by recombinant lactococci can self-assemble into structures morphologically similar to VLPs intracellularly. The presence of conformational epitopes on the L. lactis-derived VLPs was confirmed by ELISA using an anti-HPV16 L1 capsid antigen antibody. Our results support the feasibility of using recombinant food-grade LAB, such as L. lactis, for the production of L1-based VLPs and open the possibility for the development of a new safe mucosal vector for HPV-16 prophylactic vaccination.

  20. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Konold Timm

    2012-03-01

    Full Text Available Abstract Background The majority of atypical bovine spongiform encephalopathy (BSE cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes. Results Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry. Conclusions The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to

  1. Corrosion testing of type 304L stainless steel in tuff groundwater environments

    International Nuclear Information System (INIS)

    Westerman, R.E.; Pitman, S.G.; Haberman, J.H.

    1987-11-01

    The stress-corrosion cracking (SCC) resistance of Type 304L stainless steel (SS) to elevated temperatures in tuff rock and tuff groundwater environments was determined under irradiated and nonirradiated conditions using U-bend specimens and slow-strain-rate tests. The steel was tested both in the solution-annealed condition and after sensitization heat treatments. The material was found to be susceptible to SCC in both the solution-annealed and solution-annealed-and-sensitized conditions when exposed to an irradiated crushed tuff rock environment containing air and water vapor at 90 0 C. A similar exposure at 50 0 C did not result in failure after a 25-month test duration. Specimens of sensitized 304 SS conditioned with a variety of sensitization heat treatments resisted failure during a test of 1-year duration in which a nonirradiated environment of tuff rock and groundwater held at 200 0 C was allowed to boil to dryness on a cyclical basis. All specimens of sensitized 304 SS exposed to this environment failed. Slow-strain-rate studies were performed on 304L, 304, and 316L SS specimens. The 304L SS was tested in J-13 well water at 150 0 C, and the 316L SS at 95 0 C. Neither material showed evidence of SCC in these tests. Sensitized 304 SS did exhibit SCC in J-13 well water in tests conducted at 150 0 C. 12 refs., 27 figs., 13 tabs

  2. Invasive potential of Borrelia burgdorferi sensu stricto ospC type L strains increases the possible disease risk to humans in the regions of their distribution

    Czech Academy of Sciences Publication Activity Database

    Golovchenko, Maryna; Šíma, Radek; Hajdušek, Ondřej; Grubhoffer, Libor; Oliver, J. H., Jr.; Rudenko, Natalia

    2014-01-01

    Roč. 7, NOV 28 2014 (2014), s. 538 ISSN 1756-3305 R&D Projects: GA ČR GP13-27630P; GA ČR GP13-12816P Institutional support: RVO:60077344 Keywords : B. burgdorferi ospC type * Invasive potential * Lyme disease * Southeastern U.S.A. * Tick vector * Vertebrate host Subject RIV: EC - Immunology Impact factor: 3.430, year: 2014

  3. Color evaluation of seventeen European unifloral honey types by means of spectrophotometrically determined CIE L*Cab*h(ab)° chromaticity coordinates.

    Science.gov (United States)

    Tuberoso, Carlo Ignazio Giovanni; Jerković, Igor; Sarais, Giorgia; Congiu, Francesca; Marijanović, Zvonimir; Kuś, Piotr Marek

    2014-02-15

    CIE (Commission Internationale de l'Eclairage) L(*)Cab(*)h(ab)° color coordinates for 305 samples of 17 unifloral honeys types (asphodel, buckwheat, black locust, sweet chestnut, citrus, eucalyptus, Garland thorn, honeydew, heather, lime, mint, rapeseed, sage, strawberry tree, sulla flower, savory and thistle) from different geographic locations in Europe were spectrophotometrically assessed and statistically evaluated. Preliminary separation of unifloral honeys was obtained by means of L(*)-C(ab)(*) color coordination correlation. Hierarchical Cluster Analysis (HCA) revealed an expected segregation of the honeys types according to their chromatic characteristics. Principal Component Analysis (PCA) allowed to obtain a more defined distinction of the 17 unifloral honey types, particularly when using 3D graphics. CIE L(*)C(ab)(*)hab(*) color coordinates were useful for the identification of several honey types. The proposed method represents a simple and efficient procedure that can be used as a basis for the authentication of unifloral honeys worldwide. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Comparison of Ribotyping, Randomly Amplified Polymorphic DNA Analysis, and Pulsed-Field Gel Electrophoresis in Typing of Lactobacillus rhamnosus and L. casei Strains

    OpenAIRE

    Tynkkynen, Soile; Satokari, Reetta; Saarela, Maria; Mattila-Sandholm, Tiina; Saxelin, Maija

    1999-01-01

    A total of 24 strains, biochemically identified as members of the Lactobacillus casei group, were identified by PCR with species-specific primers. The same set of strains was typed by randomly amplified polymorphic DNA (RAPD) analysis, ribotyping, and pulsed-field gel electrophoresis (PFGE) in order to compare the discriminatory power of the methods. Species-specific primers for L. rhamnosus and L. casei identified the type strain L. rhamnosus ATCC 7469 and the neotype strain L. casei ATCC 33...

  5. Potential for phytoextraction of copper, lead, and zinc by rice (Oryza sativa L.), soybean (Glycine max [L.] Merr.), and maize (Zea mays L.).

    Science.gov (United States)

    Murakami, Masaharu; Ae, Noriharu

    2009-03-15

    Phytoextraction by hyperaccumulators has been proposed for decreasing toxic-metal concentrations of contaminated soils. However, hyperaccumulators have several shortcomings to introduce these species into Asian Monsoon's agricultural fields contaminated with low to moderate toxic-metals. To evaluate the phytoextraction potential, maize (Gold Dent), soybean (Enrei and Suzuyutaka), and rice (Nipponbare and Milyang 23) were pot-grown under aerobic soil conditions for 60d on the Andosol or Fluvisol with low to moderate copper (Cu), lead (Pb), and zinc (Zn) contamination. After 2 months cultivation, the Gold Dent maize and Milyang 23 rice shoots took up 20.2-29.5% and 18.5-20.2% of the 0.1molL(-1) HCl-extractable Cu, 10.0-37.3% and 8.5-34.3% of the DTPA-extractable Cu, and 2.4-6.5% and 2.1-5.9% of the total Cu, respectively, in the two soils. Suzuyutaka soybean shoot took up 23.0-29.4% of the 0.1molL(-1) HCl-extractable Zn, 35.1-52.6% of the DTPA-extractable Zn, and 3.8-5.3% of the total Zn in the two soils. Therefore, there is a great potential for Cu phytoextraction by the Gold Dent maize and the Milyang 23 rice and for Zn phytoextraction by the Suzuyutaka soybean from paddy soils with low to moderate contamination under aerobic soil conditions.

  6. Leishmania (L. mexicana infected bats in Mexico: novel potential reservoirs.

    Directory of Open Access Journals (Sweden)

    Miriam Berzunza-Cruz

    2015-01-01

    Full Text Available Leishmania (Leishmania mexicana causes cutaneous leishmaniasis, an endemic zoonosis affecting a growing number of patients in the southeastern states of Mexico. Some foci are found in shade-grown cocoa and coffee plantations, or near perennial forests that provide rich breeding grounds for the sand fly vectors, but also harbor a variety of bat species that live off the abundant fruits provided by these shade-giving trees. The close proximity between sand flies and bats makes their interaction feasible, yet bats infected with Leishmania (L. mexicana have not been reported. Here we analyzed 420 bats from six states of Mexico that had reported patients with leishmaniasis. Tissues of bats, including skin, heart, liver and/or spleen were screened by PCR for Leishmania (L. mexicana DNA. We found that 41 bats (9.77%, belonging to 13 species, showed positive PCR results in various tissues. The infected tissues showed no evidence of macroscopic lesions. Of the infected bats, 12 species were frugivorous, insectivorous or nectarivorous, and only one species was sanguivorous (Desmodus rotundus, and most of them belonged to the family Phyllostomidae. The eco-region where most of the infected bats were caught is the Gulf Coastal Plain of Chiapas and Tabasco. Through experimental infections of two Tadarida brasiliensis bats in captivity, we show that this species can harbor viable, infective Leishmania (L. mexicana parasites that are capable of infecting BALB/c mice. We conclude that various species of bats belonging to the family Phyllostomidae are possible reservoir hosts for Leishmania (L. mexicana, if it can be shown that such bats are infective for the sand fly vector. Further studies are needed to determine how these bats become infected, how long the parasite remains viable inside these potential hosts and whether they are infective to sand flies to fully evaluate their impact on disease epidemiology.

  7. Leishmania (L.) mexicana Infected Bats in Mexico: Novel Potential Reservoirs

    Science.gov (United States)

    Berzunza-Cruz, Miriam; Rodríguez-Moreno, Ángel; Gutiérrez-Granados, Gabriel; González-Salazar, Constantino; Stephens, Christopher R.; Hidalgo-Mihart, Mircea; Marina, Carlos F.; Rebollar-Téllez, Eduardo A.; Bailón-Martínez, Dulce; Balcells, Cristina Domingo; Ibarra-Cerdeña, Carlos N.; Sánchez-Cordero, Víctor; Becker, Ingeborg

    2015-01-01

    Leishmania (Leishmania) mexicana causes cutaneous leishmaniasis, an endemic zoonosis affecting a growing number of patients in the southeastern states of Mexico. Some foci are found in shade-grown cocoa and coffee plantations, or near perennial forests that provide rich breeding grounds for the sand fly vectors, but also harbor a variety of bat species that live off the abundant fruits provided by these shade-giving trees. The close proximity between sand flies and bats makes their interaction feasible, yet bats infected with Leishmania (L.) mexicana have not been reported. Here we analyzed 420 bats from six states of Mexico that had reported patients with leishmaniasis. Tissues of bats, including skin, heart, liver and/or spleen were screened by PCR for Leishmania (L.) mexicana DNA. We found that 41 bats (9.77%), belonging to 13 species, showed positive PCR results in various tissues. The infected tissues showed no evidence of macroscopic lesions. Of the infected bats, 12 species were frugivorous, insectivorous or nectarivorous, and only one species was sanguivorous (Desmodus rotundus), and most of them belonged to the family Phyllostomidae. The eco-region where most of the infected bats were caught is the Gulf Coastal Plain of Chiapas and Tabasco. Through experimental infections of two Tadarida brasiliensis bats in captivity, we show that this species can harbor viable, infective Leishmania (L.) mexicana parasites that are capable of infecting BALB/c mice. We conclude that various species of bats belonging to the family Phyllostomidae are possible reservoir hosts for Leishmania (L.) mexicana, if it can be shown that such bats are infective for the sand fly vector. Further studies are needed to determine how these bats become infected, how long the parasite remains viable inside these potential hosts and whether they are infective to sand flies to fully evaluate their impact on disease epidemiology. PMID:25629729

  8. Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.

    Science.gov (United States)

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-12-09

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.

  9. Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle.

    Science.gov (United States)

    Bowles, D K; Maddali, K K; Ganjam, V K; Rubin, L J; Tharp, D L; Turk, J R; Heaps, C L

    2004-11-01

    Evidence indicates that gender and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca2+ current (ICa,L) in coronary arterial smooth muscle (CASM) of male compared with female swine. The promoter region of the L-type voltage-gated Ca2+ channel (VGCC) (Cav1.2) gene contains a hormone response element that is activated by testosterone. Thus the purpose of the present study was to determine whether endogenous testosterone regulates CASM ICa,L through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7-8 mo; 35-45 kg) were obtained from the breeder. Males were left intact (IM, n=8), castrated (CM, n=8), or castrated with testosterone replacement (CMT, n=8; 10 mg/day Androgel). Females remained gonad intact (n=8). In right coronary arteries, both Cav1.2 mRNA and protein were greater in IM compared with intact females. Cav1.2 mRNA and protein were reduced in CM compared with IM and restored in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM compared with IM and restored in CMT. In males, a linear relationship was found between serum testosterone levels and ICa. In vitro, both testosterone and the nonaromatizable androgen, dihydrotestosterone, increased Cav1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist cyproterone. We conclude that endogenous testosterone is a primary regulator of Cav1.2 expression and activity in coronary arteries of males.

  10. Imaging the L-type amino acid transporter-1 (LAT1 with Zr-89 immunoPET.

    Directory of Open Access Journals (Sweden)

    Oluwatayo F Ikotun

    Full Text Available The L-type amino acid transporter-1 (LAT1, SLC7A5 is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[(18F]fluoroethyl-L-tyrosine (FET that are transport substrates for system L amino acid transporters including LAT1 have met limited success for oncologic imaging outside of the brain, and thus new strategies are needed for imaging LAT1 in systemic cancers. Here, we describe the development and biological evaluation of a novel zirconium-89 labeled antibody, [(89Zr]DFO-Ab2, targeting the extracellular domain of LAT1 in a preclinical model of colorectal cancer. This tracer demonstrated specificity for LAT1 in vitro and in vivo with excellent tumor imaging properties in mice with xenograft tumors. PET imaging studies showed high tumor uptake, with optimal tumor-to-non target contrast achieved at 7 days post administration. Biodistribution studies demonstrated tumor uptake of 10.5 ± 1.8 percent injected dose per gram (%ID/g at 7 days with a tumor to muscle ratio of 13 to 1. In contrast, the peak tumor uptake of the radiolabeled amino acid [(18F]FET was 4.4 ± 0.5 %ID/g at 30 min after injection with a tumor to muscle ratio of 1.4 to 1. Blocking studies with unlabeled anti-LAT1 antibody demonstrated a 55% reduction of [(89Zr]DFO-Ab2 accumulation in the tumor at 7 days. These results are the first report of direct PET imaging of LAT1 and demonstrate the potential of immunoPET agents for imaging specific amino acid transporters.

  11. Delay in the issuing of D-type Swiss cartes de légitimation

    CERN Multimedia

    DSU Department

    2007-01-01

    The Permanent Mission of Switzerland to the International Organisations in Geneva has informed CERN that, for technical reasons, the Federal Department of Foreign Affairs (Département fédéral des Affaires étrangères - DFAE) will be unable to issue D-type cartes de légitimation until after 15 December 2007. This is because, following the introduction of a new graphic design decided by the Swiss Federal Council, stocks of this type of card have run out. In the meantime, the Mission will issue E-type cards to the individuals concerned. These are valid for six months and will be gradually exchanged for D-type cards between December 2007 and February 2008. The Mission points out that the holding of an E-type card for a limited period will have no impact on the status of the officials in question, who will continue to benefit from immunity from jurisdiction in the discharge of their duties and be exempt from the payment of the annual tax on vehicles (a special note to this e...

  12. Radiological protection in two types of human activities and from potential exposure

    International Nuclear Information System (INIS)

    Li Deping

    1991-01-01

    The new ICPR recommendations emphasize the distinction in radiological protection in two different types of human activities, practice and intervention. The purpose of emphases and measures for controlling or reduction of exposure for each type of activity are discussed. Potential exposure is regarded as an part of radiological protection system in this new recommendations, in a practice, it can be significantly reduced by proper prevention and mitigation measures in design and management. It is pointed out that with modern safety technology, the probability of potential exposure situations can be lowered to many orders of magnitude, even though the estimated value of probability is not accurate. Situations requiring intervention and the principles in protection are also discussed

  13. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    Science.gov (United States)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  14. Potential for yield in red clover (Trifolium pratense L. varieties

    Directory of Open Access Journals (Sweden)

    Vasiljević Sanja

    2010-01-01

    Full Text Available Red clover (Trifolium pratense L. is botanically a perennial, although it often behaves as a biennial. The crop usually lives 2 to 3 seasons in most clover-growing regions of the world and is generally conceded to be lacking in persistence. The objective of this investigation was to analyze the production potential and persistence of domestic and imported red clover varieties. Experiments were conducted at Rimski Šančevi Experiment Field during the period 2004-2006. The experimental materials were six varieties (K-17, Kolubara, Una, Viola, Start, Nike which were analyzed for the most important production characteristics: yield of green mass, dry matter yield and persistence. .

  15. Probing the interaction of human serum albumin with vitamin B2 (riboflavin) and L-Arginine (L-Arg) using multi-spectroscopic, molecular modeling and zeta potential techniques

    International Nuclear Information System (INIS)

    Memarpoor-Yazdi, Mina; Mahaki, Hanie

    2013-01-01

    This study was designed to examine the interaction of Riboflavin (RB) and L-Arginine (L-Arg) with human serum albumin (HSA) using different spectroscopic, zeta potential and molecular modeling techniques under imitated physiological conditions. The resonance light scattering (RLS) method determined the critical aggregation concentration of RB on HSA in the presence and absence of L-Arg which confirmed the zeta potential results. The binding constants (K a ) of HSA–RB were 2.5×10 4 and 9.7×10 3 M −1 , respectively in binary and ternary system at the excitation wavelength of 280 nm, also were 7.5×10 3 and 7.3×10 3 , respectively in binary and ternary system at the excitation wavelength of 295 nm. Fluorescence spectroscopy demonstrated that in the presence of L-Arg, the binding constant of HSA–RB was increased. Static quenching was confirmed to results in the fluorescence quenching and FRET. The binding distances between HSA and RB in two- and three-component systems were estimated by the Forster theory which revealed that nonradiative energy transfer from HSA to RB occurred with a high probability. The effect of RB on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy and circular dichroism (CD) in both systems. Docking studies demonstrated a reduction in the binding affinity between RB and HSA in the presence of L-Arg. -- Highlights: ► We studied the interaction of riboflavin with HSA in presence and absence of L-Arg. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We compared the binding mechanism of riboflavin (RB) to HSA in both systems. ► We determined critical aggregation concentration of RB on HSA in both systems. ► The binding site of RB on HSA in both systems has been determined

  16. Probing the interaction of human serum albumin with vitamin B2 (riboflavin) and L-Arginine (L-Arg) using multi-spectroscopic, molecular modeling and zeta potential techniques

    Energy Technology Data Exchange (ETDEWEB)

    Memarpoor-Yazdi, Mina [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Mahaki, Hanie, E-mail: hanieh.mahaki@gmail.com [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of)

    2013-04-15

    This study was designed to examine the interaction of Riboflavin (RB) and L-Arginine (L-Arg) with human serum albumin (HSA) using different spectroscopic, zeta potential and molecular modeling techniques under imitated physiological conditions. The resonance light scattering (RLS) method determined the critical aggregation concentration of RB on HSA in the presence and absence of L-Arg which confirmed the zeta potential results. The binding constants (K{sub a}) of HSA–RB were 2.5×10{sup 4} and 9.7×10{sup 3} M{sup −1}, respectively in binary and ternary system at the excitation wavelength of 280 nm, also were 7.5×10{sup 3} and 7.3×10{sup 3}, respectively in binary and ternary system at the excitation wavelength of 295 nm. Fluorescence spectroscopy demonstrated that in the presence of L-Arg, the binding constant of HSA–RB was increased. Static quenching was confirmed to results in the fluorescence quenching and FRET. The binding distances between HSA and RB in two- and three-component systems were estimated by the Forster theory which revealed that nonradiative energy transfer from HSA to RB occurred with a high probability. The effect of RB on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy and circular dichroism (CD) in both systems. Docking studies demonstrated a reduction in the binding affinity between RB and HSA in the presence of L-Arg. -- Highlights: ► We studied the interaction of riboflavin with HSA in presence and absence of L-Arg. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We compared the binding mechanism of riboflavin (RB) to HSA in both systems. ► We determined critical aggregation concentration of RB on HSA in both systems. ► The binding site of RB on HSA in both systems has been determined.

  17. Glycoprotein H of herpes simplex virus type 1 requires glycoprotein L for transport to the surfaces of insect cells

    NARCIS (Netherlands)

    Westra, DF; Glazenburg, KL; Harmsen, MC; Tiran, A; Scheffer, AJ; Welling, GW; The, TH; WellingWester, S

    In mammalian cells, formation of heterooligomers consisting of the glycoproteins H and L (gH and gL) of herpes simplex virus type 1 is essential for the cell-to-cell spread of virions and for the penetration of virions into cells. We examined whether formation of gH1/gL1 heterooligomers and cell

  18. Maltese Mushroom (Cynomorium coccineum L. as Source of Oil with Potential Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Antonella Rosa

    2015-01-01

    Full Text Available The present study aimed to examine the potential anticancer properties of fixed oil obtained from Maltese mushroom (Cynomorium coccineum L., an edible, non-photosynthetic plant, used in traditional medicine of Mediterranean countries to treat various ailments and as an emergency food during the famine. We investigated the effect of the oil, obtained from dried stems by supercritical fractioned extraction with CO2, on B16F10 melanoma and colon cancer Caco-2 cell viability and lipid profile. The oil, rich in essential fatty acids (18:3n-3 and 18:2n-6, showed a significant growth inhibitory effect on melanoma and colon cancer cells. The incubation (24 h with non-toxic oil concentrations (25 and 50 μg/mL induced in both cancer cell lines a significant accumulation of the fatty acids 18:3n-3 and 18:2n-6 and an increase of the cellular levels of eicosapentaenoic acid (20:5n-3 with anticancer activity. Moreover, the oil exhibited the ability to potentiate the growth inhibitory effect of the antitumor drug 5-fluorouracil in Caco-2 cells and to influence the melanin content in B16F10 cells. The results qualify C. coccineum as a resource of oil, with potential benefits in cancer prevention, for nutraceutical and pharmaceutical applications.

  19. Sequential creep-fatigue interaction in austenitic stainless steel type 316L-SPH

    International Nuclear Information System (INIS)

    Tavassoli, A.A.; Mottot, M.; Petrequin, P.

    1986-01-01

    Influence of a prior creep or fatigue exposure on subsequent fatigue or creep properties of stainless steel type 316 L SPH has been investigated. The results obtained are used to verify the validity of time and cycle fraction rule and to obtain information on the effect of very long intermittent hold times on low cycle fatigue properties, as well as on transitory loads occurring during normal service of some structural components of LMFBR reactors. Creep and fatigue tests have been carried out at 600 0 C and under conditions yielding equal or different fatigue saturation and creep stresses. Prior creep damage levels introduced range from primary to tertiary creep, whilst those of fatigue span from 20 to 70 percent of fatigue life. In both creep-fatigue and fatigue-creep sequences in the absence of a permanent prior damage (cavitation or cracking) the subsequent resistance of 316 L-SPH to fatigue or creep is unchanged, if not improved. Thin foils prepared from the specimens confirmed these observations and showed that the dislocation substructure developed during the first mode of testing is quickly replaced by that of the second mode. Grain boundary cavitation does not occur in 316 L-SPH during creep exposures to well beyond the apparent end of secondary stage and as a result prior creep exposures up to approximately 80% of rupture life do not affect fatigue properties. Conversely, significant surface cracks were found in the prior fatigue tested specimens after above about 50% life. In the presence of such cracks the subsequent creep damage was localized at the tip of the main crack and the remaining creep life was found to be usually proportional to the effective specimen cross section. Creep and fatigue sequential damage are not necessarily additive and this type of loadings are in general less severe than the repeated creep-fatigue cycling. 17 refs.

  20. Magnetic and structural properties of L1{sub 1} type CoPt-C ordered alloy perpendicular films as a function of C content

    Energy Technology Data Exchange (ETDEWEB)

    Shimatsu, T; Kataoka, H; Aoi, H [Research Institute of Electrical Communication, Tohoku University, Sendai, 980-8577 (Japan); Sato, H; Okamoto, S; Kitakami, O, E-mail: shimatsu@riec.tohoku.ac.j [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, 980-8577 (Japan)

    2010-01-01

    Magnetic and structural properties of L1{sub 1} type (Co{sub 0.5}Pt{sub 0.5}){sub 100-X}-C{sub X} ordered alloy perpendicular films, fabricated on 2.5 inch size glass disks by sputter deposition, were examined as a function of C content, X. L1{sub 1} type Co{sub 0.5}Pt{sub 0.5}-C polycrystalline films (10 nm thickness), with <111> axis (the easy axis) perpendicular to the film plane, were successfully fabricated even for a 30 vol% C content. Structural analysis indicated the segregation of C to the grain boundaries. Uniaxial magnetic anisotropy, K{sub u}, of Co{sub 0.5}Pt{sub 0.5} films without C addition was relatively low, about 1.5x10{sup 7} erg/cm{sup 3} under the present deposition conditions. However, the addition of 5 vol.% C to Co-Pt films enhanced the ordering, resulting in an increase in K{sub u} to around 2.5 x10{sup 7} erg/cm{sup 3}. A further increase in C content reduced K{sub u}; however, K{sub u} maintained a relatively large value of about 1.8x10{sup 7} erg/cm{sup 3} even for a 20vol% C content, without degrading the easy axis orientation perpendicular to the film plane. Experimental results demonstrated the potential of the L1{sub 1} type Co{sub 0.5}Pt{sub 0.5}-C films for use in granular media applications, due to their very high K{sub u}, the relatively low fabrication temperature, and good controllability of the grain orientation.

  1. The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses

    Directory of Open Access Journals (Sweden)

    Liheng Shi

    2017-12-01

    Full Text Available L-type voltage-gated calcium channels (LTCCs regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4 expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3−/− mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG recordings and immunohistochemical staining, we found that Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3−/− mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT. Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Cav1.3−/− mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported.

  2. The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses.

    Science.gov (United States)

    Shi, Liheng; Chang, Janet Ya-An; Yu, Fei; Ko, Michael L; Ko, Gladys Y-P

    2017-01-01

    L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Ca v 1.2, Ca v 1.3, and Ca v 1.4) expressed in the retina. While Ca v 1.2 is expressed in all retinal cells including the Müller glia and neurons, Ca v 1.3 and Ca v 1.4 are expressed in the retinal neurons with Ca v 1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Ca v 1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Ca v 1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Ca v 1.3 are not associated with severe vision impairment in humans or in Ca v 1.3-null (Ca v 1.3 -/- ) mice. However, a failure to regulate Ca v 1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Ca v 1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Ca v 1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Ca v 1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Ca v 1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Ca v 1.3 -/- mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Ca v 1.3 -/- mice retinas. Hence, Ca v 1.3 plays a more prominent role in retinal physiology and function than previously reported.

  3. Policing starter unit selection of the enterocin type II polyketide synthase by the type II thioesterase EncL.

    Science.gov (United States)

    Kalaitzis, John A; Cheng, Qian; Meluzzi, Dario; Xiang, Longkuan; Izumikawa, Miho; Dorrestein, Pieter C; Moore, Bradley S

    2011-11-15

    Enterocin is an atypical type II polyketide synthase (PKS) product from the marine actinomycete 'Streptomyces maritimus'. The enterocin biosynthesis gene cluster (enc) codes for proteins involved in the assembly and attachment of the rare benzoate primer that initiates polyketide assembly with the addition of seven malonate molecules and culminates in a Favorskii-like rearrangement of the linear poly-β-ketone to give its distinctive non-aromatic, caged core structure. Fundamental to enterocin biosynthesis, which utilizes a single acyl carrier protein (ACP), EncC, for both priming with benzoate and elongating with malonate, involves maintaining the correct balance of acyl-EncC substrates for efficient polyketide assembly. Here, we report the characterization of EncL as a type II thioesterase that functions to edit starter unit (mis)priming of EncC. We performed a series of in vivo mutational studies, heterologous expression experiments, in vitro reconstitution studies, and Fourier-transform mass spectrometry-monitored competitive enzyme assays that together support the proposed selective hydrolase activity of EncL toward misprimed acetyl-ACP over benzoyl-ACP to facilitate benzoyl priming of the enterocin PKS complex. While this system resembles the R1128 PKS that also utilizes an editing thioesterase (ZhuC) to purge acetate molecules from its initiation module ACP in favor of alkylacyl groups, the enterocin system is distinct in its usage of a single ACP for both priming and elongating reactions with different substrates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hossein Mirmiranpour

    2016-01-01

    Full Text Available Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine, amino acids (e.g. L-lysine and polyols (e.g. glycerol. They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM were randomly divided into two groups of 25 (test and control. All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients.

  5. Evaluation of Antioxidant and Antibacterial Potentials of Nigella sativa L. Suspension Cultures under Elicitation

    Directory of Open Access Journals (Sweden)

    Hera Chaudhry

    2015-01-01

    Full Text Available Nigella sativa L. (family Ranunculaceae is an annual herb of immense medicinal properties because of its major active components (i.e., thymoquinone (TQ, thymohydroquinone (THQ, and thymol (THY. Plant tissue culture techniques like elicitation, Agrobacterium mediated transformation, hairy root culture, and so on, are applied for substantial metabolite production. This study enumerates the antibacterial and antioxidant potentials of N. sativa epicotyl suspension cultures under biotic and abiotic elicitation along with concentration optimization of the elicitors for enhanced TQ and THY production. Cultures under different concentrations of pectin and manganese chloride (MnCl2 elicitation (i.e., 5 mg/L, 10 mg/L, and 15 mg/L showed that the control, MnCl2 10 mg/L, and pectin 15 mg/L suspension extracts greatly inhibited the growth of E. coli, S. typhimurium, and S. aureus (MIC against E. coli, i.e., 2.35±0.8, 2.4±0.2, and 2.46±0.5, resp.. Elicitation decreased SOD enzyme activity whereas CAT enzyme activity increased remarkably under MnCl2 elicitation. MnCl2 10 mg/L and pectin 15 mg/L elicitation enhanced the DPPH radical inhibition ability, but ferric scavenging activity was comparable to the control. TQ and THY were quantified by LC-MS/MS in the cultures with high bioactive properties revealing maximum content under MnCl2 10 mg/L elicitation. Therefore, MnCl2 elicitation can be undertaken on large scale for sustainable metabolite production.

  6. Evaluation of Antioxidant and Antibacterial Potentials of Nigella sativa L. Suspension Cultures under Elicitation.

    Science.gov (United States)

    Chaudhry, Hera; Fatima, Nida; Ahmad, Iffat Zareen

    2015-01-01

    Nigella sativa L. (family Ranunculaceae) is an annual herb of immense medicinal properties because of its major active components (i.e., thymoquinone (TQ), thymohydroquinone (THQ), and thymol (THY)). Plant tissue culture techniques like elicitation, Agrobacterium mediated transformation, hairy root culture, and so on, are applied for substantial metabolite production. This study enumerates the antibacterial and antioxidant potentials of N. sativa epicotyl suspension cultures under biotic and abiotic elicitation along with concentration optimization of the elicitors for enhanced TQ and THY production. Cultures under different concentrations of pectin and manganese chloride (MnCl2) elicitation (i.e., 5 mg/L, 10 mg/L, and 15 mg/L) showed that the control, MnCl2 10 mg/L, and pectin 15 mg/L suspension extracts greatly inhibited the growth of E. coli, S. typhimurium, and S. aureus (MIC against E. coli, i.e., 2.35 ± 0.8, 2.4 ± 0.2, and 2.46 ± 0.5, resp.). Elicitation decreased SOD enzyme activity whereas CAT enzyme activity increased remarkably under MnCl2 elicitation. MnCl2 10 mg/L and pectin 15 mg/L elicitation enhanced the DPPH radical inhibition ability, but ferric scavenging activity was comparable to the control. TQ and THY were quantified by LC-MS/MS in the cultures with high bioactive properties revealing maximum content under MnCl2 10 mg/L elicitation. Therefore, MnCl2 elicitation can be undertaken on large scale for sustainable metabolite production.

  7. Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India.

    Science.gov (United States)

    Dutta, Prachurjya; Dey, Tapan; Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Elevated oxidative stress plays an important role in the pathogenesis of health disorders, like arthritis. Traditionally, Vespa affinis L., a common edible insect among many tribes in North-East India, is believed to have a beneficial role in extenuating health disorders, such as arthritis. The present study investigated the molecular mechanism underlying medicinal benefit of the Aqueous Extract of Vespa affinis L. (AEVA) against oxidative stress pathophysiology. The free radical scavenging activities of AEVA were examined against DPPH, hydroxyl, and superoxide radicals and the effect on the activities of antioxidant enzyme (GST and CAT) was determined using both recombinant proteins and human plasma. The antioxidant potential of AEVA was again investigated using THP-1 monocytes. AEVA possesses a significant free radical scavenging activity as evident from the DPPH, superoxide, and hydroxyl radical scavenging assay. Incubation of AEVA (2.5, 5, 7.5, and 10 μg/μL) with the recombinant antioxidant enzymes, rGST and rCAT significantly increased the enzyme activities compared to those observed in corresponding enzyme alone or AEVA itself. AEVA supplementation (5, 7.5, and 10 μg/μL) also stimulates the activities of GST and CAT when incubated with human plasma. A cell culture study also confirmed the beneficial role of AEVA (0.8 and 1.2 μg/μL) which enhances the activities of GST and CAT, and also reduces the intercellular ROS production in monocytes treated with or without H2O2 and the effects are at par with what is observed in N-acetyl cysteine-treated cells. The antioxidant potential of the aqueous extract of Vespa affinis L. may mediate its therapeutic activities in oxidative stress-associated health disorders.

  8. Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India.

    Directory of Open Access Journals (Sweden)

    Prachurjya Dutta

    Full Text Available Elevated oxidative stress plays an important role in the pathogenesis of health disorders, like arthritis. Traditionally, Vespa affinis L., a common edible insect among many tribes in North-East India, is believed to have a beneficial role in extenuating health disorders, such as arthritis. The present study investigated the molecular mechanism underlying medicinal benefit of the Aqueous Extract of Vespa affinis L. (AEVA against oxidative stress pathophysiology.The free radical scavenging activities of AEVA were examined against DPPH, hydroxyl, and superoxide radicals and the effect on the activities of antioxidant enzyme (GST and CAT was determined using both recombinant proteins and human plasma. The antioxidant potential of AEVA was again investigated using THP-1 monocytes.AEVA possesses a significant free radical scavenging activity as evident from the DPPH, superoxide, and hydroxyl radical scavenging assay. Incubation of AEVA (2.5, 5, 7.5, and 10 μg/μL with the recombinant antioxidant enzymes, rGST and rCAT significantly increased the enzyme activities compared to those observed in corresponding enzyme alone or AEVA itself. AEVA supplementation (5, 7.5, and 10 μg/μL also stimulates the activities of GST and CAT when incubated with human plasma. A cell culture study also confirmed the beneficial role of AEVA (0.8 and 1.2 μg/μL which enhances the activities of GST and CAT, and also reduces the intercellular ROS production in monocytes treated with or without H2O2 and the effects are at par with what is observed in N-acetyl cysteine-treated cells.The antioxidant potential of the aqueous extract of Vespa affinis L. may mediate its therapeutic activities in oxidative stress-associated health disorders.

  9. Abnormalities in auditory evoked potentials of 75 patients with Arnold-Chiari malformations types I and II

    Directory of Open Access Journals (Sweden)

    Henriques Filho Paulo Sergio A.

    2006-01-01

    Full Text Available OBJECTIVE: To evaluate the frequency and degree of severity of abnormalities in the auditory pathways in patients with Chiari malformations type I and II. METHOD: This is a series-of-case descriptive study in which the possible presence of auditory pathways abnormalities in 75 patients (48 children and 27 adults with Chiari malformation types I and II were analyzed by means of auditory evoked potentials evaluation. The analysis was based on the determination of intervals among potentials peak values, absolute latency and amplitude ratio among potentials V and I. RESULTS: Among the 75 patients studied, 27 (36% disclosed Arnold-Chiari malformations type I and 48 (64% showed Arnold-Chiari malformations type II. Fifty-three (71% of these patients showed some degree of auditory evoked potential abnormalities. Tests were normal in the remaining 22 (29% patients. CONCLUSION: Auditory evoked potentials testing can be considered a valuable instrument for diagnosis and evaluation of brain stem functional abnormalities in patients with Arnold-Chiari malformations type I and II. The determination of the presence and degree of severity of these abnormalities can be contributory to the prevention of further handicaps in these patients either through physical therapy or by means of precocious corrective surgical intervention.

  10. A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

    International Nuclear Information System (INIS)

    Galvis-Pareja, David; Zapata-Torres, Gerald; Hidalgo, Jorge; Ayala, Pedro

    2014-01-01

    Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca 2+ channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca 2+ channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca 2+ channel-blocking activity and antioxidant properties. The Ca 2+ channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca 2+ channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca 2+ channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca 2+ entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca 2+ blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca 2+ blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties

  11. C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1.

    Science.gov (United States)

    Meng, Xiangzhi; Schoggins, John; Rose, Lloyd; Cao, Jingxin; Ploss, Alexander; Rice, Charles M; Xiang, Yan

    2012-04-01

    Vaccinia virus (VACV) K1L and C7L function equivalently in many mammalian cells to support VACV replication and antagonize antiviral activities induced by type I interferons (IFNs). While K1L is limited to orthopoxviruses, genes that are homologous to C7L are found in diverse mammalian poxviruses. In this study, we showed that the C7L homologues from sheeppox virus and swinepox virus could rescue the replication defect of a VACV mutant deleted of both K1L and C7L (vK1L(-)C7L(-)). Interestingly, the sheeppox virus C7L homologue could rescue the replication of vK1L(-)C7L(-) in human HeLa cells but not in murine 3T3 and LA-4 cells, in contrast to all other C7L homologues. Replacing amino acids 134 and 135 of the sheeppox virus C7L homologue, however, made it functional in the two murine cell lines, suggesting that these two residues are critical for antagonizing a putative host restriction factor which has some subtle sequence variation in human and murine cells. Furthermore, the C7L family of host range genes from diverse mammalian poxviruses were all capable of antagonizing type I IFN-induced antiviral activities against VACV. Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV. Expression of either K1L or C7L, however, rendered vK1L(-)C7L(-) resistant to IRF1-induced antiviral activities. Altogether, our data show that K1L and C7L antagonize IRF1-induced antiviral activities and that the host modulation function of C7L is evolutionally conserved in all poxviruses that can readily replicate in tissue-cultured mammalian cells.

  12. Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

    NARCIS (Netherlands)

    Verkerk, Arie O.; den Ruijter, Hester M.; de Jonge, Nicolaas; Coronel, Ruben

    2009-01-01

    Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased

  13. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen

    2011-01-01

    Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved......-type subtype (Ca(v) 3.1 and Ca(v) 3.2) voltage-gated calcium channels (Ca(v)s), and quantitative PCR showed highest expression of L-type channels in renal arteries and variable expression between patients of subtypes of calcium channels in intrarenal vessels. Immunohistochemical labeling of kidney sections...

  14. Study on Effect of Type of Explant and Hormone on Callus Induction and Regeneration in Saffron (Crocus sativus L.

    Directory of Open Access Journals (Sweden)

    Mohsen Sajjadi

    2015-10-01

    Full Text Available Saffron (Crocus sativus L. is one of the medicinal plants that contain active components and medicinal materials. Tissue culture of saffron can improve the quality and quantity of the saffron product, increase its export and the farmers’ income. In this study, 36 different types of hormone combinations in the dark and 9 different treatments of hormone combinations in cold (4°C, using different saffron explants (bulb, leaf, scales around leaf and distal parts of the leaf were studied in tissue culture. To investigate the growth of corms, the callus formation and the regeneration rate, three replications for each treatment were used and the length of shoot (cm, the callus formation percentage and the regeneration percentage were measured and statistical analysis was performed. Among the types of explants, only explants from bulbs produced the callus on MS medium containing 2 mg.l-1 BAP and 1 mg.l-1 IBA in both the dark and cold conditions. The highest percentage of regeneration was obtained in MS medium with hormonal composition of 0.3 mg.l-1 TDZ, 1 mg.l-1 BAP, 2 mg.l-1 IBA and 0.01 mg.l-1 GA3 in the cold conditions.

  15. Structural instability of sheath potential distribution and its possible implications for the L/H transition in tokamak plasmas

    International Nuclear Information System (INIS)

    Yoshida, Zensho; Yamada, Hiroshi.

    1988-07-01

    The Bohm equation of electrostatic potential distributions in one-dimensional plasmas has been studied for various Mach numbers and plasma potentials. Solvability and structural stability have been discussed using the Sagdeev potential. Implications of the structural stability for the L/H transitions in tokamak plasmas has been also discussed. (author)

  16. l-Ergothioneine improves the developmental potential of in vitro sheep embryos without influencing OCTN1-mediated cross-membrane transcript expression.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Dhali, A; Javvaji, P K

    2018-04-02

    SummaryThe objective of the study was to investigate the effect of l-ergothioneine (l-erg) (5 mM or 10 mM) supplementation in maturation medium on the developmental potential and OCTN1-dependant l-erg-mediated (10 mM) change in mRNA abundance of apoptotic (Bcl2, Bax, Casp3 and PCNA) and antioxidant (GPx, SOD1, SOD2 and CAT) genes in sheep oocytes and developmental stages of embryos produced in vitro. Oocytes matured with l-erg (10 mM) reduced their embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH in matured oocytes that in turn improved developmental potential, resulting in significantly (P l-erg without change in maturation rate. l-Erg (10 mM) treatment did not influence the mRNA abundance of the majority of apoptotic and antioxidant genes studied in the matured oocytes and developmental stages of embryo. A gene expression study found that the SLC22A4 gene that encodes OCTN1, an integral membrane protein and specific transporter of l-erg was not expressed in oocytes and developmental stages of embryos. Therefore it was concluded from the study that although there was improvement in the developmental potential of sheep embryos by l-erg supplementation in maturation medium, there was no change in the expression of the majority of the genes studied due to the absence of the SLC22A4 gene in oocytes and embryos that encode OCTN1, which is responsible for transportation of l-erg across the membrane to alter gene expression.

  17. Thermal fatigue behaviour for a 316 L type steel

    Science.gov (United States)

    Fissolo, A.; Marini, B.; Nais, G.; Wident, P.

    1996-10-01

    This paper deals with initiation and growth of cracks produced by thermal fatigue loadings on 316 L steel, which is a reference material for the first wall of the next fusion reactor ITER. Two types of facilities have been built. As for true components, thermal cycles have been repeatedly applied on the surface of the specimen. The first is mainly concerned with initiation, which is detected with a light microscope. The second allows one to determine the propagation of a single crack. Crack initiation is analyzed using the French RCC-MR code procedure, and the strain-controlled isothermal fatigue curves. To predict crack growth, a model previously proposed by Haigh and Skelton is applied. This is based on determination of effective stress intensity factors, which takes into account both plastic strain and crack closure phenomena. It is shown that estimations obtained with such methodologies are in good agreement with experimental data.

  18. Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.).

    Science.gov (United States)

    Leivas, Carolina Lopes; Iacomini, Marcello; Cordeiro, Lucimara M C

    2016-05-15

    A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. After the purification steps, two homogeneous fractions were obtained. Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. These arabinogalactans were linked to type I rhamnogalacturonans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Genetic Transformation and Hairy Root Induction Enhance the Antioxidant Potential of Lactuca serriola L.

    Directory of Open Access Journals (Sweden)

    Mohamed A. El-Esawi

    2017-01-01

    Full Text Available Lactuca serriola L. is a herbaceous species, used for human nutrition and medicinal purposes. The high antioxidant capacity of L. serriola indicates the possibility of enhancing its edible and health potential by increasing the flavonoid and phenolic contents. The present study aimed at enhancing the production of phenolics and flavonoids by hairy root cultures in Lactuca serriola transformed with Agrobacterium rhizogenes strain AR15834 harbouring the rolB gene. The genetic transformation of rolB in transformed roots was validated, and rolB expression level was evaluated using real-time qPCR analysis. Expression levels of flavonoid biosynthesis genes (CHI, PAL, FLS, and CHS were assessed in the hairy and nontransformed roots. Results showed higher expression levels in the transgenic roots than in the nontransformed ones (p<0.01. Transgenic hairy roots exhibited a 54.8–96.7% increase in the total phenolic content, 38.1–76.2% increase in the total flavonoid content, and 56.7–96.7% increase in the total reducing power when compared with the nontransgenic roots (p<0.01. DPPH results also revealed that the transgenic hairy roots exhibited a 31.6–50% increase in antioxidant potential, when compared to normal roots. This study addressed the enhancement of secondary metabolite biosynthesis by hairy root induction in L. serriola.

  20. Geology and potential of the formation of sandstone type uranium mineralization at Hatapang region, North Sumatera

    International Nuclear Information System (INIS)

    Ngadenin

    2013-01-01

    The Study based on geological setting of Hatapang region, North Sumatera, identified as a favourable area to the formation of sandstone type uranium mineralization. This characterized by the occurred of anomalous radioactivity, uranium contents of the upper cretaceous granite intrusions and radioactivity anomalous of tertiary sedimentary rocks deposited in terrestrial environments. The study is objective to find out the potential formation of sandstone type-uranium mineralization within tertiary sedimentary rocks based on data’s studies of geological, geochemical, mineralogy, radioactivity of rocks. Stratigraphy of Hatapang area of the oldest to youngest are quartz units (permian-carboniferous), sandstone units (upper Triassic), granite (upper cretaceous), conglomerate units (Lower –middle Miocene) and tuff units (Pleistocene). Hatapang’s granite is S type granite which is not only potential as source of radioactive minerals, particularly placer type monazite, but also potential as source rocks of sandstone type-uranium mineralization on lighter sedimentary rocks. Sedimentary rock of conglomerate units has potential as host rock, even though uranium did not accumulated in its rocks since the lack number of carbon as precipitant material and dissolved U"+"6 in water did not reduced into U"+"4 caused the uranium mineralization did not deposited. (author)

  1. Relationships and their potential for change developed in difficult type 1 diabetes

    DEFF Research Database (Denmark)

    Zoffmann, Vibeke; Kirkevold, Marit

    2007-01-01

    Few researchers have explored how relationships between patients and providers might change problem solving in clinical practice. The authors used grounded theory to study dyads of 11 people with diabetes and poor glycemic control, and 8 nurses interacting in diabetes teams. Relational Potential...... for Change was identified as a core category that involved three types of relationships. Professionals mostly shifted between less effective relationships characterized by I-you-distant provider dominance and I-you-blurred sympathy. Although rarely seen, a third relationship, I-you-sorted mutuality proved...... more effective than the others in exploiting the Relational Potential for Change. The three types of relationship differed in (a) scope of problem solving, (b) the roles assigned to the patient and the professionals, (c) use of difficult feelings and different points of view, and (d) quality...

  2. The effect of Punica granatum L. along with aerobic training on resistin, serum adiponectin and insulin resistance in women with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ahmad Abdi

    2018-04-01

    Full Text Available Background: Factors secreted from adipocytes, such as resistin and adiponectin can affect peripheral insulin resistance and type 2 diabetes. Physical activity and pomegranate, which has both anti-inflammatory and antioxidant properties can affect resistin and adiponectin. The aim of this study was to examine the effect of Punica granatum L. along with aerobic training on serum resistin, adiponectin and insulin resistance in women with type 2 diabetes. Materials and Methods: In this study, 33 diabetic women with type 2 diabetes were selected from Babol city and were randomly divided into four groups (control, P. granatum L., training and P. granatum L.+ training. The training groups participated in an aerobic training for six weeks, three sessions a week (60% to 75% of the reserved heart rate and for 25 to 45 min. The control groups of P. granatum L. and P. granatum L. + training were fed 150 mL of P. granatum L. for six weeks (at about 18 p.m. Two days before and after the protocol, blood samples were taken. Results: The results showed that there was no significant difference in the serum resistin levels among the three experimental groups. Also, the results showed a significant difference between adiponectin levels and insulin resistance in four groups. Conclusions: It seems that aerobic training and P. granatum L. and combination of both can have anti-inflammatory and antioxidant effects on reduction of adiponectin and insulin resistance in women with type 2 diabetes.

  3. Semiclassical approach to Regge poles trajectories calculations for nonsingular potentials: Thomas-Fermi type

    International Nuclear Information System (INIS)

    Belov, S M; Avdonina, N B; Felfli, Z; Marletta, M; Msezane, A Z; Naboko, S N

    2004-01-01

    A simple semiclassical approach, based on the investigation of anti-Stokes line topology, is presented for calculating Regge poles for nonsingular (Thomas-Fermi type) potentials, namely potentials with singularities at the origin weaker than order -2. The anti-Stokes lines for Thomas-Fermi potentials have a more complicated structure than those of singular potentials and require careful application of complex analysis. The explicit solution of the Bohr-Sommerfeld quantization condition is used to obtain approximate Regge poles. We introduce and employ three hypotheses to obtain several terms of the Regge pole approximation

  4. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

    Directory of Open Access Journals (Sweden)

    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  5. Antiulcerogenic Potential Activity of Free and Nanoencapsulated Passiflora serratodigitata L. Extracts

    Directory of Open Access Journals (Sweden)

    Marc Strasser

    2014-01-01

    Full Text Available This paper provides evidence that the leaves and stem of Passiflora serratodigitata L. dry crude extract (DCE, ethylacetate fraction (EAF, and residual water fraction show potential antiulcerogenic activity. Interestingly, the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug delivery systems and allowed overcoming challenges such as poor aqueous solubility as well as the physical-chemical instability of the organic extract, which presented 90% (w/w of the flavonoid content. The entrapment efficiency of the total flavonoid was 90.6 ± 2.5% (w/v for the DCE and 79.9 ± 2.7% (w/v for the EAF. This study shows that nanoencapsulation improves both the physicochemical properties and the efficacy of the herbal formulations. Therefore, free and encapsulated extracts have the potential to be suitable drug design candidates for the therapeutic management of ulcer.

  6. MASA SIMPAN BUAH MANGGIS (Garcinia mangostana L. PADA BERBAGAI TINGKAT KEMATANGAN, SUHU DAN JENID KEMASAN [Shelf life of Manggis Fruit (Garcinia mangostana L. at Various Fruit Maturity Levels, Temperature, and Types of Packaging

    Directory of Open Access Journals (Sweden)

    Hasbi1

    2005-12-01

    Full Text Available The objective of this research was to study the effect of manggis fruit maturity levels, temperature, and types of packaging on the shelf fife of manggis fruit (Garcinia mangostana L, The experimental design used was Factorial Completely Randomized Design with three factors consisting of manggis fruit maturity levels (tinged with purple and brown, packaging types (flexible and stretch film, and storage temperature (l50C and 250C using two replication for each treatment. The result showed that maturity level had significant effect on weight toss, color but had no significant effect on hardness, total sugar and total acid of manggis fruit during storage. The suitable packaging type to maintain the quality of manggis fruit with maturity level of tinged purple was the flexible type, which result n a shelf life of 33 days. Packaging suitable for manggis fruit with maturity level of brown was the stretch type, which had the shelf life of 39 days. Storage temperature to maintain quality was l50C.

  7. Le type et l'authenticité du texte et leur influence sur la compréhension

    OpenAIRE

    Meta Lah

    2004-01-01

    L'objet de cette étude est d'analyser le rôle du texte dans la compréhension écrite, notamment sous deux de ses aspects: le type et l'authenticité. Le but est surtout pra­ tique: en apprendre plus sur le rôle du texte pour pouvoir ensuite mieux enseigner et évaluer la compréhension écrite. Dans la pratique pédagogique il arrive souvent que les exercices de compréhen­ sion écrite proposés aux élèves ne les differencient pas assez, ce qui soulève certai­ nes questions sur ce qui est plus facile...

  8. Bioactivity of Nonedible Parts of Punica granatum L.: A Potential Source of Functional Ingredients

    Directory of Open Access Journals (Sweden)

    Nawraj Rummun

    2013-01-01

    Full Text Available Punica granatum L. has a long standing culinary and medicinal traditional use in Mauritius. This prompted a comparative study to determine the bioefficacy of the flower, peel, leaf, stem, and seed extracts of the Mauritian P. granatum. The flower and peel extracts resulting from organic solvent extraction exhibited strong antioxidant activities which correlated with the high levels of total phenolics, flavonoids, and proanthocyanidins. The peel extract had the most potent scavenging capacity reflected by high Trolox equivalent antioxidant capacity value ( μmol/g air dry weight, very low IC50 values for hypochlorous acid ( mg air dry weight/mL, and hydroxyl radicals scavenging ( mg air dry weight/mL. Peel extracts also significantly inhibited S. mutans (, S. mitis (, and L. acidophilus ( growth compared to ciprofloxacin. The flower extract exhibited high ferric reducing, nitric oxide scavenging, and iron (II ions chelation and significantly inhibited microsomal lipid peroxidation. Furthermore, it showed a dose-dependent inhibition of xanthine oxidase with an IC50 value of  mg air dry weight/mL. This study showed that nonedible parts of cultivated pomegranates, that are generally discarded, are bioactive in multiassay systems thereby suggesting their potential use as natural prophylactics and in food applications.

  9. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  10. Potential Propagation by Seed and Cuttings of the Azorean Native Calluna vulgaris (L. Hull

    Directory of Open Access Journals (Sweden)

    Maria João Pereira

    2014-01-01

    Full Text Available This work investigates the potential propagation by seed and cuttings of the Azorean native Calluna vulgaris (L. Hull. for landscape conservation. With that purpose we have performed several germination and cuttings trials, using plant material from wild populations of this species. In the germination trials, we tested the effects of photoperiod length (8 and 16 h, temperature (10, 15, 20, and 20–10°C, seed age (6, 108, and 270 days, temperature of seed storage (4°C and room temperature, and seed surface sterilization on the germination characteristics. In the cuttings trials, we tested the effects of stem cutting type, cultural conditions, cuttings’ harvest month, and rooting substrates on the rooting percentages. The best percentages of germination, 93 and 90%, were obtained with fresh seeds and surface sterilized and sown under an 8 h photoperiod and with temperatures of 10°C or 15°C, respectively; germination after seed storage during 270 days is significantly superior (71% when seeds are stored at 4°C. The best percentages of rooting were achieved for straight (96% or heel cuttings (90% harvested in March, planted on soil from natural stands of C. vulgaris and Erica azorica Hochst., outdoors in half shade, and partially covered with transparent polyethylene film.

  11. Velocity potential formulations of highly accurate Boussinesq-type models

    DEFF Research Database (Denmark)

    Bingham, Harry B.; Madsen, Per A.; Fuhrman, David R.

    2009-01-01

    , B., 2006. A Boussinesq-type method for fully nonlinear waves interacting with a rapidly varying bathymetry. Coast. Eng. 53, 487-504); Jamois et al. (Jamois, E., Fuhrman, D.R., Bingham, H.B., Molin, B., 2006. Wave-structure interactions and nonlinear wave processes on the weather side of reflective...... with the kinematic bottom boundary condition. The true behaviour of the velocity potential formulation with respect to linear shoaling is given for the first time, correcting errors made by Jamois et al. (Jamois, E., Fuhrman, D.R., Bingham, H.B., Molin, B., 2006. Wave-structure interactions and nonlinear wave...... processes on the weather side of reflective structures. Coast. Eng. 53, 929-945). An exact infinite series solution for the potential is obtained via a Taylor expansion about an arbitrary vertical position z=(z) over cap. For practical implementation however, the solution is expanded based on a slow...

  12. The potential roles of T-type Ca2+ channels in motor coordination

    Directory of Open Access Journals (Sweden)

    Young-Gyun ePark

    2013-10-01

    Full Text Available Specific behavioral patterns are expressed by complex combinations of muscle coordination. Tremors are simple behavioral patterns and are the focus of studies investigating motor coordination mechanisms in the brain. T-type Ca2+ channels mediate intrinsic neuronal oscillations and rhythmic burst spiking, and facilitate the generation of tremor rhythms in motor circuits. Despite substantial evidence that T-type Ca2+ channels mediate pathological tremors, their roles in physiological motor coordination and behavior remain unknown. Here, we review recent progress in understanding the roles that T-type Ca2+ channels play under pathological conditions, and discuss the potential relevance of these channels in mediating physiological motor coordination.

  13. Total phenolic compounds, antioxidant potential and α-glucosidase inhibition by Tunisian Euphorbia paralias L.

    Directory of Open Access Journals (Sweden)

    Malek Besbes Hlila

    2016-08-01

    Full Text Available Objective: To examine the potential antioxidant and anti-α-glucosidase inhibitory activities of Tunisian Euphorbia paralias L. leaves and stems extracts and their composition of total polyphenol and flavonoids. Methods: The different samples were tested for their antiradical activities by using 2, 2’- azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS and 1,1-diphenyl-2-picrylhydrazyl (DPPH assays. In α-glucosidase activity, α-glucosidase (0.3 IU/mL and substrate, 2500 µmol/ L p-nitrophenyl α-D-glucopyranoside were used; absorbance was registered at 405 nm. Results: The leaves acetonic extract exhibited the strongest α-glucosidase inhibition [IC50 = (0.0035 ± 0.001 µg/mL], which was 20-fold more active than the standard product (acarbose [IC50 = (0.07 ± 0.01 µg/mL]. Acetonic extract of the leaves exhibited the highest quantity of total phenolic [(95.54 ± 0.04 µg gallic acid equivalent/mg] and flavonoid [(55.16 ± 0.25 µg quercetin equivalent/mg]. The obtained findings presented also that this extract was detected with best antioxidant capacity [IC50 = (0.015 ± 0.01 µg/mL] against DPPH and a value of IC50 equal to (0.02 ± 0.01 µg/mL against ABTS. Positive relationship between polyphenolic content of the tested Euphorbia paralias L. leaves and stems extracts and its antioxidant activity (DPPH and ABTS was detected. Elevated positive linear correlation was got between ABTS and total phenolic (R2 = 0.751. Conclusions: The findings clearly demonstrate that the use of a polar solvent enables extraction of significant quantities of phenol compounds and flavonoids.

  14. Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons.

    Directory of Open Access Journals (Sweden)

    Guo-Sheng Yi

    Full Text Available Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding.

  15. Field differential equations for a potential flow from a Hamilton type variational principle

    International Nuclear Information System (INIS)

    Fierros Palacios, A.

    1992-01-01

    The same theoretical frame that was used to solve the problem of the field equations for a viscous fluid is utilized in this work. The purpose is to obtain the differential field equations for a potential flow from the Lagrangian formalism as in classical field theory. An action functional is introduced as a space-time integral over a region of three-dimensional Euclidean space, of a Lagrangian density as a function of certain field variables. A Hamilton type extremum action principle is postulated with adequate boundary conditions, and a set of differential field equations is derived. A particular Lagrangian density of the T-V type leads to the wave equation for the velocity potential. (Author)

  16. Thermal fatigue behaviour for a 316 L type steel

    International Nuclear Information System (INIS)

    Fissolo, A.; Marini, B.; Nais, G.; Wident, P.

    1996-01-01

    This paper deals with initiation and growth of cracks produced by thermal fatigue loadings on 316 L steel, which is a reference material for the first wall of the next fusion reactor ITER. Two types of facilities have been built. As for true components, thermal cycles have been repeatedly applied on the surface of the specimen. The first is mainly concerned with initiation, which is detected with a light microscope. The second allows one to determine the propagation of a single crack. Crack initiation is analyzed using the French RCC-MR code procedure, and the strain-controlled isothermal fatigue curves. To predict crack growth, a model previously proposed by Haigh and Skelton is applied. This is based on determination of effective stress intensity factors, which takes into account both plastic strain and crack closure phenomena. It is shown that estimations obtained with such methodologies are in good agreement with experimental data. (orig.)

  17. Multilocus microsatellite typing (MLMT of strains from Turkey and Cyprus reveals a novel monophyletic L. donovani sensu lato group.

    Directory of Open Access Journals (Sweden)

    Evi Gouzelou

    Full Text Available BACKGROUND: New foci of human CL caused by strains of the Leishmania donovani (L. donovani complex have been recently described in Cyprus and the Çukurova region in Turkey (L. infantum situated 150 km north of Cyprus. Cypriot strains were typed by Multilocus Enzyme Electrophoresis (MLEE using the Montpellier (MON system as L. donovani zymodeme MON-37. However, multilocus microsatellite typing (MLMT has shown that this zymodeme is paraphyletic; composed of distantly related genetic subgroups of different geographical origin. Consequently the origin of the Cypriot strains remained enigmatic. METHODOLOGY/PRINCIPAL FINDINGS: The Cypriot strains were compared with a set of Turkish isolates obtained from a CL patient and sand fly vectors in south-east Turkey (Çukurova region; CUK strains and from a VL patient in the south-west (Kuşadasi; EP59 strain. These Turkish strains were initially analyzed using the K26-PCR assay that discriminates MON-1 strains by their amplicon size. In line with previous DNA-based data, the strains were inferred to the L. donovani complex and characterized as non MON-1. For these strains MLEE typing revealed two novel zymodemes; L. donovani MON-309 (CUK strains and MON-308 (EP59. A population genetic analysis of the Turkish isolates was performed using 14 hyper-variable microsatellite loci. The genotypic profiles of 68 previously analyzed L. donovani complex strains from major endemic regions were included for comparison. Population structures were inferred by combination of bayesian model-based and distance-based approaches. MLMT placed the Turkish and Cypriot strains in a subclade of a newly discovered, genetically distinct L. infantum monophyletic group, suggesting that the Cypriot strains may originate from Turkey. CONCLUSION: The discovery of a genetically distinct L. infantum monophyletic group in the south-eastern Mediterranean stresses the importance of species genetic characterization towards better understanding

  18. Moduli Potentials in Type IIA Compactifications with RR and NS Flux

    Energy Technology Data Exchange (ETDEWEB)

    Kachru, S.

    2004-12-01

    We describe a simple class of type IIA string compactifications on Calabi-Yau manifolds where background fluxes generate a potential for the complex structure moduli, the dilaton, and the Kaehler moduli. This class of models corresponds to gauged {Nu} = 2 supergravities, and the potential is completely determined by a choice of gauging and by data of the {Nu} = 2 Calabi-Yau model--the prepotential for vector multiplets and the quaternionic metric on the hypermultiplet moduli space. Using mirror symmetry, one can determine many (though not all) of the quantum corrections which are relevant in these models.

  19. L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation

    NARCIS (Netherlands)

    Zeimet, A.G.; Reimer, D.; Huszar, M.; Winterhoff, B.; Puistola, U.; Azim, S.A.; Muller-Holzner, E.; Ben-Arie, A.; Kempen, L.C.L.T. van; Petru, E.; Jahn, S.; Geels, Y.P.; Massuger, L.F.A.G.; Amant, F.; Polterauer, S.; Lappi-Blanco, E.; Bulten, J.; Meuter, A.; Tanouye, S.; Oppelt, P.; Stroh-Weigert, M.; Reinthaller, A.; Mariani, A.; Hackl, W.; Netzer, M.; Schirmer, U.; Vergote, I.; Altevogt, P.; Marth, C.; Fogel, M.

    2013-01-01

    BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to

  20. The potential of hemp (Cannabis sativa L.) for sustainable fibre production: a crop physiological appraisal.

    NARCIS (Netherlands)

    Werf, van der H.M.G.; Mathijssen, E.W.J.M.; Haverkort, A.J.

    1996-01-01

    Hemp (Cannabis sativa L.) fibre can be used as a raw material for paper and textile production. A comprehensive research programme in the Netherlands has concluded that fibre hemp is a potentially profitable crop, having the right profile to fit into sustainable farming systems. This paper presents

  1. Vocabulary Glossing: A Meta-Analysis of the Relative Effectiveness of Different Gloss Types on L2 Vocabulary Acquisition

    Science.gov (United States)

    Vahedi, Vahideh Sadat; Ghonsooly, Behzad; Pishghadam, Reza

    2016-01-01

    In recent years there has been a growing interest to incorporate hypertext glosses into L2 reading materials and accordingly, it has provoked researchers to uncover to what extent and under which moderator variables a specific type of gloss yields more effective outcomes than other types of glossing. The present meta-analysis attempts to examine…

  2. A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Galvis-Pareja, David [Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Zapata-Torres, Gerald [Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago (Chile); Hidalgo, Jorge [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago (Chile); Ayala, Pedro [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); and others

    2014-08-15

    Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca{sup 2+} channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca{sup 2+} channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca{sup 2+} channel-blocking activity and antioxidant properties. The Ca{sup 2+} channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca{sup 2+} channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca{sup 2+} channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca{sup 2+} entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca{sup 2+} blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca{sup 2+} blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties.

  3. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

    Directory of Open Access Journals (Sweden)

    Hüseyin Ilgü

    2018-03-01

    Full Text Available The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg, agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5, an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  4. Food and biomass potential of Prunus virginiana L. (chokecherry).

    Science.gov (United States)

    Wang, Sunmin; Young, Lester; Faye, Amberly; Li, Bonnie; Clancy, Johanna; Bors, Bob; Reaney, Martin

    2012-03-14

    Prunus virginiana L. (chokecherry) fruit has potential to provide both food and energy and as annual yield of biomass and energy are much greater than annual crops such as canola and wheat. We determined chokecherry fruit weight fractions as well as pit and extracted seed oil concentrations and fatty acid composition. Gross energy for each of the fractions was determined, as were carbon and nitrogen content. Extrapolation of these data suggests that gross energy from pits alone over a 24-year period (890 GJ·ha(-1)) is equivalent to that from an entire canola/wheat rotation (850 GJ·ha(-1)). After maturity, pulp contributes an additional 1130 GJ·ha(-1) over 21 years from ~3.4 t·ha(-1)·year(-1) (dw), while wood from pruning could add another 60 GJ·ha(-1)·year(-1). Over this time period, chokecherry would produce 1.5-2.5 times the amount of oil produced by a canola/wheat rotation.

  5. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    Science.gov (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  6. Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal.

    Science.gov (United States)

    Masetto, Sergio; Zampini, Valeria; Zucca, Giampiero; Valli, Paolo

    2005-11-01

    Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

  7. Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

    Science.gov (United States)

    Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

    2016-06-01

    A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L.

    Science.gov (United States)

    Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S Hande; Lillicrap, David

    2017-10-01

    Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E' domain, and significant loss of β-sheet secondary structure. The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion.

  9. In vitro plant regeneration of two cucumber (Cucumis sativum L. genotypes: Effects of explant types and culture medium

    Directory of Open Access Journals (Sweden)

    Grozeva Stanislava

    2014-01-01

    Full Text Available The effect of different phytohormone concentrations on callusogenesis and organogenesis in two cucumber genotypes were studied. It was established that the rate of plant regeneration depends on genotype, explant type and culture medium. Hypocotyls were found to be more responsive than cotyledons in morphogenesis. In vitro planlet-regenerants have been obtained in hypocotyls explants on culture medium with 1.0 and 2.0 mgL-1 BA for cultivar Gergana and in 1.0 and 3.0 mgL-1K-line 15B. Induction of regeneration in cotyledons were established only in cultivar Gergana on culture medium supplemented with 3.0 mgL-1 BA and in combination of 0.5 mgL-1IAA.

  10. The calmodulin-binding, short linear motif, NSCaTE is conserved in L-type channel ancestors of vertebrate Cav1.2 and Cav1.3 channels.

    Directory of Open Access Journals (Sweden)

    Valentina Taiakina

    Full Text Available NSCaTE is a short linear motif of (xWxxx(I or Lxxxx, composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca(2+ concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Cav1.1 and Cav1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCav1 from pond snail Lymnaea stagnalis has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA, but disappears in high buffer conditions (10 mM EGTA. Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca(2+-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels.

  11. Cross-cultural analysis of type D (distressed) personality in 6222 patients with ischemic heart disease: a study from the International HeartQoL Project.

    Science.gov (United States)

    Kupper, Nina; Pedersen, Susanne S; Höfer, Stefan; Saner, Hugo; Oldridge, Neil; Denollet, Johan

    2013-06-20

    Type D (distressed) personality, the conjoint effect of negative affectivity (NA) and social inhibition (SI), predicts adverse cardiovascular outcomes, and is assessed with the 14-item Type D Scale (DS14). However, potential cross-cultural differences in Type D have not been examined yet in a direct comparison of countries. To examine the cross-cultural validity of the Type D construct and its relation with cardiovascular risk factors, cardiac symptom severity, and depression/anxiety. In 22 countries, 6222 patients with ischemic heart disease (angina, 33%; myocardial infarction, 37%; or heart failure, 30%) completed the DS14 as part of the International HeartQoL Project. Type D personality was assessed reliably across countries (αNA>.80; αSI>.74; except Russia, which was excluded from further analysis). Cross-cultural measurement equivalence was established for Type D personality at all measurement levels, as the factor-item configuration, factor loadings, and error structure were not different across countries (fit: CFI=.91; NFI=.88; RMSEA=.018), as well as across gender and diagnostic subgroups. Type D personality was more prevalent in Southern (37%) and Eastern (35%) European countries compared to Northern (24%) and Western European and English-speaking (both 27%) countries (pcultural measurement equivalence was demonstrated for the Type D scale in 21 countries. There is a pan-cultural relationship between Type D personality and some cardiovascular risk factors, supporting the role of Type D personality across countries and cardiac conditions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Trifolium pratense L. as a Potential Natural Antioxidant

    Directory of Open Access Journals (Sweden)

    Sanja Vlaisavljevic

    2014-01-01

    Full Text Available The essential oils of three different growth stages of Trifolium pratense L. (TP1, TP2 and TP3 were investigated by gas chromatography-mass spectrometry and tested for their antioxidant and antimicrobial activities. The highest content of volatile compounds was found in the essential oil sample TP1, where terpenes such as β-myrcene (4.55%, p-cymene (3.59%, limonene (0.86%, tetrahydroionone (1.56% were highlighted due to their biological activity. The antioxidant activity was determined by following the scavenging capacity of the essential oils for the free radicals DPPH·, NO· and O2·-, as well as effects of the investigated oils on lipid peroxidation (LP. In all three cases, the sample TP1 showed the best radical-capturing capacity for DPPH· (27.61 ± 0.12 µg/mL, NO· (16.03 ± 0.11 µg/mL, O2·− (16.62 ± 0.29 µg/mL and also had the best lipid peroxidation effects in the Fe2+/ascorbate induction system (9.35 ± 0.11 µg/mL. Antimicrobial activity was evaluated against the following bacteria cultures: Escherichia coli (ATCC10526, Salmonella typhimurium (ATCC 14028, Staphylococcus aureus (ATCC 11632 and Bacillus cereus (ATCC 10876. None of the examined essential oil samples showed inhibitory effects on the tested bacterial strains.

  13. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-03-20

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  14. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol.

    Science.gov (United States)

    Zeka, Keti; Ruparelia, Ketan C; Continenza, Maria A; Stagos, Dimitrios; Vegliò, Francesco; Arroo, Randolph R J

    2015-12-01

    Saffron from the province of L'Aquila, in the Abruzzo region of Italy, is highly prized and has been awarded a formal recognition by the European Union with EU Protected Designation of Origin (PDO) status. Despite this, the saffron regions are abandoned by the younger generations because the traditional cultivation of saffron (Crocus sativus L.) is labour intensive and yields only one crop of valuable saffron stamens per year. Petals of the saffron Crocus have had additional uses in traditional medicine and may add value to the crops for local farmers. This is especially important because the plant only flowers between October and November, and farmers will need to make the best use of the flowers harvested in this period. Recently, the petals of C. sativus L., which are considered a waste material in the production of saffron spice, were identified as a potential source of natural antioxidants. The antioxidants crocin and kaempferol were purified by flash column chromatography, and identified by thin layer chromatography (TLC), HPLC-DAD, infrared (IR), and nuclear magnetic resonance ((1)H &(13)C NMR) spectroscopy. The antioxidant activity was determined with the ABTS and DPPH tests. The antioxidant activities are mainly attributed to carotenoid and flavonoid compounds, notably glycosides of crocin and kaempferol. We found in dried petals 0.6% (w/w) and 12.6 (w/w) of crocin and kaempferol, respectively. Petals of C. sativus L. have commercial potential as a source for kaempferol and crocetin glycosides, natural compounds with antioxidant activity that are considered to be the active ingredients in saffron-based herbal medicine. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Lactobacillus crispatus L1: high cell density cultivation and exopolysaccharide structure characterization to highlight potentially beneficial effects against vaginal pathogens.

    Science.gov (United States)

    Donnarumma, Giovanna; Molinaro, Antonio; Cimini, Donatella; De Castro, Cristina; Valli, Vivien; De Gregorio, Vincenza; De Rosa, Mario; Schiraldi, Chiara

    2014-05-30

    Vaginal lactic acid bacteria defend the host against pathogens through a combination of competitive exclusion, competition for nutrients, production of antimicrobial substances and through the activation of the immune system. A new human isolate named Lactobacillus crispatus L1 was characterized in this work, and a preliminary evaluation of its probiotic potential is described together with a process to obtain a high productivity of viable biomass. In a simulated digestion process 1.8⋅10(10) cells∙ml(-1) survived the gastric environment with 80% viability, without being affected by small intestine juices. Experiments on six different C sources were performed to analyze growth and organic acids production and, glucose, provided the best performances. A microfiltration strategy was exploited to improve the cellular yield in 2 L-fermentation processes, reaching 27 g · l(-1) of dry biomass. Moreover, L. crispatus L1 demonstrated a greater stability to high concentrations of lactic acid, compared to other lactobacilli. The specific L. crispatus L1 exopolysaccharide was purified from the fermentation broth and characterized by NMR showing structural features and similarity to exopolysaccharides produced by pathogenic strains. Live L. crispatus L1 cells strongly reduced adhesion of a yeast pathogenic strain, Candida albicans in particular, in adherence assays. Interestingly a higher expression of the human defensin HBD-2 was also observed in vaginal cells treated with the purified exopolysaccharide, indicating a possible correlation with C. albicans growth inhibition. The paper describes the evaluation of L. crispatus L1 as potential vaginal probiotic and the fermentation processes to obtain high concentrations of viable cells.

  16. The effect of chronic stimulation of serotonin receptor type 7 on recognition, passive avoidance memory, hippocampal long-term potentiation, and neuronal apoptosis in the amyloid β protein treated rat.

    Science.gov (United States)

    Shahidi, Siamak; Asl, Sara Soleimani; Komaki, Alireza; Hashemi-Firouzi, Nasrin

    2018-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Long-term potentiation (LTP), a type of synaptic plasticity, occurs during learning and memory. Serotonin receptor type 7 (5-HTR7) activation is suggested as a possible therapeutic target for AD. The aim of the present study was to examine the effects of chronic treatment with the 5-HTR7 agonist, AS19, on cognitive function, memory, hippocampal plasticity, amyloid beta (Aβ) plaque accumulation, and apoptosis in an adult rat model of AD. AD was induced in rats using Aβ (single 1 μg/μL intracerebroventricular (icv) injection during surgery). The following experimental groups were included: control, sham-operated, Aβ + saline (1 μL icv for 30 days), and Aβ + AS19 (1 μg/μL icv for 30 days) groups. The animals were tested for cognition and memory performance using the novel object recognition and passive avoidance tests, respectively. Next, anesthetized rats were placed in a stereotaxic apparatus for electrode implantation, and field potentials were recorded in the hippocampal dentate gyrus. Lastly, brains were removed and Aβ plaques and neuronal apoptosis were evaluated using Congo red staining and TUNEL assay, respectively. Administration of AS19 in the Aβ rats increased the discrimination index of the novel object recognition test. Furthermore, AS19 treatment decreased time spent in the dark compartment during the passive avoidance test. AS19 also enhanced both the population spike (PS) amplitude and the field excitatory postsynaptic potential (fEPSP) slope evoked potentials of the LTP components. Aβ plaques and neuronal apoptosis were decreased in the AS19-treated Aβ rats. These results indicate that chronic treatment with a 5-HTR7 agonist can prevent Aβ-related impairments in cognition and memory performance by alleviating Aβ plaque accumulation and neuronal apoptosis, hence improving neuronal

  17. Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

    Science.gov (United States)

    El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

    2003-03-01

    Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

  18. Potential of kenaf (Hibiscus cannabinus L.) and corn (Zea mays L.) for phytoremediation of dredging sludge contaminated by trace metals.

    Science.gov (United States)

    Arbaoui, Sarra; Evlard, Aricia; Mhamdi, Mohamed El Wafi; Campanella, Bruno; Paul, Roger; Bettaieb, Taoufik

    2013-07-01

    The potential of kenaf (Hibiscus cannabinus L.) and corn (Zea mays L.) for accumulation of cadmium and zinc was investigated. Plants have been grown in lysimetres containing dredging sludge, a substratum naturally rich in trace metals. Biomass production was determined. Sludge and water percolating from lysimeters were analyzed by atomic absorption spectrometry. No visible symptoms of toxicity were observed during the three- month culture. Kenaf and corn tolerate trace metals content in sludge. Results showed that Zn and Cd were found in corn and kenaf shoots at different levels, 2.49 mg/kg of Cd and 82.5 mg/kg of Zn in kenaf shoots and 2.1 mg/kg of Cd and 10.19 mg/kg in corn shoots. Quantities of extracted trace metals showed that decontamination of Zn and Cd polluted substrates is possible by corn and kenaf crops. Tolerance and bioaccumulation factors indicated that both species could be used in phytoremediation.

  19. Assessment of serum levels of soluble CD40L in Egyptian children and adolescents with type 1 diabetes mellitus: Relationship to microalbuminuria and glycemic control

    Directory of Open Access Journals (Sweden)

    Kotb Abbass Metwalley

    2013-01-01

    Full Text Available Context: Soluble CD40 ligand (sCD40L is known to be elevated in different clinical situations including hypercholesterolemia, acute coronary syndromes, and type 2 diabetes mellitus (T2DM, Data about the relationship between type 1 diabetes mellitus (T1DM and sCD40L is limited. In addition, the potential role ofsCD40Lin the pathogenesis of vascular complications in children and adolescents with T1DM is to be clarified. Hence, the study aimed at assessment of sCD40L levels in children and adolescents with T1DM and correlation of these levels with glycemic control and microalbuminuria. Settings and Design: Cross-sectional controlled study. Materials and Methods: The study was performed in the Pediatric Endocrinology and Diabetes Unit, Assuit University Children Hospital, Assiut, Egypt. It included 70 children and adolescents with T1DM (mean age 14. 76 ± 2.21 years. Cases were further subdivided into 43 cases with normoalbuminuria and 27 cases with microalbuminuria according to presence or absence or microalbuminuria in fresh urine samples. Twentyfive healthy subjects, age- and sex-matched were included as control group (mean age = 13.62 ± 2.11 years. Studied cases were subjected to medical history, clinical examination, and laboratory assessment of fasting blood glucose (FBG, lipid profile, glycosylated hemoglobin (HbA1c, and sCD40L were performed. Results: Mean HbA1c and sCD40L were significantly higher in diabetic children (n = 70 compared to control (n = 25 (P < 0.001 for each. Mean HbA1c and sCD40L levels were significantly higher in microalbuminuric cases (n = 27 compared to normoalbuminuric cases (n = 43 (P < 0.05 and <0.01, respectively.We also observed a significant positive correlation between sCD40L levels and the age, diabetes duration, HbA1c, and urinary albumin creatinine ratio. Conclusions: The high serum sCD40L levels in children and adolescents with T1DM particularly in those with microalbminuria and its positive correlation with

  20. Role of L-type Ca2+ channel isoforms in the extinction of conditioned fear.

    Science.gov (United States)

    Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J; Striessnig, Jörg; Singewald, Nicolas

    2008-05-01

    Dihydropyridine (DHP) L-type Ca(2+) channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the treatment of specific anxiety disorders. Ca(V)1.2 and Ca(V)1.3 are the predominant LTCCs in the mammalian brain. However, since no isoform-selective DHP blockers are available, their individual contribution to fear memory extinction is unknown. We used a novel mouse model expressing DHP-insensitive Ca(V)1.2 LTCCs (Ca(V)1.2DHP(-/-) mice) to address this question. In line with previous studies, wild-type (WT) mice treated with systemic nifedipine displayed markedly impaired fear extinction. This DHP effect was completely abolished in Ca(V)1.2DHP(-/-) mice, indicating that it is mediated by Ca(V)1.2, but not by Ca(V)1.3 LTCCs. Supporting this conclusion, Ca(V)1.3-deficient mice (Ca(V)1.3(-/-)) showed extinction identical to the respective WT mice. The inhibition of fear extinction was not observed after intracerebroventricular (i.c.v.) application of different doses of nifedipine, suggesting that this effect is secondary to inhibition of peripheral Ca(V)1.2 channels. The LTCC activator BayK, which lacks neurotoxic effects in Ca(V)1.2DHP(-/-) mice, did not influence the extinction time course. In summary, we demonstrate that LTCC signaling through the Ca(V)1.2 isoform of LTCCs interferes with fear memory extinction, presumably via a peripherally mediated mechanism. Activation of other LTCC isoforms (predominantly Ca(V)1.3) is not sufficient to accelerate extinction of conditioned fear in mice.

  1. Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia

    Directory of Open Access Journals (Sweden)

    A. Hunyadi

    2013-01-01

    Full Text Available The leaves of Morus alba L. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each other’s important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevant in vitro and in vivo studies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel. In vivo antihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well as in vitro glucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents of M. alba (chlorogenic acid, rutin, isoquercitrin, and loliolide were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.

  2. Bioactivity of Nonedible Parts of Punica granatum L.: A Potential Source of Functional Ingredients

    Science.gov (United States)

    Somanah, Jhoti; Ramsaha, Srishti; Bahorun, Theeshan; Neergheen-Bhujun, Vidushi S.

    2013-01-01

    Punica granatum L. has a long standing culinary and medicinal traditional use in Mauritius. This prompted a comparative study to determine the bioefficacy of the flower, peel, leaf, stem, and seed extracts of the Mauritian P. granatum. The flower and peel extracts resulting from organic solvent extraction exhibited strong antioxidant activities which correlated with the high levels of total phenolics, flavonoids, and proanthocyanidins. The peel extract had the most potent scavenging capacity reflected by high Trolox equivalent antioxidant capacity value (5206.01 ± 578.48 μmol/g air dry weight), very low IC50 values for hypochlorous acid (0.004 ± 0.001 mg air dry weight/mL), and hydroxyl radicals scavenging (0.111 ± 0.001 mg air dry weight/mL). Peel extracts also significantly inhibited S. mutans (P < 0.001), S. mitis (P < 0.001), and L. acidophilus (P < 0.05) growth compared to ciprofloxacin. The flower extract exhibited high ferric reducing, nitric oxide scavenging, and iron (II) ions chelation and significantly inhibited microsomal lipid peroxidation. Furthermore, it showed a dose-dependent inhibition of xanthine oxidase with an IC50 value of 0.058 ± 0.011 mg air dry weight/mL. This study showed that nonedible parts of cultivated pomegranates, that are generally discarded, are bioactive in multiassay systems thereby suggesting their potential use as natural prophylactics and in food applications. PMID:26904607

  3. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes.

    Science.gov (United States)

    Martina, Valentino; Masha, Andi; Gigliardi, Valentina Ramella; Brocato, Loredana; Manzato, Enzo; Berchio, Arrigo; Massarenti, Paola; Settanni, Fabio; Della Casa, Lara; Bergamini, Stefania; Iannone, Anna

    2008-05-01

    Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of l-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation. A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC + ARG for 6 months. The NAC + ARG treatment caused a reduction of both systolic (P < 0.05) and diastolic (P < 0.05) mean arterial blood pressure, total cholesterol (P < 0.01), LDL cholesterol (P < 0.005), oxidized LDL (P < 0.05), high-sensitive C-reactive protein (P < 0.05), intracellular adhesion molecule (P < 0.05), vascular cell adhesion molecule (P < 0.01), nitrotyrosine (P < 0.01), fibrinogen (P < 0.01), and plasminogen activator inhibitor-1 (P < 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P < 0.02). HDL cholesterol increased (P < 0.05). No changes in other parameters studied were observed. NAC + ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients.

  4. Status and development potential of proven reactor types and fuel cycles, and their role in a medium-to-long range energy supply strategy

    International Nuclear Information System (INIS)

    Maerkl, H.

    1982-01-01

    After a general review of the present world-wide energy situation (with particular reference to those of the Federal Republic of Germany and of Argentina) the possible contribution of nuclear energy in general, and of proven light water and heavy water reactor types in particular, to meeting the energy demand is discussed. The technical and economic development potential of those reactors is evaluated, both regarding plant components technology as well as fuel and fuel cycle improvement, with special emphasis on the Pressure Vessel Heavy Water Reactor type. The last section presents some results of nuclear reactor strategy calculations made for a scenario similar to that of Argentina over the period from 1970 through 2040 and involving the use of: A) heavy water reactors (HWR's) only, with and without plutonium recycling, and B) the use of HWR's plus fast breeder reactors. (M.E.L.) [es

  5. Transient receptor potential canonical type 3 channels and blood pressure in humans

    DEFF Research Database (Denmark)

    Thilo, Florian; Baumunk, Daniel; Krause, Hans

    2009-01-01

    There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blood...

  6. Passivation Behavior of Type-316L Stainless Steel in the Presence of Hydrogen Sulfide Ions Generated from a Local Anion Generating System

    International Nuclear Information System (INIS)

    Lee, Jun-Seob; Kitagawa, Yuichi; Nakanishi, Takayuki; Hasegawa, Yasuchika; Fushimi, Koji

    2016-01-01

    The passivity of type 316L stainless steel was studied in a pH 8.4 boric acid-borate buffer solution containing hydrogen sulfide ions (HS − ) by using a local anion-generating system. During potentiostatic polarization of the stainless steel at a primary passive potential of 0.4 V SSE and at a secondary passive potential of 0.9 V SSE in solutions with and without HS − , the current density flowing for passive film formation was increased by the presence of HS − at both potentials, while 15 Hz impedance at 0.9 V SSE in the solution with HS − was larger than that in the solution without HS − . It was thought that the presence of HS − in the solution during film formation made the film less resistive and affected the film capacitance depending on the polarization potential. X-ray photoelectron spectroscopy (XPS) showed an increase in metal cation and oxygen anion vacancies in the passive film formed at the primary passive state in the solution containing HS − . Auger electron spectroscopy (AES) and Raman spectroscopy revealed that a sulfide layer was deposited on the stainless steel surface that was oxidized at the secondary passive state in the solution containing HS − . It is thought that application of a high potential changes the passivity of the stainless steel surface in the solution containing HS − .

  7. Rainbow-shift mechanism behind discrete optical-potential ambiguities

    International Nuclear Information System (INIS)

    Brandan, M.E.; McVoy, K.W.

    1991-01-01

    Some years ago, Drisko et al. suggested that the discrete ambiguity often encountered for elastic scattering optical potentials could be understood as being due to the interior or small-l S-matrix elements for two ''equivalent'' potentials differing in phase by 2π, l-by-l. We point out that the absence of this phase change for peripheral partial waves is equally essential, and suggest that a deeper understanding of the ambiguity may be achieved by viewing it as a consequence of a farside interference between interior and peripheral partial waves. It is this interference which produces the broad ''Airy maxima'' of a nuclear rainbow, and we show that a Drisko-type phase-shift increment δ l →(δ l +π) for low-l phases relative to the high-l ones is exactly what is needed to shift a farside rainbow pattern by one Airy maximum, thus providing an equivalent ''rainbow-shift'' interpretation of the discrete ambiguity. The physical importance of both interpretations lies in the fact that the existence of discrete ambiguities (as well as of nuclear rainbows) is explicit evidence for low-l transparency in nucleus-nucleus collisions. The essential role played by low partial waves explains why peripheral reactions have generally not proven helpful in resolving this ambiguity

  8. Susceptibility of ocean- and stream-type Chinook salmon to isolates of the L, U, and M genogroups of infectious hematopoietic necrosis virus (IHNV)

    Science.gov (United States)

    Hernandez, Daniel; Purcell, Maureen K.; Friedman, Carolyn S.; Kurath, Gael

    2016-01-01

    This study examined the susceptibility of Chinook salmon Oncorhynchus tshawytscha to viral strains from the L, U, and M genogroups of infectious hematopoietic necrosis virus (IHNV) present in western North America. The goal of this investigation was to establish a baseline understanding of the susceptibility of ocean- and stream-type Chinook salmon to infection and mortality caused by exposure to commonly detected strains of L, U, and M IHNV. The L IHNV strain tested here was highly infectious and virulent in both Chinook salmon populations, following patterns previously reported for Chinook salmon. Furthermore, ocean- and stream-type Chinook salmon fry at 1 g can also become subclinically infected with U and M strains of IHNV without experiencing significant mortality. The stream-type life history phenotype was generally more susceptible to infection and suffered greater mortality than the ocean-type phenotype. Between the U and M genogroup strains tested, the U group strains were generally more infectious than the M group strains in both Chinook salmon types. Substantial viral clearance occurred by 30 d post exposure, but persistent viral infection was observed with L, U, and M strains in both host populations. While mortality decreased with increased host size in stream-type Chinook salmon, infection prevalence was not lower for all strains at a greater size. These results suggest that Chinook salmon may serve as reservoirs and/or vectors of U and M genogroup IHNV.

  9. Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging

    Science.gov (United States)

    Firuzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Shafiee-Ardestani, Mahdi; Khalaj, Ali

    2016-01-01

    Aim: In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. Materials and Methods: Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [68Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. Results: [68Ga] DOTA AMLO was prepared at pH 4–5 in 7–10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9–2.1 GBq/mmol) and was stable up to 4 h with a log P of −0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. Conclusions: The complex can be a candidate for further positron emission tomography imaging for L type calcium channels. PMID:27833311

  10. Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Schulz, Nico

    2010-01-01

    The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1-...... alpha transgenic mice compared to wild-type mice and TRPV1-/- mice (8.6±1.3mg/g; 5.4±0.3mg/g; and 5.4±0.4mg/g; respectively; p...

  11. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

    Directory of Open Access Journals (Sweden)

    Mostafa Wanees Ahmed El husseny

    2017-01-01

    Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

  12. Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

    Science.gov (United States)

    Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

    2018-03-16

    Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

  13. Calcium influx through L-type channels attenuates skeletal muscle contraction via inhibition of adenylyl cyclases.

    Science.gov (United States)

    Menezes-Rodrigues, Francisco Sandro; Pires-Oliveira, Marcelo; Duarte, Thiago; Paredes-Gamero, Edgar Julian; Chiavegatti, Tiago; Godinho, Rosely Oliveira

    2013-11-15

    Skeletal muscle contraction is triggered by acetylcholine induced release of Ca(2+) from sarcoplasmic reticulum. Although this signaling pathway is independent of extracellular Ca(2+), L-type voltage-gated calcium channel (Cav) blockers have inotropic effects on frog skeletal muscles which occur by an unknown mechanism. Taking into account that skeletal muscle fiber expresses Ca(+2)-sensitive adenylyl cyclase (AC) isoforms and that cAMP is able to increase skeletal muscle contraction force, we investigated the role of Ca(2+) influx on mouse skeletal muscle contraction and the putative crosstalk between extracellular Ca(2+) and intracellular cAMP signaling pathways. The effects of Cav blockers (verapamil and nifedipine) and extracellular Ca(2+) chelator EGTA were evaluated on isometric contractility of mouse diaphragm muscle under direct electrical stimulus (supramaximal voltage, 2 ms, 0.1 Hz). Production of cAMP was evaluated by radiometric assay while Ca(2+) transients were assessed by confocal microscopy using L6 cells loaded with fluo-4/AM. Ca(2+) channel blockers verapamil and nifedipine had positive inotropic effect, which was mimicked by removal of extracellular Ca(+2) with EGTA or Ca(2+)-free Tyrode. While phosphodiesterase inhibitor IBMX potentiates verapamil positive inotropic effect, it was abolished by AC inhibitors SQ22536 and NYK80. Finally, the inotropic effect of verapamil was associated with increased intracellular cAMP content and mobilization of intracellular Ca(2+), indicating that positive inotropic effects of Ca(2+) blockers depend on cAMP formation. Together, our results show that extracellular Ca(2+) modulates skeletal muscle contraction, through inhibition of Ca(2+)-sensitive AC. The cross-talk between extracellular calcium and cAMP-dependent signaling pathways appears to regulate the extent of skeletal muscle contraction responses. © 2013 Published by Elsevier B.V.

  14. A SEARCH FOR L/T TRANSITION DWARFS WITH PAN-STARRS1 AND WISE. II. L/T TRANSITION ATMOSPHERES AND YOUNG DISCOVERIES

    International Nuclear Information System (INIS)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Chambers, K. C.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Deacon, Niall R.; Redstone, Joshua; Burgett, W. S.; Draper, P.; Metcalfe, N.

    2015-01-01

    The evolution of brown dwarfs from L to T spectral types is one of the least understood aspects of the ultracool population, partly for lack of a large, well-defined, and well-characterized sample in the L/T transition. To improve the existing census, we have searched ≈28,000 deg 2 using the Pan-STARRS1 and Wide-field Infrared Survey Explorer surveys for L/T transition dwarfs within 25 pc. We present 130 ultracool dwarf discoveries with estimated distances ≈9–130 pc, including 21 that were independently discovered by other authors and 3 that were previously identified as photometric candidates. Seventy-nine of our objects have near-IR spectral types of L6–T4.5, the most L/T transition dwarfs from any search to date, and we have increased the census of L9–T1.5 objects within 25 pc by over 50%. The color distribution of our discoveries provides further evidence for the “L/T gap,” a deficit of objects with (J − K) MKO  ≈ 0.0–0.5 mag in the L/T transition, and thus reinforces the idea that the transition from cloudy to clear photospheres occurs rapidly. Among our discoveries are 31 candidate binaries based on their low-resolution spectral features. Two of these candidates are common proper motion companions to nearby main sequence stars; if confirmed as binaries, these would be rare benchmark systems with the potential to stringently test ultracool evolutionary models. Our search also serendipitously identified 23 late-M and L dwarfs with spectroscopic signs of low gravity implying youth, including 10 with vl-g or int-g gravity classifications and another 13 with indications of low gravity whose spectral types or modest spectral signal-to-noise ratio do not allow us to assign formal classifications. Finally, we identify 10 candidate members of nearby young moving groups (YMG) with spectral types L7–T4.5, including three showing spectroscopic signs of low gravity. If confirmed, any of these would be among the coolest known YMG members and would

  15. CagI is an essential component of the Helicobacter pylori Cag type IV secretion system and forms a complex with CagL.

    Directory of Open Access Journals (Sweden)

    Kieu Thuy Pham

    Full Text Available Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly.

  16. Allelopathic potential of leaf and seed of Mucuna bracteata DC. ex Kurz on Eleusine indica (L.) gaertn

    Science.gov (United States)

    Halimshah, Syamimi; Ismail B., S.; Ahmad, Wan Juliana Wan

    2015-09-01

    A study was conducted to determine the allelopathic potential of leaf and seed of Mucuna bracteata on the growth of E. indica through aqueous extract and debris (incorporated into the soil) experiment. Three concentrations of leaf and seed aqueous extract (16.7, 33.3 and 66.7 g/L) and debris (2.5, 5.0 and 10.0 g/500 g soil) of M. bracteata were used in the experiment. Complete randomized design (CRD) with three replications was applied in this experiment which was conducted twice. Results demonstrated that the leaf and seed extracts of M. bracteata exhibited higher suppression effect on the growth and germination of E. indica as the concentration increased. The leaf and seed extracts significantly reduced all measured parameters at all concentrations except for the shoot length and germination of E. indica by seed extract at 16.7 g/L which recorded insignificant reduction by 40.5% and 4% respectively. The leaf and seed debris significantly reduced the root length of E. indica at all treatments. Seed debris also showed significant reduction on the germination at all treatments and other seedling growth parameters (shoot length, fresh weight and dry weight) at 2.5 and 10.0 g/500 g soil. Meanwhile, the leaf debris demonstrated stimulation effect on the seedling growth parameters. As a whole, the leaf showed higher suppression effect in aqueous extract experiment while the seed recorded higher suppression effect in the debris experiment. Further studies need to be conducted to investigate the type of inhibition mechanism involved in both experiments.

  17. Loss-of-flow test L5 on FFTF-type irradiated fuel

    International Nuclear Information System (INIS)

    Simms, R.; Gehl, S.M.; Lo, R.K.; Rothman, A.B.

    1978-03-01

    Test L5 simulated a hypothetical loss-of-flow accident in an LMFBR using three (Pu, U)O 2 fuel elements of the FTR type. The test elements were irradiated before TREAT Test L5 in the General Electric Test Reactor to 8 at. % burnup at about 40 kW/m. The preirradiation in GETR caused a fuel-restructuring range characteristic of moderate-power structure relative to the FTR. The test transient was devised so that a power burst would be initiated at incipient cladding melting after the loss of flow. The test simulation corresponds to a scenario for FTR in which fuel in high-power-structure subassemblies slump, resulting in a power excursion. The remaining subassemblies are subjected to this power burst. Test L5 addressed the fuel-motion behavior of the subassemblies in this latter category. Data from test-vehicle sensors, hodoscope, and post-mortem examinations were used to construct the sequence of events within the test zone. From these observations, the fuel underwent a predominantly dispersive event just after reaching a peak power six times nominal at, or after, scram. The fuel motion was apparently driven by the release of entrained fission-product gases, since fuel vapor pressure was deliberately kept below significant levels for the transient. The test remains show a wide range of microstructural evolution, depending on the extent of heat deposition along the active fuel column. Extensive fuel swelling was also observed as a result of the lack of the cladding restraint. The results of the thermal-hydraulic calculations with the SAS3A code agreed qualitatively with the postmortem results with respect to the extent of the melting and the dispersal of cladding and fuel. However, the calculated times of certain events did not agree with the observed times

  18. Evaluation of antioxidant potential of pepper sauce (Capsicum frutescens L.

    Directory of Open Access Journals (Sweden)

    Pamela Freire de Moura Pereira

    2016-12-01

    Full Text Available Functional properties of substances present in in natura foods such as fruits and vegetables are well documented; however, the activity that remains after processing needs more research. The present study aimed to evaluate the antioxidant potential in fruit processed as sauce and quantify the compounds able to contribute to such activity. Three different treatments were developed varying only the concentration of pepper Capsicum frutescens L., with treatment ratios (fruit: water: vinegar: salt being: treatment 1 (0.5: 1: 0.5: 0.33, 2 (1: 1: 0.5: 0.33, and 3 (2: 1: 0.5: 0.33. By the DPPH method, the values found for EC50 (g g DPPH−1 from 3726.9 to 5425.9 for the alcoholic extract were the most significant. The content of total phenols did not vary between the three treatments. While the content of carotenoids found was significantly different in the treatment with lower content of the fruit in natura, when compared to the treatment with higher content (44.02 and 56.09 μg of β-carotene 100 g−1, respectively and the content of ascorbic acid varied between 10.95 and 21.59 mg 100−1 g. Therefore, the pepper sauce was presented as an alternative to the consumption of bioactive compounds that may have antioxidant potential.

  19. Convergence of an L2-approach in the coupled-channels optical potential method for e-H scattering

    International Nuclear Information System (INIS)

    Bray, I.; Konovalov, D.A.; McCarthy, I.E.

    1990-08-01

    An L 2 approach to the coupled-channels optical method is studied. The investigation is done for electron-hydrogen elastic scattering at projectile energies of 30, 50, 100 and 200 eV. Weak coupling, free-particle Green's function and no exchange in Q-space are appoximations used to calculate the polarization potential. This model problem is solved exactly using actual hydrogen discrete and continuum functions. The convergence of an L 2 approach with the Laguerre basis to the exact result is investigated. It is found that a basis of 10 Laguerre functions is sufficient for convergence of approximately 5% in the polarization potential matrix elements and 2% in the differential cross sections for non-large angles. The convergence is faster for smaller energies. In general, the convergence to the exact result is slow. 12 refs., 2 tabs., 2 figs

  20. Fragilisinins A–L, new briarane-type diterpenoids from gorgonian Junceella fragilis

    KAUST Repository

    Lei, Hui; Sun, Jian Fan; Han, Zhuang; Zhou, Xue Feng; Yang, Bin; Liu, Yonghong

    2014-01-01

    Our continuous study on the South China Sea gorgonian Junceella fragilis led to the isolation of twelve new briarane type diterpenoids, fragilisinins A-L (1-12), along with seven known analogues (13-19), including four naturally produced organoiodides (9-12), they are the first four iodine-containing briarane diterpenoids from this gorgonian species. Their structures were determined by MS, 1D and 2D NMR spectra analyses and by comparison with those reported in the literature. The configuration of 1 was confirmed by single-crystal X-ray diffraction data. The antifouling test showed that compounds 5, 6, 10, 13, and 15 had potent antifouling activities at nontoxic concentrations with EC50 values of 14.0, 12.6, 11.9, 5.6, and 10.0 μM, respectively. © 2014 The Royal Society of Chemistry.

  1. Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats

    DEFF Research Database (Denmark)

    Liu, Daoyan; Yang, Dachun; He, Hongbo

    2009-01-01

    We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochem...

  2. Rapid L2 Word Learning through High Constraint Sentence Context: An Event-Related Potential Study

    Directory of Open Access Journals (Sweden)

    Baoguo Chen

    2017-12-01

    Full Text Available Previous studies have found quantity of exposure, i.e., frequency of exposure (Horst et al., 1998; Webb, 2008; Pellicer-Sánchez and Schmitt, 2010, is important for second language (L2 contextual word learning. Besides this factor, context constraint and L2 proficiency level have also been found to affect contextual word learning (Pulido, 2003; Tekmen and Daloglu, 2006; Elgort et al., 2015; Ma et al., 2015. In the present study, we adopted the event-related potential (ERP technique and chose high constraint sentences as reading materials to further explore the effects of quantity of exposure and proficiency on L2 contextual word learning. Participants were Chinese learners of English with different English proficiency levels. For each novel word, there were four high constraint sentences with the critical word at the end of the sentence. Learners read sentences and made semantic relatedness judgment afterwards, with ERPs recorded. Results showed that in the high constraint condition where each pseudoword was embedded in four sentences with consistent meaning, N400 amplitude upon this pseudoword decreased significantly as learners read the first two sentences. High proficiency learners responded faster in the semantic relatedness judgment task. These results suggest that in high quality sentence contexts, L2 learners could rapidly acquire word meaning without multiple exposures, and L2 proficiency facilitated this learning process.

  3. Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

    Science.gov (United States)

    Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

    2018-06-01

    Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

  4. Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

    Directory of Open Access Journals (Sweden)

    Naoya Maekawa

    Full Text Available Programmed death 1 (PD-1, an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1, its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.

  5. A qualitative examination of the content validity of the EQ-5D-5L in patients with type 2 diabetes.

    Science.gov (United States)

    Matza, Louis S; Boye, Kristina S; Stewart, Katie D; Curtis, Bradley H; Reaney, Matthew; Landrian, Amanda S

    2015-12-01

    The EQ-5D is frequently used to derive utilities for patients with type 2 diabetes (T2D). Despite widely available quantitative psychometric data on the EQ-5D, little is known about content validity in this population. Thus, the purpose of this qualitative study was to examine content validity of the EQ-5D in patients with T2D. Patients with T2D in the UK completed concept elicitation interviews, followed by administration of the EQ-5D-5L and cognitive interviewing focused on the instrument's relevance, clarity, and comprehensiveness. A total of 25 participants completed interviews (52.0 % male; mean age = 53.5 years). Approximately half (52 %) reported that the EQ-5D-5L was relevant to their experience with T2D. When asked if each individual item was relevant to their experience with T2D, responses varied widely (24.0 % said the self-care item was relevant; 68.0 % said the anxiety/depression item was relevant). Participants frequently said items were not relevant to themselves, but could be relevant to patients with more severe diabetes. Most participants (92.0 %) reported that T2D and/or its treatment/monitoring requirements had an impact on their quality of life that was not captured by the EQ-5D-5L. Common missing concepts included food awareness/restriction (n = 13, 52.0 %); activities (n = 11, 44.0 %); emotional functioning other than depression/anxiety (n = 8, 32.0 %); and social/relationship functioning (n = 8, 32.0 %). The results highlight strengths and potential limitations of the EQ-5D-5L, including missing content that could be important for some patients with T2D. Suggestions for addressing limitations are provided.

  6. The potential of wild vegetation species of Eleusine indica L., and Sonchus arvensis L. for phytoremediation of Cd-contaminated soil

    Directory of Open Access Journals (Sweden)

    Amir Hamzah

    2017-04-01

    Full Text Available Phytoremediation has been intensively studied due its costs effectiveness and environmentally sound. Studies of heavy metal pollution phytoremediation has been done in develop countries, but still limited in Indonesia. This study aims to explore the potential of wild plant species Eleusine indica L. and Sonchus arvensis L. as an agent of phytoremediation on Cd-contaminated soil. This study was done descriptively in Pujon, Malang, Indonesia, to test the ability of two species of wild plants E. indica and S. arvensis in absorbing Cd. Along this research, plant growth and the concentration of Cd in roots, stems and leaves, was monitored. Plant growth was measured every week for three months. The plant roots, stems, and leaves collected separately, then analyzed its Cd levels. The results showed that both of two species of wild plants grew well on soil contaminated Cd. Plant roots can accumulate higher Cd than the stem part. In addition, E indica has the ability to accumulate Cd higher than S. arvensis, i.e. 57.11% and 35.84%, respectively

  7. Enterprise Potential: Essence, Classification and Types

    Directory of Open Access Journals (Sweden)

    Turylo Anatolii M.

    2014-02-01

    Full Text Available The article considers existing approaches to classification of the enterprise potential as an economic notion. It offers own vision of classification of enterprise potential, which meets modern tendencies of enterprise development. Classification ensures a possibility of a wider description and assessment of enterprise potential and also allows identification of its most significant characteristics. Classification of the enterprise potential is developed by different criteria: by functions, by resource support, by ability to adapt, by the level of detection, by the spectrum of taking into account possibilities, by the period of coverage of possibilities and by the level of use. Analysis of components of the enterprise potential allows obtaining a complete and trustworthy assessment of the state of an enterprise. Adaptation potential of an enterprise is based on principles systemacy and dynamism, it characterises possibilities of adjustment of an enterprise to external and internal economic conditions.

  8. Potencial antioxidativo da lágrima de adultos jovens Tear antioxidant potential in young adults

    Directory of Open Access Journals (Sweden)

    Patrícia Ioschpe Gus

    2006-08-01

    smoking, alcohol ingestion, fruit, vegetable, cereal, and vitamin intake and/or intake of other drugs, and physical exercise habits. Chemoluminescensce of luminol was used to analyze the total reactive antioxidant potential (TRAP, inhibition of piragollol was used to measure superoxide dismutase (SOD and absorbance of H2O2 at 240 nm was used to identify catalase. RESULTS: Mean ± SD value for total reactive antioxidant potential was 33.8±11.5 µM and for superoxide dismutase 10.8±1.9 U/mL. Catalase was not identified. Regular exercise was associated with increased total reactive antioxidant potential values (p=0.021, with a difference of 18.6 µM between individuals who exercise at least once a week and sedentary individuals. Male gender and total reactive antioxidant potential values were statistically associated (p=0.013, with a difference of 16.3 µM between genders. There was an association between smoking and increased superoxide dismutase values (p=0.041, with a difference of 3.3 U/mL between smokers of more than five cigarettes/day and non-smokers. Also, vitamin C intake and superoxide dismutase values were associated (p=0.018; the difference for vitamin C takers was 3.3 U/mL. CONCLUSION: Reflex tearing antioxidants were measurable in healthy young adults, and different variables apparently influenced their values.

  9. Genotypic and phenotypic evaluation of off-type grasses in hybrid Bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy] putting greens using genotyping-by-sequencing and morphological characterization.

    Science.gov (United States)

    Reasor, Eric H; Brosnan, James T; Staton, Margaret E; Lane, Thomas; Trigiano, Robert N; Wadl, Phillip A; Conner, Joann A; Schwartz, Brian M

    2018-01-01

    Interspecific hybrid bermudagrass [ Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy] is one of the most widely used grasses on golf courses, with cultivars derived from 'Tifgreen' or 'Tifdwarf' particularly used for putting greens. Many bermudagrass cultivars established for putting greens can be genetically unstable and lead to the occurrence of undesirable off-type grasses that vary in phenotype. The objective of this research was to genetically and phenotypically differentiate off-type grasses and hybrid cultivars. Beginning in 2013, off-type and desirable hybrid bermudagrass samples were collected from golf course putting greens in the southeastern United States and genetically and phenotypically characterized using genotyping-by-sequencing and morphology. Genotyping-by-sequencing determined that 11% (5) of off-type and desirable samples from putting greens were genetically divergent from standard cultivars such as Champion, MiniVerde, Tifdwarf, TifEagle, and Tifgreen. In addition, genotyping-by-sequencing was unable to genetically distinguish all standard cultivars from one another due to their similar origin and clonal propagation; however, over 90,000 potentially informative nucleotide variants were identified among the triploid hybrid cultivars. Although few genetic differences were found in this research, samples harvested from golf course putting greens had variable morphology and were clustered into three distinct phenotypic groups. The majority of off-type grasses in hybrid bermudagrass putting greens were genetically similar with variable morphological traits. Off-type grasses within golf course putting greens have the potential to compromise putting surface functionality and aesthetics.

  10. The pathogenic potential of different pulsed-field gel electrophoresis types of Listeria monocytogenes strains isolated from food in Northeast Bosnia and Herzegovina.

    Science.gov (United States)

    Hodžić, Snjezana; Hukić, Mirsada; Franciosa, Giovanna; Aureli, Paolo

    2011-09-01

    Listeria monocytogenes is often present in meat and meat products that are sold in the area of northeast Bosnia and Herzegovina. The major objective of this study was to examine the virulence of L. monocytogenes strains isolated from these types of food in that geographic area. Polymerase chain reaction was used to detect eight genes responsible for virulence of this pathogen, namely, prfA, inlA, inlB, hly, plcA, plcB, actA, and mpl. All examined isolates were confirmed to possess the eight virulence genes. Ten different pulsed-field gel electrophoresis (PFGE) macrorestriction profiles were recognized among 19 L. monocytogenes strains after restriction with two different endonucleases (ApaI and AscI). The pathogenicity of three different PFGE types of L. monocytogenes was confirmed through in vivo tests, which were performed on female white mice (Pasteur strain), and it ranged from 3.55 × 10(8) LD50 to 1.58 × 10(10) LD50. All of the three different PFGE types of L. monocytogenes were regarded as moderately virulent in relation to the reference strain L. monocytogenes Scott A. This result might be one of the reasons for the absence of reported listeriosis in northeast Bosnia and Herzegovina, despite the high degree of food contamination with this pathogen.

  11. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity.

    Science.gov (United States)

    Zaccard, Colleen R; Watkins, Simon C; Kalinski, Pawel; Fecek, Ronald J; Yates, Aarika L; Salter, Russell D; Ayyavoo, Velpandi; Rinaldo, Charles R; Mailliard, Robbie B

    2015-02-01

    The ability of dendritic cells (DC) to mediate CD4(+) T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread. Copyright © 2015 by The American Association of Immunologists, Inc.

  12. Bound and scattering wave functions for a velocity-dependent Kisslinger potential for l>0

    International Nuclear Information System (INIS)

    Jaghoub, M.I.

    2002-01-01

    Using formal scattering theory, the scattering wave functions are extrapolated to negative energies corresponding to bound-state poles. It is shown that the ratio of the normalized scattering and the corresponding bound-state wave functions, at a bound-state pole, is uniquely determined by the bound-state binding energy. This simple relation is proved analytically for an arbitrary angular momentum quantum number l>0, in the presence of a velocity-dependent Kisslinger potential. The extrapolation relation is tested analytically by solving the Schroedinger equation in the p-wave case exactly for the scattering and the corresponding bound-state wave functions when the Kisslinger potential has the form of a square well. A numerical resolution of the Schroedinger equation in the p-wave case and of a square-well Kisslinger potential is carried out to investigate the range of validity of the extrapolated connection. It is found that the derived relation is satisfied best at low energies and short distances. (orig.)

  13. Nutraceutical potential of hemp (Cannabis sativa L.) seeds and sprouts.

    Science.gov (United States)

    Frassinetti, Stefania; Moccia, Eleonora; Caltavuturo, Leonardo; Gabriele, Morena; Longo, Vincenzo; Bellani, Lorenza; Giorgi, Gianluca; Giorgetti, Lucia

    2018-10-01

    In this study the antioxidant effect of Cannabis sativa L. seeds and sprouts (3 and 5 days of germination) was evaluated. Total polyphenols, flavonoids and flavonols content, when expressed on dry weight basis, were highest in sprouts; ORAC and DPPH (in vitro assays), CAA-RBC (cellular antioxidant activity in red blood cells) and hemolysis test (ex vivo assays) evidenced a good antioxidant activity higher in sprouts than in seeds. Untargeted analysis by high resolution mass spectrometry in negative ion mode allowed the identification of main polyphenols (caffeoyltyramine, cannabisin A, B, C) in seeds and of ω-6 (linoleic acid) in sprouts. Antimutagenic effect of seeds and sprouts extracts evidenced a significant decrease of mutagenesis induced by hydrogen peroxide in Saccharomyces cerevisiae D7 strain. In conclusion our results show that C. sativa seeds and sprouts exert beneficial effects on yeast and human cells and should be further investigated as a potential functional food. Copyright © 2018. Published by Elsevier Ltd.

  14. Rapid detection and typing of pathogenic nonpneumophila Legionella spp. isolates using a multiplex real-time PCR assay.

    Science.gov (United States)

    Benitez, Alvaro J; Winchell, Jonas M

    2016-04-01

    We developed a single tube multiplex real-time PCR assay that allows for the rapid detection and typing of 9 nonpneumophila Legionella spp. isolates that are clinically relevant. The multiplex assay is capable of simultaneously detecting and discriminating L. micdadei, L. bozemanii, L. dumoffii, L. longbeachae, L. feeleii, L. anisa, L. parisiensis, L. tucsonensis serogroup (sg) 1 and 3, and L. sainthelensis sg 1 and 2 isolates. Evaluation of the assay with nucleic acid from each of these species derived from both clinical and environmental isolates and typing strains demonstrated 100% sensitivity and 100% specificity when tested against 43 other Legionella spp. Typing of L. anisa, L. parisiensis, and L. tucsonensis sg 1 and 3 isolates was accomplished by developing a real-time PCR assay followed by high-resolution melt (HRM) analysis targeting the ssrA gene. Further typing of L. bozemanii, L. longbeachae, and L. feeleii isolates to the serogroup level was accomplished by developing a real-time PCR assay followed by HRM analysis targeting the mip gene. When used in conjunction with other currently available diagnostic tests, these assays may aid in rapidly identifying specific etiologies associated with Legionella outbreaks, clusters, sporadic cases, and potential environmental sources. Published by Elsevier Inc.

  15. Non-perturbative scalar potential inspired by type IIA strings on rigid CY

    Energy Technology Data Exchange (ETDEWEB)

    Alexandrov, Sergei [Laboratoire Charles Coulomb (L2C), UMR 5221, CNRS-Université de Montpellier,F-34095, Montpellier (France); Ketov, Sergei V. [Department of Physics, Tokyo Metropolitan University,1-1 Minami-ohsawa, Hachioji-shi, Tokyo 192-0397 (Japan); Kavli Institute for the Physics and Mathematics of the Universe (IPMU), The University of Tokyo,Chiba 277-8568 (Japan); Institute of Physics and Technology, Tomsk Polytechnic University,30 Lenin Ave., Tomsk 634050 (Russian Federation); Wakimoto, Yuki [Department of Physics, Tokyo Metropolitan University,1-1 Minami-ohsawa, Hachioji-shi, Tokyo 192-0397 (Japan)

    2016-11-10

    Motivated by a class of flux compactifications of type IIA strings on rigid Calabi-Yau manifolds, preserving N=2 local supersymmetry in four dimensions, we derive a non-perturbative potential of all scalar fields from the exact D-instanton corrected metric on the hypermultiplet moduli space. Applying this potential to moduli stabilization, we find a discrete set of exact vacua for axions. At these critical points, the stability problem is decoupled into two subspaces spanned by the axions and the other fields (dilaton and Kähler moduli), respectively. Whereas the stability of the axions is easily achieved, numerical analysis shows instabilities in the second subspace.

  16. Effects of soil type, moisture content, redox potential and methyl bromide fumigation on Kd values of radio-selenium in soil

    International Nuclear Information System (INIS)

    Ashworth, D.J.; Moore, J.; Shaw, G.

    2008-01-01

    Understanding the processes that determine the solid-liquid partitioning (K d value) of Se is of fundamental importance in assessing the risk associated with the disposal of radio-selenium-containing waste. Using a mini-column (rather than batch) approach, K d values for 75 Se were determined over time in relation to soil moisture content (field capacity or saturated), redox potential and methyl bromide fumigation (used to disrupt the soil microbial population) in three contrasting soil types: clay loam, organic and sandy loam. The K d values were generally in the range 50-500 L kg -1 , with mean soil K d increasing with increasing organic matter content. Saturation with water lowered the measured redox potentials in the soils. However, only in the sandy loam soil did redox potential become negative, and this led to an increase in 75 Se K d value in this soil. Comparison of the data with the Eh-pH stability diagram for Se suggested that such strong reduction may have been consistent with the formation of the insoluble Se species, selenide. These findings, coupled with the fact that methyl bromide fumigation had no discernible effect on 75 Se K d value in the sandy loam soil, suggest that geochemical, rather than microbial, processes controlled 75 Se partitioning. The inter-relations between soil moisture content, redox potential and Se speciation should be considered in the modelling and assessment of radioactive Se fate and transport in the environment

  17. Comparison of the Tastes of L-Alanine and Monosodium Glutamate in C57BL/6J Wild Type and T1r3 Knockout Mice.

    Science.gov (United States)

    Eddy, Meghan C; Eschle, Benjamin K; Delay, Eugene R

    2017-09-01

    Previous research showed that L-alanine and monosodium L-glutamate elicit similar taste sensations in rats. This study reports the results of behavioral experiments designed to compare the taste capacity of C57BL/6J wild type and T1r3- mice for these 2 amino acids. In conditioned taste aversion (CTA) experiments, wild-type mice exhibited greater sensitivity than knockout mice for both L-amino acids, although knockout mice were clearly able to detect both amino acids at 50 mM and higher concentrations. Generalization of CTA between L-alanine and L-glutamate was bidirectionally equivalent for both mouse genotypes, indicating that both substances elicited similar tastes in both genotypes. This was verified by the discrimination experiments in which both mouse genotypes performed at or near chance levels at 75 and 150 mM. Above 150 mM, discrimination performance improved, suggesting the taste qualities of the 2 L-amino acids are not identical. No differences between knockout and wild-type mice in discrimination ability were detected. These results indicate that while the T1r3 receptor is important for tasting L-alanine and L-glutamate, other receptors are also important for tasting these amino acids. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. The potential of Lemna gibba L. and Lemna minor L. to remove Cu, Pb, Zn, and As in gallery water in a mining area in Keban, Turkey.

    Science.gov (United States)

    Sasmaz, Merve; Arslan Topal, Emine Işıl; Obek, Erdal; Sasmaz, Ahmet

    2015-11-01

    This study was designed to investigate removal efficiencies of Cu, Pb, Zn, and As in gallery water in a mining area in Keban, Turkey by Lemna gibba L. and Lemna minor L. These plants were placed in the gallery water of Keban Pb-Zn ore deposits and adapted individually fed to the reactors. During the study period (8 days), the plant and water samples were collected daily and the temperature, pH, and electric conductivity of the gallery water were measured daily. The plants were washed, dried, and burned at 300 °C for 24 h in a drying oven. These ash and water samples were analyzed by ICP-MS to determine the amounts of Cu, Pb, Zn, and As. The Cu, Pb, Zn and As concentrations in the gallery water of the study area detected 67, 7.5, 7230, and 96 μg L(-1), respectively. According to the results, the obtained efficiencies in L. minor L. and L. gibba L. are: 87% at day 2 and 36% at day 3 for Cu; 1259% at day 2 and 1015% at day 2 for Pb; 628% at day 3 and 382% at day 3 for Zn; and 7070% at day 3 and 19,709% at day 2 for As, respectively. The present study revealed that both L. minor L. and L. gibba L. had very high potential to remove Cu, Pb, Zn, and As in gallery water contaminated by different ores. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. A comparative analysis of physical and chemical properties of Jatropha Curcas. L, Calophyllum Inophyllum. L and Sterculia Feotida. L oil

    Energy Technology Data Exchange (ETDEWEB)

    Silitonga, A.S. [Department of Mechanical Engineering, Medan State Polytechnic (Indonesia)], email: ardinsu@yahoo.co.id, email: a_atabani2@msn.com; Atabani, A.E. [Department of Mechanical Engineering, University of Khartoum (Sudan); Mahlia, T.M.I. [Department of Mechanical Engineering, Syiah Kuala University, (Indonesia); Masjuki, H.H.; Badruddin, I.A. [Department of Mechanical Engineering, University of Malaya (Malaysia)

    2011-07-01

    Production of bio-diesel converted from edible oil has raised the issue of competition for resources between food production and fuel production, as well as other questions of environmental impact. It has been established that producing bio-diesel from non-edible vegetable oils was one of the effective ways to resolve these issues. Jatropha curcas L., Calophyllum inophyllum L., and Sterculia foetida L. are all non-edible oils and all can be potential sources for future energy supply. The purpose of this paper is to reveal the results of a comparative analysis of the physical and chemical properties of Jatropha curcas L., Calophyllum inophyllum L., and Sterculia foetida L. oils. Physical and chemical properties of these vegetable oils, such as density, iodine value, free fatty acid, etc. were investigated and measured. These properties were then compared with those of other non-edible vegetable oils in terms of potential. This paper finds that the results of analysis indicate that there is high potential for using Jatropha curcas L., Calophyllum inophyllum L., and Sterculia foetida L. crude oil as an alternative fuel.

  20. Alpha-L-Arabinofuranosidases: The potential applications in biotechnology

    Digital Repository Service at National Institute of Oceanography (India)

    Numan, M.Th.; Bhosle, N.B.

    in the dough [44,45,59,79]. This positively interferes with the metabolism of sourdough lactic acid bacterium Lactobacillus hilgardii [44]. This bacterium increases the acidification rates and the production of acetic acid. For example, Gobbetti et al [45...] showed that, by using pentosans, �D�D -L-AFase from Aspergillus niger and Lactobacillus plantarum 20B, soluble carbohydrate availability, acidification rate and production of acetic acid increased during sourdough fermentation. ���D���D���D���D -L...

  1. Characterization of different native american physalis species and evaluation of their processing potential as jelly in combination with brie-type cheese

    Directory of Open Access Journals (Sweden)

    Paula Nogueira CURI

    Full Text Available Abstract Faced with the need for greater knowledge of the different physalis species, the aim of this study was to characterize different Native American physalis species (Physalis peruviana L., Physalis pubescens L., Physalis angulata L., Physalis mínimos L. and Physalis ixocarpa Brot as to their physicochemical characteristics, bioactive compounds and antioxidant activity. Besides that, in order to increase their use and add even more value to this fruit, we also evaluate the influence of these different species on the physicochemical, rheological and sensory characteristics of physalis jelly. In addition, this study evaluated the sensory acceptance of the combination of physalis jellies obtained from different species with brie-type cheese. The Peruviana, Pubences and Angulata, are highlighted for being the nutritionally richest species, with the highest levels of phenolic compounds, vitamin C and antioxidant. Moreover, they stand out for originating the most widely sensory accepted jellies, either in pure form or in combination with brie-type cheese.

  2. Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene.

    Science.gov (United States)

    Pinés Corrales, Pedro José; López Garrido, María P; Aznar Rodríguez, Silvia; Louhibi Rubio, Lynda; López Jiménez, Luz M; Lamas Oliveira, Cristina; Alfaro Martínez, Jose J; Lozano García, Jose J; Hernández López, Antonio; Requejo Castillo, Ramón; Escribano Martínez, Julio; Botella Romero, Francisco

    2010-01-01

    The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1alpha gene. The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1alpha gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene had no family history of diabetes (p MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene (p MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  3. Combined effects of changing-sign potential and critical nonlinearities in Kirchhoff type problems

    Directory of Open Access Journals (Sweden)

    Gao-Sheng Liu

    2016-08-01

    Full Text Available In this article, we study the existence and multiplicity of positive solutions for a class of Kirchhoff type problems involving changing-sign potential and critical growth terms. Using the concentration compactness principle and Nehari manifold, we obtain the existence and multiplicity of nonzero non-negative solutions.

  4. TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population

    Directory of Open Access Journals (Sweden)

    Mill JG

    2008-12-01

    Full Text Available Abstract Background Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. Methods We genotyped the single nucleotide polymorphisms (SNP rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. Results SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032, confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776. Conclusion TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world

  5. Preliminary nutritional and biological potential of Artocarpus heterophyllus L. shell powder.

    Science.gov (United States)

    Sharma, Anubhuti; Gupta, Priti; Verma, A K

    2015-03-01

    Artocarpus heterophyllus shell powder was investigated in terms of its nutritional and biological potential. A thorough examination of shell powder demonstrated its potential as a source of minerals, β carotene and dietary fiber, which were assessed gravimetrically & spectrophotometrically. This showed 3.05 ± 0.19 g 100 g(-1) DW of alkaloids followed by saponins and tannins. Three different extracts; acetone, methanol, & mix solvent were used to evaluate phenolic & flavonoid content, antioxidant & antimicrobial activity, GC/MS screening and quantitative analysis of polyphenols. Among all, the methanol extract showed highest antioxidant activity evaluated by DPPH, FRAP & ABTS assays and was significantly correlated with phenolic and flavonoid contents. Phenolic & flavonoid content was found to be 158 ± 0.34 mg (GAE) and 10.0 ± 0.64 mg (CE) respectively. The results of antimicrobial activity showed that L. monocytogenes was more susceptible to all extracts followed by other microorganisms. Catechin, ascorbic & chlorogenic acids were identified as major polyphenols analyzed by LC-MS/MS. GC/MS analysis showed that it contains a variety of compounds with different therapeutic activities. The study revealed that A. heterophyllus shell is a good source of natural antioxidants & other bioactive compounds and can be used in cosmetics, medicines and functional food application.

  6. DSC analysis of irradiated proteins from Crotalus durissus terrificus

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Karina Corleto de; Silva, Monica Nascimento da; Goncalves, Karina de Oliveira; Spencer, Patrick Jack; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Full text: Snake bites are a serious public health problem, especially in subtropical countries. In Brazil, the serum, the only effective treatment in case of snake bites, is produced in horses which, despite the large size, have a reduced lifespan due to the high toxicity of the antigen. It is known that ionizing radiation effects - direct and indirect - can modify the molecular structure, affecting the biological properties of proteins. Ionizing radiation has been employed to attenuate the toxicity of snake venoms, aiming to generate an improved antigen with low toxicity. Two proteins, purified from Crotalus durissus terrificus (Cdt) venom were tested in this work: crotoxin and crotamine. Crotoxin, the main toxic compound of Cdt venom, is a heterodimeric protein composed of two subunits: crotapotin and phospholipase A2. Crotamine is a highly basic polypeptide (pI - 10.3), with myotoxic activity and molecular weight of 4882 Da. It is composed of 42 amino acids residues and reticulated by three disulfide bonds. This study aimed to investigate the effects of radiation on crotoxin and crotamine using Differential Scanning Calorimetry (DSC). After isolation of the toxins by chromatographic techniques, they were irradiated with 2.0 kGy from {sup 60}Co source. The thermodynamics analysis, carried out in a METTLER TOLEDO, DSC 822e calorimeter, showed that irradiation promoted changes of the calorimetric profile. These changes suggest that, although radiation induced structural modifications of the protein, denaturation was only partial, since transition states could still be detected, suggesting that some structural elements were still present after irradiation. Taken together, our data suggest that following irradiation, the molecules underwent conformational changes, and that the remaining structural elements displayed a lower enthalpy, clearly indicating that the previously described loss of toxicity of irradiated toxins can be mostly ascribed to structural changes

  7. DSC analysis of irradiated proteins from Crotalus durissus terrificus

    International Nuclear Information System (INIS)

    Oliveira, Karina Corleto de; Silva, Monica Nascimento da; Goncalves, Karina de Oliveira; Spencer, Patrick Jack; Nascimento, Nanci do

    2011-01-01

    Full text: Snake bites are a serious public health problem, especially in subtropical countries. In Brazil, the serum, the only effective treatment in case of snake bites, is produced in horses which, despite the large size, have a reduced lifespan due to the high toxicity of the antigen. It is known that ionizing radiation effects - direct and indirect - can modify the molecular structure, affecting the biological properties of proteins. Ionizing radiation has been employed to attenuate the toxicity of snake venoms, aiming to generate an improved antigen with low toxicity. Two proteins, purified from Crotalus durissus terrificus (Cdt) venom were tested in this work: crotoxin and crotamine. Crotoxin, the main toxic compound of Cdt venom, is a heterodimeric protein composed of two subunits: crotapotin and phospholipase A2. Crotamine is a highly basic polypeptide (pI - 10.3), with myotoxic activity and molecular weight of 4882 Da. It is composed of 42 amino acids residues and reticulated by three disulfide bonds. This study aimed to investigate the effects of radiation on crotoxin and crotamine using Differential Scanning Calorimetry (DSC). After isolation of the toxins by chromatographic techniques, they were irradiated with 2.0 kGy from 60 Co source. The thermodynamics analysis, carried out in a METTLER TOLEDO, DSC 822e calorimeter, showed that irradiation promoted changes of the calorimetric profile. These changes suggest that, although radiation induced structural modifications of the protein, denaturation was only partial, since transition states could still be detected, suggesting that some structural elements were still present after irradiation. Taken together, our data suggest that following irradiation, the molecules underwent conformational changes, and that the remaining structural elements displayed a lower enthalpy, clearly indicating that the previously described loss of toxicity of irradiated toxins can be mostly ascribed to structural changes

  8. At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

    DEFF Research Database (Denmark)

    Hansen, Thomas; Ingason, Andrés; Djurovic, Srdjan

    2011-01-01

    BACKGROUND: Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication. METHODS: Eleven known risk variants of type...... (SGENE+) using Mantel-Haenszel test. RESULTS: One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033). CONCLUSION...... II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls...

  9. Relativistic effect of pseudospin symmetry and tensor coupling on the Mie-type potential via Laplace transformation method

    International Nuclear Information System (INIS)

    Eshghi, M.; Ikhdair, S. M.

    2014-01-01

    A relativistic Mie-type potential for spin-1/2 particles is studied. The Dirac Hamiltonian contains a scalar S(r) and a vector V(r) Mie-type potential in the radial coordinates, as well as a tensor potential U(r) in the form of Coulomb potential. In the pseudospin (p-spin) symmetry setting Σ = C ps and Δ = V(r), an analytical solution for exact bound states of the corresponding Dirac equation is found. The eigenenergies and normalized wave functions are presented and particular cases are discussed with any arbitrary spin—orbit coupling number κ. Special attention is devoted to the case Σ = 0 for which p-spin symmetry is exact. The Laplace transform approach (LTA) is used in our calculations. Some numerical results are obtained and compared with those of other methods. (general)

  10. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

    Science.gov (United States)

    De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

    2008-06-01

    The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

  11. Type 2C Phosphatase 1 of Artemisia annua L. Is a Negative Regulator of ABA Signaling

    Directory of Open Access Journals (Sweden)

    Fangyuan Zhang

    2014-01-01

    Full Text Available The phytohormone abscisic acid (ABA plays an important role in plant development and environmental stress response. Additionally, ABA also regulates secondary metabolism such as artemisinin in the medicinal plant Artemisia annua L. Although an earlier study showed that ABA receptor, AaPYL9, plays a positive role in ABA-induced artemisinin content improvement, many components in the ABA signaling pathway remain to be elucidated in Artemisia annua L. To get insight of the function of AaPYL9, we isolated and characterized an AaPYL9-interacting partner, AaPP2C1. The coding sequence of AaPP2C1 encodes a deduced protein of 464 amino acids, with all the features of plant type clade A PP2C. Transcriptional analysis showed that the expression level of AaPP2C1 is increased after ABA, salt, and drought treatments. Yeast two-hybrid and bimolecular fluorescence complementation assays (BiFC showed that AaPYL9 interacted with AaPP2C1. The P89S, H116A substitution in AaPYL9 as well as G199D substitution or deletion of the third phosphorylation site-like motif in AaPP2C1 abolished this interaction. Furthermore, constitutive expression of AaPP2C1 conferred ABA insensitivity compared with the wild type. In summary, our data reveals that AaPP2C1 is an AaPYL9-interacting partner and involved in the negative modulation of the ABA signaling pathway in A. annua L.

  12. Phytoremediation potential of Cd and Zn by wetland plants, Colocasia esculenta L. Schott., Cyperus malaccensis Lam. and Typha angustifolia L. grown in hydroponics.

    Science.gov (United States)

    Chayapan, P; Kruatrachue, M; Meetam, M; Pokethitiyook, P

    2015-09-01

    Cadmium and zinc phytoremediation potential of wetland plants, Colocasia esculenta, Cyperus malaccensis, and Typha angustifolia, was investigated. Plants were grown for 15 days in nutrient solutions containing various concentrations of Cd (0, 5, 10, 20, 50 mg l(-1)) and Zn (0, 10, 20, 50, 100 mg l(-1)). T angustifolia was tolerant to both metals as indicated by high RGR when grown in 50 mg I(-1) Cd and 100 mg I(-1) Zn solutions. All these plants accumulated more metals in their underground parts and > 100 mg kg(-1) in their aboveground with TF values 10,000 mg kg(-1) in its aboveground parts with TF > 1. T angustifolia exhibited highest biomass production and highest Cd and Zn uptake, confirming that this plant is a suitable candidate for treating of Cd contaminated soil/sediments.

  13. Phytochemical Composition and Antioxidant Potential of Ruta graveolens L. In Vitro Culture Lines

    Directory of Open Access Journals (Sweden)

    Renuka Diwan

    2012-01-01

    Full Text Available Ruta graveolens L. is a medicinal plant used in traditional systems of medicine for treatment of psoriasis, vitiligo, leucoderma, and lymphomas with well-known anti-inflammatory and anticancer properties. Therefore antioxidant potential of R. graveolens (in planta and in vitro was investigated. As antioxidants present in plant extracts are multifunctional, their activity and mechanism depends on the composition and conditions of the test system. Therefore, the total antioxidant capacity was evaluated using assays that detect different antioxidants: free radical scavenging (DPPH and ABTS, transition metal ion reduction (phosphomolybdenum assay, reducing power, and nitric oxide reduction. Content of furanocoumarin-bergapten in the extracts showed good corelation with free radical scavenging, transition metal reduction and reducing power, while total phenolic content showed good corelation with nitric oxide reduction potential. Antioxidant activity of in vitro cultures was significantly higher compared to in vivo plant material. The present study is the first report on comprehensive study of antioxidant activity of R. graveolens and its in vitro cultures.

  14. Cloud Atlas: Discovery of Rotational Spectral Modulations in a Low-mass, L-type Brown Dwarf Companion to a Star

    Science.gov (United States)

    Manjavacas, Elena; Apai, Dániel; Zhou, Yifan; Karalidi, Theodora; Lew, Ben W. P.; Schneider, Glenn; Cowan, Nicolas; Metchev, Stan; Miles-Páez, Paulo A.; Burgasser, Adam J.; Radigan, Jacqueline; Bedin, Luigi R.; Lowrance, Patrick J.; Marley, Mark S.

    2018-01-01

    Observations of rotational modulations of brown dwarfs and giant exoplanets allow the characterization of condensate cloud properties. As of now, rotational spectral modulations have only been seen in three L-type brown dwarfs. We report here the discovery of rotational spectral modulations in LP261-75B, an L6-type intermediate surface gravity companion to an M4.5 star. As a part of the Cloud Atlas Treasury program, we acquired time-resolved Wide Field Camera 3 grism spectroscopy (1.1–1.69 μm) of LP261-75B. We find gray spectral variations with the relative amplitude displaying only a weak wavelength dependence and no evidence for lower-amplitude modulations in the 1.4 μm water band than in the adjacent continuum. The likely rotational modulation period is 4.78 ± 0.95 hr, although the rotational phase is not well sampled. The minimum relative amplitude in the white light curve measured over the whole wavelength range is 2.41% ± 0.14%. We report an unusual light curve, which seems to have three peaks approximately evenly distributed in rotational phase. The spectral modulations suggests that the upper atmosphere cloud properties in LP261-75B are similar to two other mid-L dwarfs of typical infrared colors, but differ from that of the extremely red L-dwarf WISE0047.

  15. Fuel type characterization and potential fire behavior estimation in Sardinia and Corsica islands

    Science.gov (United States)

    Bacciu, V.; Pellizzaro, G.; Santoni, P.; Arca, B.; Ventura, A.; Salis, M.; Barboni, T.; Leroy, V.; Cancellieri, D.; Leoni, E.; Ferrat, L.; Perez, Y.; Duce, P.; Spano, D.

    2012-04-01

    Wildland fires represent a serious threat to forests and wooded areas of the Mediterranean Basin. As recorded by the European Commission (2009), during the last decade Southern Countries have experienced an annual average of about 50,000 forest fires and about 470,000 burned hectares. The factor that can be directly manipulated in order to minimize fire intensity and reduce other fire impacts, such as three mortality, smoke emission, and soil erosion, is wildland fuel. Fuel characteristics, such as vegetation cover, type, humidity status, and biomass and necromass loading are critical variables in affecting wildland fire occurrence, contributing to the spread, intensity, and severity of fires. Therefore, the availability of accurate fuel data at different spatial and temporal scales is needed for fire management applications, including fire behavior and danger prediction, fire fighting, fire effects simulation, and ecosystem simulation modeling. In this context, the main aims of our work are to describe the vegetation parameters involved in combustion processes and develop fire behavior fuel maps. The overall work plan is based firstly on the identification and description of the different fuel types mainly affected by fire occurrence in Sardinia (Italy) and Corsica (France) Islands, and secondly on the clusterization of the selected fuel types in relation to their potential fire behavior. In the first part of the work, the available time series of fire event perimeters and the land use map data were analyzed with the purpose of identifying the main land use types affected by fires. Thus, field sampling sites were randomly identified on the selected vegetation types and several fuel variables were collected (live and dead fuel load partitioned following Deeming et al., (1977), depth of fuel layer, plant cover, surface area-to-volume ratio, heat content). In the second part of the work, the potential fire behavior for every experimental site was simulated using

  16. Tipo de luz na multiplicação in vitro de framboeseira (Rubus idaeus L. 'Batum' Light type in the in vitro multiplication of raspberry plants (Rubus idaeus L. 'Batum'

    Directory of Open Access Journals (Sweden)

    Alan Cristiano Erig

    2005-12-01

    Full Text Available O objetivo deste trabalho foi determinar um possível tipo de luz mais ativo que a luz branca, de forma a aumentar a eficiência da multiplicação in vitro de framboeseira 'Batum', em relação ao número de brotos, de folhas e a taxa de multiplicação. Para isso, os tratamentos consistiram em cinco diferentes tipos de luz sob os quais os explantes cresceram (branca - testemunha, vermelha, amarela, azul e verde, fornecidas por meio da modificação do espectro luminoso das lâmpadas fluorescentes brancas-frias, utilizando filtros coloridos de acetato celulose, do tipo Lee Filters (Walworth Ind. Estate, Andover, England. O meio de cultura constituiu-se dos sais e vitaminas de MS, adicionado de mioinositol (100mgL-1, sacarose (30gL-1, ágar (6gL-1 e de BAP (4,44µM. A eficiência da multiplicação in vitro de framboeseira 'Batum', em relação às variáveis analisadas, aumentou com a utilização da luz verde. A luz vermelha também incrementou o número médio de brotos; no entanto, sua morfologia foi modificada, com uma menor expansão das folhas, os brotos finos e os entrenós alongados.The aim of this work was to determine a possible light type more active than the white light, in way to increase the efficiency of the in vitro multiplication of raspberry 'Batum', in relation to the shoots and leaves number, and the multiplication rate. For that, the treatments consisted of five different light types (white - control, red, yellow, blue and green, under which the explants grew, supplied through the modification of the luminous spectrum of the white-cold fluorescent lamps, using colored filters of acetate cellulose, Lee Filters type (Walworth Ind. Estate, Andover, England. The culture medium was constituted of MS salts and vitamins, added of myo-inositol (100mgL-1, sucrose (30gL-1, agar (6gL-1 and BAP (4.44µM. The efficiency of the in vitro multiplication of raspberry 'Batum', in relation to the analyzed variables, increased with the use of

  17. Sol-Generating Chemical Vapor into Liquid (SG-CViL) deposition – a facile method for encapsulation of diverse cell types in silica matrices

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Robert [New Mexico Inst. of Mining and Technology, Socorro, NM (United States). Materials Engineering Dept.; Rogelj, Snezna [New Mexico Inst. of Mining and Technology, Socorro, NM (United States). Biology Dept.; Harper, Jason C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Bioenergy and Biodefense Technologies Dept.; Tartis, Michaelann [New Mexico Inst. of Mining and Technology, Socorro, NM (United States). Materials and Chemical Engineering Dept.

    2014-12-12

    In nature, cells perform a variety of complex functions such as sensing, catalysis, and energy conversion which hold great potential for biotechnological device construction. However, cellular sensitivity to ex vivo environments necessitates development of bio–nano interfaces which allow integration of cells into devices and maintain their desired functionality. In order to develop such an interface, the use of a novel Sol-Generating Chemical Vapor into Liquid (SG-CViL) deposition process for whole cell encapsulation in silica was explored. In SG-CViL, the high vapor pressure of tetramethyl orthosilicate (TMOS) is utilized to deliver silica into an aqueous medium, creating a silica sol. Cells are then mixed with the resulting silica sol, facilitating encapsulation of cells in silica while minimizing cell contact with the cytotoxic products of silica generating reactions (i.e. methanol), and reduce exposure of cells to compressive stresses induced from silica condensation reactions. Using SG-CVIL, Saccharomyces cerevisiae (S. cerevisiae) engineered with an inducible beta galactosidase system were encapsulated in silica solids and remained both viable and responsive 29 days post encapsulation. By tuning SG-CViL parameters, thin layer silica deposition on mammalian HeLa and U87 human cancer cells was also achieved. Thus, the ability to encapsulate various cell types in either a multi cell (S. cerevisiae) or a thin layer (HeLa and U87 cells) fashion shows the promise of SG-CViL as an encapsulation strategy for generating cell–silica constructs with diverse functions for incorporation into devices for sensing, bioelectronics, biocatalysis, and biofuel applications.

  18. Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Ramadan, L.A.

    2003-01-01

    In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

  19. Effect of nitrogen on creep properties of type 316L(N) stainless steels

    International Nuclear Information System (INIS)

    Kim, Dae Whan; Lee, Yoon Kyu; Kim, Woo Gon; Ryu, Woo Seog

    2001-01-01

    The effects of nitrogen on the creep properties of type 316(N) stainless steels with three different nitrogen contents from 0.04% to 0.15% were investigated. Creep tests were carried out using constant-load single-lever machines at 550∼650 .deg. C in the air. The time to rupture increased and the minimum creep rate decreased with the addition of nitrogen. At constant stress, the rupture elongation decreased with the addition of nitrogen. Intergranular and transgranular fracture mode were mixed in all specimens. Cavity and carbides were nucleated at grain boundary and the number of cavity and carbide at constant stress was increased with the addition of nitrogen because of the increase in the time to rupture and carbide precipitation due to the addition of nitrogen. The increase of rupture time with the addition of nitrogen for type 316L(N) stainless steel was attributed to the combined effect of the decrease of minimum creep rate due to the increase of tensile strength and the rupture elongation due to the precipitation at grain boundaries

  20. Cytotoxic and Immunomodulatory Potential Activity of Physalis peruviana Fruit Extracts on Cervical Cancer (HeLa) and Fibroblast (L929) Cells.

    Science.gov (United States)

    Mier-Giraldo, Helen; Díaz-Barrera, Luis Eduardo; Delgado-Murcia, Lucy Gabriela; Valero-Valdivieso, Manuel Fernando; Cáez-Ramírez, Gabriela

    2017-10-01

    It was purposed to evaluate the biological potential of ethanol and isopropanol crude extracts of ripe Physalis peruviana fruits. Cytotoxic and immunomodulatory effects of the expression of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 (MCP-1) were evaluated on human cervical cancer (HeLa) and murine fibroblast (L929) cells. The composition was evaluated by high-performance liquid chromatography diode-array detection and high-performance liquid chromatography ultraviolet/visible detection. The presence of ursolic acid and rosmarinic acid was found in both solvents. However, gallic acid, quercetin, and epicatechin were higher in isopropanol extracts ( P < .05). The results indicated a relationship among the total polyphenol content, antioxidant activity, and cytotoxic activity that was dependent on the solvent used. Isopropanol extracts presented a half-maximal inhibition concentration value (IC 50 ) of 60.48 ± 3.8 μg/mL for HeLa cells and 66.62 ± 2.67 μg/mL for L929 fibroblasts. The extracts reduced the release of interleukin-6, interleukin-8, and MCP-1 in a dose-dependent manner. Extracts showed anticancer and immunomodulatory potential for new complementary pharmaceutical products development.

  1. Evaluation of the Nutraceutical and Cosmeceutical Potential of Two Cultivars of Rubus fruticosus L. under Different Cultivation Conditions.

    Science.gov (United States)

    Papaioanou, Maria; Chronopoulou, Evangelia G; Ciobotari, Gheorghii; Efrose, Rodica C; Sfichi-Duke, Liliana; Chatzikonstantinou, Marianna; Pappa, Evangelia; Ganopoulos, Ioannis; Madesis, Panagiotis; Nianiou-Obeidat, Irini; Zeng, Taofen; Labrou, Nikolaos E

    2017-01-01

    The starting point for the development of new, functional products derived from Rubus fruticosus L. is to determine the optimal cultivation conditions that produce maximal yield of fruits containing desirable bioactive properties. Towards that goal, the effect of soil, soil/peat mixture and light intensity on the nutraceutical and cosmeceutical potential of two cultivars ('Thornfree' and 'Loch Ness') of Rubus fruticosus L. were evaluated. The assessment was carried out employing a range of methods for evaluating fruit properties associated with promoting good health such as total antioxidant capacity, secondary metabolites content (vitamin C, polyphenols, flavonoids and anthocyanins) and inhibition analysis of skin-regulating enzymes. 'Thornfree' cultivar produced fruits in all light conditions, while 'Loch Ness' did not produce fruits in low light conditions. The results showed that in Rubus fruticosus L. fruit, the chemical composition and bioactivity are strongly affected by both genetics factors and growing conditions. Extract from 'Thornfree' fruits obtained under low light and soil/peat conditions displayed superior properties such as high antioxidant capacity, high concentrations of phenolics, flavonoids and anthocyanins and high inhibitory potency towards the enzymes tyrosinase and elastase. This extract was used for the development of a topical skin care cream with excellent compatibility and stability. Our findings conclude that Rubus fruticosus L. cultivation may be efficiently and effectively manipulated through conventional cultivation techniques to produce promising bioactive ingredients with potential use in commercial cosmetics and pharmaceuticals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. The role of the l1-norm in quantum information theory and two types of the Yang-Baxter equation

    International Nuclear Information System (INIS)

    Niu Kai; Ge Mollin; Xue Kang; Zhao Qing

    2011-01-01

    The role of the l 1 -norm in the Yang-Baxter system has been studied through Wigner's D-functions, where l 1 -norm means Σ i |C i | for |Ψ) = Σ i C i |ψ i ) with |ψ i ) being the orthonormal basis. It is shown that the existing two types of braiding matrices, which can be viewed as particular solutions of the Yang-Baxter equation (YBE) with different spectral parameters can be unified in the 2D YBE. We prove that the maximum of the l 1 -norm is connected with the maximally entangled states and topological quantum field theory with two-component anyons, while the minimum leads to the deformed permutation related to the familiar integrable models.

  3. Pharmacologically induced long QT type 2 can be rescued by activation of IKs with benzodiazepine R-L3 in isolated guinea pig cardiomyocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob Dahl; Diness, Jonas Goldin; Diness, Thomas Goldin

    2009-01-01

    of this study was to evaluate potential antiarrhythmic effects of compound induced IKs activation using the benzodiazepine L-364,373 (R-L3). Ventricular myocytes from guinea pigs were isolated and whole-cell current clamping was performed at 35 degrees C. It was found that 1 microM R-L3 significantly reduced...

  4. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

    Directory of Open Access Journals (Sweden)

    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  5. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

    2001-01-01

    The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... on vascular diameter in the afferent arteriole. We conclude that voltage-dependent L- and T-type calcium channels are expressed and of functional significance in renal cortical preglomerular vessels, in juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in cortical efferent...

  6. Ethanol yield and energy potential of stems from a spectrum of sorghum biomass types

    Energy Technology Data Exchange (ETDEWEB)

    McBee, G.G.; Creelman, R.A.; Miller, F.R.

    1988-01-01

    Sorghum biomass is a renewable resource that offers significant potential for energy utilization. Six sorghum cultivars, representing an array of stem types, were evaluated for ethanol yield. Ethanol production was individually obtained for both the total stem and the pith of each type by anaerobic yeast fermentation. Value of the energy contained in the rind was determined by calorimetry. The highest yield of ethanol from total stem fermentation was 3418.3 liters ha/sup -1/ produced from Rio. Fermentation of Rio pith to ethanol and combustion of the rind resulted in the highest total energy value of the cultivars. The least and greatest energy values were 6.3 and 44.3 x 10/sup 6/ kcal ha/sup -1/ for SC0056-14 and Rio, respectively. Conversion ratios of potentially fermentable carbohydrates (within the vegetative biomass) to ethanol produced, averaged 0.438 for the pith and 0.406 for total stems.

  7. Potential improvement of Lymantria dispar L. management by quercetin

    Directory of Open Access Journals (Sweden)

    Perić-Mataruga Vesna

    2014-01-01

    Full Text Available Lymantria dispar, a polyphagous insect pest, copes with a wide variety of host-specific allelochemicals. Glutathione S-transferases (GST are important for catalyzing detoxification in L. dispar. Larval mortality, GST activity in midgut tissue and mass of L. dispar with different trophic adaptations (originating from two forests with a suitable host, Quercus robur, and an unsuitable host, Robinia pseudoacacia, differed after feeding on quercetin supplemented diets (2% or 5% w/w. Quercetin inhibited GST most potently in oak forest larvae that were less adapted to flavonoids in their diet. The larvicidal effect of quercetin on L. dispar larvae depended on the host-use history. We believe this is important in strategies for sustainable control of insect pests. [Projekat Ministarstva nauke Republike Srbije, br. 173027

  8. Test and evaluation report for Westinghouse Hanford Company's 1-L Liquid Shipper, Docket 95-41-7A, Type A container

    International Nuclear Information System (INIS)

    Kelly, D.L.

    1995-11-01

    This report documents the U.S. Department of Transportation Specification 7A Type A (DOT-7A) compliance test results of the 1-L Liquid Shipper packaging. The 1-L Liquid Shipper consists of the 3M SafeSend polyethylene canister base and cap with integral sorbent material, a quad ring gasket, a plastic bag, and six foam inserts. A 1-L narrow-mouth, Teflon bottle with Tefzel lid holds contents. The inner bottle is placed inside the SafeSend container. The inner bottle content weight cannot exceed 2000 g (4.4 lb). Total bottle weight, including contents cannot exceed 2167.5 g (4.78 lb). The nominal gross weight of the assembled packaging is to be no more that 3830.5 g (8.4 lb). The approved packaging system is designed to ship Type A quantities of radioactive materials, normal form. Contents may be liquid or solid form. Liquid contents may have a specific gravity less than or equal to (<2). Solid materials are limited in weight, to include packaging, to the gross weight of the as-tested liquids and bottles

  9. Assessment of the biomass energy potentials and environmental benefits of Jatropha curcas L. in Southwest China

    International Nuclear Information System (INIS)

    Liu, Lei; Zhuang, Dafang; Jiang, Dong; Fu, Jingying

    2013-01-01

    Jatropha curcas L. (JCL) is believed to be the most promising tree species used to produce biodiesel in China. Due to its abundant marginal land resource and good meteorological conditions, Southwest China is the major region to develop JCL. With Southwest China being taken as the study area in this paper, multi-factor comprehensive analysis is used to identify marginal land resources suitable to JCL plantation and make suitability assessment, thus obtaining their spatial distribution, suitability degree and total amount. With life cycle analysis (LCA), the life cycle net energy and greenhouse gas emission reduction capacity of marginal land resources with different suitability degrees used to produce biodiesel are investigated. Based on the research results, the life cycle model is expanded to obtain the potentiality of total net energy production and greenhouse gas emission reduction of large-scale plantation of JCL in southwest China. The results show that the area of land resources suitable and moderately suitable for JCL plantation is 1.99 × 10 6 ha and 5.57 × 10 6 ha, respectively. If all of these land resources are put into use, the maximum net production potential of biodiesel from JCL would be 1.51 × 10 8 GJ/a, and the total greenhouse gas emission reduction capacity 1.59 × 10 7 t/a in Southwest China. -- Highlights: •A LCA based approach for assessing net energy potential of Jatropha curcas L. was presented. •The net production potential of biodiesel from JCL is 1.51 × 10 8 GJ/a in Southwest China. •The total GHG emission reduction capacity from JCL is 1.59 × 10 7 t/a in Southwest China

  10. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

    Science.gov (United States)

    Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

    2010-05-01

    Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

  11. Ground state solutions for Choquard type equations with a singular potential

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2017-02-01

    Full Text Available This article concerns the Choquard type equation $$ -\\Delta u+V(xu=\\Big(\\int_{\\mathbb{R}^N}\\frac{|u(y|^p}{|x-y|^{N-\\alpha}}dy\\Big |u|^{p-2}u,\\quad x\\in \\mathbb{R}^N, $$ where $N\\geq3$, $\\alpha\\in ((N-4_+,N$, $2\\leq p <(N+\\alpha/(N-2$ and V(x is a possibly singular potential and may be unbounded below. Applying a variant of the Lions' concentration-compactness principle, we prove the existence of ground state solution of the above equations.

  12. Formation mechanism of self-potential at ISL-amenable interlayer oxidation zone sandstone-type uranium deposit and the simulation and application of self-potential anomalies

    International Nuclear Information System (INIS)

    Tang Hongzhi; Liu Qingcheng; Su Zhaofeng; Gong Yuling

    2006-01-01

    Based on the analysis of geochemical characteristics and metallogenic physico-chemical conditions of ISL-amenable sandstone-type uranium deposits, the formation mechanism of self-potential field is discussed, a mathematic calculation model has been set up, and the simulation calculation has been performed for self-potential anomalies above uranium ore bodies of ordinary form, features of survey curve are analysed and methods for correcting topography at self-potential anomalies are discussed, and a simulation curve of self-potential in the area of slope topography has been presented. Finally, the availability of the method is demonstrated by an example. (authors)

  13. Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

    Science.gov (United States)

    Satou, M; Anzai, S; Huruno, M

    2005-05-01

    Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting 1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

  14. L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

    Science.gov (United States)

    Arévalo, Miguel; Núñez-Gómez, Elena; Pérez-Roque, Lucía; Pericacho, Miguel; González-Núñez, María; Langa, Carmen; Martínez-Salgado, Carlos; Perez-Barriocanal, Fernando; Bernabeu, Carmelo; Lopez-Novoa, José M.

    2014-01-01

    Transforming growth factor-β (TGF-β) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-β co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of α-smooth muscle actin (α-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of α-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development. PMID:25313562

  15. Rotational hypersurfaces with $L_r$-pointwise 1-type Gauss map

    Directory of Open Access Journals (Sweden)

    Akram Mohammadpouri

    2018-07-01

    Full Text Available In this paper, we study hypersurfaces in $\\E^{n+1}$ which Gauss map $G$ satisfies the equation $L_rG = f(G + C$ for a smooth function $f$ and a constant vector $C$, where $L_r$ is the linearized operator of the $(r + 1$th mean curvature of the hypersurface, i.e., $L_r(f=tr(P_r\\circ\

  16. Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Li, Shizhong; Hinsby, Anders Mørkeberg

    2008-01-01

    The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II...

  17. The L-L oligomerization domain resides at the very N-terminus of the sendai virus L RNA polymerase protein

    International Nuclear Information System (INIS)

    Cevik, Bayram; Smallwood, Sherin; Moyer, Sue A.

    2003-01-01

    The Sendai virus RNA-dependent RNA polymerase is composed of the L and P proteins. We previously showed that the L protein gives intragenic complementation and forms an oligomer where the L-L interaction site mapped to the N-terminal half of the protein (S. Smallwood et al., 2002, Virology, 00, 000-000). We now show that L oligomerization does not depend on P protein and progressively smaller N-terminal fragments of L from amino acids (aa) 1-1146 through aa 1-174 all bind wild-type L. C-terminal truncations up to aa 424, which bind L, can complement the transcription defect in an L mutant altered at aa 379, although these L truncation mutants do not bind P. The fragment of L comprising aa 1-895, furthermore, acts as a dominant-negative mutant to inhibit transcription of wild-type L. N-terminal deletions of aa 1-189 and aa 1-734 have lost the ability to form the L-L complex as well as the L-P complex, although they still bind C protein. These data are consistent with the L-L interaction site residing in aa 1-174. Site-directed mutations in the N-terminal 347 aa, of L which abolish P binding, do not affect L-L complex formation, so while the L and P binding sites on L are overlapping they are mediated by different amino acids. The N-terminal portions of L with aa 1-424, aa 1-381, and to a lesser extent aa 1-174, can complement the transcription defect in an L mutant altered at aa 77-81, showing their L-L interaction is functional

  18. Type - rolle - formål

    DEFF Research Database (Denmark)

    Hermansen, Judy

    2008-01-01

    kategoriseringer af brands, som er nødvendige for en strategisk styring af samspillet. Hans brand taksonomi er en systematisk tilgang, som gør det muligt, at klassificere alle de brandede elementer i et tilbud, uanset om de er repræsenteret af ét brand alene eller er en kombination af to eller flere brands....... Taksonomien redegør for de forskellige strategiske roller og formål, som hvert enkelt brand element kan spille. Udgivelsesdato: maj......I dag handler brand building mere om at få mest muligt ud af de brands, der allerede er på markedet, end om at launche nye brands. For at få brands til at spille sammen kræver det organisering af deres indbyrdes relationer. Rob Oslers brand taksonomier er et redskab til at foretage de analyser og...

  19. Characterization of 5-(2- 18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas

    OpenAIRE

    Abbas, Ahmed; Beamish, Christine; McGirr, Rebecca; Demarco, John; Cockburn, Neil; Krokowski, Dawid; Lee, Ting-Yim; Kovacs, Michael; Hatzoglou, Maria; Dhanvantari, Savita

    2016-01-01

    Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- 18F-fluoroethoxy)-L-tryptophan ( 18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodis...

  20. GABA(A) Increases Calcium in Subventricular Zone Astrocyte-Like Cells Through L- and T-Type Voltage-Gated Calcium Channels

    DEFF Research Database (Denmark)

    Young, Stephanie Z; Platel, Jean-Claude; Nielsen, Jakob V

    2010-01-01

    In the adult neurogenic subventricular zone (SVZ), the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca(2+) levels and tonic GABA(A) receptor activation. However, it is unknown whether, and if so how, GABA(A) receptor activity regulates...... intracellular Ca(2+) dynamics in SVZ astrocytes. To monitor Ca(2+) activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP) promoter. GABA(A) receptor activation...... induced Ca(2+) increases in 40-50% of SVZ astrocytes. GABA(A)-induced Ca(2+) increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC). The L-type Ca(2+) channel activator BayK 8644 increased the percentage of GABA(A)-responding astrocyte...

  1. Relation between Streaming Potential and Streaming Electrification Generated by Streaming of Water through a Sandwich-type Cell

    OpenAIRE

    Maruyama, Kazunori; Nikaido, Mitsuru; Hara, Yoshinori; Tanizaki, Yoshie

    2012-01-01

    Both streaming potential and accumulated charge of water flowed out were measured simultaneously using a sandwich-type cell. The voltages generated in divided sections along flow direction satisfied additivity. The sign of streaming potential agreed with that of streaming electrification. The relation between streaming potential and streaming electrification was explained from a viewpoint of electrical double layer in glass-water interface.

  2. L-type calcium channel CaV 1.2 in transgenic mice overexpressing human AbetaPP751 with the London (V717I) and Swedish (K670M/N671L) mutations.

    Science.gov (United States)

    Willis, Michael; Kaufmann, Walter A; Wietzorrek, Georg; Hutter-Paier, Birgit; Moosmang, Sven; Humpel, Christian; Hofmann, Franz; Windisch, Manfred; Knaus, Hans-Günther; Marksteiner, Josef

    2010-01-01

    Cumulative evidence indicates that amyloid-beta peptides exert some of their neurodegenerative effects through modulation of L-type voltage gated calcium channels, which play key roles in a diverse range of CNS functions. In this study we examined the expression of CaV1.2 L-type voltage gated calcium channels in transgenic mice overexpressing human AbetaPP751 with the London (V717I) and Swedish (K670M/N671L) mutations by immunohistochemistry in light and electron microscopy. In hippocampal layers of wild type and transgenic mice, CaV1.2 channels were predominantly localized to somato-dendritic domains of neurons, and to astrocytic profiles with an age-dependent increase in labeling density. In transgenic animals, CaV1.2-like immunoreactive clusters were found in neuronal profiles in association with amyloid-beta plaques. Both the number and density of these clusters depended upon age of animals and number of plaques. The most striking difference between wild type and transgenic mice was the age-dependent expression of CaV1.2 channels in reactive astrocytes. At the age of 6 month, CaV1.2 channels were rarely detected in reactive astrocytes of transgenic mice, but an incremental number of CaV1.2 expressing reactive astrocytes was found with increasing age of animals and number of amyloid-beta plaques. This study demonstrates that CaV1.2 channels are highly expressed in reactive astrocytes of 12-months of age transgenic mice, which might be a consequence of the increasing amyloid burden. Further studies should clarify which functional implications are associated with the higher availability of CaV1.2 channels in late stage Alzheimer's disease.

  3. Genome Sequence of the Enterobacter mori Type Strain, LMG 25706, a Pathogenic Bacterium of Morus alba L. ▿

    Science.gov (United States)

    Zhu, Bo; Zhang, Guo-Qing; Lou, Miao-Miao; Tian, Wen-Xiao; Li, Bin; Zhou, Xue-Ping; Wang, Guo-Feng; Liu, He; Xie, Guan-Lin; Jin, Gu-Lei

    2011-01-01

    Enterobacter mori is a plant-pathogenic enterobacterium responsible for the bacterial wilt of Morus alba L. Here we present the draft genome sequence of the type strain, LMG 25706. To the best of our knowledge, this is the first genome sequence of a plant-pathogenic bacterium in the genus Enterobacter. PMID:21602328

  4. Rational design of Bacillus stearothermophilus US100 L-arabinose isomerase: potential applications for D-tagatose production.

    Science.gov (United States)

    Rhimi, Moez; Aghajari, Nushin; Juy, Michel; Chouayekh, Hichem; Maguin, Emmanuelle; Haser, Richard; Bejar, Samir

    2009-05-01

    L-arabinose isomerases catalyze the bioconversion of D-galactose into D-tagatose. With the aim of producing an enzyme optimized for D-tagatose production, three Bacillus stearothermophilus US100 L-arabinose isomerase mutants were constructed, purified and characterized. Our results indicate that mutant Q268K was significantly more acidotolerant and more stable at acidic pH than the wild-type enzyme. The N175H mutant has a broad optimal temperature range from 50 to 65 degrees C. With the aim of constructing an acidotolerant mutant working at relatively low temperatures we generated the Q268K/N175H construct. This double mutant displays an optimal pH in the range 6.0-7.0 and an optimal activity around 50-65 degrees C, temperatures at which the enzyme was stable without addition of metal ions.

  5. The formation and repair of cisplatin-DNA adducts in wild-type and cisplatin-resistant L1210 cells : comparison of immunocytochemical determination with detection in isolated DNA

    NARCIS (Netherlands)

    Blommaert, F.A.; Floot, B.G.J.; Dijk-Knijnenburg, H.C.M. van; Berends, F.; Baan, R.A.; Schornagel, J.H.; Engelse, L. den; Fichtinger-Schepman, A.M.J.

    1998-01-01

    We have studied the formation and repair of cisplatin-DNA adducts in wild-type mouse leukemia L1210/0 cells and in the sublines L1210/2 and L1210/5, which differ in cisplatin sensitivity. In a colony-formation assay these sublines were 9- and 22-fold more resistant compared to L1210/0, respectively.

  6. Characterization of polyphenols and antioxidant potential of white grape pomace byproducts (Vitis vinifera L.).

    Science.gov (United States)

    González-Centeno, María Reyes; Jourdes, Michael; Femenia, Antoni; Simal, Susana; Rosselló, Carmen; Teissedre, Pierre-Louis

    2013-11-27

    A detailed assessment of the total phenolic and total tannin contents, the monomeric and oligomeric flavan-3-ol composition, the proanthocyanidin profile, and the antioxidant potential of the grape pomace byproducts (considered as a whole, both skins and seeds), derived from four white grape varieties (Vitis vinifera L.), was performed. Significant differences (p grape pomace byproducts were observed among the different grape varieties studied. For the first time in the literature, the particular flavan-3-ol composition of the four grape varieties investigated was described for the whole fraction of their grape pomace byproducts. The phenolic composition and antioxidant capacity of grape pomaces were compared to those of their corresponding stems. The global characterization of these white grape varieties provided a basis for an integrated exploitation of both winemaking byproducts as potential, inexpensive, and easily available sources of bioactive compounds for the pharmaceutical, cosmetic, and food industries.

  7. Oxynitrides decorated 316L SS for potential bioimplant application

    Science.gov (United States)

    Saravanan Kaliaraj, Gobi; Kumar, N.

    2018-03-01

    Titanium oxynitride (TiON) and zirconium oxynitride (ZrON) were deposited onto 316L stainless steel (316L SS) using reactive magnetron sputtering technique. The monoclinic and cubic phase of TiON and ZrON were obtained by x-ray diffraction (XRD). Nanoindentation and wear test analysis exhibited the better mechanical properties of TiON and ZrON films. Wettability studies showed hydrophilic nature on coated films; whereas bare 316L SS substrate was least hydrophilic. Drastic reduction of bacterial adhesion (Pseudomonas aeruginosa), as well as biofilm formation, was observed in both the films at different time duration. TiON and ZrON films were exhibited excellent hemocompatibility by preventing the platelet activation. Furthermore, the coated films exhibited corrosion protection in presence and absence of hydrogen peroxide (H2O2) in artificial blood plasma (ABP) solution.

  8. Rapid change of ion energy distribution and floating potential at L/H transition in the JFT-2M tokamak

    International Nuclear Information System (INIS)

    Miura, Y.; Nagashima, K.; Okano, F.

    1994-01-01

    Rapid changes of the main ion energy distribution at transitions from L-to-H, H-to-L and during ELMs are studied with the time of flight neutral measurement in the JFT-2M tokamak. The change of the main ion energy distribution after sawtooth crash during an L-mode phase is also studied. The change of the ion energy distribution just after sawtooth crash is the same as that at L/H-transition. The floating potential measured in the SOL also shows the rapid jump to more positive just after the sawtooth crash (at the same time of the change of an ion energy distribution). This shows the increase of ion outflux in the SOL and might correspond to the change of the ion energy distribution. This may be the reason why most of H-modes are triggered by a sawtooth. (author)

  9. Characterization of N-type glycosylation sites and glycan structures of Purple Acid Phosphatase Phytases from Wheat (Triticum aestivum L.)

    DEFF Research Database (Denmark)

    Dionisio, Giuseppe; Brinch-Pedersen, Henrik; Welinder, Karen Gjesing

    2011-01-01

    Wheat (Triticum aestivum L.) possesses preformed phytase activity in the grain that is essential to make phosphate available to cell metabolism and in food and feed (Brejnholt S. et al., 2011). Cereals contain the purple acid phosphatase type of phytases, PAPhy (Dionisio G. et al., 2011a). Mature......., Skov L. Brinch-Pedersen H. (2011). The degradation of phytate by microbial and wheat phytases is dependent on the phytate matrix and the phytase origin. J. Sci. Food Agri. (in press). Dionisio G., Madsen C.K., Holm P.B., Welinder K.G., Jørgensen M., Stoger E., Arcalis E., Brinch-Pedersen H. (2011a......) Cloning and Characterization of Purple Acid Phosphatase Phytases from Wheat (Triticum aestivum L.), Barley (Hordeum vulgare L.), Maize (Zea maize L.) and Rice (Oryza sativa L.). Plant Physiol. [in press, Jan 10, Epub ahead of print] Dionisio G., Brinch-Pedersen H., Welinder K.G., Jørgensen M. (2011b...

  10. Infinitely many solutions for sublinear fractional Schrodinger-type equations with general potentials

    Directory of Open Access Journals (Sweden)

    Gang-Ling Hou

    2018-04-01

    Full Text Available This article concerns the fractional Schrodinger type equations $$ (-\\Delta^\\alpha u+V(xu =f(x,u \\quad\\text{in } \\mathbb{R}^N, $$ where $N\\geq 2$, $\\alpha\\in(0,1$, $(-\\Delta^\\alpha$ stands for the fractional Laplacian, $V$ is a positive continuous potential, $f\\in C(\\mathbb{R}^N\\times\\mathbb{R},\\mathbb{R}$. We establish criteria that guarantee the existence of infinitely many solutions by using the genus properties in critical point theory.

  11. On the solution of an inverse problem for confining potentials in quantum mechanics

    International Nuclear Information System (INIS)

    Gostev, V.B.; Mineev, V.S.; Frenkin, A.R.

    1982-01-01

    The problem of plotting confining (unlimitedly increasing on the infinity) potentials of the central field by the given energy spectrum is discussed. The radial Schroedinger equation has pure discrete spectrum with infinite number of levels for these potentials. The problem is solved using the Helfand-Levitan equation with a certain reference potential V(r) for which spectral characteristics differ from the given ones only in the finite number of elements. The regular solutions PHIsub(l)(E, r) of the Schroedinger equation for the reference potential V(r) are supposed to be known. The initial potential and regular solutions of the Schroedinger equation are restored by the reference potential V(r) and regular PHIsub(l)(E, r) functions by means of the known formulas. It is observed from the paper data that confining potentials with any type of spectrum can be restored. Choice of the corresponding reference potential providing Fredholm nature of the Helfand-Levitan equation is the basic problem in this case

  12. Corrosion and microstructural aspects of dissimilar joints of titanium and type 304L stainless steel

    International Nuclear Information System (INIS)

    Mudali, U. Kamachi.; Ananda Rao, B.M.; Shanmugam, K.; Natarajan, R.; Raj, Baldev

    2003-01-01

    To link titanium and zirconium metal based (Ti, Zr-2, Ti-5%Ta, Ti-5%Ta-1.8Nb) dissolver vessels containing highly radioactive and concentrated corrosive nitric acid solution to other nuclear fuel reprocessing plant components made of AISI type 304L stainless steel (SS), high integrity and corrosion resistant dissimilar joints between them are necessary. Fusion welding processes produce secondary precipitates which dissolve in nitric acid, and hence solid-state processes are proposed. In this work, various dissimilar joining processes available for producing titanium-304L SS joints with adequate strength, ductility and corrosion resistance for this critical application are highlighted. Developmental efforts made at IGCAR, Kalpakkam are outlined. The possible methods and the microstructural-metallurgical properties of the joints along with corrosion results obtained with three phase (liquid, vapour, condensate) corrosion testing are discussed. Based on the results, dissimilar joint produced by the explosive joining process was adopted for plant application

  13. Estradiol up-regulates L-type Ca2+ channels via membrane-bound estrogen receptor/phosphoinositide-3-kinase/Akt/cAMP response element-binding protein signaling pathway.

    Science.gov (United States)

    Yang, Xiaoyan; Mao, Xiaofang; Xu, Gao; Xing, Shasha; Chattopadhyay, Ansuman; Jin, Si; Salama, Guy

    2018-05-01

    In long QT syndrome type 2, women are more prone than men to the lethal arrhythmia torsades de pointes. We previously reported that 17β-estradiol (E2) up-regulates L-type Ca 2+ channels and current (I Ca,L ) (∼30%) in rabbit ventricular myocytes by a classic genomic mechanism mediated by estrogen receptor-α (ERα). In long QT syndrome type 2 (I Kr blockade or bradycardia), the higher Ca 2+ influx via I Ca,L causes Ca 2+ overload, spontaneous sarcoplasmic reticulum Ca 2+ release, and reactivation of I Ca,L that triggers early afterdepolarizations and torsades de pointes. The purpose of this study was to investigate the molecular mechanisms whereby E2 up-regulates I Ca,L , which are poorly understood. H9C2 and rat myocytes were incubated with E2 ± ER antagonist, or inhibitors of downstream transcription factors, for 24 hours, followed by western blots of Cav1.2α1C and voltage-clamp measurements of I Ca,L . Incubation of H9C2 cells with E2 (10-100 nM) increased I Ca,L density and Cav1.2α1C expression, which were suppressed by the ER antagonist ICI182,780 (1 μM). Enhanced I Ca,L and Cav1.2α1C expression by E2 was suppressed by inhibitors of phosphoinositide-3-kinase (Pi3K) (30 μM LY294002; P L via plasma membrane ER and by activating Pi3K, Akt, and CREB signaling. The promoter regions of the CACNA1C gene (human-rabbit-rat) contain adjacent/overlapping binding sites for p-CREB and ERα, which suggests a synergistic regulation by these pathways. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. New potential phytotherapeutics obtained from white mulberry (Morus alba L.) leaves.

    Science.gov (United States)

    Gryn-Rynko, Anna; Bazylak, Grzegorz; Olszewska-Slonina, Dorota

    2016-12-01

    The present work demonstrates the profound and unique phyto-pharmacological and nutritional profile of white mulberry (Morus alba L.) leaves which containing considerable amounts of easy digestive proteins, carbohydrates, micro- and macronutrients, polyphenols, free amino acids, organic acids. The wide range of significant biopharmaceutical activities of the aqueous and polar organic solvents extracts from mulberry leaves - including antidiabetic, antibacterial, anticancer, cardiovascular, hypolipidemic, antioxidant, antiatherogenic, and anti-inflammatory - have been critically discussed. The main objective was to demonstrate the results of recently published study on the components of white mulberry leaves exhibiting their biological activity in the various pathological and health human ailments. In addition, we intend to drawn the attention of researchers and public health workers for the extended exploration of this deciduous plant leaves as the source of potential indigenous nutraceuticals and functional food products to enable development of alternative prevention and treatment protocols offered in therapy of the common non-communicable diseases and malignances. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Vitamin E isomer δ-tocopherol enhances the efficiency of neural stem cell differentiation via L-type calcium channel.

    Science.gov (United States)

    Deng, Sihao; Hou, Guoqiang; Xue, Zhiqin; Zhang, Longmei; Zhou, Yuye; Liu, Chao; Liu, Yanqing; Li, Zhiyuan

    2015-01-12

    The effects of the vitamin E isomer δ-tocopherol on neural stem cell (NSC) differentiation have not been investigated until now. Here we investigated the effects of δ-tocopherol on NSC neural differentiation, maturation and its possible mechanisms. Neonatal rat NSCs were grown in suspended neurosphere cultures, and were identified by their expression of nestin protein and their capacity for self-renewal. Treatment with a low concentration of δ-tocopherol induced a significant increase in the percentage of β-III-tubulin-positive cells. δ-Tocopherol also stimulated morphological maturation of neurons in culture. We further observed that δ-tocopherol stimulation increased the expression of voltage-dependent Ca(2+) channels. Moreover, a L-type specific Ca(2+) channel blocker verapamil reduced the percentage of differentiated neurons after δ-tocopherol treatment, and blocked the effects of δ-tocopherol on NSC differentiation into neurons. Together, our study demonstrates that δ-tocopherol may act through elevation of L-type calcium channel activity to increase neuronal differentiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. ANALISIS TUMBUH SELADA (LACTUCA SATIVA L) PADA PERBEDAAN JENIS PUPUK ORGANIK CAIR ( Lettuce (Lactuca Sativa L) Growth Analysis At Different Type Of Liquid Organic Fertilizer)

    OpenAIRE

    Duaja, Made Deviani; Arzita, .; Redo, Yan

    2012-01-01

    The objectives of this research are to analysis the growth and yield of Lettuce (Lactuca sativa L) at different type of organic liquid fertilizers. The experiment has conducted at Agriculture Faculty Research Farm, Jambi University. Six treatments were arranged in Randomized Completed Block Design. The treatments are kinds of liquid organic fertilizers, they are P0 (none of liquid organic fertilizers), P1 (Golden Harvest liquid organic fertilizers), P2 (NASA liquid organic fertilizers), P3 (C...

  17. The role of L-type calcium channels in the vascular effect of Trigonella foenum-graecum L. in diabetic rats

    Directory of Open Access Journals (Sweden)

    Mehrdad Roghani

    2006-03-01

    Full Text Available Some ion channels like voltage-operated calcium channels (VOCC within the plasma membrane of vascular muscle cells from the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. On the basis of reports about the beneficial attenuating effect of fenugreek (Trigonella foenum-graecum L.; TFG on the contractile reactivity of aortic rings of diabetic rats, this study was carried out to evaluate the possible involvement of L-type voltage-operated calcium channels in the vascular effect of this medicinal plant. For this purpose, male Wistar rats were made diabetic using streptozotocin (STZ, 60 mg/Kg, i.p. The extract-treated control and diabetic rats received aqueous leaf extract of TFG (200 mg/Kg, i.p. every other day for two months. At the end of the study, contractile response of isolated aortic rings to KCl and noreadrenaline (NA was determined in the absence and presence of the calcium channel blocker nifedipine. The results showed that aortic rings from diabetic rats are more responsive to the effect of KCl and NA than those of controls, TFG extract treatment could attenuate the enhanced contractile response of aortic rings of diabetic rats, and nifedipine pretreatment could partially neutralize the beneficial effect of this extract. It is concluded that TFG extract attenuates the enhanced vascular reactivity in chronic diabetic rats and voltage-operated calcium channels are in part responsible for this effect of TFG extract.

  18. High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas

    International Nuclear Information System (INIS)

    Yanagisawa, Nobuyuki; Hana, Kiyomi; Nakada, Norihiro; Ichinoe, Masaaki; Koizumi, Wasaburo; Endou, Hitoshi; Okayasu, Isao; Murakumo, Yoshiki

    2014-01-01

    Oncocytic L-type amino acid transporter (LAT) 1 may be a prognostic indicator and target of new molecular therapeutic agents against malignancies. To investigate whether LAT1 expression influence the outcomes of patients with bile duct cancer, the expression of LAT1, LAT2, CD98, and Ki-67 was investigated immunohistochemically in 134 surgically resected bile duct adenocarcinomas, including 84 distal extrahepatic bile duct adenocarcinomas, 21 hilar cholangiocarcinomas, 15 intrahepatic cholangiocarcinomas, and 14 ampullary adenocarcinomas. LAT1 expression was weakly correlated with CD98 expression and Ki-67 labeling index (LI). Kaplan–Meier analysis showed a significant difference in prognosis between patients with bile duct adenocarcinomas having LAT1-high and -low scores, whereas LAT2 and CD98 expression and Ki-67 LI were not predictive of poor prognosis. Prognosis tended to be worse in patients having tumors with LAT1-high/LAT2-low than LAT1-low/LAT2-high scores (P = 0.0686). Multivariable analyses revealed that LAT1 expression, surgical margin, pT stage were independent prognostic factors. In conclusion, aberrant overexpression of LAT1 in bile duct adenocarcinoma predicts poor prognosis, suggesting that LAT1 may be a potential target of anticancer therapy

  19. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    Science.gov (United States)

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

  20. A SEARCH FOR PHOTOMETRIC VARIABILITY IN L- AND T-TYPE BROWN DWARF ATMOSPHERES

    International Nuclear Information System (INIS)

    Khandrika, Harish; Burgasser, Adam J.; Melis, Carl; Luk, Christopher; Bowsher, Emily; Swift, Brandon

    2013-01-01

    Using the Gemini infrared camera on the 3 m Shane telescope at Lick Observatory, we have searched for broadband J and K' photometric variability for a sample of 15 L- and T-type brown dwarfs, including 7 suspected spectral binaries. Four of the dwarfs—2MASS J0939–2448, 2MASS J1416+1348A, 2MASS J1711+2232, and 2MASS J2139+0220—exhibit statistically significant variations over timescales ranging from ∼0.5 hr to 6 days. Our detection of variability in 2MASS J2139+0220 confirms that reported by Radigan et al., and periodogram and phase dispersion minimization analysis also confirms a variability period of approximately 7.6 ± 0.2 hr. Remarkably, two of the four variables are known or candidate binary systems, including 2MASS J2139+0220, for which we find only marginal evidence of radial velocity variation over the course of a year. This result suggests that some spectral binary candidates may appear as such due to the blending of cloudy and non-cloudy regions in a single ''patchy'' atmosphere. Our results are consistent with an overall variability fraction of 35% ± 5%, with no clear evidence of greater variability among brown dwarfs at the L dwarf/T dwarf transition.

  1. D-Dimensional Dirac Equation for Energy-Dependent Pseudoharmonic and Mie-type Potentials via SUSYQM

    International Nuclear Information System (INIS)

    Ikot, A.N.; Hassanabadi, H.; Maghsoodi, E.; Zarrinkamar, S.

    2014-01-01

    We investigate the approximate solution of the Dirac equation for energy-dependent pseudoharmonic and Mie-type potentials under the pseudospin and spin symmetries using the supersymmetry quantum mechanics. We obtain the bound-state energy equation in an analytical manner and comment on the system behavior via various figures and tables

  2. Children at risk of diabetes type 1. Treatment with acetyl-L-carnitine plus nicotinamide - case reports.

    Science.gov (United States)

    Fernandez, Ivana Cristina; Del Carmen Camberos, María; Passicot, Gisel Anabel; Martucci, Lucía Camila; Cresto, Juan Carlos

    2013-01-01

    Abstract Objectives: The aim was to evaluate the treatment with acetyl-L-carnitine (50 mg/kg/day) and nicotinamide (25 mg/kg/day) in children at risk of type 1 diabetes. This treatment was effective and harmless in experimental type 1 diabetes in mice. Nine out of seventy healthy participants of the type 1 diabetes risk study were treated. They were typified for diabetes with HLA-DQB1 and positive autoantibodies. Children with a first peak of insulin response ≤48 µU were randomly distributed in control and treated patients. Children evolution was followed with an intravenous glucose tolerance test. Control children were treated when was another risk parameter was added. During their evolution all children were treated. Treatment periods differ (range: 120-16 months) because children began treatment at different times. During the treatment 4 patients recovered their parameters and the medication was suspended; 2 patients continued the treatment with favorable evolution. Two children evolved slowly with normal growth and development. One girl became diabetic because she was treated late. In children at risk, this treatment delays the development or remits the evolution of type 1 diabetes.

  3. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

  4. Relationship Between Redox Potential, Disinfectant, and pH in Drinking Water

    Science.gov (United States)

    This work will examine the effects of pH and oxidant type (chlorine [Cl2], oxygen [O2], hydrogen peroxide [H2O2], monochloramine [MCA], and potassium permanganate [KMnO4]) and concentration (mg/L) on the redox potential of buffered test water. Also, the effects of incrementing ir...

  5. Energy potential of the modified excess sludge

    Science.gov (United States)

    Zawieja, Iwona

    2017-11-01

    On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4), it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  6. Energy potential of the modified excess sludge

    Directory of Open Access Journals (Sweden)

    Zawieja Iwona

    2017-01-01

    Full Text Available On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4, it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  7. Potential biological pathways linking Type-D personality and poor health: A cross-sectional investigation.

    Directory of Open Access Journals (Sweden)

    Vera K Jandackova

    Full Text Available Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample.Data from a total of 646 respondents (age 41.6±11.5, 12,2% women were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10 were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG, cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c, creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV measures were calculated for the 24hr recording period and for nighttime separately.Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index.Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality.

  8. Higgs potential in the type II seesaw model

    International Nuclear Information System (INIS)

    Arhrib, A.; Benbrik, R.; Chabab, M.; Rahili, L.; Ramadan, J.; Moultaka, G.; Peyranere, M. C.

    2011-01-01

    The standard model Higgs sector, extended by one weak gauge triplet of scalar fields with a very small vacuum expectation value, is a very promising setting to account for neutrino masses through the so-called type II seesaw mechanism. In this paper we consider the general renormalizable doublet/triplet Higgs potential of this model. We perform a detailed study of its main dynamical features that depend on five dimensionless couplings and two mass parameters after spontaneous symmetry breaking, and highlight the implications for the Higgs phenomenology. In particular, we determine (i) the complete set of tree-level unitarity constraints on the couplings of the potential and (ii) the exact tree-level boundedness from below constraints on these couplings, valid for all directions. When combined, these constraints delineate precisely the theoretically allowed parameter space domain within our perturbative approximation. Among the seven physical Higgs states of this model, the mass of the lighter (heavier) CP even state h 0 (H 0 ) will always satisfy a theoretical upper (lower) bound that is reached for a critical value μ c of μ (the mass parameter controlling triple couplings among the doublet/triplet Higgses). Saturating the unitarity bounds, we find an upper bound m h 0 or approx. μ c and μ c . In the first regime the Higgs sector is typically very heavy, and only h 0 that becomes SM-like could be accessible to the LHC. In contrast, in the second regime, somewhat overlooked in the literature, most of the Higgs sector is light. In particular, the heaviest state H 0 becomes SM-like, the lighter states being the CP odd Higgs, the (doubly) charged Higgses, and a decoupled h 0 , possibly leading to a distinctive phenomenology at the colliders.

  9. Application potential of sequence stratigraphy to prospecting for sandstone-type uranium deposit in continental depositional basins

    International Nuclear Information System (INIS)

    Li Shengxiang; Chen Zhaobo; Chen Zuyi; Xiang Weidong; Cai Yuqi

    2001-01-01

    Sequence stratigraphy has been widely used in hydrocarbon exploration and development, and great achievements have been achieved. However, its application to the prospecting for sandstone-type uranium deposits is just beginning. The metallogenic characteristics of sandstone-type uranium deposits and those of oil and gas are compared, and the relationship between sandstone-type uranium metallogenesis and the system tracts of sequence stratigraphy is studied. The authors propose that highest and system tracts are the main targets for prospecting interlayer oxidation zone type sandstone uranium deposits, and the incised valleys of low stand system tracts are favourable places for phreatic oxidation zone type sandstone uranium deposits, and transgressive system tracts are generally unfavorable to the formation of in-situ leachable sandstone-type uranium deposits. Finally, the authors look ahead the application potential of sequence stratigraphy to the prospecting for sandstone-type uranium deposits in continental depositional basins

  10. Corrosion of high Ni-Cr alloys and Type 304L stainless steel in HNO3-HF

    International Nuclear Information System (INIS)

    Ondrejcin, R.S.; McLaughlin, B.D.

    1980-04-01

    Nineteen alloys were evaluated as possible materials of construction for steam heating coils, the dissolver vessel, and the off-gas system of proposed facilities to process thorium and uranium fuels. Commercially available alloys were found that are satisfactory for all applications. With thorium fuel, which requires HNO 3 -HF for dissolution, the best alloy for service at 130 0 C when complexing agents for fluoride are used is Inconel 690; with no complexing agents at 130 0 C, Inconel 671 is best. At 95 0 C, six other alloys tested would be adequate: Haynes 25, Ferralium, Inconel 625, Type 304L stainless steel, Incoloy 825, and Haynes 20 (in order of decreasing preference); based on composition, six untested alloys would also be adequate. The ions most effective in reducing fluoride corrosion were the complexing agents Zr 4+ and Th 4+ ; Al 3+ was less effective. With uranium fuel, modestly priced Type 304L stainless steel is adequate. Corrosion will be most severe in HNO 3 -HF used occasionally for flushing and in solutions of HNO 3 and corrosion products (ferric and dichromate ions). HF corrosion can be minimized by complexing the fluoride ion and by passivation of the steel with strong nitric acid. Corrosion caused by corrosion products can be minimized by operating at lower temperatures

  11. Pigmentation and vitamin D metabolism in Caucasians: low vitamin D serum levels in fair skin types in the UK.

    Directory of Open Access Journals (Sweden)

    Daniel Glass

    2009-08-01

    Full Text Available Vitamin D may play a protective role in many diseases. Public health messages are advocating sun avoidance to reduce skin cancer risk but the potential deleterious effects of these recommendations for vitamin D metabolism have been poorly investigated.We investigated the association between 25-hydroxy-vitamin D (25(OHD, skin type and ultraviolet exposure in 1414 Caucasian females in the UK. Mean age of the cohort was 47 years (18-79 and mean 25(OHD levels were 77 nmol/L (6-289. 25(OHD levels were strongly associated with season of sampling with higher levels in the spring and summer months (p<0.0001. Light skin types (skin type 1 and 2 have lower levels of 25(OHD (mean 71 nmol/L compared to darker skin types (skin type 3 and 4 (mean 82 nmol/L after adjusting for multiple confounders (p<0.0001. The trend for increasing risk of low vitamin D with fairer skin types was highly significant despite adjustment for all confounders (p = 0.001.Contrary to previous studies across different ethnic backgrounds, this study within Caucasian UK females shows that fair skin types have lower levels of 25(OHD compared to darker skin types with potential detrimental health effects. Public health campaigns advocating sun avoidance in fair skinned individuals may need to be revised in view of their risk of vitamin D deficiency.

  12. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action

    OpenAIRE

    Rodrigues, Klinger Antonio da Franca; Amorim, Layane Val?ria; de Oliveira, Jamylla Mirck Guerra; Dias, Clarice Noleto; Moraes, Denise Fernandes Coutinho; Andrade, Eloisa Helena de Aguiar; Maia, Jose Guilherme Soares; Carneiro, Sabrina Maria Portela; Carvalho, Fernando A?cio de Amorim

    2013-01-01

    Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components...

  13. Classification of Hand Grasp Kinetics and Types Using Movement-Related Cortical Potentials and EEG Rhythms

    Directory of Open Access Journals (Sweden)

    Mads Jochumsen

    2017-01-01

    Full Text Available Detection of single-trial movement intentions from EEG is paramount for brain-computer interfacing in neurorehabilitation. These movement intentions contain task-related information and if this is decoded, the neurorehabilitation could potentially be optimized. The aim of this study was to classify single-trial movement intentions associated with two levels of force and speed and three different grasp types using EEG rhythms and components of the movement-related cortical potential (MRCP as features. The feature importance was used to estimate encoding of discriminative information. Two data sets were used. 29 healthy subjects executed and imagined different hand movements, while EEG was recorded over the contralateral sensorimotor cortex. The following features were extracted: delta, theta, mu/alpha, beta, and gamma rhythms, readiness potential, negative slope, and motor potential of the MRCP. Sequential forward selection was performed, and classification was performed using linear discriminant analysis and support vector machines. Limited classification accuracies were obtained from the EEG rhythms and MRCP-components: 0.48±0.05 (grasp types, 0.41±0.07 (kinetic profiles, motor execution, and 0.39±0.08 (kinetic profiles, motor imagination. Delta activity contributed the most but all features provided discriminative information. These findings suggest that information from the entire EEG spectrum is needed to discriminate between task-related parameters from single-trial movement intentions.

  14. Conservation of cardiac L-type Ca2+ channels and their regulation in Drosophila: A novel genetically-pliable channelopathic model.

    Science.gov (United States)

    Limpitikul, Worawan B; Viswanathan, Meera C; O'Rourke, Brian; Yue, David T; Cammarato, Anthony

    2018-04-21

    Dysregulation of L-type Ca 2+ channels (LTCCs) underlies numerous cardiac pathologies. Understanding their modulation with high fidelity relies on investigating LTCCs in their native environment with intact interacting proteins. Such studies benefit from genetic manipulation of endogenous channels in cardiomyocytes, which often proves cumbersome in mammalian models. Drosophila melanogaster, however, offers a potentially efficient alternative as it possesses a relatively simple heart, is genetically pliable, and expresses well-conserved genes. Fluorescence in situ hybridization confirmed an abundance of Ca-α1D and Ca-α1T mRNA in fly myocardium, which encode subunits that specify hetero-oligomeric channels homologous to mammalian LTCCs and T-type Ca 2+ channels, respectively. Cardiac-specific knockdown of Ca-α1D via interfering RNA abolished cardiac contraction, suggesting Ca-α1D (i.e. A1D) represents the primary functioning Ca 2+ channel in Drosophila hearts. Moreover, we successfully isolated viable single cardiomyocytes and recorded Ca 2+ currents via patch clamping, a feat never before accomplished with the fly model. The profile of Ca 2+ currents recorded in individual cells when Ca 2+ channels were hypomorphic, absent, or under selective LTCC blockage by nifedipine, additionally confirmed the predominance of A1D current across all activation voltages. T-type current, activated at more negative voltages, was also detected. Lastly, A1D channels displayed Ca 2+ -dependent inactivation, a critical negative feedback mechanism of LTCCs, and the current through them was augmented by forskolin, an activator of the protein kinase A pathway. In sum, the Drosophila heart possesses a conserved compendium of Ca 2+ channels, suggesting that the fly may serve as a robust and effective platform for studying cardiac channelopathies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. The morphogenesis of herpes simplex virus type 1 in infected parental mouse L fibroblasts and mutant gro29 cells

    DEFF Research Database (Denmark)

    Jensen, Helle Lone; Norrild, Bodil

    2003-01-01

    Mutants of cell lines and viruses are important biological tools. The pathway of herpesvirus particle maturation and egress are contentious issues. The mutant gro29 line of mouse L cells is defective for egress of herpes simplex virus type 1 (HSV-1) virions, and a candidate for studies of virus...

  16. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  17. Do cysteine residues regulate transient receptor potential canonical type 6 (TRPC6) channel protein expression?

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Krueger, Katharina

    2012-01-01

    The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed that patie......The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed...... that patients with chronic renal failure had significantly elevated homocysteine levels and TRPC6 mRNA expression levels in monocytes compared to control subjects. We further observed that administration of homocysteine or acetylcysteine significantly increased TRPC6 channel protein expression compared...... to control conditions. We therefore hypothesize that cysteine residues increase TRPC6 channel protein expression in humans....

  18. Dependence of the cross polar cap potential saturation on the type of solar wind streams

    OpenAIRE

    Nikolaeva, N. S.; Yermolaev, Yu. I.; Lodkina, I. G.

    2013-01-01

    We compare of the cross polar cap potential (CPCP) saturation during magnetic storms induced by various types of the solar wind drivers. By using the model of Siscoe-Hill \\citep{Hilletal1976,Siscoeetal2002a,Siscoeetal2002b,Siscoeetal2004,Siscoe2011} we evaluate criteria of the CPCP saturation during the main phases of 257 magnetic storms ($Dst_{min} \\le -50$ nT) induced by the following types of the solar wind streams: magnetic clouds (MC), Ejecta, the compress region Sheath before MC ($Sh_{M...

  19. Nutrient cycling potential of camelina (Camelina sativa L. Crantz.) as a cover crop in the US Northern Great Plains

    Science.gov (United States)

    Berti, Marisol; Samarappuli, Dulan

    2017-04-01

    Camelina [Camelina sativa (L.) Crantz.] is an industrial oilseed crop in the Brassicaceae family with multiple uses. Currently, camelina is not used as a cover crop, but it has the potential to be used as such in maize-soybean-wheat cropping systems. The objectives of this study were to determine the agronomic performance and nutrient scavenging potential of winter camelina in comparison with other common cover crops. Experiments were conducted in Fargo, ND in 2015 and 2016, and in Prosper, ND in 2015. The experimental design was a randomized complete block design with a split-plot arrangement with three replicates. The main plot was the sowing date and the subplot were camelina cultivars as well as other common cover crops in the area. Sowing dates were targeted to 15 August and September 1, although the final dates varied slightly each year. Biomass yield, N content of the biomass N uptake and P uptake was evaluated. Winter camelina N and P uptake ranged between 21 and 30.5 kg N ha-1 and 3.4 to 5.3 kg P ha-1. The nutrient scavenging potential of winter camelina was similar to other cover crops although slightly lower than turnip (Brassica rapa L.), radish (Raphanus sativus L.), and rape (Brassica napus L.) cultivars which had significantly higher P uptake than winter camelina and the other cover crops in the study. An evaluation of spring regrowth and cover indicated that only rye, winter camelina, and pennycress (Thlaspi arvense L.) survived the winter, although a few plants of triticale (x Trticosecale Witt.) and rape were found on a few plots. Because of the high variability on the plots there were no significant differences among the surviving cover crops on soil coverage. The soil coverage for rye cultivars was 25 and 35% and for camelina cv. Bison was 27%.In 2016, biomass yield was not significant for sowing date, cultivars, or their interaction. Winter camelina cultivars biomass yield fluctuated between 1.15 and 2.33 Mg dry matter ha-1 on the first sowing

  20. Antibody fragments directed against different portions of the human neural cell adhesion molecule L1 act as inhibitors or activators of L1 function.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available The neural cell adhesion molecule L1 plays important roles in neuronal migration and survival, neuritogenesis and synaptogenesis. L1 has also been found in tumors of different origins, with levels of L1 expression correlating positively with the metastatic potential of tumors. To select antibodies targeting the varied functions of L1, we screened the Tomlinson library of recombinant human antibody fragments to identify antibodies binding to recombinant human L1 protein comprising the entire extracellular domain of human L1. We obtained four L1 binding single-chain variable fragment antibodies (scFvs, named I4, I6, I13, and I27 and showed by enzyme-linked immunosorbent assay (ELISA that scFvs I4 and I6 have high affinity to the immunoglobulin-like (Ig domains 1-4 of L1, while scFvs I13 and I27 bind strongly to the fibronectin type III homologous (Fn domains 1-3 of L1. Application of scFvs I4 and I6 to human SK-N-SH neuroblastoma cells reduced proliferation and transmigration of these cells. Treatment of SK-N-SH cells with scFvs I13 and I27 enhanced cell proliferation and migration, neurite outgrowth, and protected against the toxic effects of H(2O(2 by increasing the ratio of Bcl-2/Bax. In addition, scFvs I4 and I6 inhibited and scFvs I13 and I27 promoted phosphorylation of src and Erk. Our findings indicate that scFvs reacting with the immunoglobulin-like domains 1-4 inhibit L1 functions, whereas scFvs interacting with the fibronectin type III domains 1-3 trigger L1 functions of cultured neuroblastoma cells.

  1. Analytic solution of the potential and electric field of a jet type drift chamber

    Energy Technology Data Exchange (ETDEWEB)

    Weltin, A

    1988-02-15

    Starting from the known two-dimensional potential of a multiwire proportional chamber, the analytic expressions of the potential and the electric field are derived for a jet type drift chamber with a central wire plane of alternating sense and potential wires. The design goal of any jet chamber, namely the periodicity of the electric drift field, is imposed as a boundary condition at the beginning. In this way, the formulae are short and can be easily evaluated. In particular, expressions are given for the mean potential of the central wire plane, the drift field and the wire surface fields. Moreover, wire cathodes frequently used in jet chambers are described by analytic expressions. For a given drift field the difference of the potential as compared to a continuous metal cathode is presented. These results allowed to construct a two-dimensional computer simulation of the full OPAL jet chamber with no explicit periodicity but all its boundaries. Using field shaping electrodes a geometrically short yet quite satisfactory termination of a sense wire plane is demonstrated. Finally an example is presented, which is calculated in detail.

  2. Strong transthyretin immunostaining: potential pitfall in cardiac amyloid typing.

    Science.gov (United States)

    Satoskar, Anjali A; Efebera, Yvonne; Hasan, Ayesha; Brodsky, Sergey; Nadasdy, Gyongyi; Dogan, Ahmet; Nadasdy, Tibor

    2011-11-01

    Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ. Our study demonstrates the unreliability of transthyretin immunostaining in subtyping cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for κ, λ, transthyretin, and serum amyloid A protein was performed on formalin-fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected amyloid material was performed on selected cases. Fifteen patients had monoclonal gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53%) showed strong transthyretin staining in the cardiac amyloid deposits. MS was performed in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type amyloid. Two of these 5 light chain amyloid biopsies did not even have concomitant strong staining for the appropriate light chain. Among the 15 cases with plasma cell dyscrasia, only 7 biopsies showed strong staining for the corresponding monoclonal light chain. Strong, false-positive immunostaining for transthyretin in cardiac amyloid is a potential pitfall, augmented by the frequent lack of staining for immunoglobulin light chains. Therefore, the presence of amyloid in the cardiac biopsy should prompt a search for plasma cell dyscrasia irrespective of transthyretin staining. Confirmation with MS should be sought, particularly if there is any discrepancy between κ/λ staining and serum immunofixation results.

  3. Effect of welding process, type of electrode and electrode core diameter on the tensile property of 304L austenitic stainless steel

    Directory of Open Access Journals (Sweden)

    Akinlabi OYETUNJI

    2014-11-01

    Full Text Available The effect of welding process, type of electrode and electrode core diameter on the tensile property of AISI 304L Austenitic Stainless Steel (ASS was studied. The tensile strength property of ASS welded samples was evaluated. Prepared samples of the ASS were welded under these three various variables. Tensile test was then carried out on the welded samples. It was found that the reduction in ultimate tensile strength (UTS of the butt joint samples increases with increase in core diameter of the electrode. Also, the best electrode for welding 304L ASS is 308L stainless steel-core electrode of 3.2 mm core diameter. It is recommended that the findings of this work can be applied in the chemical, food and oil industries where 304L ASS are predominantly used.

  4. Phytotoxic Potential of Onopordum acanthium L. (Asteraceae)

    OpenAIRE

    Watanabe, Yusuke; Novaes, Paula; Kato-Noguchi, Hisashi; Varela Montoya, Rosa; González Molinillo, José María; Macías Domínguez, Francisco Antonio

    2014-01-01

    Onopordum acanthium L. (Asteraceae) is a plant native to southern Europe and southwestern Asia, but it is invasive in disturbed areas and agricultural fields around the world, causing many agronomic problems by interfering with crops or preventing animals from grazing on pastures. Allelopathy could be one of the reasons that this plant has spread over different continents. The aim of the present study was to bioprospect O. acanthium leaf extracts through the isolation and purification of alle...

  5. Allergic complications of L-asparaginase therapy in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Konstantinidis Georgios

    2011-01-01

    Full Text Available Introduction. L-asparaginase (L-ASP is one of the most effective medications for the treatment of acute lymphoblastic leukaemia (ALL in children, and allergic reactions to the therapy are considered the most significant side effects. Objective. The aim of this study was to determine the prevalence and type of allergic reactions, as well as to identify potential risk factors for the development of allergic reactions during L-ASP therapy in children with ALL. Methods. The study encompassed 70 patients under 18 years of age, who were treated at the Institute for Child and Youth Healthcare of Vojvodina, Novi Sad in the period January 2000 - June 2009. We analyzed the frequency and type of allergic reactions during the administration of L-ASP, the onset of allergic reaction in relation to the phase of therapy of underlying disease, as well as the prevalence of allergic reactions in relation to drug administration method. Results. Allergic reaction manifested in 17 patients (24%. In 14 patients (82% allergic reaction to L-ASP manifested as urticaria, bronchospasm or anaphylaxis, whereas a mild local reaction was observed in only three patients (18%. In a group treated, according to the high-risk protocol, the prevalence of allergic reactions was statistically significantly higher in the intermediate-risk group of patients (p<0.01, i.e. statistically significantly more frequent, as compared to the standard-risk group of patients (p<0.05. The majority of patients (11; 65% developed allergic reactions to the 9th dose of L-ASP, i.e. the first dose during the reinduction phase. The time interval between the last L-ASP dose in the induction phase and the 1st dose in the reinduction phase was at least four weeks. With respect to administration method, the majority of patients (16; 94% developed allergic reaction after intravenous application of L-ASP. Conclusion. Potential risk factors for the development of allergic reaction to L-ASP are a high-risk therapy

  6. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  7. On the effects on a Landau-type system for an atom with no permanent electric dipole moment due to a Coulomb-type potential

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Abinael B.; Bakke, Knut, E-mail: kbakke@fisica.ufpb.br

    2016-02-15

    We analyse the bound states for a Landau-type system for an atom with no permanent electric dipole moment subject to a Coulomb-type potential. By comparing the energy levels for bound states of the system with the Landau quantization for an atom with no permanent electric dipole moment (Furtado et al., 2006), we show that the energy levels of the Landau-type system are modified, where the degeneracy of the energy levels is broken. Another quantum effect investigated is a dependence of the angular frequency of the system on the quantum numbers associated with the radial modes and the angular momentum. As examples, we obtain the angular frequency and the energy levels associated with the ground state and the first excited state of the system.

  8. On the effects on a Landau-type system for an atom with no permanent electric dipole moment due to a Coulomb-type potential

    International Nuclear Information System (INIS)

    Oliveira, Abinael B.; Bakke, Knut

    2016-01-01

    We analyse the bound states for a Landau-type system for an atom with no permanent electric dipole moment subject to a Coulomb-type potential. By comparing the energy levels for bound states of the system with the Landau quantization for an atom with no permanent electric dipole moment (Furtado et al., 2006), we show that the energy levels of the Landau-type system are modified, where the degeneracy of the energy levels is broken. Another quantum effect investigated is a dependence of the angular frequency of the system on the quantum numbers associated with the radial modes and the angular momentum. As examples, we obtain the angular frequency and the energy levels associated with the ground state and the first excited state of the system.

  9. Purple head broccoli (Brassica oleracea L. var. italica Plenck), a functional food crop for antioxidant and anticancer potential.

    Science.gov (United States)

    Chaudhary, Ashun; Choudhary, Sonika; Sharma, Upendra; Vig, Adarsh Pal; Singh, Bikram; Arora, Saroj

    2018-05-01

    Natural foods are used in many folks and household treatments and have immense potential to treat a serious complication and health benefits, in addition to the basic nutritional values. These food products improve health, delay the aging process, increase life expectancy, and possibly prevent chronic diseases. Purple head Brassica oleracea L. var. italica Plenck is one of such foods and in current studies was explored for chemical compounds at different development stages by gas chromatography-mass spectrometry. Antioxidant potential was explored employing different assays like molybdate ion reduction, DPPH, superoxide anion radical scavenging and plasmid nicking assay. Inspired by antioxidant activity results, we further explored these extracts for antiproliferative potential by morphological changes, cell cycle analysis, measurement of intracellular peroxides and mitochondrial membrane potential changes. Current study provides the scientific basis for the use of broccoli as easily affordable potent functional food.

  10. Geodesics in Goedel-type space-times

    International Nuclear Information System (INIS)

    Calvao, M.O.; Soares, I.D.; Tiomno, J.

    1988-01-01

    The geodesic curves of the homogeneous Goedel-type space-times, which constitute a two-parameter ({ l and Ω}) class of solutions presented to several theories of gravitation (general relativity, Einstein-Cartan and higher derivative) are investigated. The qualitative properties of those curves by means of the introduction of an effective potential and then accomplish the analytical integration of the equations of motion are examined. It is shown that some of the qualitative features of the free motion in Godel's universe (l 2 =2Ω 2 ) are preserved in all space-times, namely the projections of the geodesics onto the 2-surface (r,ψ) are simple closed curves, and the geodesics for which the ratio of azymuthal angular momentum to total energy, υ is equal to zero always cross the origin r = o. However, two new cases appear: (i) radially unbounded geodesics with υ assuming any (real) value, which may occur only for the causal space-times (l 2 ≥ 4 Ω 2 ), and (ii) geodesics with υ bounded both below and above, which always occur for the circular family (l 2 [pt

  11. l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.

    Science.gov (United States)

    Cho, Do-Yeon; Lim, Dong-Jin; Mackey, Calvin; Weeks, Christopher G; Peña Garcia, Jaime A; Skinner, Daniel; Grayson, Jessica W; Hill, Harrison S; Alexander, David K; Zhang, Shaoyan; Woodworth, Bradford A

    2018-05-01

    Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms. P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs. l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone. Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned. © 2018 ARS-AAOA, LLC.

  12. Rôle de l'inflammasome NLRP3 dans l'athérosclérose et le diabète de type 2

    OpenAIRE

    Abderrazak , Amna

    2015-01-01

    The NLRP3 inflammasome activity is abnormally elevated in many human inflammatory diseases, including cardiovascular and metabolic diseases such as atherosclerosis and type 2 diabetes mellitus (T2DM) respectively. Therefore, there is considerable interest in the identification of effective therapeutics that selectively inhibit the NLRP3 inflammasome pathway. In this study, we have identified Arglabin as a potential small molecule inhibitor that targets the NLRP3 inflammasome activity in cell ...

  13. Lactobacillus reuteri ATCC 55730 and L22 display probiotic potential in vitro and protect against Salmonella-induced pullorum disease in a chick model of infection.

    Science.gov (United States)

    Zhang, Dexian; Li, Rui; Li, Jichang

    2012-08-01

    Lactobacillus reuteri ATCC 55730 (L. reuteri ATCC 55730) and L. reuteri L22 were studied for their probiotic potential. These two strains were able to produce an antimicrobial substance, termed reuterin, the maximum production of reuterin by these two strains was detected in the late logarithmic growth phase (16 h in MRS and 20 h in LB broths). These two strains could significantly reduce the growth of Salmonella pullorum ATCC 9120 in MRS broth, L. reuteri ATCC 55730 with a reduction of 48.2±4.15% (in 5 log) and 89.7±2.59% (in 4 log) respectively, at the same time, L. reuteri L22 was 69.4±3.48% (in 5 log) and 80.4±3.22% respectively. L. reuteri ATCC 55730 was active against the majority of the pathogenic species, including S. pullorum ATCC 9120 and Escherichia coli O(78), while L. reuteri L22 was not as effective as L. reuteri ATCC 55730. The two potential strains were found to survive variably at pH 2.5 and were unaffected by bile salts, while neither of the strains was haemolytic. Moreover, L. reuteri ATCC 55730 exhibited variable susceptibility towards commonly used antibiotics; but L. reuteri L22 showed resistant to most antibiotics in this study. L. reuteri ATCC 55730 consequently was found to significantly increase survival rate in a Salmonella-induced pullorum disease model in chick. To conclude, strain L. reuteri ATCC 55730 possesses desirable probiotic properties, such as antimicrobial activity and immunomodulation in vitro, which were confirmed in vivo by the use of animal models. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The performance of solar collector CPC (compound parabolic concentrator) type with three pipes covered by glass tubes

    Science.gov (United States)

    Gaos, Yogi Sirodz; Yulianto, Muhamad; Juarsa, Mulya; Nurrohman, Marzuki, Edi; Yuliaji, Dwi; Budiono, Kabul

    2017-03-01

    Indonesia is a tropical country that has potential energy of solar radiation worth of 4.5 until 4.8 kWh/m2. However, this potential has not been utilized regularly. This paper will discuss the performance of solar collector compound parabolic concentrator (CPC) type with water as the working fluid. This CPC solar collector utilized three pipes covered by glass tubes. This paper has contribution to provide the temperature achievement between three pipes covered by glass tubes with and without glass cover of solar collector CPC type. The research conducted by varying the water flow rate of 1 l/m up to 6 l/m with three pipes arranged in series and parallel. From the results, the used of solar collector CPC type in the current study shows that the decrease of solar radiation, which was caused by climate change, did not influence the heat absorbance by water in the pipe. Therefore, the design of the solar collector in this research has potential to be used in future when solar radiation are used as the energy source.

  15. Molecular typing of Legionella pneumophila from air-conditioning cooling waters using mip gene, SBT, and FAFLP methods.

    Science.gov (United States)

    Gong, Xiangli; Li, Juntao; Zhang, Ying; Hou, Shuiping; Qu, Pinghua; Yang, Zhicong; Chen, Shouyi

    2017-08-01

    Legionella spp. are important waterborne pathogens. Molecular typing has become an important method for outbreaks investigations and source tracking of Legionnaires. In a survey program conducted by the Guangzhou Center for Disease Control and Prevention, multiple serotypes Legionella pneumophila (L. pneumophila) were isolated from waters in air-conditioning cooling towers in urban Guangzhou region, China between 2008 and 2011. Three genotyping methods, mip (macrophage infectivity potentiator) genotyping, SBT (sequence-based typing), and FAFLP (fluorescent amplified fragment length polymorphism analysis) were used to type these waterborne L. pneumophila isolates. The three methods were capable of typing all the 134 isolates and a reference strain of L. pneumophila (ATCC33153), with discriminatory indices of 0.7034, 0.9218, and 0.9376, for the mip, SBT, and FAFLP methods respectively. Among the 9 serotypes of the 134 isolates, 10, 50, and 34 molecular types were detected by the mip, SBT, and FAFLP methods respectively. The mip genotyping and SBT typing are more feasible for inter-laboratory results sharing and comparison of different types of L. pneumophila. The SBT and FAFLP typing methods were rapid with higher discriminatory abilities. Combinations of two or more of the typing methods enables more accurate typing of Legionella isolates for outbreak investigations and source tracking of Legionnaires. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Caper spurge (Euphorbia lathyris L. ) as a potential crop plant of oleochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Hondelmann, W.; Dambroth, M.

    1987-01-01

    Caper Spurge (Euphorbia lathyris L.) on account of the high seed oil content and the dominating position of oleic acid (> 80%) calls for special attention as potential creep plant for oleochemistry. In domesticating this wild species the characters 'biennial life cycle' and 'dehiscent fruits' could be eliminated in favour of their corresponding crop plant characters 'annual life cycle' and 'indehiscent fruits'. The genetic variation hitherto available seems to be relatively limited. Very high is the amount of 'variation between populations'. Estimates of heritability generally are high, but response to selection is predominantly lower. Because of the rather low fracture resistance of the seed coat the adaption for harvesting by means of a combine is not yet existing. Furthermore, caper spurge exhibits a strongly expressed seed dormancy. Therefore, selection in favour of a diminished primary dormancy is needed. (orig.)

  17. Synthesis and characterization of Mn(III) chloro complexes with salen-type ligands

    International Nuclear Information System (INIS)

    Byun, Jong Chul; Han, Chung Hun; Lee, Nam Ho; Baik, Jong Seok; Park, Yu Chul

    2002-01-01

    A series of novel salen-type complexes ((Mn(III)(L acn )Cl): n=1∼11) containing Cl - ion were obtained by reactions of the Mn(CH 3 COO) 2 ·4H 2 O with the potentially tetradentate compartmental ligand (H 2 L acn ), prepared by condensation the of one mole of diamine (ethylenediamine, 1,3-propanediamine, o-phenylenediamine, and 2,2-dimethyl-1,3-propanediamine) with two moles of aldehyde (salicylaldehyde, 5-chloro- salicylaldehyde, 3,5-dichlorosalicylal-dehyde, and 3,5-di-tert-butyl-2-hydroxy-benzaldehyde) in a methanol solution . The resulting salen-type ligands and their Mn(III) complexes were identified and characterized by elemental analysis, conductivity, thermogravimetry and UV-VIS, IR, and NMR spectroscopy

  18. Evidence from adult L1 Afrikaans L2 French

    African Journals Online (AJOL)

    results of this study show that a large number of the L2 learners had indeed acquired ... position in V2-languages (such as German) and in third position in non-V2 ... L1, allows construction types x and y but he will have no problem acquiring .... Modern Foreign Languages at Stellenbosch University at the time of testing.

  19. Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus.

    Science.gov (United States)

    Fenske, Rachel J; Kimple, Michelle E

    2018-03-01

    Since its discovery and purification by Frederick Banting in 1921, exogenous insulin has remained almost the sole therapy for type 1 diabetes mellitus. While insulin alleviates the primary dysfunction of the disease, many other aspects of the pathophysiology of type 1 diabetes mellitus are unaffected. Research aimed towards the discovery of novel type 1 diabetes mellitus therapeutics targeting different cell signaling pathways is gaining momentum. The focus of these efforts has been almost entirely on the impact of immunomodulatory drugs, particularly those that have already received FDA-approval for other autoimmune diseases. However, these drugs can often have severe side effects, while also putting already immunocompromised individuals at an increased risk for other infections. Potential therapeutic targets in the insulin-producing beta-cell have been largely ignored by the type 1 diabetes mellitus field, save the glucagon-like peptide 1 receptor. While there is preliminary evidence to support the clinical exploration of glucagon-like peptide 1 receptor-based drugs as type 1 diabetes mellitus adjuvant therapeutics, there is a vast space for other putative therapeutic targets to be explored. The alpha subunit of the heterotrimeric G z protein (Gα z ) has been shown to promote beta-cell inflammation, dysfunction, death, and failure to replicate in the context of diabetes in a number of mouse models. Genetic loss of Gα z or inhibition of the Gα z signaling pathway through dietary interventions is protective against the development of insulitis and hyperglycemia. The multifaceted effects of Gα z in regards to beta-cell health in the context of diabetes make it an ideal therapeutic target for further study. It is our belief that a low-risk, effective therapy for type 1 diabetes mellitus will involve a multidimensional approach targeting a number of regulatory systems, not the least of which is the insulin-producing beta-cell. Impact statement The expanding

  20. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population.

    Science.gov (United States)

    Vaxillaire, Martine; Cavalcanti-Proença, Christine; Dechaume, Aurélie; Tichet, Jean; Marre, Michel; Balkau, Beverley; Froguel, Philippe

    2008-08-01

    Hepatic glucokinase (GCK) is a key regulator of glucose storage and disposal in the liver, where its activity is competitively modulated, with respect to glucose, by binding to glucokinase regulatory protein (GCKR) in the presence of fructose 6-phosphate. Genome-wide association studies for type 2 diabetes identified GCKR as a potential locus for modulating triglyceride levels. We evaluated, in a general French population, the contribution of the GCKR rs1260326-P446L polymorphism to quantitative metabolic parameters and to dyslipidemia and hyperglycemia risk. Genotype effects of rs1260326 were studied in 4,833 participants from the prospective DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort both at inclusion and using the measurements at follow-up. The minor T-allele of rs1260326 was strongly associated with lower fasting glucose (-1.43% per T-allele; P = 8 x 10(-13)) and fasting insulin levels (-4.23%; P = 3 x 10(-7)), lower homeostasis model assessment of insulin resistance index (-5.69%; P = 1 x 10(-8)), and, conversely, higher triglyceride levels (3.41%; P = 1 x 10(-4)) during the 9-year study. These effects relate to a lower risk of hyperglycemia (odds ratio [OR] 0.79 [95% CI 0.70-0.88]; P = 4 x 10(-5)) and of incident cases during the study (hazard ratio [HR] 0.83 [0.74-0.95]; P = 0.005). Moreover, an additive effect of GCKR rs1260326(T) and GCK (-30G) alleles conferred lower fasting glycemia (P = 1 x 10(-13)), insulinemia (P = 5 x 10(-6)), and hyperglycemia risk (P = 1 x 10(-6)). GCKR-L446 carriers are protected against type 2 diabetes despite higher triglyceride levels and risk of dyslipidemia, which suggests a potential molecular mechanism by which these two components of the metabolic syndrome can be dissociated.

  1. Gestational hypothyroidism-induced changes in L-type calcium channels of rat aorta smooth muscle and their impact on the responses to vasoconstrictors

    Directory of Open Access Journals (Sweden)

    Katayoun Sedaghat

    2015-02-01

    Conclusion: This study suggests that in hypothyroid offspring L-type Ca2+ channels are less functional, while intracellular Ca2+ handling systems are less modified by low levels of maternal thyroid hormones.

  2. Optimal Embeddings of Bessel-Potential-Type Spaces into Generalized Hölder Spaces Involving k-Modulus of Smoothness

    Czech Academy of Sciences Publication Activity Database

    Gogatishvili, Amiran; Neves, J. S.; Opic, Bohumír

    2010-01-01

    Roč. 32, č. 3 (2010), s. 201-228 ISSN 0926-2601 R&D Projects: GA ČR GA201/05/2033; GA ČR GA201/08/0383 Institutional research plan: CEZ:AV0Z10190503 Keywords : slowly varying functions * Lorentz-Karamata spaces * Rearrangement-invariant Banach function spaces * Bessel potentials * (fractional) Sobolev-type spaces * Hölder-type spaces * Zygmund-type spaces Subject RIV: BA - General Mathematics Impact factor: 0.853, year: 2010 http://link.springer.com/article/10.1007%2Fs11118-009-9148-2

  3. Rab5 regulates internalisation of P2X4 receptors and potentiation by ivermectin.

    Science.gov (United States)

    Stokes, Leanne

    2013-03-01

    The P2X4 receptor is an ATP-gated ion channel expressed in neurons, endothelia and immune cells. Plasma membrane expression of P2X4 is regulated by dynamin-dependent endocytosis, and this study identifies a Rab5-dependent pathway of receptor internalisation. Expression of Rab5 constructs altered the distribution of P2X4 in HEK-293 cells, and both constitutive internalisation and agonist-induced desensitisation of P2X4 were increased by co-expression of wild-type Rab5 or constitutively active Rab5 (Q79L). Expression of inactive dynamin K44A and Rab5 S34N constructs abolished agonist-induced desensitisation, suggesting internalisation as the underlying mechanism. Blocking P2X4 internalisation in this way also abolished potentiation of ATP-induced currents by the allosteric modulator ivermectin. This suggests that the dynamin-Rab5 internalisation pathway is essential for the ivermectin potentiation effect. In agreement with this hypothesis, the co-expression of wild-type dynamin, wild-type Rab5 or active Rab5 (Q79L) could increase the potentiation of the ATP-induced P2X4 response by ivermectin. These findings highlight Rab5 GTPase as a key regulator of P2X4 receptor cell surface expression and internalisation.

  4. Comparison of the phytoremediation potentials of Medicago falcata L. And Medicago sativa L. in aged oil-sludge-contaminated soil.

    Science.gov (United States)

    Panchenko, Leonid; Muratova, Anna; Turkovskaya, Olga

    2017-01-01

    Thirteen-year monitoring of the vegetation growing in the industrial and adjacent areas of an oil refinery showed the prevalence of yellow medick (Medicago falcata L.) over other plant species, including alfalfa (Medicago sativa L.). A comparative field study of the two Medicago species established that yellow medick and alfalfa exhibited similar resistance to soil petroleum hydrocarbons and that the pollutant concentration in their rhizosphere was 30% lower than that in the surrounding bulk soil. In laboratory pot experiments, yellow medick reduced the contaminant content by 18% owing to the degradation of the major heavy oil fractions, such as paraffins, naphthenes, and alcohol and benzene tars; and it was more successful than alfalfa. Both species were equally effective in stimulating the total number of soil microorganisms, but the number of hydrocarbon-oxidizing microorganisms, including polycyclic aromatic hydrocarbon degraders, was larger in the root zone of alfalfa. In turn, yellow medick provided a favorable balance of available nitrogen. Both Medicago species equally stimulated the dehydrogenase and peroxidase activities of the soil, and yellow medick increased the activity of soil polyphenol oxidase but reduced the activity of catalase. The root tissue activity of catalase, ascorbate oxidase, and tyrosinase was grater in alfalfa than in yellow medick. The peroxidase activity of plant roots was similar in both species, but nondenaturing polyacrylamide gel electrophoresis showed some differences in the peroxidase profiles of the root extracts of alfalfa and yellow medick. Overall, this study suggests that the phytoremediation potentials of yellow medick and alfalfa are similar, with some differences.

  5. Genetic variability in Cynara cardunculus L. domestic and wild types for grain oil production and fatty acids composition

    International Nuclear Information System (INIS)

    Raccuia, Salvatore Antonino; Piscioneri, Ilario; Sharma, Neeta; Melilli, Maria Grazia

    2011-01-01

    This paper aimed to study the genetic variability within different types of Cynara cardunculus L., domestic and wild types, for their grain oil amount and oil fatty acid composition. The grain oils were extracted from 8 domestic cardoons and 4 wild cardoons, by Soxhlet method, and obtained oils were characterized for palmitic, stearic, oleic and linoleic acids by gas chromatography. The oil amount, resulted on average of accessions 216 g kg -1 DM with a good range of variability (CV = 11.7%). Unsaturated acids (oleic and linoleic) predominated over saturated ones (stearic and palmitic acids), the chemical characterization of extracted oil, showed the main compound (as % of analysed fatty acids), averaged for all populations, was linoleic acid (44.5%), followed by oleic acid (42.6%), palmitic acid (9.8%) and stearic acid (3.1%). In particular referring the oleic acid wild cardoon populations showed a mean value of 289 g kg -1 oil, against a mean value of 472 g kg -1 oil showed by domestic cardoon accessions. Three of the studied domestic cardoon ('DC1', 'DC3' and 'DC7') showed values higher than 795 g kg -1 oil, while all the other accessions had concentration lower than 370 g kg -1 oil. The three types of domestic cardoon 'DC1', 'DC3' and 'DC7' showed a fatty acids profile similar to genetic modified sunflower oil, representing new genetic material that potentially could be used for high quality biodiesel production, characterised by a low Iodine Number. -- Highlights: → The grain oils from 12 cardoons were characterized for fatty acids composition. → The oil amount, resulted on average of accessions 216 g kg -1 DM. → Oleic and linoleic acids predominated over stearic and palmitic acids. → Three domestic cardoons grain oil showed high oleic acid content (795 g kg -1 oil). → This oil could be used for high quality biodiesel production, with a low IN.

  6. Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Raciti, Gregory Alexander; Fiory, Francesca; Campitelli, Michele; Desiderio, Antonella; Spinelli, Rosa; Longo, Michele; Nigro, Cecilia; Pepe, Giacomo; Sommella, Eduardo; Campiglia, Pietro; Formisano, Pietro; Beguinot, Francesco; Miele, Claudia

    2018-01-01

    Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro. We found that CAde enhances terminal adipocyte differentiation of 3T3-L1 cells raising the expression of CCAAT/enhancer binding protein beta (C/Ebpβ), peroxisome proliferator activated receptor gamma (Pparγ), glucose transporter type 4 (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases occurring in the pre-adipocytes differentiation to mature adipocytes furthermore revealed that CAde promotes the early differentiation stage by up-regulating C/ebpβ expression at 2, 4 and 8 h post the adipogenic induction and anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal expansion (MCE). These findings provide evidence that the exposure to CAde enhances in vitro fat cell differentiation of pre-adipocytes and functional capacity of mature adipocytes, and pave the way to the development of products derived from Citrus aurantium L. fruit juice, which may improve WAT functional capacity and may be effective for the prevention and/or treatment of T2D.

  7. Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi; Elkind, M.M.

    1994-01-01

    The purpose of this study was to examine whether 3-amino-benzamide (3ABA), an inhibitor of poly (ADP-ribose) synthesis, inhibits the two types of potentially lethal damage (PLD) repair, termed slow and fast. The fast-type PLD repair was measured by the decrease in survival of V79 Chinese hamster cells by postirradiation treatment with 3ABA. The slow-type PLD repair was measured by the increase in survival by posttreatment with conditioned medium (CM), which became conditioned by growing a crowed culture of cells and supports the slow-type PLD repair. Up to 1 mM 3-ABA inhibited the slow type repair; at doses of 2 mM and above, it inhibited the fast type of PLD repair. There are quantitative differences in cellular effects of 3ABA dependent on concentration. Poly (ADP-ribose) appears to play an important role in the PLD repairs and has little effect on the repair of sublethal damage. 10 refs., 2 figs

  8. Comparison of invitro cytotoxic and genotoxic potential of glass ionomer cement type IX on human lymphocytes before and after electron beam irradiation

    International Nuclear Information System (INIS)

    Hegde, Mithra N.; Brijesh; Shetty, Shilpa S.; Hegde, Nidarsh D.; Suchetha Kumari; Sanjeev, Ganesh

    2013-01-01

    Glass ionomer cements are widely used in dentistry as an adhesive restorative materials. However, the results of cytotoxicity and genotoxicity studies using these materials are inconclusive in literature. The aim of this study was to examine the cytotoxic and genotoxic potential of glass ionomer cement type IX available commercially before and after irradiation. Glass ionomer cement type IX was obtained commercially. Samples were prepared as per the ISO standard size of 25x2x2 mm using polytetrafluoroethylene teflon mould and divided into two groups - non irradiated and irradiated groups. The samples in radiated category were exposed to 10 KGy of electron beam irradiation at Microtron Centre, Mangalore University, Mangalore, India. For hemolysis assay, the samples were immersed in phosphate buffer saline and incubated at 370℃ for 24 hrs, 7 days and 14 days. 200 μL of 24 hr material extract was mixed with human peripheral blood lymphocyte tested for comet assay by single cell DNA comet assay and apoptosis by DNA diffusion assay. Hemolytic activity of non irradiated Glass ionomer cement type IX after 24 hrs, 7 days and 14 days was 78.18±10.13, 32.57±12.28, 38.56±4.68 respectively whereas hemolytic activity of irradiated Glass ionomer cement type IX after 24 hrs, 7 days and 14 days was 58.90±2.28, 35.04±1.09 and 34.26±7.71 respectively. The irradiation of Glass ionomer cement type IX with 10 KGy dose of electron beam irradiation did not show significant increase in the frequency of DNA damage when compared to that of the nonirradiated group. Apoptotic index did not show much difference between non-irradiated and irradiated groups. Taken together, we conclude that some components of glass ionomer cements show both genotoxic and cytotoxic effects. (author)

  9. Contributory roles of two l-lactate dehydrogenases for l-lactic acid production in thermotolerant Bacillus coagulans.

    Science.gov (United States)

    Sun, Lifan; Zhang, Caili; Lyu, Pengcheng; Wang, Yanping; Wang, Limin; Yu, Bo

    2016-11-25

    Thermotolerant Bacillus coagulans is considered to be a more promising producer for bio-chemicals, due to its capacity to withstand harsh conditions. Two L-lactate dehydrogenase (LDH) encoding genes (ldhL1 and ldhL2) and one D-LDH encoding gene (ldhD) were annotated from the B. coagulans DSM1 genome. Transcriptional analysis revealed that the expression of ldhL2 was undetectable while the ldhL1 transcription level was much higher than that of ldhD at all growth phases. Deletion of the ldhL2 gene revealed no difference in fermentation profile compared to the wild-type strain, while ldhL1 single deletion or ldhL1ldhL2 double deletion completely blocked L-lactic acid production. Complementation of ldhL1 in the above knockout strains restored fermentation profiles to those observed in the wild-type strain. This study demonstrates ldhL1 is crucial for L-lactic acid production and NADH balance in B. coagulans DSM1 and lays the fundamental for engineering the thermotolerant B. coagulans strain as a platform chemicals producer.

  10. Evaluating potential of borage ( Borago officinalis L.) in ...

    African Journals Online (AJOL)

    Bioremediation is an efficient, economical and environmentally acceptable strategy used for coping with the salinization of agricultural soils. In this study, borage has been proposed as possible candidate for bioremediation of Na+ and Cl−. In this order, the borage (Borago officinalis L.) seeds were sown under four levels of ...

  11. Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

    Science.gov (United States)

    Vulfius, Catherine A; Kasheverov, Igor E; Kryukova, Elena V; Spirova, Ekaterina N; Shelukhina, Irina V; Starkov, Vladislav G; Andreeva, Tatyana V; Faure, Grazyna; Zouridakis, Marios; Tsetlin, Victor I; Utkin, Yuri N

    2017-01-01

    Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by

  12. Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Catherine A Vulfius

    Full Text Available Phospholipases A2 (PLA2s are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which

  13. Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Riya, M P; Antu, K A; Pal, S; Srivastava, A K; Sharma, S; Raghu, K G

    2014-09-01

    Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients.

  14. The transformative potential of action research and ICT in the Second Language (L2 classroom

    Directory of Open Access Journals (Sweden)

    Farren Margaret

    2015-12-01

    Full Text Available This study shows the transformative potential of action research and information and communications technology (ICT in the second language (L2 classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT creatively in their classroom. Gee (2008 advocates the use of the preferred media of our classroom students in order to address their learning. Prensky (2001 urges us to feel the fear and do it anyway with our digital native classes. A post-primary teacher and a primary teacher show us how they felt the fear, did it and transformed aspects of their own teaching in the process. The Masters programme required the teachers to engage with innovative practices, informed by their own values, and integrate technologies that were new to them into their repertoire of classroom strategies. Peer validation meetings with colleagues enabled meaningful insights to emerge from the research. The teachers improve and transform their second language (L2 practice in collaboration and validation with others.

  15. Cytotoxic and antioxidative potentials of ethanolic extract of Eugenia uniflora L. (Myrtaceae) leaves on human blood cells.

    Science.gov (United States)

    da Cunha, Francisco Assis Bezerra; Waczuk, Emily Pansera; Duarte, Antonia Eliene; Barros, Luiz Marivando; Elekofehinti, Olusola Olalekan; Matias, Edinardo Fagner Ferreira; da Costa, José Galberto Martins; Sanmi, Adekunle Adeniran; Boligon, Aline Augusti; da Rocha, João Batista Teixeira; Souza, Diogo Onofre; Posser, Thaís; Coutinho, Henrique Douglas Melo; Franco, Jeferson Luis; Kamdem, Jean Paul

    2016-12-01

    Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal disorders and hypertension. However, scanty information exist on its potential toxicity to human, and little is known on its antioxidant activity in biological system. Hence, we investigated for the first time the potential toxic effects of ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and erythrocytes, as well as its influence on membrane erythrocytes osmotic fragility. In addition, EEEU was chemically characterized and its antioxidant capacity was evaluated. We found that EEEU (1-480μg/mL) caused neither cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay, respectively. EEEU (1-480μg/mL) did not have any effect on membrane erythrocytes fragility. In addition, EEEU inhibited Fe 2+ -induced lipid peroxidation in rat brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some polyphenolic compounds with high content such as quercetin, quercitrin, isoquercitrin, luteolin and ellagic acid, which may be at least in part responsible for its beneficial effects. Our results suggest that consumption of EEEU at relatively higher concentrations may not result in toxicity. However, further in vitro and in vivo studies should be conducted to ascertain its safety. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Corrosion of type 304L stainless steel in boiling dilute neptunium nitrate solution

    International Nuclear Information System (INIS)

    Motooka, Takafumi; Kiuchi, Kiyoshi

    2003-01-01

    Corrosion of type 304L stainless steel in nitric acid solution containing neptunium was studied under immersion and heat-transfer condition. Corrosion rates of stainless steel were obtained by the weight loss measurement and the quantitative analysis of metallic ions dissolved in solution. The surface morphology was observed by scanning electron microscopy. The corrosion acceleration mechanism was investigated by polarization measurement and spectrophotometry. The corrosion rate in boiling 9M nitric acid was accelerated by addition of neptunium. The corrosion of stainless steel was promoted under heat-transfer condition compared to immersion condition. In polarization measurements, the cathodic current was increased by addition of neptunium. Spectrophotometric measurements showed the oxidization of neptunium in boiling nitric acid. It was suggested that the accelerated corrosion in nitric acid solution containing neptunium was caused by re-oxidation of neptunium. (author)

  17. Experimental study of selection rules following from the existence of two types of neutrinos; Etude experimentale des regles de selection decoulant de l'existence de deux types de neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Gaillard, J M [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-05-15

    Interactions of high energy neutrinos with matter have been observed In the course of an experiment done in collaboration with G. Danby, K. Goulianos, L. M. Lederman, N. Mistry, M. Schwartz and J. Steinberger at the Brookhaven AGS. The neutrinos were produced mainly in the decay {pi}{sup {+-}} {yields} {mu}{sup {+-}} + {upsilon}({upsilon}-bar); the experiment leads to the conclusion that thee neutrinos are very likely different from the ones produced in beta decay reactions. We use the result of this experiment to study the selection rules applicable in the framework of a two neutrino theory. (author) [French] Nous avons observe l'interaction des neutrinos de haute energie avec la matiere au court dune experience effectuee en collaboration avec G. Danby, K. Goulianos, L. M. Lederman, N. Mistry, M. Schwartz et J. Steinberger sur l'accelerateur AGS du Brookhaven National Laboratory. Les neutrinos utilites provenaient principalement de la desintegration {pi}{sup {+-}} {yields} {mu}{sup {+-}} + {upsilon}({upsilon}-bar) l'experience conduit a la conclusion que ces neutrinos sont tres probablement differents de ceux produits par la desintegration beta. Nous utilisons les resultats de cette experience pour etudier quelles sont les regles de selection a utiliser dans le cadre d'une theorie a deux types de neutrinos. (auteur)

  18. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. THE EFFECT OF L- ARGININE ON OXIDATIVE STRESS AND MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE

    Directory of Open Access Journals (Sweden)

    L. P. Martynyuk

    2017-07-01

    Full Text Available Background. One of the severest complications of diabetes is diabetic kidney disease (DKD. Microalbuminuria (MAU is one of the first signals of DKD and an important pathogenetic mechanism of disease progression. With diabetes dramatically antioxidant properties worsen. Objective. The aim was to investigate the effect of L-arginine on oxidative stress parameters and microalbuminuria in type 2 diabetes mellitus and chronic kidney disease patients. Methods. Total of 57 patients with type 2 diabetes mellitus and chronic kidney disease and 30 healthy subjects (control group were included in the study. The patients were divided into 2 congruent groups. The 1-st group of patients (n=33, in addition to standard therapy, received L-arginine 4.2 g intravenously for 5 days, after that they took it 1,0 g orally three times a day during meals for 1 month. The second group of patients (n=24 received a standard therapy. The concentration of lipid peroxidation products was measured by a spectrophotometric method. The determination of MAU was carried out in morning portion of urine immunological semiquantitative using test strips. Results. Significant improvement in indexes of lipid peroxidation was observed in both groups after therapy (p˂0.01, but in patients treated with L-arginine it was more expressed (p˂0,01. The standard therapy did not significantly affect the level of MAU (p˃0,05. The patients treated with L-Arginine, showed a significant reduction in MAU (p˂0.01. Conclusions. The usage of L-arginine facilitates the correction of lipid peroxidation processes and reduces the severity of microalbuminuria in patients with diabetic kidney disease that slowing its progression.

  20. Potential-controlled filtering in quantum star graphs

    International Nuclear Information System (INIS)

    Turek, Ondřej; Cheon, Taksu

    2013-01-01

    We study the scattering in a quantum star graph with a Fülöp–Tsutsui coupling in its vertex and with external potentials on the lines. We find certain special couplings for which the probability of the transmission between two given lines of the graph is strongly influenced by the potential applied on another line. On the basis of this phenomenon we design a tunable quantum band-pass spectral filter. The transmission from the input to the output line is governed by a potential added on the controlling line. The strength of the potential directly determines the passband position, which allows to control the filter in a macroscopic manner. Generalization of this concept to quantum devices with multiple controlling lines proves possible. It enables the construction of spectral filters with more controllable parameters or with more operation modes. In particular, we design a band-pass filter with independently adjustable multiple passbands. We also address the problem of the physical realization of Fülöp–Tsutsui couplings and demonstrate that the couplings needed for the construction of the proposed quantum devices can be approximated by simple graphs carrying only δ potentials. - Highlights: ► Spectral filtering devices based on quantum graphs are designed theoretically. ► The passband is controlled by the application of macroscopic potentials on lines. ► The filters are built upon special Fulop–Tsutsui type couplings at graph vertices. ► A method of construction of Fulop–Tsutsui vertices from delta potentials is devised.

  1. Mechanisms of Nifedipine-Downregulated CD40L/sCD40L Signaling in Collagen Stimulated Human Platelets.

    Directory of Open Access Journals (Sweden)

    Tso-Hsiao Chen

    Full Text Available The platelet-derived soluble CD40L (sCD40L release plays a critical role in the development of atherosclerosis. Nifedipine, a dihydropyridine-based L-type calcium channel blocker (CCB, has been reported to have an anti-atherosclerotic effect beyond its blood pressure-lowering effect, but the molecular mechanisms remain unclear. The present study was designed to investigate whether nifedipine affects sCD40L release from collagen-stimulated human platelets and to determine the potential role of peroxisome proliferator-activated receptor-β/-γ (PPAR-β/-γ. We found that treatment with nifedipine significantly inhibited the platelet surface CD40L expression and sCD40L release in response to collagen, while the inhibition was markedly reversed by blocking PPAR-β/-γ activity with specific antagonist such as GSK0660 and GW9662. Meanwhile, nifedipine also enhanced nitric oxide (NO and cyclic GMP formation in a PPAR-β/-γ-dependent manner. When the NO/cyclic GMP pathway was suppressed, nifedipine-mediated inhibition of sCD40L release was abolished significantly. Collagen-induced phosphorylation of p38MAPK, ERK1/2 and HSP27, matrix metalloproteinase-2 (MMP-2 expression/activity and reactive oxygen species (ROS formation were significantly inhibited by nifedipine, whereas these alterations were all attenuated by co-treatment with PPAR-β/-γ antagonists. Collectively, these results demonstrate that PPAR-β/-γ-dependent pathways contribute to nifedipine-mediated downregulation of CD40L/sCD40L signaling in activated platelets through regulation of NO/ p38MAPK/ERK1/2/HSP27/MMP-2 signalings and provide a novel mechanism regarding the anti-atherosclerotic effect of nifedipine.

  2. Gravitropic reaction of primary seminal roots of Zea mays L. influenced by temperature and soil water potential.

    Science.gov (United States)

    Nakamoto, T

    1995-03-01

    The growth of the primary seminal root of maize (Zea mays L.) is characterized by an initial negative gravitropic reaction and a later positive one that attains a plagiotropic liminal angle. The effects of temperature and water potential of the surrounding soil on these gravitropic reactions were studied. Temperatures of 32, 25, and 18C and soil water potentials of -5, -38, and -67 kPa were imposed and the direction of growth was measured for every 1 cm length of the root. The initial negative gravitropic reaction extended to a distance of about 10 cm from the grain. Higher temperatures reduced the initial negative gravitropic reaction. Lower soil water potential induced a downward growth at root emergence. A mathematical model, in which it was assumed that the rate of the directional change of root growth was a sum of a time-dependent negative gravitropic reaction and an establishment of the liminal angle, adequately fitted the distance-angle relations. It was suggested that higher temperatures and/or a lower water potential accelerated the diminution of the initial negative gravitropic reaction.

  3. The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes

    Science.gov (United States)

    FALCONER, CATHERINE L.; PAGE, ANGIE S.; ANDREWS, ROB C.; COOPER, ASHLEY R.

    2015-01-01

    ABSTRACT Purpose Sedentary time, in particular, prolonged unbroken sedentary time, is detrimental to health and displaces time spent in either light or moderate intensity physical activity. This cross-sectional study aimed to identify the potential impact of reallocating time from sedentary behaviors to more active behaviors on measures of body composition and metabolic health in people with type 2 diabetes. Methods Participants were 519 adults with newly diagnosed type 2 diabetes who had been recruited to the Early Activity in Diabetes (Early ACTID) randomized controlled trial. Waist-worn accelerometers were used to obtain objective measurement of sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) at baseline alongside clinical measurements and fasting blood samples to determine cholesterol, triglycerides, HOMA-IR, and glucose. Isotemporal substitution modeling was performed to determine the potential impact of reallocating 30 min of sedentary time accumulated in a single bout (long bout) with 30 min of interrupted sedentary time, LPA, or MVPA. Results Sedentary time accounted for 65% of the waking day, of which 45% was accumulated in prolonged (≥30 min) bouts. Reallocation of 30 min of long-bout sedentary time with 30 min of short-bout sedentary time was associated with lower body mass index (BMI) (adjusted β, −0.60; 95% confidence interval [CI], −1.00, −0.21) and waist circumference (WC) (adjusted β, −1.16; 95% CI, −2.08, −0.25). Stronger effects were seen for LPA and MVPA. Reallocation of 30 min of long-bout sedentary time with LPA was associated with higher HDL-cholesterol (adjusted β, 0.02; 95% CI, 0.00–0.03 mmol·L−1). Conclusions Encouraging adults with newly diagnosed type 2 diabetes to break up prolonged periods of sedentary time may be an effective strategy for improving body composition and metabolic health. PMID:26378943

  4. Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection

    Directory of Open Access Journals (Sweden)

    Poyin Chen

    2017-12-01

    Full Text Available Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization and infection often via receptor glycosylation. Bacterial interactions with host glycans are intimately involved in modulating cellular responses through signaling cascades at the membrane and in intracellular compartments. Characterizing the mechanisms underpinning these modulations is essential for predictive use of dietary prebiotics to diminish pathogen association. We demonstrated that human milk oligosaccharide (HMO pretreatment of colonic epithelial cells (Caco-2 led to a 50% decrease in Listeria association, while Biomos pretreatment increased host association by 150%. L. monocytogenes-induced gene expression changes due to oligosaccharide pretreatment revealed global alterations in host signaling pathways that resulted in differential subcellular localization of L. monocytogenes during early infection. Ultimately, HMO pretreatment led to bacterial clearance in Caco-2 cells via induction of the unfolded protein response and eIF2 signaling, while Biomos pretreatment resulted in the induction of host autophagy and L. monocytogenes vacuolar escape earlier in the infection progression. This study demonstrates the capacity of prebiotic oligosaccharides to minimize infection through induction of host-intrinsic protective responses.

  5. Contribution of the cashew gum (Anacardium occidentale L.) for development of layer-by-layer films with potential application in nanobiomedical devices

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, I.M.S. [Departamento de Quimica, Centro de Ciencias da Natureza, CCN, Universidade Federal do Piaui, UFPI, Teresina, PI, 64049-550 (Brazil); Nucleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus Parnaiba, CMRV, Universidade Federal do Piaui, UFPI, Parnaiba, PI, 64202-020 (Brazil); Zampa, M.F. [Nucleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus Parnaiba, CMRV, Universidade Federal do Piaui, UFPI, Parnaiba, PI, 64202-020 (Brazil); Campus Parnaiba, Instituto Federal de Educacao Ciencia e Tecnologia do Piaui, IFPI, Parnaiba, PI, 64210-260 (Brazil); Moura, J.B.; Santos, J.R. dos [Departamento de Quimica, Centro de Ciencias da Natureza, CCN, Universidade Federal do Piaui, UFPI, Teresina, PI, 64049-550 (Brazil); Eaton, P. [REQUIMTE, Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre, Porto, 4169-007 (Portugal); Zucolotto, V. [Grupo de Biofisica Molecular Sergio Mascarenhas, Instituto de Fisica de Sao Carlos, IFSC, USP, Sao Carlos, SP, 13566-590 (Brazil); and others

    2012-08-01

    The search for bioactive molecules to be employed as recognition elements in biosensors has stimulated researchers to pore over the rich Brazilian biodiversity. In this sense, we introduce the use of natural cashew gum (Anacardium occidentale L.) as an active biomaterial to be used in the form of layer-by-layer films, in conjunction with phthalocyanines, which were tested as electrochemical sensors for dopamine detection. We investigated the effects of chemical composition of cashew gum from two different regions of Brazil (Piaui and Ceara states) on the physico-chemical characteristics of these nanostructures. The morphology of the nanostructures containing cashew gum was studied by atomic force microscopy which indicates that smooth films punctuated by globular features were formed that showed low roughness values. The results indicate that, independent of the origin, cashew gum stands out as an excellent film forming material with potential application in nanobiomedical devices as electrochemical sensors. Highlights: Black-Right-Pointing-Pointer This study focused on the use of cashew gum for the formation of LbL films. Black-Right-Pointing-Pointer LbL films containing cashew gums were investigated by AFM and cyclic voltammetry. Black-Right-Pointing-Pointer Cashew gum contributed to obtain stable films with well-defined redox processes. Black-Right-Pointing-Pointer Cashew gum films detected dopamine in low concentrations. Black-Right-Pointing-Pointer These LbL films presented potential application in nanobiomedical devices.

  6. Contribution of the cashew gum (Anacardium occidentale L.) for development of layer-by-layer films with potential application in nanobiomedical devices

    International Nuclear Information System (INIS)

    Araújo, I.M.S.; Zampa, M.F.; Moura, J.B.; Santos, J.R. dos; Eaton, P.; Zucolotto, V.

    2012-01-01

    The search for bioactive molecules to be employed as recognition elements in biosensors has stimulated researchers to pore over the rich Brazilian biodiversity. In this sense, we introduce the use of natural cashew gum (Anacardium occidentale L.) as an active biomaterial to be used in the form of layer-by-layer films, in conjunction with phthalocyanines, which were tested as electrochemical sensors for dopamine detection. We investigated the effects of chemical composition of cashew gum from two different regions of Brazil (Piauí and Ceará states) on the physico-chemical characteristics of these nanostructures. The morphology of the nanostructures containing cashew gum was studied by atomic force microscopy which indicates that smooth films punctuated by globular features were formed that showed low roughness values. The results indicate that, independent of the origin, cashew gum stands out as an excellent film forming material with potential application in nanobiomedical devices as electrochemical sensors. Highlights: ► This study focused on the use of cashew gum for the formation of LbL films. ► LbL films containing cashew gums were investigated by AFM and cyclic voltammetry. ► Cashew gum contributed to obtain stable films with well-defined redox processes. ► Cashew gum films detected dopamine in low concentrations. ► These LbL films presented potential application in nanobiomedical devices.

  7. DISCOVERY OF AN UNUSUALLY RED L-TYPE BROWN DWARF

    International Nuclear Information System (INIS)

    Gizis, John E.; Castro, Philip J.; Faherty, Jacqueline K.; Liu, Michael C.; Aller, Kimberly M.; Shaw, John D.; Vrba, Frederick J.; Harris, Hugh C.; Deacon, Niall R.

    2012-01-01

    We report the discovery of an unusually red brown dwarf found in a search for high proper motion objects using WISE and 2MASS data. WISEP J004701.06+680352.1 is moving at 0.''44 yr –1 and lies relatively close to the Galactic plane (b = 5. 0 2). Near-infrared photometry and spectroscopy reveals that this is one of the reddest (2MASS J – K s 2.55 ± 0.08 mag) field L dwarfs yet detected, making this object an important member of the class of unusually red L dwarfs. We discuss evidence for thick condensate clouds and speculate on the age of the object. Although models by different research groups agree that thick clouds can explain the red spectrum, they predict dramatically different effective temperatures, ranging from 1100 K to 1600 K. This brown dwarf is well suited for additional studies of extremely dusty substellar atmospheres because it is relatively bright (K s = 13.05 ± 0.03 mag), which should also contribute to an improved understanding of young gas-giant planets and the transition between L and T brown dwarfs.

  8. The Potential Role of Yogurt in Weight Management and Prevention of Type 2 Diabetes.

    Science.gov (United States)

    Panahi, Shirin; Tremblay, Angelo

    2016-01-01

    Yogurt is a semisolid fermented milk product that originated centuries ago and is viewed as an essential food and important source of nutrients in the diet of humans. Over the last 30 years, overweight and obesity have become characteristic of Western and developing countries, which has led to deleterious health outcomes, including cardiovascular disease, type 2 diabetes, hypertension, and other chronic conditions. Recent epidemiological and clinical evidence suggests that yogurt is involved in the control of body weight and energy homeostasis and may play a role in reducing the risk for type 2 diabetes partly via the replacement of less healthy foods in the diet, its food matrix, the effect of specific nutrients such as calcium and protein on appetite control and glycemia, and alteration in gut microbiota. This review will discuss the specific properties that make yogurt a unique food among the dairy products, epidemiological and clinical evidence supporting yogurt's role in body weight, energy balance, and type 2 diabetes, including its potential mechanisms of action and gaps that need to be explored. Key teaching points • Several epidemiological and clinical studies have suggested a beneficial effect of yogurt consumption in the control of body weight and energy homeostasis, although this remains controversial. • Yogurt possesses unique properties, including its nutritional composition; lactic acid bacteria, which may affect gut microbiota; and food matrix, which may have a potential role in appetite and glycemic control. • Potential mechanisms of action of yogurt include an increase in body fat loss, decrease in food intake and increase in satiety, decrease in glycemic and insulin response, altered gut hormone response, replacement of less healthy foods, and altered gut microbiota. • The relative energy and nutrient content and contribution of a standard portion of yogurt to the overall diet suggest that the percentage daily intake of these nutrients

  9. Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.

    Science.gov (United States)

    Bkaily, Ghassan; El-Bizri, Nesrine; Bui, Michel; Sukarieh, Rami; Jacques, Danielle; Fu, Michael L X

    2003-03-01

    The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.

  10. Metabolome classification of Brassica napus L. organs via UPLC-QTOF-PDA-MS and their anti-oxidant potential.

    Science.gov (United States)

    Farag, Mohamed A; Sharaf Eldin, Mohamed G; Kassem, Hanaa; Abou el Fetouh, Mohamed

    2013-01-01

    Brassica napus L. is a crop widely grown for its oil production and other nutritional components in the seed. In addition to the seed, other organs contain a wide range of phenolic metabolites although they have not been investigated to the same extent as in seeds. To define and compare the phytochemical composition of B. napus L. organs, namely the root, stem, leaf, inflorescence and seeds. Non-targeted metabolomic analysis via UPLC-QTOF-MS was utilised in order to localise compounds belonging to various chemical classes (i.e. oxygenated fatty acids, flavonols, phenolic acids and sinapoyl choline derivatives). The vast majority of identified metabolites were flavonol glycosides that accumulated in most of the plant organs. Whereas other classes were detected predominantly in specific organs, i.e. sinapoyl cholines were present uniquely in seeds. Furthermore, variation in the accumulation pattern of metabolites from the same class was observed, particularly in the case of quercetin, kaempferol and isorhamnetin flavonols. Anti-oxidant activity, based on 2,2-diphenyl-1-picrylhdrazyl analysis was observed for all extracts, and correlated to some extent with total flavonoid content. This study provides the most complete map for polyphenol composition in B. napus L. organs. By describing the metabolites profile in B. napus L., this study provides the basis for future investigations of seeds for potential health and/or medicinal use. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Volcanic hazards from Bezymianny- and Bandai-type eruptions

    Science.gov (United States)

    Siebert, L.; Glicken, H.; Ui, T.

    1987-01-01

    kilometers. When not confined by valley walls, avalanches can affect wide areas beyond the volcano's flanks. Tsunamis from debris avalanches at coastal volcanoes have caused more fatalities than have the landslides themselves or associated eruptions. The probable travel distance (L) of avalanches can be estimated by considering the potential vertical drop (H). Data from a catalog of around 200 debris avalanches indicates that the H/L rations for avalanches with volumes of 0.1-1 km3 average 0.13 and range 0.09-0.18; for avalanches exceeding 1 km3, H/L ratios average 0.09 and range 0.5-0.13. Large-scale deformation of the volcanic edefice and intense local seismicity precede many slope failures and can indicate the likely failure direction and orientation of potential lateral blasts. The nature and duration of precursory activity vary widely, and the timing of slope faliure greatly affects the type of associated eruption. Bandai-type eruptions are particularly difficult to anticipate because they typically climax suddenly without precursory eruptions and may be preceded by only short periods of seismicity. ?? 1987 Springer-Verlag.

  12. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2.

    Science.gov (United States)

    Churqui, Marianela Patzi; Lind, Liza; Thörn, Karolina; Svensson, Alexandra; Savolainen, Otto; Aranda, Katty Terrazas; Eriksson, Kristina

    2018-01-10

    Equisetum giganteum L and Copaifera reticulate Ducke have been traditionally used by women of the Tacana tribe in the Bolivian Amazonas for genital hygiene and for treatment of genital infection/inflammation. To assess the ability of extracts from Equisetum giganteum L and Copaifera reticulate Ducke to block genital viral infection by herpes simplex virus type 2. Equisetum giganteum L and Copaifera reticulate Ducke were collected from the Amazon region of La Paz, Bolivia. Extracts were prepared and screened for anti-viral activity against herpes simplex virus type 2 (HSV-2) using both in vitro and in in vivo models of infection. Equisetum giganteum L and Copaifera reticulate Ducke efficiently blocked HSV-2 infection of cell cultures without major cell cytotoxic effects. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke could prevent HSV-2 disease development when administered together with virus in a mouse model of genital HSV-2 infection. In vitro analyses revealed that both plant extracts exerted their anti-HSV-2 effects by interfering with viral cell attachment and entry, but could not block viral replication post entry. These studies show that extracts of Equisetum giganteum L and Copaifera reticulate Ducke have potent antiviral activities against HSV-2 comparable to those two previously identified plants, Croton lechleri Müll. Arg. and Uncaria tomentosa (Willd. ex Schult.) DC. These studies confirm that plants used by the Tacana tribe could be explored further for the development of novel topical antiviral microbicides. Copyright © 2017. Published by Elsevier B.V.

  13. Event-related brain potentials and second language learning: syntactic processing in late L2 learners at different L2 proficiency levels

    NARCIS (Netherlands)

    Hell, J.G. van; Tokowicz, N.

    2010-01-01

    There are several major questions in the literature on late second language (L2) learning and processing. Some of these questions include: Can late L2 learners process an L2 in a native-like way? What is the nature of the differences in L2 processing among L2 learners at different levels of L2

  14. C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.

    Science.gov (United States)

    Lieb, Andreas; Ortner, Nadine; Striessnig, Jörg

    2014-04-01

    Activity of voltage-gated Cav1.3 L-type Ca(2+) channels is required for proper hearing as well as sinoatrial node and brain function. This critically depends on their negative activation voltage range, which is further fine-tuned by alternative splicing. Shorter variants miss a C-terminal regulatory domain (CTM), which allows them to activate at even more negative potentials than C-terminally long-splice variants. It is at present unclear whether this is due to an increased voltage sensitivity of the Cav1.3 voltage-sensing domain, or an enhanced coupling of voltage-sensor conformational changes to the subsequent opening of the activation gate. We studied the voltage-dependence of voltage-sensor charge movement (QON-V) and of current activation (ICa-V) of the long (Cav1.3L) and a short Cav1.3 splice variant (Cav1.342A) expressed in tsA-201 cells using whole cell patch-clamp. Charge movement (QON) of Cav1.3L displayed a much steeper voltage-dependence and a more negative half-maximal activation voltage than Cav1.2 and Cav3.1. However, a significantly higher fraction of the total charge had to move for activation of Cav1.3 half-maximal conductance (Cav1.3: 68%; Cav1.2: 52%; Cav3.1: 22%). This indicated a weaker coupling of Cav1.3 voltage-sensor charge movement to pore opening. However, the coupling efficiency was strengthened in the absence of the CTM in Cav1.342A, thereby shifting ICa-V by 7.2 mV to potentials that were more negative without changing QON-V. We independently show that the presence of intracellular organic cations (such as n-methyl-D-glucamine) induces a pronounced negative shift of QON-V and a more negative activation of ICa-V of all three channels. These findings illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1. Weak coupling of voltage sensing to pore opening is enhanced in the absence of the CTM, allowing short Cav1.342A splice variants to activate at lower voltages

  15. Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

    Science.gov (United States)

    Heath, Tahirah K; Lutz, Marlon R; Reidl, Cory T; Guzman, Estefany R; Herbert, Claire A; Nocek, Boguslaw P; Holz, Richard C; Olsen, Kenneth W; Ballicora, Miguel A; Becker, Daniel P

    2018-01-01

    A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

  16. Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

    Directory of Open Access Journals (Sweden)

    Tahirah K Heath

    Full Text Available A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18 is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I(COD(S,S-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

  17. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

    Science.gov (United States)

    Valladares, Ricardo; Sankar, Dhyana; Li, Nan; Williams, Emily; Lai, Kin-Kwan; Abdelgeliel, Asmaa Sayed; Gonzalez, Claudio F; Wasserfall, Clive H; Larkin, Joseph; Schatz, Desmond; Atkinson, Mark A; Triplett, Eric W; Neu, Josef; Lorca, Graciela L

    2010-05-06

    The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data

  18. Technetium(I) complexes Tc(CO)3BrL2 (L = phosphine, pyridine, isocyanide)

    International Nuclear Information System (INIS)

    Lorenz, B.; Findeisen, M.; Olk, B.; Schmidt, K.

    1988-01-01

    Technetium pentacarbonyl bromide reacts with π-acceptor ligands L (L = phosphine, pyridine, isocyanide) to form disubstituted compounds of the type Tc(CO) 3 BrL 2 . The stereochemistry of the complexes was established by infrared and 1 H-NMR measurement. Chemical shifts and the half-widths of the 99 Tc-NMR signals are discussed. (author)

  19. Evaluation the Growth Potential of Artichoke (Synara scolymus L. and Milk thistle (Sylibum marianum L. in Petroleum-contaminated Soil

    Directory of Open Access Journals (Sweden)

    Sahar Zamani

    2018-04-01

    Full Text Available Petroleum hydrocarbons are one of the most common pollutants groups in the environment and threaten the human, animals and plants health. Phytoremediation is a method for cleaning the contaminated areas. Medicinal plants because of their defense mechanisms able to resist and thwart destructive effect of stressors. Some plants have better resistance, including Artichoke (Cynara scolymus L. and Milk Thistle (Silybum marianum L.; from Asteraceae family that has polyphenolic compounds with antioxidant properties and hepatoprotectors. To evaluation the growth potential of Artichoke and Milk Thistle in petroleum-contaminated soil, an experiment in a completely randomized design was done with 6 levels of gas oil and 3 replications in Gorgan University of Agricultural Sciences and Natural Resources. The results showed that, gas oil hydrocarbon had a significant effect at %1 on germination percent of seed and indexes involved in seedling growth including plant height, length, and width, fresh and dry weight of artichoke leaf. In Milk Thistle, gas oil had no significant effect on germination percent. Opposite to that, significant effect at %1 on growth indexes was observed. The maximum germination percent in Artichoke and Milk Thistle seeds was observed in 20 and 10 g/kg gas oil, respectively and the minimum of germination percent was observed in seeds samples that treated with 80 g gas oil per kg soil. Artichoke seedlings were more tolerance than Milk Thistle to the contaminated soil as better growth was observed in this condition. Generally, it seems that these two valuable medicinal plants had relatively resistance to the gas oli pollution and are suggestible to use in oil contaminated soil for cleaning purpose

  20. Accumulation of D- vs. L-isomers of alanine and leucine in rat prostatic adenocarcinoma

    International Nuclear Information System (INIS)

    Conti, P.S.; Schmall, B.; Bigler, R.E.; Zanzonico, P.B.; Kleinert, E.; Whitmore, W.F. Jr.

    1985-01-01

    It has been reported that tumor tissue may accumulate some D-amino acids preferentially over the L-isomers. In order to investigate the potential use of carbon-11 labeled amino acid isomers for in vivo tumor studies with positron emission tomography in patients, the tissue distributions of alanine and leucine, substrates for the A-type and L-type amino acid transport systems, respectively, were studied in Copenhagen rates bearing the Dunning R3327G prostatic adenocarcinoma. The authors have previously reported differences in the accumulation of A-type vs. L-type amino acids in rat prostatic adenocarcinoma and normal tissues. All compounds were labeled with C-14 in the carboxyl position with specific activities of 30.0-56.6 mCi/mmol. Higher levels of C-14 activity (Relative Concentration (RC)=dpm found per gm tissue + dpm inject per gm animal mass) were observed in tumor tissue using D-alanine (0.71) compared to L- (0.21) or DL-alanine (0.27) at 45 min post-injection. While tumor/prostate and tumor/liver ratios were above 2 for all three substrates, tumor/blood and tumor/muscle were above one for only the D-isomer. Comparisons made with D-, L-, and DL-leucine also demonstrated a higher level of RC in tumor tissue with the D-isomer (0.84) vs. the L-(0.66) and DL-leucine (0.63). In this case, however, tumor/blood, tumor/prostate, and tumor/muscle ratios were above one for all three substrates, while tumor/liver ratios were below one. These results support the observation of a preferential accumulation of D-amino acids in tumor tissue over the natural L-isomers. Observed differences in the accumulation of the isomers in normal tissues are discussed

  1. Fuzzy logic type 1 and type 2 based on LabVIEW FPGA

    CERN Document Server

    Ponce-Cruz, Pedro; MacCleery, Brian

    2016-01-01

    This book is a comprehensive introduction to LabVIEW FPGA™, a package allowing the programming of intelligent digital controllers in field programmable gate arrays (FPGAs) using graphical code. It shows how both potential difficulties with understanding and programming in VHDL and the consequent difficulty and slowness of implementation can be sidestepped. The text includes a clear theoretical explanation of fuzzy logic (type 1 and type 2) with case studies that implement the theory and systematically demonstrate the implementation process. It goes on to describe basic and advanced levels of programming LabVIEW FPGA and show how implementation of fuzzy-logic control in FPGAs improves system responses. A complete toolkit for implementing fuzzy controllers in LabVIEW FPGA has been developed with the book so that readers can generate new fuzzy controllers and deploy them immediately. Problems and their solutions allow readers to practice the techniques and to absorb the theoretical ideas as they arise. Fuzzy L...

  2. The potential of L. scoparium, K. robusta and P. radiata to mitigate N-losses in silvopastural systems.

    Science.gov (United States)

    Esperschuetz, J; Balaine, N; Clough, T; Bulman, S; Dickinson, N M; Horswell, J; Robinson, B H

    2017-06-01

    Silvopastoral systems aim to enhance economic, cultural and social principles by sustainably combining forest management with agriculture. In these typically high-nitrogen (N) environments, plant species selection can profoundly influence N fluxes. For grazed pastures, plants may be exposed to urine patches that have received the equivalent of up to 1000 kg N ha -1 . We aimed to determine the growth and N fluxes in three potential trees that may be used in silvopastoral systems: L. scoparium, K. robusta and P. radiata. Plants were grown in a greenhouse lysimeter experiment, with controlled irrigation and temperature and exposed to N at rates of 200 kg ha -1 equiv. for 15 weeks, followed by the addition of 800 kg ha -1 N equiv, to simulate a urine patch. Urea produced a positive growth response of all plant species. Treatments containing L. scoparium and K. robusta leached lower amounts of nitrate (NO 3 - ) (2 kg ha -1 NO 3 - ) compared to P. radiata (53 kg ha -1 ). Measurements of N 2 O over 20 days after the application of 800 kg N ha -1 indicated an inhibitory effect of L. scoparium and K. robusta on denitrification, hence loss of N via N 2 O. Both L. scoparium and K. robusta demonstrated that they have potential to reduce N-losses in silvopastural systems, while producing valuable biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The Prediction Methods for Potential Suspended Solids Clogging Types during Managed Aquifer Recharge

    Directory of Open Access Journals (Sweden)

    Xinqiang Du

    2014-04-01

    Full Text Available The implementation and development of managed aquifer recharge (MAR have been limited by the clogging attributed to physical, chemical, and biological reactions. In application field of MAR, physical clogging is usually the dominant type. Although numerous studies on the physical clogging mechanism during MAR are available, studies on the more detailed suspended clogging types and its prediction methods still remain few. In this study, a series of column experiments were inducted to show the process of suspended solids clogging process. The suspended solids clogging was divided into three types of surface clogging, inner clogging and mixed clogging based on the different clogging characteristics. Surface clogging indicates that the suspended solids are intercepted by the medium surface when suspended solids grain diameter is larger than pore diameter of infiltration medium. Inner clogging indicates that the suspended solids particles could transport through the infiltration medium. Mixed clogging refers to the comprehensive performance of surface clogging and inner clogging. Each suspended solids clogging type has the different clogging position, different changing laws of hydraulic conductivity and different deposition profile of suspended solids. Based on the experiment data, the ratio of effective medium pore diameter (Dp and median grain size of suspended solids (d50 was proposed as the judgment index for suspended solids clogging types. Surface clogging occurred while Dp/d50 was less than 5.5, inner clogging occurred while Dp/d50 was greater than 180, and mixed clogging occurred while Dp/d50 was between 5.5 and 180. In order to improve the judgment accuracy and applicability, Bayesian method, which considered more ratios of medium pore diameter (Dp and different level of grain diameter of suspended solids (di, were developed to predict the potential suspended solids types.

  4. Folding-type coupling potentials in the context of the generalized rotation-vibration model

    Science.gov (United States)

    Chamon, L. C.; Morales Botero, D. F.

    2018-03-01

    The generalized rotation-vibration model was proposed in previous works to describe the structure of heavy nuclei. The model was successfully tested in the description of experimental results related to the electron-nucleus elastic and inelastic scattering. In the present work, we consider heavy-ion collisions and assume this model to calculate folding-type coupling potentials for inelastic states, through the corresponding transition densities. As an example, the method is applied to coupled-channel data analyses for the α + 70,72,74,76Ge systems.

  5. Potential Use of Avocado Oil on Structured Lipids MLM-Type Production Catalysed by Commercial Immobilised Lipases

    Science.gov (United States)

    Caballero, Eduardo; Soto, Carmen; Olivares, Araceli; Altamirano, Claudia

    2014-01-01

    Structured Lipids are generally constituents of functional foods. Growing demands for SL are based on a fuller understanding of nutritional requirements, lipid metabolism, and improved methods to produce them. Specifically, this work was aimed to add value to avocado oil by producing dietary triacylglycerols (TAG) containing medium-chain fatty acids (M) at positions sn-1,3 and long-chain fatty acids (L) at position sn-2. These MLM-type structured lipids (SL) were produced by interesterification of caprylic acid (CA) (C8:0) and avocado oil (content of C18:1). The regiospecific sn-1,3 commercial lipases Lipozyme RM IM and TL IM were used as biocatalysts to probe the potential of avocado oil to produce SL. Reactions were performed at 30–50°C for 24 h in solvent-free media with a substrate molar ratio of 1∶2 (TAG:CA) and 4–10% w/w enzyme content. The lowest incorporation of CA (1.1% mol) resulted from Lipozyme RM IM that was incubated at 50°C. The maximum incorporation of CA into sn-1,3 positions of TAG was 29.2% mol. This result was obtained at 30°C with 10% w/w Lipozyme TL IM, which is the highest values obtained in solvent-free medium until now for structured lipids of low-calories. This strategy opens a new market to added value products based on avocado oil. PMID:25248107

  6. Potential use of avocado oil on structured lipids MLM-type production catalysed by commercial immobilised lipases.

    Science.gov (United States)

    Caballero, Eduardo; Soto, Carmen; Olivares, Araceli; Altamirano, Claudia

    2014-01-01

    Structured Lipids are generally constituents of functional foods. Growing demands for SL are based on a fuller understanding of nutritional requirements, lipid metabolism, and improved methods to produce them. Specifically, this work was aimed to add value to avocado oil by producing dietary triacylglycerols (TAG) containing medium-chain fatty acids (M) at positions sn-1,3 and long-chain fatty acids (L) at position sn-2. These MLM-type structured lipids (SL) were produced by interesterification of caprylic acid (CA) (C8:0) and avocado oil (content of C18:1). The regiospecific sn-1,3 commercial lipases Lipozyme RM IM and TL IM were used as biocatalysts to probe the potential of avocado oil to produce SL. Reactions were performed at 30-50°C for 24 h in solvent-free media with a substrate molar ratio of 1∶2 (TAG:CA) and 4-10% w/w enzyme content. The lowest incorporation of CA (1.1% mol) resulted from Lipozyme RM IM that was incubated at 50°C. The maximum incorporation of CA into sn-1,3 positions of TAG was 29.2% mol. This result was obtained at 30°C with 10% w/w Lipozyme TL IM, which is the highest values obtained in solvent-free medium until now for structured lipids of low-calories. This strategy opens a new market to added value products based on avocado oil.

  7. Potential use of avocado oil on structured lipids MLM-type production catalysed by commercial immobilised lipases.

    Directory of Open Access Journals (Sweden)

    Eduardo Caballero

    Full Text Available Structured Lipids are generally constituents of functional foods. Growing demands for SL are based on a fuller understanding of nutritional requirements, lipid metabolism, and improved methods to produce them. Specifically, this work was aimed to add value to avocado oil by producing dietary triacylglycerols (TAG containing medium-chain fatty acids (M at positions sn-1,3 and long-chain fatty acids (L at position sn-2. These MLM-type structured lipids (SL were produced by interesterification of caprylic acid (CA (C8:0 and avocado oil (content of C18:1. The regiospecific sn-1,3 commercial lipases Lipozyme RM IM and TL IM were used as biocatalysts to probe the potential of avocado oil to produce SL. Reactions were performed at 30-50°C for 24 h in solvent-free media with a substrate molar ratio of 1∶2 (TAG:CA and 4-10% w/w enzyme content. The lowest incorporation of CA (1.1% mol resulted from Lipozyme RM IM that was incubated at 50°C. The maximum incorporation of CA into sn-1,3 positions of TAG was 29.2% mol. This result was obtained at 30°C with 10% w/w Lipozyme TL IM, which is the highest values obtained in solvent-free medium until now for structured lipids of low-calories. This strategy opens a new market to added value products based on avocado oil.

  8. Berry phases for 3D Hartree-type equations with a quadratic potential and a uniform magnetic field

    International Nuclear Information System (INIS)

    Litvinets, F N; Shapovalov, A V; Trifonov, A Yu

    2007-01-01

    A countable set of asymptotic space-localized solutions is constructed for a 3D Hartree-type equation with a quadratic potential by the complex germ method in the adiabatic approximation. The asymptotic parameter is 1/T, where T >> 1 is the adiabatic evolution time. A generalization of the Berry phase of the linear Schroedinger equation is formulated for the Hartree-type equation. For the solutions constructed, the Berry phases are found in an explicit form

  9. The [Fe(III)[Fe(III)(L1)2]3] star-type single-molecule magnet.

    Science.gov (United States)

    Saalfrank, Rolf W; Scheurer, Andreas; Bernt, Ingo; Heinemann, Frank W; Postnikov, Andrei V; Schünemann, Volker; Trautwein, Alfred X; Alam, Mohammad S; Rupp, Holger; Müller, Paul

    2006-06-21

    Star-shaped complex [Fe(III)[Fe(III)(L1)2]3] (3) was synthesized starting from N-methyldiethanolamine H2L1 (1) and ferric chloride in the presence of sodium hydride. For 3, two different high-spin iron(III) ion sites were confirmed by Mössbauer spectroscopy at 77 K. Single-crystal X-ray structure determination revealed that 3 crystallizes with four molecules of chloroform, but, with only three molecules of dichloromethane. The unit cell of 3.4CHCl3 contains the enantiomers (delta)-[(S,S)(R,R)(R,R)] and (lambda)-[(R,R)(S,S)(S,S)], whereas in case of 3.3CH2Cl2 four independent molecules, forming pairs of the enantiomers [lambda-(R,R)(R,R)(R,R)]-3 and [lambda-(S,S)(S,S)(S,S)]-3, were observed in the unit cell. According to SQUID measurements, the antiferromagnetic intramolecular coupling of the iron(III) ions in 3 results in a S = 10/2 ground state multiplet. The anisotropy is of the easy-axis type. EPR measurements enabled an accurate determination of the ligand-field splitting parameters. The ferric star 3 is a single-molecule magnet (SMM) and shows hysteretic magnetization characteristics below a blocking temperature of about 1.2 K. However, weak intermolecular couplings, mediated in a chainlike fashion via solvent molecules, have a strong influence on the magnetic properties. Scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) were used to determine the structural and electronic properties of star-type tetranuclear iron(III) complex 3. The molecules were deposited onto highly ordered pyrolytic graphite (HOPG). Small, regular molecule clusters, two-dimensional monolayers as well as separated single molecules were observed. In our STS measurements we found a rather large contrast at the expected locations of the metal centers of the molecules. This direct addressing of the metal centers was confirmed by DFT calculations.

  10. The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.

    Science.gov (United States)

    Salman, Zenat K; Refaat, Rowaida; Selima, Eman; El Sarha, Ashgan; Ismail, Menna A

    2013-08-15

    Increasing evidence has established causative links between obesity, chronic inflammation and insulin resistance; the core pathophysiological feature in type 2 diabetes mellitus. This study was designed to examine whether the combination of L-cysteine and metformin would provide additional benefits in reducing oxidative stress, inflammation and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 weeks to induce insulin resistance after which they were rendered diabetic with low-dose streptozotocin. Diabetic rats were treated with metformin (300 mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for another 2 weeks. Control rats were fed normal rat chow throughout the experiment. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and nitrite/nitrate were also determined. The liver was isolated and used for determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded that of metformin and L-cysteine monotherapies with more improvement in insulin resistance. All treated groups exhibited significant reductions in serum FFAs, oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels compared to untreated diabetic rats with the highest improvement observed in the combination group. In conclusion, the present results clearly suggest that L-cysteine can be strongly considered as an adjunct to metformin in management of type 2 diabetes. © 2013 Elsevier B.V. All rights reserved.

  11. The development of functional mapping by three sex-related loci on the third whorl of different sex types of Carica papaya L.

    Directory of Open Access Journals (Sweden)

    Chen-Yu Lee

    Full Text Available Carica papaya L. is an important economic crop worldwide and is used as a model plant for sex-determination research. To study the different flower sex types, we screened sex-related genes using alternative splicing sequences (AS-seqs from a transcriptome database of the three flower sex types, i.e., males, females, and hermaphrodites, established at 28 days before flowering using 15 bacterial artificial chromosomes (BACs of C. papaya L. After screening, the cDNA regions of the three sex-related loci, including short vegetative phase-like (CpSVPL, the chromatin assembly factor 1 subunit A-like (CpCAF1AL, and the somatic embryogenesis receptor kinase (CpSERK, which contained eight sex-related single-nucleotide polymorphisms (SNPs from the different sex types of C. papaya L., were genotyped using high-resolution melting (HRM. The three loci were examined regarding the profiles of the third whorl, as described below. CpSVPL, which had one SNP associated with the three sex genotypes, was highly expressed in the male and female sterile flowers (abnormal hermaphrodite flowers that lacked the fourth whorl structure. CpCAF1AL, which had three SNPs associated with the male genotype, was highly expressed in male and normal hermaphrodite flowers, and had no AS-seqs, whereas it exhibited low expression and an AS-seqs in intron 11 in abnormal hermaphrodite flowers. Conversely, carpellate flowers (abnormal hermaphrodite flowers showed low expression of CpSVPL and AS-seqs in introns 5, 6, and 7 of CpSERK, which contained four SNPs associated with the female genotype. Specifically, the CpSERK and CpCAF1AL loci exhibited no AS-seq expression in the third whorl of the male and normal hermaphrodite flowers, respectively, and variance in the AS-seq expression of all other types of flowers. Functional mapping of the third whorl of normal hermaphrodites indicated no AS-seq expression in CpSERK, low CpSVPL expression, and, for CpCAF1AL, high expression and no AS

  12. Corrosion testing of a degraded moderator: L-Area Tuff Tanks

    International Nuclear Information System (INIS)

    Mickalonis, J.I.

    2000-01-01

    Based on test results, storage of the degraded moderator in 55-gallon 304L drums (0.065 inches thick) would not cause failure by general corrosion for up to 5 plus years storage. Acidic degraded moderator was temporarily stored in Tuff Tanks located in L-area. The moderator characteristics included a D 2 O content of 5.02--5.33%, a pH of 1.25--1.31, a conductivity of 29,300--31,200 m mhos/cm, tritium activity of 114--141 m Ci/mL, and levels of approximately 6,000 ppm for chloride and 500 ppm for chromium. The compatibility of the degraded with AISI Type 304L stainless steel (304L) was investigated in this study. Following ASTM standard practice, coupon immersion tests were conducted in both treated and untreated moderator. Treatment included the addition of either a 40 wt % NaOH solution, distilled water to serially dilute the chloride, or concentrated nitric acid to increase the nitrate concentration. Type 304L stainless steel exposed to the Tuff Tank moderator was found from these tests to: have a general corrosion rate of less than 5 mils per year (mpy) for 304L plate, which bounds that of the 304L storage drum, passivate at chloride concentrations up to 5,000 ppm for 304L sheet, resist corrosion for nitrate/chloride ratios ranging from 0.1 to 1,000, and be susceptible to crevice corrosion. Based on these test results, storage of the degraded moderator in 55-gallon 304L drums (0.065 inch thick) would not cause failure by general corrosion for up to 5+ years storage. The chloride concentration, [Cl], in the degraded moderator has been measured up to 6000 ppm. The potential or risk for aggressive localized attack of 304L increases with [Cl] concentration. A qualitative range is as follows: [Cl minus ] minus ] minus ] < 600 ppm, reasonable resistance, medium risk. The degraded moderator should be treated to reduce the chloride concentration to reduce the potential for localized corrosion and the risk for a leakage failure of the drum. A good practice would be to

  13. Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects.

    Science.gov (United States)

    Frank, Thomas; Netzel, Gabriele; Kammerer, Dietmar R; Carle, Reinhold; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard; Bitsch, Roland; Netzel, Michael

    2012-08-15

    To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.

  14. DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription.

    Directory of Open Access Journals (Sweden)

    Natasha M Zamudio

    Full Text Available Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L, have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an auto-regulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative non-coding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter's and Turner's syndromes.

  15. Space Density of Optically Selected Type 2 Quasars

    Science.gov (United States)

    Reyes, Reinabelle; Zakamska, Nadia L.; Strauss, Michael A.; Green, Joshua; Krolik, Julian H.; Shen, Yue; Richards, Gordon T.; Anderson, Scott F.; Schneider, Donald P.

    2008-12-01

    Type 2 quasars are luminous active galactic nuclei whose central regions are obscured by large amounts of gas and dust. In this paper, we present a catalog of type 2 quasars from the Sloan Digital Sky Survey, selected based on their optical emission lines. The catalog contains 887 objects with redshifts z < 0.83; this is 6 times larger than the previous version and is by far the largest sample of type 2 quasars in the literature. We derive the [O III]5007 luminosity function (LF) for 108.3 L sun < L [O III] < 1010 L sun (corresponding to intrinsic luminosities up to M[2500 Å] ~= -28 mag or bolometric luminosities up to 4 × 1047 erg s-1). This LF provides robust lower limits to the actual space density of obscured quasars due to our selection criteria, the details of the spectroscopic target selection, and other effects. We derive the equivalent LF for the complete sample of type 1 (unobscured) quasars and determine the ratio of type 2 to type 1 quasar number densities. Our data constrain this ratio to be at least ~1.5:1 for 108.3 L sun < L [O III] < 109.5 L sun at z < 0.3, and at least ~1.2:1 for L [O III] ~ 1010 L sun at 0.3 < z < 0.83. Type 2 quasars are at least as abundant as type 1 quasars in the relatively nearby universe (z <~ 0.8) for the highest luminosities.

  16. High-quality permanent draft genome sequence of the Bradyrhizobium elkanii type strain USDA 76T, isolated from Glycine max (L.) Merr

    Science.gov (United States)

    Bradyrhizobium elkanii USDA 76T (INSCD = ARAG00000000), the type strain for Bradyrhizobium elkanii, is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen-fixing root nodule of Glycine max (L. Merr) grown in the USA. Because of its significance as a ...

  17. Test and evaluation report for Westinghouse Hanford Company's 1-L liquid shipper, docket 95-41-7A, Type A container

    International Nuclear Information System (INIS)

    Kelly, D.L.

    1996-01-01

    This report incorporates the U.S. Department of Energy, Office of Facility Safety Analysis (DOE/EH-32) approval letter for packaging use. This report documents the U.S. Department of Transportation Specification 7A Type A (DOT-7A) compliance test results of the 1-L Liquid Shipper packaging. The approved packaging system is designed to ship Type A quantities of radioactive materials, normal form. Contents may be liquid or solid form. Liquid contents must have a specific gravity <2. Solid materials are limited in weight, to include packaging, to the gross weight of the as-tested liquids and bottles

  18. Semantic Categorization of Placement Verbs in L1 and L2 Danish and Spanish

    Science.gov (United States)

    Cadierno, Teresa; Ibarretxe-Antuñano, Iraide; Hijazo-Gascón, Alberto

    2016-01-01

    This study investigates semantic categorization of the meaning of placement verbs by Danish and Spanish native speakers and two groups of intermediate second language (L2) learners (Danish learners of L2 Spanish and Spanish learners of L2 Danish). Participants described 31 video clips picturing different types of placement events. Cluster analyses…

  19. Growth potential of Salmonella spp. and Listeria monocytogenes in nine types of ready-to-eat vegetables stored at variable temperature conditions during shelf-life.

    Science.gov (United States)

    Sant'Ana, Anderson S; Barbosa, Matheus S; Destro, Maria Teresa; Landgraf, Mariza; Franco, Bernadette D G M

    2012-06-15

    Growth potential (δ) is defined as the difference between the population of a microorganism at the end of shelf-life of specific food and its initial population. The determination of δ of Salmonella and Listeria monocytogenes in RTE vegetables can be very useful to determine likely threats to food safety. However, little is known on the behavior of these microorganisms in several RTE vegetables. Therefore, the aim of this study was to determine the δ of both pathogens in nine different types of RTE vegetables (escarole, collard green, spinach, watercress, arugula, grated carrot, green salad, and mix for yakisoba) stored at refrigeration (7°C) and abuse temperature (15°C). The population of aerobic microorganisms and lactic acid bacteria, including those showing antimicrobial activity has been also determined. Results indicated that L. monocytogenes was able to grow (δ≥0.5 log(10)) in more storage conditions and vegetables than Salmonella. Both microorganisms were inhibited in carrots, although a more pronounced effect has been observed against L. monocytogenes. The highest δ values were obtained when the RTE vegetables were stored 15°C/6days in collard greens (δ=3.3) and arugula (δ=3.2) (L. monocytogenes) and arugula (δ=4.1) and escarole (δ=2.8) (Salmonella). In most vegetables and storage conditions studied, the counts of total aerobic microorganisms raised significantly independent of the temperature of storage (pvegetables partially or fully stored at abuse temperature with recovery of isolates showing antimicrobial activity. In conclusion, the results of this study show that Salmonella and L. monocytogenes may grow and reach high populations in RTE vegetables depending on storage conditions and the definition of effective intervention strategies are needed to control their growth in these products. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Anaerobic digestion of cheese whey: Energetic and nutritional potential for the dairy sector in developing countries.

    Science.gov (United States)

    Escalante, H; Castro, L; Amaya, M P; Jaimes, L; Jaimes-Estévez, J

    2018-01-01

    Cheese whey (CW) is the main waste generated in the cheesemaking process and has high organic matter content and acidity. Therefore, CW disposal is a challenge for small to medium enterprises (SMEs) in the dairy industry that do not have any type of treatment plant. Anaerobic digestion (AD) is an attractive process for solving this problem. The aim of this research was to determine the biomethane and struvite precipitation potentials of CW from four dairy SMEs. First, changes in CW properties (organic matter and pH) were evaluated. Second, biomethane and struvite potentials were assessed using cattle slurry as inoculum. The organic matter in CW varied from 40 to 65gVS/kg, 65 to 140g COD/L, and 2 to 10g/L for VFAs depending on the sampling time and type of sample. The pH of the CW samples ranged from 3 to 6.5. In the anaerobic biodegradability analysis, methane yields reached 0.51 to 0.60L CH 4 /g VS added , which represented electrical and caloric potentials of 54 and 108kWh/m 3 for CW, respectively. Organic matter removal in all experiments was above 83%. Moreover, anaerobic digestates presented NH 4 + /PO 4 3- molar ratios between 2.6 and 4.0, which are adequate for struvite precipitation with potential production of 8.5-10.4g struvite/L CW. Finally, the use of biogas as energetic supplement and struvite as soil fertilizer, represents economics saves of US$ 6.91/m 3 CW and US$ 5.75/m 3 CW in therms of electricity and fertilizer use, respectively. The energetic, agricultural and economic potentials, evidence that AD process is a feasible alternative for cheese whey treatment. Copyright © 2017. Published by Elsevier Ltd.

  1. Amino acid differences in glycoproteins B (gB, C (gC, H (gH and L(gL are associated with enhanced herpes simplex virus type-1 (McKrae entry via the paired immunoglobulin-like type-2 receptor α

    Directory of Open Access Journals (Sweden)

    Chowdhury Sona

    2012-06-01

    Full Text Available Abstract Background Herpes simplex virus type-1 (HSV-1 enters into cells via membrane fusion of the viral envelope with plasma or endosomal membranes mediated by viral glycoproteins. HSV-1 virions attach to cell surfaces by binding of viral glycoproteins gC, gD and gB to specific cellular receptors. Here we show that the human ocular and highly neurovirulent HSV-1 strain McKrae enters substantially more efficiently into cells via the gB-specific human paired immunoglobulin-like type-2 receptor-α (hPILR-α. Comparison of the predicted amino acid sequences between HSV-1(F and McKrae strains indicates that amino acid changes within gB, gC, gH and gL may cause increased entry via the hPILR- α receptor. Results HSV-1 (McKrae entered substantially more efficiently than viral strain F in Chinese hamster ovary (CHO cells expressing hPIRL-α but not within CHO-human nectin-1, -(CHO-hNectin-1, CHO-human HVEM (CHO-hHVEM or Vero cells. The McKrae genes encoding viral glycoproteins gB, gC, gD, gH, gL, gK and the membrane protein UL20 were sequenced and their predicted amino acid (aa sequences were compared with virulent strains F, H129, and the attenuated laboratory strain KOS. Most aa differences between McKrae and F were located at their gB amino termini known to bind with the PILRα receptor. These aa changes included a C10R change, also seen in the neurovirulent strain ANG, as well as redistribution and increase of proline residues. Comparison of gC aa sequences revealed multiple aa changes including an L132P change within the 129-247 aa region known to bind to heparan sulfate (HS receptors. Two aa changes were located within the H1 domain of gH that binds gL. Multiple aa changes were located within the McKrae gL sequence, which were preserved in the H129 isolate, but differed for the F strain. Viral glycoproteins gD and gK and the membrane protein UL20 were conserved between McKrae and F strains. Conclusions The results indicate that the observed

  2. Biological evaluation of [18F]-nifedipine as a novel PET tracer for L-type calcium channel imaging

    International Nuclear Information System (INIS)

    Sadeghpour, H.; Jalilian, A.R.; Akhlaghi, M.; Mirzaii, M.; Saddadi, F.; Shafiee, A.; Miri, R.

    2008-01-01

    Due to interesting role of dihydropyridines in cardiovascular diseases and drug resistance studies and lack of a fluorine-18 labeled imaging agent for L-type calcium channel studies, this study was designed. [ 18 F] Dimethyl 2 - (fluoromethyl) - 6 - methyl - 4 - (2 - nitrophenyl) - 1,4 - dihydropyridine - 3,5 - dicarboxylate 2 was prepared in no-carrier-added (n.c.a.) form from a starting brominated compound in one step at 80 o C in Kryptofix2.2.2/[ 18 F]. Compound 2 was administered to normal rats via their tail veins for preliminary biodistribution studies and the ID/g % of the labeled compound was determined up to 3 h post injections. Coincidence images were obtained in rats 5 to 120 min. Radiofluorination on bromo precursor gave a fluorinated compound in 95 % radiochemical purity and a 8% yield shown by RTLC and HPLC. Biodistribution studies showed that the tracer is accumulated in the heart in the first few minutes, followed by metabolism resulting in very soluble 18 F-containing metabolites eliminated through the urinary tract. In coincidence images, the target organ was shown to be the heart. Lung had high accumulation possibly due to the presence of Ca 2+ channels and/or hydrolyzing enzymes showing a significant myocardial uptake at 120 min. The data demonstrates a significant agreement with the reported L-type calcium channels throughout the animal body. To our knowledge, this is the first example of 18 F-DHPs in the literature. (authors)

  3. L-arginine mediated renaturation enhances yield of human, α6 Type IV collagen non-collagenous domain from bacterial inclusion bodies.

    Science.gov (United States)

    Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Sudhakar, Yakkanti Akul

    2012-10-01

    The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated.

  4. L-type calcium channels play a crucial role in the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Li [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Wang, Yu [Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wang, Huan [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Kong, Lingmin [Department of Fundamental Medicine, Cell Engineering Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Liang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Chen, Xin [Department of General Dentistry, The 174th Hospital of Chinese PLA, Xiamen 361003 (China); Ding, Yin, E-mail: dingyin@fmmu.edu.cn [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer We detect the functional Ca{sup 2+} currents and mRNA expression of VDCC{sub L} in rMSCs. Black-Right-Pointing-Pointer Blockage of VDCC{sub L} exert antiproliferative and apoptosis-inducing effects on rMSCs. Black-Right-Pointing-Pointer Inhibiting VDCC{sub L} can suppress the ability of rMSCs to differentiate into osteoblasts. Black-Right-Pointing-Pointer {alpha}1C of VDCC{sub L} may be a primary functional subunit in VDCC{sub L}-regulating rMSCs. -- Abstract: L-type voltage-dependent Ca{sup 2+} channels (VDCC{sub L}) play an important role in the maintenance of intracellular calcium homeostasis, and influence multiple cellular processes. They have been confirmed to contribute to the functional activities of osteoblasts. Recently, VDCC{sub L} expression was reported in mesenchymal stem cells (MSCs), but the role of VDCC{sub L} in MSCs is still undetermined. The aim of this study was to determine whether VDCC{sub L} may be regarded as a new regulator in the proliferation and osteogenic differentiation of rat MSC (rMSCs). In this study, we examined functional Ca{sup 2+} currents (I{sub Ca}) and mRNA expression of VDCC{sub L} in rMSCs, and then suppressed VDCC{sub L} using nifedipine (Nif), a VDCC{sub L} blocker, to investigate its role in rMSCs. The proliferation and osteogenic differentiation of MSCs were analyzed by MTT, flow cytometry, alkaline phosphatase (ALP), Alizarin Red S staining, RT-PCR, and real-time PCR assays. We found that Nif exerts antiproliferative and apoptosis-inducing effects on rMSCs. ALP activity and mineralized nodules were significantly decreased after Nif treatment. Moreover, the mRNA levels of the osteogenic markers, osteocalcin (OCN), bone sialoprotein (BSP), and runt-related transcription factor 2 (Runx2), were also down-regulated. In addition, we transfected {alpha}1C-siRNA into the cells to further confirm the role of VDCC{sub L} in rMSCs, and a similar effect on osteogenesis was found. These

  5. Z L GAN

    Indian Academy of Sciences (India)

    Z L GAN. Articles written in Sadhana. Volume 43 Issue 4 April 2018 pp 59. Effect of scale size, orientation type and dispensing method on void formation in the CUF encapsulation of BGA · AIZAT ABAS FEI CHONG NG Z L GAN M H H ISHAK M Z ABDULLAH GEAN YUEN CHONG · More Details Abstract Fulltext PDF.

  6. Synthesis of 1-[11C]-D,L-homocysteine thiolactone: a potential tracer for myocardial ischemia using PET

    International Nuclear Information System (INIS)

    Hamacher, K.; Hanus, J.

    1989-01-01

    The synthesis of 1-[ 11 C]-D,L-homocysteine thiolactone, a potential tracer for PET imaging of ischemic heart regions, is described. The labelling is achieved by reaction of [ 11 C]carbon dioxide with α-lithiated S-(tetrahydro-pyran-2-yl)3-thiopropylisonitrile. Deprotection of the mercapto group and lactonisation of the resulting thioamino acid is accomplished in an acid catalysed reaction. The radiochemical yield obtained is 10 to 15% and the synthesis time, including the HPLC purification is about 45 min. (author)

  7. Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

    Directory of Open Access Journals (Sweden)

    Pedro L. Flores

    2017-06-01

    Full Text Available Maitotoxin (MTX is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP. Several reports indicate that MTX is an activator of non-selective cation channels (NSCC in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA approach and the two-electrode voltage-clamp technique (TEVC. The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1 protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

  8. GIS-based identification of areas that have resource potential for critical minerals in six selected groups of deposit types in Alaska

    Science.gov (United States)

    Karl, Susan M.; Jones, James V.; Hayes, Timothy S.

    2016-11-16

    each 12-digit hydrologic unit through color shading. Accompanying tables describe the data layers employed to score favorability for the presence of each mineral deposit group, the values assigned for specific analysis parameters, and the relative weighting of each data layer that contributes to estimated measures of potential and certainty. Core datasets used include the Alaska Geochemical Database, Version 2.0 (AGDB2); the Alaska Division of Geological & Geophysical Surveys (ADGGS) web-based geochemical database; the digital “Geologic Map of Alaska;” the Alaska Resource Data File (ARDF); and aerial gamma-ray surveys flown as part of the National Uranium Resource Evaluation (NURE) Program by the U.S. Department of Energy.Maps accompanying this report illustrate the scores for estimated mineral resource potential for the six deposit groups for the state of Alaska. Areas that have known potential, as well as new areas that were not previously known to have potential, for the targeted minerals and deposit groups are identified and described. Numerous areas in Alaska, some of them large, have high potential for one or more of the selected groups of deposit types within Alaska.ContributorsMatthew Granitto, Timothy S. Hayes, James V. Jones, III, Susan M. Karl, Keith A. Labay, Jeffrey L. Mauk, Jeanine M. Schmidt, Nora B. Shew, Erin Todd, Bronwen Wang, Melanie B. Werdon, and Douglas B. Yager

  9. Evaluation of C.L.I.N.D.E. as potent peripheral-type benzodiazepine receptor tracer in a rat model of micro-glial activation

    Energy Technology Data Exchange (ETDEWEB)

    Arlicot, N.; Guilloteau, D.; Chalon, S. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Universite Francois Rabelais de Tours, 37 (France); Katsifis, A.; Mattner, F. [ANSTO, Sydney (Australia)

    2008-02-15

    The peripheral-type benzodiazepine receptors (P.B.R.) are localized in mitochondria of glial cells and are very low expressed in normal brain. Their expression rises after micro-glial activation consecutive to brain injury. Accordingly, P.B.R. are potential targets to evaluate neuro inflammatory changes in a variety of C.N.S. disorders. To date no effective tool is available to explore P.B.R. by SPECT. We characterized here 6-chloro-2-(4 iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine- 3-acetamide, C.L.I.N.D.E., in a rat model of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intra striatal injection of different amounts of quinolinic acid (Q.A.: 75, 150 or 300 nmol). One week later, 2 groups of rats (n = 5-6/group) were i.v. injected with [{sup 125}I]-C.L.I.N.D.E. (0.4 MBq), one group being pre-injected with P.K.11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography and immunohistochemical studies using O.X.-42 were performed on brain sections In the control group, [{sup 125}I]-C.L.I.N.D.E. binding was significantly higher ( p < 0.001) in lesioned than that in intact side (striatum: 0.552 {+-} 0.109 vs. 0.123 {+-} 0.012% I.D./g tissue; cortex: 0.385 {+-} 0.126 vs. 0.131 {+-} 0.007% with 300 nmol Q.A.). This binding disappeared in rats pretreated with P.K.11195 ( p < 0.001), showing specific binding of C.L.I.N.D.E. to P.B.R.. Ex vivo autoradiography and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated micro-glia. Regression analysis yielded a significant correlation ( p < 0.001) between the ligand binding and the dose of Q.A.. These results demonstrate that C.L.I.N.D.E. is suitable for P.B.R. in vivo SPECT imaging to explore their involvement in neuro degenerative disorders associated with micro-glial activation. (authors)

  10. Born-Mayer type molybdenum-helium and helium-helium interaction potentials, fitted to the results of the helium desorption experiments

    International Nuclear Information System (INIS)

    Heugten, W.F.W.M. van; Veen, A. van; Caspers, L.M.

    1979-01-01

    Classes of Born-Mayer type Mo-He and He-He potentials have been derived from helium desorption experiments. The classes are described by linear relations between the Born-Mayer parameters A and b. For computer simulations the Mo-He potential phisub(MoHe)(r)=exp (6.5-3.63 r) and the He-He potential phisub(HeHe)(r)=exp(5.3-5.51 r) are proposed. (Auth.)

  11. A Stranger in the Midst: Searching for Relict Grains from Rare Meteorite Types in Mid-Ordovician Limestone Strata

    Science.gov (United States)

    Martin, E.; Schmitz, B.

    2016-08-01

    A layer of Mid-Ordovician limestone harbors exceptional amounts of L-chondritic chromite grains. The layer also contains grains from potentially rarer types of meteorites, following the discovery of the fossil meteorite Österplana 065.

  12. Combining Amplification Typing of L1 Active Subfamilies (ATLAS) with High-Throughput Sequencing.

    Science.gov (United States)

    Rahbari, Raheleh; Badge, Richard M

    2016-01-01

    With the advent of new generations of high-throughput sequencing technologies, the catalog of human genome variants created by retrotransposon activity is expanding rapidly. However, despite these advances in describing L1 diversity and the fact that L1 must retrotranspose in the germline or prior to germline partitioning to be evolutionarily successful, direct assessment of de novo L1 retrotransposition in the germline or early embryogenesis has not been achieved for endogenous L1 elements. A direct study of de novo L1 retrotransposition into susceptible loci within sperm DNA (Freeman et al., Hum Mutat 32(8):978-988, 2011) suggested that the rate of L1 retrotransposition in the germline is much lower than previously estimated (ATLAS L1 display technique (Badge et al., Am J Hum Genet 72(4):823-838, 2003) to investigate de novo L1 retrotransposition in human genomes. In this chapter, we describe how we combined a high-coverage ATLAS variant with high-throughput sequencing, achieving 11-25× sequence depth per single amplicon, to study L1 retrotransposition in whole genome amplified (WGA) DNAs.

  13. The Effect of L-arginine Supplementation on Blood Pressure in Patients with Type 2 Diabetes: A Double-Blind Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Sara Asadi

    2016-10-01

    Full Text Available Background: The prevalence of hypertension in patients with type 2 diabetes (T2D is approximately twice as much as healthy people. This study was designed to determine the effect of L-arginine supplementation on blood pressure in patients with T2D. Methods: In a double-blind randomized clinical trial, 75 T2D were randomly divided into three groups (3 g/d and 6g/d of L-arginine and placebo for 3 months. Height, weight, waist circumference, dietary intake, and blood pressure (BP were measured before and after intervention. Results: In patients who received 3g/d L-arginine, no significant difference was observed between BP before and after the intervention, however, subgroup analysis among patients with high BP showed significant reduction in systolic (P = 0.036 and diastolic BP (P = 0.027 after L-arginine supplementation. After 3 months of intervention, systolic and diastolic BP were significantly different compared to the baseline values and also with placebo value in patients receiving 6g/d of L-arginine (P < 0.05. Conclusions: The daily intake of 6g of L-arginine for 3 months in T2D may improve BP. Taking 3g/d of this supplement may help to improve BP only in patients with hypertension.

  14. Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Nien Yee Kow

    2013-01-01

    Full Text Available System lupus erythematosus (SLE is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

  15. Dosimetric properties of the pocket alarm dosimeter type Alnor RAD 21L, RAD 21H, RAD 22

    International Nuclear Information System (INIS)

    Hauser, M.; Burgkhardt, B.; Piesch, E.

    1981-02-01

    In personnel monitoring pocket dosimeters with build-in alarm devices are increasingly in use. The report presents results of a test performed at Karlsruhe for the pocket dose and alarm meter type Alnor RAD 21L, RAD 21H, RAD 22. The properties investigated are above all linearity and reproducibility of the dose reading as well as of the acoustic alarm indication, dependence of the dose reading on the photon energy, the direction of the radiation incidence, the dose rate, the temperature, operational characteristic of the batteries. (orig.) [de

  16. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    Science.gov (United States)

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  17. Biological Evaluation of Flexible Polyurethane/Poly l-Lactic Acid Composite Scaffold as a Potential Filler for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Yuk Fai Lui

    2017-09-01

    Full Text Available Degradable bone graft substitute for large-volume bone defects is a continuously developing field in orthopedics. With the advance in biomaterial in past decades, a wide range of new materials has been investigated for their potential in this application. When compared to common biopolymers within the field such as PLA or PCL, elastomers such as polyurethane offer some unique advantages in terms of flexibility. In cases of bone defect treatments, a flexible soft filler can help to establish an intimate contact with surrounding bones to provide a stable bone-material interface for cell proliferation and ingrowth of tissue. In this study, a porous filler based on segmented polyurethane incorporated with poly l-lactic acid was synthesized by a phase inverse salt leaching method. The filler was put through in vitro and in vivo tests to evaluate its potential in acting as a bone graft substitute for critical-sized bone defects. In vitro results indicated there was a major improvement in biological response, including cell attachment, proliferation and alkaline phosphatase expression for osteoblast-like cells when seeded on the composite material compared to unmodified polyurethane. In vivo evaluation on a critical-sized defect model of New Zealand White (NZW rabbit indicated there was bone ingrowth along the defect area with the introduction of the new filler. A tight interface formed between bone and filler, with osteogenic cells proliferating on the surface. The result suggested polyurethane/poly l-lactic acid composite is a material with the potential to act as a bone graft substitute for orthopedics application.

  18. The Effects of Cultural Familiarity and Question Preview Type on the Listening Comprehension of L2 Learners at the Secondary Level

    Science.gov (United States)

    Li, Chen-Hong; Chen, Cai-Jun; Wu, Meng-Jie; Kuo, Ya-Chu; Tseng, Yun-Ting; Tsai, Shi-Yi; Shih, Hung-Chun

    2017-01-01

    We examined the effect of cultural familiarity and question-preview types on the listening comprehension of L2 learners. The results showed that the participants who received the full question-preview format scored higher than those receiving either the answer-option preview or question-stem preview, despite a statistically nonsignificant…

  19. Type D personality and coronary atherosclerotic plaque vulnerability: The potential mediating effect of health behavior.

    Science.gov (United States)

    Cheng, Fangman; Lin, Ping; Wang, Yini; Liu, Guojie; Li, Ling; Yu, Huai; Yu, Bo; Zhao, Zhenjuan; Gao, Xueqin

    2018-05-01

    The association between type D personality and coronary plaque vulnerability has been suggested. The objective of the study was to evaluate the potential mediating effects of health behavior on the association between type D personality and plaque vulnerability in coronary artery disease (CAD) patients. A total of 319 CAD patients were assessed for type D personality and health behavior via self-administered questionnaires. The plaque vulnerability, evaluated according to characteristics, accompaniment, and outcomes of plaque, was assessed by optical coherence tomography. Regression analysis showed that type D personality was independently associated with lipid plaque (odds ratio [OR] = 2.387, p = 0.001), thin cap fibroatheroma (TCFA) (OR = 2.366, p = 0.001), rupture (OR = 2.153, p = 0.002), and lipid arc (β = -0.291, p vulnerability. Psychological stress mediated the relationship between type D and lipid plaque (p = 0.030), TCFA (p = 0.034), and rupture (p = 0.013). Living habits significantly mediated the relationship between type D and lipid plaque (p = 0.028), TCFA (p = 0.036), but not rupture (p = 0.066). Participating in activities was not a significant mediator of the relationship between type D personality and lipid plaque (p = 0.115), TCFA (p = 0.115), or rupture (p = 0.077). Health behaviors (psychological stress and living habits) may be mediators of the association between type D personality and plaque vulnerability. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Solution of Dirac equation for Eckart potential and trigonometric Manning Rosen potential using asymptotic iteration method

    International Nuclear Information System (INIS)

    Arum Sari, Resita; Suparmi, A; Cari, C

    2016-01-01

    The Dirac equation for Eckart potential and trigonometric Manning Rosen potential with exact spin symmetry is obtained using an asymptotic iteration method. The combination of the two potentials is substituted into the Dirac equation, then the variables are separated into radial and angular parts. The Dirac equation is solved by using an asymptotic iteration method that can reduce the second order differential equation into a differential equation with substitution variables of hypergeometry type. The relativistic energy is calculated using Matlab 2011. This study is limited to the case of spin symmetry. With the asymptotic iteration method, the energy spectra of the relativistic equations and equations of orbital quantum number l can be obtained, where both are interrelated between quantum numbers. The energy spectrum is also numerically solved using the Matlab software, where the increase in the radial quantum number n r causes the energy to decrease. The radial part and the angular part of the wave function are defined as hypergeometry functions and visualized with Matlab 2011. The results show that the disturbance of a combination of the Eckart potential and trigonometric Manning Rosen potential can change the radial part and the angular part of the wave function. (paper)

  1. Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1.

    Science.gov (United States)

    Sassi, A Ben; Harzallah-Skhiri, F; Bourgougnon, N; Aouni, M

    2008-01-10

    Fifteen species of Tunisian traditional medicinal plants, belonging to 10 families, were selected for this study. They were Inula viscosa (L.) Ait and Reichardia tingitana (L.) Roth ssp. discolor (Pom.) Batt. (Asteraceae), Mesembryanthemum cristallinum L. and M. nodiflorum L. (Aizoaceae), Arthrocnemum indicum (Willd.) Moq., Atriplex inflata Muell., A. parvifolia Lowe var. ifiniensis (Caball) Maire, and Salicornia fruticosa L. (Chenopodiaceae), Cistus monspeliensis L. (Cistaceae), Juniperus phoenicea L. (Cupressaceae), Erica multiflora L. (Ericaceae), Frankenia pulverulenta L. (Frankeniaceae), Hypericum crispum L. (Hypericaceae), Plantago coronopus L. ssp. eu-coronopus Pilger var. vulgaris G.G. (Plantaginaceae) and Zygophyllum album L. (Zygophyllaceae). Fifty extracts prepared from those plants were screened in order to assay their antiviral activity against Herpes simplex virus type 1 (HSV-1), using neutral red incorporation. Extracts from eight plants among these 15 showed some degree of antiviral activity, while the methanolic extract of E. multiflora was highly active with EC(50) of 132.6 microg mL(-1). These results corroborate that medicinal plants from Tunisia can be a rich source of potential antiviral compounds.

  2. A vaccine of L2 epitope repeats fused with a modified IgG1 Fc induced cross-neutralizing antibodies and protective immunity against divergent human papillomavirus types.

    Science.gov (United States)

    Chen, Xue; Liu, Hongyang; Zhang, Ting; Liu, Yanchun; Xie, Xixiu; Wang, Zhirong; Xu, Xuemei

    2014-01-01

    Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17-36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development.

  3. Preliminary discussion on prospecting potential for sandstone-type uranium deposits in meso-cenozoic basins, northern Ordos

    International Nuclear Information System (INIS)

    Di Yongqiang

    2002-01-01

    Characteristics of the regional stratigraphy, tectonic movement, geologic evolution and hydrogeology are briefly introduced. Using the metallogenic theory and prospecting criteria for interlayer oxidation zone sandstone-type uranium deposits, the author analyses the prospecting potential and main prospecting targets in the region, and proposes suggestions for further prospecting work as well

  4. Sécurité alimentaire en Afrique : fonds Cultiver l'avenir de l'Afrique 2 ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2 mars 2018 ... Type. Subventions. Admissibilité. Le présent appel est destiné aux organismes souhaitant mener des activités de recherche en partenariat dans l'un ou plusieurs des pays admissibles : le Burundi ;; l'Éthiopie ;; le Kenya ;; le Malawi ;; le Mozambique ;; l'Ouganda ;; le Rwanda ;; la Tanzanie ;; la Zambie et ...

  5. Deep comparative genomics among Chlamydia trachomatis lymphogranuloma venereum isolates highlights genes potentially involved in pathoadaptation.

    Science.gov (United States)

    Borges, Vítor; Gomes, João Paulo

    2015-06-01

    Lymphogranuloma venereum (LGV) is a human sexually transmitted disease caused by the obligate intracellular bacterium Chlamydia trachomatis (serovars L1-L3). LGV clinical manifestations range from severe ulcerative proctitis (anorectal syndrome), primarily caused by the epidemic L2b strains, to painful inguinal lymphadenopathy (the typical LGV bubonic form). Besides potential host-related factors, the differential disease severity and tissue tropism among LGV strains is likely a function of the genetic backbone of the strains. We aimed to characterize the genetic variability among LGV strains as strain- or serovar-specific mutations may underlie phenotypic signatures, and to investigate the mutational events that occurred throughout the pathoadaptation of the epidemic L2b lineage. By analyzing 20 previously published genomes from L1, L2, L2b and L3 strains and two new genomes from L2b strains, we detected 1497 variant sites and about 100 indels, affecting 453 genes and 144 intergenic regions, with 34 genes displaying a clear overrepresentation of nonsynonymous mutations. Effectors and/or type III secretion substrates (almost all of those described in the literature) and inclusion membrane proteins showed amino acid changes that were about fivefold more frequent than silent changes. More than 120 variant sites occurred in plasmid-regulated virulence genes, and 66% yielded amino acid changes. The identified serovar-specific variant sites revealed that the L2b-specific mutations are likely associated with higher fitness and pointed out potential targets for future highly discriminatory diagnostic/typing tests. By evaluating the evolutionary pathway beyond the L2b clonal radiation, we observed that 90.2% of the intra-L2b variant sites occurring in coding regions involve nonsynonymous mutations, where CT456/tarp has been the main target. Considering the progress on C. trachomatis genetic manipulation, this study may constitute an important contribution for prioritizing

  6. HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations.

    Science.gov (United States)

    Aulicino, Paula C; Rocco, Carlos A; Mecikovsky, Debora; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

    2010-01-01

    Patterns and pathways of HIV type-1 (HIV-1) antiretroviral (ARV) drug resistance-associated mutations in clinical isolates are conditioned by ARV history and factors such as viral subtype and fitness. Our aim was to analyse the frequency and association of ARV drug resistance mutations in a group of long-term vertically infected patients from Argentina. Plasma samples from 71 patients (38 children and 33 adolescents) were collected for genotypic HIV-1 ARV resistance testing during the period between February 2006 and October 2008. Statistically significant pairwise associations between ARV resistance mutations in pol, as well as associations between mutations and drug exposure, were identified using Fisher's exact tests with Bonferroni and false discovery rate corrections. Phylogenetic analyses were performed for subtype assignment. In protease (PR), resistance-associated mutations M46I/L, I54M/L/V/A/S and V82A/F/T/S/M/I were associated with each other and with minor mutations at codons 10, 24 and 71. Mutations V82A/F/T/S/M/I were primarily selected by the administration of ritonavir (RTV) in an historical ARV regimen. In reverse transcriptase, thymidine analogue mutation (TAM)1 profile was more common than TAM2. The non-nucleoside K103N+L100I mutations were observed at high frequency (15.5%) and were significantly associated with the nucleoside mutation L74V in BF recombinants. Associations of mutations at PR sites reflect the frequent use of RTV at an early time in this group of patients and convergent resistance mechanisms driven by the high exposure to protease inhibitors, as well as local HIV-1 diversity. The results provide clinical evidence of a molecular interaction between K103N+L100I and L74V mutations at the reverse transcriptase gene in vivo, limiting the future use of second-generation non-nucleoside reverse transcriptase inhibitors such as etravirine.

  7. Screening of six Ayurvedic medicinal plants for anti-obesity potential: An investigation on bioactive constituents from Oroxylum indicum (L.) Kurz bark.

    Science.gov (United States)

    Mangal, Priyanka; Khare, Pragyanshu; Jagtap, Sneha; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Bhutani, Kamlesh Kumar

    2017-02-02

    As an effort to identify newer anti-obesity lead(s) we have selected 13 plant materials from the six plant species which have been reported in Indian Ayurvedic medicine as remedy against complications affecting glucose and lipid homeostasis. In vitro screening of six Indian Ayurvedic medicinal plants on anti-adipogenic and pancreatic lipase (PL) inhibition potential followed by bioactivity guided isolation from most active plant material. In vitro anti-adipogenic assay using 3T3-L1 preadipocytes and pancreatic lipase (PL) inhibition assay were performed for hexanes, dichloromethane, ethyl acetate and methanolic extracts of all the plant materials. Bioactivity guided isolation approach was used to identify active constituent for anti-adipogenesis and PL inhibition assay. Inhibition of lipid accumulation and adipogenic transcription factor was measured by oil Red 'O' staining and quantitative real-time PCR method respectively. Ethyl acetate extract of Oroxylum indicum bark was found to be most active in screening of anti-adipogenesis (59.12±1.66% lipid accumulation as compared to control at 50μg/mL dose) and PL inhibition (89.12±6.87% PL inhibition at 250μg/mL dose) assays. Further, three bioactive flavonoids were isolated and identified as oroxylin A, chrysin and baicalein from O. indicum bark. Oroxylin A, chrysin, and baicalein were inhibited lipid accumulation in 3T3-L1 preadipocytes (75.00±5.76%, 70.21±4.23% and 77.21±5.49% lipid accumulation respectively in comparison to control at 50μM dose) and PL enzyme (69.86±2.96%, 52.08±2.14% and 45.06±2.42% PL inhibition respectively at 250μg/mL dose). In addition, oroxylin A and chrysin also inhibited PPARγ and C/EBPα, major adipogenic transcription factors, in 3T3L-1 preadipocytes during adipogenesis process at 50μM dose. The present study augurs the anti-obesity potential of well practiced Ayurvedic herb O. indicum and its flavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. A diterpenoid sugiol from Metasequoia glyptostroboides with α-glucosidase and tyrosinase inhibitory potential

    Directory of Open Access Journals (Sweden)

    Vivek K. Bajpai

    2014-08-01

    Full Text Available Nowadays use of plant derived natural compounds have become a topic of increasing interest in food and medicine industries due to their multitude of biological and therapeutic properties. In this study, a diterpenoid compound sugiol, isolated from Metasequoia glyptostroboides was evaluated for α–glucosidase and tyrosinase inhibitory efficacy in terms of its potent anti-diabetic and anti-melanogenesis potential, respectively. As a result, sugiol at the concentration range of (100-10,000 µg/mL and (20-500 µg/mL showed potent efficacy on inhibiting α-glucosidase and tyrosinase enzymes in vitro ranging from 12.34-63.47% and 28.22-67.43%, respectively. These findings confirm the therapeutic potential of diterpenoid compound sugiol from M. glyptostroboides as a novel candidate for using in food and medicine industry which may have practical potential to cure skin and diabetes mellitus type-2 related disorders.

  9. A potential human hepatocellular carcinoma inhibitor from Bauhinia purpurea L. seeds: from purification to mechanism exploration.

    Science.gov (United States)

    Fang, Evandro Fei; Bah, Clara Shui Fern; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Ye, Xiu Juan; Ng, Tzi Bun

    2012-02-01

    A 20-kDa Kunitz-type trypsin-chymotrypsin inhibitor, Bauhinia purpurea trypsin inhibitor (BPLTI), has been isolated from the seeds of B. purpurea L. by using liquid chromatography procedures that involved ion exchange chromatography on Sp-Sepharose and Mono S and gel filtration on Superdex 75. BPLTI demonstrated protease inhibitory activities of 7226 BAEE units/mg and 65 BTEE units/mg toward trypsin and α-chymotrypsin, respectively. BPLTI was relatively thermal (0-60°C) and pH (3-10) stable and its activity could be decreased by dithiothreitol treatment. BPLTI exhibited a wide spectrum of anti-proliferative and pro-apoptotic activities especially on human hepatocellular carcinoma Hep G2 cells. However, it was devoid of a significant antiproliferative effect on immortal human hepatic WRL 68 cells. We show here that BPLTI stimulates apoptosis in Hep G2 cells, including (1) evoking DNA damage including the production of chromatin condensation and apoptotic bodies; (2) induction of cell apoptosis/necrosis; (3) mitochondrial membrane depolarization; and (4) increasing the production of cytokines. Taken together, our findings show for the first time that purified protease inhibitor from B. purpurea L. seeds is a promising candidate for the treatment of human hepatocellular carcinoma.

  10. Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L. Jaeq.

    Directory of Open Access Journals (Sweden)

    Muhammad Khurram

    2015-08-01

    Full Text Available Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16, 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC = 64–128 µg/mL against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.

  11. Use of a Potential Probiotic, Lactobacillus plantarum L7, for the Preparation of a Rice-Based Fermented Beverage

    Directory of Open Access Journals (Sweden)

    Sib Sankar Giri

    2018-03-01

    Full Text Available This study aimed to isolate potential probiotic lactic acid bacteria from a traditional rice-based fermented beverage “bhaati jaanr” and to evaluate their role during preparation of the beverage. Among various isolates, Lactobacillus plantarum strain L7 exhibited satisfactory in vitro probiotic characteristics such as acid resistance and bile tolerance, cell surface hydrophobicity, auto-aggregation, antibiotic susceptibility, and antimicrobial activities. Therefore, performance of L7 as a starter culture in rice fermentation was determined during a 6-day rice fermentation study. L. plantarum L7 decreased the pH, associated with an increase in total titratable acidity and organic acid production up to the 4th day of fermentation. The highest concentrations of succinic acid (0.37 mg/g, lactic acid (4.95 mg/g, and acetic acid (0.36 mg/g were recorded on the 3rd, 4th, and 5th days of fermentation, respectively. Saccharifying (148.13 μg/min g−1 and liquefying (89.47 μg/min g−1 activities were the highest on days 3 and 2, respectively, and thereafter, they decreased. Phytase activity and the cleavage of free minerals (sodium, calcium, magnesium, manganese, and ferrous increased up to days 3–4. The concentration of various accumulated malto-oligosaccharides (glucose, fructose, maltotriose, and maltoterose was noted to be the maximum on days 4 and 5. Furthermore, gas chromatography-mass spectrometry analysis indicated the presence of various volatile compounds. The fermented material also exhibited 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical scavenging activity. Therefore, the probiotic, L. plantarum L7, has a significant role in the fermentation of this beverage and enhances its functional properties.

  12. [Influence of genotype, explant type and component of culture medium on in vitro callus induction and shoot organogenesis of tomato (Solanum lycopersicum L.)].

    Science.gov (United States)

    Khaliluev, M R; Bogoutdinova, L R; Baranova, G B; Baranova, E N; Kharchenko, P N; Dolgov, S V

    2014-01-01

    The influence of explant type as well as of the type of growth regulators and concentration on callus induction processes and somatic organogenesis of shoots was studied in vitro on four tomato genotypes of Russian breeding. Cytological study of callus tissue was conducted. It was established that tomato varieties possess a substantially greater ability to indirect shoot organogenesis compared with the F1 hybrid. The highest frequency of somatic organogenesis of shoots, as well as their number per explant, was observed for most of the genotypes studied during the cultivation of cotyledons on Murashige-Skoog culture medium containing 2 mg/l of zeatin in combination with 0.1 mg/l of 3-indoleacetic acid. An effective protocol of indirect somatic organogenesis of shoots from different explants of tomato varieties with a frequency of more than 80% was developed.

  13. Imminent perspectives for industrial application of atomic energy; Perspectives imminentes de l'application industrielle de l'energie atomique

    Energy Technology Data Exchange (ETDEWEB)

    Kowarski, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1955-07-01

    This conference raises an inventory of industrial applications and their perspectives for the year 1955. The speaker extrapolate for the forthcoming years the evolution of the role of the nuclear, the nuclear fuel, the different, types of atomic reactors and the state of advancement for different countries. (M.B.) [French] Cette conference dresse un etat des lieux des applications industrielles et de leurs perspectives pour l'annee 1955. L'orateur aborde entre autre l'evolution du role du nucleaire dans les annees a venir, le combustible nucleaire, les differents types de piles atomiques et l'etat d'avancement des differents pays. (M.B.)

  14. Comparison of anti-inflammatory activity of extracts with supercritical carbon dioxide from radiation mutant perilla frutescens(L.) Britton and wild-type

    Energy Technology Data Exchange (ETDEWEB)

    Park, Han Chul; So, Yang Kang; Kim, Jin Baek; Jin, Chang Hyun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Yuk, Hong Sun [Dept. of Food and Nutrition, Chungnam National University Daejeon (Korea, Republic of)

    2016-11-15

    In previous study, the radiation mutant Perilla frutescens (L.) Britton with a higher anti-inflammatory activity was selected. The extracts were obtained from the mutant and wildtype using a supercritical carbon dioxide technique. This study aimed to compare the antiinflammatory activities between the mutant supercritical extract (MSE) and wild-type supercritical extract (WSE). The contents of isoegomaketone (IK) of MSE and WSE were measured through an HPLC analysis. MSE contained IK contents approximately 7-fold higher than those of WSE. To compare the anti-inflammatory activities of MSE and WSE, the expression levels of the mRNA and protein of pro-inflammatory mediators were measured in lipopolysaccharide (LPS)-induced RAW264.7 cells. As a result, MSE inhibited the expression levels of the mRNA and protein of pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) to a much greater extent than did WSE. Taken together, MSE had more IK contents and higher antiinflammatory activities than WSE. Therefore, MSE is proposed based on its therapeutic potential in the prevention of inflammatory disease.

  15. Screening and Evaluation of the Bioremediation Potential of Cu/Zn-Resistant, Autochthonous Acinetobacter sp. FQ-44 from Sonchus oleraceus L.

    Science.gov (United States)

    Fang, Qing; Fan, Zhengqiu; Xie, Yujing; Wang, Xiangrong; Li, Kun; Liu, Yafeng

    2016-01-01

    The quest for new, promising and indigenous plant growth-promoting rhizobacteria and a deeper understanding of their relationship with plants are important considerations in the improvement of phytoremediation. This study focuses on the screening of plant beneficial Cu/Zn-resistant strains and assessment of their bioremediation potential (metal solubilization/tolerance/biosorption and effects on growth of Brassica napus seedlings) to identify suitable rhizobacteria and examine their roles in microbes-assisted phytoremediation. Sixty Cu/Zn-resistant rhizobacteria were initially isolated from Sonchus oleraceus grown at a multi-metal-polluted site in Shanghai, China. From these strains, 19 isolates that were all resistant to 300 mg⋅L -1 Cu as well as 300 mg⋅L -1 Zn, and could simultaneously grow on Dworkin-Foster salt minimal medium containing 1-aminocyclopropane-1-carboxylic acid were preliminarily selected. Of those 19 isolates, 10 isolates with superior plant growth-promoting properties (indole-3-acetic acid production, siderophore production, and insoluble phosphate solubilization) were secondly chosen and further evaluated to identify those with the highest bioremediation potential and capacity for bioaugmentation. Strain S44, identified as Acinetobacter sp. FQ-44 based on 16S rDNA sequencing, was specifically chosen as the most favorable strain owing to its strong capabilities to (1) promote the growth of rape seedlings (significantly increased root length, shoot length, and fresh weight by 92.60%, 31.00%, and 41.96%, respectively) under gnotobiotic conditions; (2) tolerate up to 1000 mg⋅L -1 Cu and 800 mg⋅L -1 Zn; (3) mobilize the highest concentrations of water-soluble Cu, Zn, Pb, and Fe (16.99, 0.98, 0.08, and 3.03 mg⋅L -1 , respectively); and (4) adsorb the greatest quantities of Cu and Zn (7.53 and 6.61 mg⋅g -1 dry cell, respectively). Our findings suggest that Acinetobacter sp. FQ-44 could be exploited for bacteria-assisted phytoextraction

  16. Comprehensive behavioral analysis of ENU-induced Disc1-Q31L and -L100P mutant mice

    Directory of Open Access Journals (Sweden)

    Shoji Hirotaka

    2012-02-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 is considered to be a candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. A recent study reported that N-ethyl-N-nitrosourea (ENU-induced mutations in exon 2 of the mouse Disc1 gene, which resulted in the amino acid exchange of Q31L and L100P, caused an increase in depression-like behavior in 31 L mutant mice and schizophrenia-like behavior in 100P mutant mice; thus, these are potential animal models of psychiatric disorders. However, remaining heterozygous mutations that possibly occur in flanking genes other than Disc1 itself might induce behavioral abnormalities in the mutant mice. Here, to confirm the effects of Disc1-Q31L and Disc1-L100P mutations on behavioral phenotypes and to investigate the behaviors of the mutant mice in more detail, the mutant lines were backcrossed to C57BL/6JJcl through an additional two generations and the behaviors were analyzed using a comprehensive behavioral test battery. Results Contrary to expectations, 31 L mutant mice showed no significant behavioral differences when compared with wild-type control mice in any of the behavioral tests, including the Porsolt forced swim and tail suspension tests, commonly used tests for depression-like behavior. Also, 100P mutant mice exhibited no differences in almost all of the behavioral tests, including the prepulse inhibition test for measuring sensorimotor gating, which is known to be impaired in schizophrenia patients; however, 100P mutant mice showed higher locomotor activity compared with wild-type control mice in the light/dark transition test. Conclusions Although these results are partially consistent with the previous study in that there was hyperactivity in 100P mutant mice, the vast majority of the results are inconsistent with those of the previous study; this discrepancy may be explained by differences in the genetic background of the

  17. Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis in Long QT Syndrome Type 8: CACNA1C R858H Mutation Linked to Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Jieyun Bai

    2017-10-01

    Full Text Available Functional analysis of the L-type calcium channel has shown that the CACNA1C R858H mutation associated with severe QT interval prolongation may lead to ventricular fibrillation (VF. This study investigated multiple potential mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF. The Ten Tusscher-Panfilov (TP06 human ventricular cell models incorporating the experimental data on the kinetic properties of L-type calcium channels were integrated into one-dimensional (1D fiber, 2D sheet, and 3D ventricular models to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying changes in intracellular calcium handling, action potential profiles, action potential duration restitution (APDR curves, dispersion of repolarization (DOR, QT interval and spiral wave dynamics. R858H “mutant” L-type calcium current (ICaL augmented sarcoplasmic reticulum calcium content, leading to the development of afterdepolarizations at the single cell level and focal activities at the tissue level. It also produced inhomogeneous APD prolongation, causing QT prolongation and repolarization dispersion amplification, rendering R858H “mutant” tissue more vulnerable to the induction of reentry compared with other conditions. In conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia risk due to afterdepolarizations and increased tissue vulnerability to unidirectional conduction block. However, the observed reentry is not due to afterdepolarizations (not present in our model, but rather to a novel blocking mechanism.

  18. Topology on the spectrum of the algebra of entire symmetric functions of bounded type on the complex $L_\\infty$

    Directory of Open Access Journals (Sweden)

    T. V. Vasylyshyn

    2017-07-01

    Full Text Available It is known that the so-called elementary symmetric polynomials $R_n(x = \\int_{[0,1]}(x(t^n\\,dt$ form an algebraic basis in the algebra of all symmetric continuous polynomials on the complex Banach space $L_\\infty,$ which is dense in the Fr\\'{e}chet algebra $H_{bs}(L_\\infty$ of all entire symmetric functions of bounded  type on $L_\\infty.$ Consequently, every continuous homomorphism $\\varphi: H_{bs}(L_\\infty \\to \\mathbb{C}$ is uniquely determined by the sequence $\\{\\varphi(R_n\\}_{n=1}^\\infty.$ By the continuity of the homomorphism $\\varphi,$ the sequence $\\{\\sqrt[n]{|\\varphi(R_n|}\\}_{n=1}^\\infty$ is bounded. On the other hand, for every sequence $\\{\\xi_n\\}_{n=1}^\\infty \\subset \\mathbb{C},$ such that the sequence $\\{\\sqrt[n]{|\\xi_n|}\\}_{n=1}^\\infty$ is bounded,  there exists  $x_\\xi \\in L_\\infty$ such that $R_n(x_\\xi = \\xi_n$ for every $n \\in \\mathbb{N}.$ Therefore, for the point-evaluation functional $\\delta_{x_\\xi}$ we have $\\delta_{x_\\xi}(R_n = \\xi_n$ for every $n \\in \\mathbb{N}.$ Thus, every continuous complex-valued homomorphism of $H_{bs}(L_\\infty$ is a point-evaluation functional at some point of $L_\\infty.$ Note that such a point is not unique. We can consider an equivalence relation on $L_\\infty,$ defined by $x\\sim y \\Leftrightarrow \\delta_x = \\delta_y.$ The spectrum (the set of all continuous complex-valued homomorphisms $M_{bs}$ of the algebra $H_{bs}(L_\\infty$ is one-to-one with the quotient set $L_\\infty/_\\sim.$ Consequently, $M_{bs}$ can be endowed with the quotient topology. On the other hand, it is naturally to identify $M_{bs}$ with the set of all sequences $\\{\\xi_n\\}_{n=1}^\\infty \\subset \\mathbb{C}$ such that the sequence $\\{\\sqrt[n]{|\\xi_n|}\\}_{n=1}^\\infty$ is bounded.We show that the quotient topology is Hausdorffand that $M_{bs}$ with the operation of coordinate-wise addition of sequences forms an abelian topological group.

  19. ‘Candidatus Phytoplasma palmicola’, a novel taxon associated with a lethal yellowing-type disease (LYD) of coconut (Cocos nucifera L.) in Mozambique

    Science.gov (United States)

    In this study, the taxonomic position and group classification of the phytoplasma associated with a lethal yellowing-type disease (LYD) of coconut (Cocos nucifera L.) in Mozambique were addressed. Pairwise sequence similarity values based on alignment of near full-length 16SrRNA genes (1530 bp) reve...

  20. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

    Directory of Open Access Journals (Sweden)

    Ricardo Valladares

    Full Text Available BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat. In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in Bio