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Sample records for embryonic succinate semialdehyde

  1. Genetics Home Reference: succinic semialdehyde dehydrogenase deficiency

    Science.gov (United States)

    ... Additional NIH Resources (1 link) National Institute of Neurological Disorders and Stroke: Epilepsy Information Page Educational Resources (5 links) Boston Children's Hospital: Seizures and Epilepsy Disease InfoSearch: Succinic semialdehyde ...

  2. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

    NARCIS (Netherlands)

    Lapalme-Remis, S.; Lewis, E.C.; De Meulemeester, C.; Chakraborty, P.; Gibson, K.M.; Torres, C.; Guberman, A.; Salomons, G.; Jakobs, C.; Ali-Ridha, A.; Parviz, M.; Pearl, P.L.

    2015-01-01

    Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following

  3. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Anna-Kaisa Niemi

    2014-01-01

    Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

  4. The ALDH21 gene found in lower plants and some vascular plants codes for a NADP+ -dependent succinic semialdehyde dehydrogenase.

    Science.gov (United States)

    Kopečná, Martina; Vigouroux, Armelle; Vilím, Jan; Končitíková, Radka; Briozzo, Pierre; Hájková, Eva; Jašková, Lenka; von Schwartzenberg, Klaus; Šebela, Marek; Moréra, Solange; Kopečný, David

    2017-10-01

    Lower plant species including some green algae, non-vascular plants (bryophytes) as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated during dehydration. However, the gene is absent in flowering plants. Here, we show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP + -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic semialdehyde, an intermediate of the γ-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol. NAD + is a very poor coenzyme for ALDH21 unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH members. Structural comparison between the apoform and the coenzyme complex reveal that NADP + binding induces a conformational change of the loop carrying Arg-228, which seals the NADP + in the coenzyme cavity via its 2'-phosphate and α-phosphate groups. The crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg-121 and Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre-formed for substrate/product binding, Tyr-296 moves by more than 1 Å. Both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis. Our study implies that bryophytes but presumably also some green algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize SSAL to succinate in both cytosol and mitochondria, indicating a more diverse GABA shunt pathway compared with higher plants carrying only the mitochondrial ALDH5. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  5. Mutants of GABA transaminase (POP2 suppress the severe phenotype of succinic semialdehyde dehydrogenase (ssadh mutants in Arabidopsis.

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    Frank Ludewig

    Full Text Available BACKGROUND: The gamma-aminubutyrate (GABA shunt bypasses two steps of the tricarboxylic acid cycle, and is present in both prokaryotes and eukaryotes. In plants, the pathway is composed of the calcium/calmodulin-regulated cytosolic enzyme glutamate decarboxylase (GAD, the mitochondrial enzymes GABA transaminase (GABA-T; POP2 and succinic semialdehyde dehydrogenase (SSADH. We have previously shown that compromising the function of the GABA-shunt, by disrupting the SSADH gene of Arabidopsis, causes enhanced accumulation of reactive oxygen intermediates (ROIs and cell death in response to light and heat stress. However, to date, genetic investigations of the relationships between enzymes of the GABA shunt have not been reported. PRINCIPAL FINDINGS: To elucidate the role of succinic semialdehyde (SSA, gamma-hydroxybutyrate (GHB and GABA in the accumulation of ROIs, we combined two genetic approaches to suppress the severe phenotype of ssadh mutants. Analysis of double pop2 ssadh mutants revealed that pop2 is epistatic to ssadh. Moreover, we isolated EMS-generated mutants suppressing the phenotype of ssadh revealing two new pop2 alleles. By measuring thermoluminescence at high temperature, the peroxide contents of ssadh and pop2 mutants were evaluated, showing that only ssadh plants accumulate peroxides. In addition, pop2 ssadh seedlings are more sensitive to exogenous SSA or GHB relative to wild type, because GHB and/or SSA accumulate in these plants. SIGNIFICANCE: We conclude that the lack of supply of succinate and NADH to the TCA cycle is not responsible for the oxidative stress and growth retardations of ssadh mutants. Rather, we suggest that the accumulation of SSA, GHB, or both, produced downstream of the GABA-T transamination step, is toxic to the plants, resulting in high ROI levels and impaired development.

  6. In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency (SSADHD using brain-derived neural stem cells.

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    Kara R Vogel

    Full Text Available We explored the utility of neural stem cells (NSCs as an in vitro model for evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase-deficient (SSADHD mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH. Multiple parameters were evaluated including: (1 production of GHB (γ-hydroxybutyrate, the biochemical hallmark of SSADHD; (2 rescue from cell death with the dual mTOR (mechanistic target of rapamycin inhibitor, XL-765, an agent previously shown to rescue aldh5a1-/- mice from premature lethality; (3 mitochondrial number, total reactive oxygen species, and mitochondrial superoxide production, all previously documented as abnormal in aldh5a1-/- mice; (4 total ATP levels and ATP consumption; and (5 selected gene expression profiles associated with epilepsy, a prominent feature in both experimental and human SSADHD. Patterns of dysfunction were observed in all of these parameters and mirrored earlier findings in aldh5a1-/- mice. Patterns of dysregulated gene expression between hypothalamus and NSCs centered on ion channels, GABAergic receptors, and inflammation, suggesting novel pathomechanisms as well as a developmental ontogeny for gene expression potentially associated with the murine epileptic phenotype. The NSC model of SSADHD will be valuable in providing a first-tier screen for centrally-acting therapeutics and prioritizing therapeutic concepts of preclinical animal studies applicable to SSADHD.

  7. Comparative genomics of aldehyde dehydrogenase 5a1 (succinate semialdehyde dehydrogenase and accumulation of gamma-hydroxybutyrate associated with its deficiency

    Directory of Open Access Journals (Sweden)

    Malaspina Patrizia

    2009-01-01

    Full Text Available Abstract Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5A1 [ALDH5A1]; locus 6p22 occupies a central position in central nervous system (CNS neurotransmitter metabolism as one of two enzymes necessary for γ-aminobutyric acid (GABA recycling from the synaptic cleft. Its importance is highlighted by the neurometabolic disease associated with its inherited deficiency in humans, as well as the severe epileptic phenotype observed in Aldh5a1-/- knockout mice. Expanding evidence now suggests, however, that even subtle decreases in human SSADH activity, associated with rare and common single nucleotide polymorphisms, may produce subclinical pathological effects. SSADH, in conjunction with aldo-keto reductase 7A2 (AKR7A2, represent two neural enzymes responsible for further catabolism of succinic semialdehyde, producing either succinate (SSADH or γ-hydroxybutyrate (GHB; AKR7A2. A GABA analogue, GHB is a short-chain fatty alcohol with unusual properties in the CNS and a long pharmacological history. Moreover, SSADH occupies a further role in the CNS as the enzyme responsible for further metabolism of the lipid peroxidation aldehyde 4-hydroxy-2-nonenal (4-HNE, an intermediate known to induce oxidant stress. Accordingly, subtle decreases in SSADH activity may have the capacity to lead to regional accumulation of neurotoxic intermediates (GHB, 4-HNE. Polymorphisms in SSADH gene structure may also associate with quantitative traits, including intelligence quotient and life expectancy. Further population-based studies of human SSADH activity promise to reveal additional properties of its function and additional roles in CNS tissue.

  8. A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family.

    Science.gov (United States)

    Püttmann, Lucia; Stehr, Henning; Garshasbi, Masoud; Hu, Hao; Kahrizi, Kimia; Lipkowitz, Bettina; Jamali, Payman; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans-Hilger; Musante, Luciana; Kuss, Andreas W

    2013-08-01

    Succinic semialdehyde dehydrogenase (SSADH) deficiency is a disorder of the catabolism of the neurotransmitter gamma-aminobutyric acid (GABA) with a very variable clinical phenotype ranging from mild intellectual disability to severe neurological defects. We report here on a large Iranian family with four affected patients presenting with severe intellectual disability, developmental delay and generalized tonic-clonic seizures. Molecular genetic analysis revealed a missense mutation c.901A>G (p.K301E, RefSeq number NM_001080) in ALDH5A1 co-segregating with the disease in the family. The missense mutation affects an amino acid residue that is highly conserved across the animal kingdom. Protein modeling showed that p.K301E most likely leads to a loss of NAD(+) binding and a predicted decrease in the free energy by 6.67 kcal/mol furthermore suggests a severe destabilization of the protein. In line with these in silico observations, no SSADH enzyme activity could be detected in patient lymphoblasts. Copyright © 2013 Wiley Periodicals, Inc.

  9. A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

    Science.gov (United States)

    Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

    2016-10-01

    Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. THE SUCCINATED PROTEOME

    OpenAIRE

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John W.; Frizzell, Norma

    2013-01-01

    The post-translational modifications (PTMs) of cysteine residues include oxidation, S-glutathionylation, S-nitrosylation, and succination, all of which modify protein function or turnover in response to a changing intracellular redox environment. Succination is a chemical modification of cysteine in proteins by the Krebs cycle intermediate, fumarate, yielding S-(2-succino) cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of th...

  11. The Succinated Proteome

    Energy Technology Data Exchange (ETDEWEB)

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  12. X-Ray crystal structure of GarR—tartronate semialdehyde reductase from Salmonella typhimurium

    OpenAIRE

    Osipiuk, J.; Zhou, M.; Moy, S.; Collart, F.; Joachimiak, A.

    2009-01-01

    Tartronate semialdehyde reductases (TSRs), also known as 2-hydroxy-3-oxopropionate reductases, catalyze the reduction of tartronate semialdehyde using NAD as cofactor in the final stage of D-glycerate biosynthesis. These enzymes belong to family of structurally and mechanically related β-hydroxyacid dehydrogenases which differ in substrate specificity and catalyze reactions in specific metabolic pathways. Here, we present the crystal structure of GarR a TSR from Salmonella typhimurium determi...

  13. Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency

    DEFF Research Database (Denmark)

    Johansen, S S; Wang, X.; Pedersen, Daniel Sejer

    2017-01-01

    shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD. We quantified GHB in hair derived from ten patients with SSADHD, and documented...

  14. Characterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry

    DEFF Research Database (Denmark)

    Brody, S; Andersen, Jens S.; Kannangara, C G

    1995-01-01

    Glutamate 1-semialdehyde aminotransferase produces delta-aminolevulinate for the synthesis of chlorophyll, heme, and other tetrapyrrole pigments. The native enzyme from Synechococcus is pale yellow and has absorption maxima at 338 and 418 nm from vitamin B6. Yellow, colorless, and pink forms...

  15. Mutations in ALDH6A1 encoding methylmalonate semialdehyde dehydrogenase are associated with dysmyelination and transient methylmalonic aciduria

    NARCIS (Netherlands)

    Marcadier, Julien L.; Smith, Amanda M.; Pohl, Daniela; Schwartzentruber, Jeremy; Al-Dirbashi, Osama Y.; Majewski, Jacek; Ferdinandusse, Sacha; Wanders, Ronald J. A.; Bulman, Dennis E.; Boycott, Kym M.; Chakraborty, Pranesh; Geraghty, Michael T.; Boycott, Kym; Friedman, Jan; Michaud, Jacques; Bernier, Francois; Brudno, Michael; Fernandez, Bridget; Knoppers, Bartha; Samuels, Mark; Scherer, Steve

    2013-01-01

    Methylmalonate semialdehyde dehydrogenase (MMSDH) deficiency is a rare autosomal recessive disorder with varied metabolite abnormalities, including accumulation of 3-hydroxyisobutyric, 3-hydroxypropionic, 3-aminoisobutyric and methylmalonic acids, as well as β-alanine. Existing reports describe a

  16. X-Ray crystal structure of GarR—tartronate semialdehyde reductase from Salmonella typhimurium

    Science.gov (United States)

    Osipiuk, J.; Zhou, M.; Moy, S.; Collart, F.

    2009-01-01

    Tartronate semialdehyde reductases (TSRs), also known as 2-hydroxy-3-oxopropionate reductases, catalyze the reduction of tartronate semialdehyde using NAD as cofactor in the final stage of D-glycerate biosynthesis. These enzymes belong to family of structurally and mechanically related β-hydroxyacid dehydrogenases which differ in substrate specificity and catalyze reactions in specific metabolic pathways. Here, we present the crystal structure of GarR a TSR from Salmonella typhimurium determined by the single-wavelength anomalous diffraction method and refined to 1.65 Å resolution. The active site of the enzyme contains L-tartrate which most likely mimics a position of a glycerate which is a product of the enzyme reaction. The analysis of the TSR structure shows also a putative NADPH binding site in the enzyme. PMID:19184529

  17. X-ray crystal structure of GarR-tartronate semialdehyde reductase from Salmonella typhimurium.

    Science.gov (United States)

    Osipiuk, J; Zhou, M; Moy, S; Collart, F; Joachimiak, A

    2009-09-01

    Tartronate semialdehyde reductases (TSRs), also known as 2-hydroxy-3-oxopropionate reductases, catalyze the reduction of tartronate semialdehyde using NAD as cofactor in the final stage of D-glycerate biosynthesis. These enzymes belong to family of structurally and mechanically related beta-hydroxyacid dehydrogenases which differ in substrate specificity and catalyze reactions in specific metabolic pathways. Here, we present the crystal structure of GarR a TSR from Salmonella typhimurium determined by the single-wavelength anomalous diffraction method and refined to 1.65 A resolution. The active site of the enzyme contains L-tartrate which most likely mimics a position of a glycerate which is a product of the enzyme reaction. The analysis of the TSR structure shows also a putative NADPH binding site in the enzyme.

  18. Crystal structure of glutamate-1-semialdehyde-2,1-aminomutase from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yingxian; Pu, Hua; Jiang, Tian; Zhang, Lixin; Ouyang, Min, E-mail: ouyangmin@ibcas.ac.cn [Chinese Academy of Sciences, Beijing 100093, People’s Republic of (China)

    2016-05-23

    A structural study of A. thaliana glutamate-1-semialdehyde-2,1-aminomutase (GSAM) has revealed asymmetry in cofactor binding as well as in the gating-loop orientation, which supports the previously proposed negative cooperativity between monomers of GSAM. Glutamate-1-semialdehyde-2,1-aminomutase (GSAM) catalyzes the isomerization of glutamate-1-semialdehyde (GSA) to 5-aminolevulinate (ALA) and is distributed in archaea, most bacteria and plants. Although structures of GSAM from archaea and bacteria have been resolved, a GSAM structure from a higher plant is not available, preventing further structure–function analysis. Here, the structure of GSAM from Arabidopsis thaliana (AtGSA1) obtained by X-ray crystallography is reported at 1.25 Å resolution. AtGSA1 forms an asymmetric dimer and displays asymmetry in cofactor binding as well as in the gating-loop orientation, which is consistent with previously reported Synechococcus GSAM structures. While one monomer binds PMP with the gating loop fixed in the open state, the other monomer binds either PMP or PLP and the gating loop is ready to close. The data also reveal the mobility of residues Gly163, Ser164 and Gly165, which are important for reorientation of the gating loop. Furthermore, the asymmetry of the AtGSA1 structure supports the previously proposed negative cooperativity between monomers of GSAM.

  19. Succinic acid production from Jerusalem artichoke

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Karakashev, Dimitar Borisov; Angelidaki, Irini

    In this work, A. succinogenes 130Z was used to produce succinic acid from Jerusalem artichoke tuber hydrolysate. Results showed that both fructose and glucose in the tuber hydrolysate were utilized for succinic acid production. The sugar utilization was found to be dependent on process control...... that Jerusalem artichoke tubers could be utilized for production of bio-succinic acid....

  20. 21 CFR 582.1091 - Succinic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  1. Escherichia coli yjjPB genes encode a succinate transporter important for succinate production.

    Science.gov (United States)

    Fukui, Keita; Nanatani, Kei; Hara, Yoshihiko; Yamakami, Suguru; Yahagi, Daiki; Chinen, Akito; Tokura, Mitsunori; Abe, Keietsu

    2017-09-01

    Under anaerobic conditions, Escherichia coli produces succinate from glucose via the reductive tricarboxylic acid cycle. To date, however, no genes encoding succinate exporters have been established in E. coli. Therefore, we attempted to identify genes encoding succinate exporters by screening an E. coli MG1655 genome library. We identified the yjjPB genes as candidates encoding a succinate transporter, which enhanced succinate production in Pantoea ananatis under aerobic conditions. A complementation assay conducted in Corynebacterium glutamicum strain AJ110655ΔsucE1 demonstrated that both YjjP and YjjB are required for the restoration of succinate production. Furthermore, deletion of yjjPB decreased succinate production in E. coli by 70% under anaerobic conditions. Taken together, these results suggest that YjjPB constitutes a succinate transporter in E. coli and that the products of both genes are required for succinate export.

  2. Preparation of deuterated succinic acids

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Masashi; Tsuzuki, Hirohisa; Goto, Hideyuki; Ogasahara, Shoji; Mataka, Shuntaro (Kyushu Univ., Fukuoka (Japan)); Isobe, Shin-ichiro; Yonemitsu, Tadashi (Kyushu Sangyo Univ., Fukuoka (Japan). Dept. of Industrial Chemistry)

    1991-04-01

    Succinic (2,3-{sup 2}H{sub 2})- and (2,2,3,3-{sup 2}H{sub 4})-acids were prepared from maleic anhydride and dimethyl fumarate, and acetylene dicarboxylic acid and its dimethyl ester by treatment with Cu-Al and Ni-Al alloys in 10% NaOD-D{sub 2}0 in 95% to 100% isotopic purity. The succinic {sup 2}H{sub 4} acid having high isotopic purity was also obtained on the hydrolysis of 1,2-ethanedinitrile with alkaline deuterium oxide. Based on the {sup 1}H({sup 2}H) spectra analysis of N-(o-biphenyl)(2,3-{sup 2}H{sub 2})succinimide, it was elucidated that the Raney alloy reduction with alkaline deuterium oxide proceeds stepwise. (author).

  3. 21 CFR 184.1091 - Succinic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  4. Succinic Acid: Technology Development and Commercialization

    Directory of Open Access Journals (Sweden)

    Nhuan P. Nghiem

    2017-06-01

    Full Text Available Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. It was once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. However, it was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology Institute (MBI, which was capable of producing succinic acid up to about 50 g/L under optimum conditions, that the commercial feasibility of producing the compound by biological processes was realized. Other microbial strains capable of producing succinic acid to high final concentrations subsequently were isolated and engineered, followed by development of fermentation processes for their uses. Processes for recovery and purification of succinic acid from fermentation broths were simultaneously established along with new applications of succinic acid, e.g., production of biodegradable deicing compounds and solvents. Several technologies for the fermentation-based production of succinic acid and the subsequent conversion to useful products are currently commercialized. This review gives a summary of the development of microbial strains, their fermentation, and the importance of the down-stream recovery and purification efforts to suit various applications in the context of their current commercialization status for biologically derived succinic acid.

  5. Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors.

    Science.gov (United States)

    Thangavelu, Bharani; Bhansali, Pravin; Viola, Ronald E

    2015-10-15

    Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is absent in mammals. Therefore, the key microbial enzymes involved in this pathway are attractive potential targets for development of new antibiotics with novel modes of action. The ASADH enzyme family shares the same substrate binding and active site catalytic groups; however, the enzymes from representative bacterial and fungal species show different inhibition patterns when previously screened against low molecular weight inhibitors identified from fragment library screening. In the present study several approaches, including fragment based drug discovery (FBDD), inhibitor docking, kinetic, and structure-activity relationship (SAR) studies have been used to guide ASADH inhibitor development. Elaboration of a core structure identified by FBDD has led to the synthesis of low micromolar inhibitors of the target enzyme, with high selectivity introduced between the Gram-negative and Gram-positive orthologs of ASADH. This new set of structures open a novel direction for the development of inhibitors against this validated drug-target enzyme. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. 2-Amino-5-bromopyridinium hydrogen succinate

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    Hoong-Kun Fun

    2010-03-01

    Full Text Available In the title compound, C5H6BrN2+·C4H5O4−, the pyridine N atom of the 2-amino-5-bromopyridine molecule is protonated. The protonated N atom and the amino group are linked via N—H...O hydrogen bonds to the carboxylate O atoms of the singly deprotonated succinate anion. The hydrogen succinate anions are linked via O—H...O hydrogen bonds. A weak intermolecular C—H...O hydrogen bond is also observed.

  7. Prospects for a bio-based succinate industry.

    Science.gov (United States)

    McKinlay, James B; Vieille, C; Zeikus, J Gregory

    2007-09-01

    Bio-based succinate is receiving increasing attention as a potential intermediary feedstock for replacing a large petrochemical-based bulk chemical market. The prospective economical and environmental benefits of a bio-based succinate industry have motivated research and development of succinate-producing organisms. Bio-based succinate is still faced with the challenge of becoming cost competitive against petrochemical-based alternatives. High succinate concentrations must be produced at high rates, with little or no by-products to most efficiently use substrates and to simplify purification procedures. Herein are described the current prospects for a bio-based succinate industry, with emphasis on specific bacteria that show the greatest promise for industrial succinate production. The succinate-producing characteristics and the metabolic pathway used by each bacterial species are described, and the advantages and disadvantages of each bacterial system are discussed.

  8. Effect of succinic acid concentration in poly(glycerol citrate/succinate) properties

    International Nuclear Information System (INIS)

    Brioude, Michel M.; Guimaraes, Danilo H.; Fiuza, Raigenis P.; Jose, Nadia M.

    2011-01-01

    In this work were prepared and characterized polymer based on glycerol, citric and succinic acid, in three different ratios to evaluate the effect of succinic acid concentration in materials properties. The polymers were obtained by polycondensation reaction between polyol and poly acids, and were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning differential calorimetry (DSC), scanning electron microscopy (SEM). The materials are amorphous polyesters and its thermal and morphological properties change depending on the succinic acid concentration. (author)

  9. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic paraffin and succinic derivatives. 172... FOOD FOR HUMAN CONSUMPTION Coatings, Films and Related Substances § 172.275 Synthetic paraffin and succinic derivatives. Synthetic paraffin and succinic derivatives identified in this section may be safely...

  10. The effect of alpha-tocopheryl succinate on succinate respiration in rat liver mitochondria

    Czech Academy of Sciences Publication Activity Database

    Sobotka, O.; Drahota, Zdeněk; Kučera, O.; Endlicher, R.; Rauchová, Hana; Červinková, Z.

    2015-01-01

    Roč. 64, Suppl.5 (2015), S609-S615 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : tocopheryl succinate * Complex II * liver * mitochondria * homogenate * hepatocytes Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  11. Tartronate semialdehyde reductase defines a novel rate-limiting step in assimilation and bioconversion of glycerol in Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Yanbin Liu

    Full Text Available BACKGROUND: Glycerol is a by-product of biodiesel production. Currently, it has limited applications with low bioconversion efficiency to most metabolites reported. This is partly attributed to the poor knowledge on the glycerol metabolic pathway in bacteria and fungi. METHODOLOGY/PRINCIPAL FINDINGS: We have established a fast screening method for identification of genes that improve glycerol utilization in Ustilago maydis. This was done by comparing the growth rates of T-DNA tagged mutant colonies on solid medium using glycerol as the sole carbon source. We present a detailed characterization of one of the mutants, GUM1, which contains a T-DNA element inserted into the promoter region of UM02592 locus (MIPS Ustilago maydis database, MUMDB, leading to enhanced and constitutive expression of its mRNA. We have demonstrated that um02592 encodes a functional tartronate semialdehyde reductase (Tsr1, which showed dual specificity to cofactors NAD(+ and NADP(+ and strong substrate specificity and enantioselectivity for D-glycerate. Improved glycerol assimilation in GUM1 was associated with elevated expression of tsr1 mRNA and this could be phenocopied by over-expression of the gene. Glycolipid accumulation was reduced by 45.2% in the knockout mutant whereas introduction of an extra copy of tsr1 driven by the glyceraldehyde phosphate dehydrogenase promoter increased it by 40.4%. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that tartronate semialdehyde reductase (TSR plays an important role in glycerol assimilation in U. maydis and defines a novel target in genetic engineering for improved conversion of glycerol to higher value products. Our results add significant depth to the understanding of the glycerol metabolic pathway in fungi. We have demonstrated, for the first time, a biological role of a eukaryotic TSR.

  12. BER-Myriant Succinic Acid Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    Shmorhun, Mark [Myriant Lake Providence, Inc., Lake Providence, LA (United States)

    2015-12-31

    Myriant Corporation (Myriant) has successfully produced the bioproduct succinic acid by the fermentation of glucose at a commercial scale operation in Lake Providence, Louisiana. The MySAB facility (Myriant Succinic Acid Biorefinery) came on stream in May 2013 and has been producing product since then. The MySAB facility is a demonstration-scale plant, capable of utilizing sorghum grits and commercially available dextrose, to ferment glucose into succinic acid. A downstream processing train has demonstrated the ability to produce an industrial, a standard and a polymer grade product. It consists of cell separation, membrane filtration, continuous chromatography, polishing to remove ionic and color bodies impurities, and final evaporation and crystallization. A by-product of the process is ammonium sulfate which is sold as a liquid fertilizer product. Since 2007 when development work began in the Woburn, Massachusetts R&D laboratories, the succinic acid bio-process has evolved through: Process development (microbiology, fermentation, and downstream) – R&D development laboratories; Piloting efforts at Fermic S.A. de C.V., Mexico City, Mexico – upstream and downstream processes; Design, construction, commissioning, and commercial production operations at the MySAB facility Additionally, Myriant became a wholly-owned subsidiary of the PTT Global Chemical Plc., Thailand, in late 2015, their investment into and support of Myriant goes back to 2011. The support of PTT Global Chemical Plc. helped to improve the upstream and downstream processes, and produce significant metric ton quantities of high quality bio-based succinic acid. The product has gone into a number of commercial markets worldwide for customer applications, development and production. The experience base gained via operations at the MySAB facility since May 2013, along with continued R&D development efforts involving Microbiology, Fermentation, and Downstream processes, at both the Woburn, Massachusetts

  13. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

    DEFF Research Database (Denmark)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine

    2016-01-01

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date......, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose...

  14. Citrate and succinate uptake by potato mitochondria

    International Nuclear Information System (INIS)

    Jung, D.W.; Laties, G.G.

    1979-01-01

    Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate. Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar. Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels

  15. Spurious cooperativity in alkylated succinic acids

    Science.gov (United States)

    Ben-Naim, A.

    1998-03-01

    The proton-proton correlation, as measured by the ratio between the second and the first dissociation constants of dibasic acid, is sometimes very large and far beyond what could be explained by electrostatic theories. We propose a novel interpretation of this phenomenon based on the idea of spurious cooperativity. The general theoretical framework underlying the onset of spurious cooperativity is developed first. The basic result is that whenever a binding (or dissociating) two-site (or more) system splits into a mixture of noninterconverting isomers the binding isotherm (or the titration curve) behaves as if it is more negatively cooperative compared with the genuine cooperativities of the individual isomer. The theory is applied to a specific system of α-α' dialkyl succinic acid. It is known that the Meso form of these alkylated derivatives show a normal correlation of the same order of magnitude as in succinic acid. On the other hand, the Racemic form of these alkylated derivatives shows anomalous strong negative correlations when the alkyl groups become large (e.g., isopropyl and tert butyl). It is shown that the theory of spurious cooperativity can explain the different behavior of the Racemic and the Meso forms, as well as the onset of anomalous strong negative correlations when the alkyl groups become large.

  16. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2012-01-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  17. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2015-12-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  18. Structural and magnetic studies on copper succinate dihydrate ...

    Indian Academy of Sciences (India)

    M P BINITHA

    2017-08-21

    Aug 21, 2017 ... rials chemistry, heterogeneous catalysis, gas storage, polymer magnets, etc. ... super exchange interactions among copper atoms through bridging .... Thus, these two water molecules in the structure of copper succinate are.

  19. Succinic acid production by escherichia coli under anaerobic fermentation

    International Nuclear Information System (INIS)

    El Shafey, H.M.; Meleigy, S.A.

    2009-01-01

    The effect of alteration of growth conditions, addition of different sodium salts, and irradiation by gamma rays on succinic acid production by E. coli was studied. Twenty one isolates were obtained from buffalo's rumen, and anaerobic screening of the isolated bacterial strains showed the abilities of seventeen strains to produce succinic acid. The two bacterial strains having highest succinic acid production were identified as escherichia coli SP9 and SP16, and were selected for further studies. Results showed that growth conditions yielded highest succinic acid production for the two isolates were: 72 hours incubation, 37 degree c incubation temperature, initial ph of the fermentation medium 6.0,and 3% (v/v)inoculum size. Addition of 5 mm of nine different sodium salts to the fermentation medium showed stimulating effect on succinic acid production of the nine tried sodium salts, sodium carbonate was found to have the highest enhancing effect, especially if used at 15 mm concentration. Gamma irradiation doses tried were in the range of (0.25-1.50 kGy). An enhancing effect on succinic acid production was shown in the range of 0.25-0.75 kGy with a maximal production at 0.75 kGy (giving 8.36% increase) for e.coli SP9, and in the range of 0.25-1.00 kGy with a maximal production at 1.0 kGy (7.60% increase) for e.coli SP16. higher gamma doses led to a decrease in the enhancing effect. An overall increase in the succinic acid yield of 79.45% and 94.26% for e. coli SP9 and SP16, respectively, was achieved in implicating all optimized factors for succinic acid production in one time

  20. The Succinated Proteome of FH-Mutant Tumours

    Directory of Open Access Journals (Sweden)

    Ming Yang

    2014-08-01

    Full Text Available Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC. Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succinocysteine (2SC. Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH, kelch-like ECH-associated protein 1 (KEAP1 and mitochondrial aconitase (ACO2 can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC.

  1. Effect of Hydroxyl Monomers on the Enzymatic Degradation of Poly(ethylene succinate, Poly(butylene succinate, and Poly(hexylene succinate

    Directory of Open Access Journals (Sweden)

    Zhenhui Bai

    2018-01-01

    Full Text Available Poly(ethylene succinate (PES, poly(butylene succinate (PBS, and poly(hexylene succinate (PHS, were synthesized using succinic acid and different dihydric alcohols as materials. Enzymatic degradability by cutinase of the three kinds of polyesters was studied, as well as their solid-state properties. The biodegradation behavior relied heavily on the distance between ester groups, crystallinity, and the hydrophilicity-hydrophobicity balance of polyester surfaces. The weight loss through degradation of the three kinds of polyesters with different hydroxyl monomers took place in the order PHS > PBS > PES. The degradation behavior of the polyesters before and after degradation was analyzed by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The decrease in relative intensity at 1800–1650 estedpolyesters were degraded simultaneously. The frequencies of the crystalline and amorphous bands were almost identical before and after degradation. Thus, enzymatic degradation did not change the crystalline structure but destroyed it, and the degree of crystallinity markedly decreased. The molecular weight and polydispersity index only changed slightly. The thermal stability of the three kinds of polyesters decreased during enzymatic degradation.

  2. MODIFIKASI ASAM SUKSINAT - GELOMBANG PENDEK UNTUK\tPRODUKSI TAPIOKA SUKSINAT Succinic Acid-Microwave Modification to Produce Succinic Tapioca

    Directory of Open Access Journals (Sweden)

    Heny Herawati

    2012-05-01

    Full Text Available Indonesia as tropical country has great cassava potency. The great chance of cassava product development could be increased its added value through modified tapioca processing. One of modified starch that could be implemented as a food additive is succinic starch. The tapioca succinilation processed through combination process of reacting tapioca with succinic acid and microwave treatment. The research method was conducted by factorial design with 3 factors: substrate concentration (30 %, 40 %, succinic acid concentration (1 %, 3 %, 5 %, and drying method (oven and microwave. Succinic tapioca was analyzed both physical and chemical characteristics, while optimal product was fur- ther analyzed for nutrition contents and surface microstructure using SEM. Succinic acid and microwave modification influenced to the physical and chemical succinic tapioca, except ash content. The highest substitution degree value was 0.929 which was obtained by combination of substrate concentration 40 %, succinic acid added 5 % and microwave processed. The change of granule size was not significant, just the distribution among granule correlated with the tapi- oca modification. The succinic tapioca granule size ranged 5.35 µm until 17.20 µm with average 11.15 µm. Succinic tapioca characteristic hopefully could be advanced food implementation. ABSTRAK Indonesia merupakan negara tropis yang memiliki potensi produksi ubi kayu yang cukup besar. Peluang pengem- bangan produk berbasis ubi kayu di Indonesia masih cukup besar diantaranya yaitu peningkatan nilai tambah ubi kayu melalui proses modifikasi tapioka. Salah satu potensi pati termodifikasi yang dapat dipergunakan untuk bahan tambahan makanan yaitu pati suksinat. Pada penelitian ini proses suksinilasi tapioka dilakukan dengan cara mereak- sikan asam suksinat yang dikombinasikan dengan mempergunakan microwave. Metodologi penelitian yang dilakukan menggunakan rancangan faktorial dengan 3 faktor, yaitu konsentrasi

  3. Crystallization behavior of partially miscible biodegradable poly(butylene succinate)/poly(ethylene succinate) blends

    International Nuclear Information System (INIS)

    He, Yi-Song; Zeng, Jian-Bing; Li, Shao-Long; Wang, Yu-Zhong

    2012-01-01

    Graphical abstract: Crystallization rate of PBS in the blends decreased first and then increased with increase in PES content, and that of PES increased steadily with increase in PBS content. The rich component formed a continuous phase and the other formed a dispersed phase of the blend. Crystal structures of PBS and PES were almost unchanged after blending with each other. Highlights: ► PBS/PES blend systems are partially miscible. ► Blending did not change the crystallization mechanisms of PBS and PES not affects the crystallization rates. ► The rich component formed the continuous phase while the poor component formed the dispersed phase of the blends. ► Crystal structures of PBS and PES were almost unchanged after blending with each other. - Abstract: Biodegradable blend of poly(butylene succinate) (PBS) and poly(ethylene succinate) (PES) was prepared by solution blending and casting method with chloroform as a mutual solvent. Miscibility of the blends was investigated by differential scanning calorimetry (DSC). The results indicated that PBS and PES were partially miscible. Crystallization kinetics, crystalline morphology and crystal structure of the blends were studied by DSC, polarized optical microscope (POM), and wide-angle X-ray diffraction (WAXD), respectively. Nonisothermal and isothermal crystallization kinetics suggested that the crystallizability of PBS in the blends decreased first and then increased with increase in PES content, and that of PES increased steadily with increase in PBS content. POM observation illustrated that the rich component formed a continuous phase and the other formed a dispersed phase. The results of WAXD indicated that the crystal structures of PBS and PES were almost unchanged before and after blending, since the positions of characteristic diffraction peaks of both components remain almost unchanged.

  4. Mutant E. coli strain with increased succinic acid production

    Science.gov (United States)

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  5. Mutant E. coli strain with increased succinic acid production

    Science.gov (United States)

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  6. Biophysical properties of phenyl succinic acid derivatised hyaluronic acid

    DEFF Research Database (Denmark)

    Neves-Petersen, Maria Teresa; Klitgaard, Søren; Skovsen, Esben

    2010-01-01

    Modification of hyaluronic acid (HA) with aryl succinic anhydrides results in new biomedical properties of HA as compared to non-modified HA, such as more efficient skin penetration, stronger binding to the skin, and the ability to blend with hydrophobic materials. In the present study, hyaluronic...... acid has been derivatised with the anhydride form of phenyl succinic acid (PheSA). The fluorescence of PheSA was efficiently quenched by the HA matrix. HA also acted as a singlet oxygen scavenger. Fluorescence lifetime(s) of PheSA in solution and when attached to the HA matrix has been monitored...

  7. An efficient method for synthesis of succinate-based MMP inhibitors.

    Science.gov (United States)

    Sibi, Mukund P; Hasegawa, Hikaru

    2002-10-03

    A differentially protected fumarate undergoes radical addition followed by allylstannane trapping to provide disubstituted succinates in good yields and high anti diastereoselectivity. The conversion of the succinate to a known MMP inhibitor has been accomplished. [reaction: see text

  8. SMALL SCALE PREPARATION OF C14 LABELED SUCCINIC, MALIC, FUMARICAND TARTARIC ACIDS

    Energy Technology Data Exchange (ETDEWEB)

    Jorgensen, E.C.; Bassham, J.A.; Calvin, M.; Tolbert, B.M.

    1951-06-12

    The directions for preparing the following acids from labeled acetic acid on a 1 to 20 millimole scale is presented: Succinic acid, malic acid, fumaric acid and tartaric acid. Two methods for preparing the succinic acid are detailed.

  9. 78 FR 76567 - Tall Oil, Polymer With Polyethylene Glycol and Succinic Anhydride Monopolyisobutylene Derivs...

    Science.gov (United States)

    2013-12-18

    ..., Polymer With Polyethylene Glycol and Succinic Anhydride Monopolyisobutylene Derivs.; Tolerance Exemption... an exemption from the requirement of a tolerance for residues of tall oil, polymer with polyethylene..., polymer with polyethylene glycol and succinic anhydride monopolyisobutylene derivs. on food or feed...

  10. Stopped-flow studies of the reaction of D-tartronate semialdehyde-2-phosphate with human neuronal enolase and yeast enolase 1.

    Science.gov (United States)

    Brewer, John M; McKinnon, Jared S; Phillips, Robert S

    2010-03-05

    We determined the kinetics of the reaction of human neuronal enolase and yeast enolase 1 with the slowly-reacting chromophoric substrate D-tartronate semialdehyde phosphate (TSP), each in tris (tris (hydroxymethyl) aminomethane) and another buffer at several Mg2+ concentrations, 50 or 100 microM, 1 mM and 30 mM. All data were biphasic, and could be satisfactorily fit, assuming either two successive first-order reactions or two independent first-order reactions. Higher Mg2+ concentrations reduce the relative magnitude of the slower reaction. The results are interpreted in terms of a catalytically significant interaction between the two subunits of these enzymes. Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Structural and magnetic studies on copper succinate dihydrate

    Indian Academy of Sciences (India)

    The four bis-bidendate succinate anions form syn–syn bridges among two copper atomsto form a polymeric two-dimensional chain. From room temperature vibrating sample magnetometer (VSM) studies themagnetic moment of the material is calculated as 1.35 Bohr magneton (BM), indicating antiferromagnetic interaction ...

  12. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  13. A novel organic nonlinear optical crystal: Creatininium succinate

    Energy Technology Data Exchange (ETDEWEB)

    Thirumurugan, R.; Anitha, K., E-mail: singlecerystalxrd@gmail.ciom [School of Physics, Madurai Kamraj University, Madurai 625021 (India)

    2015-06-24

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV–Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  14. Molecular and Supramolecular Changes in Polybutylene Succinate (PBS and Polybutylene Succinate Adipate (PBSA Copolymer during Degradation in Various Environmental Conditions

    Directory of Open Access Journals (Sweden)

    Michał Puchalski

    2018-03-01

    Full Text Available In this paper, the influence of the various degradation conditions, on the molecular and supramolecular structure of polybutylene succinate (PBS and polybutylene succinate adipate (PBSA copolymer during degradation is described. The experiment was carried out by the use of injection molded samples and normalized conditions of biodegradation in soil, composting and artificial weathering. Materials were studied by size-exclusion chromatography (SEC coupled with multiangle laser light scattering (MALLS detection and wide-angle X-ray diffraction (WAXD. Additionally, the physical and mechanical properties of the samples were determined. The performed experiments clearly show difference impacts of the selected degradation conditions on the macroscopic, supramolecular and molecular parameters of the studied aliphatic polyesters. The structural changes in PBS and PBSA explain the observed changes in the physical and mechanical properties of the obtained injection molded samples.

  15. Recovery of succinic acid produced by fermentation of a metabolically engineered Mannheimia succiniciproducens strain.

    Science.gov (United States)

    Song, Hyohak; Huh, Yun Suk; Lee, Sang Yup; Hong, Won Hi; Hong, Yeon Ki

    2007-12-01

    There have recently been much advances in the production of succinic acid, an important four-carbon dicarboxylic acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is able to produce succinic acid with high efficiency, but also produces acetic, formic and lactic acids just like other anaerobic succinic acid producers. We recently reported the development of an engineered M. succiniciproducens LPK7 strain which produces succinic acid as a major fermentation product while producing much reduced by-products. Having an improved succinic acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of succinic acid. In this paper, we report the development of a simpler and more efficient method for the recovery of succinic acid. For the recovery of succinic acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified succinic acid (greater than 99.5% purity, wt%) with a high yield of 67.05wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of succinic acid were obtained. These results suggest that succinic acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for succinic acid production.

  16. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    Science.gov (United States)

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-12-01

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Fermentative Succinate Production: An Emerging Technology to Replace the Traditional Petrochemical Processes

    Directory of Open Access Journals (Sweden)

    Yujin Cao

    2013-01-01

    Full Text Available Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed.

  18. Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum.

    Science.gov (United States)

    Chung, Soon-Chun; Park, Joon-Song; Yun, Jiae; Park, Jin Hwan

    2017-03-01

    Succinate is a renewable-based platform chemical that may be used to produce a wide range of chemicals including 1,4-butanediol, tetrahydrofurane, and γ-butyrolactone. However, industrial fermentation of organic acids is often subject to end-product inhibition, which significantly retards cell growth and limits metabolic activities and final productivity. In this study, we report the development of metabolically engineered Corynebacterium glutamicum for high production of succinate by release of end-product inhibition coupled with an increase of key metabolic flux. It was found that the rates of glucose consumption and succinate production were significantly reduced by extracellular succinate in an engineered strain, S003. To understand the mechanism underlying the inhibition by succinate, comparative transcriptome analysis was performed. Among the downregulated genes, overexpression of the NCgl0275 gene was found to suppress the inhibition of glucose consumption and succinate production, resulting in a 37.7% increase in succinate production up to 55.4g/L in fed-batch fermentation. Further improvement was achieved by increasing the metabolic flux from PEP to OAA. The final engineered strain was able to produce 152.2g/L succinate, the highest production reported to date, with a yield of 1.1g/g glucose under anaerobic condition. These results suggest that the release of end-product inhibition coupled with an increase in key metabolic flux is a promising strategy for enhancing production of succinate. Copyright © 2017. Published by Elsevier Inc.

  19. Identification of anti-filarial leads against aspartate semialdehyde dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular docking and molecular dynamics approaches.

    Science.gov (United States)

    Amala, Mathimaran; Rajamanikandan, Sundaraj; Prabhu, Dhamodharan; Surekha, Kanagarajan; Jeyakanthan, Jeyaraman

    2018-02-06

    Lymphatic filariasis is a debilitating vector borne parasitic disease that infects human lymphatic system by nematode Brugia malayi. Currently available anti-filarial drugs are effective only on the larval stages of parasite. So far, no effective drugs are available for humans to treat filarial infections. In this regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic pathway from Wolbachia endosymbiont Brugia malayi represents an attractive therapeutic target for the development of novel anti-filarial agents. In this present study, molecular modeling combined with molecular dynamics simulations and structure-based virtual screening were performed to identify potent lead molecules against ASDase. Based on Glide score, toxicity profile, binding affinity and mode of interactions with the ASDase, five potent lead molecules were selected. The molecular docking and dynamics results revealed that the amino acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and Asn321 plays a crucial role in effective binding of Top leads into the active site of ASDase. The stability of the ASDase-lead complexes was confirmed by running the 30 ns molecular dynamics simulations. The pharmacokinetic properties of the identified lead molecules are in the acceptable range. Furthermore, density functional theory and binding free energy calculations were performed to rank the lead molecules. Thus, the identified lead molecules can be used for the development of anti-filarial agents to combat the pathogenecity of Brugia malayi.

  20. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Akute, O.

    1999-02-01

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  1. Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

    Science.gov (United States)

    Banerjee, Arnab; Meenakumari, K J; Krishna, Amitabh

    2007-01-01

    The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

  2. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters.

    Science.gov (United States)

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by (1)H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t1/2, Zc and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters

    International Nuclear Information System (INIS)

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by 1 H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t 1/2 , Z c and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. - Highlights: • The incorporation of NPGS units reduced the spherulite size of BS unit. • The existence of NPGS units did not change the crystal structure of BS unit. • The NPGS units incorporated in PBS could significantly improve the ductility of PBS. • The

  4. Synthesis, stability and bioavailability of astaxanthin succinate diester.

    Science.gov (United States)

    Qiao, Xing; Yang, Lu; Zhang, Ting; Zhou, Qingxin; Wang, Yuming; Xu, Jie; Xue, Changhu

    2018-06-01

    We synthesized astaxanthin succinate diester (ASD), a novel astaxanthin (AST) derivate, with succinic anhydride and free AST. ASD was purified and characterized using silica gel column chromatography and spectrometry, respectively. The ASD final synthesis rate was 82.63%. A stability test revealed a high AST and ASD retention rate at pH 5.0-7.0. ASD showed better stability than did AST under acidic conditions. Both sample ions showed lower retention rates under Fe 2+ and Fe 3+ states. The ASD metabolic curve showed serum and liver area under the curve from 0 h to time t (AUC 0-t ) values of 45.05 ± 4.58 and 120.38 ± 23.66 µg h -1  mL -1 , respectively. The long-term accumulation was significantly higher in the ASD group than in the AST group, which showed higher accumulation in the heart, muscle and spleen than in other tissues in vivo. The thermal stability and bioavailability of ASD were higher than that of the non-esterified free AST and common free AST, respectively. Additionally, AST accumulation in different tissues of the ASD group was multifold higher than that of free AST. These results prove that ASD may serve as a better source of AST for human nutrition than does free AST. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha V

    2006-01-01

    .... Vitamin E succinate or alpha tocopheryl succinate ( -TOS) is a non-toxic, esterified analogue of Vitamin E that has been shown to be selectively toxic to tumor cell lines in vitro as well as inhibit the growth of tumors in animal models in vivo...

  6. Vitamin E Succinate as an Adjuvant for Dendritic Cell-Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha V; Akporiaye, Emmanuel T

    2005-01-01

    .... Vitamin E succinate or alpha tocopheryl succinate (a-TOS) is a non-toxic, esterified analogue of Vitamin E that has been shown to be selectively toxic to tumor cell lines in vitro as well as inhibit the growth of tumors in animal models in vivo...

  7. Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha

    2004-01-01

    .... In this study we have employed Vitamin E succinate also known as alpha-tocopheryl succinate (alpha-TOS), a non-toxic esterified analogue of Vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine mammary...

  8. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

    DEFF Research Database (Denmark)

    Trauelsen, Mette; Rexen Ulven, Elisabeth; Hjorth, Siv A

    2017-01-01

    OBJECTIVE: Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS: Here we first determined that the cis conformation of the succinate...

  9. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency

    NARCIS (Netherlands)

    Richter, S; Peitzsch, M.; Rapizzi, E.; Lenders, J.W.M.; Qin, N.; Cubas, A.A. de; Schiavi, F.; Rao, J.U.; Beuschlein, F.; Quinkler, M.; Timmers, H.J.L.M.; Opocher, G.; Mannelli, M.; Pacak, K.; Robledo, M.; Eisenhofer, G.

    2014-01-01

    CONTEXT: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. OBJECTIVE: We assessed whether altered succinate dehydrogenase

  10. Evaporation of methyl- and dimethyl-substituted malonic, succinic, glutaric and adipic acid particles at ambient temperatures

    DEFF Research Database (Denmark)

    Mønster, Jacob Garbrecht; Rosenørn, Thomas; Svenningsson, Birgitta

    2004-01-01

    Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid......Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid...

  11. Bio-succinic acid production: Escherichia coli strains design from genome-scale perspectives

    Directory of Open Access Journals (Sweden)

    Bashir Sajo Mienda

    2017-10-01

    Full Text Available Escherichia coli (E. coli has been established to be a native producer of succinic acid (a platform chemical with different applications via mixed acid fermentation reactions. Genome-scale metabolic models (GEMs of E. coli have been published with capabilities of predicting strain design strategies for the production of bio-based succinic acid. Proof-of-principle strains are fundamentally constructed as a starting point for systems strategies for industrial strains development. Here, we review for the first time, the use of E. coli GEMs for construction of proof-of-principles strains for increasing succinic acid production. Specific case studies, where E. coli proof-of-principle strains were constructed for increasing bio-based succinic acid production from glucose and glycerol carbon sources have been highlighted. In addition, a propose systems strategies for industrial strain development that could be applicable for future microbial succinic acid production guided by GEMs have been presented.

  12. Genetic manipulation of a metabolic enzyme and a transcriptional regulator increasing succinate excretion from unicellular cyanobacterium

    Directory of Open Access Journals (Sweden)

    Takashi eOsanai

    2015-10-01

    Full Text Available Succinate is a building block compound that the U.S. Department of Energy has declared as important in biorefineries, and it is widely used as a commodity chemical. Here, we identified the two genes increasing succinate production of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Succinate was excreted under dark, anaerobic conditions, and its production level increased by knocking out ackA, which encodes an acetate kinase, and by overexpressing sigE, which encodes an RNA polymerase sigma factor. Glycogen catabolism and organic acid biosynthesis were enhanced in the mutant lacking ackA and overexpressing sigE, leading to an increase in succinate production reaching 5 times of the wild-type levels. Our genetic and metabolomic analyses thus demonstrated the effect of genetic manipulation of a metabolic enzyme and a transcriptional regulator on succinate excretion from this cyanobacterium with the data based on metabolomic technique.

  13. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.).

    Science.gov (United States)

    Gunnarsson, Ingólfur B; Kuglarz, Mariusz; Karakashev, Dimitar; Angelidaki, Irini

    2015-04-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9 g L(-1)), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid. Copyright © 2015. Published by Elsevier Ltd.

  14. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.)

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Kuglarz, Mariusz; Karakashev, Dimitar Borisov

    2015-01-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior...... to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted...... in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9gL-1), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid....

  15. Incorporation of 14C-succinate in Synechococcus

    International Nuclear Information System (INIS)

    Doehler, G.

    1983-01-01

    The cyanobacterium Synechococcus (= Anacystis nidulans) was grown under normal air conditions (0.03 vol.% CO 2 ) and in low white light (0.5 x 10 3 μW/cm 2 ) at 37 0 C. Kinetics of 14 C incorporation into several soluble products and pigments were studied after adding 14 C-succinate during photosynthesis and in the dark using the autoradiographic method. Radioactivity was found mainly in glutamate and aspartate during the photosynthetic period independent on 3-(3',4'-dichlorphenyl)-1,1-dimethylurea preincubation. In the dark period 14 C label could also be detected in malate. Short-term kinetics experiments showed a decrease in 14 C label of glutamate and a parallel increase of aspartate. Results were discussed in respect to the interrupted tricarboxylic acid cycle. (author)

  16. Embryonic duplications in sheep.

    Science.gov (United States)

    Dennis, S M

    1975-02-01

    Twenty-seven embryonic duplications were examined during a 3-year investigation into the causes of perinatal lamb mortality. Twenty of the 27 were anomalous twins with 19 being conjoined (diplopagus 9 and heteropagus 10). The various duplications were: haloacardius acephalus 1, diprosopus 2, dicephalus 2, dipypus 3, diprosopus dipygus 1, syncephalus dipygus 1, pygopagus parasiticus 1, heteropagus dipygus 3, melodidymus 6, polyury 4, penile duplication 2, and bilateral otognathia 1. Four lambs were living and the time of death of the others was: parturient 8, and post-parturient 15. Average dry weight of the lambs was 3.35 kg (range 1.59 to 5.45 kg). Breed distribution was: Merino 77.8%, Crossbred 14.8%, Dorset Horn 3.7%, and Corriedale 3.7%. The caudal region was involved in 10 of the conjoined twins (52.6%), anterior region in 7 (36.9%), and both anterior and caudal regions in 2 (10.5%). Associated defects were present in 70.4% of the 27 lambs, the most common being atresia ani.

  17. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    Directory of Open Access Journals (Sweden)

    Ana Carolina eAriza

    2012-02-01

    Full Text Available The succinate receptor (also known as GPR91 is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: The succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  18. Succinate modulates Ca(2+) transient and cardiomyocyte viability through PKA-dependent pathway.

    Science.gov (United States)

    Aguiar, Carla J; Andrade, Vanessa L; Gomes, Enéas R M; Alves, Márcia N M; Ladeira, Marina S; Pinheiro, Ana Cristina N; Gomes, Dawidson A; Almeida, Alvair P; Goes, Alfredo M; Resende, Rodrigo R; Guatimosim, Silvia; Leite, M Fatima

    2010-01-01

    GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, a citric acid cycle intermediate, in several tissues. In the heart, the role of succinate is unknown. We now report that rat ventricular cardiomyocytes express GPR91. We found that succinate, through GPR91, increases the amplitude and the rate of decline of global Ca(2+) transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca(2+) handling proteins. The effects of succinate on Ca(2+) transient were abolished by pre-treatment with adenylyl cyclase and cAMP-dependent protein kinase (PKA) inhibitors. Direct PKA activation by succinate was further confirmed using a FRET-based A-kinase activity reporter. Additionally, succinate decreases cardiomyocyte viability through a caspase-3 activation pathway, effect also prevented by PKA inhibition. Taken together, these observations show that succinate acts as a signaling molecule in cardiomyocytes, modulating global Ca(2+) transient and cell viability through a PKA-dependent pathway. 2009 Elsevier Ltd. All rights reserved.

  19. Study of the radiolysis of succinic acid - applications in the dosimetry of high doses

    International Nuclear Information System (INIS)

    Andrade e Silva, L.G.

    1978-01-01

    A study is made of the effect of the gama radiation dose and of particle size of succinic acid (fine powder of large crystals) in relation with the formation of CO 2 and CO + H 2 , which are the main gaseous products of radiolysis. A different yield of CO + H 2 is found when the succinic acid is used as powder compared to the material in the form of large crystals. The reason for this difference is searched, studying the influence of heating and sublimation of the succinic acid prior to irradiation. The influence, in the mentioned yield, of the surface area of succinic acid particles, of the presence of oxygen (air) and of the rapid recrystallization of the acid are also studied. The formation of intermediate species in the radiolysis of succinic acid is examined. The system used in ethanol-succinic acid at 77K. Analysis are made using an electronic paramagnetic resonance spectrometer. The possibility of using succinic acid as a dosimeter for high level gama radiation doses is discussed [pt

  20. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    Directory of Open Access Journals (Sweden)

    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  1. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept

    DEFF Research Database (Denmark)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar Borisov

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery...... productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149 kg of EtOH and 115 kg of succinic acid can be obtained per 1 ton of dry hemp....... Results obtained in this study clearly document the potential of industrial hemp for a biorefinery....

  2. Synthesis and characterization of a novel multiblock copolyester containing poly(ethylene succinate) and poly(butylene succinate)

    International Nuclear Information System (INIS)

    Zhu Qunying; He Yisong; Zeng Jianbing; Huang Qing; Wang Yuzhong

    2011-01-01

    Highlights: → High-molecular-weight biodegradable multiblock copolyester containing PBS and PES segments was achieved. → PBS and PES are miscible with a single glass transition regardless of composition. → The multiblock copolyester showed excellent tensile strength and elongation at break. → The multiblock copolyester can serve as a potential substitute for conventional non-biodegradable commodity plastics. - Abstract: Multiblock copolyester (PBS-b-PES) containing poly(butylene succinate) (PBS) and poly(ethylene succinate) (PES) was successfully synthesized by chain-extension of dihydroxyl terminated PBS (HO-PBS-OH) and PES (HO-PES-OH) using 1,6-hexmethylene diisocyanate (HDI) as a chain extender. The chemical structures, molecular weights, crystallization behaviors, thermal and mechanical properties of the copolyesters were characterized by proton nuclear magnetic resonance spectroscopy ( 1 H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), wide-angle X-ray diffraction (WAXD), tensile testing and hydrolytic degradation. High-molecular-weight copolyesters with M w more than 2.0 x 10 5 g mol -1 were easily obtained through chain-extension. The copolyesters showed a single glass transition temperature (T g ) which increased with PES content. The melting point temperature (T m ) and relative degree of crystallinity (X c ) of the copolyesters decreased first and then increased with PES content. The copolyesters manifested excellent mechanical properties, for example, PBS 5 -b-PES 5 had fracture stress of 61.8 MPa and fracture strain of 1173%. The chain-extension reaction provided a very effective way to produce high molecular weight multiblock copolyesters.

  3. Metabolic Effects of a Succinic Acid

    Directory of Open Access Journals (Sweden)

    B. N. Shakh

    2014-01-01

    Full Text Available The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing  substrate  antihypoxants  on  systemic  oxygen  consumption,  blood  buffer  capacity,  and  changes  in  the  mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution  in  a  total  dose  of  800  ml.  A  comparison  group  included  15  patients  who  had  undergone  emergency  extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min and carbon dioxide production (VCO2ml/min were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min. During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the

  4. Multifunctional nanobiocomposite of Poly[(butylene succinate)-co-adipate] and clay

    CSIR Research Space (South Africa)

    Al-Thabaiti, SA

    2015-03-01

    Full Text Available The processing and characterization of multifunctional nanobiocomposite of biodegradable poly[(butylene succinate)-co-adipate] (PBSA) and organically modified synthetic fluorine mica (OSFM) are reported. The nanobiocomposite of PBSA with OSFM...

  5. Separation and Concentration of Succinic Adic from Multicomponent Aqueous Solutions by Nanofiltration Technique

    Directory of Open Access Journals (Sweden)

    Antczak Jerzy

    2014-06-01

    Full Text Available This paper applies the determined suitability of nanofiltration (NF membrane separation for selective isolation and concentration of succinic acid from aqueous solutions which are post-fermentation multicomponent fluids. The study analyzed the influence of concentration and the pH of the separated solutions on the efficiency and selectivity of NF process that runs in a module equipped with a ceramic membrane. Moreover, the effect of applied trans-membrane pressure on the retention of succinic acid and sodium succinate has been studied. The investigations have shown that in the used NF module the retention of succinic acid salt is equal almost 50% in the case of a three-component model solution, although the degree of retention depends on both the transmembrane pressure and the initial concentration of separated salt.

  6. 76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

    Science.gov (United States)

    2011-09-23

    ... Applicant NDA 017525 LOXITANE (loxapine Watson Laboratories succinate) Inc., 417 Wakara Capsules, Way, Suite.../milliliter. NDA 020828 FORTOVASE Hoffmann La Roche (saquinavir) Inc., 340 Kingsland Capsule, 200 mg. St...

  7. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: Identification and characterization

    NARCIS (Netherlands)

    K.W.A. Grinsven; S. Rosnowsky (Silke); S.W.H. van Weelden (Susanne); S. Pütz (Simone); M. van der Giezen (Mark); W. Martin (William); J.J. van Hellemond (Jaap); A.G.M. Tielens (Aloysius); K. Henze (Katrin)

    2008-01-01

    textabstractAcetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial

  8. Mechanobiology of embryonic limb development.

    Science.gov (United States)

    Nowlan, Niamh C; Murphy, Paula; Prendergast, Patrick J

    2007-04-01

    Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton.

  9. Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory.

    Directory of Open Access Journals (Sweden)

    José Manuel Otero

    Full Text Available Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol, and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2(nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we

  10. Improved sugar-free succinate production by Synechocystis sp. PCC 6803 following identification of the limiting steps in glycogen catabolism

    Directory of Open Access Journals (Sweden)

    Tomohisa Hasunuma

    2016-12-01

    Full Text Available Succinate produced by microorganisms can replace currently used petroleum-based succinate but typically requires mono- or poly-saccharides as a feedstock. The cyanobacterium Synechocystis sp. PCC6803 can produce organic acids such as succinate from CO2 not supplemented with sugars under dark anoxic conditions using an unknown metabolic pathway. The TCA cycle in cyanobacteria branches into oxidative and reductive routes. Time-course analyses of the metabolome, transcriptome and metabolic turnover described here revealed dynamic changes in the metabolism of Synechocystis sp. PCC6803 cultivated under dark anoxic conditions, allowing identification of the carbon flow and rate-limiting steps in glycogen catabolism. Glycogen biosynthesized from CO2 assimilated during periods of light exposure is catabolized to succinate via glycolysis, the anaplerotic pathway, and the reductive TCA cycle under dark anoxic conditions. Expression of the phosphoenolpyruvate (PEP carboxylase gene (ppc was identified as a rate-limiting step in succinate biosynthesis and this rate limitation was alleviated by ppc overexpression, resulting in improved succinate excretion. The sugar-free succinate production was further enhanced by the addition of bicarbonate. In vivo labeling with NaH13CO3 clearly showed carbon incorporation into succinate via the anaplerotic pathway. Bicarbonate is in equilibrium with CO2. Succinate production by Synechocystis sp. PCC6803 therefore holds significant promise for CO2 capture and utilization. Keywords: Autofermentation, Cyanobacteria, Dynamic metabolic profiling, Metabolomics, Succinate, Synechocystis

  11. Production of succinic acid from oil palm empty fruit bunch cellulose using Actinobacillus succinogenes

    Science.gov (United States)

    Pasma, Satriani Aga; Daik, Rusli; Maskat, Mohamad Yusof

    2013-11-01

    Succinic acid is a common metabolite in plants, animals and microorganisms. It has been used widely in agricultural, food and pharmaceutical industries. Enzymatic hydrolysate glucose from oil palm empty fruit bunch (OPEFB) cellulose was used as a substrate for succinic acid production using Actinobacillus succinogenes. Using cellulose extraction from OPEFB can enhance the production of glucose as a main substrate for succinic acid production. The highest concentration of glucose produced from enzymatic hydrolysis is 167 mg/mL and the sugar recovery is 0.73 g/g of OPEFB. By optimizing the culture medium for succinic acid fermentation with enzymatic hydrolysate of OPEFB cellulose, the nitrogen sources could be reduced to just only 2.5 g yeast extract and 2.5 g corn step liquor. Batch fermentation was carried out using enzymatic hydrolysate of OPEFB cellulose with yeast extract, corn steep liquor and the salts mixture, 23.5 g/L succinic acid was obtained with consumption of 72 g/L glucose in enzymatic hydrolysate of OPEFB cellulose at 38 hours and 37°C. This study suggests that enzymatic hydrolysate of OPEFB cellulose maybe an alternative substrate for the efficient production of succinic acid by Actinobacillus succinogenes.

  12. Succinic acid production from xylose mother liquor by recombinant Escherichia coli strain.

    Science.gov (United States)

    Wang, Honghui; Pan, Jiachuan; Wang, Jing; Wang, Nan; Zhang, Jie; Li, Qiang; Wang, Dan; Zhou, Xiaohua

    2014-11-02

    Succinic acid (1,4-butanedioic acid) is identified as one of important building-block chemicals. Xylose mother liquor is an abundant industrial residue in xylitol biorefining industry. In this study, xylose mother liquor was utilized to produce succinic acid by recombinant Escherichia coli strain SD121, and the response surface methodology was used to optimize the fermentation media. The optimal conditions of succinic acid fermentation were as follows: 82.62 g L -1 total initial sugars, 42.27 g L -1 MgCO 3 and 17.84 g L -1 yeast extract. The maximum production of succinic acid was 52.09 ± 0.21 g L -1 after 84 h with a yield of 0.63 ± 0.03 g g -1 total sugar, approaching the predicted value (53.18 g L -1 ). It was 1.78-fold of the production of that obtained with the basic medium. This was the first report on succinic acid production from xylose mother liquor by recombinant E. coli strains with media optimization using response surface methodology. This work suggested that the xylose mother liquor could be an alternative substrate for the economical production of succinic acid by recombinant E. coli strains.

  13. Succinic acid production by Actinobacillus succinogenes using hydrolysates of spent yeast cells and corn fiber.

    Science.gov (United States)

    Chen, Ke-Quan; Li, Jian; Ma, Jiang-Feng; Jiang, Min; Wei, Ping; Liu, Zhong-Min; Ying, Han-Jie

    2011-01-01

    The enzymatic hydrolysate of spent yeast cells was evaluated as a nitrogen source for succinic acid production by Actinobacillus succinogenes NJ113, using corn fiber hydrolysate as a carbon source. When spent yeast cell hydrolysate was used directly as a nitrogen source, a maximum succinic acid concentration of 35.5 g/l was obtained from a glucose concentration of 50 g/l, with a glucose utilization of 95.2%. Supplementation with individual vitamins showed that biotin was the most likely factor to be limiting for succinic acid production with spent yeast cell hydrolysate. After supplementing spent yeast cell hydrolysate and 90 g/l of glucose with 150 μg/l of biotin, cell growth increased 32.5%, glucose utilization increased 37.6%, and succinic acid concentration was enhanced 49.0%. As a result, when biotin-supplemented spent yeast cell hydrolysate was used with corn fiber hydrolysate, a succinic acid yield of 67.7% was obtained from 70.3 g/l of total sugar concentration, with a productivity of 0.63 g/(l h). Our results suggest that biotin-supplemented spent yeast cell hydrolysate may be an alternative nitrogen source for the efficient production of succinic acid by A. succinogenes NJ113, using renewable resources. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  14. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources.

    Science.gov (United States)

    Luthfi, Abdullah Amru Indera; Manaf, Shareena Fairuz Abdul; Illias, Rosli Md; Harun, Shuhaida; Mohammad, Abdul Wahab; Jahim, Jamaliah Md

    2017-04-01

    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

  15. Radioprotective properties of tocopherol succinate against ionizing radiation in mice

    International Nuclear Information System (INIS)

    Singh, V.K.; Singh, P.K.; Wise, S.Y.; Posarac, A.; Fatanmi, O.O.

    2013-01-01

    Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60 Co γ-radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3 (pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (bcl-associated X protein (BAX), caspase 3 and cleaved poly (ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. (author)

  16. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    Directory of Open Access Journals (Sweden)

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  17. Compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in multilayer polyolefin containers.

    Science.gov (United States)

    Bougouin, Christelle; Thelcide, Chloë; Crespin-Maillard, Fabienne; Maillard, Christian; Kinowski, Jean Marie; Favier, Mireille

    2005-10-01

    The compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in 5% dextrose injection and 0.9% sodium chloride injection was studied. Test solutions of ondansetron hydrochloride 0.16 mg/mL and methylprednisolone sodium succinate 2.4 mg/mL were prepared in triplicate and tested in duplicate. Total volumes of 4 and 2 mL of ondansetron hydrochloride solution and methylprednisolone sodium succinate solution, respectively, were added to 50-mL multilayer polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection. Bags were stored for 24 hours at 20-25 degrees C and for 48 hours at 4-8 degrees C. Chemical compatibility was measured with high-performance liquid chromatography, and physical compatibility was determined visually. Ondansetron hydrochloride was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Methylprednisolone sodium succinate was stable for up to 48 hours at 4-8 degrees C. When stored at 20-25 degrees C, methylprednisolone sodium succinate was stable for up to 7 hours in 5% dextrose injection and up to 24 hours in 0.9% sodium chloride injection. Compatibility data for solutions containing ondansetron hydrochloride plus methylprednisolone sodium succinate revealed that each drug was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Ondansetron 0.16 mg/mL (as the hydrochloride) and methylprednisolone 2.4 mg/mL (as the sodium succinate) mixed in 50-mL multilayer polyolefin bags were stable in both 5% dextrose injection and 0.9% sodium chloride injection for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C.

  18. Bio-oil based biorefinery strategy for the production of succinic acid

    Science.gov (United States)

    2013-01-01

    Background Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid was investigated. Results The transgenic E. coli strain could grow in modified M9 medium containing 20 v/v% AP-bio-oil with an increase in OD from 0.25 to 1.09. And 0.38 g/L succinic acid was produced. With the presence of 4 g/L glucose in the medium, succinic acid concentration increased from 1.4 to 2.4 g/L by addition of 20 v/v% AP-bio-oil. When enzymatic hydrolysate of corn stover was used as carbon source, 10.3 g/L succinic acid was produced. The obtained succinic acid concentration increased to 11.5 g/L when 12.5 v/v% AP-bio-oil was added. However, it decreased to 8 g/L when 50 v/v% AP-bio-oil was added. GC-MS analysis revealed that some low molecular carbon compounds in the AP-bio-oil were utilized by E. coli. Conclusions The results indicate that AP-bio-oil can be used by E. coli for cell growth and succinic acid production. PMID:23657107

  19. Genotoxicity of meso-2,3-dimercapto succinic acid-coated silver sulfide quantum dot

    Directory of Open Access Journals (Sweden)

    Deniz Özkan Vardar

    2015-06-01

    Full Text Available Nanotecnology products have been used in wide applications in chemistry, electronics, energy generation, and medicine. Despite significant interest in developing quantum dots (QDs for biomedical applications, many researchers are convinced that QDs will never be used for the treatment of patients because of their potential toxicity. In various in vitro cell culture studies, the cytotoxic properties of some QD have been demonstrated and they have been suggested to be toxic in humans. In this study, the cytotoxic properties of Ag2S-(Meso-2,3-Dimercapto Succinic acid nanomaterials in V79 cells (Chinese lung fibroblast cell line were determined by MTT assay. The genotoxic effects of Ag2S-(Meso-2,3-Dimercapto Succinic acid were evaluated by the alkaline single cell gel electrophoresis. The cells were treated with Ag2S-(Meso-2,3-Dimercapto Succinic acid at the concentrations of 5- 2000 µg/ml. No cytotoxic effect of Ag2S-(Meso-2,3-Dimercapto Succinic acid at all concentrations studied was observed. No significant increases in DNA damage were found at the studied concentrations when compared to negative control in V79 cells. In conclusion, further in vitro and in vivo studies are required to determine the safety doses of Ag2S-(Meso-2,3-Dimercapto Succinic acid.

  20. A novel process for recovery of fermentation-derived succinic acid: process design and economic analysis.

    Science.gov (United States)

    Orjuela, Alvaro; Orjuela, Andrea; Lira, Carl T; Miller, Dennis J

    2013-07-01

    Recovery and purification of organic acids produced in fermentation constitutes a significant fraction of total production cost. In this paper, the design and economic analysis of a process to recover succinic acid (SA) via dissolution and acidification of succinate salts in ethanol, followed by reactive distillation to form succinate esters, is presented. Process simulation was performed for a range of plant capacities (13-55 million kg/yr SA) and SA fermentation titers (50-100 kg/m(3)). Economics were evaluated for a recovery system installed within an existing fermentation facility producing succinate salts at a cost of $0.66/kg SA. For a SA processing capacity of 54.9 million kg/yr and a titer of 100 kg/m(3) SA, the model predicts a capital investment of $75 million and a net processing cost of $1.85 per kg SA. Required selling price of diethyl succinate for a 30% annual return on investment is $1.57 per kg. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Highly Carboxylated Cellulose Nanofibers via Succinic Anhydride Esterification of Wheat Fibers and Facile Mechanical Disintegration.

    Science.gov (United States)

    Sehaqui, H; Kulasinski, K; Pfenninger, N; Zimmermann, T; Tingaut, P

    2017-01-09

    We report herein the preparation of 4-6 nm wide carboxyl-functionalized cellulose nanofibers (CNF) via the esterification of wheat fibers with cyclic anhydrides (maleic, phtalic, and succinic) followed by an energy-efficient mechanical disintegration process. Remarkable results were achieved via succinic anhydride esterification that enabled CNF isolation by a single pass through the microfluidizer yielding a transparent and thick gel. These CNF carry the highest content of carboxyl groups ever reported for native cellulose nanofibers (3.8 mmol g -1 ). Compared to conventional carboxylated cellulose nanofibers prepared via Tempo-mediated oxidation of wheat fibers, the present esterified CNF display a higher molar-mass and a better thermal stability. Moreover, highly carboxylated CNF from succinic anhydride esterification were effectively integrated into paper filters for the removal of lead from aqueous solution and are potentially of interest as carrier of active molecules or as transparent films for packaging, biomedical or electronic applications.

  2. Thermodynamics of U(VI) complexation by succinate at variable temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Rawat, Neetika [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Tomar, B.S., E-mail: bstomar@barc.gov.in [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Manchanda, V.K. [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2011-07-15

    Research highlights: > lg {beta} and {Delta}H{sub C} for U(VI)-succinate determined at variable temperatures. > Increase in lg {beta} with temperature well explained by Born equation. > {Delta}S{sub C} plays the dominant role in variation of {Delta}G{sub C} with temperature. > {Delta}H{sub C} for U(VI)-succinate increases linearly with temperature. > {Delta}C{sub P} of U(VI)-succinate is higher than that of oxalate and malonate complexes. - Abstract: Complexation of U(VI) by succinate has been studied at various temperatures in the range of (298 to 338) K by potentiometry and isothermal titration calorimetry at constant ionic strength (1.0 M). The potentiometric titrations revealed the formation of 1:1 uranyl succinate complex in the pH range of 1.5 to 4.5. The stability constant of uranyl succinate complex was found to increase with temperature. Similar trend was observed in the case of enthalpy of complex formation. However, the increase in entropy with temperature over-compensated the increase in enthalpy, thereby favouring the complexation reaction at higher temperatures. The linear increase of enthalpy of complexation with temperature indicates constancy of the change in heat capacity during complexation. The temperature dependence of stability constant data was well explained with the help of Born equation for electrostatic interaction between the metal ion and the ligand. The data have been compared with those for uranyl complexes with malonate and oxalate to study the effect of ligand size and hydrophobicity on the temperature dependence of thermodynamic quantities.

  3. Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization.

    Science.gov (United States)

    Ober, Courtney A; Gupta, Ram B

    2012-12-01

    Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

  4. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

    DEFF Research Database (Denmark)

    Trauelsen, Mette; Rexen Ulven, Elisabeth; Hjorth, Siv A

    2017-01-01

    therefore binds in a very different mode than generally believed. Importantly, an empty side-pocket is identified next to the succinate binding site. All this information formed the basis for a substructure-based search query, which, combined with molecular docking, was used in virtual screening of the ZINC...... database to pick two serial mini-libraries of a total of only 245 compounds from which sub-micromolar, selective GPR91 agonists of unique structures were identified. The best compounds were backbone-modified succinate analogs in which an amide-linked hydrophobic moiety docked into the side-pocket next...

  5. Metabolic Engineering of Saccharomyces cerevisiae Microbial Cell Factories for Succinic Acid Production

    DEFF Research Database (Denmark)

    Otero, José Manuel; Nielsen, Jens; Olsson, Lisbeth

    2007-01-01

    anhydride. There are several biomass platforms, all prokaryotic, for succinic acid production; however, overproduction of succinic acid in S. cerevisiae offers distinct process advantages. For example, S. cerevisiae has been awarded GRAS status for use in human consumables, grows well at low p......H significantly minimizing purification and acidification costs associated with organic acid production, and can utilize diverse carbon substrates in chemically defined medium. S. cerevisiae offers the unique advantage of being the most well characterized eukaryotic expression system. Here we describe the use...

  6. Modification of cellulose with succinic anhydride in TBAA/DMSO mixed solvent under catalyst-free conditions

    Science.gov (United States)

    Homogeneous modification of cellulose with succinic anhydride was performed in tetrabutylammonium acetate (TBAA)/dimethyl sulfoxide (DMSO) mixed solvent. The molar ratio of succinic anhydride (SA) to free hydroxyl groups in the anhydroglucose units (AGU) and TBAA dosage were investigated as paramete...

  7. Modification of cellulose with succinic anhydride in TBAA/DMSO mixed solvent under catalyst-free conditions

    Science.gov (United States)

    Ping-Ping Xin; Yao-Bing Huang; Chung-Yun Hse; Huai N. Cheng; Chaobo Huang; Hui. Pan

    2017-01-01

    Homogeneous modification of cellulose with succinic anhydride was performed using tetrabutylammonium acetate (TBAA)/dimethyl sulfoxide (DMSO) mixed solvent. The molar ratio of succinic anhydride (SA) to free hydroxyl groups in the anhydroglucose units (AGU), TBAA dosage, reaction temperature, and reaction time were investigated. The highest degree of substitution (DS)...

  8. How the embryonic chick brain twists

    OpenAIRE

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A.

    2016-01-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left–right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic m...

  9. Bio-oil based biorefinery strategy for the production of succinic acid

    DEFF Research Database (Denmark)

    Wang, Caixia; Thygesen, Anders; Liu, Yilan

    2013-01-01

    Background: Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic...

  10. Formation and stability of Vitamin E enriched nanoemulsions stabilized by Octenyl Succinic Anhydride modified starch

    Science.gov (United States)

    Vitamin E (VE) is highly susceptible to autoxidation; therefore, it requires systems to encapsulate and protect it from autoxidation.In this study,we developed VE delivery systems, which were stabilized by Capsul® (MS), a starch modified with octenyl succinic anhydride. Influences of interfacial ten...

  11. Succinate-based preparation alleviates manifestations of the climacteric syndrome in women.

    Science.gov (United States)

    Peskov, A B; Maevskii, E I; Uchitel', M L; Sakharova, N Yu; Vize-Khripunova, M A

    2005-09-01

    Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

  12. Intracellular product recycling in high succinic acid producing yeast at low pH

    NARCIS (Netherlands)

    Wahl, S.A.; Bernal Martinez, C.; Zhao, Zheng; van Gulik, W.M.; Jansen, Mickel L.A.

    2017-01-01

    Background: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering

  13. Integration of Succinic Acid Production in a Dry Mill Ethanol Facility

    Energy Technology Data Exchange (ETDEWEB)

    None

    2006-08-01

    This project seeks to address both issues for a dry mill ethanol biorefinery by lowering the cost of sugars with the development of an advanced pretreatment process, improving the economics of succinic acid (SA), and developing a model of an ethanol dry mill to evaluate the impact of adding different products and processes to a dry mill.

  14. Viscoelastic and electrical properties of carbon nanotubes filled poly(butylene succinate)

    CSIR Research Space (South Africa)

    Bandyopadhyay, J

    2014-03-01

    Full Text Available The carbon nanotubes (CNTs)-containing composites of poly(butylene succinate) (PBS) were prepared by melt-blending in a batch mixer with three concentrations by weight of CNTs: 1, 2 and 3 %. State of dispersion-distribution of the CNTs in the PBS...

  15. Succinic Acid as a Byproduct in a Corn-based Ethanol Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    MBI International

    2007-12-31

    MBI endeavored to develop a process for succinic acid production suitable for integration into a corn-based ethanol biorefinery. The project investigated the fermentative production of succinic acid using byproducts of corn mill operations. The fermentation process was attuned to include raw starch, endosperm, as the sugar source. A clean-not-sterile process was established to treat the endosperm and release the monomeric sugars. We developed the fermentation process to utilize a byproduct of corn ethanol fermentations, thin stillage, as the source of complex nitrogen and vitamin components needed to support succinic acid production in A. succinogenes. Further supplementations were eliminated without lowering titers and yields and a productivity above 0.6 g l-1 hr-1was achieved. Strain development was accomplished through generation of a recombinant strain that increased yields of succinic acid production. Isolation of additional strains with improved features was also pursued and frozen stocks were prepared from enriched, characterized cultures. Two recovery processes were evaluated at pilot scale and data obtained was incorporated into our economic analyses.

  16. Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop

    Czech Academy of Sciences Publication Activity Database

    Stapelberg, M.; Gellert, N.; Swettenham, E.; Tomasetti, M.; Witting, P. K.; Procopio, A.; Neužil, Jiří

    2005-01-01

    Roč. 280, č. 27 (2005), s. 25369-25376 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-tocopheryl succinate * malignant mesothelioma * fibroblast growth factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.854, year: 2005

  17. Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by alpha-tocopheryl succinate

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Vokurková, Martina; Drahota, Zdeněk

    2014-01-01

    Roč. 53, AUG (2014), s. 409-413 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : brown adipose tissue mitochondria * oxygen consumption * glycerol-3-phosphate * succinate * reactive oxygen species Subject RIV: ED - Physiology Impact factor: 4.046, year: 2014

  18. Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dong, L.F.; Wang, X.F.; Zingg, J.M.

    2006-01-01

    Roč. 343, č. 4 (2006), s. 1113-1117 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : apoptosis * tocopherol-associated protein * alpha-tocopheryl succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.855, year: 2006

  19. Efficient production of succinic acid in immobilized fermentation with crude glycerol from Escherichia coli

    Directory of Open Access Journals (Sweden)

    Nik Nor Aziati, A.A.

    2017-10-01

    Full Text Available The increase in the price of commercial succinic acid has necessitated the need for its synthesis from waste materials such as glycerol. Glycerol residue is a waste product of Oleochemical production which is cheaply available and a very good source of carbon. The use of immobilized cells can further reduce the overall cost of the production process. This study primarily aims to produce succinic acid from glycerol residue through the use of immobilized Escherichia coli in a batch fermentation process. The parameters which affect bacterial fermentation process such as the mass substrate, temperature, inoculum size and duration of fermentation were screened using One-Factor-At-a-Time (OFAT method. The result of the screening process shows that a substrate (glycerol concentration of 30 g, inoculum size 20% v/v, and time 4 h produced the maximum succinic acid concentration of 117.99 g/L. The immobilized cells were found to be stable as well as retain their fermentative ability up to the 6th cycle of recycling, thereby presenting as an advantage over the free cell system. Therefore, conclude that using immobilized cells can contribute immensely to the cost-effective production of succinic acid from glycerol residue.

  20. Amorphous/crystal and polymer/filler interphases in biocomposites from poly(butylene succinate)

    Energy Technology Data Exchange (ETDEWEB)

    Signori, Francesca [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Pelagaggi, Martina [Universita di Pisa - Dipartimento di Chimica e Chimica Industriale, Via Risorgimento 35, I-56126 Pisa (Italy); Bronco, Simona [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Righetti, Maria Cristina, E-mail: righetti@ipcf.cnr.it [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy)

    2012-09-10

    Highlights: Black-Right-Pointing-Pointer The existence of intermolecular interactions between poly(butylene succinate) and hemp fibres was proved from specific heat capacities data. Black-Right-Pointing-Pointer Different degrees of mobility of the poly(butylene succinate) amorphous segments were evidenced at the amorphous/crystal interphase. Black-Right-Pointing-Pointer Devitrification of the rigid amorphous fraction in poly(butylene succinate) was found to occur before and simultaneously with the fusion. - Abstract: Poly(butylene succinate)-hemp composites (PBS-hemp), with hemp content in the range 0-40 wt.%, were prepared in the melt and characterized. This paper focuses on the detailed analysis of the thermal behaviour of the PBS-hemp composites, investigated by differential scanning calorimetry (DSC), to enlighten the polymer/fibre interphase features. The occurrence of specific intermolecular interactions between PBS and hemp was assessed from specific heat capacity data. Different degrees of mobility of the PBS amorphous segments were found at the amorphous/crystal interphases. A broadening of the bulk glass transition was observed, and attributed to the presence of polymer segments slightly constrained. Moreover, a rigid amorphous fraction that devitrifies at temperatures higher than the bulk glass transition, partly before the melting region and partly simultaneously with the fusion, was observed and quantified, and attributed to the presence of major constraints probably occurring in geometrically restricted areas.

  1. Fourier Transform Infrared Spectroscopy Study on Cation adsorption on Viscose Rayon Succinate

    Directory of Open Access Journals (Sweden)

    D Khasbaatar

    2014-09-01

    Full Text Available Ion-exchange materials have been considered as suitable material for the recovery of heavy metals in water. A viscose rayon succinate, synthesized from viscose rayon and succinic anhydride in presence of DMSO, to remove trace bivalent metal ions such as Ag+, Cu2+, Ni2+, Pb2+, Zn2+ and Cr3+, was studied using FT-IR for the behavior of metal adsorption. Both esterification and carboxyl bonding of viscose rayon succinate were assigned essentially at 1729 and 1693cm-1, respectively. And the essential band of bonding between metal and the material was determined at 1625cm-1. The available adsorption capacity of this fiber was 6.2 mequiv/g. The adsorption of metal ions on the viscose rayon succinate follows the order of Cu2+>Cr3+>Ni2+>Pb2+>Zn2+>Ag+ with maximum adsorptions capacities 4.2, 1.42, 0.91, 0.83, 0.69 and 0.35 mmol/g, respectively.DOI: http://dx.doi.org/10.5564/mjc.v12i0.189 Mongolian Journal of Chemistry Vol.12 2011: 136-141

  2. Volatility of Organic Aerosol: Evaporation of Ammonium Sulfate/Succinic Acid Aqueous Solution Droplets

    Science.gov (United States)

    2013-01-01

    Condensation and evaporation modify the properties and effects of atmospheric aerosol particles. We studied the evaporation of aqueous succinic acid and succinic acid/ammonium sulfate droplets to obtain insights on the effect of ammonium sulfate on the gas/particle partitioning of atmospheric organic acids. Droplet evaporation in a laminar flow tube was measured in a Tandem Differential Mobility Analyzer setup. A wide range of droplet compositions was investigated, and for some of the experiments the composition was tracked using an Aerosol Mass Spectrometer. The measured evaporation was compared to model predictions where the ammonium sulfate was assumed not to directly affect succinic acid evaporation. The model captured the evaporation rates for droplets with large organic content but overestimated the droplet size change when the molar concentration of succinic acid was similar to or lower than that of ammonium sulfate, suggesting that ammonium sulfate enhances the partitioning of dicarboxylic acids to aqueous particles more than currently expected from simple mixture thermodynamics. If extrapolated to the real atmosphere, these results imply enhanced partitioning of secondary organic compounds to particulate phase in environments dominated by inorganic aerosol. PMID:24107221

  3. Studies on Cross-linking of succinic acid with chitosan/collagen

    Directory of Open Access Journals (Sweden)

    Tapas Mitra

    2013-01-01

    Full Text Available The present study summarizes the cross-linking property of succinic acid with chitosan /collagen. In detail, the chemistry behind the cross-linking and the improvement in mechanical and thermal properties of the cross-linked material were discussed with suitable instruments and bioinformatics tools. The concentration of succinic acid with reference to the chosen polymers was optimized. A 3D scaffold prepared using an optimized concentration of succinic acid (0.2% (w/v with chitosan (1.0% (w/v and similarly with collagen (0.5% (w/v, was subjected to surface morphology, FT-IR analysis, tensile strength assessment, thermal stability and biocompatibility. Results revealed, cross-linking with succinic acid impart appreciable mechanical strength to the scaffold material. In silico analysis suggested the prevalence of non-covalent interactions, which played a crucial role in improving the mechanical and thermal properties of the cross-linked scaffold. The resultant 3D scaffold may find application as wound dressing material, as an implant in clinical applications and as a tissue engineering material.

  4. Vertebrate Embryonic Cleavage Pattern Determination.

    Science.gov (United States)

    Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

    2017-01-01

    The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

  5. CLINICAL AND ECONOMICAL ASSESSMENTS OF METOPROLOL TARTRATE/SUCCINATE USAGE IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Soura

    2008-01-01

    Full Text Available Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI. In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate, decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed → metoprolol tartrate (Betaloc → metoprolol succinate (Betaloc ZOK → bisoprolol (Concor → nebivolol (Nebilet. In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

  6. Succinic acid production from orange peel and wheat straw by batch fermentations of Fibrobacter succinogenes S85.

    Science.gov (United States)

    Li, Qiang; Siles, Jose A; Thompson, Ian P

    2010-10-01

    Succinic acid is a platform molecule that has recently generated considerable interests. Production of succinate from waste orange peel and wheat straw by consolidated bioprocessing that combines cellulose hydrolysis and sugar fermentation, using a cellulolytic bacterium, Fibrobacter succinogenes S85, was studied. Orange peel contains D-limonene, which is a well-known antibacterial agent. Its effects on batch cultures of F. succinogenes S85 were examined. The minimal concentrations of limonene found to inhibit succinate and acetate generation and bacterial growth were 0.01%, 0.1%, and 0.06% (v/v), respectively. Both pre-treated orange peel by steam distillation to remove D: -limonene and intact wheat straw were used as feedstocks. Increasing the substrate concentrations of both feedstocks, from 5 to 60 g/L, elevated succinate concentration and productivity but lowered the yield. In addition, pre-treated orange peel generated greater succinate productivities than wheat straw but had similar resultant titres. The greatest succinate titres were 1.9 and 2.0 g/L for pre-treated orange peel and wheat straw, respectively. This work demonstrated that agricultural waste such as wheat straw and orange peel can be biotransformed to succinic acid by a one-step consolidated bioprocessing. Measures to increase fermentation efficiency are also discussed.

  7. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency.

    Science.gov (United States)

    Richter, Susan; Peitzsch, Mirko; Rapizzi, Elena; Lenders, Jacques W; Qin, Nan; de Cubas, Aguirre A; Schiavi, Francesca; Rao, Jyotsna U; Beuschlein, Felix; Quinkler, Marcus; Timmers, Henri J; Opocher, Giuseppe; Mannelli, Massimo; Pacak, Karel; Robledo, Mercedes; Eisenhofer, Graeme

    2014-10-01

    Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.

  8. THE EFFECTS OF WATER TEMPERATURE REGIME FLUCTUATIONS ON THE EMBRYONIC DEVELOPMENT OF SILVER CARP (HYPOPHTHALMICHTHYS MOLITRIX

    Directory of Open Access Journals (Sweden)

    А. Vodyanitskyi

    2015-03-01

    Full Text Available Purpose. To determine the effect of temperature regime fluctuations on the development of silver carp embryos, as well as the activity of enzymatic reactions in fish eggs. Methodology. The studies were conducted at the experimental station of the Institute of Hydrobiology of Bila Tserkov, Ukrainian National Academy of Sciences, from June to July. The biological materials were silver carp eggs, embryos and larvae. The dissolved oxygen content was determined using the Winkler method at four o’clock in the morning. Alkalinity phosphatase and LDG activity were determined using a set of reagents «Alkalinity phosphatase» and «LDG» (Phyllis diagnosis, Ukraine. SDH activity was determined by Vexy. The activity of Na, K-Mg-dependent-activated ATPase was determined as growth of inorganic phosphorus in the incubation medium by Kindratova M.N. et al. Protease activity was determined using immune enzymatic method of Tyurina et al. The obtained results were processed statistically in Statistica 5.5, Epaprobit analysis was used for calculating LC/EC values (Version 1.5. Findings The results showed that a delay of embryonic stages of development occur, the number of abnormal embryos increases, and the reproduction efficiency of fish reduces with an increase in water temperature and decrease in the dissolved oxygen content in water. The temperature factor had a significant effect on the activity of key enzymes, in particular the energetic metabolism changed from aerobic to anaerobic. Originality. It was found a negative effect of abiotic factors of water medium and drastic fluctuations in water temperature and gas regime of water bodies on the course of embryogenesis of silver carp that is especially important in the conditions of climate change. Practical value. The obtained results showed that the level of optimum and unfavorable environmental factors during the change of embryonic stages in embryonic and larval fish can be established based on the

  9. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  10. [Embryonic stem cells. Future perspectives].

    Science.gov (United States)

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  11. Enterobacter sp. LU1 as a novel succinic acid producer - co-utilization of glycerol and lactose.

    Science.gov (United States)

    Podleśny, Marcin; Jarocki, Piotr; Wyrostek, Jakub; Czernecki, Tomasz; Kucharska, Jagoda; Nowak, Anna; Targoński, Zdzisław

    2017-03-01

    Succinic acid is an important C4-building chemical platform for many applications. A novel succinic acid-producing bacterial strain was isolated from goat rumen. Phylogenetic analysis based on the 16S rRNA sequence and physiological analysis indicated that the strain belongs to the genus Enterobacter. This is the first report of a wild bacterial strain from the genus Enterobacter that is capable of efficient succinic acid production. Co-fermentation of glycerol and lactose significantly improved glycerol utilization under anaerobic conditions, debottlenecking the utilization pathway of this valuable biodiesel waste product. Succinic acid production reached 35 g l -1 when Enterobacter sp. LU1 was cultured in medium containing 50 g l -1 of glycerol and 25 g l -1 of lactose as carbon sources. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  12. The impact of nanoclay on the crystal growth kinetics and morphology of biodegradable poly(ethylene succinate) composite

    CSIR Research Space (South Africa)

    Bandyopadhyay, J

    2012-07-01

    Full Text Available The impact of nanoclay on the isothermal crystal growth kinetics and morphology of biodegradable poly(ethylene succinate) (PES) is reported. A PES composite (PESNC) containing 5 wt% organically modified montmorillonite, was prepared via solvent...

  13. [Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears].

    Science.gov (United States)

    Khunderyakova, N V; Zakharchenko, A V; Zakharchenko, M V; Muller, H; Fedotcheva, I; Kondrashova, M N

    2015-01-01

    Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress.

  14. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle

    International Nuclear Information System (INIS)

    Lahouel, Mesbah; Zini, Roland; Zellagui, Ammar; Rhouati, Salah; Carrupt, Pierre-Alain; Morin, Didier

    2007-01-01

    The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity

  15. Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

    Science.gov (United States)

    Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

    2018-02-07

    Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

  16. Influence of VO2+ ions on structural and optical properties of potassium succinate-succinic acid single crystal for non-linear optical applications

    Science.gov (United States)

    Juliet sheela, K.; Subramanian, P.

    2018-04-01

    A transparent and good optical quality semi organic single crystal of vanadium doped potassium succinate-succinic acid (KSSA) was synthesized by slow evaporation technique at room temperature. The structural perfection was supported by the powder XRD of the KSSA-VO2+ single crystal. Optical behavior of the material was discovered from the absorption and transmission spectra of UV-vis-NIR characterization. Functional group and presence of metal ion in the specimen are depicted from FTIR traces. From the photoluminescence studies, emission of wavelength in the violet region (418 nm) at the excitation of 243 nm could be ascertained. EDAX, SEM measurements identify presence of elements and pictures the step-line growth and the imperfection presents in the grown crystal. EPR analysis extracts the information about the local site symmetry around the impurity ion, molecular orbital coefficients, admixture coefficients and ground state wave function of VO2+ doped KSSA single crystal. Second harmonic generation (SHG) efficiency of the grown crystal was investigated to explore the NLO characteristic of the material.

  17. Miscibility, crystallization and mechanical properties of biodegradable blends of poly(L-lactic acid) and poly(butylene succinate-b-ethylene succinate) multiblock copolymer

    International Nuclear Information System (INIS)

    Jiao, Ling; Huang, Cai-Li; Zeng, Jian-Bing; Wang, Yu-Zhong; Wang, Xiu-Li

    2012-01-01

    Highlights: ► The blend of PLLA and PBES showed limited miscibility. ► The crystallization rate of PLLA was accelerated by blending with PBES. ► The crystal structures of PLLA and PBES did not change. - Abstract: Poly(L-lactic acid) (PLLA) is regarded as one of the most promising biobased and biodegradable polymers. However, its application was restricted due to the brittle nature. In the present study, PLLA was blended with a novel biodegradable flexible multiblock copolymer, poly(butylene succinate-b-ethylene succinate) (PBES) to produce new biodegradable materials. PLLA/PBES blends with different composition were prepared by solution blending and casting method with chloroform as a mutual solvent. Miscibility, crystallization behavior, and mechanical properties of the blends were investigated by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and tensile tests. The results indicated that PLLA and PBES showed limited miscibility in the amorphous phase. The crystallization rate of PLLA was accelerated with the increase of PBES in the blends while the crystallization mechanism did not change. The results of tensile tests suggest that the blends showed longer elongation at break than neat PLLA. The elongation at break of PLLA was obtained to be 10%, and those of PLLA/PBES 80/20, 60/40, 40/60 and 20/80 were 29, 110, 442, and 455%, respectively.

  18. DIFFERENTIATION OF EMBRYONIC STEM CELLS: LESSONS FROM EMBRYONIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    EMOKE PALL

    2008-05-01

    Full Text Available Embryonic stem (ES cells, the undifferentiated cells of early embryos are established as permanent lines and are characterised by their self-renewal capacity and the ability to retain their developmental capacity in vivo and in vitro. The pluripotent properties of ES cells are the basis of gene targeting technologies used to create mutant mouse strains with inactivated genes by homologous recombination. There are several methods to induce the formation of EBs. One of them the formation by aggregating ES cells in hanging drops, using gravity as an aggregation force. This method presents the advantage of obtaining well-calibrated EBs almost identical in size. We used at our experiment the mouse ES cell line KA1/11/C3/C8 with a normal karyotype, at 14th passages. Immunohistochemical examination was aimed to identify tissue-restricted proteins for the two differentiated lineages: titin as a cell-specific antigen for cardiac and skeletal muscle, betaIII-tubulin for the neuronal differentiation, cytokeratin Endo-A (TROMA for the presence of mesenchymal progenitor cells, Oct-4 for the presence of the undifferentiated ES cells. The beating cardiac muscle clumps showed more synchronous rhythm than those seen in EBs obtained from suspension culture method, where the beating cardiac muscle clumps appeared later, had a lower frequency and were uneven. The synaptic networks of neuronal cells were best developed in EBs from suspension, compared to those observed in EBs from hanging-drop method.

  19. Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

    Czech Academy of Sciences Publication Activity Database

    Procházka, L.; Dong, L.F.; Vališ, Karel; Freeman, R.; Ralph, S.J.; Turánek, J.; Neužil, Jiří

    2010-01-01

    Roč. 15, č. 7 (2010), s. 782-794 ISSN 1360-8185 R&D Projects: GA AV ČR(CZ) KAN200520703; GA AV ČR(CZ) IAA500520702; GA AV ČR(CZ) IAA500520602 Institutional research plan: CEZ:AV0Z50520701 Keywords : Vitamin E succinate * apoptosis * Noxa-Bak Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.397, year: 2010

  20. Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory

    DEFF Research Database (Denmark)

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran Raosaheb

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought......-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals....

  1. Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure.

    Science.gov (United States)

    Fröhlich, Hanna; Torres, Lorella; Täger, Tobias; Schellberg, Dieter; Corletto, Anna; Kazmi, Syed; Goode, Kevin; Grundtvig, Morten; Hole, Torstein; Katus, Hugo A; Cleland, John G F; Atar, Dan; Clark, Andrew L; Agewall, Stefan; Frankenstein, Lutz

    2017-09-01

    Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95% CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR 1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.

  2. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    Directory of Open Access Journals (Sweden)

    Hadi Sarir

    2015-01-01

    Full Text Available Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-a and interleukin-6 (IL-6 production induced by high-intensity interval training (HIIT. Materials and Methods: In the present study, 24 rats were randomly divided into control (C, supplementation (S, HIIT, and HIIT + supplementation (HIIT+S groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min and vitamin E succinate supplementation (60 mg/kg/day was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002. Also, serum TNF-a concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001 in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-a when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05. However, no significant changes were observed in serum TNF-a (P = 0.31 and IL-6 (P = 0.52 concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  3. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training.

    Science.gov (United States)

    Sarir, Hadi; Emdadifard, Ghodsieh; Farhangfar, Homayoun; TaheriChadorneshin, Hossein

    2015-12-01

    The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). In the present study, 24 rats were randomly divided into control (C), supplementation (S), HIIT, and HIIT + supplementation (HIIT+S) groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min) and vitamin E succinate supplementation (60 mg/kg/day) was conducted for 6 weeks. Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002). Also, serum TNF-α concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001) in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-α when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05). However, no significant changes were observed in serum TNF-α (P = 0.31) and IL-6 (P = 0.52) concentrations in the HIIT + S group compared with the C group. HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  4. Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

    Science.gov (United States)

    Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

    2017-09-01

    Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Enhanced Bioactivity of α-Tocopheryl Succinate Based Block Copolymer Nanoparticles by Reduced Hydrophobicity.

    Science.gov (United States)

    Palao-Suay, Raquel; Aguilar, María Rosa; Parra-Ruiz, Francisco J; Maji, Samarendra; Hoogenboom, Richard; Rohner, Nathan A; Thomas, Susan N; Román, Julio San

    2016-12-01

    Well-structured amphiphilic copolymers are necessary to obtain self-assembled nanoparticles (NPs) based on synthetic polymers. Highly homogeneous and monodispersed macromolecules obtained by controlled polymerization have successfully been used for this purpose. However, disaggregation of the organized macromolecules is desired when a bioactive element, such as α-tocopheryl succinate, is introduced in self-assembled NPs and this element must be exposed or released to exert its action. The aim of this work is to demonstrate that the bioactivity of synthetic NPs based on defined reversible addition-fragmentation chain transfer polymerization copolymers can be enhanced by the introduction of hydrophilic comonomers in the hydrophobic segment. The amphiphilic terpolymers are based on poly(ethylene glycol) (PEG) as hydrophilic block, and a hydrophobic block based on a methacrylic derivative of α-tocopheryl succinate (MTOS) and small amounts of 2-hydroxyethyl methacrylate (HEMA) (PEG-b-poly(MTOS-co-HEMA)). The introduction of HEMA reduces hydrophobicity and introduces "disorder" both in the homogeneous blocks and the compact core of the corresponding NPs. These NPs are able to encapsulate additional α-tocopheryl succinate (α-TOS) with high efficiency and their biological activity is much higher than that described for the unmodified copolymers, proposedly due to more efficient degradation and release of α-TOS, demonstrating the importance of the hydrophilic-hydrophobic balance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. [Effects of different neutralizing agents on succinate production by Actinobacillus succinogenes NJ113].

    Science.gov (United States)

    Yang, Zhuona; Jiang, Min; Li, Jian; Fang, Xiaojiang; Ye, Guizi; Bai, Xuefei; Zheng, Xiaoyu; Wei, Ping

    2010-11-01

    Different neutralizing agents were used as pH controller to investigate their effects on the growth and succinic acid production of Actinobacillus succinogenes NJ113. The fermentation results showed that Ca(OH)2, CaCO3 and NH4OH were not suitable for succinic acid production by A. succinogenes NJ113 because of their negative effects on cell growth. When Na-base was used, cells would flocculate and lump, and due to the sodium ion concentration reaching to a high level, OD660 dropped sharply after 12 h of fermentation. Mg-base was better because there was no significant inhibition by magnesium ion. Two combined neutralizing agents were used to maintain pH level, one with NaOH and Mg(OH)2 while the other with Na2CO3 and Mg(OH)2. The optimum ratios of the combined neutralizing agents were both 1:1 (g:g) when using 100 g/L glucose. When NaOH and Mg(OH)2 were chosen with the ratio of 1:1(g:g), 69.8 g/L of the succinic acid and 74.5% of the yield was obtained.

  7. Co-Consumption of Methanol and Succinate by Methylobacterium extorquens AM1

    Science.gov (United States)

    Peyraud, Rémi; Kiefer, Patrick; Christen, Philipp; Portais, Jean-Charles; Vorholt, Julia A.

    2012-01-01

    Methylobacterium extorquens AM1 is a facultative methylotrophic Alphaproteobacterium and has been subject to intense study under pure methylotrophic as well as pure heterotrophic growth conditions in the past. Here, we investigated the metabolism of M. extorquens AM1 under mixed substrate conditions, i.e., in the presence of methanol plus succinate. We found that both substrates were co-consumed, and the carbon conversion was two-thirds from succinate and one-third from methanol relative to mol carbon. 13C-methanol labeling and liquid chromatography mass spectrometry analyses revealed the different fates of the carbon from the two substrates. Methanol was primarily oxidized to CO2 for energy generation. However, a portion of the methanol entered biosynthetic reactions via reactions specific to the one-carbon carrier tetrahydrofolate. In contrast, succinate was primarily used to provide precursor metabolites for bulk biomass production. This work opens new perspectives on the role of methylotrophy when substrates are simultaneously available, a situation prevailing under environmental conditions. PMID:23133625

  8. Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Quang M Tran

    Full Text Available The role of the heme b in Escherichia coli succinate dehydrogenase is highly ambiguous and its role in catalysis is questionable. To examine whether heme reduction is an essential step of the catalytic mechanism, we generated a series of site-directed mutations around the heme binding pocket, creating a library of variants with a stepwise decrease in the midpoint potential of the heme from the wild-type value of +20 mV down to -80 mV. This difference in midpoint potential is enough to alter the reactivity of the heme towards succinate and thus its redox state under turnover conditions. Our results show both the steady state succinate oxidase and fumarate reductase catalytic activity of the enzyme are not a function of the redox potential of the heme. As well, lower heme potential did not cause an increase in the rate of superoxide production both in vitro and in vivo. The electron paramagnetic resonance (EPR spectrum of the heme in the wild-type enzyme is a combination of two distinct signals. We link EPR spectra to structure, showing that one of the signals likely arises from an out-of-plane distortion of the heme, a saddled conformation, while the second signal originates from a more planar orientation of the porphyrin ring.

  9. Succinic acid production from acid hydrolysate of corn fiber by Actinobacillus succinogenes.

    Science.gov (United States)

    Chen, Kequan; Jiang, Min; Wei, Ping; Yao, Jiaming; Wu, Hao

    2010-01-01

    Dilute acid hydrolysate of corn fiber was used as carbon source for the production of succinic acid by Actinobacillus succinogenes NJ113. The optimized hydrolysis conditions were obtained by orthogonal experiments. When corn fiber particles were of 20 mesh in size and treated with 1.0% sulfuric acid at 121 degrees C for 2 h, the total sugar yield could reach 63.3%. It was found that CaCO(3) neutralization combined with activated carbon adsorption was an effective method to remove fermentation inhibitors especially furfural that presented in the acid hydrolysate of corn fiber. Only 5.2% of the total sugar was lost, while 91.9% of furfural was removed. The yield of succinic acid was higher than 72.0% with the detoxified corn fiber hydrolysate as the carbon source in anaerobic bottles or 7.5 L fermentor cultures. It was proved that the corn fiber hydrolysate could be an alternative to glucose for the production of succinic acid by A. succinogenes NJ113.

  10. Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production.

    Science.gov (United States)

    Agren, Rasmus; Otero, José Manuel; Nielsen, Jens

    2013-07-01

    In this work, we describe the application of a genome-scale metabolic model and flux balance analysis for the prediction of succinic acid overproduction strategies in Saccharomyces cerevisiae. The top three single gene deletion strategies, Δmdh1, Δoac1, and Δdic1, were tested using knock-out strains cultivated anaerobically on glucose, coupled with physiological and DNA microarray characterization. While Δmdh1 and Δoac1 strains failed to produce succinate, Δdic1 produced 0.02 C-mol/C-mol glucose, in close agreement with model predictions (0.03 C-mol/C-mol glucose). Transcriptional profiling suggests that succinate formation is coupled to mitochondrial redox balancing, and more specifically, reductive TCA cycle activity. While far from industrial titers, this proof-of-concept suggests that in silico predictions coupled with experimental validation can be used to identify novel and non-intuitive metabolic engineering strategies.

  11. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    Science.gov (United States)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  13. Biomechanical forces promote embryonic haematopoiesis

    Science.gov (United States)

    Adamo, Luigi; Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Yoshimoto, Momoko; Lensch, M. William; Yoder, Mervin C.; García-Cardeña, Guillermo; Daley, George Q.

    2009-01-01

    Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system1,2. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential6. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41+c-Kit+ haematopoietic progenitor cells7,concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the paraaortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling8, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development. PMID:19440194

  14. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  15. Direct Succinic Acid Production from Minimally Pretreated Biomass Using Sequential Solid-State and Slurry Fermentation with Mixed Fungal Cultures

    Directory of Open Access Journals (Sweden)

    Jerico Alcantara

    2017-06-01

    Full Text Available Conventional bio-based succinic acid production involves anaerobic bacterial fermentation of pure sugars. This study explored a new route for directly producing succinic acid from minimally-pretreated lignocellulosic biomass via a consolidated bioprocessing technology employing a mixed lignocellulolytic and acidogenic fungal co-culture. The process involved a solid-state pre-fermentation stage followed by a two-phase slurry fermentation stage. During the solid-state pre-fermentation stage, Aspergillus niger and Trichoderma reesei were co-cultured in a nitrogen-rich substrate (e.g., soybean hull to induce cellulolytic enzyme activity. The ligninolytic fungus Phanerochaete chrysosporium was grown separately on carbon-rich birch wood chips to induce ligninolytic enzymes, rendering the biomass more susceptible to cellulase attack. The solid-state pre-cultures were then combined in a slurry fermentation culture to achieve simultaneous enzymatic cellulolysis and succinic acid production. This approach generated succinic acid at maximum titers of 32.43 g/L after 72 h of batch slurry fermentation (~10 g/L production, and 61.12 g/L after 36 h of addition of fresh birch wood chips at the onset of the slurry fermentation stage (~26 g/L production. Based on this result, this approach is a promising alternative to current bacterial succinic acid production due to its minimal substrate pretreatment requirements, which could reduce production costs.

  16. Radiation-induced alterations in succinate dehydrogenase activity in the muscle of pigeon

    International Nuclear Information System (INIS)

    Gadhia, P.K.; Shah, V.C.

    1983-01-01

    The histochemical changes in succinate dehydrogenase were investigated in pectoralis major muscle of pigeon exposed to sub-lethal dose (400 rad) of γ-irradiation. Biochemical study was also carried out after 200, 300 and 400 rad of irradiation. In the present study the overall decrease in enzyme activity could be due to the structural and/or functional damage to mitochondria after treatment of pigeon to different sub-lethal doses of γ-irradiation. The significance of these results has been discussed with special reference to oxidative metabolism. (author)

  17. Mitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis

    Czech Academy of Sciences Publication Activity Database

    Truksa, Jaroslav; Dong, L.F.; Rohlena, Jakub; Stursa, J.; Vondrusová, Magdaléna; Goodwin, J.; Nguyen, M.; Klučková, Katarína; Rychtarčíková, Zuzana; Lettlová, Sandra; Spáčilová, Jana; Stapelberg, M.; Zoratti, M.; Neužil, Jiří

    2015-01-01

    Roč. 22, č. 11 (2015), s. 883-900 ISSN 1523-0864 R&D Projects: GA ČR GAP301/10/1937; GA AV ČR KAN200520703; GA ČR GAP305/12/1708; GA ČR GAP301/12/1851; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 Keywords : ALPHA-TOCOPHERYL SUCCINATE * ELECTRON-TRANSPORT CHAIN * RESPIRATORY COMPLEX-II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.093, year: 2015

  18. Influence of adrenaline on the activity of succinate dehydrogenase in peripheral blood lymphocytes of irradiated rats

    International Nuclear Information System (INIS)

    Koroleva, L.V.; Vasin, M.V.

    1988-01-01

    In experiments with albino mongrel female rats, the influence of adrenaline on succinate dehydrogenase (SDG) activity in the peripheral blood lymphocytes of irradiated and intact animals has been investigated. Two minutes after the intraperitoneal administration of adrenaline (1 mg/kg) to intact rats SDG activity sharply rises and 3-4 min it drastically falls. In 6 to 8 min the second peak in the enzyme activity is registered. Twenty minutes after irradiation of rats in the crano-caudal direction with a dose of 75 Gy delivered to head, the reaction to adrenaline, manifested by the rise in SDG activity, is absent

  19. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  20. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  1. NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

    Science.gov (United States)

    Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

    2014-08-01

    Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

  2. Nb-Based Zeolites: Efficient bi-Functional Catalysts for the One-Pot Synthesis of Succinic Acid from Glucose

    Directory of Open Access Journals (Sweden)

    Magdi El Fergani

    2017-12-01

    Full Text Available The one-pot production of succinic acid from glucose was investigated in pure hot water as solvent using Nb (0.02 and 0.05 moles%-Beta zeolites obtained by a post-synthesis methodology. Structurally, they are comprised of residual framework Al-acid sites, extra-framework isolated Nb (V and Nb2O5 pore-encapsulated clusters. The Nb-modified Beta-zeolites acted as bi-functional catalysts in which glucose is dehydrated to levulinic acid (LA which, further, suffers an oxidation process to succinic acid (SA. After the optimization of the reaction conditions, that is, at 180 °C, 18 bar O2, and 12 h reaction time, the oxidation of glucose occurred with a selectivity to succinic acid as high as 84% for a total conversion.

  3. [Pathomorphology of regenerative processes in mandibular fracture after sodium succinate treatment and laser magnetotherapy in an experimental setting].

    Science.gov (United States)

    Faustov, L A; Nedel'ko, N A; Morozova, M V

    2001-01-01

    Morphological reactions in tissue adjacent to mandibular angular fracture were studied in guinea pigs treated with sodium succinate and laser magnetotherapy. Due to succinate therapy the exudative component of inflammation was less expressed in comparison with the control, macrophagal reaction and neoangiogenesis were activated, the volume of damaged muscle tissue and the incidence of suppurations decreased. The number of osteoblasts increased and new bone structures acquired a lamellar pattern earlier than in the control. Sodium succinate therapy in combination with laser magnetotherapy had a more pronounced positive effect as regards activation of macrophagal reaction and neoangiogenesis and a decrease in the area of fibrosclerotic changes in the zone of damaged muscles, where newly formed myosymplasts differentiated into myotubes and even in muscle fibers. Suppuration of the wound was prevented. Bone tissue in the fracture zone formed without preliminary formation of cartilaginous tissue, which resulted in more rapid osteogenesis (lamellar bone growth in the fracture zone).

  4. Succinate production positively correlates with the affinity of the global transcription factor Cra for its effector FBP in Escherichia coli.

    Science.gov (United States)

    Wei, Li-Na; Zhu, Li-Wen; Tang, Ya-Jie

    2016-01-01

    Effector binding is important for transcription factors, affecting both the pattern and function of transcriptional regulation to alter cell phenotype. Our previous work suggested that the affinity of the global transcription factor catabolite repressor/activator (Cra) for its effector fructose-1,6-bisphosphate (FBP) may contribute to succinate biosynthesis. To support this hypothesis, single-point and three-point mutations were proposed through the semi-rational design of Cra to improve its affinity for FBP. For the first time, a positive correlation between succinate production and the affinity of Cra for FBP was revealed in Escherichia coli . Using the best-fit regression function, a cubic equation was used to examine and describe the relationship between succinate production and the affinity of Cra for FBP, demonstrating a significant positive correlation between the two factors (coefficient of determination R 2  = 0.894, P  = 0.000 Cra and DNA showed that Cra bound to the promoter regions of pck and aceB to activate the corresponding genes. Normally, Cra-regulated operons under positive control are deactivated in the presence of FBP. Therefore, theoretically, the enhanced affinity of Cra for FBP will inhibit the activation of pck and aceB . However, the activation of genes involved in CO 2 fixation and the glyoxylate pathway was further improved by the Cra mutant, ultimately contributing to succinate biosynthesis. Enhanced binding of Cra to FBP or active site mutations may eliminate the repressive effect caused by FBP, thus leading to increased activation of genes associated with succinate biosynthesis in the Cra mutant. This work demonstrates an important transcriptional regulation strategy in the metabolic engineering of succinate production and provides useful information for better understanding of the regulatory mechanisms of transcription factors.

  5. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... hepatocyte transplantation therapy and toxicity screening in drug discovery. Key words: Embryonic stem cells, hepatic-like cells, in vitro differentiation, sodium butyrate, ... from embryonic stem (ES) cell or induced pluripotent.

  6. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    Energy Technology Data Exchange (ETDEWEB)

    Sun Wen [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Du Yingxiang, E-mail: du_yingxiang@126.co [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Wang Yunqing [Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China)

    2010-08-15

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10{sup -5}-5.0x10{sup -4} mol L{sup -1}, and the limit of detection is 11.2 {mu}mol L{sup -1}. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  7. Crystallization and degradation behaviors of poly(butylene succinate)/poly(Z-L-lysine) composites

    International Nuclear Information System (INIS)

    Tan, Licheng; Hu, Jun; Ye, Suwen; Wei, Junchao; Chen, Yiwang

    2014-01-01

    Highlights: • A new biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were successfully prepared through physical blend. • PZlys may greatly affected the crystallization behaviors of PBS without changing its crystalline structure. • The degradation speed of PBS may be greatly accelerated by introduction of PZlys in PBS matrix. - Abstract: A new type of biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were prepared. The crystallization behaviors were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM) and the results showed that PZlys can restrict the crystallization of PBS, the crystallization speed of PBS/PZlys were slower than that of PBS, and the crystallization degree of the composites were smaller than that of PBS. However, the WAXD results showed that the incorporation of PZlys did not change the crystalline structure of PBS. The in vitro degradation experiments demonstrated that the degradation speed of the composites were faster than that of PBS. Moreover, the mechanical properties of the composites showed that the composites with a proper composition (for example, 80/20) can keep the mechanical properties of PBS without evident difference, which implied that the composites might be potentially useful as biodegradable materials

  8. Succinate Functionalization of Hyperbranched Polyglycerol-Coated Magnetic Nanoparticles as a Draw Solute During Forward Osmosis.

    Science.gov (United States)

    Yang, Hee-Man; Choi, Hye Min; Jang, Sung-Chan; Han, Myeong Jin; Seo, Bum-Kyoung; Moon, Jei-Kwon; Lee, Kune-Woo

    2015-10-01

    Hyperbranched polyglycerol-coated magnetic nanoparticles (SHPG-MNPs) were functionalized with succinate groups to form a draw solute for use in a forward osmosis (FO). After the one-step synthesis of hyperbranched polyglycerol-coated magnetic nanoparticles (HPG-MNPs), the polyglycerol groups on the surfaces of the HPG-MNPs were functionalized with succinic anhydride moieties. The resulting SHPG-MNPs showed no change of size and magnetic property compared with HPG-MNPs and displayed excellent dispersibility in water up to the concentration of 400 g/L. SHPG-MNPs solution showed higher osmotic pressure than that of HPG-MNPs solution due to the presence of surface carboxyl groups in SHPG-MNPs and could draw water from a feed solution across an FO membrane without any reverse draw solute leakage during FO process. Moreover, the water flux remained nearly constant over several SHPG-MNP darw solute regeneration cycles applied to the ultrafiltration (UF) process. The SHPG-MNPs demonstrate strong potential for use as a draw solute in FO processes.

  9. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

    Directory of Open Access Journals (Sweden)

    Naoto Kuroda

    2016-05-01

    Full Text Available Succinate dehydrogenase (SDH-deficient renal cell carcinoma (RCC was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD. The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB , SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

  10. Role of O2 in the Growth of Rhizobium leguminosarum bv. viciae 3841 on Glucose and Succinate

    OpenAIRE

    Wheatley, Rachel M.; Ramachandran, Vinoy K.; Geddes, Barney A.; Perry, Benjamin J.; Yost, Chris K.; Poole, Philip S.

    2016-01-01

    Insertion sequencing (INSeq) analysis of Rhizobium leguminosarum bv. viciae 3841 (Rlv3841) grown on glucose or succinate at both 21% and 1% O2 was used to understand how O2 concentration alters metabolism. Two transcriptional regulators were required for growth on glucose (pRL120207 [eryD] and RL0547 [phoB]), five were required on succinate (pRL100388, RL1641, RL1642, RL3427, and RL4524 [ecfL]), and three were required on 1% O2 (pRL110072, RL0545 [phoU], and RL4042). A novel toxin-antitoxin s...

  11. the production of mouse embryonic stem cells

    Indian Academy of Sciences (India)

    MADU

    What history tells us VII. Twenty-five years ago: the production of mouse embryonic stem cells ... cells into the cavity of the blastocyst, it will be possible to test the effect of .... to the use of efficient immunosuppressive drugs like cyclosporin – was ...

  12. Testicular Embryonic Rhabdomyosarcoma, Case report with brief ...

    African Journals Online (AJOL)

    Testicular Embryonic Rhabdomyosarcoma, Case report with brief literature review. AM Adam, MMAM Ibnouf, IAF Allah. Abstract. Background: Rhabdomyosarcoma (RMS) is a malignant solid tumour arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites.

  13. How the embryonic chick brain twists.

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A

    2016-11-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).

  14. Embryonal rhabdomyosarcoma of the cervix | Ocheke | African ...

    African Journals Online (AJOL)

    Embryonal rhabdomyosarcoma (sarcoma botyroides) of the cervix, which is rare, is described in a 16-yearold. The combined use of chemotherapy, radiotherapy and surgery has markedly improved survival in those with this condition. However, our patient did not benefit from this treatment modality due to late presentation ...

  15. Embryonic Stem Cells and their Genetic Modification

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 2. Embryonic Stem Cells and their Genetic Modification - The Nobel Prize in Physiology or Medicine 2007. Mitradas M Panicker. General Article Volume 13 Issue 2 February 2008 pp 172-180 ...

  16. Transcriptome Landscapes of Mammalian Embryonic Cells

    NARCIS (Netherlands)

    Brinkhof, B.

    2015-01-01

    This thesis describes research on gene expression profiles from different embryonic stages and cell types to identify genes involved in pluripotency or differentiation in bovine and porcine cells. The results are compared with data from other mammals. RNA expression profiles of morula and blastocyst

  17. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

    Directory of Open Access Journals (Sweden)

    Chaithra Prasad

    2014-10-01

    Full Text Available Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

  18. Influence of salicylic and succinic acids on antioxidant enzymes activity, heat resistance and productivity of Panicum miliaceum L.

    Directory of Open Access Journals (Sweden)

    Miroshnichenko N.N.

    2011-05-01

    Full Text Available The influence of treatment of millet (Panicum miliaceum L. seeds with the solutions of salicylic and succinic acids on the heat resistance of plantlets and activity of antioxidant enzymes – superoxide dismutase (SOD, catalase and peroxidase – in them have been investigated. In the micro-field experiment the influence of these acids on the millet yield was estimated. The action of salicylic (10 μM and succinic (1 mM acids caused the increase of plantlets resistance to the damaging heating that expressed in the rise of relative quantity of survived plantlets in 5 days after heating at the temperature of 47°С and in the reduced content of lipid peroxidation product malonic dialdehyde during the poststress period. The increase of activity of SOD, catalase and peroxidase took place in millet plantlets under the influence of salicylic and succinic acids. The increase of productivity of millet grain under the action of salicylic and succinic acids on 13,3-52,0 and 6,4-38,8% respectively depending on weather conditions in the field experiments was noted.

  19. Linkage and radiation hybrid mapping of the porcine gene for subunit C of succinate dehydrogenase complex (SDHC)

    Czech Academy of Sciences Publication Activity Database

    Stratil, Antonín; Reiner, G.; Peelman, L. J.; Poucke, M.; Geldermann, H.

    2001-01-01

    Roč. 32, č. 2 (2001), s. 110-112 ISSN 0268-9146 R&D Projects: GA AV ČR KSK5052113; GA ČR GA523/00/0669 Keywords : succinate dehydrogenase complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.020, year: 2001

  20. Discovering novel Alternaria solani succinate dehydrogenase inhibitors by in silico modeling and virtual screening strategies to combat early blight

    NARCIS (Netherlands)

    Iftikhar, Sehrish; Shahid, Ahmad A.; Halim, Sobia A.; Wolters, Pieter J.; Vleeshouwers, Vivianne G.A.A.; Khan, Ajmal; Al-Harrasi, Ahmed; Ahmad, Shahbaz

    2017-01-01

    Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against

  1. Utilization of CO2 fixating bacterium Actinobacillus succinogenes 130Z for simultaneous biogas upgrading and bio-succinic acid production

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Alvarado-Morales, Merlin; Angelidaki, Irini

    2014-01-01

    Biogas is an attractive renewable energy carrier. However, it contains CO2 which limits certain applications of biogas. Here we report a novel approach for removing CO2 from biogas and capturing it as a biochemical through a biological process. This approach entails converting CO2 into bio...... and titre, CO2 consumption rate and CH4 purity. When using biogas as the only CO2 source at 140 kPa, the CO2 consumption rate corresponded to 2.59 L CO2 L-1 d-1 with a final succinic acid titre of 14.4 g L-1. Under this pressure condition the highest succinic acid yield and biogas quality reached......-succinic acid using the bacterial strain Actinobacillus succinogenes 130Z, and simultaneously producing high purity CH4 (>95%). Results showed that when pressure during fermentation was increased from 101.325 to 140 kPa, higher CO2 solubility was achieved, thereby positively affecting final succinic acid yield...

  2. Enhancing succinic acid biosynthesis in Escherichia coli by engineering its global transcription factor, catabolite repressor/activator (Cra).

    Science.gov (United States)

    Zhu, Li-Wen; Xia, Shi-Tao; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Tang, Ya-Jie

    2016-11-04

    This study was initiated to improve E. coli succinate production by engineering the E. coli global transcription factor, Cra (catabolite repressor/activator). Random mutagenesis libraries were generated through error-prone PCR of cra. After re-screening and mutation site integration, the best mutant strain was Tang1541, which provided a final succinate concentration of 79.8 ± 3.1 g/L: i.e., 22.8% greater than that obtained using an empty vector control. The genes and enzymes involved in phosphoenolpyruvate (PEP) carboxylation and the glyoxylate pathway were activated, either directly or indirectly, through the mutation of Cra. The parameters for interaction of Cra and DNA indicated that the Cra mutant was bound to aceBAK, thereby activating the genes involved in glyoxylate pathway and further improving succinate production even in the presence of its effector fructose-1,6-bisphosphate (FBP). It suggested that some of the negative effect of FBP on Cra might have been counteracted through the enhanced binding affinity of the Cra mutant for FBP or the change of Cra structure. This work provides useful information about understanding the transcriptional regulation of succinate biosynthesis.

  3. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

  4. Bid integrates intrinsic and extrinsic signaling in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells

    Czech Academy of Sciences Publication Activity Database

    Zhao, Y.; Li, R.; Xia, W.; Neužil, Jiří; Lu, Y.; Zhang, H.; Zhao, X.; Zhang, X.; Sun, C.; Wu, K.

    2010-01-01

    Roč. 288, č. 1 (2010), s. 42-49 ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Alpha-tocopheryl succinate * signaling * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.864, year: 2010

  5. Alpha-Tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Benassi, M.S.; Tomasetti, M.; Gellert, N.; Ponticelli, F.; Borghi, B.; Picci, P.; Neužil, Jiří

    2005-01-01

    Roč. 331, č. 4 (2005), s. 1515-1521 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z5052915 Keywords : osteosarcoma * alpha-tocopheryl succinate * E2F1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  6. Physical and chemical stability of palonosetron hydrochloride with dacarbazine and with methylprednisolone sodium succinate during simulated y-site administration.

    Science.gov (United States)

    Trissel, Lawrence A; Zhang, Yanping; Xu, Quanyun A

    2006-01-01

    The objective of this study was to evaluate the physical and chemical stability of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with dacarbazine 4 mg/mL and with methylprednisolone sodium succinate 5 mg/mL in 5% dextrose injection during simulated Y-site administration. Triplicate test samples were prepared by admixing 7.5 mL of palonosetron hydrochloride with 7.5 mL of dacarbazine solution and, separately, methylprednisolone sodium succinate solution. Physical stability was assessed by using a multistep evaluation procedure that included both turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by using stability-indicating high-performance liquid chromatographic analytical techniques that determined drug concentrations. Evaluations were performed immediately after mixing and 1 and 4 hours after mixing. The palonosetron hydrochloride-dacarbazine samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidities remained unchanged; particulate contents were low and exhibited little change. High-performance liquid chromatography analysis revealed that palonosetron hydrochloride and dacarbazine remained stable throughout the 4-hour test with no drug loss. Palonosetron hydrochloride is, therefore, physically compatible and chemically stable with dacarbazine during Y-site administration. Within 4 hours, the mixtures of palonosetron hydrochloride and methylprednisolone sodium succinate developed a microprecipitate that became a white precipitate visible to the unaided eye. The precipitate was analyzed and identified as methylprednisolone. Palonosetron hydrochloride is incompatible with methylprednisolone sodium succinate.

  7. Development of chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis.

    Science.gov (United States)

    Davoudi, Zahra; Rabiee, Mohammad; Houshmand, Behzad; Eslahi, Niloofar; Khoshroo, Kimia; Rasoulianboroujeni, Morteza; Tahriri, Mohammadreza; Tayebi, Lobat

    2018-01-01

    The aim of this research was to develop chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis, which was fabricated through an environmental friendly process. Mucoadhesive films increase the advantage of higher efficiency and drug localization in the affected region. In this research, mucoadhesive films, for the release of hydrocortisone sodium succinate, were prepared using different ratios of chitosan, gelatin and keratin. In the first step, chitosan and gelatin proportions were optimized after evaluating the mechanical properties, swelling capacity, water uptake, stability, and biodegradation of the films. Then, keratin was added at different percentages to the optimum composite of chitosan and gelatin together with the drug. The results of surface pH showed that none of the samples were harmful to the buccal cavity. FTIR analysis confirmed the influence of keratin on the structure of the composite. The presence of a higher amount of keratin in the composite films resulted in high mechanical, mucoadhesive properties and stability, low water uptake and biodegradation in phosphate buffer saline (pH = 7.4) containing 10 4  U/ml lysozyme. The release profile of the films ascertained that keratin is a rate controller in the release of the hydrocortisone sodium succinate. Finally, chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate can be employed in dental applications.

  8. Hepatoprotective Activity of a Complex Compound of 5-Hydroxy-6-Methyluracil and Succinic Acid in Experimental Peritonitis

    Directory of Open Access Journals (Sweden)

    D. A. Yenikeyev

    2008-01-01

    Full Text Available Objective: to evaluate the hepatoprotective efficacy of a complex compound of 5-hydroxy-6-methyluracil and succinic acid in experimental peritonitis. Materials and methods. Experiments were carried out on 48 male albino rats in which peritonitis was simulated via intraperitoneal administration of 7% fecal suspension in a dose of 0.6 ml per 100 g bodyweight. The rate of free radical oxidation processes, the activity of antioxidative protection, the degree of endogenous intoxication and cytolytic syndrome, and the effect of the test compound on these parameters were estimated in the experiment. Results. With the development of an abdominal inflammatory process, there were increases in rates of endogenous intoxication and free radical oxidation (FRO, a change in the activity of antioxidative protection enzymes, and a reduction in the levels of ceruloplasmin and sulfahydryl groups. The complex compound, that comprised 5-hydroxy-6-methyluracil and succinic acid used as monotherapy, reduced the degree of endogenous intoxication, FRO, and lipid peroxidation-antioxidative defense system imbalance. Conclusion. The experimental data suggest that the use of the complex compound containing succinic acid and 5-hydroxy-6-methy-luracil is pathogenetically warranted. Key words: peritonitis, lipid peroxidation, antioxidants, succinic acid, pyrim-idine derivatives.

  9. Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations

    DEFF Research Database (Denmark)

    Kacso, Gergely; Ravasz, Dora; Doczi, Judit

    2016-01-01

    Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and a substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with or without methylmalonyl aciduria, in addition to result...

  10. Surface Functionalization of WO3 Thin Films with (3-Aminopropyl)triethoxysilane and Succinic Anhydride

    Science.gov (United States)

    Ta, Thi Kieu Hanh; Tran, Thi Nhu Hoa; Tran, Quang Minh Nhat; Pham, Duy Phong; Pham, Kim Ngoc; Cao, Thi Thanh; Kim, Yong Soo; Tran, Dai Lam; Ju, Heongkyu; Phan, Bach Thang

    2017-06-01

    We report effects of oxygen plasma treatment on the surface functionalization of WO3 thin films with (3-aminopropyl)triethoxysilane (APTES) and succinic anhydride (SA). X-ray diffraction and x-ray photoelectron spectroscopy results indicate the existence of the WO3 phase. Fourier transform infrared spectroscopy measurement shows clear bands at 1040 cm-1 (Si-O-Si), 1556 cm-1 (N-H), 1655 cm-1 (C=O), 2937 cm-1 (C-H) and 3298 cm-1 (N-H), confirming the surface functionalization efficiency enhanced by prior treatment of oxygen plasma. It thus follows that the prior oxygen plasma treatment activates hydroxylation with more -OH groups on the WO3 surface, which can pave a highly efficient way to the surface functionalization by APTES and SA.

  11. Vickers microhardness studies on solution-grown single crystals of potassium boro-succinate

    Science.gov (United States)

    Lakshmipriya, M.; Rajan Babu, D.; Ezhil Vizhi, R.

    2015-02-01

    The semiorganic crystals of potassium boro-succinate (KBS) were grown by slow evaporation method. KBS crystallizes in monoclinic system which was confirmed by powder XRD analysis. Vickers microhardness study has been carried out over a load range of 25-100 g. The Vickers hardness numbers (Hv) of the material increases as the load increases so the material is suitable for device fabrication. The Meyer index 'n' is estimated to be greater than 1.6, the crystal system belongs to the soft material category. The elastic stiffness coefficient, c11, has also been calculated using Wooster's empirical relation from the hardness data. The fracture toughness values 'Kc', determined from measurements of crack lengths, were estimated to be 0.15166 MN/m3/2. The brittleness indices 'Bi' were estimated as 276 m-1/2.

  12. Enhanced performance of biodegradable poly(butylene succinate)/graphene oxide nanocomposites via in situ polymerization.

    Science.gov (United States)

    Wang, X W; Zhang, C-A; Wang, P L; Zhao, J; Zhang, W; Ji, J H; Hua, K; Zhou, J; Yang, X B; Li, X P

    2012-05-08

    Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely prepared via in situ polymerization. The properties of the nanocomposites were studied using FTIR, XRD, and (1)H NMR, and the state of dispersion of GO in the PBS matrix was examined by SEM. The crystallization and melting behavior of the PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC and polarized optical microscopy. Through the mechnical testing machine and DMA, PBS/GO nanocomposites with 3% GO have shown a 43% increase in tensile strength and a 45% improvement in storage modulus. This high performance of the nanocomposites is mainly attributed to the high strength of graphene oxide combined with the strong interfacial interactions in the uniformly dispersed PBS/GO nanocomposites.

  13. Preparation of nanocomposites based on poly(Butylene Succinate) and montmorillonite organoclay via in situ polymerization

    International Nuclear Information System (INIS)

    Ferreira, Leticia P.; Moreira, Andrei N.; Souza Junior, Fernando G. de; Pinto, Jose Carlos Costa da Silva

    2014-01-01

    Nanocomposites based on poly(butylene succinate) (PBS) and organophilic montmorillonite were synthesized via in situ polymerization using three different clay compositions (4, 6 and 8 wt%). The products were characterized by several different techniques. X-ray diffraction was useful to confirm the increase of the interlayer spacing of the clay due to the presence of the polymer chains among layers. Thermal analysis indicated that the polymerization method chosen led to materials with lower thermal stability compared to the pure PBS, due to the difficulty of chain growth in the presence of the clay. Low-field NMR technique was used to assess clay dispersion in the polymer, with exfoliated structures predominating in the nanocomposites. (author)

  14. Unconventional biomasses as feedstocks for production of biofuels and succinic acid in a biorefinery concept

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi

    composition of the specific biomass feedstock, as well as which pretreatment, saccharification, fermentation and extraction techniques are used. Furthermore, integrating biological processes into the biorefinery that effectively consume CO2 will become increasingly important. Such process integration could...... significantly improve the sustainability indicators of the overall biorefinery process. In this study, unconventional lignocellulosic- and aquatic biomasses were investigated as biorefinery feedstocks. The studied biomasses were Jerusalem artichoke, industrial hemp and macroalgae species Laminaria digitata....... The chemical composition of biomasses was determined in order to demonstrate their biorefinery potential. Bioethanol and biogas along with succinic acid production were the explored bioconversion routes, while potential production of other compounds was also investigated. Differences and changes in biomass...

  15. Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery of sumatriptan succinate.

    Science.gov (United States)

    Ronnander, P; Simon, L; Spilgies, H; Koch, A; Scherr, S

    2018-03-01

    In-vitro permeation studies were conducted to assess the feasibility of fabricating dissolving-microneedle-array systems to release sumatriptan succinate. The formulations consisted mainly of the encapsulated active ingredient and a water-soluble biologically compatible polymer, polyvinylpyrrolidone (PVP), approved by the U.S. Food and Drug Administration (FDA). Tests with Franz-type diffusion cells and Göttingen minipig skins showed an increase of the transdermal flux compared to passive diffusion. A preparation, containing 30% by mass of PVP and 8.7mg sumatriptan, produced a delivery rate of 395±31μg/cm 2 h over a 7-hour period after a negligible lag time of approximately 39min. Theoretically, a 10.7cm 2 microneedle-array patch loaded with 118.8mg of the drug would provide the required plasma concentration, 72ng/mL, for nearly 7h. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Determination of vitamin E acid succinate in biodegradable microspheres by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Martínez Sancho, C; Herrero Vanrell, R; Negro, S

    2004-01-01

    A simple, rapid, and reproducible reversed-phase high-performance liquid chromatographic (HPLC) method is applied to the routine assay of vitamin E acid succinate in biodegradable microspheres. Vitamin E acid-succinate-containing poly-(D,L-lactic-co-glycolic acid) microspheres are prepared by the solvent evaporation method. The starting drug-polymer ratio is 1:10 (w/w) and the total amount of drug and polymer processed is always 440 mg. The content of vitamin E acid succinate in the microspheres is evaluated by HPLC. Chromatography is carried out isocratically at 25 degrees C +/- 0.5 degrees C on an Extrasil ODS-2 column with a mobile phase composed of methanol-water (97:3, v/v) (pH 5.6) at a flow rate of 2 mL/min and UV detection at 284 nm. Parameters such as linearity, limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery, specificity, and ruggedness are studied as reported in the International Conference on Harmonization guidelines. The stability of vitamin E acid succinate is also studied with satisfactory results after 48 h at 25 degrees C. The method is selective and linear for drug concentrations in the range 15-210 micro g/mL. The LOQ and LOD are 15 and 3 micro g/mL, respectively. The results for accuracy studies are good. Values for coefficient of variation for intra- and interassay are 2.08% and 2.32%, respectively. The mean percentage of vitamin E acid succinate in the recovery studies is 99.52% +/- 0.81%. The mean loading efficiency for microspheres is 96.53% +/- 1.31%.

  17. Gamma radiation effects on random copolymers based on poly(butylene succinate) for packaging applications

    Science.gov (United States)

    Negrin, M.; Macerata, E.; Consolati, G.; Quasso, F.; Genovese, L.; Soccio, M.; Giola, M.; Lotti, N.; Munari, A.; Mariani, M.

    2018-01-01

    Within the context of new bioplastic materials, poly(butylene succinate) (PBS) and four novel poly(butylene/thiodiethylene succinate) random copolymers (PBS-PTDGS), in sheets as well as in films, were exposed to gamma radiation, in air and in water, and their behavior along with the effect on their biodegradability was investigated. The molecular weight data obtained from gel permeation chromatography indicate that the sensibility to radiation increases with the amount of sulfur-containing co-unit (TDGS). At 200 kGy the average molecular weight of PBS film halves, while for P(BS60TDGS40) the residual molecular weight is about 20%. The calculated intermolecular crosslink Gx and scissioning Gs yields confirmed that degradation is predominant over crosslink for all the aliphatic systems. As shown by thermal analyses, gamma radiation affects the thermal properties, leading to an increased crystallinity of the systems, remarkable for PBS, and lower decomposition temperatures. Variations of crystallinity with the increasing absorbed dose were confirmed also by PALS analyses. Water contact angle measurements revealed post-irradiation wettability alterations that could positively affect polymer biodegradability. In particular, when irradiated in water at 100 kGy PBS film exhibits a water contact angle decrease of about 17%, indicating an enhanced wettability. After degradation in compost, changes in the surface morphology were observed by means of SEM and sample weight losses were determined, at different extent, according to the irradiation environment. Interestingly, after 52 days in compost PBS films, both pristine and irradiated in air at 25 kGy, showed a residual weight of about 60%, while the ones irradiated in water at 25 kGy of about 44%. Experimental data confirmed that gamma irradiation could represent a viable treatment to enhance biodegradation in compost of PBS and PBS-based copolymers.

  18. Metabolism of 14C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    International Nuclear Information System (INIS)

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-01-01

    The time-course of the metabolic fate of [ 14 C]doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus [ 14 C]doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-[1-phenyl-1-(2-pyridinyl)ethoxy] acetic acid, 1-[1-phenyl-1(2-pyridinyl)ethoxy] methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination

  19. Succinate overproduction: A case study of computational strain design using a comprehensive Escherichia coli kinetic model

    Directory of Open Access Journals (Sweden)

    Ali eKhodayari

    2015-01-01

    Full Text Available Computational strain design prediction accuracy has been the focus for many recent efforts through the selective integration of kinetic information into metabolic models. In general, kinetic model prediction quality is determined by the range and scope of genetic and/or environmental perturbations used during parameterization. In this effort, we apply the k-OptForce procedure on a kinetic model of E. coli core metabolism constructed using the Ensemble Modeling (EM method and parameterized using multiple mutant strains data under aerobic respiration with glucose as the carbon source. Minimal interventions are identified that improve succinate yield under both aerobic and anaerobic conditions to test the fidelity of model predictions under both genetic and environmental perturbations. Under aerobic condition, k-OptForce identifies interventions that match existing experimental strategies pointing at a number of unexplored flux redirections such as routing glyoxylate flux through the glycerate metabolism to improve succinate yield. Many of the identified interventions rely on the kinetic descriptions and would not be discoverable by a purely stoichiometric description. In contrast, under fermentative (anaerobic conditions, k-OptForce fails to identify key interventions including up-regulation of anaplerotic reactions and elimination of competitive fermentative products. This is due to the fact that the pathways activated under anaerobic conditions were not properly parameterized as only aerobic flux data were used in the model construction. This study shed light on the importance of condition-specific model parameterization and provides insight onto how to augment kinetic models so as to correctly respond to multiple environmental perturbations.

  20. Mechanical and thermal properties of basalt fiber reinforced poly(butylene succinate) composites

    International Nuclear Information System (INIS)

    Zhang Yihe; Yu Chunxiao; Chu, Paul K.; Lv Fengzhu; Zhang Changan; Ji Junhui; Zhang Rui; Wang Heli

    2012-01-01

    Highlights: ► Novel basalt fiber-reinforced biodegradable poly(butylene succinate) composites have been successfully fabricated with various fiber loadings. ► The tensile and flexural properties of the PBS matrix resin are improved significantly by increasing the fiber loading in the composites. ► The impact strength of the BF/PBS composite decreases with the addition fibers primarily and increases with increasing fiber loading due to energy dissipation when the fibers are pulled out. ► Heat deflection temperature tests clearly show that the HDT of the basalt fiber reinforced PBS composites is significantly higher than the HDT of the PBS resin. - Abstract: Basalt fiber (BF) reinforced poly(butylene succinate) (PBS) composites have been fabricated with different fiber contents by a injection molding method and their tensile, flexural and impact properties, as well as thermal stability have been investigated. The tensile and flexural properties of the PBS matrix resin are improved markedly by increasing the fiber contents in the composites. The values are relatively higher than the natural fiber/PP systems reported earlier by other research groups. The heat deflection temperature (HDT) and Vicat softening temperature (VST) of the composites are significantly higher than those of the neat PBS resin. Scanning electron microscopy (SEM) conducted on the fracture surfaces of the composites reveals superior interfacial linkage between the basalt fibers and PBS matrix. The results suggest that the BF/PBS composites may be a potential candidate of PP or PP composites to manufacturing some daily commodities to solve the “white pollution” in environmental management.

  1. Differences between the succinate dehydrogenase sequences of isopyrazam sensitive Zymoseptoria tritici and insensitive Fusarium graminearum strains.

    Science.gov (United States)

    Dubos, Tiphaine; Pasquali, Matias; Pogoda, Friederike; Casanova, Angèle; Hoffmann, Lucien; Beyer, Marco

    2013-01-01

    Forty-one Zymoseptoria tritici strains isolated in Luxembourg between 2009 and 2010 were highly sensitive towards the new succinate dehydrogenase inhibitor (SDHI) isopyrazam, with concentrations inhibiting fungal growth by 50% (EC50) ranging from 0.0281 to 4.53μM, whereas 41 Fusarium graminearum strains isolated in Europe and Northern America between 1969 and 2009 were insensitive with the average rate of inhibition converging towards 28% with increasing isopyrazam concentration. Seven isolates of both species covering the range of isopyrazam sensitivities observed in the present study were selected for the sequencing of the subunits B, C and D of the succinate dehydrogenase (sdh) gene. Predicted sdh amino acid sequences of subunits B, C and D were identical among F. graminearum strains. By comparing with fungal strains where resistance towards SDHIs was previously reported, three variations were unique to F. graminearum; B-D130N located in the iron-sulfur cluster [2Fe-2S], B-A275T located in the [3Fe-4S] cluster and an additional S at amino acid position 83-84 of sdhC, probably modifying structurally the ubiquinone binding site and therefore the biological activity of the fungicide. No variation was found among the Z. tritici strains in subunits B and D. Two variations were observed within the subunit C sequences of Z. tritici strains: C-N33T and C-N34T. The difference in EC50 values between Z. tritici strains with the NN and TT configuration was non-significant at P=0.289. Two outliers in the Z. tritici group with significantly higher EC50 values that were not related to mutations in the sdhB, sdhC, or sdhD were detected. The role of isopyrazam for the control of F. graminearum and Z. tritici in Luxembourg is discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Embryonic vaccines against cancer: an early history.

    Science.gov (United States)

    Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

    2009-06-01

    Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

  3. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  4. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation.

  5. Ear embryonic rabdomiosarcoma. A case report

    International Nuclear Information System (INIS)

    Cueto, L.; Canabal, A.; Blanco, A.; Sabate, J.

    2002-01-01

    A case of embryonic rabdomiosarcoma in the ear of a 5-year-old girl who initially shows clinical symptoms of otitis media. The CT reveals a dense lesion of soft tissue which shows up slightly in the right external auditory channel. Also of interest were osteolytic areas in the petrous, clivus and zygomatic arch. A hypointensive lesion with marked enhancement after Gd-DPTA injection is observed. Discussed are the imaging methods used in the diagnosis of this tumor. (Author) 10 refs

  6. The Use of Embryonic Stem Cells

    OpenAIRE

    Corkery, Padraig

    2002-01-01

    Over the past year there has been great interest, optimism and anxiety in many societies about developments in the use of embryonic stem cells (ES cells). Within the scientific community there has been debate for some time on the merits and ethical implications of using ES cells. The discussion entered the public domain inthe decisive way during the past year when there were significant changes in legislation governing the use of such cells in Britain and the United States. These changes c...

  7. Do embryonic polar bodies commit suicide?

    Science.gov (United States)

    Fabian, Dušan; Čikoš, Štefan; Rehák, Pavol; Koppel, Juraj

    2014-02-01

    The extrusion and elimination of unnecessary gametic/embryonic material is one of the key events that determines the success of further development in all living organisms. Oocytes produce the first polar body to fulfill the maturation process just before ovulation, and release the second polar body immediately after fertilization. The aim of this study was to compile a physiological overview of elimination of polar bodies during early preimplantation development in mice. Our results show that three-quarters of the first polar bodies were lost even at the zygotic stage; the 4-cell stage embryos contained only one (second) polar body, and the elimination of second polar bodies proceeded continuously during later development. Both first and second polar bodies showed several typical features of apoptosis: phosphatidylserine redistribution (observed for the first time in the first polar body), specific DNA degradation, condensed nuclear morphology, and inability to exclude cationic dye from the nucleus during the terminal stage of the apoptotic process. Caspase-3 activity was recorded only in the second polar body. From the morphological point of view, mouse polar bodies acted very similarly to damaged embryonic cells which have lost contact with their neighboring blastomeres. In conclusion, polar bodies possess all the molecular equipment necessary for triggering and executing an active suicide process. Furthermore, similarly as in dying embryonic cells, stressing external conditions (culture in vitro) might accelerate and increase the incidence of apoptotic elimination of the polar bodies in embryos.

  8. Mechanical signaling coordinates the embryonic heartbeat

    Science.gov (United States)

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  9. Binary and ternary solid-liquid phase equilibrium for the systems formed by succinic acid, urea and diethylene glycol: Determination and modelling

    International Nuclear Information System (INIS)

    Li, Yanxun; Li, Congcong; Han, Shuo; Zhao, Hongkun

    2017-01-01

    Highlights: • Solubility of succinic acid in diethylene glycol was determined. • Solubility of succinic acid + urea + diethylene glycol was determined. • Three ternary phase diagrams were constructed for the ternary system. • The ternary phase diagrams were correlated using NRTL model. - Abstract: In this work, the solid-liquid phase equilibrium for binary system of succinic acid + diethylene glycol at the temperatures ranging from (298.15 to 333.15) K and ternary system of (succinic acid + urea + diethylene glycol) at 298.15 K, 313.15 K and 333.15 K was built by using the isothermal saturation method under atmospheric pressure (101.2 kPa), and the solubilities were determined by a high-performance liquid chromatography. The solid-phases formed in the ternary system of ((succinic acid + urea + diethylene glycol)) were confirmed by Schreinemaker’s method of wet residue, which corresponded to urea, succinic acid, and adduct 2:1 urea-succinic acid (mole ratio). Three isothermal phase diagrams for the ternary system were constructed based on the measured mutual solubility. Each isothermal phase diagram included six crystallization fields, three invariant curves, two invariant points and two co-saturated points. The crystalline region of adduct 2:1 urea-succinic acid is larger than those of the other two solids. The solubility of succinic acid in diethylene glycol was correlated with the modified Apelblat equation, λh equation and NRTL model; and the mutual solubility of the ternary ((succinic acid + urea + diethylene glycol)) system was correlated and calculated by the NRTL model. The interaction parameters’ values of succinic acid-urea were acquired. The value of RMSD was 7.11 × 10 −3 for the ternary system. The calculation results had good agreement with the experiment values. Furthermore, the densities of equilibrium liquid phase were acquired. The phase diagrams and the thermodynamic model of the ternary system could provide the basis for design of

  10. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1

    DEFF Research Database (Denmark)

    Carrozzo, Rosalba; Verrigni, Daniela; Rasmussen, Magnhild

    2016-01-01

    BACKGROUND: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings...... deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently...

  11. Culture conditions for bovine embryonic stem cell-like cells isolated from blastocysts after external fertilization

    OpenAIRE

    Jin, Muzi; Wu, Asga; Dorzhin, Sergei; Yue, Qunhua; Ma, Yuzhen; Liu, Dongjun

    2012-01-01

    Although isolation and characterization of embryonic stem cells have been successful in cattle, maintenance of bovine embryonic stem cells in culture remains difficult. In this study, we compared different methods of cell passaging, feeder cell layers and medium conditions for bovine embryonic stem cell-like cells. We found that a murine embryonic fibroblast feeder layer is more suitable for embryonic stem cell-like cells than bovine embryonic fibroblasts. When murine embryonic fibroblasts we...

  12. Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish

    OpenAIRE

    Xiang, Fan; Hagos, Engda G.; Xu, Bo; Sias, Christina; Kawakami, Koichi; Burdine, Rebecca D.; Dougan, Scott T.

    2007-01-01

    In many vertebrates, extra-embryonic tissues are important signaling centers that induce and pattern the germ layers. In teleosts, the mechanism by which the extra-embryonic yolk syncytial layer (YSL) patterns the embryo is not understood. Although the Nodal-related protein Squint is expressed in the YSL, its role in this tissue is not known. We generated a series of stable transgenic lines with GFP under the control of squint genomic sequences. In all species, nodal-related genes induce thei...

  13. Beta-hydroxybutyrate increases reactive oxygen species in late but not in early postimplantation embryonic cells in vitro.

    Science.gov (United States)

    Forsberg, H; Eriksson, U J; Melefors, O; Welsh, N

    1998-02-01

    Embryonic dysmorphogenesis has been blocked by antioxidant treatment in vivo and in vitro, suggesting that embryonic excess of reactive oxygen species (ROS) has a role in the teratogenic process of diabetic pregnancy. We report that the basal levels of ROS in dispersed rat embryonic cells in vitro, as determined by fluorescence of dichlorofluorescein (DCF), were not different in cells from control and diabetic pregnancy at day 10 or 12. Beta-hydroxybutyrate (beta-HB) and succinic acid monomethyl ester both augmented DCF fluorescence in cells from day 12 embryos of normal and diabetic rats but not from day 10 embryos. Cells of day 10 and day 12 embryos from normal and diabetic rats responded to increasing glucose concentrations with a dosage-dependent alleviation of DCF fluorescence. Day 10 embryonic cells exhibited high glucose utilization rates and high pentose phosphate shunt rates, but low mitochondrial oxidation rates. Moreover, in vitro culture of embryos between gestational days 9 and 10 in the presence of 20% oxygen induced an increased and glucose-sensitive oxidation of glucose compared with embryos not cultured in vitro. At gestation day 12, however, pentose phosphate shunt rates showed a decrease, whereas the mitochondrial beta-HB oxidation rates were increased compared with those at gestation day 10. This was paralleled by a lower expression of glucose 6-phosphate dehydrogenase- and phosphofructokinase-mRNA levels at day 12 than at day 10. On the other hand, H-ferritin mRNA expression at day 12 was high compared with day 10. None of the mRNA species investigated were affected by the diabetic state of the mother. It was concluded that beta-HB-induced stimulation of mitochondrial oxidative events may lead to the generation of ROS at gestational day 12, but probably not at day 10, when only a minute amount of mitochondrial activity occurs. Thus our results do not support the notion of diabetes-induced mitochondrial oxidative stress before the development of

  14. Isolation of a primate embryonic stem cell line.

    OpenAIRE

    Thomson, J A; Kalishman, J; Golos, T G; Durning, M; Harris, C P; Becker, R A; Hearn, J P

    1995-01-01

    Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, st...

  15. Polymer blends of polylactic acid (PLA) and polybutylene succinate-adipate

    Science.gov (United States)

    Ma, Wenguang

    A series of blends consisting of polylactic acid (PLA) and aliphatic succinate polyester (BionolleRTM #3000) had been prepared and investigated. The results of mechanical property investigations showed that using 20 wt% Bionolle#3000 can significantly increase the toughness of PLA. BionolleRTM #3000 also reduces the physical aging rate of PLA so blends remain tough longer. Conversely, the stiffness of BionolleRTM #3000 can be significantly increased by blending in PLA. DMA and DSC results show that PLA/BionolleRTM 3000 blends are not thermodynamically miscible, but are compatible blends. Studies have also been performed to determine the amount and rate of aerobic biodegradation of PLA/aliphatic succinate polyester blends in biologically active composting, enzymatic, and soil environments. The changes in molecular weight, molecular structure and thermal properties in the composting environment were also studied by GPC, NMR and DSC analyses. The research results showed BionolleRTM #3000 had a high degradation rate, while PLA had a low degradation rate. PLA/BionolleRTM #3000 blends had moderate degradation rates that increased with BionolleRTM #3000 content. The melt flow behavior of PLA/BionolleRTM #3000 blends has been studied by capillary rheometry. The relationship of the blends' viscosity with their composition, shear stress, shear rate, and temperature has been investigated. Power law index and activation energy of PLA, BionolleRTM #3000 and their blends have been calculated. The experimental and theoretical data can let us understand the processability of PLA/BionolleRTM #3000 blends. A scanning electron microscope (SEM) was used to investigate the morphological structure of the PLA/BionolleRTM #3000 blends. Micrographs of the samples made from different methods (blown film, extrudate and compression molding sheet) were taken; their differences in morphology were compared. For comparison, the micrographs of blend PLA/BionolleRTM #6000 was also studied. The

  16. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-07-01

    Full Text Available Yuling Liu,1,* Yingqi Xu,2,* Minghui Wu,3 Lijiao Fan,1 Chengwei He,2 Jian-Bo Wan,2 Peng Li,2 Meiwan Chen,2 Hui Li11Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 3Department of Cell Biology and Anatomy, School of Medicine, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: Mitoxantrone (MIT is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50 value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines. In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. Keywords: F68, vitamin E

  17. Mapping of Saccharomyces cerevisiae metabolites in fermenting wheat straight-dough reveals succinic acid as pH-determining factor.

    Science.gov (United States)

    Jayaram, Vinay B; Cuyvers, Sven; Lagrain, Bert; Verstrepen, Kevin J; Delcour, Jan A; Courtin, Christophe M

    2013-01-15

    Fermenting yeast does not merely cause dough leavening, but also contributes to the bread aroma and might alter dough rheology. Here, the yeast carbon metabolism was mapped during bread straight-dough fermentation. The concentration of most metabolites changed quasi linearly as a function of fermentation time. Ethanol and carbon dioxide concentrations reached up to 60 mmol/100g flour. Interestingly, high levels of glycerol (up to 10 mmol/100g flour) and succinic acid (up to 1.6 mmol/100g flour) were produced during dough fermentation. Further tests showed that, contrary to current belief, the pH decrease in fermenting dough is primarily caused by the production of succinic acid by the yeast instead of carbon dioxide dissolution or bacterial organic acids. Together, our results provide a comprehensive overview of metabolite production during dough fermentation and yield insight into the importance of some of these metabolites for dough properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources.

    Science.gov (United States)

    Tsuge, Yota; Hasunuma, Tomohisa; Kondo, Akihiko

    2015-03-01

    Recent increasing attention to environmental issues and the shortage of oil resources have spurred political and industrial interest in the development of environmental friendly and cost-effective processes for the production of bio-based chemicals from renewable resources. Thus, microbial production of commercially important chemicals is viewed as a desirable way to replace current petrochemical production. Corynebacterium glutamicum, a Gram-positive soil bacterium, is one of the most important industrial microorganisms as a platform for the production of various amino acids. Recent research has explored the use of C. glutamicum as a potential cell factory for producing organic acids such as lactate and succinate, both of which are commercially important bulk chemicals. Here, we summarize current understanding in this field and recent metabolic engineering efforts to develop C. glutamicum strains that efficiently produce L- and D-lactate, and succinate from renewable resources.

  19. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria. Reply to a commentary.

    Science.gov (United States)

    Lehninger, A L; Reynafarje, B; Hendler, R W; Shrager, R I

    1985-11-18

    Costa, L.E., Reynafarje, B. and Lehninger, A.L. [(1984) J. Biol. Chem. 259, 4802-4811] have reported 'second-generation' measurements of the H+/O ratio approaching 8.0 for vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria. In a Commentary in this Journal [Krab, K., Soos, J. and Wikström, M. (1984) FEBS Lett. 178, 187-192] it was concluded that the measurements of Costa et al. significantly overestimated the true H+/O stoichiometry. It is shown here that the mathematical simulation on which Krab et al. based this claim is faulty and that data reported by Costa et al. had already excluded the criticism advanced by Krab et al. Also reported are new data, obtained under conditions in which the arguments of Krab et al. are irrelevant, which confirm that the H+/O ratio for succinate oxidation extrapolated to level flow is close to 8.

  20. Gold-nanoparticle-based catalysts for the oxidative esterification of 1,4-butanediol into dimethyl succinate.

    Science.gov (United States)

    Brett, Gemma L; Miedziak, Peter J; He, Qian; Knight, David W; Edwards, Jennifer K; Taylor, Stuart H; Kiely, Christopher J; Hutchings, Graham J

    2013-10-01

    The oxidation of 1,4-butanediol and butyrolactone have been investigated by using supported gold, palladium and gold-palladium nanoparticles. The products of such reactions are valuable chemical intermediates and, for example, can present a viable pathway for the sustainable production of polymers. If both gold and palladium were present, a significant synergistic effect on the selective formation of dimethyl succinate was observed. The support played a significant role in the reaction, with magnesium hydroxide leading to the highest yield of dimethyl succinate. Based on structural characterisation of the fresh and used catalysts, it was determined that small gold-palladium nanoalloys supported on a basic Mg(OH)2 support provided the best catalysts for this reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Vitamin E analogue, D-alpha tocopherol succinate, enhances x-ray induced growth delay of human adenocarcinoma cancer cell line

    International Nuclear Information System (INIS)

    Jaworska, A.; Ottesen, T.E.

    2003-01-01

    The purpose of this study was to assess the effects of d-alpha Tocopherol succinate (alpha-TS) in modifying radiation-induced viability reduction and apoptosis occurrence in the model for normal and cancer cells. Our hypothesis was that alpha-TS enhances the growth-inhibitory effect of x-irradiation in cancer cells and that the effect is more pronounced in these cells than in normal cells. Murine NIH 3T3 Swiss albino embryonic cells and HT29 human Caucasian colon adenocarcinoma cells were used in the experiments. Alpha-TS was added to the cultures 1 h prior to irradiation with doses of 2 or 5Gy of x-ray. After irradiation cells were incubated for 73 h. Trypan blue exclusion viability test and estimation of apoptosis and necrosis were made. Apoptotic and necrotic cells were counted in fluorescence microscope using fluorescence dyes: propidium iodide and Hoechst 33342. For experiments with the dose of 5 Gy at least five series of experiments were performed. At lower doses (up to approximately 25μM/ml) treatment with alpha-TS alone enhanced growth of both cell lines. At higher doses treatment with alpha-TS alone delayed the growth of the cell cultures, accompanied by 20-25% necrosis. At the concentrations higher than 25μM/mL alpha-TS alone caused growth delay of both cell cultures, being much more pronounced for the cancer cell line HT29. At the concentrations of 50 μM/mL, responsible for about 30-60% of growth delay, there was observed a synergy effect for x-rays and alpha-TS for both cell lines. The effect was more pronounced for HT29 cells (DMF=0.48 for HT29 versus DMF=0.73 for NIH 3T3). These results may confirm the views of the literature reports suggesting that use of vitamin E together with radiation could be favorable for colon cancer treatment; however, more experiments using more advanced techniques are needed

  2. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    Science.gov (United States)

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-02

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube

    NARCIS (Netherlands)

    Fijnvandraat, Arnoud C.; van Ginneken, Antoni C. G.; de Boer, Piet A. J.; Ruijter, Jan M.; Christoffels, Vincent M.; Moorman, Antoon F. M.; Lekanne Deprez, Ronald H.

    2003-01-01

    OBJECTIVE: After formation of the linear heart tube a chamber-specific program of gene expression becomes active that underlies the formation of the chamber myocardium. To assess whether this program is recapitulated in in vitro differentiated embryonic stem cells, we performed qualitative and

  4. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    Science.gov (United States)

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. Copyright © 2016. Published by Elsevier Ltd.

  5. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sultana Mehbuba Hossain

    2018-03-01

    Full Text Available Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA exhibited the highest (31.38% binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug.

  6. Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

    Directory of Open Access Journals (Sweden)

    Sungyup Jung

    2013-12-01

    Full Text Available The polymorphic phase transformation in the cocrystallization of adefovir dipivoxil (AD and succinic acid (SUC was investigated. Inspired by biological and biomimetic crystallization, polymeric additives were utilized to control the phase transformation. With addition of poly(acrylic acid, the metastable phase newly identified through the analysis of X-ray diffraction was clearly isolated from the previously reported stable form. Without additives, mixed phases were obtained even at the early stage of cocrystallization. Also, infrared spectroscopy analysis verified the alteration of the hydrogen bonding that was mainly responsible for the cocrystal formation between AD and SUC. The hydrogen bonding in the metastable phase was relatively stronger than that in the stable form, which indicated the locally strong AD/SUC coupling in the initial stage of cocrystallization followed by the overall stabilization during the phase transformation. The stronger hydrogen bonding could be responsible for the faster nucleation of the initially observed metastable phase. The present study demonstrated that the polymeric additives could function as effective regulators for the polymorph-selective cocrystallization.

  7. Synthesized cellulose/succinic anhydride as an ion exchanger. Calorimetry of divalent cations in aqueous suspension

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Julio C.P. [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil); Silva Filho, Edson C. [LIMAV, Federal University of Piaui, 64049-550 Teresina, Piaui (Brazil); Santana, Sirlane A.A. [Departamento de Quimica/CCET, Universidade Federal do Maranhao, Av. dos Portugueses S/N, Campus do Bacanga, 65080-540 Sao Luiz, MA (Brazil); Airoldi, Claudio, E-mail: airoldi@iqm.unicamp.br [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil)

    2011-09-20

    Highlights: {yields} Synthetic route based on anhydride melting point. {yields} Cellulosic biopolymer/anhydride as ion exchanger. {yields} Calorimetry of cation exchange at solid/liquid interface. {yields} Favorable thermodynamic data of exchanging process. - Abstract: A synthetic route to a biopolymer/anhydride ion exchanger adds cellulose directly to molten succinic anhydride in a quasi solvent-free procedure. An amount of 3.07 {+-} 0.05 mmol of pendant groups incorporated onto the polymeric structure, which was characterized by elemental analysis, solid state carbon NMR, infrared, X-ray and thermogravimetry. The new polysaccharide is able to exchange cations from aqueous solution through a batchwise methodology, to obtain 2.46 {+-} 0.09 mmol g{sup -1} for divalent cobalt and nickel cations. The net thermal effects obtained from calorimetric titrations gave endothermic values of 3.81 {+-} 0.02 and 2.35 {+-} 0.01 kJ mol{sup -1}. The spontaneity of this ion-exchange process reflected in negative Gibbs energies and also a positive entropic contribution. These thermodynamic data at the solid/liquid interface suggests a favorable ion exchange process for this anchored biopolymer, for cation removal from the environment.

  8. Processing Conditions, Thermal and Mechanical Responses of Stretchable Poly (Lactic Acid)/Poly (Butylene Succinate) Films.

    Science.gov (United States)

    Fortunati, Elena; Puglia, Debora; Iannoni, Antonio; Terenzi, Andrea; Kenny, José Maria; Torre, Luigi

    2017-07-16

    Poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) based films containing two different plasticizers [Acetyl Tributyl Citrate (ATBC) and isosorbide diester (ISE)] at three different contents (15 wt %, 20 wt % and 30 wt %) were produced by extrusion method. Thermal, morphological, mechanical and wettability behavior of produced materials was investigated as a function of plasticizer content. Filmature parameters were also adjusted and optimized for different formulations, in order to obtain similar thickness for different systems. Differential scanning calorimeter (DSC) results and evaluation of solubility parameter confirmed that similar miscibility was obtained for ATBC and ISE in PLA, while the two selected plasticizers resulted as not efficient for plasticization of PBS, to the limit that the PBS-30ATBC resulted as not processable. On the basis of these results, isosorbide-based plasticizer was considered a suitable agent for modification of a selected blend (PLA/PBS 80:20) and two mixing approaches were used to identify the role of ISE in the plasticization process: results from mechanical analysis confirmed that both produced PLA-PBS blends (PLA85-ISE15)-PBS20 and (PLA80-PBS20)-ISE15 could guarantee advantages in terms of deformability, with respect to the PLA80-PBS20 reference film, suggesting that the promising use of these stretchable PLA-PBS based films plasticized with isosorbide can provide novel solutions for food packaging applications.

  9. Mechanical properties and crystallization behavior of hydroxyapatite/poly(butylenes succinate) composites.

    Science.gov (United States)

    Guo, Wenmin; Zhang, Yihe; Zhang, Wei

    2013-09-01

    Biodegradable synthetic polymers have attracted much attention nowadays, and more and more researches have been done on biodegradable polymers due to their excellent mechanical properties, biocompatibility, and biodegradability. In this work, hydroxyapatite (HA) particles were melt-mixing with poly (butylenes succinate) (PBS) to prepare the material, which could be used in the biomedical industry. To develop high-performance PBS for cryogenic engineering applications, it is necessary to investigate the cryogenic mechanical properties and crystallization behavior of HA/PBS composites. Cryogenic mechanical behaviors of the composites were studied in terms of tensile and impact strength at the glass transition temperature (-30°C) and compared to their corresponding behaviors at room temperature. With the increase of HA content, the crystallization of HA/PBS composites decreased and crystallization onset temperature shifted to a lower temperature. The diameter of spherulites increased at first and decreased with a further HA content. At the same time, the crystallization rate became slow when the HA content was no more than 15wt% and increased when HA content reached 20wt%. In all, the results we obtained demonstrate that HA/PBS composites reveal a better tensile strength at -30°C in contrast to the strength at room temperature. HA particles with different amount affect the crystallization of PBS in different ways. Copyright © 2013 Wiley Periodicals, Inc.

  10. Cloning and functional analysis of succinate dehydrogenase gene PsSDHA in Phytophthora sojae.

    Science.gov (United States)

    Pan, Yuemin; Ye, Tao; Gao, Zhimou

    2017-07-01

    Succinate dehydrogenase (SDH) is one of the key enzymes of the tricarboxylic acid cycle (TCA cycle) and a proven target of fungicides for true fungi. To explore the roles of the SDHA gene in Phytophthora sojae, we first cloned PsSDHA to construct the PsSDHA silenced expression vector pHAM34-PsSDHA, and then utilized PEG to mediate the P. sojae protoplast transformation experiment. Through transformation screening, we obtained the silenced mutants A1 and A3, which have significant suppressive effect. Further study showed that the hyphae of the silenced mutant strains were shorter and more bifurcated; the growth of the silenced mutants was clearly inhibited in 10% V8 agar medium containing sodium chloride (NaCl), hydrogen peroxide (H 2 O 2 ) or Congo Red, respectively. The pathogenicity of the silenced mutants was significantly reduced compared with the wild-type strain and the mock. The results could help us better to understand the position and function of SDH in P. sojae and provide a proven target of fungicides for the oomycete. Copyright © 2017. Published by Elsevier Ltd.

  11. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    Science.gov (United States)

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  12. Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana against gastrointestinal nematodes of goats

    Directory of Open Access Journals (Sweden)

    Nathália Silva de Souza Santos

    Full Text Available ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide test. The SA induced a significant inhibition of egg hatching (P<0.05 at all concentrations tested (60 to 250µg mL-1, and the concentrations to inhibit 50% (EC50 and 90% (EC90 values (mean ± standard deviation were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.

  13. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    Energy Technology Data Exchange (ETDEWEB)

    Milione, Massimo [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pusceddu, Sara [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Gasparini, Patrizia [Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Melotti, Flavia [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Maisonneuve, Patrick [Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141 (Italy); Mazzaferro, Vincenzo [Division of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Braud, Filippo G. de [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pelosi, Giuseppe, E-mail: giuseppe.pelosi@unimi.it [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Department of Medicine, Surgery and Dentistry, Università degli Studi, Facoltà di Medicina, Milan 20122 (Italy)

    2012-08-16

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

  14. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    International Nuclear Information System (INIS)

    Milione, Massimo; Pusceddu, Sara; Gasparini, Patrizia; Melotti, Flavia; Maisonneuve, Patrick; Mazzaferro, Vincenzo; Braud, Filippo G. de; Pelosi, Giuseppe

    2012-01-01

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene

  15. Effects of Radiation on Mechanical Properties of Poly (butylene succinate) and Cassava Starch Blends

    International Nuclear Information System (INIS)

    Hemvichian, K.; Dechasasawat, K.; Kangsumrith, W.; Suwanmala, P.

    2014-01-01

    This research compared the effects of gamma and electron beam irradiation at different doses on the mechanical properties of polymer blends between poly(butylene succinate) (PBS) and cassava starch. Two types of starch were used to prepare thermoplastic starch (TPS), native cassava starch and hydrophobic starch. PBS/TPS blends were compounded at five different weight ratios using a twin-screw extruder. Mechanical properties and degradation were evaluated in comparison to unirradiated samples. Results indicated that the incorpora- tion of TPS prepared from native cassava starch decreased the mechanical properties of PBS/TPS blends, whereas the addition of TPS prepared from hydrophobic starch improved the mechanical properties of the blends. In addition, the maximum mechanical properties of PBS/TPS blends were achieved when samples were exposed to irradiation at 120 kGy. Using soil burial evaluation, the degradation rate of blends was found to increase with the addition of TPS. Therefore we have demonstrated in this study that the type of TPS and irradiation treatment can significantly alter the mechanical properties and degradation of PBS/TPS blends.

  16. The use of chemical modified chitosan with succinic anhydride in the methylene blue adsorption

    International Nuclear Information System (INIS)

    Lima, Ilauro S.; Ribeiro, Emerson S.; Airoldi, Claudio

    2006-01-01

    The adsorption capacity of a-chitosan and its modified form with succinic anhydride was compared with the traditional adsorbent active carbon by using the dye methylene blue, employed in the textile industry. The isotherms for both biopolymers were classified as SSA systems in the Giles model, more specifically in L class and subgroup 3. The dye concentration in the supernatant in the adsorption assay was determined through electronic spectroscopy. By calorimetric titration thermodynamic data of the interaction between methylene blue and the chemically modified chitosan at the solid/liquid interface were obtained. The enthalpy of the dye/chitosan interaction gave 2.47 ± 0.02 kJ mol-1 with an equilibrium constant of 7350 ± 10 and for the carbon/dye interaction this constant gave 5951 ± 8. The spontaneity of these adsorptions are reflected by the free Gibbs energies of -22.1 ± 0.4 and -21.5 ± 0.2 kJ mol-1, respectively, found for these systems. This new adsorbent derived from a natural polysaccharide is as efficient as activated carbon. However 97% of the bonded dye can be eluted by sodium chloride solution, while this same operation elutes only 42% from carbon. Chitosan is efficient in dye removal with the additional advantage of being cheap, non-toxic, biocompatible and biodegradable. (author)

  17. Preparation And Physicochemical Properties of Octenyl Succinic Anhydride (OSA) Modified Sago Starch

    International Nuclear Information System (INIS)

    Nur Farhana Zainal Abiddin; Anida Yusoff; Noorlaila Ahmad

    2016-01-01

    Starch from sago (Metroxylon sagu) was esterified with octenyl succinic anhydride (OSA) in order to regulate its shortcoming by adding amphiphilic properties. The objective of this work is to determine the physicochemical properties of native sago and OSA sago starches. The OSA sago starch was produced according to the optimum condition generated via response surface methodology (RSM) with 5.00 % OSA at pH 7.20 and a reaction time of 9.65 hours. The esterified sago starch gives a degree of substitution (DS) value of 0.012. The physicochemical properties of OSA sago starch was determined by measuring the amylose content, laser diffraction particle size analyzer, scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR). The amylose content for OSA sago starch was found to be reduced after esterification reaction. The particle size of OSA sago starch was found to increase significantly (p<0.05) compared to their native starches. Scanning electron microscopy (SEM) revealed that OSA starch developed slightly rough surface and their edges lost some definition. FT-IR spectroscopy shows that there was appearance of new absorption correspond to ester carbonyl group (1717 cm -1 ) and carboxylate RCOO- (1569 cm -1 ). This study showed that the physicochemical properties of modified starches were influenced not only by DS but also on the botanical origin of the starches. (author)

  18. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

    Science.gov (United States)

    Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

    2014-05-07

    Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

  19. Thermal and Mechanical Properties of Poly(butylene succinate Films Reinforced with Silica

    Directory of Open Access Journals (Sweden)

    Sangviroon Nanthaporn

    2015-01-01

    Full Text Available In recent year, bioplastics have become more popular resulting from the growing concerns on environmental issues and the rising fossil fuel price. However, their applications were limited by its mechanical and thermal properties. The aim of this research is thus to improve mechanical and thermal properties of PBS bioplastic films by reinforcing with silica. Due to the poor interfacial interaction between the PBS matrix and silica, glycidyl methacrylate grafted poly(butylene succinate (PBS-g-GMA was used as a compatibilizer in order to improve the interaction between bioplastic films and filler. PBS-g-GMA was prepared in a twin-screw extruder and analyzed by the FTIR spectrometer. PBS and silica were then mixed in a twin-screw extruder and processed into films by a chill-roll cast extruder. The effects of silica loading on thermal and mechanical properties of the prepared bioplastic films were investigated. It was found that the mechanical properties of PBS/silica composite films were improved when 1%wt of silica was added. However, the mechanical properties decreased with increasing silica loading due to the agglomeration of silica particles. The results also show that the silica/PBS films with PBS-g-GMA possessed improved mechanical properties over the films without the compatibilizer.

  20. Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

    Science.gov (United States)

    Kumar, M. Suresh; Aruna, P.; Ganesan, S.

    2018-03-01

    One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

  1. Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy.

    Science.gov (United States)

    Kamalov, Marat I; Đặng, Trinh; Petrova, Natalia V; Laikov, Alexander V; Luong, Duong; Akhmadishina, Rezeda A; Lukashkin, Andrei N; Abdullin, Timur I

    2018-04-01

    A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

    Science.gov (United States)

    Fattoretti, P; Bertoni-Freddari, C; Caselli, U; Paoloni, R; Meier-Ruge, W

    1998-03-16

    The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

  3. Effect of Rubberwood Content on Biodegradability of Poly(butylene succinate Biocomposites

    Directory of Open Access Journals (Sweden)

    Hemhong Anankaphong

    2015-01-01

    Full Text Available Poly(butylene succinate (PBS biocomposites incorporated with rubberwood powder (RWP were fabricated with various RWP weight fractions (i.e., 0 to 40% wt by injection moulding process. The soil burial test was employed to examine the biodegradability of such biocomposites under outdoor environment for 60 days. The physical appearance, percentage weight loss, chemical structure, and mechanical properties before and after the soil burial test were determined. Apparent changes in physical appearance of the biocomposites from optical micrographs were detected in terms of surface morphology and colour. The percentage of crystallinity of PBS/RWP biocomposites was studied by the X-ray diffraction (XRD technique, and the XRD pattern revealed a decrease in percentage of crystallinity due to enhancing RWP weight fractions. This may be attributed to a presence of rubberwood powders providing more disordered molecular chain arrangement of PBS matrix and also an agglomeration of the rubberwood powder content at greater concentration as seen in SEM micrographs. With increasing RWP weight fractions and burial time, the results exhibited a considerable change in chemical structure (essentially ester linkage due to biodegradation mechanism of PBS, relatively greater percentage weight loss, and a substantial decrease in flexural properties. Consequently, the results indicate that incorporating RWP enhances biodegradability of PBS/RWP biocomposites; that is, the biodegradation rate of biocomposites increases with increasing RWP weight fractions and burial time.

  4. Stoichiometry of mitochondrial H+ translocation coupled to succinate oxidation at level flow.

    Science.gov (United States)

    Costa, L E; Reynafarje, B; Lehninger, A L

    1984-04-25

    The mechanistic stoichiometry of vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria in the presence of a permeant cation has been determined under level flow conditions with a membraneless fast responding O2 electrode kinetically matched with a glass pH electrode. The reactions were initiated by rapid injection of O2 into the anaerobically preincubated test system under conditions in which interfering H+ backflow was minimized. The rates of O2 uptake and H+ ejection, obtained from computer-fitted regression lines, were monotonic and first order over 75% of the course of O2 consumption. Extrapolation of the observed rates to zero time, at which zero delta mu H+ and thus level flow prevails, yielded vectorial H+/O flow ratios above 7 and closely approaching 8. The mitochondria undergo no irreversible change and give identical H+/O ratios on repeated tests. In a further refinement, the lower and upper limits of the mechanistic H+/O ratio were determined to be 7.55 and 8.56, respectively, from plots of the rates of O2 uptake versus H+ ejection at increasing malonate and increasing valinomycin concentrations, respectively. It is therefore concluded that the mechanistic H+/O ratio for energy-conserving sites 2 + 3 is 8, in confirmation of earlier measurements. KCl concentration is critical for maximal observed H+/O ratios. Optimum conditions and possible errors in determination of mechanistic H+/O translocation ratios are discussed.

  5. Application of finite inverse gas chromatography in hypromellose acetate succinate-water-acetone systems.

    Science.gov (United States)

    Chiu, Sheng-Wei; Sturm, Derek R; Moser, Justin D; Danner, Ronald P

    2016-09-30

    A modification of a GC was developed to investigate both infinitely dilute and finite concentrations of solvents in polymers. Thermodynamic properties of hypromellose acetate succinate (HPMCAS-L)-acetone-water systems are important for the optimization of spray-drying processes used in pharmaceutical manufacturing of solid dispersion formulations. These properties, at temperatures below the glass transition temperature, were investigated using capillary column inverse gas chromatography (CCIGC). Water was much less soluble in the HPMCAS-L than acetone. Experiments were also conducted at infinitely dilute concentrations of one of the solvents in HPMCAS-L that was already saturated with the other solvent. Overall the partitioning of the water was not significantly affected by the presence of either water or acetone in the polymer. The acetone partition coefficient decreased as either acetone or water was added to the HPMCAS-L. A representation of the HPMCAS-L structure in terms of UNIFAC groups has been developed. With these groups, the UNIFAC-vdw-FV model did a reasonable job of predicting the phase equilibria in the binary and ternary systems. The Flory-Huggins correlation with fitted interaction parameters represented the data well. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Rheological, pasting, thermal and retrogradation properties of octenyl succinic anhydride modified potato starch

    Directory of Open Access Journals (Sweden)

    Chuin WON

    Full Text Available Abstract The objective of the present study was to investigate the rheological, pasting, and thermal properties of octenyl succinic anhydrate (OSA-modified potato starch. Potato starch was modified using different concentrations of OSA (0, 1, 3, and 5%, v/v. The degree of substitution (DS for the OSA-modified starch ranged from 0.0012 to 0.0055. The amylose leaching values of native and OSA-modified potato starch with different DS levels were in the range of 47.09-87.32%. The gel strength values of the OSA-modified starch were lower than those of native potato starch. Rapid Visco Analyzer data showed that peak, hot pasting, final and setback viscosities of the native starch decreased after OSA modification. Dynamic shear rheological tests, conducted at 4 °C, indicated that OSA-modified potato starch had weak gel-like behavior with the storage moduli (G' higher than the loss moduli (G” over most of the frequency ranges (0.63-63.8 rad·s-1.

  7. Structural control of co-continuous poly(L-lactide)/poly(butylene succinate)/clay nanocomposites.

    Science.gov (United States)

    Zhao, Li; Li, Yongjin; Shimizu, Hiroshi

    2009-04-01

    Poly(L-lactide) (PLLA)/poly(butylene succinate) (PBS) (55/45 w/w) blends with different amounts of nanoclay loadings were prepared using a specially designed high-shear extruder, HSE3000mini, which can reach a maximum shear rate of 4400 sec(-1). The resulted co-continuous structural morphologies were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM observation revealed that through the combination of various amounts of nanoclay loadings and processing under various shear conditions, the phase size of co-continuous structures of PLLA/PBS blends can be controlled over a wide range from several tens of micrometers to submicrometers. TEM observation shows that all the nanoclays are selectively dispersed in the PBS phase. We also found that clays in low-shear processed sample were mainly located at the interface of PBS phase, while in high-shear sample, the clays were mainly located inside of the PBS phase. It was considered that the dependence of nanoclay location in the PBS phase on the shear conditions, as well as the changing of the viscosity ratio of PBS and PLLA phase with different amounts of clay loading, play important roles in controlling the phase size of the co-continuous structures of PLLA/PBS blends.

  8. Structural properties of pepsin-solubilized collagen acylated by lauroyl chloride along with succinic anhydride

    International Nuclear Information System (INIS)

    Li, Conghu; Tian, Zhenhua; Liu, Wentao; Li, Guoying

    2015-01-01

    The structural properties of pepsin-solubilized calf skin collagen acylated by lauroyl chloride along with succinic anhydride were investigated in this paper. Compared with native collagen, acylated collagen retained the unique triple helix conformation, as determined by amino acid analysis, circular dichroism and X-ray diffraction. Meanwhile, the thermostability of acylated collagen using thermogravimetric measurements was enhanced as the residual weight increased by 5%. With the temperature increased from 25 to 115 °C, the secondary structure of native and acylated collagens using Fourier transform infrared spectroscopy measurements was destroyed since the intensity of the major amide bands decreased and the positions of the major amide bands shifted to lower wavenumber, respectively. Meanwhile, two-dimensional correlation spectroscopy revealed that the most sensitive bands for acylated and native collagens were amide I and II bands, respectively. Additionally, the corresponding order of the groups between native and acylated collagens was different and the correlation degree for acylated collagen was weaker than that of native collagen, suggesting that temperature played a small influence on the conformation of acylated collagen, which might be concluded that the hydrophobic interaction improved the thermostability of collagen. - Highlights: • Acylated collagen retained the unique triple helix conformation. • Acylated collagen had stronger thermostability than native collagen. • Amide I was the most sensitive band to the temperature for acylated collagen. • Amide II was the most sensitive band to the temperature for native collagen. • Auto-peak at 1680 cm −1 for acylated collagen disappeared at higher temperature

  9. Analysis of Gas Permeability Characteristics of Poly(Lactic Acid/Poly(Butylene Succinate Nanocomposites

    Directory of Open Access Journals (Sweden)

    Amita Bhatia

    2012-01-01

    Full Text Available Gas permeability and morphological properties of nanocomposites prepared by the mixing of poly(lactic acid (PLA, poly(butylene succinate (PBS, and clay was investigated. While the composition of PLA and PBS polymers was fixed as 80% and 20% by weight, respectively, for all the nanocomposites, clay contents varied from 1 to 10 wt%. From the morphological studies using both wide angle X-ray diffraction and transmission electron microscopy, the nanocomposite having 1 wt% of clay was considered to have a mixed morphology of intercalated and delaminated structure, while some clusters or agglomerated particles were detected for nanocomposites having 3 and more than 3 wt% of clay content. However, the average particle size of the dispersed PBS phase was reduced significantly from 7 μm to 30–40 nm with the addition of clay in the blend. The oxygen barrier property was improved significantly as compared to the water vapor. A model based on gas barrier property was used for the validation of the oxygen relative permeabilities of PLA/PBS/clay nanocomposites. PLA/PBS/clay nanocomposites validated the Bharadwaj model up to 3 wt% of clay contents only, while for nanocomposites of higher clay contents the Bharadwaj model was invalid due to the clusters and agglomerates formed.

  10. File list: Oth.Emb.10.AllAg.Embryonic_palates [Chip-atlas[Archive

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  1. File list: Pol.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

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  3. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  4. Pathways in pluripotency and differentiation of embryonic cells

    NARCIS (Netherlands)

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew

  5. Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

    DEFF Research Database (Denmark)

    Wright, A; Andrews, N; Bardsley, K

    2011-01-01

    The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state...... of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment....... and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range...

  6. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  7. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  8. Embryonic stem cells in pig and cattle

    DEFF Research Database (Denmark)

    Maddox-Hyttel, Poul; Wolf, Xenia Asbæk; Rasmussen, Mikkel Aabech

    2007-01-01

    Porcine and bovine cell lines derived from the inner cell mass (ICM) or epiblasts of blastocysts have been maintained over extended periods of time and characterized by morphology, identification of some stem cell markers and, in few cases, by production of chimaeric offspring. However, germ line...... transmission in chimaeras has never been obtained. Due to this incomplete characterization of the cell lines, the expression embryonic stem (ES)-like cells is presently used in pig and cattle. The ICM or epiblast can be isolated from the blastocyst by whole blastocyst culture, mechanical isolation......, or immunosurgery, and they are generally cultured on feeder cells. The resulting ES-like cells may be differentiated in vivo by chimaera and teratoma formation or in vitro by embryoid body formation and monolayer induction. It is likely that more well characterized and stable porcine and bovine ES cell lines...

  9. Sugar-Based Ethanol Biorefinery: Ethanol, Succinic Acid and By-Product Production

    Energy Technology Data Exchange (ETDEWEB)

    Donal F. Day

    2009-03-31

    The work conducted in this project is an extension of the developments itemized in DE-FG-36-04GO14236. This program is designed to help the development of a biorefinery based around a raw sugar mill, which in Louisiana is an underutilized asset. Some technical questions were answered regarding the addition of a biomass to ethanol facility to existing sugar mills. The focus of this work is on developing technology to produce ethanol and valuable by-products from bagasse. Three major areas are addressed, feedstock storage, potential by-products and the technology for producing ethanol from dilute ammonia pre-treated bagasse. Sugar mills normally store bagasse in a simple pile. During the off season there is a natural degradation of the bagasse, due to the composting action of microorganisms in the pile. This has serious implications if bagasse must be stored to operate a bagasse/biorefinery for a 300+ day operating cycle. Deterioration of the fermentables in bagasse was found to be 6.5% per month, on pile storage. This indicates that long term storage of adequate amounts of bagasse for year-round operation is probably not feasible. Lignin from pretreatment seemed to offer a potential source of valuable by-products. Although a wide range of phenolic compounds were present in the effluent from dilute ammonia pretreatment, the concentrations of each (except for benzoic acid) were too low to consider for extraction. The cellulosic hydrolysis system was modified to produce commercially recoverable quantities of cellobiose, which has a small but growing market in the food process industries. A spin-off of this led to the production of a specific oligosaccharide which appears to have both medical and commercial implications as a fungal growth inhibitor. An alternate use of sugars produced from biomass hydrolysis would be to produce succinic acid as a chemical feedstock for other conversions. An organism was developed which can do this bioconversion, but the economics of

  10. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  11. In-vitro responses of T lymphocytes to poly(butylene succinate) based biomaterials.

    Science.gov (United States)

    Toso, Montree; Patntirapong, Somying; Janvikul, Wanida; Singhatanadgit, Weerachai

    2017-04-01

    Polybutylene succinate (PBSu) and PBSu/β-tricalcium phosphate (TCP) composites are biocompatible and good candidates as bone graft materials. However, little is known about the responses of T lymphocytes to these biomaterials, which play an important role in the success of bone grafting. Activated T lymphocytes were cultured onto 32 mm diameter films (PBSu/TCP films), that had previously been placed in 6-well culture plates, for 8, 24 and 72 hours. A plastic-well culture plate was used as a control surface. The effects of PBSu-based biomaterials on T lymphocytes were examined by the using flow cytometry and reverse-transcription polymerase chain reaction. These biomaterials were non-toxic to T lymphocytes, allowing their normal DNA synthesis and activation. All materials induced only transient activation of T lymphocytes, which existed no longer than 72 hours. Proportions of four main CD4/CD8 T lymphocyte subpopulations were not affected by these biomaterials. Moreover, PBSu and PBSu/TCP significantly suppressed the expression of IL-1β and IL-6 genes by 15-35% and 21-26%, respectively. In contrast, a PBSu/TCP composite (at PBSu:TCP=60:40) significantly stimulated the expression of IL-10 and IL-13 genes by 17% and 19%, respectively. PBSu and PBSu/TCP composites were non-toxic to T lymphocytes and did not induce unfavorable responses of T lymphocytes. The tested biomaterials down-regulated key proinflammatory cytokine genes and up-regulated anti-inflammatory cytokine genes in T lymphocytes. These suggest that the biomaterials studied are good candidates as bone graft materials.

  12. CRISPR-Cas9 for the genome engineering of cyanobacteria and succinate production.

    Science.gov (United States)

    Li, Hung; Shen, Claire R; Huang, Chun-Hung; Sung, Li-Yu; Wu, Meng-Ying; Hu, Yu-Chen

    2016-11-01

    Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-guided genome editing system, yet its application for cyanobacteria engineering has yet to be reported. Here we demonstrated that CRISPR-Cas9 system can effectively trigger programmable double strand break (DSB) at the chromosome of PCC 7942 and provoke cell death. With the co-transformation of template plasmid harboring the gene cassette and flanking homology arms, CRISPR-Cas9-mediated DSB enabled precise gene integration, ameliorated the homologous recombination efficiency and allowed the use of lower amount of template DNA and shorter homology arms. The CRISPR-Cas9-induced cell death imposed selective pressure and enhanced the chance of concomitant integration of gene cassettes into all chromosomes of PCC 7942, hence accelerating the process of obtaining homogeneous and stable recombinant strains. We further explored the feasibility of engineering cyanobacteria by CRISPR-Cas9-assisted simultaneous glgc knock-out and gltA/ppc knock-in, which improved the succinate titer to 435.0±35.0μg/L, an ≈11-fold increase when compared with that of the wild-type cells. These data altogether justify the use of CRISPR-Cas9 for genome engineering and manipulation of metabolic pathways in cyanobacteria. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  13. Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Śmiga-Matuszowicz, Monika, E-mail: monika.smiga-matuszowicz@polsl.pl [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Kaczmarek, Marcin [Silesian University of Technology, Department of Biomaterials and Medical Devices Engineering, de Gaulle' a Street 66, 41-800 Zabrze (Poland); Lesiak, Marta; Sieroń, Aleksander L. [Medical University of Silesia, Department of General and Molecular Biology and Genetics, Medyków Street 18, 40-752 Katowice (Poland); Simka, Wojciech [Silesian University of Technology, Department of Chemistry, Inorganic Technology and Fuels, B. Krzywoustego Street 6, 44-100 Gliwice (Poland); Mierzwiński, Maciej; Kusz, Damian [Medical University of Silesia, Department of Orthopedics and Traumatology, Ziołowa Street 45, 40-635 Katowice (Poland)

    2014-12-01

    In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3 h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers. - Highlights: • Isosorbide-based resin was used as a component of biodegradable scaffolds. • CAC/carboxylic acid system was proven as facile method to obtain porous scaffolds. • Porous scaffolds displayed the formation of hydroxyapatite at their surfaces.

  14. Emulsion stabilizing capacity of intact starch granules modified by heat treatment or octenyl succinic anhydride.

    Science.gov (United States)

    Timgren, Anna; Rayner, Marilyn; Dejmek, Petr; Marku, Diana; Sjöö, Malin

    2013-03-01

    Starch granules are an interesting stabilizer candidate for food-grade Pickering emulsions. The stabilizing capacity of seven different intact starch granules for making oil-in-water emulsions has been the topic of this screening study. The starches were from quinoa; rice; maize; waxy varieties of rice, maize, and barley; and high-amylose maize. The starches were studied in their native state, heat treated, and modified by octenyl succinic anhydride (OSA). The effect of varying the continuous phase, both with and without salt in a phosphate buffer, was also studied. Quinoa, which had the smallest granule size, had the best capacity to stabilize oil drops, especially when the granules had been hydrophobically modified by heat treatment or by OSA. The average drop diameter (d 32) in these emulsions varied from 270 to 50 μm, where decreasing drop size and less aggregation was promoted by high starch concentration and absence of salt in the system. Of all the starch varieties studied, quinoa had the best overall emulsifying capacity, and OSA modified quinoa starch in particular. Although the size of the drops was relatively large, the drops themselves were in many instances extremely stable. In the cases where the system could stabilize droplets, even when they were so large that they were visible to the naked eye, they remained stable and the measured droplet sizes after 2 years of storage were essentially unchanged from the initial droplet size. This somewhat surprising result has been attributed to the thickness of the adsorbed starch layer providing steric stabilization. The starch particle-stabilized Pickering emulsion systems studied in this work has potential practical application such as being suitable for encapsulation of ingredients in food and pharmaceutical products.

  15. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    International Nuclear Information System (INIS)

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60 Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. (author)

  16. Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

    Directory of Open Access Journals (Sweden)

    Vaidya V

    2012-02-01

    Full Text Available Varun Vaidya, Pranav PatelCollege of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USABackground: Metoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS and metoprolol tartarate (MT. Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokinetic properties and are therefore priced differently. The primary objective of this study was to compare the overall health care expenditures of hypertensive patients on MT and MS to see if the price difference in the two preparations is offset by savings in overall expenditure.Methods: Two cohorts of patients using MT and MS were selected from the 2008 Medical Expenditure Panel Survey. Propensity score matching technique was used to balance the cohorts on various parameters such as demographic information, insurance status, and comorbidity score. Patients using MT were matched to patients using MS on the logit of propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. Multiple regression analysis was carried out to examine the association between health expenditure and type of metoprolol salt, adjusting for other covariates.Results: A total of 742 patients were found to use metoprolol (MT-388, MS-354. After propensity score matching, a total of 582 patients were left in the sample for final analysis (291 patients in each cohort. The average annual health care expenditure was slightly higher in the MT cohort; however, after adjusting for covariates in a multivariate analysis, the difference was found to be statistically insignificant (P = 0.23.Conclusion: Both the products of metoprolol were found to have similar average annual total health care expenditure; however, MS once a day has higher out

  17. Chiral separation of (d- and (l-enantiomers of doxylamine succinate in rat plasma

    Directory of Open Access Journals (Sweden)

    Tadiboyina Sirisha

    2015-12-01

    Full Text Available A selective chiral ultra fast liquid chromatography (UFLC-DAD method was developed and validated to separate and quantify the (d- and (l-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate column with a mobile phase of 20 mM ammonium bicarbonate buffer–acetonitrile (65:35 v/v with 0.15% diethylamine in the buffer at a flow rate of 1.0 mL/min. The diode array (DAD detection wavelength was set at 220 nm. The peaks obtained were identified as (d and (l by injecting the pure (d form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100–1400 ng/mL in plasma for both enantiomers (R2 > 0.995. The mean extraction recoveries were 94.5–104.7% of rat plasma. The mean relative standard deviation (RSD% of accuracy and intra-day and inter-day precision for both enantiomers were ⩽10%. The method can be further applied to determine the pharmacokinetics of (d- and (l-enantiomers in rat plasma.

  18. Influences of hyperbranched poly(amide-ester) on the properties of poly(butylene succinate)

    International Nuclear Information System (INIS)

    Run, Mingtao; Wang, Jian; Yao, Meng; Guo, Lijie; Wang, Hai-jun; Ba, Xinwu

    2013-01-01

    The polymer blends of hyperbranched poly(amide-ester) and poly(butylene succinate) (HBP/PBS) were prepared by melt-blending method. The molecular interaction within the blends, phase morphology, crystal morphology, mechanical, rheological and dynamic mechanical properties were investigated by using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), tensile machine, polarized optical microscopy, rotational rheometer and dynamic mechanical analyzer (DMA), respectively. The results suggest that PBS and HBP have a certain compatibility at amorphous state. A certain number of H-bonding was detected between PBS and HBP phases and it influences the material properties. HBP not only serves partially as a nucleating agent for the crystallization of PBS but also plays a role of plasticizer for the rheology of PBS. The glass transition temperatures of the blends slightly decrease with increasing HBP content. The proper amount of HBP (4–6%) has a reinforcement effect on the PBS matrix at glassy state. However, the blend with 10%HBP content has an improved impact strength mainly due to the plasticization effect or H-bonding effect of HBP on PBS matrix. The storage modulus is increased with increasing HBP contents, and the loss modulus is much smaller than the storage modulus in each blend at glassy state. At rubbery state the storage modulus of different samples is independent of HBP content. The complex viscosity of the melt decreases with increasing HBP content; however, the blend with 10%HBP is a special sample because of its abnormal larger complex viscosity at low shear frequencies. In addition, the melt’s elasticity behavior increases slightly with increasing HBP content. - Highlights: ► H-bonding was detected between PBS and HBP phases by FTIR. ► HBP serves partly as a nucleating agent for the crystallization of PBS. ► HBP plays a role of plasticizer for PBS. ► The blend with 10%HBP has abnormal larger complex viscosity

  19. The Effect of Nebivolol versus Metoprolol Succinate Extended Release on Asymmetric Dimethylarginine in Hypertension

    Science.gov (United States)

    Kandavar, Ramprasad; Higashi, Yusuke; Chen, Wei; Blackstock, Christopher; Vaughn, Charlotte; Sukhanov, Sergiy; Sander, Gary E.; Roffidal, Louise E.; Delafontaine, Patrice; Giles, Thomas D.

    2011-01-01

    Objectives This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. Background It was hypothesized that NEB, a β1-AR antagonist and β3-AR agonist with NO- releasing properties and MET, only a β1-AR antagonist, would have different effects on plasma ADMA concentration. Methods Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and IGF-1 were measured by ELISA kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Results Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 μmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (p < 0.05 for both), respectively, without increase in the NEB group. At week 8 augmentation index was increased in the MET group (p<0.05). IGF-1 and EPC were unchanged by treatment. Conclusions Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB. PMID:21251896

  20. Successful chemotherapy of hepatic metastases in a case of succinate dehydrogenase subunit B-related paraganglioma.

    Science.gov (United States)

    He, J; Makey, D; Fojo, T; Adams, K T; Havekes, B; Eisenhofer, G; Sullivan, P; Lai, E W; Pacak, K

    2009-10-01

    Compared to other familial pheochromocytoma/paragangliomas (PHEO/PGLs), the succinate dehydrogenase subunit B (SDHB)-related PHEO/PGLs often present with aggressive and rapidly growing metastatic lesions. Currently, there is no proven effective treatment for malignant PHEO/PGLs. Here, we present a 35-year-old white man with primary malignant abdominal extra-adrenal 11 cm paraganglioma underwent surgical successful resection. But 6 months later, he developed extensive bone, liver, and lymph nodes metastasis, which were demonstrated by computed tomography scan and the (18)F-fluorodeoxyglucose positron emission tomography. However, his (123)I-metaiodobenzylguanidine scintigraphy was negative; therefore, the cyclophosphamide, vincristine, and dacarbazine (CVD) combination chemotherapy was initiated. The combination chemotherapy was very effective showing 80% overall reduction in the liver lesions and 75% overall reduction in the retroperitoneal mass and adenopathy, and normalization of plasma catecholamine and metanephrine levels. However, plasma levels of dopamine (DA) and methoxytyramine (MTY) were only partially affected and remained consistently elevated throughout the remaining period of follow-up evaluation. Genetic testing revealed an SDHB gene mutation. Here, we present an SDHB-related PHEO/PGL patient with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to CVD therapy. We conclude patients with SDHB-related PHEO/PGLs can be particularly sensitive to CVD chemotherapy and may have an excellent outcome if this therapy is used and continued on periodic basis. The data in this patient also illustrate the importance of measuring plasma levels of DA and MTY to provide a more complete and accurate assessment of the biochemical response to therapy than provided by measurements restricted to other catecholamines and O-methylated metabolites.

  1. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  2. γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

    DEFF Research Database (Denmark)

    Daneshvar, B.; Frandsen, H.; Autrup, Herman

    1997-01-01

    proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found......Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...

  3. Function of JARID2 in bovines during early embryonic development

    Directory of Open Access Journals (Sweden)

    Yao Fu

    2017-12-01

    Full Text Available Histone lysine modifications are important epigenetic modifications in early embryonic development. JARID2, which is a member of the jumonji demethylase protein family, is a regulator of early embryonic development and can regulate mouse development and embryonic stem cell (ESC differentiation by modifying histone lysines. JARID2 can affect early embryonic development by regulating the methylation level of H3K27me3, which is closely related to normal early embryonic development. To investigate the expression pattern of JARID2 and the effect of JARID2-induced H3K27 methylation in bovine oocytes and early embryonic stages, JARID2 mRNA expression and localization were detected in bovine oocytes and early embryos via qRT-PCR and immunofluorescence in the present study. The results showed that JARID2 is highly expressed in the germinal vesicle (GV, MII, 2-cell, 4-cell, 8-cell, 16-cell and blastocyst stages, but the relative expression level of JARID2 in bovine GV oocytes is significantly lower than that at other oocyte/embryonic stages (p < 0.05, and JARID2 is expressed primarily in the nucleus. We next detected the mRNA expression levels of embryonic development-related genes (OCT4, SOX2 and c-myc after JARID2 knockdown through JARID2-2830-siRNA microinjection to investigate the molecularpathwayunderlying the regulation of H3K27me3 by JARID2 during early embryonic development. The results showed that the relative expression levels of these genes in 2-cell embryos weresignificantly higher than those in the blastocyst stage, and expression levels were significantly increased after JARID2 knockdown. In summary, the present study identified the expression pattern of JARID2 in bovine oocytes and at each early embryonic stage, and the results suggest that JARID2 plays a key role in early embryonic development by regulating the expression of OCT4, SOX2 and c-myc via modification of H3K27me3 expression. This work provides new data for improvements in the

  4. Structural studies on the actinide carboxylates. 4. The crystal and molecular structure of succinate dioxouranium(VI) monohydrate

    Energy Technology Data Exchange (ETDEWEB)

    Bombieri, G; Benetollo, F [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi; Del Pra, A; Rojas, R

    1979-01-01

    The structure of the title compound, UO/sub 2/(CH/sub 2/COO)/sub 2/.H/sub 2/O, has been determined from three-dimensional X-ray data. The crystals are orthorhombic, space group Pbcn with four formula units in a cell. The coordination geometry about the uranium atom is pentagonal bipyramidal. The uranyl ions are equatorially surrounded by one water oxygen and by four carboxylate oxygen atoms of different succinic ligands. Each ligand is shared by four uranyl units giving rise to a polymeric-like structure.

  5. Comparative analysis of succinate dehydrogenase activity in mammalian peripheral blood lymphocytes and radiomodifying action of gas hypoxis mixtures

    International Nuclear Information System (INIS)

    Gajdamakin, A.N.; Abramov, M.M.

    1987-01-01

    Radiprotective efficiency of gas hypoxic mixtures (GHM) containing 5-12% of oxygen and the rate of the reaction of succinate dehydrogenase (V SDG ) activity in peripheral blood lymphocytes upon breathing GHM were comparatively studied in rats and dogs. V SDG was 4393.5 (%O 2 ) -2,58 and 130.76 (%O 2 ) -1.42 in dogs and rats respectively. Taking into account that DMF in rats is a function of oxygen concentration in the mixture one can obtain a formula for determining a dose modifying factors (DMF) as a function of the rate of SDG activity reaction

  6. Blend membrane of succinic acid-crosslinked chitosan grafted with heparin/PVA-PEG (polyvinyl alcohol-polyethylene glycol) and its characterization

    Science.gov (United States)

    Sangkota, V. D. A.; Lusiana, R. A.; Astuti, Y.

    2018-04-01

    Crosslinking and grafting reactions are required to modify the functional groups on chitosan to increase the number of its active groups. In this study, crosslinking reaction of succinic acid and grafting reaction of heparin on chitosan were conducted to produce a membrane as a candidate of a hemodialysis membrane. The mole ratio between chitosan and succinate acids was varied to obtain the best composition of modified materials. By blending all the material composition with PVA-PEG, the blend was transformed into a membrane. The resulted membrane was then characterized by various test methods such as tests of thickness, weight, water uptake, pH resistance, tensile strength and membrane hydrophilicity. The results showed that the best composition of the membrane reached in the addition of 0.011 gram of succinic acid proved by its highest mechanical strength compared to the other membranes.

  7. Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

    Science.gov (United States)

    Przybyla, Laralynne; Voldman, Joel

    2012-07-01

    Although stem cell fate is traditionally manipulated by exogenously altering the cells' extracellular signaling environment, the endogenous autocrine and paracrine signals produced by the cells also contribute to their two essential processes: self-renewal and differentiation. Autocrine and/or paracrine signals are fundamental to both embryonic stem cell self-renewal and early embryonic development, but the nature and contributions of these signals are often difficult to fully define using conventional methods. Microfluidic techniques have been used to explore the effects of cell-secreted signals by controlling cell organization or by providing precise control over the spatial and temporal cellular microenvironment. Here we review how such techniques have begun to be adapted for use with embryonic stem cells, and we illustrate how many remaining questions in embryonic stem cell biology could be addressed using microfluidic technologies.

  8. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Jane

    2011-08-01

    Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

  9. Graphene for enhanced embryonic stem cell photo-transfection efficiency

    CSIR Research Space (South Africa)

    Mthunzi, P

    2013-04-01

    Full Text Available Due to their pluripotency properties, embryonic stem (ES) cells possess great potential in regenerative therapy. Since reported a promising tissue engineering scaffold material, here, graphene is demonstrated to significantly improve the ES cell...

  10. A toolbox to explore the mechanics of living embryonic tissues

    Science.gov (United States)

    Campàs, Otger

    2016-01-01

    The sculpting of embryonic tissues and organs into their functional morphologies involves the spatial and temporal regulation of mechanics at cell and tissue scales. Decades of in vitro work, complemented by some in vivo studies, have shown the relevance of mechanical cues in the control of cell behaviors that are central to developmental processes, but the lack of methodologies enabling precise, quantitative measurements of mechanical cues in vivo have hindered our understanding of the role of mechanics in embryonic development. Several methodologies are starting to enable quantitative studies of mechanics in vivo and in situ, opening new avenues to explore how mechanics contributes to shaping embryonic tissues and how it affects cell behavior within developing embryos. Here we review the present methodologies to study the role of mechanics in living embryonic tissues, considering their strengths and drawbacks as well as the conditions in which they are most suitable. PMID:27061360

  11. Monoclonal antibodies to carcino-embryonic antigen

    International Nuclear Information System (INIS)

    Teh, Jinghee; McKenzie, I.F.C.

    1990-01-01

    With the aim of producing new MoAb to colorectal carcinoma, immunization with cell suspensions of a fresh colonic tumour was performed and MoAb 17C4 was obtained. To produce other MoAb to colon cancer, an immunization protocol using fresh tumour, colonic cell lines and sera from patients with colonic tumours was employed and resulted in MoAb JGT-13, LK-4 and XPX-13. MoAb I-1 and O-1 were raised against sera from patients with colon cancer to produce MoAb directed against circulating tumour associated antigens. The six antibodies gave a range of reactions with normal and malignant tissues, indicating that they most likely reacted with different epitopes. Thus, apart from the reactions of 17C4, LK-4 and XPX-13 with fresh and formalin-fixed granulocytes, none of the antibodies reacted with formalin-fixed normal tissues. Despite the apparent specificity of these MoAb for colon cancer, serum testing using MoAb gave similar results to carcino-embryonic antigen polyclonal antibodies, that is the MoAb gave no obvious advantage. 9 refs., 1 tab., 3 figs

  12. The epigenomics of embryonic stem cell differentiation.

    Science.gov (United States)

    Kraushaar, Daniel C; Zhao, Keji

    2013-01-01

    Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes but must also, through gene priming, facilitate rapid and cell type-specific activation of developmental genes upon lineage commitment. Trans-generational inheritance ensures that the ESC chromatin state is stably transmitted from one generation to the next; yet at the same time, epigenetic marks are highly dynamic, reversible and responsive to extracellular cues. Once committed to differentiation, the ESC epigenome is remodeled and resolves into a more compact chromatin state. A thorough understanding of the role of chromatin modifiers in ESC fate and differentiation will be important if they are to be used for therapeutic purposes. Recent technical advances, particularly in next-generation sequencing technologies, have provided a genome-scale view of epigenetic marks and chromatin modifiers. More affordable and faster sequencing platforms have led to a comprehensive characterization of the ESC epigenome and epigenomes of differentiated cell types. In this review, we summarize and discuss the recent progress that has highlighted the central role of histone modifications, histone variants, DNA methylation and chromatin modifiers in ESC pluripotency and ESC fate. We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development.

  13. Ovarian Embryonal Carcinoma in a Dog.

    Science.gov (United States)

    Banco, B; Ferrari, R; Stefanello, D; Groppetti, D; Pecile, A; Faverzani, S; Longo, M; Zani, D D; Ravasio, G; Caniatti, M; Grieco, V

    2017-11-01

    A 17-month-old female doberman pinscher was referred for an abdominal mass and ascites. Exploratory laparotomy revealed the presence of a large neoplastic mass replacing the right ovary and associated with multiple mesovarian, mesometrial and peritoneal nodules. An ovariohysterectomy was performed. Grossly, the tumour was soft and multilocular with large areas of haemorrhage and necrosis. Microscopically, it was infiltrative and composed of round and polygonal cells arranged respectively in solid sheets or forming distorted tubular structures separated by thick fibrovascular septae. Tubules contained necrotic debris, proteinaceous fluid or small endoluminal papillary structures. Marked cellular atypia, multiple neoplastic emboli and high mitotic count were observed. Immunohistochemically, the round cells uniformly expressed placental alkaline phosphatase, while the polygonal cells arranged in tubules and papillae expressed cytokeratin (CK) AE1/AE3 and CK7. A final diagnosis of metastasizing ovarian embryonal carcinoma (EC), a primitive germ cell tumour characterized by rudimentary epithelial differentiation was made. Canine ovarian EC should be considered as a differential diagnosis for undifferentiated aggressive ovarian tumours in young dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Microglia Modulate Wiring of the Embryonic Forebrain

    Directory of Open Access Journals (Sweden)

    Paola Squarzoni

    2014-09-01

    Full Text Available Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1−/−, CR3−/−, and DAP12−/− mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.

  15. Retinol improves bovine embryonic development in vitro

    Directory of Open Access Journals (Sweden)

    Edwards J Lannett

    2004-12-01

    Full Text Available Abstract Retinoids are recognized as important regulators of vertebrate development, cell differentiation, and tissue function. Previous studies, performed both in vivo and in vitro, indicate that retinoids influence several reproductive events, including follicular development, oocyte maturation and early embryonic development. The present study evaluated in vitro effects of retinol addition to media containing maturing bovine oocytes and developing embryos in both a low oxygen atmosphere (7% and under atmospheric oxygen conditions (20%. In the first experiment, abbatoir collected bovine oocytes were matured in the presence or absence of varying concentrations of retinol. After a 22–24 hour maturation period the oocytes were fertilized, denuded 18 hours later and cultured in a modified synthetic oviductal fluid (mSOF in a humidified atmosphere at 38.5 degrees C, 5% CO2, 7% O2 and 88% N2. Cleavage rates did not differ among control and retinol-treated oocytes in all three experiments. Addition of 5 micromolar retinol to the maturation medium (IVM tended (p

  16. Targeting embryonic signaling pathways in cancer therapy.

    Science.gov (United States)

    Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

    2012-01-01

    The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

  17. ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

    OpenAIRE

    Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

    2010-01-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

  18. Generation of hematopoietic lineage cells from embryonic like cells

    Directory of Open Access Journals (Sweden)

    Gholam Reza Khamisipour

    2014-10-01

    Full Text Available Background: Epigenetic reprogramming of somatic cells into embryonic stem cells has attracted much attention, because of the potential for stem cell transplantation and compatibility with recipient. However, the therapeutic application of either nuclear transfer or nuclear fusion of somatic cell has been hindered by technical complications as well as ethical objections. Recently, a new method is reported whereby ectopic expression of embryonic specific transcription factors was shown to induce fibroblasts to become embryonic like SCs (induced pluripotent stem cells. A major limitation of this method is the use of potentially harmful genome integrating viruses such as reto- or lentivirus. The main aim of this investigation was generation of human hematopoietic stem cells from induced fibroblasts by safe adenovectors carrying embryonically active genes. Material and Methods: Isolated fibroblasts from foreskin were expanded and recombinant adenoviruses carrying human Sox2, Oct4, Klf4, cMyc genes were added to culture. After formation of embryonic like colonies and cell expansion, they were transferred to embryonic media without bFGF, and embryoid bodies were cultured on stromal and non-stromal differentiation media for 14 days. Results: Expression of CD34 gene and antigenic markers, CD34, CD38 & CD133 in stromal culture showed significant difference with non-differentiation and non-stromal media. Conclusion: These findings show high hematopoietic differentiation rate of Adeno-iPS cells in stromal culture and no need to use growth factors. While, there was no difference between non-differentiation and non-stromal media.

  19. The Deletion of the Succinate Dehydrogenase Gene KlSDH1 in Kluyveromyces lactis Does Not Lead to Respiratory Deficiency

    Science.gov (United States)

    Saliola, Michele; Bartoccioni, Paola Chiara; De Maria, Ilaria; Lodi, Tiziana; Falcone, Claudio

    2004-01-01

    We have isolated a Kluyveromyces lactis mutant unable to grow on all respiratory carbon sources with the exception of lactate. Functional complementation of this mutant led to the isolation of KlSDH1, the gene encoding the flavoprotein subunit of the succinate dehydrogenase (SDH) complex, which is essential for the aerobic utilization of carbon sources. Despite the high sequence conservation of the SDH genes in Saccharomyces cerevisiae and K. lactis, they do not have the same relevance in the metabolism of the two yeasts. In fact, unlike SDH1, KlSDH1 was highly expressed under both fermentative and nonfermentative conditions. In addition to this, but in contrast with S. cerevisiae, K. lactis strains lacking KlSDH1 were still able to grow in the presence of lactate. In these mutants, oxygen consumption was one-eighth that of the wild type in the presence of lactate and was normal with glucose and ethanol, indicating that the respiratory chain was fully functional. Northern analysis suggested that alternative pathway(s), which involves pyruvate decarboxylase and the glyoxylate cycle, could overcome the absence of SDH and allow (i) lactate utilization and (ii) the accumulation of succinate instead of ethanol during growth on glucose. PMID:15189981

  20. 99mtechnetium-dimercapto-succinic acid renal scanning and excretory urography in diagnosis of renal scars in children

    International Nuclear Information System (INIS)

    McLorie, G.A.; Aliabadi, H.; Churchill, B.M.; Ash, J.M.; Gilday, D.L.

    1989-01-01

    We compared the ability of excretory urography (without tomography) and 99mtechnetium-dimercapto-succinic acid renal scanning to detect renal scars in 32 children with primary vesicoureteral reflux. These children did not have hydronephrosis, renal failure or urinary tract obstruction. In all cases both studies were conducted within a 10-month period. The findings from both modalities were in agreement for 51 of the 64 renal units evaluated (80%). Evaluation of the excretory urogram indicated 6 cases of diffuse and 2 of focal scarring that were not detected by evaluation of the renal scan. The sensitivity of excretory urography to detect renal scars was 84% and the specificity was 83%. The 99mtechnetium-dimercapto-succinic acid renal scan showed 5 cases of focal renal scarring not detected by excretory urography. The sensitivity of the renal scan to detect renal scars was 77% and the specificity was 75%. We conclude that neither study alone could effectively replace the other for the detection of renal scars, and recommend that both be included in the initial evaluation and followup of patients with renal scars

  1. [Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after dietary succinate supplementation].

    Science.gov (United States)

    Ogneva, I V; Veselova, O M; Larina, I M

    2011-01-01

    The intensity of cell respiration of the rat m. soleus, m. gastrocnemius c.m. and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the discharge. This may be associated with the transition to the glycolytic energy path due to a decrease in the EMG-activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.

  2. Mixed ligand complexes of essential metal ions with L-glutamine and succinic acid in SLS-water mixtures

    Directory of Open Access Journals (Sweden)

    Bindu Hima Gandham

    2012-01-01

    Full Text Available Speciation of mixed ligand complexes of Co(II, Ni(II and Cu(II with L-glutamine and succinic acid was studied in varying amounts (0.0-2.5% w/v of sodium lauryl sulphate in aqueous solutions maintaining an ionic strength of 0.16 mol L-1 (NaCl at 303.0 K. Titrations were carried out in the presence of different relative concentrations (M : L : X = 1 : 2 : 2, 1 : 4 : 2, 1 : 2 : 4 of metal (M to L-glutamine (L to succinic acid (X with sodium hydroxide. Stability constants of ternary complexes were refined with MINIQUAD75. The best-fit chemical models were selected based on statistical parameters and residual analysis. The species detected were ML2X, MLX, MLXH and MLXH2 for Co(II, Ni(II and Cu(II. Extra stability of ternary complexes compared to their binary complexes was believed to be due to electrostatic interactions of the side chains of ligands, charge neutralization, chelate effect, stacking interactions and hydrogen bonding. The species distribution with pH at different compositions of SLS and plausible equilibria for the formation of species were also presented.

  3. Physical Stability of Octenyl Succinate-Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems.

    Science.gov (United States)

    Puerta-Gomez, Alex F; Castell-Perez, M Elena

    2015-06-01

    The high cost and potential toxicity of biodegradable polymers like poly(lactic-co-glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate-modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α-lactalbumin (α-L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim-Andersen-de Boer model indicated that native waxy corn had significantly (P whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%-OSA modification had a "melted" appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA-modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications. © 2015 Institute of Food Technologists®

  4. Effect of stretching on the mechanical properties in melt-spun poly(butylene succinate)/microfibrillated cellulose (MFC) nanocomposites.

    Science.gov (United States)

    Zhou, Mi; Fan, Mao; Zhao, Yongsheng; Jin, Tianxiang; Fu, Qiang

    2016-04-20

    In order to prepare poly(butylene succinate)/microfibrillated cellulose composites with high performance, in this work, microfibrillated cellulose (MFC) was first treated by acetylchloride with ball-milling to improve its interfacial compatibility with poly(butylene succinate) (PBS). Then melt stretching processing was adopted to further improve the dispersion and orientation of MFC in as-spun PBS fiber. And the effect of MFC on the crystalline structure and mechanical properties were systematically investigated for the melt-spun fibers prepared with two different draw ratios. The dispersion, alignment of the MFC and interfacial crystalline structure in the composite fibers are significantly influenced by the stretching force during the melt spinning. The possible formation of nanohybrid shish kebab (NHSK) superstructure where aligned MFC as shish and PBS lamellae as kebab has been suggested via SEM and SAXS in the composite fibers prepared at the high draw ratio. Large improvement in tensile strength has been realized at the high draw ratio due to the enhanced orientation and dispersion of MFC as well as the formation of NHSK. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  6. Succinate Dehydrogenase Activity Assay in situ with Blue Tetrazolium Salt in Crabtree-Positive Saccharomyces cerevisiae Strain

    Directory of Open Access Journals (Sweden)

    Joanna Berlowska

    2008-01-01

    Full Text Available A spectrophotometric method for determining succinate dehydrogenase (SDH activity assay in azide-sensitive yeast Saccharomyces cerevisiae has been developed. The permeabilization of yeast cells by 0.05 % digitonin permitted to study yeast enzymatic activity in situ. The reduction of blue tetrazolium salt (BT to blue tetrazolium formazan (BTf was conducted in the presence of phenazine methosulphate (PMS as an exogenous electron carrier, and sodium azide (SA as an inhibitor of cytochrome oxidase (Cyt pathway. Various factors such as type of substrate, BT concentration, cell number, temperature and time of incubation, and different Cyt pathway blockers were optimized. In earlier studies, dimethyl sulfoxide (DMSO had been selected as the best solvent for extraction of BTf from yeast cells. The linear correlation between permeabilized yeast cell density and amount of formed formazan was evidenced in the range from 9·10^7 to 5·10^8 cells per sample solution. Below the yeast cell concentration of 10^7 the absorbance values were too low to detect formazans with good precision. This standarized procedure allows the estimation of SDH activity in whole cells, depending on vitality level of yeast populations. Significant increases of succinate dehydrogenase activities were observed in sequential passages as the result of the increase of activity of the strain and adaptation to cultivation conditions.

  7. Rapid liquid–liquid extraction of thallium(III from succinate media with 2-octylaminopyridine in chloroform as the extractant

    Directory of Open Access Journals (Sweden)

    SANDIP V. MAHAMUNI

    2008-04-01

    Full Text Available A simple solvent extraction study of thallium(III was conducted. Selective and quantitative extraction of thallium(III by 2-octylaminopyridine (2-OAP in chloroform occurred from aqueous sodium succinate medium (0.0075 M at pH 3.0. Thallium(III was back extracted with acetate buffer (pH 4.63. The effect of the concentration of succinate and 2-OAP, the role of various diluents, stripping agents, loading capacity of 2-OAP, equilibrium time and aqueous:organic volume ratio on the extraction of thallium(III was studied. The stoichiometry of the extracted species was determined based on the slope analysis method and found to be 1: 2: 1 (metal:acid:extractant. The temperature dependence of the extraction equilibrium constant was also examined to estimate the apparent thermodynamic functions ∆H, ∆G and ∆S for the extraction reaction. The method is free from interference of a large number of cations and anions. The method was used for the selective extraction of thallium(III from its binary mixture with Zn(II, Cd(II, Hg(II, Bi(III, Pb(II, Se(IV, Te(IV, Sb(III, Ga(III, In(III, Al(III, Tl(I and Fe(III. The proposed method was applied to the synthetic mixtures and alloys. It is simple, selective, rapid and eco-friendly.

  8. Extraction behaviour of 2-octylaminopyridine towards lead(II) from succinate media and its separation from other toxic metals

    International Nuclear Information System (INIS)

    Mane, Chandrashekhar P.; Anuse, Mansing A.

    2008-01-01

    Liquid-liquid extraction of lead(II) from succinate media was carried out with 2-octylaminopyridine (2-OAP) in chloroform. Lead(II) was quantitatively extracted with 0.036 M 2-OAP in chloroform from 0.005-0.007 M sodium succinate when equilibrated for 5 min. Lead(II) from the organic phase was stripped with three 10 mL portions of 0.4 M acetic acid and determined titrimetrically with EDTA. The nature of extracted species was determined from the log-log plot. The optimum conditions have been evaluated based on a critical study of weak acid concentration, extractant concentration, period of equilibration and effect of diluents. The metal loading capacity of the reagent was found to be 8 mg of lead(II) with 10 mL 0.036 M of the extractant. The extraction of the lead(II) was carried out in presence of various ions to ascertain the tolerance limit of individual. Temperature dependence of the extraction equilibrium constants was examined to estimate the apparent thermodynamic functions (ΔH, ΔS and ΔG) for extraction reaction. Lead(II) was successfully separated from commonly associated metal ions such as Bi(III), Hg(II), Cr(VI), Cd(II), Zn(II), Al(III), Ca(II), Ba(II) and from binary and ternary mixtures. The method was extended for determination of lead(II) in real samples

  9. Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death.

    Science.gov (United States)

    Landry, Greg M; Dunning, Cody L; Conrad, Taylor; Hitt, Mallory J; McMartin, Kenneth E

    2013-08-29

    Diethylene glycol (DEG) is a solvent used in consumer products allowing the increased risk for consumer exposure. DEG metabolism produces two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA). DGA has been shown to be the toxic metabolite responsible for the proximal tubule cell necrosis seen in DEG poisoning. The mechanism of DGA toxicity in the proximal tubule cell is not yet known. The chemical structure of DGA is very similar to citric acid cycle intermediates. Studies were designed to assess whether its mechanism of toxicity involves disruption of cellular metabolic pathways resulting in mitochondrial dysfunction. First, DGA preferentially inhibited succinate dehydrogenase, including human kidney cell enzyme, but had no effect on other citric acid cycle enzyme activities. DGA produces a cellular ATP depletion that precedes cell death. Human proximal tubule (HPT) cells, pre-treated with increasing DGA concentrations, showed significantly decreased oxygen consumption. DGA did not increase lactate levels, indicating no effect on glycolytic activity. DGA increased reactive oxygen species (ROS) production in HPT cells in a concentration and time dependent manner. These results indicate that DGA produced proximal tubule cell dysfunction by specific inhibition of succinate dehydrogenase and oxygen consumption. Disruption of these processes results in decreased energy production and proximal tubule cell death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Influence of the course prescription of sodium succinate on functional state and general physical working ability of footballers organism during the training sessions

    Directory of Open Access Journals (Sweden)

    Олексій Володимирович Чернєв

    2015-09-01

    Full Text Available Pharmacological purpose of metabotropic preparations including burshtin acid and its derivative succinate sodium copes with the number of tasks the main of which is an activation of alternative ways of energoproduction at the work of submaximal and maximal force and preliminary training of the separate links of metabolism.The task of research is to ascertain changes that take place in functional state of sportsmen during long physical loadings and optimization of the work of cardiovascular system (CVS and prophylaxis of psychical strains with the help of succinate sodium.Methods and organization of research. There were examined 84 sportsmen to ascertain changes that take place in the functional state of sportsmen during the long physical loadings and optimization of the work of CVS with the help of succinate sodium. Examinations took place during the training sessions (TS in January, February and July 2012-2013 years.Results of research and its discussion. There was studied an efficiency of the course use of succinate sodium in footballers 100 mg 3 times a day during 14 days. Energetic supply of processes of intracellular homeostasis in erythrocytes realizes by means of ATP that is created in the process of glycolysis. According to the results of research after course prescription of succinate sodium in sportsmen the content of ATP in erythrocytes increased and an amount of ADP and AMP decreased. An improvement of general metabolic situation under an influence of succinate sodium was proved by the decrease of products of reactions of peroxidation in blood plasma of footballers.These results indicated an essential antiacidotic effect of the course use of succinate sodium by footballers after loading in anaerobic and glycolytic zone of intensity. At the same time there was ascertain in our research that the use of succinate sodium had a positive effect on the dynamics of lactate content during the processes of renewal after training in aerobic

  11. Acetate and succinate production in amoebae, helminths, diplomonads, trichomonads and trypanosomatids: common and diverse metabolic strategies used by parasitic lower eukaryotes.

    Science.gov (United States)

    Bringaud, F; Ebikeme, C; Boshart, M

    2010-08-01

    Parasites that often grow anaerobically in their hosts have adopted a fermentative strategy relying on the production of partially oxidized end products, including lactate, glycerol, ethanol, succinate and acetate. This review focuses on recent progress in understanding acetate production in protist parasites, such as amoebae, diplomonads, trichomonads, trypanosomatids and in the metazoan parasites helminths, as well as the succinate production pathway(s) present in some of them. We also describe the unconventional organisation of the tricarboxylic acid cycle associated with the fermentative strategy adopted by the procyclic trypanosomes, which may resemble the probable structure of the primordial TCA cycle in prokaryotes.

  12. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  13. Comparison of Teratoma Formation between Embryonic Stem Cells and Parthenogenetic Embryonic Stem Cells by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Hongyan Tao

    2018-01-01

    Full Text Available With their properties of self-renewal and differentiation, embryonic stem (ES cells hold great promises for regenerative therapy. However, teratoma formation and ethical concerns of ES cells may restrict their potential clinical applications. Currently, parthenogenetic embryonic stem (pES cells have attracted the interest of researchers for its self-renewing and pluripotent differentiation while eliciting less ethic concerns. In this study, we established a model with ES and pES cells both stably transfected with a double-fusion reporter gene containing renilla luciferase (Rluc and red fluorescent protein (RFP to analyze the mechanisms of teratoma formation. Transgenic Vegfr2-luc mouse, which expresses firefly luciferase (Fluc under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc, was used to trace the growth of new blood vessel recruited by transplanted cells. Bioluminescence imaging (BLI of Rluc/Fluc provides an effective tool in estimating the growth and angiogenesis of teratoma in vivo. We found that the tumorigenesis and angiogenesis capacity of ES cells were higher than those of pES cells, in which VEGF/VEGFR2 signal pathway plays an important role. In conclusion, pES cells have the decreased potential of teratoma formation but meanwhile have similar differentiating capacity compared with ES cells. These data demonstrate that pES cells provide an alternative source for ES cells with the risk reduction of teratoma formation and without ethical controversy.

  14. Immunostaining of dissected zebrafish embryonic heart.

    Science.gov (United States)

    Yang, Jingchun; Xu, Xiaolei

    2012-01-10

    Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments

  15. Nucleosome Organization in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  16. Succinic acid production derived from carbohydrates: An energy and greenhouse gas assessment of a platform chemical toward a bio-based economy

    NARCIS (Netherlands)

    Cok, B.|info:eu-repo/dai/nl/371750679; Tsiropoulos, I.; Roes, A.L.|info:eu-repo/dai/nl/303022388; Patel, M.K.|info:eu-repo/dai/nl/18988097X

    2014-01-01

    Bio-based succinic acid has the potential to become a platform chemical, i.e. a key building block for deriving both commodity and high-value chemicals, which makes it an attractive compound in a bio-based economy. A few companies and industrial consortia have begun to develop its industrial

  17. Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Massa, H.

    2005-01-01

    Roč. 327, č. 4 (2005), s. 1024-1027 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E * alpha-tocopheryl succinate * hepatic processing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  18. Polystyrene/TiO2 composite electrospun fibers as fillers for poly(butylene succinate-co-adipate): Structure, morphology and properties

    CSIR Research Space (South Africa)

    Neppalli, R

    2014-01-01

    Full Text Available In this work, composite polystyrene/titanium dioxide (PS/TiO(sub2)) electrospun fibers were used as a reinforcement for a poly(butylene succinate-co-adipate) (PBSA) matrix. The structure, morphology, mechanical properties and degradation behavior...

  19. Effect of nanoclay loading on the thermal and mechanical properties of biodegradable Polylactide/Poly[(butylene succinate)- co-adipate] blend composites

    CSIR Research Space (South Africa)

    Ojijo, Vincent O

    2012-04-01

    Full Text Available Polylactide/poly[(butylene succinate)-co-adipate] (PLA/PBSA)-organoclay composites were prepared via melt compounding in a batch mixer. The weight ratio of PLA to PBSA was kept at 70:30, while the weight fraction of the organoclay was varied from 0...

  20. The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

    Science.gov (United States)

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

  1. The 'ventral organs' of Pycnogonida (Arthropoda are neurogenic niches of late embryonic and post-embryonic nervous system development.

    Directory of Open Access Journals (Sweden)

    Georg Brenneis

    Full Text Available Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i immunolabeling, (ii histology and (iii scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida, the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two

  2. Are there factors preventing cancer development during embryonic life

    International Nuclear Information System (INIS)

    Einhorn, L.

    1983-01-01

    On the basis of the following literature observations, a hypothesis is advanced that the development of cancer is actively inhibited during embryonic life. Although the processes of cell differentiation and proliferation are - without comparison - most pronounced during embryonic life, cancer is rarely found in the newborn and is seldom a cause of neonatal death or spontaneous abortion. Attempts to induce cancer in early-stage animal embryos by irradiation or by transplacental chemical carcinogenesis have been unsuccessful, even when exposed animals have been observed throughout their lifetime. After the period of major organogenesis, however, the embryos become susceptible to carcinogenesis. In humans, the most common embryonic tumors arise in tissues which have an unusually late ongoing development and are still partly immature at or shortly before birth. For many human embryonic tumors the survival rates are higher, and spontaneous regression more frequent, in younger children, i.e. prognosis is age-dependent. Thus, although cancer generally appears in tissues capable of proliferation and differentiation, induction of malignancy in the developmentally most active tissues seems to be beset with difficulty. One possible explanation for this paradox could be that cancer is controlled by the regulators influencing development, regulators that are most active during embryonic life. (Auth.)

  3. Endolymphatic potassium of the chicken vestibule during embryonic development.

    Science.gov (United States)

    Masetto, Sergio; Zucca, Giampiero; Bottà, Luisa; Valli, Paolo

    2005-08-01

    The endolymph fills the lumen of the inner ear membranous labyrinth. Its ionic composition is unique in vertebrates as an extracellular fluid for its high-K(+)/low-Na(+) concentration. The endolymph is actively secreted by specialized cells located in the vestibular and cochlear epithelia. We have investigated the early phases of endolymph secretion by measuring the endolymphatic K(+) concentration in the chicken vestibular system during pre-hatching development. Measurements were done by inserting K(+)-selective microelectrodes in chicken embryo ampullae dissected at different developmental stages from embryonic day 9 up to embryonic day 21 (day of hatching). We found that the K(+) concentration is low (<10mM/L) up to embryonic day 11, afterward it increases steeply to reach a plateau level of about 140 mM/L at embryonic day 19--21. We have developed a short-term in vitro model of endolymph secretion by culturing vestibular ampullae dissected from embryonic day 11 chicken embryos for a few days. The preparation reproduced a double compartment system where the luminal K(+) concentration increased along with the days of culturing. This model could be important for (1) investigating the development of cellular mechanisms contributing to endolymph homeostasis and (2) testing compounds that influence those mechanisms.

  4. Tension (re)builds: Biophysical mechanisms of embryonic wound repair.

    Science.gov (United States)

    Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

    2017-04-01

    Embryonic tissues display an outstanding ability to rapidly repair wounds. Epithelia, in particular, serve as protective layers that line internal organs and form the skin. Thus, maintenance of epithelial integrity is of utmost importance for animal survival, particularly at embryonic stages, when an immune system has not yet fully developed. Rapid embryonic repair of epithelial tissues is conserved across species, and involves the collective migration of the cells around the wound. The migratory cell behaviours associated with wound repair require the generation and transmission of mechanical forces, not only for the cells to move, but also to coordinate their movements. Here, we review the forces involved in embryonic wound repair. We discuss how different force-generating structures are assembled at the molecular level, and the mechanisms that maintain the balance between force-generating structures as wounds close. Finally, we describe the mechanisms that cells use to coordinate the generation of mechanical forces around the wound. Collective cell movements and their misregulation have been associated with defective tissue repair, developmental abnormalities and cancer metastasis. Thus, we propose that understanding the role of mechanical forces during embryonic wound closure will be crucial to develop therapeutic interventions that promote or prevent collective cell movements under pathological conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight

    Directory of Open Access Journals (Sweden)

    Sehrish Iftikhar

    2017-11-01

    Full Text Available Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.

  6. Succinate, iron chelation, and monovalent cations affect the transformation efficiency of Acinetobacter baylyi ATCC 33305 during growth in complex media.

    Science.gov (United States)

    Leong, Colleen G; Boyd, Caroline M; Roush, Kaleb S; Tenente, Ricardo; Lang, Kristine M; Lostroh, C Phoebe

    2017-10-01

    Natural transformation is the acquisition of new genetic material via the uptake of exogenous DNA by competent bacteria. Acinetobacter baylyi is model for natural transformation. Here we focus on the natural transformation of A. baylyi ATCC 33305 grown in complex media and seek environmental conditions that appreciably affect transformation efficiency. We find that the transformation efficiency for A. baylyi is a resilient characteristic that remains high under most conditions tested. We do find several distinct conditions that alter natural transformation efficiency including addition of succinate, Fe 2+ (ferrous) iron chelation, and substitution of sodium ions with potassium ones. These distinct conditions could be useful to fine tune transformation efficiency for researchers using A. baylyi as a model organism to study natural transformation.

  7. Preparation and structural characterisation of novel and versatile amphiphilic octenyl succinic anhydride-modified hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne Diane; Guillaumie, Fanny; Kontogeorgis, Georgios

    2010-01-01

    and structurally characterised by Fourier transform-infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (1H NMR). The influence of four reaction parameters on the DS of the derivatives was studied by means of an experimental design. The results showed that the OSA/HA molar ratio, the buffer......The purpose of the present study was to prepare amphiphilic hyaluronic acid (HA) derivatives and to study the influence of a selection of reaction parameters on the degree of substitution (DS) of the derivatives. Octenyl succinic anhydride (OSA)–modified HA (OSA–HA) derivatives were prepared...... (NaHCO3) concentration and their interaction had the largest influence while the HA concentration and the reaction time only had a negligible effect. According to 1H NMR the maximum DS achieved within the experimental conditions tested was 43% per disaccharide unit. Moreover optimal reaction...

  8. Effect of Anorganic Substance on Physical Properties of Poly (Butylene Succinate -co- Adipate) Irradiated by Electron Beam

    International Nuclear Information System (INIS)

    Meri Suhartini

    2004-01-01

    Poly(butylene succinate-co-adipate), PBSA were electron beam irradiated in the presence of inorganic materials. The samples gave high gel fraction by irradiation in the presence of 2% silicon dioxide and 2% carbon black. It was found that addition of carbon black (CB) was effective for improving the heat stability of the sample. This is because of three-dimensional carbon black- polymer networks. Irradiated PBSA sheets broke immediately at 110 o C with load 6.67 kgf/cm 2 , while irradiated the same sample mixed with 2% carbon black did not break at the same condition. Biodegradability of crosslinked PBSA by soil burial tests was accelerated by addition of carbon black. (author)

  9. Effect of low dose x irradiation on the succinate dehydrogenase activity of guinea pig, rat and mouse tissues

    Energy Technology Data Exchange (ETDEWEB)

    Shah, V C; Bhatavdekar, J M; Aravinda Babu, K [Gujarat Univ., Ahmedabad (India). Dept. of Zoology

    1976-07-01

    The histochemical changes in succinate dehydrogenase (SDH) were investigated in pectoralis major muscle of guinea pig, rat and mouse after level X-irradiation (72 R and 240 R) and compared with control animals. Biochemical studies were carried out on liver, kidney, muscle (pectoralis major), adrenal and spleen of these animals after low dose local X-irradiation and compared with control animals. Changes in SDH activity were studied up to 72-h post-irradiation, which shows that low dose local X-irradiation leads to increased enzymic activity. The increase in enzymic activity was remarkable in mouse tissues as compared with guinea pig and rat. Adrenals of all the three animals showed significant activation after all the doses of radiation studied. The significance of these results, with special reference to oxidative metabolism, has been discussed.

  10. Acylation Modification of Antheraea pernyi Silk Fibroin Using Succinic Anhydride and Its Effects on Enzymatic Degradation Behavior

    Directory of Open Access Journals (Sweden)

    Xiufang Li

    2013-01-01

    Full Text Available The degradation rate of tissue engineering scaffolds should match the regeneration rate of new tissues. Controlling the degradation behavior of silk fibroin is an important subject for silk-based tissue engineering scaffolds. In this study, Antheraea pernyi silk fibroin was successfully modified with succinic anhydride and then characterized by zeta potential, ninhydrin method, and FTIR. In vitro, three-dimensional scaffolds prepared with modified silk fibroin were incubated in collagenase IA solution for 18 days to evaluate the impact of acylation on the degradation behavior. The results demonstrated that the degradation rate of modified silk fibroin scaffolds was more rapid than unmodified ones. The content of the β-sheet structure in silk fibroin obviously decreased after acylation, resulting in a high degradation rate. Above all, the degradation behavior of silk fibroin scaffolds could be regulated by acylation to match the requirements of various tissues regeneration.

  11. RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

    Science.gov (United States)

    Yu, W; Sanders, B G; Kline, K

    1997-01-01

    RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

  12. The ethics of patenting human embryonic stem cells.

    Science.gov (United States)

    Chapman, Audrey R

    2009-09-01

    Just as human embryonic stem cell research has generated controversy about the uses of human embryos for research and therapeutic applications, human embryonic stem cell patents raise fundamental ethical issues. The United States Patent and Trademark Office has granted foundational patents, including a composition of matter (or product) patent to the Wisconsin Alumni Research Foundation (WARF), the University of Wisconsin-Madison's intellectual property office. In contrast, the European Patent Office rejected the same WARF patent application for ethical reasons. This article assesses the appropriateness of these patents placing the discussion in the context of the deontological and consequentialist ethical issues related to human embryonic stem cell patenting. It advocates for a patent system that explicitly takes ethical factors into account and explores options for new types of intellectual property arrangements consistent with ethical concerns.

  13. Impact of nutritional stress on early embryonic survival

    Directory of Open Access Journals (Sweden)

    Sukanta Mondal

    2015-09-01

    Full Text Available Background: Low reproductive efficiency is the most critical problem faced by the livestock industry across the globe. Early embryonic loss is one the major cause of poor reproductive efficiency resulting in delayed pregnancy, fewer calves born, reduced milk production, slower genetic progress and substantial financial loss to the beef or dairy industry. The establishment of pregnancy results from the interaction between the embryo and the dam and is the culmination of a series of events initiated with development of the follicle and gametes. Among numerous internal and external factors nutrition has the potency to alter the micro-environment of the oocyte and the embryo, making it more hostile to optimal fertilization and pre-implantation embryonic growth. Understanding the impact of nutritional stress on oocyte function, embryo development and reciprocal signaling networks between the embryo and uterus will lead to alleviation of the problems of early embryonic mortality.

  14. Ultrasonographic appearance of early embryonic mortality in buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Giuseppe Catone

    2010-01-01

    Full Text Available Embryonic mortality is one of the main causes responsible of the decline in fertility that occurs in buffaloes during periods of increasing daylight length (out sexual breeding season. Transrectal ultrasonography for pregnancy diagnosis offers some advantages over palpation per rectum: earlier diagnosis of pregnancy/non-pregnancy, determination of embryo/fetus viability, reduction of misdiagnosis, and reduction of .potential. iatrogenic embryo/fetal attrition. Non pregnant buffaloes on Day 25 after AI showed higher Resistive Index (RI (P<0.05 and Pulsatility Index (P=0.07 values, registered on CL on Days 10 after AI, compared to pregnant buffaloes. RI values were significantly higher (P=0.02 in non pregnant buffaloes also on Day 45 after AI. Colour Doppler sonography could be used to gain specific information relating to the ovarian blood flow in predicting early embryonic loss and to describe the ultrasonographic features of early embryonic death in buffaloes.

  15. PTBP1 is required for embryonic development before gastrulation.

    Science.gov (United States)

    Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A Francis; Solimena, Michele

    2011-02-17

    Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.

  16. Cell surface carbohydrate changes during embryonic and fetal skin development

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Holbrook, K; Clausen, H

    1986-01-01

    Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N-acetyllac......Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N...

  17. Differentiation of Mouse Embryonic Stem Cells into Ventral Foregut Precursors

    DEFF Research Database (Denmark)

    Rothová, Michaela; Hölzenspies, Jurriaan J; Livigni, Alessandra

    2016-01-01

    Anterior definitive endoderm (ADE), the ventral foregut precursor, is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other organs. Here, a method is described for the differentiation of mouse embryonic stem cells (mESCs) to definitive...... endoderm with pronounced anterior character. ADE-containing cultures can be produced in vitro by suspension (embryoid body) culture or in a serum-free adherent monolayer culture. ESC-derived ADE cells are committed to endodermal fates and can undergo further differentiation in vitro towards ventral foregut...

  18. The utilization of aconate and itaconate by Micrococcus sp

    Science.gov (United States)

    Cooper, R. A.; Itiaba, K.; Kornberg, H. L.

    1965-01-01

    1. An organism, identified as Micrococcus sp., was isolated by elective culture on aconate; it also grew on itaconate. 2. Washed suspensions of the aconate-grown organism readily oxidized intermediates of the tricarboxylic acid cycle, aconate and succinic semialdehyde, but not itaconate. Itaconate-grown cells oxidized tricarboxylic acid-cycle intermediates, succinic semialdehyde and itaconate, but not aconate. Succinate-grown cells oxidized neither itaconate nor aconate. 3. Extracts of aconate-grown cells catalysed the formation of succinic semialdehyde and carbon dioxide, in equimolar amounts, from aconate. In the presence of NAD or NADP, succinic semialdehyde was oxidized to succinate with concomitant reduction of the coenzyme. 4. Extracts of itaconate-grown cells catalysed the formation of pyruvate and acetyl-CoA from itaconyl-CoA. 5. Key enzymes involved in the formation of succinate from aconate, and of pyruvate and acetyl-CoA from itaconate, were distinct and inducible: their formation preceded growth on the appropriate substrate. PMID:14342240

  19. Somatic donor cell type correlates with embryonic, but not extra-embryonic, gene expression in postimplantation cloned embryos.

    Directory of Open Access Journals (Sweden)

    Ryutaro Hirasawa

    Full Text Available The great majority of embryos generated by somatic cell nuclear transfer (SCNT display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts. The embryos retrieved from the uteri were separated into embryonic (epiblast and extraembryonic (extraembryonic ectoderm and ectoplacental cone tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs (>2-fold vs. controls than did the extraembryonic tissues (P<1.0 × 10(-26. In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1-5% per embryos transferred in our laboratory, because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT.

  20. Photo-transfection of mouse embryonic stem cells with plasmid DNA using femtosecond laser pulses

    CSIR Research Space (South Africa)

    Thobakgale, Lebogang

    2017-01-01

    Full Text Available This presentation is about the photo-transfection of mouse embryonic stem cells with plasmid DNA using femtosecond laser pulses. It outlines the background on embryonic stem cells (ES) and phototransfection....

  1. Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions

    DEFF Research Database (Denmark)

    Morgani, Sophie M; Canham, Maurice A; Nichols, Jennifer

    2013-01-01

    Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought...... not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants....

  2. Ovarian activity and early embryonic development in the rusty bat ...

    African Journals Online (AJOL)

    The reproductive pattern of the female rusty bat, Pipistrellus rusticus, was investigated by means of a histological examination of the ovarian follicles as well as early embryonic development. Bats were collected from two localities in Limpopo Province. Female rusty bats are seasonal monestrous breeders, initiating ...

  3. Early Embryonic Heart Rate in Normal Pregnancies In Memory of ...

    African Journals Online (AJOL)

    To determine the appearance and development of embryonic heart rate a total of n = 317 Nigerian pregnant women were studied in the very early pregnancy from 23 – 56 days from the onset of last menstrual period (LMP). All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was ...

  4. optimization of protocol for m apical meristem of embryonic axes

    African Journals Online (AJOL)

    userpc

    The hypocotyl segments, prima were removed and embryonic axes were placed in culture bott nd Skoog basal + B5 vitamins (MSB5) fortified with 22.2µM, 26.6µM opurine (BAP) to induce multiple shoots. Elongated shoots we tion media consisting of MSB5 supplemented with low concentrati one free media promoted direct ...

  5. Phosphorylation dynamics during early differentiation of human embryonic stem cells

    NARCIS (Netherlands)

    van Hoof, D.; Munoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2009-01-01

    Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during

  6. Improved genetic manipulation of human embryonic stem cells.

    NARCIS (Netherlands)

    Braam, S.R.; Denning, C.; van den Brink, S.; Kats, P.; Hochstenbach, R.; Passier, R.; Mummery, C.L.

    2008-01-01

    Low efficiency of transfection limits the ability to genetically manipulate human embryonic stem cells (hESCs), and differences in cell derivation and culture methods require optimization of transfection protocols. We transiently transferred multiple independent hESC lines with different growth

  7. Twenty years of embryonic stem cell research in farm animals

    Science.gov (United States)

    Notable distinctions between an embryonic stem cell (ESC) and somatic cell are that the ESC can maintain an undifferentiated state indefinitely, self renew, and is pluripotent, meaning that the ESC can potentially generate cells representing all the three primordial germ layers and contribute to the...

  8. Meeting embryonic requirements of broilers throughout incubation: a review

    Directory of Open Access Journals (Sweden)

    R Molenaar

    2010-09-01

    Full Text Available During incubation of chicken embryos, environmental conditions, such as temperature, relative humidity, and CO2 concentration, must be controlled to meet embryonic requirements that change during the different phases of embryonic development. In the current review, the effects of embryo temperature, egg weight loss, and CO2 concentration on hatchability, hatchling quality, and subsequent performance are discussed from an embryonic point of view. In addition, new insights related to the incubation process are described. Several studies have shown that a constant eggshell temperature (EST of 37.5 to 38.0°C throughout incubation results in the highest hatchability, hatchling quality, and subsequent performance. Egg weight loss must be between 6.5 and 14.0% of the initial egg weight, to obtain an adequate air cell size before the embryo internally pips. An increased CO2 concentration during the developmental phase of incubation (first 10 days can accelerate embryonic development and hatchability, but the physiological mechanisms of this acceleration are not completely understood. Effects of ar increased CO2 concentration during late incubation also need further investigation. The preincubation warming profile, thermal manipulation, and in ovo feeding are new insights related to the incubation process and show that the optimal situation for the embryo during incubation highly depends on the conditions of the eggs before (storage duration and during incubation (environmental conditions and on the conditions of the chickens after hatching (environmental temperature.

  9. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Chicken embryonic stem (ES) cells are useful for producing transgenic chickens and preserving genetic material in avian species. In this study, the differentiation potential of chicken ES cells was investigated in vitro. Chicken ES cells were differentiated into osteoblasts cultured for 15 to 21 days in the induction media ...

  10. Impact of 2-bromopropane on mouse embryonic stem cells and ...

    African Journals Online (AJOL)

    This study shows that 2-BP (5 to 10 μM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no effects at treatment dosages below 5 μM. In ESC-B5 cells, 2-BP directly increased the content of reactive oxygen species (ROS), significantly increased the cytoplasmic free calcium and nitric oxide ...

  11. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Studies have shown that embryonic stem (ES) cells can be successfully differentiated into liver cells, which offer the potential unlimited cell source for a variety of end-stage liver disease. In our study, in order to induce mouse ES cells to differentiate into hepatocyte-like cells under chemically defined conditions, ES cells ...

  12. Derivation of the human embryonic stem cell line RCM1

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-03-01

    Full Text Available The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

  13. Ultrastructure, development, and homology of insect embryonic cuticles

    Czech Academy of Sciences Publication Activity Database

    Konopová, Barbora; Zrzavý, Jan

    2005-01-01

    Roč. 264, č. 3 (2005), s. 339-362 ISSN 0362-2525 R&D Projects: GA ČR(CZ) GD206/03/H034 Institutional research plan: CEZ:AV0Z50070508 Keywords : embryonic development * cuticle * metamorphosis Subject RIV: EA - Cell Biology Impact factor: 1.421, year: 2005

  14. On the phylogeny of the embryonic apparatus of some Foraminifera

    NARCIS (Netherlands)

    Cosijn, A.J.

    1942-01-01

    In the following pages data will be given about the size of the megalospheric embryonic apparatus, and of the size of the shell, of some Foraminifera. By comparing these data for a certain species from different samples, the relative ages of which are known, it will be possible, to get an insight

  15. Effects of Exogenous Oxytocin on Embryonic Survival in Cows

    Directory of Open Access Journals (Sweden)

    A. Yildiz

    2006-01-01

    Full Text Available The aim of this study was to evaluate the effect of oxytocin on embryonic survival in dairy cows. Pregnancy was verified using the early pregnancy factor (EPF activity on Day 4 after artificial insemination (AI. Pregnant cows were randomly allotted to two groups: treated (n = 8 and control (n = 8. Oxytocin (100 IU, 5 ml, DIF Turkey was administered twice daily by intravenous injections to treated cows and sterile saline (5 ml to control cows immediately before milking on days 4 to 7 after AI. Blood samples were taken via jugular vein every day from day 4 to 8 and every other day until Day 20 following insemination to evaluate the effect of oxytocin on embryonic survival. The embryonic loss was diagnosed in 3 of the 8 cows treated with oxytocin, and embryonic survival rate was 62.5% in this group versus 87.5% in controls. Short cycles occurred in 37.5% of oxytocin-treated cows. At the same time their serum progesterone concentrations rose more slowly than in controls. It was concluded that cows administered oxytocin on days 4 to 7 after insemination are at a higher risk of pregnancy loss.

  16. Alterations to embryonic serotonin change aggression and fearfulness

    Science.gov (United States)

    Prenatal environment, including maternal hormones, affects the development of the serotonin (5-HT) system, with long-lasting effects on mood and behavioral exhibition in children and adults. The chicken provides a unique animal model to study the effects of embryonic development on childhood and ado...

  17. Innovative virtual reality measurements for embryonic growth and development

    NARCIS (Netherlands)

    C.M. Verwoerd-Dikkeboom (Christine); A.H.J. Koning (Anton); W.C.J. Hop (Wim); P.J. van der Spek (Peter); N. Exalto (Niek); R.P.M. Steegers-Theunissen (Régine)

    2010-01-01

    textabstractBackground Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. Methods In a longitudinal study, three-dimensional

  18. Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2014-12-01

    The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

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    Lifescience Database Archive (English)

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  14. File list: Pol.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.50.AllAg.Embryonic_heart.bed ...

  15. File list: ALL.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX1437350...RX1437340,SRX1437357,SRX1437344,SRX1437336,SRX1437356,SRX377685,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.Embryonic_heart.bed ...

  16. File list: InP.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX967654,SRX377683,SRX185886,SRX698167,SRX244285,SRX377687,SRX377685 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.Embryonic_heart.bed ...

  17. File list: His.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.20.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062969,SRX106...2968,SRX1062966,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.20.AllAg.embryonic_skin.bed ...

  18. File list: ALL.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062969,S...RX1062968,SRX1062966,SRX1062967,SRX1062972,SRX1062971,SRX1062970,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.embryonic_skin.bed ...

  19. File list: His.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.50.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062969,SRX106...2968,SRX1062966,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.50.AllAg.embryonic_skin.bed ...

  20. File list: His.Emb.05.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.05.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062965,SRX106...2966,SRX1062968,SRX1062969 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.05.AllAg.embryonic_skin.bed ...

  1. File list: InP.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062967,...SRX1062972 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.embryonic_skin.bed ...

  2. File list: InP.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062972,...SRX1062967 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.embryonic_skin.bed ...

  3. File list: ALL.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062969,S...RX1062968,SRX1062966,SRX1062971,SRX1062967,SRX1062972,SRX1062965,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.embryonic_skin.bed ...

  4. File list: Oth.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.embryonic_skin.bed ...

  5. File list: ALL.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062972,S...RX1062971,SRX1062966,SRX1062969,SRX1062968,SRX1062965,SRX1062967,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.embryonic_skin.bed ...

  6. File list: Oth.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.20.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.embryonic_skin.bed ...

  7. File list: Oth.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.embryonic_skin.bed ...

  8. File list: Oth.Emb.05.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.embryonic_skin.bed ...

  9. File list: InP.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062967,...SRX1062972 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.embryonic_skin.bed ...

  10. File list: InP.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX143735...RX377685,SRX377687,SRX967654,SRX077933,SRX377683,SRX967652,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_heart.bed ...

  11. File list: ALL.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX112938,...7,SRX967654,SRX967653,SRX1100404,SRX244285,SRX112936,SRX1100405,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Embryonic_heart.bed ...

  12. File list: Pol.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Embryonic_heart.bed ...

  13. File list: Unc.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.20.AllAg.Embryonic_heart mm9 Unclassified Embryo Embryonic heart SRX248279,...SRX190172,SRX112936,SRX022494 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.20.AllAg.Embryonic_heart.bed ...

  14. File list: NoD.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.10.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.10.AllAg.Embryonic_heart.bed ...

  15. File list: ALL.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.05.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX967652,...4,SRX1437348,SRX377683,SRX377685,SRX377687,SRX190172,SRX244285,SRX1100405,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.05.AllAg.Embryonic_heart.bed ...

  16. File list: InP.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX077933,SRX377683,SRX377685,SRX377681,SRX377687,SRX967654,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Embryonic_heart.bed ...

  17. File list: ALL.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX112938,...52,SRX967653,SRX112936,SRX1100405,SRX112937,SRX185857,SRX244285,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Embryonic_heart.bed ...

  18. File list: Pol.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.10.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.10.AllAg.Embryonic_heart.bed ...

  19. File list: Pol.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Embryonic_heart.bed ...

  20. File list: Unc.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.50.AllAg.Embryonic_heart mm9 Unclassified Embryo Embryonic heart SRX248279,...SRX190172,SRX112936,SRX022494 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.50.AllAg.Embryonic_heart.bed ...

  1. File list: InP.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.05.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX698167,SRX377681,SRX967654,SRX377683,SRX377685,SRX377687,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.05.AllAg.Embryonic_heart.bed ...

  2. File list: NoD.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Embryonic_heart.bed ...

  3. File list: NoD.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...04,SRX1100402,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.05.AllAg.Embryonic_heart.bed ...

  4. File list: NoD.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.50.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.50.AllAg.Embryonic_heart.bed ...

  5. Childhood Central Nervous System Embryonal Tumors (PDQ®)—Health Professional Version

    Science.gov (United States)

    Pediatric CNS embryonal tumors are a collection of heterogeneous lesions (medulloblastoma, and nonmedulloblastoma). Molecular genetic studies are used to classify embryonal tumors, stratify risk, and plan treatment. Get detailed information about tumor biology, diagnosis, prognosis, and treatment of untreated and recurrent CNS embryonal tumors in this summary for clinicians.

  6. File list: His.Emb.10.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.10.AllAg.Embryonic_trunk mm9 Histone Embryo Embryonic trunk SRX093317,SRX09...3316 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.10.AllAg.Embryonic_trunk.bed ...

  7. File list: DNS.Emb.10.AllAg.Embryonic_limb [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.10.AllAg.Embryonic_limb mm9 DNase-seq Embryo Embryonic limb SRX191032,SRX19...1037 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.10.AllAg.Embryonic_limb.bed ...

  8. File list: InP.Emb.50.AllAg.Embryonic_eye [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_eye mm9 Input control Embryo Embryonic eye SRX804057,SRX...804055 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_eye.bed ...

  9. File list: InP.Emb.50.AllAg.Embryonic_limb [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_limb mm9 Input control Embryo Embryonic limb SRX804047,S...69,SRX083262,SRX083272 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_limb.bed ...

  10. File list: InP.Emb.50.AllAg.Embryonic_flank [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_flank mm9 Input control Embryo Embryonic flank SRX804059... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_flank.bed ...

  11. File list: NoD.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Embryonic_trunk mm9 No description Embryo Embryonic trunk ERX40226...7,ERX402264 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Embryonic_trunk.bed ...

  12. File list: Oth.Emb.05.AllAg.Embryonic_face [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Embryonic_face mm9 TFs and others Embryo Embryonic face SRX330164,...SRX139877 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_face.bed ...

  13. File list: DNS.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.20.AllAg.Embryonic_trunk mm9 DNase-seq Embryo Embryonic trunk SRX191030 htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Embryonic_trunk.bed ...

  14. File list: His.Emb.50.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.50.AllAg.Embryonic_trunk mm9 Histone Embryo Embryonic trunk SRX093317,SRX09...3316 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.50.AllAg.Embryonic_trunk.bed ...

  15. Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification

    NARCIS (Netherlands)

    Dartel, van D.A.M.; Schulpen, S.H.; Theunissen, P.T.; Bunschoten, A.; Piersma, A.H.; Keijer, J.

    2014-01-01

    Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in

  16. File list: ALL.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87023,SRX287022,SRX287021,SRX287020,SRX287016,SRX287026,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Embryonic_pancreas.bed ...

  17. File list: Oth.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287017,SRX287023,SRX287022,SRX287021,SRX287020,SRX287016 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_pancreas.bed ...

  18. File list: ALL.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87021,SRX287020,SRX287023,SRX287016,SRX287022,SRX287026,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Embryonic_pancreas.bed ...

  19. File list: Oth.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287021,SRX287020,SRX287023,SRX287016,SRX287022,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.Embryonic_pancreas.bed ...

  20. File list: InP.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.05.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.05.AllAg.Embryonic_pancreas.bed ...

  1. File list: InP.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_pancreas.bed ...

  2. File list: NoD.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.10.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.10.AllAg.Embryonic_pancreas.bed ...

  3. File list: InP.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.Embryonic_pancreas.bed ...

  4. File list: InP.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Embryonic_pancreas.bed ...

  5. File list: NoD.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.05.AllAg.Embryonic_pancreas.bed ...

  6. File list: Oth.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.20.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287023,SRX287022,SRX287021,SRX287020,SRX287016,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.Embryonic_pancreas.bed ...

  7. File list: Oth.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287023,SRX287022,SRX287020,SRX287021,SRX287016,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.Embryonic_pancreas.bed ...

  8. File list: NoD.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Embryonic_pancreas.bed ...

  9. File list: ALL.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87023,SRX287022,SRX287020,SRX287021,SRX287016,SRX287017,SRX287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.Embryonic_pancreas.bed ...

  10. File list: ALL.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.05.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87017,SRX287023,SRX287022,SRX287021,SRX287026,SRX287020,SRX287016 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.05.AllAg.Embryonic_pancreas.bed ...

  11. File list: NoD.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.50.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.50.AllAg.Embryonic_pancreas.bed ...

  12. Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Yin Liu

    Full Text Available Nitric oxide synthase-3 (NOS3 has recently been shown to promote endothelial-to-mesenchymal transition (EndMT in the developing atrioventricular (AV canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT and NOS3(-/- mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3(-/- compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3(-/- mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1(+ cells in the AV cushion were decreased in NOS3(-/- compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ, bone morphogenetic protein (BMP2 and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3(-/- compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.

  13. Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

    Science.gov (United States)

    Peoples, Jessica N; Taylor, David G; Katchman, Alexander N; Ebert, Steven N

    2018-01-22

    Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh -/- ) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca 2+ ] i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca 2+ ] i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, I Ca,L , in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through I Ca,L and that aberrant calcium signaling does not likely contribute

  14. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  15. Proteomic Analysis of Chicken Skeletal Muscle during Embryonic Development

    Directory of Open Access Journals (Sweden)

    Hongjia Ouyang

    2017-05-01

    Full Text Available Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken. To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ in leg muscle tissues of female Xinghua chicken at embryonic age (E 11, E16, and 1-day post hatch (D1. We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05. There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group. Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation. Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level. The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways. The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated. These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.

  16. Peculiarities of Embryonic and Post-Embryonic Development of Оesophagostomum dentatum (Nematoda, Strongylidae Larvae Cultured in Vitro

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    Yevstafieva V. А.

    2017-02-01

    Full Text Available Morphometric peculiarities of the development of Оesophagostomum dentatum Rudolphi, 1803 from egg to infective larva were studied under laboratory conditions at various temperatures. The determined optimum temperature for embryonic and post-embryonic development of О. dentatum larvae from domestic pig (Sus scrofa domesticus Linnaeus, 1758 is 22 °С. At this temperature, 81 % of larvae develop to the third stage (L3 on the 10th day. Temperatures of 24 °С and 20 °С are less favorable for the development of the nematode, at those temperatures only 67 and 63 % of larvae, respectively, reached infective stage by the 10th day of cultivation. Embryonic development of О. dentatum eggs is characterized by their lengthening (by 8.87-9.50 %, р < 0.01 and widening (by 6.77-9.35 %, р < 0.05-0.01, and post-embryonic larval development is associated with lengthening (by 4.59-17.33 %, р < 0.01-0.001.

  17. Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

    OpenAIRE

    Im-Sook Song; Jin-Sun Cha; Min-Koo Choi

    2016-01-01

    The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improv...

  18. Improvement of Protective Properties of Top Coatings Applied on Zinc-Rich Primer by 3-Aminopropyl-Triethoxysilan and 2-(Benzothialylthio) Succinic acid

    International Nuclear Information System (INIS)

    Truc, Trinh Anh; Hang, Thi Xuan; Oanh, Vu Ke; Dung, Nguyen Tuan

    2004-01-01

    Corrosion resistance of coating system consisting of zinc-rich primer (ZRP) and topcoat based on polyurethane resin with the presence of 3-aminopropyl-triethoxysilan (APS) and 2-(benzothialylthio) succinic acid (BSA) was studied by electrochemical impedance and wet adhesion. The interface metal/primer/topcoat was analyzed by scanning electronic microscopy. It was found that the presence of APS and BSA improved adhesion and barrier property of the topcoats

  19. Isotopomer profiling of Leishmania mexicana promastigotes reveals important roles for succinate fermentation and aspartate uptake in tricarboxylic acid cycle (TCA) anaplerosis, glutamate synthesis, and growth.

    Science.gov (United States)

    Saunders, Eleanor C; Ng, William W; Chambers, Jennifer M; Ng, Milica; Naderer, Thomas; Krömer, Jens O; Likic, Vladimir A; McConville, Malcolm J

    2011-08-05

    Leishmania parasites proliferate within nutritionally complex niches in their sandfly vector and mammalian hosts. However, the extent to which these parasites utilize different carbon sources remains poorly defined. In this study, we have followed the incorporation of various (13)C-labeled carbon sources into the intracellular and secreted metabolites of Leishmania mexicana promastigotes using gas chromatography-mass spectrometry and (13)C NMR. [U-(13)C]Glucose was rapidly incorporated into intermediates in glycolysis, the pentose phosphate pathway, and the cytoplasmic carbohydrate reserve material, mannogen. Enzymes involved in the upper glycolytic pathway are sequestered within glycosomes, and the ATP and NAD(+) consumed by these reactions were primarily regenerated by the fermentation of phosphoenolpyruvate to succinate (glycosomal succinate fermentation). The initiating enzyme in this pathway, phosphoenolpyruvate carboxykinase, was exclusively localized to the glycosome. Although some of the glycosomal succinate was secreted, most of the C4 dicarboxylic acids generated during succinate fermentation were further catabolized in the TCA cycle. A high rate of TCA cycle anaplerosis was further suggested by measurement of [U-(13)C]aspartate and [U-(13)C]alanine uptake and catabolism. TCA cycle anaplerosis is apparently needed to sustain glutamate production under standard culture conditions. Specifically, inhibition of mitochondrial aconitase with sodium fluoroacetate resulted in the rapid depletion of intracellular glutamate pools and growth arrest. Addition of high concentrations of exogenous glutamate alleviated this growth arrest. These findings suggest that glycosomal and mitochondrial metabolism in Leishmania promastigotes is tightly coupled and that, in contrast to the situation in some other trypanosomatid parasites, the TCA cycle has crucial anabolic functions.

  20. INFLUENCE OF METOPROLOL SUCCINATE ON REGULATORY AND ADAPTIVE STATUS OF PATIENTS WITH CHRONIC HEART FAILURE FUNCTIONAL CLASS I. RESULTS OF NOT COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    V. G. Tregubov

    2011-01-01

    Full Text Available Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS of patients with сhronic heart failure (CHF functional class (FC I and arterial hypertension (HT I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas. Cardio-respiratory synchronism (CRS test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р<0.05, and duration of CRS development on the minimal boundary from 18.8±2.2 to 14.3±1.2 сardiocycles (in 24%; р<0,05; RAS index considerably did not change, myocardium structure, exercise tolerance and neuro-humoral activity. Metoprolol therapy only moderately improved left ventricle diastolic function. Conclusion. Metoprolol succinate therapy has no significant effect on RAS of patients with CHF FC I and HT I-II stages.

  1. Development of a validated HPLC method for the quantitative determination of trelagliptin succinate and its related substances in pharmaceutical dosage forms.

    Science.gov (United States)

    Luo, Zhiqiang; Chen, Xinjing; Wang, Guopeng; Du, Zhibo; Ma, Xiaoyun; Wang, Hao; Yu, Guohua; Liu, Aoxue; Li, Mengwei; Peng, Wei; Liu, Yang

    2018-01-01

    Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is used as a new long-acting drug for once-weekly treatment of type 2 diabetes mellitus (DM). In the present study, a rapid, sensitive and accurate high-performance liquid chromatography (HPLC) method was developed and validated for separation and determination of trelagliptin succinate and its eight potential process-related impurities. The chromatographic separation was achieved on a Waters Xselect CSH™ C 18 (250mm×4.6mm, 5.0μm) column. The mobile phases comprised of 0.05% trifluoroacetic acid in water as well as acetonitrile containing 0.05% trifluoroacetic acid. The compounds of interest were monitored at 224nm and 275nm. The stability-indicating capability of this method was evaluated by performing stress test studies. Trelagliptin succinate was found to degrade significantly in acid, base, oxidative and thermal stress conditions and only stable in photolytic degradation condition. The degradation products were well resolved from the main peak and its impurities. In addition, the major degradation impurities formed under acid, base, oxidative and thermal stress conditions were characterized by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). The method was validated to fulfill International Conference on Harmonisation (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The developed method in this study could be applied for routine quality control analysis of trelagliptin succinate tablets, since there is no official monograph. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. EFFECT OF SUBSTITUTION POSITION OF HYDROXY GROUP AT BENZOIC ACID ON THE LUMINESCENT AND DEGRADATION PROPERTIES OF POLY[DI(CARBOXYPHENYL) SUCCINATE-co-SEBACIC ANHYDRIDE]S

    Institute of Scientific and Technical Information of China (English)

    Jun Fan; Hong-liang Jiang; Kang-jie Zhu

    2007-01-01

    In this work, two new diacids, di(m-carboxyphenyl) succinate (m-dCPS) and di(o-carboxyphenyl) succinate (o-dCPS), were synthesized by reaction of m-, o-hydroxy benzoic acid with succinic chloride, respectively. Their corresponding copolymers with sebacic acid (SA), P(m-dCPS:SA) and P(o-dCPS:SA), were prepared by melt copolycondensation and characterized by NMR, UV and DSC methods. Compared with inherently fluorescent poly[di(p-carboxyphenyl) succinateco-sebacic anhydride] (P(p-dCPS:SA)), P(m-dCPS:SA) and P(o-dCPS:SA) displayed different luminescent properties. P(m-dCPS:SA) could emit fluorescence under the excitation of both visible and UV light, while P(o-dCPS:SA) could only emit fluorescence when excited with UV light. Degradation rate of the two new copolyanhydrides increased with the increase of SA fraction in the copolymers. In addition, P(o-dCPS:SA) degraded more rapidly than P(m-dCPS:SA) with the same composition. Typical surface-degradation characteristics of these copolyanhydrides were observed.

  3. Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yubing Xie

    2011-11-01

    Full Text Available Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

  4. Biodegradability of poly(butylene succinate-co-butylene adipate) (PBSA) controlled by temperature during the dried-gel process

    Science.gov (United States)

    Yamazaki, Hana; Maeda, Tomoki; Hotta, Atsushi

    Currently there is a growing interest in biodegradable plastics that can be readily degraded into H2O and CO2. Among them, poly(butylene succinate-co-butylene adipate)(PBSA) is one of the mechanically attractive materials that can be biodegraded by surrounding water molecules and microorganisms after the disposal of the plastics. In order to expand the use of PBSA, the proper and effective control of the biodegradability of PBSA should be realized. In this work, the dried-gel process of the PBSA was carefully studied considering the temperature of the process. Three different types of dried PBSA gels were prepared at three different gel-process temperatures. From the biodegradability testing by immersing the PBSA samples in NaOH aq., it was found that the percentage of the weight loss of the PBSA was increased, indicating that the biodegradability was enhanced as the gel preparation temperature became lower. In fact, smaller spherocrystals were observed in PBSA dried at cooler temperature, studied by the scanning electron microscopy (SEM). It was therefore concluded that the microstructures of PBSA could be well controlled by changing the gel preparation temperatures for the precise control of the biodegradability of PBSA. This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI\\x9D.

  5. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

    Science.gov (United States)

    Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

    2010-04-13

    A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

  6. Succinic acid in levels produced by yeast (Saccharomyces cerevisiae) during fermentation strongly impacts wheat bread dough properties.

    Science.gov (United States)

    Jayaram, Vinay B; Cuyvers, Sven; Verstrepen, Kevin J; Delcour, Jan A; Courtin, Christophe M

    2014-05-15

    Succinic acid (SA) was recently shown to be the major pH determining metabolite produced by yeast during straight-dough fermentation (Jayaram et al., 2013), reaching levels as high as 1.6 mmol/100 g of flour. Here, the impact of such levels of SA (0.8, 1.6 and 2.4 mmol/100 g flour) on yeastless dough properties was investigated. SA decreased the development time and stability of dough significantly. Uniaxial extension tests showed a consistent decrease in dough extensibility upon increasing SA addition. Upon biaxial extension in the presence of 2.4 mmol SA/100 g flour, a dough extensibility decrease of 47-65% and a dough strength increase of 25-40% were seen. While the SA solvent retention capacity of flour increased with increasing SA concentration in the solvent, gluten agglomeration decreased with gluten yield reductions of over 50%. The results suggest that SA leads to swelling and unfolding of gluten proteins, thereby increasing their interaction potential and dough strength, but simultaneously increasing intermolecular electrostatic repulsive forces. These phenomena lead to the reported changes in dough properties. Together, our results establish SA as an important yeast metabolite for dough rheology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Fabrication of Chitin/Poly(butylene succinate/Chondroitin Sulfate Nanoparticles Ternary Composite Hydrogel Scaffold for Skin Tissue Engineering

    Directory of Open Access Journals (Sweden)

    S. Deepthi

    2014-12-01

    Full Text Available Skin loss is one of the oldest and still not totally resolved problems in the medical field. Since spontaneous healing of the dermal defects would not occur, the regeneration of full thickness of skin requires skin substitutes. Tissue engineering constructs would provide a three dimensional matrix for the reconstruction of skin tissue and the repair of damage. The aim of the present work is to develop a chitin based scaffold, by blending it with poly(butylene succinate (PBS, an aliphatic, biodegradable and biocompatible synthetic polymer with excellent mechanical properties. The presence of chondroitin sulfate nanoparticles (CSnp in the scaffold would favor cell adhesion. A chitin/PBS/CSnp composite hydrogel scaffold was developed and characterized by SEM (Scanning Electron Microscope, FTIR (Fourier Transform Infrared Spectroscopy, and swelling ratio of scaffolds were analyzed. The scaffolds were evaluated for the suitability for skin tissue engineering application by cytotoxicity, cell attachment, and cell proliferation studies using human dermal fibroblasts (HDF. The cytotoxicity and cell proliferation studies using HDF confirm the suitability of the scaffold for skin regeneration. In short, these results show promising applicability of the developed chitin/PBS/CSnps ternary composite hydrogel scaffolds for skin tissue regeneration.

  8. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Majeed Ullah

    2015-01-01

    Full Text Available The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25 in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS. At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

  9. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Science.gov (United States)

    Ullah, Majeed; Ullah, Hanif; Mahmood, Qaisar; Hussain, Izhar

    2015-01-01

    The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID:26380301

  10. A new point mutation in the iron-sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorum.

    Science.gov (United States)

    Wang, Yong; Duan, Yabing; Wang, Jianxin; Zhou, Mingguo

    2015-09-01

    Research has established that mutations in highly conserved amino acids of the succinate dehydrogenase (SDH) complex in various fungi confer SDH inhibitor (SDHI) resistance. For Sclerotinia sclerotiorum (Lib.) de Bary, a necrotrophic fungus with a broad host range and a worldwide distribution, boscalid resistance has been attributed to the mutation H132R in the highly conserved SdhD subunit protein of the SDH complex. In our previous study, however, only one point mutation, A11V in SdhB (GCA to GTA change in SdhB), was detected in S. sclerotiorum boscalid-resistant (BR) mutants. In the current study, replacement of the SdhB gene in a boscalid-sensitive (BS) S. sclerotiorum strain with the mutant SdhB gene conferred resistance. Compared with wild-type strains, BR and GSM (SdhB gene in the wild-type strain replaced by the mutant SdhB gene) mutants were more sensitive to osmotic stress, lacked the ability to produce sclerotia and exhibited lower expression of the pac1 gene. Importantly, the point mutation was not located in the highly conserved sequence of the iron-sulfur subunit of SDH. These results suggest that resistance based on non-conserved vs. conserved protein domains differs in mechanism. In addition to increasing our understanding of boscalid resistance in S. sclerotiorum, the new information will be useful for the development of alternative antifungal drugs. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  11. Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate.

    Science.gov (United States)

    Wu, Dan; Katsumi, Hidemasa; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

    2016-09-01

    Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs.

  12. Sustainable Synthesis of Oxalic and Succinic Acid through Aerobic Oxidation of C6 Polyols Under Mild Conditions.

    Science.gov (United States)

    Ventura, Maria; Williamson, David; Lobefaro, Francesco; Jones, Matthew D; Mattia, Davide; Nocito, Francesco; Aresta, Michele; Dibenedetto, Angela

    2018-03-22

    The sustainable chemical industry encompasses a shift from the use of fossil carbon to renewable carbon. The synthesis of chemicals from nonedible biomass (cellulosic or oil) represents one of the key steps for "greening" the chemical industry. In this paper, we report the aerobic oxidative cleavage of C6 polyols (5-HMF, glucose, fructose and sucrose) to oxalic acid (OA) and succinic acid (SA) in water under mild conditions using M@CNT and M@NCNT (M=Fe, V; CNT=carbon nanotubes; NCNT=N-doped CNT), which, under suitable conditions, were recoverable and reusable without any loss of efficiency. The influence of the temperature, O 2 pressure (PO2 ), reaction time and stirring rate are discussed and the best reaction conditions are determined for an almost complete conversion of the starting material and a good OA yield of 48 %. SA and formic acid were the only co-products. The former could be further converted into OA by oxidation in the presence of formic acid, resulting in an overall OA yield of >62 %. This process was clean and did not produce organic waste nor gas emissions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Direct measurement of the initial proton extrusion to oxygen uptake ratio accompanying succinate oxidation by rat liver mitochondria.

    Science.gov (United States)

    Setty, O H; Shrager, R I; Bunow, B; Reynafarje, B; Lehninger, A L; Hendler, R W

    1986-01-01

    The problem of obtaining very early ratios for the H+/O stoichiometry accompanying succinate oxidation by rat liver mitochondria was attacked using new techniques for direct measurement rather than extrapolations based on data obtained after mixing and the recovery of the electrode from initial injection of O2. Respiration was quickly initiated in a thoroughly mixed O2-containing suspension of mitochondria under a CO atmosphere by photolysis of the CO-cytochrome c oxidase complex-. Fast responding O2 and pH electrodes were used to collect data every 10 ms. The response time for each electrode was experimentally measured in each experiment and suitable corrections for electrode relaxations were made. With uncorrected data obtained after 0.8 s, the extrapolation back to zero time on the basis of single-exponential curve fitting confirmed values close to 8.0 as previously reported (Costa et al., 1984). The data directly obtained, however, indicate an initial burst in H+/O ratio that peaked to values of approximately 20 to 30 prior to 50 ms and which was no longer evident after 0.3 s. Newer information and considerations that place all extrapolation methods in question are discussed. PMID:3019443

  14. Development of hydrocortisone succinic acid/and 5-fluorouracil/chitosan microcapsules for oral and topical drug deliveries.

    Science.gov (United States)

    Lam, Pik-Ling; Lee, Kenneth Ka-Ho; Wong, Raymond Siu-Ming; Cheng, Gregory Yin Ming; Cheng, Shuk Yan; Yuen, Marcus Chun-Wah; Lam, Kim-Hung; Gambari, Roberto; Kok, Stanton Hon-Lung; Chui, Chung-Hin

    2012-05-01

    Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Potassium Dehydroandrographolide Succinate Injection for the treatment of child epidemic parotitis: A systematic review and meta-analysis.

    Science.gov (United States)

    Wu, Jia-rui; Zhang, Xiao-meng; Zhang, Bing

    2015-11-01

    To systematically evaluate the clinical efficacy and safety of Potassium Dehydroandrographolide Succinate Injection (PDSI) in the treatment of child epidemic parotitis (EP). Randomized controlled trials (RCTs) regarding PDSI in the treatment of child EP were searched in China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from inception to July 30, 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of included studies, and a meta-analysis was conducted with RevMan 5.2 software. A total of 11 studies with 818 participants were included. The quality of the studies was generally low, among which only one study mentioned the random method. The meta-analysis indicated that PDSI was more effective than the conventional therapy with Western medicine for EP in the outcomes of the total effective rate [relative risk (RR)=1.23, 95% confidence interval (CI) [1.14, 1.33], Preview, 2 of which were mainly represented rash and diarrhea in the experiment group, while another 4 ADRs occurred in the control group. Based on the systematic review, PDSI was effectiveness and relatively safety in the treatment of child EP. But further rigorously designed trials are warranted to determine its effectiveness.

  16. Effect of organo-modified montmorillonite on poly(butylene succinate/poly(butylene adipate-co-terephthalate nanocomposites

    Directory of Open Access Journals (Sweden)

    2010-07-01

    Full Text Available The composite material based on poly(butylene succinate (PBS, poly(butylene adipate-co-terephthalate (PBAT and organo-modified montmorillonite (OMMT were prepared by melt blending technique and characterized. Sodium montmorillonite (Na-MMT was successfully modified by octadecylammonium (ODA and dimethyldioctadecylammonium (DDOA salts to become OMMT through cation exchange technique which is shown by the increase of basal spacing of clay by XRD. The addition of the OMMT to the PBS/PBAT blends produced nanocomposites which is proved by XRD and TEM. Tensile tests showed increase in tensile strength and modulus which is attributed to the existence of strong interactions between PBS/PBAT and clay, particularly with OMMT. Highest tensile strength of nanocomposite was observed at 1 wt% of OMMT incorporated. TGA study showed that the thermal stability of the blend increased after the addition of clays. SEM micrographs of the fracture surfaces show that the morphology of the blend becomes homogeneous and smoother with presence of OMMT.

  17. Novel poly(butylene succinate nanocomposites containing strontium hydroxyapatite nanorods with enhanced osteoconductivity for tissue engineering applications

    Directory of Open Access Journals (Sweden)

    M. Nerantzaki

    2015-09-01

    Full Text Available Three series of poly(butylene succinate (PBSu nanocomposites containing 0.5, 1 and 2.5 wt% strontium hydroxyapatite [Sr5(PO43OH] nanorods (SrHAp nrds were prepared by in situ polymerisation. The structural effects of Sr5(PO43OH nanorods, for the different concentrations, inside the polymeric matrix (PBSu, were studied through high angle annular dark field scanning transmission electron microscopy (HAADF-STEM. HAADF-STEM measurements revealed that the SrHAp nanorods at low concentrations are dispersed inside the polymeric PBSu matrix while in 1 wt% some aggregates are formed. These aggregations affect the mechanical properties giving an enhancement for the concentration of 0.5 wt% SrHAp nrds in tensile strength, while a reduction is recorded for higher loadings of the nanofiller. Studies on enzymatic hydrolysis revealed that all nanocomposites present higher hydrolysis rates than neat PBSu, indicating that nanorods accelerate the hydrolysis degradation process. In vitro bioactivity tests prove that SrHAp nrds promote the formation of hydroxyapatite on the PBSu surface. All nanocomposites were tested also in relevant cell culture using osteoblast-like cells (MG-63 to demonstrate their biocompatibility showing SrHAp nanorods support cell attachment.

  18. Dynamics of three organic acids (malic, acetic and succinic acid) in sunflower exposed to cadmium and lead.

    Science.gov (United States)

    Niu, Zhixin; Li, Xiaodong; Sun, Lina; Sun, Tieheng

    2013-01-01

    Sunflower (Helianthus annuus L.) has been considered as a good candidate for bioaccumulation of heavy metals. In the present study, sunflower was used to enrich the cadmium and lead in sand culture during 90 days. Biomass, Cd and Pb uptake, three organic acids and pH in cultures were investigated. Results showed that the existence of Cd and Pb showed different interactions on the organic acids exudation. In single Cd treatments, malic and acetic acids in Cd10 showed an incremental tendency with time. In the mixed treatments of Cd and Pb, malic acids increased when 10 and 40 mg x L(-1) Cd were added into Pb50, but acetic acids in Pb50 were inhibited by Cd addition. The Cd10 supplied in Pb10 stimulated the secretion of malic and succinic acids. Moreover, the Cd or Pb uptake in sunflower showed various correlations with pH and some organic acids, which might be due to the fact that the Cd and Pb interfere with the organic acids secretion in rhizosphere of sunflower, and the changes of organic acids altered the form and bioavailability of Cd and Pb in cultures conversely.

  19. Fixation of radioactive elements on diethylene-glycol-succinate and its use for the determination of gross activity in urine

    International Nuclear Information System (INIS)

    Hafez, M.B.; Nazmy, A.F.; Eldesoky, M.M.

    1977-01-01

    Studies are given to illustrate surface adsorption of 144 Ce, 90 Sr, 232 Th, 235 U, 239 Pu and 241 Am on diethylene-glycol-succinate, DGS. Adsorption of these elements was studied from aqueous and phosphate solutions. A procedure for the determination of gross activity in urine, based on surface adsorption on DGS is described. Groups of nine solutions, in 30 ml 1N HNO 3 , were spiked with the investigated radioactive elements (approximately 5 pCi). The pH of the solutions was adjusted to a range of 0.5 to 10 using ammonia. Each solution was passed through the column and the fixed activity was removed from the column with 50 ml of 4N HCl, followed by two washes with 10 ml of distilled water. The acid solution was evaporated to dryness for alpha- or beta-counting. The percentage fixation was determined by comparison with a standard source of the same spiked element. Adsorption was found to depend on pH, age of the tracer solution, hydrolysis state of the radioelement and the ionic strength of the solution. The adsorption phenomenon which was particularly well observed could be used as a separation stage in a method for the determination of gross activity in urine. Recoveries of about 85% were obtained. (T.G.)

  20. Comparative Study Between Different Ready-Made Orally Disintegrating Platforms for the Formulation of Sumatriptan Succinate Sublingual Tablets.

    Science.gov (United States)

    Tayel, Saadya A; El Nabarawi, Mohamed A; Amin, Maha M; AbouGhaly, Mohamed H H

    2017-02-01

    Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol®, chitosan, or Polyox®-were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

  1. Mathematical Modeling of Flow Characteristics in the Embryonic Chick Heart

    DEFF Research Database (Denmark)

    Heebøll-Christensen, Jesper

    This ph.d. thesis contains the mathematical modeling of fluid dynamical phenomena in the tubular embryonic chick heart at HH-stages 10, 12, 14, and 16. The models are constructed by application of energy bond technique and involve the elasticity of heart walls with elliptic cross-section, Womersley...... modified inertia, and resistance due to friction and curvature of the multilayered tubular heart. Through the modeling, flow conditions in the embryonic heart are characterized. The models suggest that eccentric rather than concentric deformation of the beating heart is optimal for mean flows induced...... the models are not conclusive on this point. In addition the Liebau effect is investigated in a simpler system containing two elastic tubes joined to form a liquid filled ring, with a compression pump at an asymmetric location. Through comparison to other reports the system validates model construction...

  2. Establishing the Embryonic Axes: Prime Time for Teratogenic Insults

    Directory of Open Access Journals (Sweden)

    Thomas W. Sadler

    2017-09-01

    Full Text Available A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.

  3. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yao Xiao

    2016-09-01

    Full Text Available A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

  4. Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

    Science.gov (United States)

    Hertsenberg, Andrew J; Funderburgh, James L

    2016-01-01

    Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

  5. Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

    Science.gov (United States)

    Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

    2010-11-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Gergo Kovacs

    2016-01-01

    Full Text Available Rybp (Ring1 and Yy1 Binding Protein is a transcriptional regulator and member of the noncanonical polycomb repressive complex 1 with essential role in early embryonic development. We have previously described that alteration of Rybp dosage in mouse models induced striking neural tube defects (NTDs, exencephaly, and disorganized neurocortex. In this study we further investigated the role of Rybp in neural differentiation by utilising wild type (rybp+/+ and rybp null mutant (rybp-/- embryonic stem cells (ESCs and tried to uncover underlying molecular events that are responsible for the observed phenotypic changes. We found that rybp null mutant ESCs formed less matured neurons, astrocytes, and oligodendrocytes from existing progenitors than wild type cells. Furthermore, lack of rybp coincided with altered gene expression of key neural markers including Pax6 and Plagl1 pinpointing a possible transcriptional circuit among these genes.

  7. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess...

  8. Rat embryonic palatal shelves respond to TCDD in organ culture

    International Nuclear Information System (INIS)

    Abbott, B.D.; Birnbaum, L.S.

    1990-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental contaminant, is teratogenic in mice, inducing cleft palate (CP) and hydronephrosis at doses which are not overtly maternally or embryo toxic. Palatal shelves of embryonic mice respond to TCDD, both in vivo and in organ culture, with altered differentiation of medial epithelial cells. By contrast, in the rat TCDD produces substantial maternal, embryonic, and fetal toxicity, including fetal lethality, with few malformations. In this study the possible effects of maternal toxicity on induction of cleft palate were eliminated by exposure of embryonic rat palatal shelves in organ culture. The shelves were examined for specific TCDD-induced alterations in differentiation of the medial cells. On Gestation Day (GD) 14 or 15 palatal shelves from embryonic F344 rats were placed in organ culture for 2 to 3 days (IMEM:F12 medium, 5% FBS, 0.1% DMSO) containing 0, 1 x 10(-8), 1 x 10(-9), 1 x 10(-10), or 5 x 10(-11) M TCDD. The medial epithelial peridermal cells degenerated on shelves exposed to control media or 5 x 10(-11) M TCDD. Exposure to 10(-10), 10(-9), and 10(-8) M TCDD inhibited this degeneration in 20, 36, and 60% of the shelves, respectively, and was statistically significant at the two highest doses. A normally occurring decrease in [3H]TdR incorporation was inhibited in some GD 15 shelves cultured with 10(-10) and 10(-9) M TCDD. The medial cells of TCDD-exposed shelves continued to express high levels of immunohistochemically detected EGF receptors. The altered differentiation of rat medial epithelium is similar to that reported for TCDD-exposed mouse medial cells in vivo and in vitro. However, in order to obtain these responses, the cultured rat shelves require much higher concentrations of TCDD than the mouse shelves

  9. Epigenetic stability, adaptability, and reversibility in human embryonic stem cells

    OpenAIRE

    Tompkins, Joshua D.; Hall, Christine; Chen, Vincent Chang-yi; Li, Arthur Xuejun; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

    2012-01-01

    The stability of human embryonic stem cells (hESCs) is of critical importance for both experimental and clinical applications. We find that as an initial response to altered culture conditions, hESCs change their transcription profile for hundreds of genes and their DNA methylation profiles for several genes outside the core pluripotency network. After adaption to conditions of feeder-free defined and/or xeno-free culture systems, expression and DNA methylation profiles are quite stable for a...

  10. Engineering bone tissue from human embryonic stem cells

    OpenAIRE

    Marolt, Darja; Campos, Iván Marcos; Bhumiratana, Sarindr; Koren, Ana; Petridis, Petros; Zhang, Geping; Spitalnik, Patrice F.; Grayson, Warren L.; Vunjak-Novakovic, Gordana

    2012-01-01

    In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the i...

  11. Characterization of glycolipid galactosyltransferases from embryonic chicken brain

    International Nuclear Information System (INIS)

    Kyle, J.W.

    1985-01-01

    Glycolipid galactosyltransferases (GalT-3 and GalT-4) were solubilized from a membrane fraction isolated from embryonic chicken brain. The profiles of specific activity and total units per brain of GalT-3 and GalT-4 varied with embryonic age. GalT-4 had the highest specific activity at 9 days of embryonic development and showed a steady decrease until hatching. GalT-3 showed a gradual increase in specific activity. Both GalT3 and GalT-4 showed a steady increase in total units per brain throughout embryonic development. The solubilized enzymes could be separated using gel filtration, ion exchange chromatography or affinity chromatography on α-lactalbumin-agarose. Data obtained in the study imply that GalT-4 is involved in both glycoprotein and glycolipid biosynthesis. Glycosphingolipid products from GalT-3 and GalT-4 catalyzed reactions labeled with [ 14 C]galactose comigrated with authentic GMI and nLcOse 4 Cer, when examined by thin layer chromatography and autoradiography. Studies with galactosidases revealed that all of the enzyme products formed by GalT-3 and GalT-4 contained a [ 14 C]-galactose in a β anomeric linkage. Periodate oxidation studies of Gal-[ 14 C]GlcNAc, formed by purified GalT-4 using [ 14 C]GlcNAc as the acceptor, demonstrated that approximately 70% of the linkage formed was Galβ1-4GlcNAc and 30% was Galβ1-3GlcNAc. Studies on the susceptibility of [ 14 C]Gal-GlcNAc to base catalyzed β-elimination also suggested the presence of approximately 30% Galβ1-3GlcNAc

  12. Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

    OpenAIRE

    Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

    2008-01-01

    Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemi...

  13. Neuropeptidomic analysis of the embryonic Japanese quail diencephalon

    Directory of Open Access Journals (Sweden)

    Sköld Karl

    2010-03-01

    Full Text Available Abstract Background Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17, sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon. Results We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2 exposure and sex effects were neuropeptide K (downregulated by EE2 in males and females, gastrin-releasing peptide (more highly expressed in control and EE2 exposed males and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex. We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide. Conclusions This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model.

  14. Polycomb enables primitive endoderm lineage priming in embryonic stem cells

    DEFF Research Database (Denmark)

    Illingworth, Robert S; Hölzenspies, Jurriaan J; Roske, Fabian V

    2016-01-01

    Mouse embryonic stem cells (ESCs), like the blastocyst from which they are derived, contain precursors of the epiblast (Epi) and primitive endoderm (PrEn) lineages. While transient in vivo, these precursor populations readily interconvert in vitro. We show that altered transcription is the driver...... polycomb with dynamic changes in transcription and stalled lineage commitment, allowing cells to explore alternative choices prior to a definitive decision....

  15. Embryonic miRNA profiles of normal and ectopic pregnancies.

    Directory of Open Access Journals (Sweden)

    Francisco Dominguez

    Full Text Available Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs and controlled abortions (voluntary termination of pregnancy; VTOP. Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223 in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans.

  16. Demethylating agent, 5-azacytidine, reverses differentiation of embryonic stem cells

    International Nuclear Information System (INIS)

    Tsuji-Takayama, Kazue; Inoue, Toshiya; Ijiri, Yoshihiro; Otani, Takeshi; Motoda, Ryuichi; Nakamura, Shuji; Orita, Kunzo

    2004-01-01

    The de novo methylation activity is essential for embryonic development as well as embryonic stem (ES) cell differentiation, where the intensive and extensive DNA methylation was detected. In this study, we investigated the effects of a demethylating agent, 5-azacytidine (5-AzaC), on differentiated ES cells in order to study the possibility of reversing the differentiation process. We first induced differentiation of ES cells by forming embryoid bodies, and then the cells were treated with 5-AzaC. The cells showed some undifferentiated features such as stem cell-like morphology with unclear cell-to-cell boundary and proliferative responsiveness to LIF. Moreover, 5-AzaC increased the expressions of ES specific markers, SSEA-1, and alkaline phosphatase activity as well as ES specific genes, Oct4, Nanog, and Sox2. We also found that 5-AzaC demethylated the promoter region of H19 gene, a typical methylated gene during embryonic differentiation. These results indicate that 5-AzaC reverses differentiation state of ES cells through its DNA demethylating activity to differentiation related genes

  17. Embryonic Blood-Cerebrospinal Fluid Barrier Formation and Function

    Directory of Open Access Journals (Sweden)

    David eBueno

    2014-10-01

    Full Text Available During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF. CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS. The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF.

  18. Case Study: Organotypic human in vitro models of embryonic ...

    Science.gov (United States)

    Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell-matrix interactions that drive proliferation, differentiation, and morphogenesis. Chemical low-dose exposures can disrupt morphogenesis across space and time by interfering with key embryonic fusion events. The Morphogenetic Fusion Task uses computer and in vitro models to elucidate consequences of developmental exposures. The Morphogenetic Fusion Task integrates multiple approaches to model responses to chemicals that leaad to birth defects, including integrative mining on ToxCast DB, ToxRefDB, and chemical structures, advanced computer agent-based models, and human cell-based cultures that model disruption of cellular and molecular behaviors including mechanisms predicted from integrative data mining and agent-based models. The purpose of the poster is to indicate progress on the CSS 17.02 Virtual Tissue Models Morphogenesis Task 1 products for the Board of Scientific Counselors meeting on Nov 16-17.

  19. MRI diagnosis of embryonal tumors in the spinal canal

    International Nuclear Information System (INIS)

    Sun Jilin; Zhang Xinchuan; Zhang Huaning; Liu Lianxiang; Wu Yujin

    1997-01-01

    To evaluate MRI diagnostic value of the embryonal tumors in the spinal canal. Materials and methods: The MRI appearances of 15 cases of histologically confirmed embryonal tumors in the spinal canal were analyzed. (1) Lipoma (3 cases) had characteristic MRI appearance, demonstrating high signal intensity on T 1 WI, and moderately high signal on T 2 WI. High signal intensity of the lipoma was turned into low signal intensity by fat suppression technique. (2) Dermoids (2 cases) and epidermoid (7 cases) exhibiting low or iso-low signal on T 1 WI and high or iso-high signal on T 2 WI. All had an iso-intense capsule on T 1 WI. However, the two tumors could not be distinguished from each other. (3) Teratoma (3 cases) appeared as a mass of inhomo-generous signals in the spinal canal including soft tissue, fatty tissue and calcification within the same tumor. The diagnosis of embryonal tumors in the spinal canal mainly depend on their MRI appearances, specific tumor location and patient's age

  20. A practical guide for the identification of membrane and plasma membrane proteins in human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Mummery, C.L.; Krijgsveld, J.; Heck, A.

    2008-01-01

    The identification of (plasma) membrane proteins in cells can provide valuable insights into the regulation of their biological processes. Pluripotent cells such as human embryonic stem cells and embryonal carcinoma cells are capable of unlimited self-renewal and share many of the biological

  1. Contested embryonic culture in Japan--public discussion, and human embryonic stem cell research in an aging welfare society.

    Science.gov (United States)

    Sleeboom-Faulkner, Margaret

    2010-01-01

    This article explores the reasons for the lack of a broad discussion on bioethical regulation of human embryonic stem cell research (hESR) in Japan and asks why scientists experience difficulties accessing resources for hESR despite the acclaimed indifference of dominant Japanese culture to embryo research. The article shows how various social actors express their views on the embryo and oocyte donation in terms of dominant Japanese culture, foiled against what is regarded as Western culture. Second, it shows how the lack of concern with hESR should be understood in the context of public health policies and communications and bioethics decision making in Japan. Finally, it interprets the meaning of the embryo in the context of Japan as an aging modern welfare society, explaining how policymakers have come to emphasize the urgency of infertility problems over issues around abortion and embryonic life.

  2. Maternal Embryonic Leucine Zipper Kinase (MELK: A Novel Regulator in Cell Cycle Control, Embryonic Development, and Cancer

    Directory of Open Access Journals (Sweden)

    Pengfei Jiang

    2013-10-01

    Full Text Available Maternal embryonic leucine zipper kinase (MELK functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis. In these cellular processes, MELK functions by binding to numerous proteins. In general, the effects of multiple protein interactions with MELK are oncogenic in nature, and the overexpression of MELK in kinds of cancer provides some evidence that it may be involved in tumorigenic process. In this review, our current knowledge of MELK function and recent discoveries in MELK signaling pathway were discussed. The regulation of MELK in cancers and its potential as a therapeutic target were also described.

  3. Somatic Donor Cell Type Correlates with Embryonic, but Not Extra-Embryonic, Gene Expression in Postimplantation Cloned Embryos

    Science.gov (United States)

    Inoue, Kimiko; Ogura, Atsuo

    2013-01-01

    The great majority of embryos generated by somatic cell nuclear transfer (SCNT) display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts). The embryos retrieved from the uteri were separated into embryonic (epiblast) and extraembryonic (extraembryonic ectoderm and ectoplacental cone) tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs) (>2-fold vs. controls) than did the extraembryonic tissues (Pcloning efficiency using SCNT. PMID:24146866

  4. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    Science.gov (United States)

    Thu Ha, Phuong; Nguyen, Hoai Nam; Doan Do, Hai; Thong Phan, Quoc; Nguyet Tran Thi, Minh; Phuc Nguyen, Xuan; Nhung Hoang Thi, My; Huong Le, Mai; Nguyen, Linh Toan; Quang Bui, Thuc; Hieu Phan, Van

    2016-03-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50-100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

  5. Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers.

    Science.gov (United States)

    Tufton, Nicola; Shapiro, Lucy; Srirangalingam, Umasuthan; Richards, Polly; Sahdev, Anju; Kumar, Ajith V; McAndrew, Lorraine; Martin, Lee; Berney, Daniel; Monson, John; Chew, Shern L; Waterhouse, Mona; Druce, Maralyn; Korbonits, Márta; Metcalfe, Karl; Drake, William M; Storr, Helen L; Akker, Scott A

    2017-02-01

    For 'asymptomatic carriers' of the succinate dehydrogenase subunit B (SDHB) gene mutations, there is currently no consensus as to the appropriate modality or frequency of surveillance imaging. We present the results of a surveillance programme of SDHB mutation carriers. Review of clinical outcomes of a surveillance regimen in patients identified to have an SDHB gene mutation, based on annual MRI, in a single UK tertiary referral centre. A total of 92 patients were identified with an SDHB gene mutation. a total of 27 index patients presented with symptoms, and 65 patients were identified as asymptomatic carriers. Annual MRI of the abdomen, with alternate year MRI of the neck, thorax and pelvis. Presence of an SDHB-related tumour included paraganglioma (PGL), phaeochromocytoma (PCC), renal cell carcinoma (RCC) and gastrointestinal stromal tumour (GIST). A total of 43 PGLs, eight PCCs and one RCC occurred in the 27 index patients (23 solitary, four synchronous, five metachronous). A further 15 SDHB-related tumours (11 PGLs, three RCCs, one GIST) were identified in the asymptomatic carriers on surveillance screening (25% of screened carriers): 10 on the first surveillance imaging and five on subsequent imaging 2-6 years later. A total of 11 patients had malignant disease. SDHB-related tumours are picked up as early as 2 years after initial negative surveillance scan. We believe the high malignancy rate and early identification rate of tumours justifies the use of 1-2 yearly imaging protocols and MRI-based imaging could form the mainstay of surveillance in this patient group thereby minimizing radiation exposure. © 2016 John Wiley & Sons Ltd.

  6. Morphology, Nucleation, and Isothermal Crystallization Kinetics of Poly(Butylene Succinate Mixed with a Polycarbonate/MWCNT Masterbatch

    Directory of Open Access Journals (Sweden)

    Thandi P. Gumede

    2018-04-01

    Full Text Available In this study, nanocomposites were prepared by melt blending poly(butylene succinate (PBS with a polycarbonate (PC/multi-wall carbon nanotubes (MWCNTs masterbatch, in a twin-screw extruder. The nanocomposites contained 0.5, 1.0, 2.0, and 4.0 wt% MWCNTs. Differential scanning calorimetry (DSC, small angle X-ray scattering (SAXS and wide angle X-ray scattering (WAXS results indicate that the blends are partially miscible, hence they form two phases (i.e., PC-rich and PBS-rich phases. The PC-rich phase contained a small amount of PBS chains that acted as a plasticizer and enabled crystallization of the PC component. In the PBS-rich phase, the amount of the PC chains present gave rise to increases in the glass transition temperature of the PBS phase. The presence of two phases was supported by scanning electron microscopy (SEM and atomic force microscopy (AFM analysis, where most MWCNTs aggregated in the PC-rich phase (especially at the high MWCNTs content of 4 wt% and a small amount of MWCNTs were able to diffuse to the PBS-rich phase. Standard DSC scans showed that the MWCNTs nucleation effects saturated at 0.5 wt% MWCNT content on the PBS-rich phase, above this content a negative nucleation effect was observed. Isothermal crystallization results indicated that with 0.5 wt% MWCNTs the crystallization rate was accelerated, but further increases in MWCNTs loading (and also in PC content resulted in progressive decreases in crystallization rate. The results are explained by increased MWCNTs aggregation and reduced diffusion rates of PBS chains, as the masterbatch content in the blends increased.

  7. Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol

    Energy Technology Data Exchange (ETDEWEB)

    Llorens, E.; Ibañez, H. [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Valle, L.J. del, E-mail: luis.javier.del.valle@upc.edu [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Puiggalí, J. [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CrNE), Universitat Politècnica de Catalunya, Edifici C, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain)

    2015-04-01

    Scaffolds constituted by electrospun microfibers of poly(ethylene glycol) (PEG) and poly(butylene succinate) (PBS) were studied. Specifically, coaxial microfibers having different core–shell distributions and compositions were considered as well as uniaxial micro/nanofibers prepared from mixtures of both polymers. Processing conditions were optimized for all geometries and compositions and resulting morphologies (i.e. diameter and surface texture) characterized by scanning electron microscopy. Chemical composition, molecular interactions and thermal properties were evaluated by FTIR, NMR, XPS and differential scanning calorimetry. The PEG component of electrospun fibers could be solubilized by immersion of scaffolds in aqueous medium, giving rise to high porosity and hydrophobic samples. Nevertheless, a small amount of PEG was retained in the PBS matrix, suggesting some degree of mixing. Solubilization was slightly dependent on fiber structure; specifically, the distribution of PEG in the core or shell of coaxial fibers led to higher or lower retention levels, respectively. Scaffolds could be effectively loaded with hydrophobic drugs having antibacterial and anticarcinogenic activities like triclosan and curcumin, respectively. Their release was highly dependent on their chemical structure and medium composition. Thus, low and high release rates were observed in phosphate buffer saline (SS) and SS/ethanol (30:70 v/v), respectively. Slight differences in the release of triclosan were found depending on fiber distribution and composition. Antibacterial activity and biocompatibility were evaluated for both loaded and unloaded scaffolds. - Highlights: • Coaxial microfibers with different hydrophobicities were studied. • The surface morphology of the coaxial fiber shows the distribution of polymers. • Coaxial fiber microstructure favors the polymer molecular orientation. • These hybrid materials have greater advantages for loading and drug release. • PEG

  8. MexiB 6 AS A RESULT OF FORTIFICATION OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE WITH MAGNESIUM AND PYRIDOXINE: PROTEOME EFFECTS

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available The efficacy of ethylmethylhydroxypyridine succinate (EMHPS  depends on the concentration and activity of proteomic proteins. To provide the body with magnesium and pyridoxine is an important condition for the efficacy of EMHPS because these micronutrients are essential for maintaining neuronal function.Objective: to analyze the biological effects of pyridoxineand magnesium-dependent proteins providing the molecular mechanisms of multi-targeted action of EMHPS,  pyridoxine, and magnesium.Material and methods. Proteins that interact with both pyridoxine and magnesium were found in the genomic and proteomic databases. A list of 78 vitamin B6-dependent proteins, which is based on the available human genome records in NCBIPROTEIN, EMBL,  UNIPROT,  and HumanProteomeMap databases, was analyzed using a functional binding assay. The same assay was also applied to analyze a list 720 magnesium-dependent proteins.Results. The analysis has shown that 78 pyridoxine-dependent proteomic proteins are necessary for: 1 the synthesis and processing of amino acids; 2 cell energy metabolism (ATP synthesis, and 3 the synthesis of neurotransmitters and neuronal membranes. MexiB 6 has numerous synergistic interactions between the molecules of EMHPS,  pyridoxine, and magnesium. The combination of the components of EMHPS,  pyridoxine and magnesium in MexiB 6 (triple synergism allows prediction that the drug has more pronounced clinical effects than the molecules of EMHPS,  which emerges in its antihypoxic and antioxidant activities, the improvement of synaptic transmission of a signal, the neutralization of homocysteine, and the regulation of lipid and carbohydrate metabolism (restoration of cell sensitivity to insulin and carbohydrates in patients with atherosclerosis and in those at risk for diabetes mellitus or obesity. Pyridoxineand magnesium-induced potentiation of the effects of EMHPS may enhance its activity.

  9. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    International Nuclear Information System (INIS)

    Ha, Phuong Thu; Nguyen, Hoai Nam; Do, Hai Doan; Phan, Quoc Thong; Thi, Minh Nguyet Tran; Nguyen, Xuan Phuc; Thi, My Nhung Hoang; Le, Mai Huong; Nguyen, Linh Toan; Bui, Thuc Quang; Phan, Van Hieu

    2016-01-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50–100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment. (paper)

  10. EFFICACY AND SAFETY OF METOPROLOL SUCCINATE IN HIGH DOSES IN PATIENTS WITH STABLE COURSE OF ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2008-01-01

    Full Text Available Aim. To compare two initial doses (50 or 100mg/day ofmetoprolol succinate in control released presentation (Betaloc ZOK, AstraZeneca for achievement of target level of heart rate (HR in patients with stable course of ischemic heart disease (IHD.Material and methods. 50 patients (34 men and 16 women, aged 61,3 y.o., in average with IHD were involved into the open randomized comparative study. IHD duration was from 1 to 22 years (8,3 years in average. 47 patients completed study, 3 patients drop out because of side effects. Previous therapy with β-blockers or other HR reducing drugs was replaced on metoprolol. Patients were randomized in 2 groups (G1 and G2. The initial metoprolol dose was 50 mg in G1 patients and 100 mg - in G2 patients. The dose was enlarged twice if necessary. Study duration was 6 weeks. The change of HR, blood pressure, electrocardiogram parameters was evaluated. Patients filled in Seattle angina questionnaire initially and after 6 weeks treatment. Therapy tolerability was also estimated.Results. In 6 weeks of therapy 61% of G1 patients and 87,5% of G2 patients (p<0,01 reached HR target. Dependence of achievement of target HR and dose of metoprolol was observed (r=0,3; p=0,056. Improvement of the HR control was accompanied by reduction of frequency of angina attacks and increase of life quality.Conclusion. Metoprolol (Betaloc ZOK 200 mg/day provides more effective HR control in patients with IHD vs metoprolol 50-100 mg/day and has good tolerability.

  11. Preparation and characterization of new succinic anhydride grafted Posidonia for the removal of organic and inorganic pollutants

    International Nuclear Information System (INIS)

    Chadlia, Aguir; Mohamed, Khalfaoui; Najah, Laribi; Farouk, M'henni Mohamed

    2009-01-01

    The present work describes the preparation of new chelating materials derived from Posidonia for adsorption of heavy metal ions and dye in aqueous solution. The first part of this report deals with the chemical modification of Posidonia with succinic anhydride. Thus, we have obtained materials with various succinyl groups contents (from 29.8 to 39.2%). The obtained materials were characterized by infrared and CP/MAS 13 C-RMN spectroscopy. The rate of succinyl content of the modified Posidonia was determined by saponification. The second part is devoted to the evaluation of the adsorption capacity of metal ions such as Pb 2+ and dye such as direct red 75 (DR75) for raw and modified Posidonia materials. Two possible ways for the adsorption of these pollutants are studied: adsorption of each pollutant alone onto these supports, and cumulative adsorption of both metal ions and dye on the same supports. In the last case, the pollutant is adsorbed successively from two different solutions. The effects of pollutants concentration, support dose, pH, contact time and temperature on adsorption of each pollutant were evaluated. The results showed that the raw and modified Posidonia show a high capacity for Pb 2+ adsorption. The capacity of modified Posidonia saturated with Pb 2+ to adsorb DR75 was found 147.12 mg g -1 . While the adsorption capacity of the nonsaturated modified Posidonia was equal to 81.63 mg g -1 . The pseudo-second-order model was the best to represent adsorption kinetics of DR75. The pseudo-first-order model would be better for fitting the adsorption kinetic process of Pb 2+ onto raw and modified Posidonia. The adsorption isotherms of Pb 2+ could be described by the Jossens equation model. Any of the tested models can describe the adsorption of DR75 onto the studied materials. These results confirm that the adsorption of DR75 from aqueous solution was multilayer.

  12. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    International Nuclear Information System (INIS)

    Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

    2015-01-01

    Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

  13. Reinforcement effect of poly(butylene succinate) (PBS)-grafted cellulose nanocrystal on toughened PBS/polylactic acid blends.

    Science.gov (United States)

    Zhang, Xuzhen; Zhang, Yong

    2016-04-20

    Poly(butylene succinate) (PBS)/polylactic acid (PLA) blends modified with dicumyl peroxide (DCP) were reinforced by PBS-g-cellulose nanocrystal (CNC) through melt mixing. PBS-g-CNC was prepared through in situ polymerization and its structure was confirmed by FTIR, (13)C NMR, XPS and GPC analysis after saponification. The morphological analysis of PBS/PLA/PBS-g-CNC composites before and after etched by CH2Cl2 shows that the addition of DCP and PBS-g-CNC could decrease the size of PBS as a dispersed phase in PLA matrix and improve the dispersion of PBS-g-CNC in both PBS and PLA phases, which could affect the crystallization and mechanical properties of composites. The crystallinity of PLA α'-phase crystal in PBS/PLA/PBS-g-CNC composites is increased obviously by the addition of PBS-g-CNC, leading to an increase of the crystallinity of the composites. PBS/PLA blends modified by DCP have high Notched Izod impact strength and moduli, and the values are increased by the addition of PBS-g-CNC. Both storage modulus and glass translation temperature of PBS/PLA blend are increased by DCP and PBS-g-CNC, which is proved by DMA results, showing a weak molecular segment mobility of PBS/PLA matrix. The addition of DCP decreases the crystallization temperature and crystallinity of PBS/PLA composite, but increases the thermal stability of composites, mostly because of the crosslink effect of DCP on PBS/PLA matrix. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; McLachlan, A J; Griffith, J E; Higgins, D P; Gillett, A; Krockenberger, M B; Govendir, M

    2013-10-01

    Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.) chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.) chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n = 6). Serial plasma samples were collected over 24-48 h, and chloramphenicol concentrations were determined using a validated high-performance liquid chromatography assay. The median (range) apparent clearance (CL/F) and elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively. Although the area under the concentration-time curve was comparable for the two s.c. formulations, the absorption rate-limited disposition of chloramphenicol base resulted in a lower median C(max) (2.52; range 0.75-6.80 μg/mL) and longer median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37, range 13.88-25.15 μg/mL; t(max) 1.25, range 1.00-2.00 h). When these results were compared with susceptibility data for human Chlamydia isolates, the expected efficacy of the current chloramphenicol dosing regimen used in koalas to treat chlamydiosis remains uncertain and at odds with clinical observations. © 2012 John Wiley & Sons Ltd.

  15. Altered glucose transport to utero-embryonic unit in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Arnab, Banerjee; Amitabh, Krishna

    2011-02-10

    The aim of this study was to compare the changes in concentration of glucose and glucose transporters (GLUTs) in the utero-embryonic unit, consisting of decidua, trophoblast and embryo, during delayed and non-delayed periods to understand the possible cause of delayed embryonic development in Cynopterus sphinx. The results showed a significantly decreased concentration of glucose in the utero-embryonic unit due to decline in the expression of insulin receptor (IR) and GLUT 3, 4 and 8 proteins in the utero-embryonic unit during delayed period. The in vitro study showed suppressive effect of insulin on expression of GLUTs 4 and 8 in the utero-embryonic unit and a significant positive correlation between the decreased amount of glucose consumed by the utero-embryonic unit and decreased expression of GLUTs 4 (r=0.99; psphinx. Increased supply of fatty acid to the delayed embryo may be responsible for its survival under low glucose condition but unable to promote embryonic development in C. sphinx. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Banerjee, Arnab; Meenakumari, K J; Udin, S; Krishna, A

    2009-12-01

    The aim of the present study was to evaluate the seasonal variation in serum melatonin levels and their relationship to the changes in the serum progesterone level, ovarian steroidogenesis, and embryonic development during two successive pregnancies of Cynopterus sphinx. Circulating melatonin concentrations showed two peaks; one coincided with the period of low progesterone synthesis and delayed embryonic development, whereas the second peak coincided with regressing corpus luteum. This finding suggests that increased serum melatonin level during November-December may be responsible for delayed embryonic development by suppressing progesterone synthesis. The study showed increased melatonin receptors (MTNR1A and MTNR1B) in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed that a high dose of melatonin suppressed progesterone synthesis, whereas a lower dose of melatonin increased progesterone synthesis by the ovary. The effects of melatonin on ovarian steroidogenesis are mediated through changes in the expression of peripheral-type benzodiazepine receptor, P450 side chain cleavage enzyme, and LH receptor proteins. This study further showed a suppressive impact of melatonin on the progesterone receptor (PGR) in the utero-embryonic unit; this effect might contribute to delayed embryonic development in C. sphinx. The results of the present study thus suggest that a high circulating melatonin level has a dual contribution in retarding embryonic development in C. sphinx by impairing progesterone synthesis as well as by inhibiting progesterone action by reducing expression of PGR in the utero-embryonic unit.

  17. Differentiation of embryonic stem cells towards hematopoietic cells: progress and pitfalls.

    Science.gov (United States)

    Tian, Xinghui; Kaufman, Dan S

    2008-07-01

    Hematopoietic development from embryonic stem cells has been one of the most productive areas of stem cell biology. Recent studies have progressed from work with mouse to human embryonic stem cells. Strategies to produce defined blood cell populations can be used to better understand normal and abnormal hematopoiesis, as well as potentially improve the generation of hematopoietic cells with therapeutic potential. Molecular profiling, phenotypic and functional analyses have all been utilized to demonstrate that hematopoietic cells derived from embryonic stem cells most closely represent a stage of hematopoiesis that occurs at embryonic/fetal developmental stages. Generation of hematopoietic stem/progenitor cells comparable to hematopoietic stem cells found in the adult sources, such as bone marrow and cord blood, still remains challenging. However, genetic manipulation of intrinsic factors during hematopoietic differentiation has proven a suitable approach to induce adult definitive hematopoiesis from embryonic stem cells. Concrete evidence has shown that embryonic stem cells provide a powerful approach to study the early stage of hematopoiesis. Multiple hematopoietic lineages can be generated from embryonic stem cells, although most of the evidence suggests that hematopoietic development from embryonic stem cells mimics an embryonic/fetal stage of hematopoiesis.

  18. Can physics help to explain embryonic development? An overview.

    Science.gov (United States)

    Fleury, V

    2013-10-01

    Recent technical advances including digital imaging and particle image velocimetry can be used to extract the full range of embryonic movements that constitute the instantaneous 'morphogenetic fields' of a developing animal. The final shape of the animal results from the sum over time (integral) of the movements that make up the velocity fields of all the tissue constituents. In vivo microscopy can be used to capture the details of vertebrate development at the earliest embryonic stages. The movements thus observed can be quantitatively compared to physical models that provide velocity fields based on simple hypotheses about the nature of living matter (a visco-elastic gel). This approach has cast new light on the interpretation of embryonic movement, folding, and organisation. It has established that several major discontinuities in development are simple physical changes in boundary conditions. In other words, with no change in biology, the physical consequences of collisions between folds largely explain the morphogenesis of the major structures (such as the head). Other discontinuities result from changes in physical conditions, such as bifurcations (changes in physical behaviour beyond specific yield points). For instance, beyond a certain level of stress, a tissue folds, without any new gene being involved. An understanding of the physical features of movement provides insights into the levers that drive evolution; the origin of animals is seen more clearly when viewed under the light of the fundamental physical laws (Newton's principle, action-reaction law, changes in symmetry breaking scale). This article describes the genesis of a vertebrate embryo from the shapeless stage (round mass of tissue) to the development of a small, elongated, bilaterally symmetric structure containing vertebral precursors, hip and shoulder enlarges, and a head. Copyright © 2013. Published by Elsevier Masson SAS.

  19. Identification of mechanosensitive genes during embryonic bone formation.

    Directory of Open Access Journals (Sweden)

    Niamh C Nowlan

    2008-12-01

    Full Text Available Although it is known that mechanical forces are needed for normal bone development, the current understanding of how biophysical stimuli are interpreted by and integrated with genetic regulatory mechanisms is limited. Mechanical forces are thought to be mediated in cells by "mechanosensitive" genes, but it is a challenge to demonstrate that the genetic regulation of the biological system is dependant on particular mechanical forces in vivo. We propose a new means of selecting candidate mechanosensitive genes by comparing in vivo gene expression patterns with patterns of biophysical stimuli, computed using finite element analysis. In this study, finite element analyses of the avian embryonic limb were performed using anatomically realistic rudiment and muscle morphologies, and patterns of biophysical stimuli were compared with the expression patterns of four candidate mechanosensitive genes integral to bone development. The expression patterns of two genes, Collagen X (ColX and Indian hedgehog (Ihh, were shown to colocalise with biophysical stimuli induced by embryonic muscle contractions, identifying them as potentially being involved in the mechanoregulation of bone formation. An altered mechanical environment was induced in the embryonic chick, where a neuromuscular blocking agent was administered in ovo to modify skeletal muscle contractions. Finite element analyses predicted dramatic changes in levels and patterns of biophysical stimuli, and a number of immobilised specimens exhibited differences in ColX and Ihh expression. The results obtained indicate that computationally derived patterns of biophysical stimuli can be used to inform a directed search for genes that may play a mechanoregulatory role in particular in vivo events or processes. Furthermore, the experimental data demonstrate that ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators in translating information from the mechanical environment to the

  20. Mouse oocytes nucleoli rescue embryonic development of porcine enucleolated oocytes.

    Science.gov (United States)

    Morovic, Martin; Strejcek, Frantisek; Nakagawa, Shoma; Deshmukh, Rahul S; Murin, Matej; Benc, Michal; Fulka, Helena; Kyogoku, Hirohisa; Pendovski, Lazo; Fulka, Josef; Laurincik, Jozef

    2017-12-01

    It is well known that nucleoli of fully grown mammalian oocytes are indispensable for embryonic development. Therefore, the embryos originated from previously enucleolated (ENL) oocytes undergo only one or two cleavages and then their development ceases. In our study the interspecies (mouse/pig) nucleolus transferred embryos (NuTE) were produced and their embryonic development was analyzed by autoradiography, transmission electron microscopy (TEM) and immunofluorescence (C23 and upstream binding factor (UBF)). Our results show that the re-injection of isolated oocyte nucleoli, either from the pig (P + P) or mouse (P + M), into previously enucleolated and subsequently matured porcine oocytes rescues their development after parthenogenetic activation and some of these develop up to the blastocyst stage (P + P, 11.8%; P + M, 13.5%). In nucleolus re-injected 8-cell and blastocyst stage embryos the number of nucleoli labeled with C23 in P + P and P + M groups was lower than in control (non-manipulated) group. UBF was localized in small foci within the nucleoli of blastocysts in control and P + P embryos, however, in P + M embryos the labeling was evenly distributed in the nucleoplasm. The TEM and autoradiographic evaluations showed the formation of functional nucleoli and de novo rRNA synthesis at the 8-cell stage in both, control and P + P group. In the P + M group the formation of comparable nucleoli was delayed. In conclusion, our results indicate that the mouse nucleolus can rescue embryonic development of enucleolated porcine oocytes, but the localization of selected nucleolar proteins, the timing of transcription activation and the formation of the functional nucleoli in NuTE compared with control group show evident aberrations.