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Sample records for antitumour activity complex-formation

  1. Synthesis and antitumour activity of 4-aminoquinazoline derivatives

    Science.gov (United States)

    Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

    2016-07-01

    Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

  2. Antitumour Activity of Chitosan Hydrogen Selenites

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Chitosans reacted with selenious acid to prepare chitosan hydrogen selenites, which were found to be growth-inhibitory against sarcoma 180 solid tumor. The results indicated that the activity also depended on the molecular weight of chitosan supports.

  3. Integrin activation and focal complex formation in cardiac hypertrophy

    Science.gov (United States)

    Laser, M.; Willey, C. D.; Jiang, W.; Cooper, G. 4th; Menick, D. R.; Zile, M. R.; Kuppuswamy, D.

    2000-01-01

    Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

  4. Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone

    DEFF Research Database (Denmark)

    Brasso, Klaus; Thomsen, Frederik B; Schrader, Andres J;

    2015-01-01

    BACKGROUND: The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial. OBJECTIVE: To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone. DESIGN, SETTING, AND PARTIC...

  5. Antitumour Activity of the Microencapsulation of Annona vepretorum Essential Oil.

    Science.gov (United States)

    Bomfim, Larissa M; Menezes, Leociley R A; Rodrigues, Ana Carolina B C; Dias, Rosane B; Rocha, Clarissa A Gurgel; Soares, Milena B P; Neto, Albertino F S; Nascimento, Magaly P; Campos, Adriana F; Silva, Lidércia C R C E; Costa, Emmanoel V; Bezerra, Daniel P

    2016-03-01

    Annona vepretorum Mart. (Annonaceae), popularly known as 'bruteira', has nutritional and medicinal uses. This study investigated the chemical composition and antitumour potential of the essential oil of A. vepretorum leaf alone and complexed with β-cyclodextrin in a microencapsulation. The essential oil was obtained by hydrodistillation using a Clevenger-type apparatus and analysed using GC-MS and GC-FID. In vitro cytotoxicity of the essential oil and some of its major constituents in tumour cell lines from different histotypes was evaluated using the alamar blue assay. Furthermore, the in vivo efficacy of essential oil was demonstrated in mice inoculated with B16-F10 mouse melanoma. The essential oil included bicyclogermacrene (35.71%), spathulenol (18.89%), (E)-β-ocimene (12.46%), α-phellandrene (8.08%), o-cymene (6.24%), germacrene D (3.27%) and α-pinene (2.18%) as major constituents. The essential oil and spathulenol exhibited promising cytotoxicity. In vivo tumour growth was inhibited by the treatment with the essential oil (inhibition of 34.46%). Importantly, microencapsulation of the essential oil increased in vivo tumour growth inhibition (inhibition of 62.66%). PMID:26348780

  6. Evaluation of the purified fraction of Wilbrandia (c. f. verticillata for antitumour activity

    Directory of Open Access Journals (Sweden)

    V. S. N. Rao

    1991-01-01

    Full Text Available Cucurbatacins are known to produce cytotoxic and anticancer activities. Two novel norcucurbitacin glucosides (Wvl and Wv2 have recently been isolated from a purified fraction obtained from the rhizome of Wilbrandia verticillata. The present study evaluates the cytotoxic and anti-tumour activities of the norcucurbitacins. We have found a regular cytotoxicity in KB cells (Cy50 = 12µg/ml as well as a significant inhibition in the Walker 256 carcinosarcoma growth (approximately 75%.

  7. The synthesis of 191Pt labelled JM216, an orally active platinum anti-tumour agent

    International Nuclear Information System (INIS)

    The orally active platinum anti-tumour complex JM 216 [bis-acetatoamminedichloro cyclohexylamineplatinum (IV)] is at present in stage II clinical trials. A procedure for synthesising the complex labelled with 191Pt or 188Pt at the platinum centre has been developed. The purity (shown by HPLC) is 98% and the specific activity (0.3-0.4 Ci/kg) is enough for in vivo and in vitro studies. (author)

  8. Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Nardou Katya

    2008-06-01

    Full Text Available Abstract Background Histone deacetylase inhibitors (HDACi are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. Results We show here that the HDACi Sodium Butyrate (NaB, suberoylanilide hydroxamic acid (SAHA and Trichostatin A (TSA strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. Conclusion HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.

  9. DNA topoisomerase II structures and anthracycline activity: insights into ternary complex formation.

    Science.gov (United States)

    Dal Ben, D; Palumbo, M; Zagotto, G; Capranico, G; Moro, S

    2007-01-01

    DNA Topoisomerase II (Top2) is an essential nuclear enzyme that regulates the topological state of the DNA, and a target of very effective anticancer drugs including anthracycline antibiotics. Even though several aspects of drug activity against Top2 are understood, the drug receptor site is not yet known. Several Top2 mutants have altered drug sensitivity and have provided information of structural features determining drug action. Here, we have revised the published crystal structures of eukaryotic and prokaryotic Top2s and relevant biochemical investigations of enzyme activity and anthracycline action. In particular, we have considered Top2 mutations conferring resistance to anthracyclines and related agents. Following a previous study (Moro et al, Biochemistry, 2004; 43: 7503-13), we have then re-built a molecular model of the entire enzyme in complex with DNA after the cleavage reaction, and used it to define the receptor site of anthracyclines. The results suggest a model wherein the drug specifically contacts the cleaved DNA as well as amino acid residues of the enzyme CAP-like domain. The findings can explain several established structure-activity relationships of antitumour anthracyclines, and provide a framework for further developments of effective Top2 poison. PMID:17897022

  10. Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff. ex T. Anders (Guttiferae

    Directory of Open Access Journals (Sweden)

    Mukram M. Mackeen

    2012-01-01

    Full Text Available The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl-3-butoxycarbonyl-2-hydroxy-3-propanolide (1 and 1′,1′′-dibutyl methyl hydroxycitrate (2, that had been previously isolated from the fruits of Garcinia atroviridis Griff. ex T. Anders (Guttiferae, were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA activation, compound 1 (IC50: 70 μM showed much higher (8-fold antitumour-promoting activity than compound 2 (IC50: 560 μM. In addition, both compounds were nontoxic towards CEM-SS (human T-lymphoblastic leukemia cells (CD50: >100 μM, Raji (human B-lymphoblastoid cells (CD50: >600 μM, and brine shrimp (LD50: >300 μM. Although the antitumour-promoting activity of compound 1 is moderate compared with the known antitumour promoter genistein, its non-toxicity suggests the potential of compound 1 and related structures as chemopreventive agents. The weak antioxidant activity displayed by both compounds also suggested that the primary antitumour-promoting mechanism of compound 1 did not involve oxidative-stress quenching.

  11. Synthesis, characterisation and antitumour activity of some quercetin analogues

    Directory of Open Access Journals (Sweden)

    M K Gadhwal

    2013-01-01

    Full Text Available Quercetin is one of the most abundant naturally occurring flavonoid and is associated with a wide range of biological activities, such as antioxidant, antiinflammatory and anticancer activities. However, there are multiple problems associated with the bioavailability of quercetin, thereby restricting its use. Taking this into consideration, the structure of quercetin was modified by removal of multiple hydroxyl groups and introduction of substituents such as Cl, OCH 3 and N (CH 3 2 on the p-position of the B-ring. The effect of structural modification on the anticancer activity was studied using four different cell lines, including MCF-7, HepG2, HCT-15 and PC-3. Compound 1a has shown an activity better than quercetin in HepG2 cell lines, whereas 1c and 1e showed significant growth inhibition of the HCT-15 cell lines.

  12. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    Science.gov (United States)

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (pliver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

  13. Antitumour and antioxidant activity of some Red Sea seaweeds in Ehrlich ascites carcinoma in vivo.

    Science.gov (United States)

    Ahmed, Hanaa H; Hegazi, Muhammad M; Abd-Alla, Howaida I; Eskander, Emad F; Ellithey, Mona S

    2011-01-01

    The antitumour activities of extracts from the Red Sea seaweeds Jania rubens, Sargassum subrepandum, and Ulva lactuca were investigated in an in vivo mice model based on intramuscular injection of Ehrlich ascites tumour cells. In parallel, antioxidant activities were measured. Tumour marker levels, liver biochemical parameters, and hepatic oxidant/antioxidant status were measured to prove the anticancer and antioxidant nature of the algal extracts. Significant decreases in carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) levels, activities of liver enzymes, levels of nitric oxide (NO) and malondialdehyde (MDA), and an increase in total antioxidant capacity (TAC) were recorded in groups treated with the algal extracts. Jania rubens was selected for phytochemical screening of its phytoconstituents. In addition, carotenoids, halides, minerals, lipoidal matters, proteins, and carbohydrates were studied. Furthermore, 7-oxo-cholest-5(6)-en-3-ol (1) and cholesterol (2) were isolated from the dichloromethane fraction. PMID:21950161

  14. Structure and antitumour activity of fucoidan isolated from sporophyll of Korean brown seaweed Undaria pinnatifida

    Czech Academy of Sciences Publication Activity Database

    Synytsya, A.; Kim, W. J.; Kim, S. M.; Pohl, Radek; Synytsya, Al.; Kvasnička, F.; Čopíková, J.; Park, Y. I.

    2010-01-01

    Roč. 81, č. 1 (2010), s. 41-48. ISSN 0144-8617 Institutional research plan: CEZ:AV0Z40550506 Keywords : fucoidan from sporophyll Undaria pinnatifida * structure * antitumour activity Subject RIV: CC - Organic Chemistry Impact factor: 3.463, year: 2010

  15. Anti-tumour activities of fucoidan from the aquatic plant Utricularia aurea lour

    Directory of Open Access Journals (Sweden)

    Wilaiwan Chotigeat

    2005-12-01

    Full Text Available Fucoidan, a sulfated polysaccharide with several biological activities, is usually isolated from marine seaweeds or from echinoderms. Here, we report on the anti-tumour activity of fucoidan isolated from the aquatic plant Utricularia aurea Lour (Lentibulariaceae. A crude extract (CE prepared by incubating U.aurea with hot water at 95ºC for 12 hr was partially purified by Sephadex G-50, eluting with a 50mM sodium acetate buffer, at pH 5.0, containing 0.5M NaCl. Partially purified fucoidan (PPF had a 3- fold increase in fucose content when compared with the CE and a molecular weigÄt of 11.6 kDa as determined by Sephadex G-200. Chemical analysis showed that CE consisted of 62.5% glucuronic acid, 5.0% fucose, 1.7% sulfate and 12.0% proteins while PPF consisted of 65.0% glucuronic acid, 15.3% fucose, 2.1 % sulfate and 8.3% proteins.The anti-tumour activity of the CE and PPF was determined by the MTT test. The CE at 125 μg/mL fucoidan and PPF at 250 μg/mL inhibited the growth of KB cells (a nasopharynx tumour cell line, but did not inhibit that of normal fibroblast cells. The inhibition was postulated to occur via apoptosis as significantlymore apoptotic cells were found after treatment than in the untreated KB cells (P<0.05 by the TUNNEL (TdT-mediated dUTP Nick-End Labelling assay.

  16. Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators

    International Nuclear Information System (INIS)

    Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises angiostatin from other plasmin molecules, a process requiring a donor of a free sulfhydryl group. In previous studies, it has been demonstrated that administration of PA in combination with the free sulfhydryl donor (FSD) agents captopril or N-acetyl cysteine, resulted in angiostatin generation, and anti-angiogenic and anti-tumour activity in murine models. In this study we have investigated the angiostatin generating capacities of several FSDs. D-penicillamine proved to be most efficient in supporting the conversion of plasminogen to angiostatin in vitro. Next, from the optimal concentrations of tPA and D-penicillamine in vitro, equivalent dosages were administered to healthy Balb/c mice to explore upregulation of circulating angiostatin levels. Finally, anti-tumor effects of treatment with tPA and D-penicillamine were determined in a human melanoma xenograft model. Surprisingly, we found that despite the superior angiostatin generating capacity of D-penicillamine in vitro, both in vivo angiostatin generation and anti-tumour effects of tPA/D-penicillamine treatment were impaired compared to our previous studies with tPA and captopril. Our results indicate that selecting the most appropriate free sulfhydryl donor for anti-angiogenic therapy in a (pre)clinical setting should be performed by in vivo rather than by in vitro studies. We conclude that D-penicillamine is not suitable for this type of therapy

  17. Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators

    Directory of Open Access Journals (Sweden)

    Maass Cathy N

    2006-06-01

    Full Text Available Abstract Background Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs. Next, plasmin excises angiostatin from other plasmin molecules, a process requiring a donor of a free sulfhydryl group. In previous studies, it has been demonstrated that administration of PA in combination with the free sulfhydryl donor (FSD agents captopril or N-acetyl cysteine, resulted in angiostatin generation, and anti-angiogenic and anti-tumour activity in murine models. Methods In this study we have investigated the angiostatin generating capacities of several FSDs. D-penicillamine proved to be most efficient in supporting the conversion of plasminogen to angiostatin in vitro. Next, from the optimal concentrations of tPA and D-penicillamine in vitro, equivalent dosages were administered to healthy Balb/c mice to explore upregulation of circulating angiostatin levels. Finally, anti-tumor effects of treatment with tPA and D-penicillamine were determined in a human melanoma xenograft model. Results Surprisingly, we found that despite the superior angiostatin generating capacity of D-penicillamine in vitro, both in vivo angiostatin generation and anti-tumour effects of tPA/D-penicillamine treatment were impaired compared to our previous studies with tPA and captopril. Conclusion Our results indicate that selecting the most appropriate free sulfhydryl donor for anti-angiogenic therapy in a (preclinical setting should be performed by in vivo rather than by in vitro studies. We conclude that D-penicillamine is not suitable for this type of therapy.

  18. Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

    OpenAIRE

    Kim, Tak-Heun; Bae, Cheol-Hyeon; Jang, Eun-Ha; Yoon, Chi-Young; Bae, Young; Ko, Seung-O; Taketo, Makoto M.; Cho, Eui-Sic

    2012-01-01

    Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb+/lox(ex3) mice with Col1a1-cre...

  19. Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon.

    OpenAIRE

    Double, J A; Bibby, M. C.; Loadman, P.M.

    1986-01-01

    LM985 is one of a series of compounds based on the flavone ring structure and selected for clinical trial primarily for its activity in colon 38 as part of the NCI screen. We have investigated the anti-tumour activity against three differing transplantable adenocarcinomas of the mouse colon (MAC). Single i.p. injection at maximum tolerated dose showed no activity against the ascitic tumour MAC 15A, moderate activity against subcutaneous tumours MAC 13 and MAC 15A and produced a significant gr...

  20. Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Skjoedt, Mikkel-Ole; Garred, Peter

    2013-01-01

    complement pathway regulator MAP-1. Furthermore, we found that complex formation between recombinant collectin-11 and recombinant MASP-2 on Candida albicans leads to deposition of C4b. Native collectin-11 in serum mediated complement activation and deposition of C4b and C3b, and formation of the terminal...... complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway in...

  1. Chemistry of phosphorus ylides 31: Reaction of azidocoumarin with active phosphonium ylides, synthesis and antitumour activities of chromenones

    Indian Academy of Sciences (India)

    Soher S Maigali; Mansoura A Abd-El-Maksoud; Fouad M Soliman

    2013-11-01

    The reaction of 4- azidochromen-2-one (1) with the nucleophilic phosphacumulene ylides 2, 8, and 12 afforded the new heterocyclic triazoles, triazepines, aziridine, pyrrolone containing a coumarin moiety. Cycloaddition reactions took place first to give triazoline 3 and 9. The triazolines rearranged to the triazepines 4, 10, and 13 accompanied by elimination of triphenylphosphine leading to the phosphorus-free triazepines 5, 11, and moreover, aziridine 6 was produced via nitrogen extrusion from the triazoline 3, followed by ring expansion to the pyrrolone 7. On the other hand, the reaction of the azidocoumarin 1 with the phosphallene yield 15 behaves differently and afforded the triazine 17 and azetone 18. The antitumour activity of compounds 3, 4, 6, and 11 was evaluated, in vitro, against (breast: MCF-7 and liver: HPEG2) human solid tumour cell lines. They showed values closed to that recorded by the reference drug doxorubicin.

  2. Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff. ex T. Anders (Guttiferae)

    OpenAIRE

    Abdul M. Ali; Nashriyah Mat; Lajis, Nordin H.; Mooi, Lim Y.; Mohidin Amran; Mackeen, Mukram M.

    2012-01-01

    The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide (1) and 1′,1′′-dibutyl methyl hydroxycitrate (2), that had been previously isolated from the fruits of Garcinia atroviridis Griff. ex T. Anders (Guttiferae), were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation, compound 1 (IC50: 70  μ M) showed much higher (8-fol...

  3. The antitumour activity of maltose tetrapalmitate compared with other immunoadjuvants, and its effectiveness after tumour surgery.

    OpenAIRE

    El Kappany, H.; Chopra, C.; Nigam, V. N.; Brailovsky, C. A.; Elhilali, M.

    1980-01-01

    The effectivenss of maltose tetrapalmitate (MTP) as an antitumour immune adjuvant was verified by its comparison with other known immunopotentiators, namely BCG, Corynebacterium parvum, levamisole and pyran copolymer. Copenhagen x Fisher 344/CRBL F1 hybrid male rats inoculated s.c. with the Dunning R3327A prostatic adenocarcinoma were used as the test system. All animals treated with immunoadjuvants showed a delay in tumour appearance and inhibition of early tumour growth. MTP was found to be...

  4. In vitro platelet activation, aggregation and platelet-granulocyte complex formation induced by surface modified single-walled carbon nanotubes.

    Science.gov (United States)

    Fent, János; Bihari, Péter; Vippola, Minnamari; Sarlin, Essi; Lakatos, Susan

    2015-08-01

    Surface modification of single-walled carbon nanotubes (SWCNTs) such as carboxylation, amidation, hydroxylation and pegylation is used to reduce the nanotube toxicity and render them more suitable for biomedical applications than their pristine counterparts. Toxicity can be manifested in platelet activation as it has been shown for SWCNTs. However, the effect of various surface modifications on the platelet activating potential of SWCNTs has not been tested yet. In vitro platelet activation (CD62P) as well as the platelet-granulocyte complex formation (CD15/CD41 double positivity) in human whole blood were measured by flow cytometry in the presence of 0.1mg/ml of pristine or various surface modified SWCNTs. The effect of various SWCNTs was tested by whole blood impedance aggregometry, too. All tested SWCNTs but the hydroxylated ones activate platelets and promote platelet-granulocyte complex formation in vitro. Carboxylated, pegylated and pristine SWCNTs induce whole blood aggregation as well. Although pegylation is preferred from biomedical point of view, among the samples tested by us pegylated SWCNTs induced far the most prominent activation and a well detectable aggregation of platelets in whole blood. PMID:25956790

  5. P–C-Activated Bimetallic Rhodium Xantphos Complexes: Formation and Catalytic Dehydrocoupling of Amine–Boranes**

    Science.gov (United States)

    Johnson, Heather C; Weller, Andrew S

    2015-01-01

    {Rh(xantphos)}-based phosphido dimers form by P–C activation of xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) in the presence of amine–boranes. These dimers are active dehydrocoupling catalysts, forming polymeric [H2BNMeH]n from H3B⋅NMeH2 and dimeric [H2BNMe2]2 from H3B⋅NMe2H at low catalyst loadings (0.1 mol %). Mechanistic investigations support a dimeric active species, suggesting that bimetallic catalysis may be possible in amine–borane dehydropolymerization. PMID:26140498

  6. Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

    Science.gov (United States)

    Perucca, Paola; Savio, Monica; Cazzalini, Ornella; Mocchi, Roberto; Maccario, Cristina; Sommatis, Sabrina; Ferraro, Daniela; Pizzala, Roberto; Pretali, Luca; Fasani, Elisa; Albini, Angelo; Stivala, Lucia Anna

    2014-11-01

    The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue. PMID:25105482

  7. EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages

    International Nuclear Information System (INIS)

    Activated macrophage cytotoxicity is characterized by loss of intracellular iron and inhibition of certain enzymes that have catalytically active nonheme-iron coordinated to sulfur. This phenomenon involves the oxidation of one of the terminal guanidino nitrogen atoms of L-arginine, which results in the production of citrulline and inorganic nitrogen oxides (NO2-, NO3-, and NO). We report here the results of an electron paramagnetic resonance spectroscopic study performed on cytotoxic activated macrophage (CAM) effector cells, which develop the same pattern of metabolic inhibition as their targets. Examination of activated macrophages from mice infected with Mycobacterium bovis (strain bacillus Calmette-Guerin) that were cultured in medium with lipopolysaccharide and L-arginine showed the presence of an axial signal at g = 2.039, which is similar to previously described iron-nitrosyl complexes formed from the destruction of iron-sulfur centers by nitric oxide (NO). Inhibition of the L-arginine-dependent pathway by addition of NG-monomethyl-L-arginine (methyl group on a terminal guanidino nitrogen) inhibits the production of nitrite, nitrate, citrulline, and the g = 2.039 signal. Comparison of the hyperfine structure of the signal from cells treated with L-arginine with terminal guanidino nitrogen atoms of natural abundance N14 atoms or labeled with N15 atoms showed that the nitrosyl group in this paramagnetic species arises from one of these two atoms. These results show that loss of iron-containing enzyme function in CAM is a result of the formation of iron-nitrosyl complexes induced by the synthesis of nitric oxide from the oxidation of a terminal guanidino nitrogen atom of L-arginine

  8. Glucosylation activity and complex formation of two classes of reversibly glycosylated polypeptides.

    Science.gov (United States)

    Langeveld, Sandra M J; Vennik, Marco; Kottenhagen, Marijke; Van Wijk, Ringo; Buijk, Ankie; Kijne, Jan W; de Pater, Sylvia

    2002-05-01

    Reversibly glycosylated polypeptides (RGPs) have been implicated in polysaccharide biosynthesis. In plants, these proteins may function, for example, in cell wall synthesis and/or in synthesis of starch. We have isolated wheat (Triticum aestivum) and rice (Oryza sativa) Rgp cDNA clones to study the function of RGPs. Sequence comparisons showed the existence of two classes of RGP proteins, designated RGP1 and RGP2. Glucosylation activity of RGP1 and RGP2 from wheat and rice was studied. After separate expression of Rgp1 and Rgp2 in Escherichia coli or yeast (Saccharomyces cerevisiae), only RGP1 showed self-glucosylation. In Superose 12 fractions from wheat endosperm extract, a polypeptide with a molecular mass of about 40 kD is glucosylated by UDP-glucose. Transgenic tobacco (Nicotiana tabacum) plants, overexpressing either wheat Rgp1 or Rgp2, were generated. Subsequent glucosylation assays revealed that in RGP1-containing tobacco extracts as well as in RGP2-containing tobacco extracts UDP-glucose is incorporated, indicating that an RGP2-containing complex is active. Gel filtration experiments with wheat endosperm extracts and extracts from transgenic tobacco plants, overexpressing either wheat Rgp1 or Rgp2, showed the presence of RGP1 and RGP2 in high-molecular mass complexes. Yeast two-hybrid studies indicated that RGP1 and RGP2 form homo- and heterodimers. Screening of a cDNA library using the yeast two-hybrid system and purification of the complex by an antibody affinity column did not reveal the presence of other proteins in the RGP complexes. Taken together, these results suggest the presence of active RGP1 and RGP2 homo- and heteromultimers in wheat endosperm. PMID:12011358

  9. Arsenic-Lipid Complex Formation During the Active Transport of Arsenate in Yeast

    Science.gov (United States)

    Cerbón, Jorge

    1969-01-01

    In studying formation of an arsenic-lipid complex during the active transport of 74As-arsenate in yeast, it was found that adaptation of yeast to arsenate resulted in cell populations which showed a deficient inflow of arsenate as compared to the nonadapted yeast. Experiments with both types of cells showed a direct correlation between the arsenate taken up and the amount of As-lipid complex formed. 74As-arsenate was bound exclusively to the phosphoinositide fraction of the cellular lipids. When arsenate transport was inhibited by dinitrophenol and sodium azide, the formation of the As-lipid complex was also inhibited. Phosphate did not interfere with the arsenate transport at a non-inhibitory concentration of external arsenate (10−9m). The As-adapted cells but not the unadapted cells were able to take up phosphate when growing in the presence of 10−2m arsenate. PMID:5773018

  10. Attempts at the production of more selective antitumourals. Part II. The antineoplastic activity of cyclophosphazenes linked to spermine

    Science.gov (United States)

    Sournies, François; Labarre, Jean-François; Spreafico, Federico; Filippeschi, Stefania; Quan Jin, Xing

    1986-09-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to spermine. Synthesis, NMR and mass spectra of the vectorized drug (in which two N 3P 3Az 4 active principles are linked to spermine in a DISPIROBINO configuration) are described. Results obtained with this compound in 6 murine tumour systems (L1210 and P388 leukaemias, 3LL carcinoma, M5076 reticulum cell sarcoma, B16 melanoma and line 16 mammary carcinoma), are also described and compared with results previously obtained about the targeting of gem-N 3P 3Az 4Cl 2 through 1,3-diaminopropane and 1,4-diaminobutane (putrescine).

  11. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy

    Science.gov (United States)

    Yu, Y; Rahmanto, Y Suryo; Richardson, DR

    2012-01-01

    BACKGROUND AND PURPOSE Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led to cardiotoxicity at non-optimal doses. In this study, we examined the in vivo anti-tumour efficacy and tolerability of a new-generation 2-benzoylpyridine thiosemicarbazone iron chelator (2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone; Bp44mT) administered via the oral or i.v. routes. EXPERIMENTAL APPROACH BpT chelators were tested in vitro against human lung cancer cells (DMS-53) and in vivo in DMS-53 tumour xenografts in mice. The toxicity of Bp44mT in vivo and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. KEY RESULTS Administration of Bp44mT by either route resulted in marked dose-dependent inhibition of tumour growth. When administered at 50 mg·kg−1 via oral gavage three times per week for 23 days, the net xenograft growth was inhibited by 75%, compared with vehicle-treated mice. Toxicological examination showed reversible alterations including slight reduction of RBC count, with a decrease of liver and splenic iron levels, which confirmed iron chelation in vivo. Importantly, in contrast to Dp44mT, the chelator-treated mice did not show cardiac histological abnormalities. There was also no significant weight loss in mice, suggesting oral administration of Bp44mT was well tolerated. CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti-tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. PMID:21658021

  12. Complex formation and catalytic activation by the PII signaling protein of N-acetyl-L-glutamate kinase from Synechococcus elongatus strain PCC 7942.

    Science.gov (United States)

    Maheswaran, Mani; Urbanke, Claus; Forchhammer, Karl

    2004-12-31

    The signal transduction protein P(II) from the cyanobacterium Synechococcus elongatus strain PCC 7942 forms a complex with the key enzyme of arginine biosynthesis, N-acetyl-l-glutamate kinase (NAGK). Here we report the effect of complex formation on the catalytic properties of NAGK. Although pH and ion dependence are not affected, the catalytic efficiency of NAGK is strongly enhanced by binding of P(II), with K(m) decreasing by a factor of 10 and V(max) increasing 4-fold. In addition, arginine feedback inhibition of NAGK is strongly decreased in the presence of P(II), resulting in a tight control of NAGK activity under physiological conditions by P(II). Analysis of the NAGK-P(II) complex suggests that one P(II) trimer binds to one NAGK hexamer with a K(d) of approximately 3 nm. Complex formation is strongly affected by ATP and ADP. ADP is a strong inhibitor of complex formation, whereas ATP inhibits complex formation only in the absence of divalent cations or in the presence of Mg(2+) ions, together with increased 2-oxoglutarate concentrations. Ca(2+) is able to antagonize the negative effect of ATP and 2-oxoglutarate. ADP and ATP exert their adverse effect on NAGK-P(II) complex formation through binding to the P(II) protein. PMID:15502156

  13. Preparation, characterisation and antitumour activity of β-, γ- and HP-β-cyclodextrin inclusion complexes of oxaliplatin

    Science.gov (United States)

    Zhang, Da; Zhang, Jianqiang; Jiang, Kunming; Li, Ke; Cong, Yangwei; Pu, Shaoping; Jin, Yi; Lin, Jun

    2016-01-01

    Three water-soluble oxaliplatin complexes were prepared by inclusion complexation with β-cyclodextrin (β-CD), γ-CD and HP-β-CD. The structures of oxaliplatin/CDs were confirmed by NMR, FTIR, TGA, XRD as well as SEM analysis. The results show that the water solubility of oxaliplatin was increased in the complex with CDs in 1:1 stoichiometry inclusion modes, and the cyclohexane ring of oxaliplatin molecule was deeply inserted into the cavity of CDs. Moreover, the stoichiometry was established by a Job plot and the water stability constant (Kc) of oxaliplatin/CDs was calculated by phase solubility studies, all results show that the oxaliplatin/β-CD complex is more stable than free oxaliplatin, oxaliplatin/HP-β-CD and oxaliplatin/γ-CD. Meanwhile, the inclusion complexes displayed almost twice as high cytotoxicity compared to free oxaliplatin against HCT116 and MCF-7 cells. This satisfactory water solubility and higher cytotoxic activity of the oxaliplatin/CD complexes will potentially be useful for their application in anti-tumour therapy.

  14. Synthesis and in vitro antitumour activity of tiazofurin analogues with nitrogen functionalities at the C-2' position.

    Science.gov (United States)

    Popsavin, Mirjana; Kojić, Vesna; Torović, Ljilja; Svirčev, Miloš; Spaić, Saša; Jakimov, Dimitar; Aleksić, Lidija; Bogdanović, Gordana; Popsavin, Velimir

    2016-03-23

    Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose. A number of potential bioisosteres of 1 bearing acylamido functions at the C-2' position have also been synthesized from the same sugar precursor. In vitro cytotoxicities of target molecules against a number of human tumour cell lines were recorded and compared with those observed for lead molecule 1. Some of the synthesized compounds showed potent in vitro antitumour activity, such as 2'-azido derivative 2, which is the most potent of all molecules under evaluation (IC50 0.004 μM against MCF-7 cells). Flow cytometry data suggest that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of Western blot analysis indicate that the synthesized tiazofurin analogues induce apoptosis in a caspase-dependent way. PMID:26859071

  15. Molecular insights on the biosynthesis of antitumour compounds by actinomycetes

    OpenAIRE

    Olano Álvarez, Carlos; Méndez Fernández, María del Carmen; Salas Fernández, José Antonio

    2011-01-01

    Summary Natural products are traditionally the main source of drug leads. In particular, many antitumour compounds are either natural products or derived from them. However, the search for novel antitumour drugs active against untreatable tumours, with fewer side‐effects or with enhanced therapeutic efficiency, is a priority goal in cancer chemotherapy. Microorganisms, particularly actinomycetes, are prolific producers of bioactive compounds, including antitumour drugs, produced as secondary ...

  16. Mapping of contact sites in complex formation between light-activated rhodopsin and transducin by covalent crosslinking: Use of a chemically preactivated reagent

    OpenAIRE

    ITOH, Yoshiki; Cai, Kewen; Khorana, H. Gobind

    2001-01-01

    Contact sites in interaction between light-activated rhodopsin and transducin (T) have been investigated by using a chemically preactivated crosslinking reagent, N-succinimidyl 3-(2-pyridyldithio)propionate. The 3 propionyl-N-succinimidyl group in the reagent was attached by a disulfide exchange reaction to rhodopsin mutants containing single reactive cysteine groups in the cytoplasmic loops. Complex formation between the derivatized rhodopsin mutants and T was ...

  17. Design, synthesis and in vitro antitumour activity of new heteroaryl ethylenes.

    Science.gov (United States)

    Fortuna, Cosimo G; Barresi, Vincenza; Bonaccorso, Carmela; Consiglio, Giuseppe; Failla, Salvatore; Trovato-Salinaro, Angela; Musumarra, Giuseppe

    2012-01-01

    Almond and VolSurf + modelling procedures allowed the structural design of new di- and mono-heteroaryl-ethylenes. The structural modifications suggested by the molecular modelling were verified by the synthesis of the designed molecules and by the evaluation of their in vitro activities against two lung tumour cell lines, A549 and H226. 2-{(E)-2-[5'-(Dibutylamino)-2,2'-bithien-5-yl]vinyl}-1-methylquinolinium iodide exhibited in vitro antiproliferative activity two orders of magnitude higher than that of the most active compound previously synthesized in our laboratory. PMID:22119128

  18. Synthesis, Characterization and In Vitro Antitumour Activity of Di-n-Butyl, Tri-n-Butyl and Triphenyltin 3,6-Dioxaheptanoates and 3,6,9-Trioxadecanoates

    OpenAIRE

    Kemmer, Martine; Gielen, Marcel; Biesemans, Monique; de Vos, Dick; Willem, Rudolph

    1998-01-01

    A series of di- and triorganotin 3,6-dioxaheptanoates and 3,6,9-trioxadecanoates were synthesized and characterized by H1, C13 and S117n NMR, electrospray mass and S119mn Mössbauer spectroscopy, as well as elemental analysis. Their in vitro antitumour activity against seven tumoural cell lines of human origin, two breast cancers (MCF-7, EVSA-T), a colon carcinoma (WiDr), an ovarian cancer (IGROV), a melanoma (M 19 MEL), a renal cancer (A 498) and a non small cell lung cancer (H 226), is repor...

  19. Antitumour Activity of a pt(III) Derivative of 2-Mercaptopyrimidine

    Science.gov (United States)

    Cervantes, G.; Prieto, M. J.

    1997-01-01

    The complex [Pt2Cl2(Spym)4], where Spym = 2-mercaptopyrimidine, was synthesized and analyzed spectroscopically. The presence in the 195Pt NMR spectrum, of only one signal for the Pt(III) indicates the symmetrical arrangement of the ligands and the identical setting of N, S and Cl atoms, PtS2ClN2, for the two Pt atoms being different to other compounds described in the literature. The interaction of this complex with DNA was studied by several techniques, including circular dichroism, melting temperature determination, electron microscopy (EM) and atomic force microscopy (TMAFM). Preliminary results show a high activity against HL-60 and HeLa tumour lines for the Pt-2-mercaptopyrimidine complex in comparison with cisplatin activity. Higher values for IC50 were obtained, while the values of LD50 were lower than those for cisplatin. PMID:18475760

  20. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

    OpenAIRE

    Silconi Žana Besser; Benazic Sasa; Milovanovic Jelena; Arsenijevic Aleksandar; Stojanovic Bojana; Milovanovic Marija; Kanjevac Tatjana

    2015-01-01

    Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity...

  1. Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

    International Nuclear Information System (INIS)

    The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells

  2. Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

    Energy Technology Data Exchange (ETDEWEB)

    Gatea, Florentina; Teodor, Eugenia Dumitra, E-mail: eu-teodor@yahoo.com [National Institute for Biological Sciences, Centre of Bioanalysis (Romania); Seciu, Ana-Maria [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Covaci, Ovidiu Ilie [SARA Pharm Solutions (Romania); Mănoiu, Sorin [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Lazăr, Veronica [University of Bucharest, Faculty of Biology (Romania); Radu, Gabriel Lucian [University “Politehnica” Bucharest, Faculty of Applied Chemistry and Materials Science (Romania)

    2015-07-15

    The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

  3. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Silconi Žana Besser

    2015-09-01

    Full Text Available Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity, ototoxicity, and neurotoxicity. Although cisplatin is one of the most successful anticancer drugs to date, its biochemical mechanism of action is still unclear. Cisplatin is generally accepted as having the ability to interact with the purine bases on the DNA, causing DNA damage, interfering with DNA repair mechanisms, and subsequently inducing apoptosis in cancer cells.

  4. Formation, Structure and In Vitro Antitumour Activity of a Novel Binuclear Organotin Complex

    Institute of Scientific and Technical Information of China (English)

    Lai Jin TIAN; Yu Xi SUN; Guo Ming YANG; Bo Chu QIAN; Zhi Cai SHANG

    2005-01-01

    A 1:1 reaction of triphenyltin chloride with potassium N-[(3,5-dibromo-2-hydroxyl-phenyl)methylene]valinate in benzene led to the formation of a novel mixed organotin dinuclear phenyl-tin bond cleavage process. In the complex, there are two distinct types of carboxylate moieties and a trans-O2SnC2N and a trans-O2SnC3 in distorted trigonal bipyramidal geometries were bridged by a carboxylate group. In vitro antimmor activity of the complex against three human tumour cell lines (HeLa, CoLo205 and MCF-7) was found to be much higher than cis-platin used in clinic.

  5. MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Lothe Ragnhild A

    2011-05-01

    Full Text Available Abstract Background Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy. Methods A panel of sarcoma cell lines with different TP53 and MDM2 status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined. Results Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type TP53 and amplified MDM2, or with Methotrexate in both MDM2 normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated TP53, but inhibited the effect of Methotrexate. Conclusion The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.

  6. DNA binding, anti-tumour activity and reactivity toward cell thiols of acridin-9-ylalkenoic derivatives

    Indian Academy of Sciences (India)

    O Salem; M Vilkova; J Plsikova; A Grolmusova; M Burikova; M Prokaiova; H Paulikova; J Imrich; M Kozurkova

    2015-05-01

    In this paper, we describe the synthesis, biochemical properties and biological activity of a series of new 9-substituted acridine derivatives with a reactive alkene moiety: 9-[(E)-2-phenylethenyl] acridine (1) and methyl (2E)-3-(acridin-9-yl)-prop-2-enoate (2). The interaction of derivatives 1 and 2 with calf thymus DNA was investigated using UV-Vis, fluorescence and circular dichroism spectroscopy. The binding constants K were estimated as being in the range of 1.9 to 7.1 × 105 M−1, and the percentage of hypochromism was found to be 40–57% (from spectral titration). UV-Vis, fluorescence, and CD measurements indicate that the compounds were effective DNA-intercalating agents. Electrophoretic separation proved that ligands 1 and 2 relaxed topoisomerase I at a concentration of 5 M. Ester 2 was shown to have a stronger cytostatic effect on leukemia cell line L1210 than alkene 1. The incubation of ligands 1 and 2 with the ovarian carcinoma cell line A2780 confirmed their extensive cytotoxic effects, an effect which was particularly pronounced in the case of ligand 2. Cytotoxicity tests against A2780 cells demonstrate that a conjugate of compound 2 with -cysteine (3) is less cytotoxic than compound 2, especially at concentrations greater than 10 M.

  7. VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells

    Directory of Open Access Journals (Sweden)

    Ayumi Yoshida

    2015-09-01

    Full Text Available Neuropilin-1 (NRP1 has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

  8. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    Science.gov (United States)

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  9. Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy.

    Science.gov (United States)

    Jamdade, Vinayak Sudhir; Mundhe, Nitin A; Kumar, Parveen; Tadla, Venkatesh; Lahkar, Mangala

    2016-01-01

    Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumours like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its anti-tumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFκB). Moreover, assessment of tumour reduction was done by measuring tumour volume and percentage tumour reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-α and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-α and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumour reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumour activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity. PMID:26439246

  10. Competition between Decapping Complex Formation and Ubiquitin-Mediated Proteasomal Degradation Controls Human Dcp2 Decapping Activity

    OpenAIRE

    Erickson, Stacy L.; Corpuz, Elizabeth O.; Maloy, Jeffrey P.; Fillman, Christy; Webb, Kristofer; Bennett, Eric J.; Lykke-Andersen, Jens

    2015-01-01

    mRNA decapping is a central step in eukaryotic mRNA decay that simultaneously shuts down translation initiation and activates mRNA degradation. A major complex responsible for decapping consists of the decapping enzyme Dcp2 in association with decapping enhancers. An important question is how the activity and accumulation of Dcp2 are regulated at the cellular level to ensure the specificity and fidelity of the Dcp2 decapping complex. Here, we show that human Dcp2 levels and activity are contr...

  11. Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro

    Science.gov (United States)

    Lio, Yi-Ching; Mazin, Alexander V.; Kowalczykowski, Stephen C.; Chen, David J.

    2003-01-01

    The human Rad51 protein is essential for DNA repair by homologous recombination. In addition to Rad51 protein, five paralogs have been identified: Rad51B/Rad51L1, Rad51C/Rad51L2, Rad51D/Rad51L3, XRCC2, and XRCC3. To further characterize a subset of these proteins, recombinant Rad51, Rad51B-(His)(6), and Rad51C proteins were individually expressed employing the baculovirus system, and each was purified from Sf9 insect cells. Evidence from nickel-nitrilotriacetic acid pull-down experiments demonstrates a highly stable Rad51B.Rad51C heterodimer, which interacts weakly with Rad51. Rad51B and Rad51C proteins were found to bind single- and double-stranded DNA and to preferentially bind 3'-end-tailed double-stranded DNA. The ability to bind DNA was elevated with mixed Rad51 and Rad51C, as well as with mixed Rad51B and Rad51C, compared with that of the individual protein. In addition, both Rad51B and Rad51C exhibit DNA-stimulated ATPase activity. Rad51C displays an ATP-independent apparent DNA strand exchange activity, whereas Rad51B shows no such activity; this apparent strand exchange ability results actually from a duplex DNA destabilization capability of Rad51C. By analogy to the yeast Rad55 and Rad57, our results suggest that Rad51B and Rad51C function through interactions with the human Rad51 recombinase and play a crucial role in the homologous recombinational repair pathway.

  12. A systematic comparison of the anti-tumoural activity and toxicity of the three Adv-TKs.

    Directory of Open Access Journals (Sweden)

    Qinglei Gao

    Full Text Available Adenovirus 5 vectors, known respectively as, the first generation, second generation and oncolytic adenovirus, have been studied extensively in preclinical and clinical trials. However, hitherto few systemic evaluations of the efficacy and toxicity of these adenoviral vectors that have reflected the vertical history of adenovirus based cancer gene therapy strategies have been undertaken. This study has chosen Adv-TK, the well-established adjuvant treatment in cancer, and compared its efficacy and safety with those of the two newly synthesized oncolytic adenovirus vectors encoding the HSV-TK gene, namely M7 and M8. The results obtained showed that systemic administration of 1×10(8 pfu M7 had an anti-tumour efficacy similar to that of 3×10(10 pfu Adv-TK whilst M8 performed even better. Furthermore, compared to Adv-TK, M7 and M8 reduced the incidence of metastases and substantially prolonged the survival time of the mice xenografted with human orthotopic gastric carcinomas with disseminated metastasis. Even more exciting, however, were the similar toxic and immune safety results obtained from the administration of high doses of M7 or M8 in comparison with Adv-TK in immunocompetent and permissive syrian hamster. The data here exhibit a comprehensive display of the efficacy and safety of the three mutants and provide evidence for the future preclinical use of the M7 and M8 viruses.

  13. Differential reaction kinetics, cleavage complex formation, and nonamer binding domain dependence dictate the structure-specific and sequence-specific nuclease activity of RAGs.

    Science.gov (United States)

    Naik, Abani Kanta; Raghavan, Sathees C

    2012-01-20

    During V(D)J recombination, RAG (recombination-activating gene) complex cleaves DNA based on sequence specificity. Besides its physiological function, RAG has been shown to act as a structure-specific nuclease. Recently, we showed that the presence of cytosine within the single-stranded region of heteroduplex DNA is important when RAGs cleave on DNA structures. In the present study, we report that heteroduplex DNA containing a bubble region can be cleaved efficiently when present along with a recombination signal sequence (RSS) in cis or trans configuration. The sequence of the bubble region influences RAG cleavage at RSS when present in cis. We also find that the kinetics of RAG cleavage differs between RSS and bubble, wherein RSS cleavage reaches maximum efficiency faster than bubble cleavage. In addition, unlike RSS, RAG cleavage at bubbles does not lead to cleavage complex formation. Finally, we show that the "nonamer binding region," which regulates RAG cleavage on RSS, is not important during RAG activity in non-B DNA structures. Therefore, in the current study, we identify the possible mechanism by which RAG cleavage is regulated when it acts as a structure-specific nuclease. PMID:22119487

  14. New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ (PPARγ Antitumour Activity: Perspectives from the Insulin Receptor

    Directory of Open Access Journals (Sweden)

    Daniela P. Foti

    2009-01-01

    Full Text Available The insulin receptor (IR plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγ is a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγ agonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγ and activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγ and agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ “target” gene, supporting a potential use of PPARγ agonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR.

  15. The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia.

    Science.gov (United States)

    Tomalova, Barbora; Sirova, Milada; Rossmann, Pavel; Pola, Robert; Strohalm, Jiri; Chytil, Petr; Cerny, Viktor; Tomala, Jakub; Kabesova, Martina; Rihova, Blanka; Ulbrich, Karel; Etrych, Tomas; Kovar, Marek

    2016-02-10

    Polymer drug carriers that are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (Mw ~27kDa, Rh ~4nm) and non-degradable star (Mw ~250kDa, Rh ~13nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85mgDOX/kg) and lower for the star conjugate (22.5mgDOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate. On the other hand, treatment of EL4 lymphoma seemed to be more efficient when the linear conjugate was used. We suppose that the anti-cancer treatment of solid tumours and leukaemias requires different types of drug conjugates. We hypothesise that the most suitable HPMA copolymer-DOX conjugate for the treatment of solid tumours should have an HMW structure with increased Rh that would be stable for three to four days after the conjugate administration and then rapidly disintegrate in the short polymer chains, which are excretable from the body by glomerular filtration. On the other hand, the treatment of leukaemia requires a drug conjugate with a long circulation half-life. This would provide an active drug, whilst slowly degrading to excretable fragments. PMID:26708020

  16. Clusterin inhibition using OGX-011 synergistically enhances antitumour activity of sorafenib in a human renal cell carcinoma model

    OpenAIRE

    Kususda, Y; Miyake, H; Gleave, M. E.; Fujisawa, M.

    2012-01-01

    Background: The objective of this study was to investigate whether the therapeutic activity of sorafenib could be enhanced by combining with OGX-011, an antisense oligodeoxynucleotide (ODN) targeting clusterin, in renal cell carcinoma (RCC). Methods: We investigated the effects of combined treatment with OGX-011 and sorafenib on a human RCC ACHN model both in vitro and in vivo. Results: Although clusterin expression was increased by sorafenib, additional treatment of ACHN with OGX-011 signifi...

  17. Enhanced uptake and translocation of arsenic in Cretan brake fern (Pteris cretica L.) through siderophorearsenic complex formation with an aid of rhizospheric bacterial activity.

    Science.gov (United States)

    Jeong, Seulki; Moon, Hee Sun; Nam, Kyoungphile

    2014-09-15

    Siderophores, produced by Pseudomonas aeruginosa, released slightly more Fe (53.6 μmol) than that chelated by ethylenediaminetetraacetic acid (EDTA; i.e. 43.7 μmol) in batch experiment using As-adsorbed ferrihydrite. More importantly, about 1.79 μmol of As was found to be associated with siderophores in the aqueous phase due to siderophore-As complex formation when siderophores were used to release As from ferrihydrite. In contrast, As was not detected in the aqueous phase when EDTA was used, probably due to the readsorption of released As to ferrihydrite. A series of pot experiment was conducted to investigate the effect of siderophores as a microbial iron-chelator on As uptake by Cretan brake fern (Pteris cretica L.) during phtoextraction. Results revealed that P. cretica, a known As hyperaccumulator, grown in the siderophore-amended soil showed about 3.7 times higher As uptake (5.62 mg-Asg(-1)-plant) than the plant grown in the EDTA-treated soil (1.51 mg-Asg(-1)-plant). In addition, As taken up by roots of P. cretica in the presence of siderophores seemed to be favorably translocated to shoots (i.e. stems and leaves). About 79% of the accumulated As was detected in the shoots in the presence of siderophores after ten weeks. Fluorescence microscopic analysis confirmed that As in the roots was delivered to the leaves of P. cretica as a siderophore-As complex. PMID:25215655

  18. Attempts at the production of more selective antitumourals. Part I. The antineoplastic activity of cyclophosphazenes linked to the polyamines 1,3-diaminopropane and 1,4-diaminobutane (putrescine)

    Science.gov (United States)

    Labarre, Jean-François; Guerch, Guy; Sournies, François; Spreafico, Federico; Filippeschi, Stefania

    1984-06-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to 1,3-diaminopropane and 1,4-diaminobutane (putrescine). Synthesis, mass spectrum and NMR as well as X-ray crystal structures of the two spirocyclic N 3P 3Az 4 [HN(CH 2) 3,4NH] derivatives (in which the N 3P 3Az 4 active principle is linked to the diamine in a spiro configuration) are described. Results obtained with these compounds in 3 murine tumour systems (L1210 and P388 leukaemias and P815 mastocytoma), showing their potent antineoplastic activity in vivo obtainable at well-tolerated doses, are also described.

  19. A common role of CRP in transcription activation: CRP acts transiently to stimulate events leading to open complex formation at a diverse set of promoters.

    OpenAIRE

    Tagami, H; Aiba, H.

    1998-01-01

    We have shown previously that the cyclic AMP receptor protein (CRP) is not required after the formation of the open complex at the lac promoter (Tagami and Aiba, 1995, Nucleic Acids Res., 19, 6705-6712). In this paper, we investigate the role of CRP in transcription activation at the malT and gal promoters. At the malT promoter, RNA polymerase (RNAP) forms a nonproductive RNAP-promoter binary complex in the absence of CRP and a productive CRP-RNAP-promoter ternary complex in the presence of C...

  20. PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific α-globin expression

    OpenAIRE

    Chul Kang, Ho; Hyung Chae, Ji; Jeon, Jinseon; Kim, Won; Hyun Ha, Dae; Ho Shin, June; Gil Kim, Chan; Geun Kim, Chul

    2010-01-01

    Data presented here extends our previous observations on α-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous α-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In v...

  1. Electron-donor and -acceptor functions of physiologically active substances. XI. Influence of an alkyl substituent in phosphorylated oximes on their complex formation with chloroform-d

    International Nuclear Information System (INIS)

    Phosphorylated alkanoyl chloride oximes were prepared from trialkyl phosphites and the corresponding 1,1-dichloro-1-nitrosoalkenes. In the formation of complexes of chloroform-d with the oximes synthesized the intensity of the stretching vibrations of the carbon-deuterium bond rises considerably, and this provides a basis for the correct evaluation of the stability constants of the complexes. In the series of compounds studied a substantial change was observed in the stability of the complexes with chloroform-d with variation of the chain length and degree of branching of the alkyl group Alk, and this change goes in parallel with the change in the inhibiting activity of the given oximes with respect to certain enzymes

  2. EGF-stimulated activation of Rab35 regulates RUSC2-GIT2 complex formation to stabilize GIT2 during directional lung cancer cell migration.

    Science.gov (United States)

    Duan, Biao; Cui, Jie; Sun, Shixiu; Zheng, Jianchao; Zhang, Yujie; Ye, Bixing; Chen, Yan; Deng, Wenjie; Du, Jun; Zhu, Yichao; Chen, Yongchang; Gu, Luo

    2016-08-28

    Non-small cell lung cancer (NSCLC) remains one of the most metastasizing tumors, and directional cell migration is critical for targeting tumor metastasis. GIT2 has been known to bind to Paxillin to control cell polarization and directional migration. However, the molecular mechanisms underlying roles of GIT2 in controlling cell polarization and directional migration remain elusive. Here we demonstrated GIT2 control cell polarization and direction dependent on the regulation of Golgi through RUSC2. RUSC2 interacts with SHD of GIT2 in various lung cancer cells, and stabilizes GIT2 (Mazaki et al., 2006; Yu et al., 2009) by decreasing degradation and increasing its phosphorylation. Silencing of RUSC2 showed reduced stability of GIT2, defective Golgi reorientation toward the wound edge and decreased directional migration. Moreover, short-term EGF stimulation can increase the interaction between RUSC2 and GIT2, prolonged stimulation leads to a decrease of their interaction through activating Rab35. Silencing of Rab35 also reduced stability and phosphorylation of GIT2 and decreased cell migration. Taken together, our study indicated that RUSC2 participates in EGFR signaling and regulates lung cancer progression, and may be a new therapeutic target against lung cancer metastasis. PMID:27238570

  3. Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo

    OpenAIRE

    Leong, C-O; Gaskell, M; Martin, E. A.; Heydon, R T; Farmer, P B; Bibby, M. C.; Cooper, P.A.; Double, J A; Bradshaw, T D; Stevens, M F G

    2003-01-01

    2-(4-Aminophenyl)benzothiazoles represent a potent and highly selective class of antitumour agent. In vitro, sensitive carcinoma cells deplete 2-(4-aminophenyl)benzothiazoles from nutrient media; cytochrome P450 1A1 activity, critical for execution of antitumour activity, and protein expression are powerfully induced. 2-(4-Amino-3-methylphenyl)benzothiazole-derived covalent binding to cytochrome P450 1A1 is reduced by glutathione, suggesting 1A1-dependent production of a reactive electrophili...

  4. Integrative biological studies of anti-tumour agents

    OpenAIRE

    Johnson, L. A.

    2009-01-01

    3, 11-difluoro-6, 8, 13-trimethyl-8H- quino [4, 3, 2-kl] acridinium methosulfate (RHPS4) is a member of a series of pentacyclic acridines developed at the University of Nottingham, which bind to, and stabilise the structure of G-quadruplex DNA and inhibit the action of telomerase at sub-micromolar concentrations in the cell free TRAP assay and limit cancer cell growth therefore leading to the conclusion that RHPS4 has potential anti-tumour activity. Previous biological studies, however, have...

  5. Synthesis and spectroscopic characterization of 3,4-difluoroacetophenone-thiosemicarbazone and its palladium(II) complex: Evaluation of antimicrobial and antitumour activity

    Science.gov (United States)

    Jagadeesh, M.; Rashmi, H. K.; Subba Rao, Y.; Sreenath Reddy, A.; Prathima, B.; Uma Maheswari Devi, P.; Reddy, A. Varada

    2013-11-01

    A new cis-palladium(II)diaqua(3,4-difluoroacetophenonethiosemicarbazone complex (Pd(II) complex) is synthesized using 3,4-difluoroacetophenonethiosemicarbazone(L). The L and its Pd(II) complex are characterized and confirmed by elemental analyses, electrochemical analyses, FT-IR, FT-Raman, UV-Vis, HRMS and LC-MS techniques. Ligand L is further characterized by 1H, 13C and 19F NMR spectroscopy. The crystal structure of L is unambiguously characterized by single X-ray crystallography. The ligand (L) belongs to monoclinic system with P2(1)/C space group and the unit cell parameters are a(Å) = 9.1144(7), b(Å) = 13.7928(7), c(Å) = 8.4174(5), α(°) = 90, β(°) = 100.715, γ(°) = 90 and volume V(A3) = 1039.73(11). The Raman bands observed for the L and its Pd(II) complex are in good agreement with the FT-IR spectral data. The Pd(II) complex is found to be highly efficient in inhibiting the growth of human pathogens like Salmonella typhimurium and Klebsiella pneumonia with MIC value 10.0 μg/mL whose inhibition zones are almost comparable with the standard antibiotic. The synthesized compounds have shown antiproliferative activity against the human breast cancer cell lines MDA-MB231 by intermitting the regular pathway of ribonucleotidereductase.

  6. Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1.

    OpenAIRE

    Batchelder, R. M.; Wilson, W R; Hay, M. P.; Denny, W. A.

    1996-01-01

    The enediyne anti-tumour antibiotics are extremely potent cytotoxins, apparently because of their conversion to diradical species which induce DNA double strand breaks with high efficiency. The potency of enediynes suggests their possible utility as effector units for prodrugs which can be activated selectively in tumours, such as bioreductive drugs (BD) or radiation-activated cytotoxins (RAC). However, the similarity of the radical-induced DNA breakage reactions of the enediynes to those cau...

  7. Cadmium(II) complex formation with glutathione.

    Science.gov (United States)

    Mah, Vicky; Jalilehvand, Farideh

    2010-03-01

    Complex formation between heavy metal ions and glutathione (GSH) is considered as the initial step in many detoxification processes in living organisms. In this study the structure and coordination between the cadmium(II) ion and GSH were investigated in aqueous solutions (pH 7.5 and 11.0) and in the solid state, using a combination of spectroscopic techniques. The similarity of the Cd K-edge and L(3)-edge X-ray absorption spectra of the solid compound [Cd(GS)(GSH)]ClO(4).3H(2)O, precipitating at pH 3.0, with the previously studied cysteine compound {Cd(HCys)(2).H(2)O}(2).H(3)O(+).ClO(4) (-) corresponds to Cd(S-GS)(3)O (dominating) and Cd(S-GS)(4) four-coordination within oligomeric complexes with mean bond distances of 2.51 +/- 0.02 A for Cd-S and 2.24 +/- 0.04 A for Cd-O. For cadmium(II) solutions (C (Cd(II)) approximately 0.05 M) at pH 7.5 with moderate excess of GSH (C (GSH)/C (Cd(II)) = 3.0-5.0), a mix of Cd(S-GS)(3)O (dominating) and Cd(S-GS)(4) species is consistent with the broad (113)Cd NMR resonances in the range 632-658 ppm. In alkaline solutions (pH 11.0 and C (GSH)/C (Cd(II)) = 2.0 or 3.0), two distinct peaks at 322 and 674 ppm are obtained. The first peak indicates six-coordinated mononuclear and dinuclear complexes with CdS(2)N(2)(N/O)(2) and CdSN(3)O(2) coordination in fast exchange, whereas the second corresponds to Cd(S-GS)(4) sites. At high ligand excess the tetrathiolate complex, Cd(S-GS)(4), characterized by a sharp delta((113)Cd) NMR signal at 677 ppm, predominates. The average Cd-S distance, obtained from the X-ray absorption spectra, varied within a narrow range, 2.49-2.53 A, for all solutions (pH 7.5 and 11.0) regardless of the coordination geometry. PMID:20035360

  8. Total synthesis of furospongolide and related furanolipid analogues as potential anti-tumour agents

    OpenAIRE

    Harrold, Donal Patrick

    2014-01-01

    This thesis details the design, development and execution of innovative methodology in the total synthesis of the terpene-derived marine natural product, furospongolide. It also outlines the synthetic routes used to prepare a novel range of furanolipids derivatives and subsequent evaluation of their potential as antitumour agents. The first chapter is a review of the literature describing efforts undertaken towards the synthesis of biologically active furanosesterterpenoid marine natural prod...

  9. Marine Pharmacology in 2005-6: Antitumour and Cytotoxic Compounds

    OpenAIRE

    Mayer, Alejandro M. S.; Gustafson, Kirk R.

    2008-01-01

    During 2005 and 2006, marine pharmacology research directed towards the discovery and development of novel antitumour agents was reported in 171 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumour and cytotoxic properties of 136 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids, and peptides. The organisms yielding these bioactive marine compounds i...

  10. Construction of Ru(II) Polypyridyl Based Macrocycles: Synthesis, Characterization, Electrochemical, Li+ Binding, Antitumour and Anti-HIV properties

    OpenAIRE

    Mishra, Lallan; Sinha, Ragini; Pandey, P. C.

    2001-01-01

    Some ruthenium (II) polypyridyl complexes with a bis-chalcone (obtained by the condensation of 3-methyl-thiophene-2-carboxaldehyde and 4-acetyl pyridine) have been synthesized and characterized spectroscopically (IR, NMR, UV/Vis), conductimetric, elemental analysis and FAB mass data. Their luminescent, redox and Li+ binding properties have been studied. The anti-HIV and antitumour activities have also been reported.

  11. Complex Formation of Selected Radionuclides with Ligands Commonly Found in Ground Water: Low Molecular Organic Acids

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1985-01-01

    A general approach to the analysis of potentiometric data on complex formation between cations and polybasic amphoteric acids is described. The method is used for the characterisation of complex formation between Cs+, Sr2+, Co2+, La 3+, and Eu3+ with a α-hydroxy acids, tartaric acid and citric acid......, and with the α-amino acids, aspartic acid and L-cysteine. The cations have been chosen as typical components of reactor waste, and the acids because they are often found as products of microbial activity in pits or wherever organic material decays...

  12. Study of complex formation between different pectins with lactoglobulin

    International Nuclear Information System (INIS)

    This study describes the complex formation of different pectins obtained from apple pomace, sunflower head and citruses pectin at the low ph. The insoluble complexes formed were investigated using turbid-dimeric, potentiometric and conductometric methods. The nature of resulted complexes manly depends on the pectin methyl ether formation pattern and molecular weight

  13. Zinc isotope effects in complex formation with a crown ether

    International Nuclear Information System (INIS)

    Isotope effects for zinc upon complex formation with dicyclohexano-18-crown-6 were investigated. The single stage separation factor for unit mass difference (α = 1.013) was great compared with that of calcium isotopes. One of the isotopes, 67Zn, showed a larger isotope effect than the other isotopes of even mass number. 7 refs., 1 fig

  14. Liposomal encapsulation enhances the antitumour efficacy of the vascular disrupting agent ZD6126 in murine B16.F10 melanoma

    OpenAIRE

    Fens, M H A M; Hill, K. J.; Issa, J; Ashton, S E; Westwood, F. R.; Blakey, D C; Storm, G; Ryan, A J; Schiffelers, R.M.

    2008-01-01

    Vascular disrupting agents (VDAs) are able to affect selectively tumour endothelial cell morphology resulting in vessel occlusion and widespread tumour cell necrosis. However, single-agent antitumour activity of VDAs is typically limited, as tumour regrowth occurs rapidly following drug treatment. To improve the therapeutic effectiveness of VDAs, we investigated liposomal targeting using ZD6126 as a model VDA. ZD6126 is a phosphate-prodrug of the tubulin-binding vascular disrupting agent ZD61...

  15. Liesegang patterns: Complex formation of precipitate in an electric field

    Indian Academy of Sciences (India)

    István Lagzi

    2005-02-01

    Formation of 1D Liesegang patterns was studied numerically in precipitation and reversible complex formation of precipitate scenarios in an electric field. The Ostwald’s supersaturation model reported by Büki, Kárpáti-Smidróczki and Zrínyi (BKZ model) was extended further. In the presence of an electric field the position of the first and the last bands () measured from the junction point of the outer and the inner electrolytes can be described by the function = 1 $_{}^{1/2}$ + 2 + 3 , where is the time elapsed until the nth band formation, 1, 2 and 3 are constants. The variation of the total number of bands with different electric field strengths () has a maximum. For higher one can observe a moving precipitation zone that becomes wider due to precipitation and reversible complex formation.

  16. complex formation of americium (III) with humic acid

    International Nuclear Information System (INIS)

    The presence of humic substances in natural waters will modify the migration behavior of actinides in the geosphere due to the strong reaction properties of these ligands with actinides. Therefore, the possible reactions of humic acid with actinides have been studied widely in recent years. The complex formation of Am(III) with humic acid is studied with solvent extraction technique. The experiments are performed in the pH range from 4.0 to 8.0 in 0.1 mol/kg NaClO4 solution at ambient temperature. Experimental results show that the complex formation constants of Am(III) with humic acid are varied with the variation of pH value in solution. 1:2 complex is obtained in the experiments and the complex formation constants determined at each pH are: lgβ1 = 6.56 +- 0.05, lgβ2 = 10.77 +- 0.31 at pH 4.0. lgβ1 = 7.94 +- 0.11, lgβ2 = 11.80 +- 0.21 at pH = 5.0. lgβ1 = 10.74 +- 0.28, lgβ2 = 12.88 +- 0.49 at pH = 6.0. lgβ1 = 12.85 +- 0.30, lgβ2 = 14.80 +- 0.62 at pH = 7.0. lgβ1 = 14.88 +- 0.48, lgβ2 = 15.65 +- 0.69 at pH = 8.0, respectively. The dependence of the complex formation constant on pH is: lgβ1 = 2.16 (+-0.98)pH-2.34(+-0.93),lgβ2 1.28(+-1.04)pH+5.52(+-1.21), respectively

  17. Polyphenolic compounds with anti-tumour potential from Corchorus olitorius (L.) Tiliaceae, a Nigerian leaf vegetable.

    Science.gov (United States)

    Taiwo, Bamigboye J; Taiwo, Grace O; Olubiyi, Olujide O; Fatokun, Amos A

    2016-08-01

    Chromatographic fractionation of the methanolic extract of Corchorus olitorius (L.) (Tiliaceae), on silica gel yielded two polyphenolic compounds. The structures of the compounds were elucidated as Methyl-1,4,5-tri-O-caffeoyl quinate and trans-3-(4-Hydroxy-3-methoxyphenyl)acrylic anhydride, based on extensive use of spectroscopic techniques such as (1)H and (13)C NMR, DEPT and 2D NMR experiments (COSY, HSQC, HMBC), IR and MS. To establish an initial proof-of-concept for the biological relevance of these compounds, their cytotoxicity against the cancer cell lines HeLa, HL460 and PC3, which might indicate their anti-tumour potential, was assessed. The compounds when tested at a range of concentrations up to 1.6mM were found to possess mild cytotoxic activity which was significant against HeLa cells at ⩾800μM. The trans-3-(4-Hydroxy-3-methoxyl phenyl)acrylic anhydride was found to be related to curcumin, a compound known to have anti-cancer activity. Docking of each of the two compounds and also of curcumin into some molecular targets implicated in tumourigenesis revealed that the three compounds had binding affinities that were superior to those obtained for the co-crystallized inhibitors of metalloproteinase-9, fibroblast growth factor receptor 2 (FGFR2) and epidermal growth factor receptor (EGFR). The plant Corchorus olitorius therefore represents a potential source of natural 'lead' compounds with anti-tumour potential. PMID:27381082

  18. Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Pantouris, Georgios; Mowat, Christopher G., E-mail: C.G.Mowat@ed.ac.uk

    2014-01-03

    Highlights: •∼2800 National Cancer Institute USA compounds have been screened as potential inhibitors of TDO and/or IDO. •Seven compounds with anti-tumour properties have been identified as potent inhibitors. •NSC 36398 (taxifolin, dihydroquercetin) is selective for TDO with a K{sub i} of 16 M. •This may help further our understanding of the role of TDO in cancer. -- Abstract: The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ∼2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ∼16 μM, is the first TDO-selective inhibitor reported.

  19. Complex formation of americium (III) with humic acid

    International Nuclear Information System (INIS)

    The presence of humic substances in natural waters will modify the migration behavior of actinides in the geosphere due to the strong reaction properties of these ligands with actinides. Therefore, the possible reactions of humic acid with actinides have been studied widely in recent years. The complex formation of Am (III) with humic acid is studied with solvent extraction technique in this paper. The experiments are performed in the pH range from 4.0 to 8.0 in 0.1 M NaClO4 solution at ambient temperature. Experimental results show that the complex formation constants of Am (III) with humic acid are varied with the variation of pH value in solution. 1:2 complex is obtained in the experiments and the complex formation constants determined at each pH are: lgβ1=6.56±0.05, lgβ2=10.77±0.31 at pH=4.0; lgβ1=7.94±0.11, lgβ2=11.80±0.21 at pH=5.0; lgβ1=10.74±0.28, lgβ2=12.88±0.49 at pH=6.0; lgβ1=12.85±0.30, lgβ2=14.80±0.62 at pH=7.0; lgβ1=14.88±0.48, lgβ2=15.65±0.69 at pH=8.0, respectively. The dependence of the complex of the complex formation constant on pH is: lgβ1=2.16(±0.98)pH-2.34(±1.03), lgβ2=1.28(±1.04)pH+5.52(±1.21), respectively. (author)

  20. Redox, disproportionation, and complex formation reactions of neptunium ions

    International Nuclear Information System (INIS)

    Reduction-oxidation, complex formation, and disproportionation reactions of neptunium ions in various aqueous media were investigated by electrochemical method in combination with the spectrophotometric measurement. By flow-coulometry with multi-step column electrodes, electrolytic redox potentials, number of electrons involved in the electrode processes, and reversibilities of the processes were determined, from which the complex formation of neptunium ions and the species participating in the reactions were discussed. Based on the characteristics of the redox behavior of neptunium in sulfuric acid media, the procedure for the flow-coulometric determination and differentiation of neptunium ions was developed. The redox potentials of neptunium in concentrated carbonate solutions were determined by means of controlled-potential electrolysis and spectrophotometry, and formations of NpO2(CO3)35- and NpO2(CO3)34- complexes were evaluated. The disproportionation rate of NpO2+ in concentrated acid solutions with and without such complexing agents as SO42- and Cl- was measured and the reaction mechanism was predicted. (author)

  1. Antitumour Acitivty of Chitosan Hydrogen Selenites

    Institute of Scientific and Technical Information of China (English)

    CaiQinQIN; XiaoHaiGAO; 等

    2002-01-01

    Chitosans reacted with selenious acid to prepare chitosan hydrogen selenites, which were found to be growth-inhibitory against sarcoma 180 solid tumor. The results indicated that the activity also depended on the molecular weight of chitosan supports.

  2. SPECTROPHOTOMETRIC STUDIES OF SANGUINARINE-Β-CYCLODEXTRIN COMPLEX FORMATION

    Directory of Open Access Journals (Sweden)

    Veaceslav Boldescu

    2008-06-01

    Full Text Available The main aim of this study was to investigate the influence of pH and the presence of hydrophilic polymer polyvinylpyrrolidone on the formation of sanguinarine-β-cyclodextrin (SANG-β-CD inclusion complex. Spectrophotometric studies of the SANG-β-CD systems in the presence and without 0.1 % PVP at the pH 5.0 did not show any evidence of the complex formation. However, the same systems showed several obvious evidences at the pH 8.0: the hyperchromic and the hypochromic effects and the presence of the isosbestic point in the region of 200 – 210 nm. The association constants calculated by three linear methods: Benesi-Hildebrand, Scott and Scatchard, were two times higher for the systems with addition of 0.1% PVP than for the systems without it.

  3. Complex formation between uranyl and various thiosemicarbazide derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Chuguryan, D.G.; Dzyubenko, V.I.

    1987-01-01

    Complex formation between hexavalent uranium and salicylaldehyde thiosemicarbazone (H/sub 2/L), salicylaldehyde S-methyl-isothiosemicarbazone (H/sub 2/Q), S-methyl-N/sub 1/,N/sub 4/-bis(salicylidene)isothiosemicarbazide(H/sub 2/Z), and thiosemicarbazidodiacetic acid (H/sub 2/R) has been studied spectrophotometrically in solution. Stability constants for complexes having the composition UO/sub 2/A have been calculated. Solid uranyl derivatives having the composition UO/sub 2/L x 2H/sub 2/O, UO/sub 2/Q x 2H/sub 2/O, UO/sub 2/Z x 2H/sub 2/O, and UO/sub 2/R x 2H/sub 2/O have been obtained. These derivatives were isolated and their IR spectroscopic behavior and thermal properties were investigated.

  4. Antitumour and anti-inflammatory effects of palladium(II) complexes on Ehrlich tumour.

    Science.gov (United States)

    Quilles, Marcela B; Carli, Camila B A; Ananias, Sandra R; Ferreira, Lucas S; Ribeiro, Livia C A; Maia, Danielle C G; Resende, Flávia A; Moro, Antônio C; Varanda, Eliana A; Placeres, Marisa Campos Polesi; Mauro, Antonio E; Carlos, Iracilda Z

    2013-01-01

    Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 +/- 3.23) microM and (137.65 +/- 0.22) microM for 1 and (39.7 +/- 0.30) microM and (146.51 +/- 2.67) microM for 2, respectively. The production of NO, IL-12, and TNF-alpha, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin. PMID:24066514

  5. Reproducibility of the Bath Ankylosing Spondylitis Indices of disease activity (BASDAI), functional status (BASFI) and overall well-being (BAS-G) in anti-tumour necrosis factor-treated spondyloarthropathy patients

    DEFF Research Database (Denmark)

    Madsen, Ole R; Rytter, Anne; Hansen, Lonnie B; Suetta, Charlotte; Egsmose, Charlotte

    2010-01-01

    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI) and the Bath Ankylosing Spondylitis Global Score (BAS-G) (ranges 0-10) have gained widespread in use as self-reported measures of disease activity, functional impairment and...... overall well-being in patients with ankylosing spondylitis and other spondyloarthropathies (SpA). In Denmark, BASDAI, BASFI and BAS-G are systematically used to monitor treatment response in patients treated with tumour necrosis factor (TNF) inhibitors. The purpose of the present study was to examine the...

  6. Complex formation between polyelectrolytes and oppositely charged oligoelectrolytes

    Science.gov (United States)

    Zhou, Jiajia; Barz, Matthias; Schmid, Friederike

    2016-04-01

    We study the complex formation between one long polyanion chain and many short oligocation chains by computer simulations. We employ a coarse-grained bead-spring model for the polyelectrolyte chains and model explicitly the small salt ions. We systematically vary the concentration and the length of the oligocation and examine how the oligocations affects the chain conformation, the static structure factor, the radial and axial distribution of various charged species, and the number of bound ions in the complex. At low oligocation concentration, the polyanion has an extended structure. Upon increasing the oligocation concentration, the polyanion chain collapses and forms a compact globule, but the complex still carries a net negative charge. Once the total charge of the oligocations is equal to that of the polyanion, the collapse stops and is replaced by a slow expansion. In this regime, the net charge on the complexes is positive or neutral, depending on the microion concentration in solution. The expansion can be explained by the reduction of the oligocation bridging. We find that the behavior and the structure of the complex are largely independent of the length of oligocations, and very similar to that observed when replacing the oligocations by multivalent salt cations, and conclude that the main driving force keeping the complex together is the release of monovalent counterions and coions. We speculate on the implications of this finding for the problem of controlled oligolyte release and oligolyte substitution.

  7. Complex formation between polyelectrolytes and oppositely charged oligoelectrolytes.

    Science.gov (United States)

    Zhou, Jiajia; Barz, Matthias; Schmid, Friederike

    2016-04-28

    We study the complex formation between one long polyanion chain and many short oligocation chains by computer simulations. We employ a coarse-grained bead-spring model for the polyelectrolyte chains and model explicitly the small salt ions. We systematically vary the concentration and the length of the oligocation and examine how the oligocations affects the chain conformation, the static structure factor, the radial and axial distribution of various charged species, and the number of bound ions in the complex. At low oligocation concentration, the polyanion has an extended structure. Upon increasing the oligocation concentration, the polyanion chain collapses and forms a compact globule, but the complex still carries a net negative charge. Once the total charge of the oligocations is equal to that of the polyanion, the collapse stops and is replaced by a slow expansion. In this regime, the net charge on the complexes is positive or neutral, depending on the microion concentration in solution. The expansion can be explained by the reduction of the oligocation bridging. We find that the behavior and the structure of the complex are largely independent of the length of oligocations, and very similar to that observed when replacing the oligocations by multivalent salt cations, and conclude that the main driving force keeping the complex together is the release of monovalent counterions and coions. We speculate on the implications of this finding for the problem of controlled oligolyte release and oligolyte substitution. PMID:27131564

  8. Cytotoxic and Antitumour Studies of Acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone and its Transition Metal Complexes

    OpenAIRE

    Priya, N. P.; Firdous, A. P.; Jeevana, R.; Aravindakshan, K. K.

    2015-01-01

    Cytotoxic activities of acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone (L2H) and its seven different metal complexes were studied. Of these, IC50 value of the copper complex was found to be 46 μg/ml. Antitumour studies of this copper complex was carried out using Daltons Lymphoma Ascites cell-induced solid tumour model and Ehrlich's Ascites Carcinoma cell-induced ascites tumour model. Administration of the copper complex at different concentrations (10, 5 and 1 mg/kg b. wt) inhibited t...

  9. Green synthesis of ZnO nanoparticles via complex formation by using Curcuma longa extract

    Energy Technology Data Exchange (ETDEWEB)

    Fatimah, Is, E-mail: isfatimah@uii.ac.id; Yudha, Septian P.; Mutiara, Nur Afisa Lintang [Chemistry Department, Islamic University of Indonesia Kampus Terpadu UII, Jl. Kaliurang Km 14, Sleman, Yogyakarta (Indonesia)

    2016-02-08

    Synthesis of ZnO nanoparticles(NPs) were conducted via Zn(II) complex formation by using Curcuma longa extract as template. Curcuma longa extract has the ability to form zinc ions complex with curcumin as ligating agent. Study on synthesis was conducted by monitoring thermal degradation of the material. Successful formation of zinc oxide nanoparticles was confirmed by employing x-ray diffraction, surface area analysis and transmission electron microscopy(TEM) studies. From the XRD analysis it is denoted that ZnO in hexagonal wurtzite phase was formed and particle size was varied as varied temperature. The data are also confirmed by TEM analysis which shows the particle sie at the range 20-80nm. The NPs exhibited excelent photocatalytic activity for methylene blue degradation and also significant antibacterial activity for Eschericia coli. The activity in methylene blue degradation was also confirmed from fast chemical oxygen demand (COD) reduction.

  10. Green synthesis of ZnO nanoparticles via complex formation by using Curcuma longa extract

    Science.gov (United States)

    Fatimah, Is; Yudha, Septian P.; Mutiara, Nur Afisa Lintang

    2016-02-01

    Synthesis of ZnO nanoparticles(NPs) were conducted via Zn(II) complex formation by using Curcuma longa extract as template. Curcuma longa extract has the ability to form zinc ions complex with curcumin as ligating agent. Study on synthesis was conducted by monitoring thermal degradation of the material. Successful formation of zinc oxide nanoparticles was confirmed by employing x-ray diffraction, surface area analysis and transmission electron microscopy(TEM) studies. From the XRD analysis it is denoted that ZnO in hexagonal wurtzite phase was formed and particle size was varied as varied temperature. The data are also confirmed by TEM analysis which shows the particle sie at the range 20-80nm. The NPs exhibited excelent photocatalytic activity for methylene blue degradation and also significant antibacterial activity for Eschericia coli. The activity in methylene blue degradation was also confirmed from fast chemical oxygen demand (COD) reduction.

  11. Green synthesis of ZnO nanoparticles via complex formation by using Curcuma longa extract

    International Nuclear Information System (INIS)

    Synthesis of ZnO nanoparticles(NPs) were conducted via Zn(II) complex formation by using Curcuma longa extract as template. Curcuma longa extract has the ability to form zinc ions complex with curcumin as ligating agent. Study on synthesis was conducted by monitoring thermal degradation of the material. Successful formation of zinc oxide nanoparticles was confirmed by employing x-ray diffraction, surface area analysis and transmission electron microscopy(TEM) studies. From the XRD analysis it is denoted that ZnO in hexagonal wurtzite phase was formed and particle size was varied as varied temperature. The data are also confirmed by TEM analysis which shows the particle sie at the range 20-80nm. The NPs exhibited excelent photocatalytic activity for methylene blue degradation and also significant antibacterial activity for Eschericia coli. The activity in methylene blue degradation was also confirmed from fast chemical oxygen demand (COD) reduction

  12. Complex formation of Eu(III) with polyacrylic acid

    International Nuclear Information System (INIS)

    For the quantitative description of the interaction of metal ions with humic substances, it is necessary to clarify the effects of both polyelectrolyte and heterogeneous nature of humic substances. To estimate the polyelectrolyte effect separately, polyacrylic acid (MW = 90 000) has been selected as a representative of well-defined, homogeneous polymeric weak acids, and its interaction with Eu(III) has been investigated by a solvent extraction method using 152Eu (∝ 10-8 M) with TTA and TBP in xylene. By defining the apparent complex formation constant as βα = [ML]/([M][R]), where [M] = [Eu3+], [ML] is the concentration of Eu(III) associated with polyacrylic acid and [R] = CRα (CR is a total concentration of proton exchanging sites and α is a degree of dissociation determined by potentiometric titration), the apparent constants have been obtained at several pcH and ionic strength (0.1 M and 1.0 M NaClO4). The constants increased with pcH and decreased with an increase of ionic strength, that is, the values of log βα varied from 6.0 (at pcH = 4.7) to 7.6 (pcH = 5.5) at 0.1 M NaClO4 and from 4.8 (pcH = 4.4) to 6.5 (pcH = 5.4) at 1.0 M. The plots of log βα versus log α revealed almost linear relationship both at 0.1 and 1.0 M NaClO4. (orig.)

  13. Polyelectrolyte complex formation mediated immobilization of chitosan-invertase neoglycoconjugate on pectin-coated chitin.

    Science.gov (United States)

    Gómez, Leissy; Ramírez, Hector L; Neira-Carrillo, Andrónico; Villalonga, Reynaldo

    2006-05-01

    Saccharomyces cerevisiae invertase, chemically modified with chitosan, was immobilized on pectin-coated chitin support via polyelectrolyte complex formation. The yield of immobilized enzyme protein was determined as 85% and the immobilized biocatalyst retained 97% of the initial chitosan-invertase activity. The optimum temperature for invertase was increased by 10 degrees C and its thermostability was enhanced by about 10 degrees C after immobilization. The immobilized enzyme was stable against incubation in high ionic strength solutions and was 4-fold more resistant to thermal treatment at 65 degrees C than the native counterpart. The biocatalyst prepared retained 96 and 95% of the original catalytic activity after ten cycles of reuse and 74 h of continuous operational regime in a packed bed reactor, respectively. PMID:16775742

  14. The Safety and Effectiveness of Single and Repeat Dosing of Intra-Articular Anti-Tumour Necrosis Factor Treatment after Failure of Intra-Articular Steroids

    OpenAIRE

    Chia, Justin; POPE, JANET

    2011-01-01

    Objectives: To determine if intra-articular (ia) anti-tumour necrosis factor (TNF) yielded benefit in patients failing ia steroid injections and determine the safety and durability of single and repeated ia anti-TNF treatment in inflammatory arthritis. Methods: Patients with inflammatory arthritis having one or two active joints, and having failed previous ia steroids were injected with ia adalimumab or ia etanercept mixed with triamcinolone and lidocaine via a retrospective chart audit. Resu...

  15. Halo-substituted thiosemicarbazones and their copper(II), nickel(II) complexes: Detailed spectroscopic characterization and study of antitumour activity against HepG2 human hepatoblastoma cells

    Science.gov (United States)

    Jagadeesh, M.; Kalangi, Suresh K.; Sivarama Krishna, L.; Reddy, A. Varada

    2014-01-01

    Copper(II) and nickel(II) complexes of two different halogen substituted thiosemicarbazone ligands were synthesized. The ligands 3,4-difluoroacetophenone thiosemicarbazone (1) and 2-bromo-4'-chloroacetophenone thiosemicarbazone (2) were characterized and confirmed spectroscopically by FT-IR, FT-Raman, UV-vis and fluorescence spectral analysis, while the respective copper(II) complexes [Cu(C9H9N3F2S)2Cl2] (1a), [Cu(C9H9N3ClBrS)2Cl2] (2a) and nickel(II) complexes [Ni(C9H9N3F2S)2] (1b), [Ni(C9H9N3ClBrS)2] (2b) were characterized by FT-IR, UV-vis and electron paramagnetic spectroscopy (EPR). The EPR spectra of the Cu(II) complexes provided the rhombic octahedral and axial symmetry of the complexes 1a and 2a respectively. For the complex 1a, the g values calculated as g1 = 2.1228, g2 = 2.0706 and g3 = 2.001 between 2900 and 3300 G. While for the complex 2a, a set of two resonance absorptions were observed. The synthesized compounds were tested for antitumor activity and showed that the ability to kill liver cancer cells significantly. Out of all the synthesized compounds, copper(II) complexes 1a and 2a showed high cytotoxic effect on liver cancer cells with 67.51% and 42.77% of cytotoxicity respectively at 100 μM.

  16. Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation

    Directory of Open Access Journals (Sweden)

    Lin Chih-Li

    2010-02-01

    Full Text Available Abstract Background Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However, mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Methods & Results Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA unwinding activity and are subject to cell cycle-dependent enzymatic regulation. Interestingly, analysis of functional attributes further suggests that they act at distinct, and possibly sequential, steps during origin establishment and replication initiation. Moreover, we show that the phosphorylation profile of the FACT-associated MCM4 undergoes a cell cycle-dependent change, which is directly correlated with the catalytic activity of the FACT-MCM helicase complexes. Finally, at the quaternary structure level, physical interaction between FACT and MCM complexes is generally dependent on persistent cell cycle and further stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the complex formation and likely leads to compromised coordination and activities. Conclusions Together, our results correlate FACT-MCM functionally and temporally with S phase and DNA replication. They further demonstrate that enzymatic activities intrinsically important for DNA replication are tightly controlled at various levels, thereby ensuring proper progression of, as well as exit from, the cell cycle and ultimately euploid gene balance.

  17. The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

    Directory of Open Access Journals (Sweden)

    Anne M. Galea

    2008-01-01

    Full Text Available Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profi ling techniques. Currently, our incomplete understanding of this drug’s mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dual-fluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics.

  18. [The antitumour activity of total saponin of Clematis chinensis].

    Science.gov (United States)

    Qiu, G; Zhang, M; Yang, Y

    1999-07-01

    This paper has shown the cytocidal effects of total saponin of Clermatis chisensis Osbeck (CCS) on experimental tumours EAC cells, S180A cells and HepA cells in vitro, using microculture method 72 hours. The IC50 were 242 micrograms/ml, 193 micrograms/ml and 130 micrograms/ml respectively. In vivo the growth of transplanted mouse tumour(S180) was inhibited by the CCS with inhibitory rates 40.3% (0.25 g/kg), 55.1% (0.5 g/kg), 53.0% (1 g/kg), but CCS(0.2 g/kg, 0.4g/kg, 0.5 g/kg) hasn't effect on survival time of tumour mice(S180A). PMID:12571931

  19. Al-O complex formation in ion implanted Czochralski and floating-zone Si substrates

    Science.gov (United States)

    La Ferla, A.; Torrisi, L.; Galvagno, G.; Rimini, E.; Ciavola, G.; Carnera, A.; Gasparotto, A.

    1993-01-01

    Aluminum ions at 100 MeV were implanted into floating-zone (FZ) and Czochralski (CZ) grown Si substrates. At this energy the influence of the surface on the subsequent thermal treatment is negligible. In FZ samples the electrical active dose, as measured by spreading resistance profilometry, is independent of the annealing time at 1200 °C. In the CZ samples instead it considerably decreases with time. Secondary ion mass spectrometry analysis in CZ samples have revealed the presence of a multipeak structure around the projected range region for both Al and O signals. In FZ the structure is just detectable. The results imply that the Al-O complex formation is enhanced by the presence of oxygen but that it is catalyzed by the damage created during the implant. The carrier profiles coincide in both CZ and FZ diffused substrates by predeposition of Al from a solid source, i.e., in damage-free samples.

  20. Cadmium(II) complex formation with cysteine and penicillamine.

    Science.gov (United States)

    Jalilehvand, Farideh; Leung, Bonnie O; Mah, Vicky

    2009-07-01

    The complex formation between cadmium(II) and the ligands cysteine (H(2)Cys) and penicillamine (H(2)Pen = 3,3'-dimethylcysteine) in aqueous solutions, having C(Cd(II)) approximately 0.1 mol dm(-3) and C(H(2)L) = 0.2-2 mol dm(-3), was studied at pH = 7.5 and 11.0 by means of (113)Cd NMR and Cd K- and L(3)-edge X-ray absorption spectroscopy. For all cadmium(II)-cysteine molar ratios, the mean Cd-S and Cd-(N/O) bond distances were found in the ranges 2.52-2.54 and 2.27-2.35 A, respectively. The corresponding cadmium(II)-penicillamine complexes showed slightly shorter Cd-S bonds, 2.50-2.53 A, but with the Cd-(N/O) bond distances in a similar wide range, 2.28-2.33 A. For the molar ratio C(H(2)L)/C(Cd(II)) = 2, the (113)Cd chemical shifts, in the range 509-527 ppm at both pH values, indicated complexes with distorted tetrahedral CdS(2)N(N/O) coordination geometry. With a large excess of cysteine (molar ratios C(H(2)Cys)/C(Cd(II)) >or= 10), complexes with CdS(4) coordination geometry dominate, consistent with the (113)Cd NMR chemical shifts, delta approximately 680 ppm at pH 7.5 and 636-658 ppm at pH 11.0, and their mean Cd-S distances were 2.53 +/- 0.02 A. At pH 7.5, the complexes are almost exclusively sulfur-coordinated as [Cd(S-cysteinate)(4)](n-), while at higher pH, the deprotonation of the amine groups promotes chelate formation. At pH 11.0, a minor amount of the [Cd(Cys)(3)](4-) complex with CdS(3)N coordination is formed. For the corresponding penicillamine solutions with molar ratios C(H(2)Pen)/C(Cd(II)) >or= 10, the (113)Cd NMR chemical shifts, delta approximately 600 ppm at pH 7.5 and 578 ppm at pH 11.0, together with the average bond distances, Cd-S 2.53 +/- 0.02 A and Cd-(N/O) 2.30-2.33 A, indicate that [Cd(penicillaminate)(3)](n-) complexes with chelating CdS(3)(N/O) coordination dominate already at pH 7.5 and become mixed with CdS(2)N(N/O) complexes at pH 11.0. The present study reveals differences between cysteine and penicillamine as ligands to the

  1. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    International Nuclear Information System (INIS)

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation

  2. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi, E-mail: tajima@nirs.go.jp

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  3. From PII signaling to metabolite sensing: a novel 2-oxoglutarate sensor that details PII-NAGK complex formation.

    Science.gov (United States)

    Lüddecke, Jan; Forchhammer, Karl

    2013-01-01

    The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i) It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii) It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii) It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction. PMID:24349456

  4. From PII signaling to metabolite sensing: a novel 2-oxoglutarate sensor that details PII-NAGK complex formation.

    Directory of Open Access Journals (Sweden)

    Jan Lüddecke

    Full Text Available The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction.

  5. Localization and dynamics of amylose-lipophilic molecules inclusion complex formation in starch granules

    NARCIS (Netherlands)

    Manca, Marianna; Woortman, Albert J. J.; Mura, Andrea; Loos, Katja; Loi, Maria Antonietta

    2015-01-01

    Inclusion complex formation between lipophilic dye molecules and amylose polymers in starch granules is investigated using laser spectroscopy and microscopy. By combining confocal laser scanning microscopy (CLSM) with spatial resolved photoluminescence (PL) spectroscopy, we are able to discriminate

  6. Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents.

    Science.gov (United States)

    Wu, Lin-tao; Jiang, Zhi; Shen, Jia-jia; Yi, Hong; Zhan, Yue-chen; Sha, Ming-quan; Wang, Zhen; Xue, Si-tu; Li, Zhuo-rong

    2016-05-23

    A series of novel benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06-3.64 μM and 0.04-9.80 μM, respectively. Their antiproliferative activities were significantly better than that of 5-Fluorouracil (IC50: 56.96-174.50 μM) and were close to that of Paclitaxel (IC50: 0.026-1.53 μM). The activity of these derivatives was over 100 times more effective than other reported structures of chalcone analogues (licochalcone A). A preliminary mechanistic study suggested that these compounds inhibit p53-MDM2 binding. Compounds A1, A7 and A9 effectively inhibited tumour growth in BALB/c mice with colon carcinoma HCT116 cells. The group administered 200 mg/kg of compound A7 showed a 74.6% tumour growth inhibition with no signs of toxicity at high doses that was similar to the inhibition achieved with the 12.5 mg/kg irinotecan positive control (70.2%). Therefore, this class of benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives represents a promising lead structure for the development of possible p53-MDM2 inhibitors as new antitumour agents. PMID:27017265

  7. Complex formation of platelet thrombospondin with histidine-rich glycoprotein.

    OpenAIRE

    Leung, L L; Nachman, R L; Harpel, P C

    1984-01-01

    Thrombospondin and histidine-rich glycoprotein are two proteins with diverse biological activities which have been associated with human platelets and other cell systems. Using an enzyme-linked immunosorbent assay, we have demonstrated that purified human platelet thrombospondin formed a complex with purified human plasma histidine-rich glycoprotein. The formation of the thrombospondin-histidine-rich glycoprotein complex was specific, concentration dependent, and saturable. Significant bindin...

  8. Characterization of Hydrogen Complex Formation in III-V Semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Michael D

    2006-09-28

    Atomic hydrogen has been found to react with some impurity species in semiconductors. Hydrogenation is a methodology for the introduction of atomic hydrogen into the semiconductor for the express purpose of forming complexes within the material. Efforts to develop hydrogenation as an isolation technique for AlGaAs and Si based devices failed to demonstrate its commercial viability. This was due in large measure to the low activation energies of the formed complexes. Recent studies of dopant passivation in long wavelength (0.98 - 1.55m) materials suggested that for the appropriate choice of dopants much higher activation energies can be obtained. This effort studied the formation of these complexes in InP, This material is extensively used in optoelectronics, i.e., lasers, modulators and detectors. The experimental techniques were general to the extent that the results can be applied to other areas such as sensor technology, photovoltaics and to other material systems. The activation energies for the complexes have been determined and are reported in the scientific literature. The hydrogenation process has been shown by us to have a profound effect on the electronic structure of the materials and was thoroughly investigated. The information obtained will be useful in assessing the long term reliability of device structures fabricated using this phenomenon and in determining new device functionalities.

  9. Acceptors in II-IV Semiconductors - Incorporation and Complex Formation

    CERN Multimedia

    2002-01-01

    A strong effort is currently devoted to the investigation of defects and the electrical activation of dopant atoms in II-VI semiconductors. In particular, the knowledge about the behaviour of acceptors, prerequisite for the fabrication of p-type semiconductors, is rather limited. The perturbed $\\,{\\gamma\\gamma}$ -angular correlation technique (PAC) and the photoluminescence spectroscopy (PL) using the radioactive isotopes $^{77}\\!$Br and $^{111}\\!$Ag will be applied for investigating the behaviour of acceptor dopant atoms and their interactions with defects in II-VI semiconductors. The main topic will be the identification of the technical conditions for the incorporation of electrically active acceptors in the II-VI semiconductors ~ZnS, ZnSe, ZnTe, CdS, CdSe, and CdTe with particular emphasis on the compounds~ CdTe, ZnSe, and ZnTe. The investigations will be supplemented by first exploratory PL experiments with the group V acceptors $^{71}\\!$As and $^{121}\\!$Sb. With help of the probe $^{111}\\!$Ag, the pos...

  10. Structural basis of complement membrane attack complex formation

    Science.gov (United States)

    Serna, Marina; Giles, Joanna L.; Morgan, B. Paul; Bubeck, Doryen

    2016-02-01

    In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a `multi-hit' mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a `split-washer' configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.

  11. Cytotoxic and Antitumour Studies of Acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone and its Transition Metal Complexes

    Science.gov (United States)

    Priya, N. P.; Firdous, A. P.; Jeevana, R.; Aravindakshan, K. K.

    2015-01-01

    Cytotoxic activities of acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone (L2H) and its seven different metal complexes were studied. Of these, IC50 value of the copper complex was found to be 46 μg/ml. Antitumour studies of this copper complex was carried out using Daltons Lymphoma Ascites cell-induced solid tumour model and Ehrlich's Ascites Carcinoma cell-induced ascites tumour model. Administration of the copper complex at different concentrations (10, 5 and 1 mg/kg b. wt) inhibited the solid tumour development in mice and increased the mean survival rate and the life span of Ascites tumour bearing mice in a concentration dependent manner. PMID:26997691

  12. Cytotoxic and Antitumour Studies of Acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone and its Transition Metal Complexes.

    Science.gov (United States)

    Priya, N P; Firdous, A P; Jeevana, R; Aravindakshan, K K

    2015-01-01

    Cytotoxic activities of acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone (L2H) and its seven different metal complexes were studied. Of these, IC50 value of the copper complex was found to be 46 μg/ml. Antitumour studies of this copper complex was carried out using Daltons Lymphoma Ascites cell-induced solid tumour model and Ehrlich's Ascites Carcinoma cell-induced ascites tumour model. Administration of the copper complex at different concentrations (10, 5 and 1 mg/kg b. wt) inhibited the solid tumour development in mice and increased the mean survival rate and the life span of Ascites tumour bearing mice in a concentration dependent manner. PMID:26997691

  13. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    Science.gov (United States)

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer. PMID:27208904

  14. Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia.

    Science.gov (United States)

    Muradashvili, Nino; Tyagi, Reeta; Metreveli, Naira; Tyagi, Suresh C; Lominadze, David

    2014-09-01

    Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-β-amyloid (Fg-Aβ) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-β-synthase heterozygote (Cbs+/-, a genetic model of HHcy), MMP9 gene knockout (Mmp9-/-), and Cbs and Mmp9 double knockout (Cbs+/-/Mmp9-/-) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Aβ complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs+/- mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Aβ complex formation was the highest along with the diminished short-term memory in Cbs+/- mice. These effects of HHcy were ameliorated in Cbs+/-/Mmp9-/- mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Aβ complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies. PMID:24865997

  15. Sensitive NADH detection in a tumorigenic cell line using a nano-biosensor based on the organic complex formation.

    Science.gov (United States)

    Akhtar, Mahmood H; Mir, Tanveer A; Gurudatt, N G; Chung, Saeromi; Shim, Yoon-Bo

    2016-11-15

    A robust amperometric sensor for β-nicotinamide adenine dinucleotide (NADH) detection was developed through the organic complex formation with ethylenediaminetetraacetic acid (EDTA) bonded on the polyethylenimine (PEI)/activated graphene oxide (AGO) layer. The EDTA immobilized sensor probe (GCE/AGO/PEI-EDTA) revealed a catalytic property towards NADH oxidation that allows for the highly sensitive electrochemical detection of NADH at a low oxidation potential. Surface characterization demonstrated that the negatively charged AGO acted as nanofillers in the positively charged PEI matrix through the charge interaction. The immobilization of EDTA on the polymer layer provided more surface area for NADH to interact with through the enhanced chemical interlocking between them. We observed the strong interaction between NADH and EDTA on the AGO/PEI layer using a quartz crystal microbalance (QCM), X-ray photoelectron spectroscopy (XPS), and the calculation of the minimized energy for complex formation. The dynamic range of NADH was determined to be between 0.05μM and 500μM with a detection limit (LD) of 20.0±1.1nM. The reliability of the developed sensor for biomedical applications was examined by detecting NADH in tumorigenic lung epithelial cells using the standard addition method. PMID:27209575

  16. PECULIARITIES OF LITTER INVERTEBRATES’ MULTISPECIES COMPLEXES FORMATION ON THE KHORTITSA ISLAND (ZAPORIZHZHYA PROVINCE)

    OpenAIRE

    D. О. Fedorchenko; V. V. Brygadyrenko

    2008-01-01

    Peculiarities of litter invertebrates’ complexes formation under conditions of the Khortitsa National Reserve (Zaporizhzhya province) are studied. The dispersion of taxonomic groups of different levels (families and species) in litter mesofauna is swayed by the inter- and intrasystem factors; the largest influence has the power of litter and its humidity. The rate of ecological factors’ influence at different taxonomic levels may diverge.

  17. On the complex formation approach in modeling predator prey relations, mating, and sexual disease transmission

    Directory of Open Access Journals (Sweden)

    Horst R. Thieme

    2000-10-01

    Full Text Available Complex formation is used as a unified approach to derive representations and approximations of the functional response in predator prey relations, mating, and sexual disease transmission. Applications are given to the impact of a generalist predator on a prey population and the spread of a sexually transmitted disease in a multi-group heterosexual population.

  18. Spectroscopic characterization, antioxidant and antitumour studies of novel bromo substituted thiosemicarbazone and its copper(II), nickel(II) and palladium(II) complexes.

    Science.gov (United States)

    Jagadeesh, M; Lavanya, M; Kalangi, Suresh K; Sarala, Y; Ramachandraiah, C; Varada Reddy, A

    2015-01-25

    A new, slightly distorted octahedral complex of copper(II), square planar complexes of nickel(II) and palladium(II) with 2,4'-dibromoacetophenone thiosemicarbazone (DBAPTSC) are synthesized. The ligand and the complexes are characterized by FT-IR, FT-Raman, powder X-ray diffraction studies. The IR and Raman data are correlated for the presence of the functional groups which specifically helped in the confirmation of the compounds. In addition, the free ligand is unambiguously characterized by (1)H and (13)C NMR spectroscopy while the copper(II) complex is characterized by electron paramagnetic resonance spectroscopy (EPR). The g values for the same are found to be 2.246 (g1), 2.012 (g2) and 2.005 (g3) which suggested rhombic distortions. The HOMO-LUMO band gap calculations for these compounds are found to be in between 0.5 and 4.0 eV and these compounds are identified as semiconducting materials. The synthesized ligand and its copper(II), nickel(II) and palladium(II) complexes are subjected to antitumour activity against the HepG2 human hepatoblastoma cell lines. Among all the compounds, nickel(II) complex is found to exert better antitumour activity with 57.6% of cytotoxicity. PMID:25064500

  19. Spectroscopic characterization, antioxidant and antitumour studies of novel bromo substituted thiosemicarbazone and its copper(II), nickel(II) and palladium(II) complexes

    Science.gov (United States)

    Jagadeesh, M.; Lavanya, M.; Kalangi, Suresh K.; Sarala, Y.; Ramachandraiah, C.; Varada Reddy, A.

    2015-01-01

    A new, slightly distorted octahedral complex of copper(II), square planar complexes of nickel(II) and palladium(II) with 2,4‧-dibromoacetophenone thiosemicarbazone (DBAPTSC) are synthesized. The ligand and the complexes are characterized by FT-IR, FT-Raman, powder X-ray diffraction studies. The IR and Raman data are correlated for the presence of the functional groups which specifically helped in the confirmation of the compounds. In addition, the free ligand is unambiguously characterized by 1H and 13C NMR spectroscopy while the copper(II) complex is characterized by electron paramagnetic resonance spectroscopy (EPR). The g values for the same are found to be 2.246 (g1), 2.012 (g2) and 2.005 (g3) which suggested rhombic distortions. The HOMO-LUMO band gap calculations for these compounds are found to be in between 0.5 and 4.0 eV and these compounds are identified as semiconducting materials. The synthesized ligand and its copper(II), nickel(II) and palladium(II) complexes are subjected to antitumour activity against the HepG2 human hepatoblastoma cell lines. Among all the compounds, nickel(II) complex is found to exert better antitumour activity with 57.6% of cytotoxicity.

  20. Study of thermodynamics of complex formation of flavonoids of steviа (Stevіa rebaudіana Bertonі) leaves

    OpenAIRE

    Kuznetsova, Inga

    2014-01-01

    Scientists have studied the mechanisms of forming complexes between flavonoids of  different plants and ions of iron and copper. Stevia is one of many plants, rich in biologically active substances and which is practically uninvestigated. In particular, the antioxidant effect of flavonoids of stevia leaves is not studied and there are no data on its thermodynamic properties, namely the possibility of natural flow of the complex formation process. There are no data on the possibility of formin...

  1. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

    2012-06-22

    that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

  2. The antitumour effect of ribonucleases and antiangiogenins on human tumours in nude mice

    Czech Academy of Sciences Publication Activity Database

    Poučková, P.; Zadinová, M.; Kalous, Jaroslav; Souček, J.; Pechar, Michal; Matoušek, Josef

    2013-01-01

    Roč. 9, č. 1 (2013), s. 43-51. ISSN 0973-1040 R&D Projects: GA ČR GA521/09/1214 Institutional support: RVO:67985904 ; RVO:61389013 Keywords : angiogenin * antitumour * aspermatogenesis * bovine Subject RIV: EB - Genetics ; Molecular Biology; CD - Macromolecular Chemistry (UMCH-V) http://www.researchtrends.net/tia/abstract.asp?in=0&vn=9&tid=57&aid=5

  3. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    OpenAIRE

    Pengfei Zhao; Mingbin Zheng; Zhenyu Luo; Ping Gong; Guanhui Gao; Zonghai Sheng; Cuifang Zheng; Yifan Ma; Lintao Cai

    2015-01-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system ...

  4. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway

    Science.gov (United States)

    Ma, Ting; Fan, Bo-Yi; Zhang, Chao; Zhao, Hui-Jun; Han, Chao; Gao, Cai-Yun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-01-01

    Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed, and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds. PMID:27416811

  5. First investigations of complex formation of At(I) with phosphorous organic compounds

    International Nuclear Information System (INIS)

    Reaction of At(I) with triphenylphosphine, triethylphosphite and tri-n-octylphosphine oxide was investigated in ethanolic solution by means of electromigration. A cationic complex with triphenylphosphine was identified being stable at pH = 1,9 in the concentration range of the ligand between c = 10-5 to 10-3 M. At a higher ligand concentration and at pH>2, the reduction effect of phosphine is superimposed on the complex formation. Complex formation is confirmed by ligand exchange reactions with Br- and I-. A comparatively weak complex is formed by triethylphosphite and At(I). No compound is formed by tri-n-octylphosphine oxide and At(I). (orig.)

  6. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    Directory of Open Access Journals (Sweden)

    Nicolas Goudin

    Full Text Available Natural regulatory T (Treg cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy.

  7. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    Science.gov (United States)

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly

    2016-01-01

    Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy. PMID:27341421

  8. Events during Initiation of Archaeal Transcription: Open Complex Formation and DNA-Protein Interactions

    OpenAIRE

    Hausner, Winfried; Thomm, Michael

    2001-01-01

    Transcription in Archaea is initiated by association of a TATA box binding protein (TBP) with a TATA box. This interaction is stabilized by the binding of the transcription factor IIB (TFIIB) orthologue TFB. We show here that the RNA polymerase of the archaeon Methanococcus, in contrast to polymerase II, does not require hydrolysis of the β-γ bond of ATP for initiation of transcription and open complex formation on linearized DNA. Permanganate probing revealed that the archaeal open complex s...

  9. Complex formation constant and hydration number change of aqua-rare earth ions

    International Nuclear Information System (INIS)

    Full text: It is now well established that the inner-sphere hydration number of aqua-rare earth ions changes from nine to eight in the middle of the rare earth series. This hydration number change greatly affects the complex formation of rare earth ions as we observe irregular variations in most series behaviours of the complex formation constant (K) in aqueous solution systems when K being plotted against 1/r or r (r is ionic radius of rare earth ion). Furthermore, it shows very anomalous concentration dependence in the sense that nona-aqua Ln3+ ion increases in number with increase in salt concentration in aqueous rare earth salt solution (salt chloride, perchlorate). In this report, a theoretical derivation of the formation constant (K) for the inner-sphere complex formation of rare earth ions with a monodentate ligand was made by taking account of both the hydration number change in the middle of the series and its anomalous salt concentration dependence. The series behaviour of the formation constant against 1/r (or r) is successfully explained with using the empirical finding that K varies almost linearly with 1/r (or r) in the region where only one hydration number dominates. This success is also taken as evidence that the anomalous salt concentration dependence of the hydration number change is caused by the outer-sphere complex formation of rare earth ions with the condition that nona-aqua rare earth ions form outer-sphere complexes more easily than octa-aqua ions

  10. Peculiarities of litter invertebrates’ multispecies complexes formation on the Khortitsa island (Zaporizhzhya province

    Directory of Open Access Journals (Sweden)

    D. О. Fedorchenko

    2008-02-01

    Full Text Available Peculiarities of litter invertebrates’ complexes formation under conditions of the Khortitsa National Reserve (Zaporizhzhya province are studied. The dispersion of taxonomic groups of different levels (families and species in litter mesofauna is swayed by the inter- and intrasystem factors; the largest influence has the power of litter and its humidity. The rate of ecological factors’ influence at different taxonomic levels may diverge.

  11. Sorption of small quantities of silver on silicic acid under the conditions of complex formation

    International Nuclear Information System (INIS)

    Present article is devoted to sorption of small quantities of silver on silicic acid under the conditions of complex formation. Study of precipitation of small quantities of silver (4.2·10-5mg/l) from the solutions of oxalic, tartaric and citric acids depending on ph showed that under these conditions the precipitation does not occur. This is due to formation of stable and soluble in the water silver complex compounds with oxalic, tartaric and citric acids.

  12. Ox red-metric study of complex formation processes of manganese (II, III) in glycin aqueous solution

    International Nuclear Information System (INIS)

    Present article is devoted to ox red-metric study of complex formation processes of manganese (II, III) in glycin aqueous solution. The possibility of application of ox red-metric method for study of complex formation processes of manganese (II, III) was shown. The composition of complex compounds was determined.

  13. The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?

    Science.gov (United States)

    Boussabbeh, Manel; Ben Salem, Intidhar; Rjiba-Touati, Karima; Bouyahya, Chedy; Neffati, Fadwa; Najjar, Mohamed Fadhel; Bacha, Hassen; Abid-Essefi, Salwa

    2016-05-01

    Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models. PMID:26619846

  14. Chemical equilibrium constants of rare earth nitrates and tri-n-butyl phosphate complex formation

    Institute of Scientific and Technical Information of China (English)

    Kalaya Changkrueng; Deacha Chatsiriwech

    2011-01-01

    Mixed rare earth nitrates (REi(NO3)3) in the aqueous solution was mixed with tri-n-butyl phosphate (TBP,(n-C4H9O)3PO) dissolved in kerosene for the formation of their corresponding complexes (REi(NO3)3·n1(n-C4H9O)3PO) at 303 K.The effects of initial concentrations of both TBP and mixed rare earth nitrates on the equilibrium constants of their complex formations were investigated.The complexes were formed almost immediately after mixing.The simultaneous formations reached their chemical equilibria within a few minutes by shaking the mixture at 200 r/min.The chemical equilibrium constants of the complex formations were independent of the initial TBP concentrations.However,they were decreased by reducing the concentration of REi(NO3)3.All equilibrium constants of the simultaneous complex formations were less than 0.7,while the average molar ratio of TBP to REi(NO3)3 of the complexes varied between 1.0 and 1.6.The chemical equilibrium constant for the formation of La(NO3)3·(n-C4HgO)3PO was 0.09,while that of Dy(NO3)3·(n-CaH9O)3PO was 0.68.The ascending sequence of chemical equilibrium constants for the simultaneous formations was La,Ce,Pr,Nd,Eu,Y,Srn,Gd,and Dy.

  15. Synthesis, thermal and antitumour studies of Th(IV complexes with furan-2-carboxaldehyde4-phenyl-3-thiosemicarbazone

    Directory of Open Access Journals (Sweden)

    VINO T. CHERIYAN

    2010-06-01

    Full Text Available Thorium(IV complexes with the Schiff base furan-2-carboxaldehyde4-phenyl-3-thiosemicarbazone (L were synthesised and characterized. The composition and structure of the metal complexes were proposed based on elemental analysis, molar conductivity measurements, FTIR and 1H-NMR spectroscopy. The Schiff base behaves as a neutral bidentate ligand coordinating through the azomethine N and the thioketo S atoms. From various studies, complexes were ascertained the general formula [ThL2X4] and [ThL2Y2], where X represents NO3–, NCS–, CH3COO–, CH3CHOHCOO–, ClO4– and Y SO42–and C2O42–. The thermal behaviour of the nitrato and oxalato complexes was studied and kinetic and thermodynamic parameters were calculated using the Coats-Redfern Equation. The ligand and a representative complex [ThL2(NO34] were screened in vitro for their antitumour activity against the human cervical cancer cell line (HeLa.

  16. On the promoter complex formation rate of E. coli RNA polymerases with T7 phage DNA.

    OpenAIRE

    Belintsev, B N; Zavriev, S.K.; Shemyakin, M.F.

    1980-01-01

    Influence of ionic strength on the kinetics of the promoter complex formation between E. coli RNA polymerase and T7 phage DNA was investigated using a membrane filter assay. The enzyme-promoter association rate constant was determined. It varies from 10(9) to 3 x 10(7) M-1 sec-1 when the ionic strength is changed from zero to 0.15 M NaCl. Basing on the theoretical analysis of experimental data obtained the model for the promoter site selection assuming the enzyme sliding along the DNA is disc...

  17. Temperature induced complex formation-deformation behavior of collagen model peptides and polyelectrolytes in aqueous solution

    OpenAIRE

    Terao, Ken; Kanenaga, Ryoko; Yoshida, Tasuku; Mizuno, Kazunori; Bächinger, Hans Peter

    2015-01-01

    Since the triple-helical collagen model peptides with a free N-terminus have three cationic groups at one end, it may have strong interactions with polyelectrolytes. In this study, complex formation behavior was investigated for sodium carboxymethyl amylose (NaCMA) + H-(Pro-Pro-Gly)10-OH (PPG10), a collagen model peptide, in aqueous NaCl with ionic strength of 10 mM and 100 mM by means of small-angle X-ray scattering (SAXS) and circular dichroism at different temperatures. The previously repo...

  18. Evaluation of complex formation ability of dissolved organic matter with radionuclide in ground water based on loading capacity (LC) method

    International Nuclear Information System (INIS)

    It is important to evaluate complex formation ability of dissolved organic matter (DOM) with radionuclide, in terms of long-term safety assessment of nuclear waste. In this review, the dependence of the complex stability on environmental factors such as pH, ionic strength, and characteristics of humic substances was described based on Loading Capacity (LC) method. The effects of humic concentration on actinide speciation and its solubility in a groundwater were evaluated with consideration of mixed complex formation. (author)

  19. Cannabinoids and cancer: pros and cons of an antitumour strategy

    OpenAIRE

    Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

    2006-01-01

    In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiprol...

  20. Young T cells age during a redirected anti-tumour attack: chimeric antigen receptor (CAR-provided dual costimulation is half the battle.

    Directory of Open Access Journals (Sweden)

    Andreas A Hombach

    2013-06-01

    Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells showed spectacular efficacy in the treatment of leukaemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG-1+ CD57+ CD7- CCR7- phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134 stimulation. We discuss the strategy with respect to prolong the anti-tumour response and to improve the over-all efficacy of adoptive cell therapy.

  1. Organometallic Antitumour Agents with Alternative Modes of Action

    Science.gov (United States)

    Casini, Angela; Hartinger, Christian G.; Nazarov, Alexey A.; Dyson, Paul J.

    The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially abandoned in favour of non-genomic targets by medicinal chemists developing organic drugs. A number of organometallic drugs that target proteins/enzymes have been developed and these compounds, based on ruthenium, osmium and gold, are described in this chapter. Targets include cathepsin B, thioredoxin reductases, multidrug resistance protein (Pgp), glutathione S-transferases and kinases. It is found that compounds that inhibit these various targets are active against metastatic tumours, or tumours that are resistant to classical DNA damaging agents such as cisplatin, and therefore offer considerable potential in clinical applications.

  2. Ligand exchange and complex formation kinetics studied by NMR exemplified on fac-[(CO)3M(H2O)]+ (M = Mn, Tc, Re)

    OpenAIRE

    Helm, Lothar

    2008-01-01

    In this review ligand exchange and complex formation reactions on fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) and on fac-[(CO)2(NO)Re(H2O)3]2+ are presented. A variety of experimental NMR techniques are described and it is shown that sometimes combinations of techniques applied at variable temperature or variable pressure allowed to measure exchange rate constants and their activation parameters as well as thermodynamic parameters. Furthermore, the use of uncommon nuclei for NMR like 17O or 99Tc ext...

  3. Stability of furosemide polymorphs and the effects of complex formation with β-cyclodextrin and maltodextrin.

    Science.gov (United States)

    Garnero, Claudia; Chattah, Ana Karina; Longhi, Marcela

    2016-11-01

    The effect of the formation of supramolecular binary complexes with β-cyclodextrin and maltodextrin on the chemical and physical stability of the polymorphs I and II of furosemide was evaluated in solid state. The solid samples were placed under accelerated storage conditions and exposed to daylight into a stability chamber for a 6-month. Chemical stability was monitored by high performance liquid chromatography, while the physical stability was studied by solid state nuclear magnetic resonance, powder X-ray diffraction and scanning electron microscopy. Changes in the physical appearance of the samples were evaluated. The studies showed a significant stabilizing effect of β-cyclodextrin on furosemide form II. Our results suggest that the complex formation is a useful tool for improving the stability of furosemide polymorphs. These new complexes are promising candidates that can be used in the pharmaceutical industry for the preparation of alternative matrices that improve physicochemical properties. PMID:27516309

  4. Can arsenic-phytochelatin complex formation be used as an indicator for toxicity in Helianthus annuus?

    Science.gov (United States)

    Raab, Andrea; Ferreira, Katia; Meharg, Andrew A; Feldmann, Jörg

    2007-01-01

    The formation of arsenic-phytochelatin (As-PC) complexes is thought to be part of the plant detoxification strategy for arsenic. This work examines (i) the arsenic (As) concentration-dependent formation of As-PC complex formation and (ii) redistribution and metabolism of As after arrested As uptake in Helianthus annuus. HPLC with parallel ICP-MS/ES-MS detection was used to identify and quantify the species present in plant extracts exposed to arsenate (As(V)) (between 0 and 66.7 micromol As l-1 for 24 h). At As concentrations below the EC50 value for root growth (22 micromol As l-1) As uptake is exponential, but it is reduced at concentrations above. Translocation between root and shoot seemed to be limited to the uptake phase of arsenic. No redistribution of As between root and shoot was observed after arresting As exposure. The formation of As-PC complexes was concentration-dependent. The amount and number of As-PC complexes increased exponentially with concentration up to 13.7 micromol As l-1. As(III)-PC3 and GS-As(III)-PC2 complexes were the dominant species in all samples. The ratio of PC-bound As to unbound As increased up to 1.3 micromol As l-1 and decreased at higher concentrations. Methylation of inorganic As was only a minor pathway in H. annuus with about 1% As methylated over a 32 d period. The concentration dependence of As-PC complex formation, amount of unbound reduced and oxidized PC2, and the relative uptake rate showed that As starts to influence the cellular metabolism of H. annuus negatively at As concentrations well below the EC50 value determined by more traditional means. Generally, As-PC complexes and PC-synthesis rate seem to be the more sensitive parameters to be studied when As toxicity values are to be estimated. PMID:17283372

  5. Complexometric determination: Part I - EDTA and complex formation with the Cu2+ ion

    Directory of Open Access Journals (Sweden)

    Rajković Miloš B.

    2002-01-01

    Full Text Available Compounds forming very stable complexes - chelates, have a wide field of application in analytical chemistry. The most famous group of these compounds are complexons. Complexons represent organic polyaminocarbonic acids as for example ethylenediaminetetraacetic acid (EDTA and its salts. The EDTA molecule has six coordinative sites. It is a hexadentate ligands i.e. it has two binding nitrogen atoms and four oxygen atoms from carboxyl groups and it forms complexes with almost all metal ions. EDTA as a tetraprotonic acid, H4Y disociates through four steps, yielding the ions HsY-, H2Y2-, HY3- and Y4-. Which of the EDTA forms will be encountered in a solution, depends on the pH. Due to the poor solubility of EDTA in pure water, as well as in most organic solvents, the disodium salt of EDTA Na2H2Y-2H2O, under the commercial name complexon III, is utilized for analytical determinations. In water, EDTA forms soluble, stabile chelate complexes with all cations, at the molar ratio 1:1, regardless of the charge of the metal ion. In contrast to other equilibria, which are mainly defined by Le Chatellier's principle, equilibria related to metal-EDTA complex formation are also dependent on the influence of the secondary equilibria of EDTA complex formation. Complexing reactions, which are equilibrium reactions, are simultaneously influenced by the following factors: solution pH and the presence of complexing agents which may also form a stabile complex with metal ions. The secondary reaction influence may be viewed and monitored through conditional stability constants. In the first part of the paper, the reaction of the formation of the Cu2+-ion complex with EDTA is analyzed beginning from the main reaction through various influences of secondary reactions on the complex Cu2+-EDTA: pH effect, complexation effect and hydrolysis effect. The equations are given for conditional stability constants, which include equilibrium reactions under actual conditions.

  6. Cadmium(II) N-acetylcysteine complex formation in aqueous solution.

    Science.gov (United States)

    Jalilehvand, Farideh; Amini, Zahra; Parmar, Karnjit; Kang, Eun Young

    2011-12-21

    The complex formation between Cd(II) ions and N-acetylcysteine (H(2)NAC) in aqueous solution was investigated using Cd K- and L(3)-edge X-ray absorption and (113)Cd NMR spectroscopic techniques. Two series of 0.1 M Cd(II) solutions with the total N-acetylcysteine concentration c(H2NAC) varied between 0.2-2 M were studied at pH 7.5 and 11.0, respectively. At pH = 11 a novel mononuclear [Cd(NAC)(4)](6-) complex with the average Cd-S distance 2.53(2) Å and the chemical shift δ((113)Cd) = 677 ppm was found to dominate at a concentration of the free deprotonated ligand [NAC(2-)] > 0.1 M, consistent with our previous reports on cadmium tetrathiolate complex formation with cysteine and glutathione. At pH 7.5 much higher ligand excess ([HNAC(-)] > 0.6 M) is required to make this tetrathiolate complex the major species. The (113)Cd NMR spectrum of a solution containing c(Cd(II)) = 0.5 M and c(H2NAC) = 1.0 M measured at 288 K showed three broad signals at 421, 583 and 642 ppm, which can be attributed to CdS(3)O(3), CdS(3)O and CdS(4) coordination sites, respectively, in oligomeric Cd(II)-NAC species with single thiolate bridges between the cadmium ions. PMID:22012146

  7. Dynamics of nanoparticle-protein corona complex formation: analytical results from population balance equations.

    Directory of Open Access Journals (Sweden)

    Faryad Darabi Sahneh

    Full Text Available BACKGROUND: Nanoparticle-protein corona complex formation involves absorption of protein molecules onto nanoparticle surfaces in a physiological environment. Understanding the corona formation process is crucial in predicting nanoparticle behavior in biological systems, including applications of nanotoxicology and development of nano drug delivery platforms. METHOD: This paper extends the modeling work in to derive a mathematical model describing the dynamics of nanoparticle corona complex formation from population balance equations. We apply nonlinear dynamics techniques to derive analytical results for the composition of nanoparticle-protein corona complex, and validate our results through numerical simulations. RESULTS: The model presented in this paper exhibits two phases of corona complex dynamics. In the first phase, proteins rapidly bind to the free surface of nanoparticles, leading to a metastable composition. During the second phase, continuous association and dissociation of protein molecules with nanoparticles slowly changes the composition of the corona complex. Given sufficient time, composition of the corona complex reaches an equilibrium state of stable composition. We find analytical approximate formulae for metastable and stable compositions of corona complex. Our formulae are very well-structured to clearly identify important parameters determining corona composition. CONCLUSION: The dynamics of biocorona formation constitute vital aspect of interactions between nanoparticles and living organisms. Our results further understanding of these dynamics through quantitation of experimental conditions, modeling results for in vitro systems to better predict behavior for in vivo systems. One potential application would involve a single cell culture medium related to a complex protein medium, such as blood or tissue fluid.

  8. Studies on the kinetics and mechanism of complex formation in the reactions of ferron with iron (III) and uranium (VI)

    International Nuclear Information System (INIS)

    The equilibria and kinetics of the reactions of ferron (7-iodo-8-hydroxyquindine-5-sulphonic acid) with iron(III) and uranium(VI) have been followed by stopped flow spectrophotometry under the conditions of mono-complex formation. The equilibrium constants obtained spectrophotmetrically have been compared with those obtained from kinetic studies. In the case of iron(III), in the acidity range, [H+]=(2.8-10.0)x10-2 mol dm-3, among the different possible reaction path-ways, the reaction has been found to proceed mainly through the interaction of Fe(OH)(aq)2+ and partially deprotonated form (LH-) of the ligand. In the case of uranium(VI), in the acidity range, [H+]=(2.5-25.0)x10-5 mol dm-3, a dual path mechanism involving UO2(aq)2+ and UO2(OH)(aq)- and the partially deprotonated (LH-) form of the ligand is consistent with the observations. The results in each case are in agreement with the Eigen mechanism and the characteristic water exchange rates have been obtained in each case, as a rough estimate, from the experimental data. Activation parameters (ΔHsup(≠) and ΔSsup(≠) for each path have been determined and compared. (author). 23 refs., 5 figs., 2 tabs

  9. Complex formation of Eu(III) with humic acid and polyacrylic acid

    International Nuclear Information System (INIS)

    With the intention of estimating the effect of the heterogeneous composition in the humic acid separately from its polyelectrolyte effect, comparative study on the interaction of Eu(III) with humic acid and polyacrylic acid has been carried out by the solvent extraction method with 10-3 M TTA and 10-3 M TBP in xylene at various total concentrations of Eu(III) (10-8 M to 10-5 M), pcH (5.0 to 5.5) and ionic strengths (0.02 to 1.0 M NaClO4). The interaction has been discussed in terms of the apparent complex formation constants, βα = [ML]/([M][R]), where [M] and [ML] are the concentrations of free and bound Eu3+ ion and [R] is the concentration of dissociated proton exchanging site. For both humate and polyacrylate, log βα increased with pcH or the degree of ionization and decreased with ionic strength. The Eu3+ ion concentration had no appreciable influence on the complex formation of Eu(III)-polyacrylate, and the values of log βα were obtained to be 7.57 ± 0.05 (I = 0.1, pcH = 5.53), 7.13 ± 0.04 (I = 0.1, pcH = 5.20), 6.68 ± 0.04 (I = 1.0, pcH = 5.54) and 5.61 ± 0.09 (I = 1.0, pcH = 4.73). On the other hand, log βα of humate remarkably decreased with the Eu3+ ion concentration; from 9.32 ([Eu3+] = 10-11.9 M) to 7.20 ([Eu3+] = 10-7.5 M) at pcH = 5.53 in 0.02 M NaClO4, from 8.63 ([Eu3+] = 10-12.5 M) to 6.35 ([Eu3+] = 10-7.2 M) at pcH = 5.53 in 0.1 M and from 7.59 ([Eu3+] = 10-10.7 M) to 5.20 ([Eu3+] = 10-7.0 M) at pcH = 5.52 in 1.0 M. The observed dependence of log βα of humate on the concentration of metal ion strongly suggests the heterogeneity of the complexing sites (the coexistence of weak and strong binding sites) in the humic acid. (orig.)

  10. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn- thesizing new chiral resolving agents.

  11. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    TAN Bin; ZHAI Zheng; LUO GuangSheng; WANG JiaDing

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn-thesizing new chiral resolving agents.

  12. Analysis of the Enhanced Stability of R(+)-Alpha Lipoic Acid by the Complex Formation with Cyclodextrins

    OpenAIRE

    Hiroshi Shimosegawa; Rie Nakane; Yoshiyuki Ishida; Yukiko Uekaji; Daisuke Nakata; Kathrin Pallauf; Gerald Rimbach; Seiichi Matsugo; Naoko Ikuta; Hironori Sugiyama; Keiji Terao

    2013-01-01

    R(+)-alpha lipoic acid (RALA) is one of the cofactors for mitochondrial enzymes and, therefore, plays a central role in energy metabolism. RALA is unstable when exposed to low pH or heat, and therefore, it is difficult to use enantiopure RALA as a pharma- and nutra-ceutical. In this study, we have aimed to stabilize RALA through complex formation with cyclodextrins (CDs). α-CD, β-CD and γ-CD were used for the formation of these RALA-CD complexes. We confirmed the complex formation using diffe...

  13. Determination of Cobalt and Manganese percentages in paint driers by complex formation titration

    International Nuclear Information System (INIS)

    The use of paint can be seen in everyday life. However, authorities in many countries have laid down strict regulations on toxic metal content of paints for toys, domestic appliances and other applications. An insisting demand for quick and reliable monitoring techniques arose since. Driers, which are the main additive used in paints, contain heavy metals. Complex formation titration is carried out to determine the percentages of cobalt and manganese in different paint driers utilizing EDTA titration method. For cobalt determination, eight different samples were dissolved in an acetic acid solution diluted with ethanol and water, then treated with an excess of EDTA solution. PAN indicator was used as the metal indicator. The excess was titrated with cupric acid. The average cobalt content was 0.0710 %. The manganese-containing samples were a benzene-soluble and EDTA was used. Eight dissolved samples were treated with EDTA and then titrated with zinc chloride solution. Eriochrome Black-T was the indicator. The mean manganese content was 0.0431 %. (author)

  14. Localization and dynamics of amylose-lipophilic molecules inclusion complex formation in starch granules.

    Science.gov (United States)

    Manca, Marianna; Woortman, Albert J J; Mura, Andrea; Loos, Katja; Loi, Maria Antonietta

    2015-03-28

    Inclusion complex formation between lipophilic dye molecules and amylose polymers in starch granules is investigated using laser spectroscopy and microscopy. By combining confocal laser scanning microscopy (CLSM) with spatial resolved photoluminescence (PL) spectroscopy, we are able to discriminate the presence of amylose in the peripheral region of regular and waxy granules from potato and corn starch, associating a clear optical fingerprint with the interaction between starch granules and lipophilic dye molecules. We show in particular that in the case of regular starch the polar head of the lipophilic dye molecules remains outside the amylose helix experiencing a water-based environment. The measurements performed on samples that have been extensively washed provide a strong proof of the specific interaction between lipid dye molecules and amylose chains in regular starch. These measurements also confirm the tendency of longer amylopectin chains, located in the hilum of waxy starch granules, to form inclusion complexes with ligands. Through real-time recording of CLSM micrographs, within a time frame of tens of seconds, we measured the dynamics of occurrence of the inclusion process between lipids and amylose located at the periphery of starch granules. PMID:25715960

  15. Complex formation during dissolution of metal oxides in molten alkali carbonates

    DEFF Research Database (Denmark)

    Li, Qingfeng; Borup, Flemming; Petrushina, Irina;

    1999-01-01

    as the partial pressure of carbon dioxide varies. By combination of solubility and electromotive force measurements, a model is constructed assuming the dissolution involves complex formation. The possible species for lead are proposed to be [Pb(CO3)(2)](-2) and/or [Pb(CO3)(3)](-4). A similar complex......Dissolution of metal oxides in molten carbonates relates directly to the stability of materials for electrodes and construction of molten carbonate fuel cells. In the present work the solubilities of PbO, NiO, Fe2O3,and Bi2O3 in molten Li/K carbonates have been measured at 650 degrees C under...... carbon dioxide atmosphere. It is found that the solubilities of NiO and PbO decrease while those of Fe2O3 and Bi2O3 remain approximately constant as the lithium mole fraction increases from 0.43 to 0.62 in the melt. At a fixed composition of the melt, NiO and PbO display both acidic and basic dissolution...

  16. Complex formation between neptunium(V) and various thiosemicarbazide derivatives in aqueous solution

    International Nuclear Information System (INIS)

    Complex formation between neptunium(V) and various thiosemicarbazide derivatives in solution has been studied spectrophotometrically in the pH range 4-10. Stepwise formation of three types of complexes, with composition NpO2HA, NpO2A-, and NpOHA2-, has been demonstrated with salicylaldehyde thiosemicarbazone (H2L) and salicylaldehyde S-methyl-isothiosemicarbazone (H2Q) at t = 25 +/- 10C and μ = 0.05. The logarithmic stability constants of the first two complexes are 5.14 +/- 0.06, 11.85 +/- 0.04 and 8.42 +/- 0.09, 13.33 +/- 0.015 for H2L and H2Q, respectively; equilibrium constants for the formation of hydroxo complexes of the form NpO2OHL2- and NpO2OHQ2- were also determined, and found to be equal to (2.23 +/-0.37) x 10-5 and (5.02 +/- 0.9) x 10-5, respectively. In the case of S-methyl-N1,N4-bis(salicylidene)isothiosemicarbazide (H2Z), only one type of complex is formed under these experimental conditions, namely, NpO2Z-, with a logarithmic stability constant of 4.78 +/- 0.03. Dissociation constants for H2Q and H2Z were also determined

  17. Substrate-Na{sup +} complex formation: Coupling mechanism for {gamma}-aminobutyrate symporters

    Energy Technology Data Exchange (ETDEWEB)

    Pallo, Anna; Simon, Agnes [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Bencsura, Akos [Department of Theoretical Chemistry, Institute of Structural Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest (Hungary); Heja, Laszlo [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Kardos, Julianna, E-mail: jkardos@chemres.hu [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary)

    2009-07-24

    Crystal structures of transmembrane transport proteins belonging to the important families of neurotransmitter-sodium symporters reveal how they transport neurotransmitters across membranes. Substrate-induced structural conformations of gated neurotransmitter-sodium symporters have been in the focus of research, however, a key question concerning the mechanism of Na{sup +} ion coupling remained unanswered. Homology models of human glial transporter subtypes of the major inhibitory neurotransmitter {gamma}-aminobutyric acid were built. In accordance with selectivity data for subtype 2 vs. 3, docking and molecular dynamics calculations suggest similar orthosteric substrate (inhibitor) conformations and binding crevices but distinguishable allosteric Zn{sup 2+} ion binding motifs. Considering the occluded conformational states of glial human {gamma}-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic {gamma}-aminobutyric acid in complex with Na{sup +} ion. The existence of the minor ring-like conformation of {gamma}-aminobutyric acid in complex with Na{sup +} ion may be attributed to the strengthening of the intramolecular H-bond by the electrostatic effect of Na{sup +} ion. Coupling substrate uptake into cells with the thermodynamically favorable Na{sup +} ion movement through substrate-Na{sup +} ion complex formation may be a mechanistic principle featuring transmembrane neurotransmitter-sodium symporter proteins.

  18. Protein complex formation and intranuclear dynamics of NAC1 in cancer cells.

    Science.gov (United States)

    Nakayama, Naomi; Kato, Hiroaki; Sakashita, Gyosuke; Nariai, Yuko; Nakayama, Kentaro; Kyo, Satoru; Urano, Takeshi

    2016-09-15

    Nucleus accumbens-associated protein 1 (NAC1) is a cancer-related transcription regulator protein that is also involved in the pluripotency and differentiation of embryonic stem cells. NAC1 is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. NAC1 knock-down was previously shown to result in the apoptosis of ovarian cancer cell lines and to rescue their sensitivity to chemotherapy, suggesting that NAC1 may be a potential therapeutic target, but protein complex formation and the dynamics of intranuclear NAC1 in cancer cells remain poorly understood. In this study, analysis of HeLa cell lysates by fast protein liquid chromatography (FPLC) on a sizing column showed that the NAC1 peak corresponded to an apparent molecular mass of 300-500 kDa, which is larger than the estimated molecular mass (58 kDa) of the protein. Furthermore, live cell photobleaching analyses with green fluorescent protein (GFP)-fused NAC1 proteins revealed the intranuclear dynamics of NAC1. Collectively our results demonstrate that NAC1 forms a protein complex to function as a transcriptional regulator in cancer cells. PMID:27424155

  19. Spectroscopic Study on the Ternary Complex Formation of U(VI) with Salicylic Acid

    International Nuclear Information System (INIS)

    From the nuclear chemical point of view, ternary complex formation of actinide ions with ligands has attracted attention for understanding radionuclides' migration in the environment. There are various ligands in natural aquatic systems which can form stable ternary actinide complexes. Humic substance in a near-neutral groundwater is one of them and carboxylic groups in a humic substance are considered as the most likely functional group which interacts with actinides. In this work, the formation of the ternary complex of U(VI) with salicylic acid (SAH2) was investigated by two different laser-based spectroscopic methods, i.e., laser-induced breakdown detection (LIBD) and time-resolved laser fluorescence spectroscopy (TRLFS). The notable features are as follows: (i) the breakdown probability increases slightly, (ii) the absorbance of U(VI) increases, whereas the fluorescence intensity decreases with increasing salicylic acid concentration. The increase of the breakdown probability indicates that insoluble species are formed due to the complexation of U(VI) with SAH2. The decrease of the fluorescence intensity is due to the quenching effect of the SAH2 in the complexes. With regards to the instrumentation, the characteristics of a newly developed LIBD system adopting a probe beam deflection method are presented. We report also on the improved speciation sensitivity (∼10-9M for UO22+) of the TRLFS system

  20. A spectrophotometric investigation of the complex formation between lanthanum (III) and eriochrome cyanine R

    International Nuclear Information System (INIS)

    The complex formation between La(III) and Eriochrome Cyanine R has been investigated. Three complexes have been detected. A first one (Complex I) in the pH range of 5.3-5.5 with lambda sub(max) = 460nm. a second one (Complex II) in the pH range of 6.2-6.5 with lambda sub(max) = 490nm and a third one (complex III) in the pH range of 8.2 - 9.0 with lambda sub(max) = 545nm and a shoulder between 570-580nm. The composition and stability constants of the complexes, respectively: complex I: La(ECR)2 and 4.9 x 107, complex II: La(ECR)2 and 7.0 x 107, complex III: La.ECR and 1.0 x 104. All measurements were taken at 25.0 +- 0.10C and μ = 0.2 (NaClO4). (Author)

  1. Complex formation between neptunium(V) and various thiosemicarbazide derivatives in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Chuguryan, D.G.; Dzyubenko, V.I.; Gerbeleu, N.V.

    1987-01-01

    Complex formation between neptunium(V) and various thiosemicarbazide derivatives in solution has been studied spectrophotometrically in the pH range 4-10. Stepwise formation of three types of complexes, with composition NpO/sub 2/HA, NpO/sub 2/A/sup -/, and NpOHA/sup 2 -/, has been demonstrated with salicylaldehyde thiosemicarbazone (H/sub 2/L) and salicylaldehyde S-methyl-isothiosemicarbazone (H/sub 2/Q) at t = 25 +/- 1/sup 0/C and ..mu.. = 0.05. The logarithmic stability constants of the first two complexes are 5.14 +/- 0.06, 11.85 +/- 0.04 and 8.42 +/- 0.09, 13.33 +/- 0.015 for H/sub 2/L and H/sub 2/Q, respectively; equilibrium constants for the formation of hydroxo complexes of the form NpO/sub 2/OHL/sup 2 -/ and NpO/sub 2/OHQ/sup 2 -/ were also determined, and found to be equal to (2.23 +/-0.37) x 10/sup -5/ and (5.02 +/- 0.9) x 10/sup -5/, respectively. In the case of S-methyl-N/sub 1/,N/sub 4/-bis(salicylidene)isothiosemicarbazide (H/sub 2/Z), only one type of complex is formed under these experimental conditions, namely, NpO/sub 2/Z/sup -/, with a logarithmic stability constant of 4.78 +/- 0.03. Dissociation constants for H/sub 2/Q and H/sub 2/Z were also determined.

  2. Complex formation of uranium(VI) with fructose and glucose phosphates

    International Nuclear Information System (INIS)

    obtain: log [UO2(lig)x(2-y)+]/ [UO22+] = x log [lig(noncomplexed)] - y log [H+] + log K. From this we conclude that the 1:1 uranyl sugar phosphate species UO2(ROPO3) (R is either glucose or fructose) has formed. Using these data, the complex formation constants for the complexes were calculated to lie in the range of log K=3.7 for G6P and 3.2 for F6P. (author)

  3. Implantable biodegradable sponges: effect of interpolymer complex formation of chitosan with gelatin on the release behavior of tramadol hydrochloride.

    Science.gov (United States)

    Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

    2007-01-01

    The effect of interpolymer complex formation between positively charged chitosan and negatively charged gelatin (Type B) on the release behavior of tramadol hydrochloride from biodegradable chitosan-gelatin sponges was studied. Mixed sponges were prepared by freeze-drying the cross-linked homogenous stable foams produced from chitosan and gelatin solutions where gelatin acts as a foam builder. Generation of stable foams was optimized where concentration, pH of gelatin solution, temperature, speed and duration of whipping process, and, chitosan-gelatin ratio drastically affect the properties and the stability of the produced foams. The prepared sponges were evaluated for their morphology, drug content, and microstructure using scanning electron microscopy, mechanical properties, uptake capacity, drug release profile, and their pharmacodynamic activity in terms of the analgesic effect after implantation in Wistar rats. It was revealed that whipping 7% (w/w) gelatin solution, of pH 5.5, for 15 min at 25 degrees C with a stirring speed of 1000 rpm was the optimum conditions for stable gelatin foam generation. Moreover, homogenous, uniform chitosan-gelatin foam with small air bubbles were produced by mixing 2.5% w/w chitosan solution with 7% w/w gelatin solution in 1:5 ratio. Indeed, polyionic complexation between chitosan and gelatin overcame the drawbacks of chitosan sponge mechanical properties where, pliable, soft, and compressible sponge with high fluid uptake capacity was produced at 25 degrees C and 65% relative humidity without any added plasticizer. Drug release studies showed a successful retardation of the incorporated drug where the t50% values of the dissolution profiles were 0.55, 3.03, and 4.73 hr for cross-linked gelatin, un-cross-linked chitosan-gelatin, and cross-linked chitosan-gelatin sponges, respectively. All the release experiments followed Higuchi's diffusion mechanism over 12 hr. The achieved drug prolongation was a result of a combined effect

  4. Thermochemical study of processes of complex formation of Cu2+ ions with L-glutamine in aqueous solutions

    Science.gov (United States)

    Gorboletova, G. G.; Gridchin, S. N.; Lutsenko, A. A.

    2010-11-01

    Heats of the interaction of Cu(NO3)2 solutions with L-glutamine solutions were measured directly by calorimetry at a temperature of 298.15 K and ionic strength values of 0.5, 1.0, and 1.5 (KNO3). Using RRSU universal software, the experimental data were subjected to rigorous mathematical treatment with allowances made for several concurrent processes in the system. The heats of formation of the CuL+ and CuL2 complexes were calculated from the calorimetric measurements. The standard heats of the complex formation of Cu2+ with L-glutamine were obtained by extrapolation to zero ionic strength. The complete thermodynamic characteristic (Δr H o, Δr G o, Δr S o) of the complex formation processes in a Cu2+—L-glutamine system was obtained.

  5. Determination of complex formation constants by phase sensitive alternating current polarography: Cadmium-polymethacrylic acid and cadmium-polygalacturonic acid.

    Science.gov (United States)

    Garrigosa, Anna Maria; Gusmão, Rui; Ariño, Cristina; Díaz-Cruz, José Manuel; Esteban, Miquel

    2007-10-15

    The use of phase sensitive alternating current polarography (ACP) for the evaluation of complex formation constants of systems where electrodic adsorption is present has been proposed. The applicability of the technique implies the previous selection of the phase angle where contribution of capacitive current is minimized. This is made using Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) in the analysis of ACP measurements at different phase angles. The method is checked by the study of the complexation of Cd by polymethacrylic (PMA) and polygalacturonic (PGA) acids, and the optimal phase angles have been ca. -10 degrees for Cd-PMA and ca. -15 degrees for Cd-PGA systems. The goodness of phase sensitive ACP has been demonstrated comparing the determined complex formation constants with those obtained by reverse pulse polarography, a technique that minimizes the electrode adsorption effects on the measured currents. PMID:19073101

  6. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    Science.gov (United States)

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-09-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

  7. Influence of tumours on protective anti-tumour immunity and the effects of irradiation

    Directory of Open Access Journals (Sweden)

    Gemma Ann Foulds

    2013-02-01

    Full Text Available Innate and adaptive immunity play important roles in the development and progression of cancer and it is becoming apparent that tumours can influence the induction of potentially protective responses in a number of ways. The prevalence of immunoregulatory T cell populations in the circulation and tumours of patients with cancer is increased, and the presence of these cells appears to present a major barrier to the induction of tumour immunity. One aspect of tumour-mediated immunoregulation which has received comparatively little attention is that which is directed towards natural killer (NK cells, although evidence that the phenotype and function of NK cell populations are modified in patients with cancer is accumulating.Although the precise mechanisms underlying these localised and systemic immunoregulatory effects remain unclear, tumour-derived factors appear, in part at least, to be involved. The effects could be manifested by an altered function and/or via an influence on the migratory properties of individual cell subsets. A better insight into endogenous immunoregulatory mechanisms and the capacity of tumours to modify the phenotype and function of innate and adaptive immune cells might assist the development of new immunotherapeutic approaches and improve the management of patients with cancer.This article reviews current knowledge relating to the influence of tumours on protective anti-tumour immunity and considers the potential influence that radiation-induced effects might have on the prevalence, phenotype and function of innate and adaptive immune cells in patients with cancer.

  8. Hyperthermia improves the antitumour effect of metronomic cyclophosphamide in a rat transplantable brain tumour

    International Nuclear Information System (INIS)

    Background and purpose: As low-dose metronomic cyclophosphamide (CTX) and hyperthermia (HT) both exert antitumour effects in part through antiangiogenic mechanisms, interactive effects of the two modalities were explored. Materials and methods: Subcutaneously implanted rat tumours (BT4An) were treated with CTX 35 mg/kg i.p. three doses a week for two weeks, local water-bath HT yielding mean tumour temperature of 43 oC for one hour at day 0, both modalities combined (CTX-HT0), or saline. TUNEL assays, immunohistochemical staining of thrombospondin 1 (TSP-1) and real time RT-PCR of TSP-1 mRNA were analysed the first three hours after completed treatment day 0. Results: Metronomic dosed CTX (p = 0.006) and HT (p 0 (41%) treated rats. TSP-1 protein was specifically upregulated in the vascular matrix of tumours receiving CTX (weak), HT (moderate) and CTX-HT0 (strong). In contrast, reduced expression of TSP-1 protein was observed in tumour cells after HT alone and CTX-HT0. TUNEL assays indicated induction of apoptosis by HT and CTX-HT0 90 minutes after end of the first treatment. Conclusion: A single session of local HT enhances the effects of low-dose metronomic CTX, possibly in part mediated through a differential effect on TSP-1 protein levels in tumour cells and tumour vasculature

  9. Characterization for Binding Complex Formation with Site-Directly Immobilized Antibodies Enhancing Detection Capability of Cardiac Troponin I

    OpenAIRE

    Il-Hoon Cho; Sung-Min Seo; Jin-Woo Jeon; Se-Hwan Paek

    2009-01-01

    The enhanced analytical performances of immunoassays that employed site-directly immobilized antibodies as the capture binders have been functionally characterized in terms of antigen-antibody complex formation on solid surfaces. Three antibody species specific to cardiac troponin I, immunoglobulin G (IgG), Fab, and F(ab′)2 were site-directly biotinylated within the hinge region and then immobilized via a streptavidin-biotin linkage. The new binders were more efficient capture antibodies ...

  10. Self-motion of a phenanthroline disk on divalent metal ion aqueous solutions coupled with complex formation

    OpenAIRE

    Nakata, Satoshi; Arima, Yoshie

    2008-01-01

    The self-motion of a 1,10-phenanthroline disk on divalent metal ion aqueous solutions was investigated as a simple autonomous motor coupled with complex formation. The characteristic features of motion (continuous and oscillatory motion) and their concentration regions differed among metal ions, and the frequency of oscillatory motion depended on the temperature of the aqueous solution. The nature of the characteristic motion is discussed in relation to the stability constant of complex forma...

  11. Development of Spectrophotometry Method For Iodide Determination Based on I2-Starch Complex Formation with Hypochlorite as oxidator

    OpenAIRE

    Qurrata Ayun; Hermin Sulistyarti; Atikah Atikah

    2015-01-01

    Iodine is one of the most important elements for human body. Both, the overage and the deficiency supply of iodine give negative impact for human health. In this research, a simple and inexpensive spectrophotometric method is developed is based on starch-iodine complex formation, where iodide was oxidized with hypochlorite to form iodine, which then reacted with starch to form a blue starch-iodine complex. In this research, the common analytical parameters were optimized regarding to sensitiv...

  12. Complex formation constants and thermodynamic parameters for La(III) and Y(III) L-serine complexes

    International Nuclear Information System (INIS)

    The stoichiometric stability constants for La(III) and Y(III) L-serine complexes were determined by potentiometric methods at different ionic strenghts adjusted with NaClO4 and at different temperatures. The overall changes in free energy (ΔGO), enthalpy (ΔHO), and entropy (ΔSO) during the protonation of L-serine and that accompanying the complex formation with the metal ions have been evaluated. (author)

  13. Synthesis, structure and complex formation properties of alkyl derivatives of ethylxantogenic acids

    International Nuclear Information System (INIS)

    efficiency of metal extraction influences the structure of reactant, the concentration and the nature an acid. The derivatives of xanthogenic acid have shown to be weak extractants of noble metals from acid mediums. The most effective extractants were: S-heptyl - (3,0 M, Au, 64 %) and S-amyl-(1,0 M, Ag, 81,8 %; 3,0 M, Os, 66,7 %) from sulfuric acid medium; and S-amylxanthogenate (6,0 M, Ag, 65,5 %) from hydrochloric medium. Branching of alkyl chain (i-C4H9) results in some increase of efficiency of extraction of Au and Ag from acid mediums. Thus, alkyl derivatives of xanthogenic acid are synthesized and the structure of the obtained substances are confirmed by IR, H1 NMR, and mass spectrometry data have been studied their complex formation properties in relation to noble metals

  14. Anti-tumour necrosis factor-alpha activity in Ixodes ricinus saliva

    Czech Academy of Sciences Publication Activity Database

    Koník, Peter; Slavíková, Veronika; Salát, Jiří; Řezníčková, Jana; Dvorožňáková, E.; Kopecký, Jan

    2006-01-01

    Roč. 28, č. 12 (2006), s. 649-656. ISSN 0141-9838 R&D Projects: GA ČR GA524/05/0811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * tick saliva * TNF Subject RIV: EC - Immunology Impact factor: 2.009, year: 2006

  15. Antitumour activity and other biological actions of oligomers of ribonuclease A

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Josef; Gottes, G.; Poučková, P.; Souček, J.; Slavík, Tomáš; Vottariello, F.; Libonati, M.

    2003-01-01

    Roč. 278, č. 26 (2003), s. 23817-23822. ISSN 0021-9258 R&D Projects: GA ČR GA523/01/0114 Institutional research plan: CEZ:AV0Z5045916 Keywords : ribonuclease A Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.482, year: 2003

  16. The biological function and antitumour effect of interleukin-21%白细胞介素21的生物学功能及其抗肿瘤效应

    Institute of Scientific and Technical Information of China (English)

    李栋; 俞慧清; 魏小元; 成国祥

    2009-01-01

    白细胞介素21(IL-21)属于Ⅰ类细胞因子,主要由活化的CD4~+T产生,作用于免疫系统中的大部分骨髓、淋巴细胞,具有广泛的生物学功能,是联系主动免疫与被动免疫的中间因子.IL-21能够调节体液和细胞介导的免疫应答,促进T细胞增殖分化,调节B细胞的增殖分化与调亡,增强NK细胞的细胞毒性作用与免疫监督功能.此外,IL-21还具有抗肿瘤作用,与其他细胞因子、疫苗等联合应用,可增强其抑制肿瘤细胞生长的功能.该文综述了IL-21的生物功能及其应用于抗肿瘤治疗的研究前景.%Interleukin-21(IL-21) is a type I cytokine and mainly produced by activated CD4~+ T cells. IL-21 targets a broad range of lymphoid and myeloid cells of the immune system and therefore is able to regulate innate and acquired immune responses. IL-21 has effect on T-cell activation, B-cell Ig-production, NK-ceil activation. Moreover, Many researchs demonstrated that IL-21 has antitumour activity in several preclinical models. When combining IL-21 with other cytokines or drugs, the antitumour activity can be enhanced. Here, we provide an overview about the biological function of IL-21 and its prospect in cancer therapy.

  17. The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics

    International Nuclear Information System (INIS)

    The anti-tumour activity of the Au (I) phosphine complex [Au(dppe2]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)2]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)2]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the in vitro and in vivo studies. Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.

  18. Elevation of serum KL-6 in patients with psoriasis treated with anti-tumour necrosis factor-α therapy.

    Science.gov (United States)

    Higashi, Y; Tada, K; Shimokawa, M; Kawai, K; Kanekura, T

    2016-01-01

    We report three patients with psoriasis whose serum level of Krebs Von Den Lungen (KL)-6 increased during therapy with anti-tumour necrosis factor (TNF)-α. A diagnosis of early-phase or subclinical interstitial pneumonia was made in two patients, and their KL-6 level decreased after anti-TNF-α discontinuation. The rise in KL-6 in the other patient was attributed to methotrexate. We propose that serum KL-6 should be monitored routinely in patients treated with anti-TNF agents. PMID:25557847

  19. Local induction of a cytotoxic factor in a murine tumour by systemic administration of an antitumour polysaccharide, MGA.

    OpenAIRE

    K. Takahashi; Watanuki, Y; Yamazaki, M.; Abe, S

    1988-01-01

    When an antitumour mannoglucan prepared from Microellobosporia grisea, MGA was administered i.v. to C3H/He mice bearing the solid MH134 hepatoma, a cytotoxic factor was induced that was detectable in the tumour homogenate by an 8 h cytolysis assay against L-929 fibroblasts. Without MGA treatment, the cytotoxic factor was not detectable in the tumour homogenate. MGA induced the cytotoxic factor in tumour tissue specifically, its level reaching a maximum (24 U ml-1) 3 h after administration of ...

  20. Complex Formation of Myrosinase Isoenzymes in Oilseed Rape Seeds Are Dependent on the Presence of Myrosinase-Binding Proteins1

    Science.gov (United States)

    Eriksson, Susanna; Andréasson, Erik; Ekbom, Barbara; Granér, Georg; Pontoppidan, Bo; Taipalensuu, Jan; Zhang, Jiaming; Rask, Lars; Meijer, Johan

    2002-01-01

    The enzyme myrosinase (EC 3.2.3.1) degrades the secondary compounds glucosinolates upon wounding and serves as a defense to generalist pests in Capparales. Certain myrosinases are present in complexes together with other proteins such as myrosinase-binding proteins (MBP) in extracts of oilseed rape (Brassica napus) seeds. Immunhistochemical analysis of wild-type seeds showed that MBPs were present in most cells but not in the myrosin cells, indicating that the complex formation observed in extracts is initiated upon tissue disruption. To study the role of MBP in complex formation and defense, oilseed rape antisense plants lacking the seed MBPs were produced. Western blotting and immunohistochemical staining confirmed depletion of MBP in the transgenic seeds. The exclusive expression of myrosinase in idioblasts (myrosin cells) of the seed was not affected by the down-regulation of MBP. Using size-exclusion chromatography, we have shown that myrosinases with subunit molecular masses of 62 to 70 kD were present as free dimers from the antisense seed extract, whereas in the wild type, they formed complexes. In accordance with this, MBPs are necessary for myrosinase complex formation of the 62- to 70-kD myrosinases. The product formed from sinalbin hydrolysis by myrosinase was the same whether MBP was present or not. The performance of a common beetle generalist (Tenebrio molitor) fed with seeds, herbivory by flea beetles (Phyllotreta undulata) on cotyledons, or growth rate of the Brassica fungal pathogens Alternaria brassicae or Lepthosphaeria maculans in the presence of seed extracts were not affected by the down-regulation of MBP, leaving the physiological function of this protein family open. PMID:12177471

  1. Complex formation of myrosinase isoenzymes in oilseed rape seeds are dependent on the presence of myrosinase-binding proteins.

    Science.gov (United States)

    Eriksson, Susanna; Andréasson, Erik; Ekbom, Barbara; Granér, Georg; Pontoppidan, Bo; Taipalensuu, Jan; Zhang, Jiaming; Rask, Lars; Meijer, Johan

    2002-08-01

    The enzyme myrosinase (EC 3.2.3.1) degrades the secondary compounds glucosinolates upon wounding and serves as a defense to generalist pests in Capparales. Certain myrosinases are present in complexes together with other proteins such as myrosinase-binding proteins (MBP) in extracts of oilseed rape (Brassica napus) seeds. Immunhistochemical analysis of wild-type seeds showed that MBPs were present in most cells but not in the myrosin cells, indicating that the complex formation observed in extracts is initiated upon tissue disruption. To study the role of MBP in complex formation and defense, oilseed rape antisense plants lacking the seed MBPs were produced. Western blotting and immunohistochemical staining confirmed depletion of MBP in the transgenic seeds. The exclusive expression of myrosinase in idioblasts (myrosin cells) of the seed was not affected by the down-regulation of MBP. Using size-exclusion chromatography, we have shown that myrosinases with subunit molecular masses of 62 to 70 kD were present as free dimers from the antisense seed extract, whereas in the wild type, they formed complexes. In accordance with this, MBPs are necessary for myrosinase complex formation of the 62- to 70-kD myrosinases. The product formed from sinalbin hydrolysis by myrosinase was the same whether MBP was present or not. The performance of a common beetle generalist (Tenebrio molitor) fed with seeds, herbivory by flea beetles (Phyllotreta undulata) on cotyledons, or growth rate of the Brassica fungal pathogens Alternaria brassicae or Lepthosphaeria maculans in the presence of seed extracts were not affected by the down-regulation of MBP, leaving the physiological function of this protein family open. PMID:12177471

  2. SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.

    Directory of Open Access Journals (Sweden)

    Weina Zhao

    Full Text Available Significant insight into the signaling pathways leading to activation of the Rel transcription factor family, collectively termed NF-κB, has been gained. Less well understood is how subsets of NF-κB-dependent genes are regulated in a signal specific manner. The SIMPL protein (signaling molecule that interacts with mouse pelle-like kinase is required for full Tumor Necrosis Factor-α (TNFα induced NF-κB activity. We show that SIMPL is required for steady-state hematopoiesis and the expression of a subset of TNFα induced genes whose products regulate hematopoietic cell activity. To gain insight into the mechanism through which SIMPL modulates gene expression we focused on the Tnf gene, an immune response regulator required for steady-state hematopoiesis. In response to TNFα SIMPL localizes to the Tnf gene promoter where it modulates the initiation of Tnf gene transcription. SIMPL binding partners identified by mass spectrometry include proteins involved in transcription and the interaction between SIMPL and MED1 was characterized in more detail. In response to TNFα, SIMPL is found in p65-MED1 complexes where SIMPL enhances p65/MED1/SIMPL complex formation. Together our results indicate that SIMPL functions as a TNFα-dependent p65 co-activator by facilitating the recruitment of MED1 to p65 containing transcriptional complexes to control the expression of a subset of TNFα-induced genes.

  3. Complex formation in the system double charged metal cation-Stenhouse base in water-alcohol solution

    International Nuclear Information System (INIS)

    Using the method of potentiometric titration complex formation reaction of the system metal(II) salt cation (Me2+ = Fe2+, Cd2+, Hg2+, Zn2+, Mn2+, Co2+, Ni2+) Stenhouse base in water-alcohol solution has been studied. Compositions of equilibrium complexes, the constants of their formation and instability have been determined. CoCl2 x 6H2O, NiCl2 x 6H2O and Mn(NO3)2 x 6H2O have been shown to have the most stabilizing effect on Stenhouse base

  4. Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Doni, Andrea; Romani, Luigina; Jürgensen, Henrik Jessen; Behrendt, Niels; Mantovani, Alberto; Garred, Peter

    2013-01-01

    was affected in a pH- and divalent cation-sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a...... demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory "find me and eat me" signal to sequester altered-host cells. The fact that the ficolin-1-PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which...

  5. Study of inclusion complex formation between chlorpromazine hydrochloride, as an antiemetic drug, and β-cyclodextrin, using conductometric technique

    International Nuclear Information System (INIS)

    The behavior of micellization of chlorpromazine hydrochloride (CPH) as an antiemetic drug and its inclusion complex formation with β-cyclodextrin (β-CD) was studied using conductometric technique. The binding or association constant of the complexation equilibrium is evaluated from conductometric measurements by using a nonlinear regression method. The resulting K values for micellization as well as complexation are analyzed. The experiments were carried out at different temperatures. It has been found that CPH form only the 1:1 complex. The association constant values are used for evaluation of thermodynamic parameters of complexation, such as ΔGcomplexo, ΔHcomplexo and ΔScomplexo.

  6. Charge-transfer complex formation in gelation: the role of solvent molecules with different electron-donating capacities.

    Science.gov (United States)

    Basak, Shibaji; Bhattacharya, Sumantra; Datta, Ayan; Banerjee, Arindam

    2014-05-01

    A naphthalenediimide (NDI)-based synthetic peptide molecule forms gels in a particular solvent mixture (chloroform/aromatic hydrocarbon, 4:1) through charge-transfer (CT) complex formation; this is evident from the corresponding absorbance and fluorescence spectra at room temperature. Various aromatic hydrocarbon based solvents, including benzene, toluene, xylene (ortho, meta and para) and mesitylene, have been used for the formation of the CT complex. The role of different solvent molecules with varying electron-donation capacities in the formation of CT complexes has been established through spectroscopic and computational studies. PMID:24677404

  7. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming

    Directory of Open Access Journals (Sweden)

    Coffey Matt

    2011-02-01

    Full Text Available Abstract Background As well as inducing direct oncolysis, reovirus treatment of melanoma is associated with activation of innate and adaptive anti-tumour immune responses. Results Here we characterise the effects of conditioned media from reovirus-infected, dying human melanoma cells (reoTCM, in the absence of live virus, to address the immune bystander potential of reovirus therapy. In addition to RANTES, IL-8, MIP-1α and MIP-1β, reovirus-infected melanoma cells secreted eotaxin, IP-10 and the type 1 interferon IFN-β. To address the mechanisms responsible for the inflammatory composition of reoTCM, we show that IL-8 and IFN-β secretion by reovirus-infected melanoma cells was associated with activation of NF-κB and decreased by pre-treatment with small molecule inhibitors of NF-κB and PKR; specific siRNA-mediated knockdown further confirmed a role for PKR. This pro-inflammatory milieu induced a chemotactic response in isolated natural killer (NK cells, dendritic cells (DC and anti-melanoma cytotoxic T cells (CTL. Following culture in reoTCM, NK cells upregulated CD69 expression and acquired greater lytic potential against tumour targets. Furthermore, melanoma cell-loaded DC cultured in reoTCM were more effective at priming adaptive anti-tumour immunity. Conclusions These data demonstrate that the PKR- and NF-κB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing can recruit and activate innate and adaptive effector cells, thus potentially altering the tumour microenvironment to support bystander immune-mediated therapy as well as direct viral oncolysis.

  8. Development of Spectrophotometry Method For Iodide Determination Based on I2-Starch Complex Formation with Hypochlorite as oxidator

    Directory of Open Access Journals (Sweden)

    Qurrata Ayun

    2015-05-01

    Full Text Available Iodine is one of the most important elements for human body. Both, the overage and the deficiency supply of iodine give negative impact for human health. In this research, a simple and inexpensive spectrophotometric method is developed is based on starch-iodine complex formation, where iodide was oxidized with hypochlorite to form iodine, which then reacted with starch to form a blue starch-iodine complex. In this research, the common analytical parameters were optimized regarding to sensitivity and selectivity. It was noted that maximum wavelength for starch-iodine complex was 618 nm, optimum time for complex formation and oxidation was 15 minutes, and optimum hypochlorite concentration was 6 ppm. Under the obtained optimum conditions, the proposed method showed linearity from 0-20 ppm iodide (r2 = 0.994, with limit detection of 0.20 ppm. Determination of iodide with this method was unaffected by Cl-, and Br-; but SCN- affected the measurement of iodide at concentration of 1 ppm. Application to synthetic and urinary samples showed that the proposed method has good agreement with the standard spectrophotometry (leuco crystal violet method, and can be used as an alternative method for iodide measurement.

  9. 11B, 13C-NMR study of the complex formation of phenylboronate with catechol and L-dopa

    International Nuclear Information System (INIS)

    In the solution of phenylboronic acid and either catechol or L-dopa at various pH, the equilibrium between phenylboronate anion and catechol or L-dopa to form the anionic complex has been demonstrated by the existence of 11B-NMR signals for the complex and either phenylboronate anion or phenylboronic acid. By the pH dependence of the 11B-NMR chemical shift of phenylboronate-phenylboronic acid solution, the ionization constant of phenylboronic acid (pKa) has been estimated as 8.90. By the 11B-NMR spectra at pH below 7, the complex formation constant, log K, has been obtained as 4.5 for catechol, and as 4.6 for L-dopa. The 13C-NMR spectra have also demonstrated the complex formations, but in the pH 8 and 9 solution of phenylboronic acid and L-dopa, the 13C-NMR signal of carbonyl carbon of L-dopa disappeared. (author)

  10. Mixed ligand complex formation of FeIII with boric acid and typical N-donor multidentate ligands

    Indian Academy of Sciences (India)

    G N Mukherjee; Ansuman Das

    2002-06-01

    Equilibrium study of the mixed ligand complex formation of FeIII with boric acid in the absence and in the presence of 2,2'-bipyridine, 1,10-phenanthroline, diethylenetriamine and triethylenetetramine (L) in different molar ratios provides evidence of formation of Fe(OH)2+, Fe(OH)$^{+}_{2}$, Fe(L)3+, Fe(H2BO4), Fe(OH)(H2BO4)-, Fe(OH)2(H2BO4)2-, Fe(L)(H2BO4) and Fe2(L)2(BO4)+ complexes. Fe(L)$^{3+}_{2}$, Fe(L)2(H2BO4) and Fe2(L)4(BO4)+ complexes are also indicated with 2,2'-bipyridine and 1,10-phenanthroline. Complex formation equilibria and stability constants of the complexes at 25 ± 0 × 1° C in aqueous solution at a fixed ionic strength, = 0.1 mol -3 (NaNO3) have been determined by potentiometric method.

  11. Analysis of the Enhanced Stability of R(+-Alpha Lipoic Acid by the Complex Formation with Cyclodextrins

    Directory of Open Access Journals (Sweden)

    Hiroshi Shimosegawa

    2013-02-01

    Full Text Available R(+-alpha lipoic acid (RALA is one of the cofactors for mitochondrial enzymes and, therefore, plays a central role in energy metabolism. RALA is unstable when exposed to low pH or heat, and therefore, it is difficult to use enantiopure RALA as a pharma- and nutra-ceutical. In this study, we have aimed to stabilize RALA through complex formation with cyclodextrins (CDs. α-CD, β-CD and γ-CD were used for the formation of these RALA-CD complexes. We confirmed the complex formation using differential scanning calorimetry and showed by using HPLC analysis that complexed RALA is more stable than free RALA when subjected to humidity and high temperature or acidic pH conditions. Scanning electron microscopy studies showed that the particle size and shape differed depending on the cyclodextrin used for complexation. Further, the complexes of CD and RALA showed a different particle size distribution pattern compared with that of CD itself or that of the physical mixture of RALA and CD.

  12. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice

    Indian Academy of Sciences (India)

    Jingtao Hu; Chunfeng Wang; Liping Ye; Wentao Yang; Haibin Huang; Fei Meng; Shaohua Shi; Zhuang Ding

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN- (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

  13. Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation.

    Science.gov (United States)

    Lafferty, Michael J; Bradford, Kira C; Erie, Dorothy A; Neher, Saskia B

    2013-10-01

    Elevated triglycerides are associated with an increased risk of cardiovascular disease, and lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides from circulating lipoproteins. The N-terminal domain of angiopoietin-like protein 4 (ANGPTL4) inhibits LPL activity. ANGPTL4 was previously described as an unfolding molecular chaperone of LPL that catalytically converts active LPL dimers into inactive monomers. Our studies show that ANGPTL4 is more accurately described as a reversible, noncompetitive inhibitor of LPL. We find that inhibited LPL is in a complex with ANGPTL4, and upon dissociation, LPL regains lipase activity. Furthermore, we have generated a variant of ANGPTL4 that is dependent on divalent cations for its ability to inhibit LPL. We show that LPL inactivation by this regulatable variant of ANGPTL4 is fully reversible after treatment with a chelator. PMID:23960078

  14. Dynamics of DNA-protein complex formation in rat liver during induction by phenobarbital and triphenyldioxane.

    Science.gov (United States)

    Pustylnyak, V O; Zacharova, L Yu; Gulyaeva, L F; Lyakhovich, V V; Slynko, N M

    2004-10-01

    CYP2B gene expression in liver of rats treated with phenobarbital and triphenyldioxane at early stage of induction (40 min-18 h) was studied using electrophoretic mobility shift assay (EMSA) and RT-PCR. During first 6 h after induction, differences in the dynamics of formation of DNA-protein complexes were shown for each inducer. Later (18 h after induction), the intensity pattern of these complexes became the same for both phenobarbital and triphenyldioxane treated animals. This suggests the existence of specific signaling for each inducer only in early stages of CYP2B activation. Increase in nuclear protein (possible transcription factor) binding to Barbie-box regulatory sequence of CYP2B genes was accompanied by their increased expression. Thus, we have demonstrated for the first time that early stages of induction (40 min and 3 h after administration of phenobarbital and triphenyldioxane, respectively) are accompanied by activation of nuclear proteins that can bind to Barbie-box element of CYP2B. Although various chemical inducers cause distinct activation of such binding, this process involves activation of gene transcription. PMID:15527410

  15. Interaction between mosquito-larvicidal Lysinibacillus sphaericus binary toxin components: analysis of complex formation.

    Science.gov (United States)

    Kale, Avinash; Hire, Ramesh S; Hadapad, Ashok B; D'Souza, Stanislaus F; Kumar, Vinay

    2013-11-01

    The two components (BinA and BinB) of Lysinibacillus sphaericus binary toxin together are highly toxic to Culex and Anopheles mosquito larvae, and have been employed world-wide to control mosquito borne diseases. Upon binding to the membrane receptor an oligomeric form (BinA2.BinB2) of the binary toxin is expected to play role in pore formation. It is not clear if these two proteins interact in solution as well, in the absence of receptor. The interactions between active forms of BinA and BinB polypeptides were probed in solution using size-exclusion chromatography, pull-down assay, surface plasmon resonance, circular dichroism, and by chemically crosslinking BinA and BinB components. We demonstrate that the two proteins interact weakly with first association and dissociation rate constants of 4.5×10(3) M(-1) s(-1) and 0.8 s(-1), resulting in conformational change, most likely, in toxic BinA protein that could kinetically favor membrane translocation of the active oligomer. The weak interactions between the two toxin components could be stabilized by glutaraldehyde crosslinking. The cross-linked complex, interestingly, showed maximal Culex larvicidal activity (LC50 value of 1.59 ng mL(-1)) reported so far for combination of BinA/BinB components, and thus is an attractive option for development of new bio-pesticides for control of mosquito borne vector diseases. PMID:23974012

  16. Optimization of [67Ga]-oxinate complex formation conditions for white blood cell labeling

    International Nuclear Information System (INIS)

    In this work, the effective factors on the preparation of 67Ga-oxinate complex for white blood cell labeling were determined. Gallium-67 was produced at AMIRS 30 MeV cyclotron via 68Zn(p,2n)67Ga reaction in the from of 67GaCl3, and was used for radiolabeling of oxinate complex at optimized conditions. A mixture of 67GaCl3 (3uL, 200uCi) and ethanolic oxine solution (lmg/ml, 100μl) was evaporated and reacted at 25degreeC for 1 h in the presence of NaOAc solution (pH. 5.5). ITLC was performed using a mixture of ammonium acetate and methanol solution (1:1) followed by recording the activity using radio thin layer chromatography scanner. The radiochemical purity of %95.18 at these conditions was obtained (specific activity of 1432 GBq/rnmol). Freshly prepared white blood cells were separated from human volunteers and used for labeling by the above mentioned complex at 37dgreeC. 67Ga- oxinate complex due to it's lipophilicity and suitable gamma rays is a suitable cell labeling agent and available for blood stem cell and microorganism studies.

  17. Complex formation of CdSe/ZnS/TOPO nanocrystal vs. molecular chaperone in aqueous solution by hydrophobic interaction

    International Nuclear Information System (INIS)

    Feasibilities to stabilize CdSe/ZnS/trioctylphosphineoxide (TOPO) nanocrystals (quantum dots, QDs) in aqueous solutions with prefoldin macromolecules in their bioactive states are reported. Prefoldin is a jellyfish-shaped hexameric co-chaperone of the group II chaperonins. As a protein folding intermediate is captured within its central cavity, so CdSe/ZnS/TOPO QDs would also be included within this cavity. It is also found the QDs can be much more dispersed in aqueous solutions and suspended for certain period of time by adding trace amount of t-butanol in the buffer prior to the mixing of the QDs mother solution. While biochemical procedures are evaluated with ordinary fluorescence measurements, possible complex formations are also evaluated with TIRFM single-molecule detection techniques

  18. Complex formation equilibria of some beta-amino-alcohols with lead(II) and cadmium(II) in aqueous solution.

    Science.gov (United States)

    Canepari, S; Carunchio, V; Castellano, P; Messina, A

    1998-12-01

    A study of complex formation equilibria of some beta-amino-alcohols with lead(II) and cadmium(II) ions at 25 degrees C and in 0.5 M KNO(3) is reported. The amino-alcohols considered are 2-amino-1-propanol, 2-amino-1-butanol, 2-amino-1-pentanol and 2-amino-1,3-propanediol. sec-Buthylamine and 2-amino-1-methoxy-propane have been also considered for comparison. The results are discussed in terms of ligand structure, paying attention to the number of hydroxyl groups and to the length of the alkyl residual. A weak contribution of the alcoholic oxygen in the coordination of cadmium(II) and the presence of a mixed hydroxyl species in lead(II) containing systems are hypothesized. PMID:18967412

  19. The spectroscopic study of complex formation of rhodamine and oxazine dyes with rare-earth elements in solution

    International Nuclear Information System (INIS)

    The results of spectroscopic study of a complex formation of rhodamine and oxazine dyes with rare-earth ions in solutions are presented. Rhodamine dyes in the lactone form and oxazine dyes in the base form are found to form complex compounds of different compositions with metal ion in solution with cations of rare-earth metal. Besides, the spectral-luminescent characteristics of rhodamine and oxazine dyes, specific to their cationic form are restored. Methods of iso molar series and of the saturation curve the composition and stability of the formed complexes are determined. The monovalent metal ions form complexes with the dye molecules of composition 1:1, the divalent ions - 2:1 composition, and the trivalent ions - 3:1. (authors)

  20. Effect of pH and chemical mechanical planarization process conditions on the copper–benzotriazole complex formation

    Science.gov (United States)

    Cho, Byoung-Jun; Kim, Jin-Yong; Hamada, Satomi; Shima, Shohei; Park, Jin-Goo

    2016-06-01

    Benzotriazole (BTA) has been used to protect copper (Cu) from corrosion during Cu chemical mechanical planarization (CMP) processes. However, an undesirable Cu–BTA complex is deposited after Cu CMP processes and it should be completely removed at post-Cu CMP cleaning for next fabrication process. Therefore, it is very important to understand of Cu–BTA complex formation behavior for its applications such as Cu CMP and post-Cu CMP cleaning. The present study investigated the effect of pH and polisher conditions on the formation of Cu–BTA complex layers using electrochemical techniques (potentiodynamic polarization and electrochemical impedance spectroscopy) and the surface contact angle. The wettability was not a significant factor for the polishing interface, as no difference in the contact angles was observed for these processes. Both electrochemical techniques revealed that BTA had a unique advantage of long-term protection for Cu corrosion in an acidic condition (pH 3).

  1. Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation.

    Directory of Open Access Journals (Sweden)

    Shane E Gordon

    2016-03-01

    Full Text Available Dihydrodipicolinate synthase (DHDPS catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions.

  2. ParB Partition Proteins: Complex Formation and Spreading at Bacterial and Plasmid Centromeres.

    Science.gov (United States)

    Funnell, Barbara E

    2016-01-01

    In bacteria, active partition systems contribute to the faithful segregation of both chromosomes and low-copy-number plasmids. Each system depends on a site-specific DNA binding protein to recognize and assemble a partition complex at a centromere-like site, commonly called parS. Many plasmid, and all chromosomal centromere-binding proteins are dimeric helix-turn-helix DNA binding proteins, which are commonly named ParB. Although the overall sequence conservation among ParBs is not high, the proteins share similar domain and functional organization, and they assemble into similar higher-order complexes. In vivo, ParBs "spread," that is, DNA binding extends away from the parS site into the surrounding non-specific DNA, a feature that reflects higher-order complex assembly. ParBs bridge and pair DNA at parS and non-specific DNA sites. ParB dimers interact with each other via flexible conformations of an N-terminal region. This review will focus on the properties of the HTH centromere-binding protein, in light of recent experimental evidence and models that are adding to our understanding of how these proteins assemble into large and dynamic partition complexes at and around their specific DNA sites. PMID:27622187

  3. THE PRINCIPLES OF POWER-RISE BUILDINGS COMPLEXES FORMATION USING WIND ENERGY

    Directory of Open Access Journals (Sweden)

    NEVGAMONNIY G. U.

    2015-11-01

    Full Text Available Raising of problem. The methodology of designing energy-efficient tower building should be based on systematic analysis of the building as a unified energy system. The prominent architect Norman Foster (Sir Norman Foster writes: "Architects cannot solve all the world's environmental problems, but we can design buildings that require only a fraction of current energy consumption, in addition, through proper urban planning we can affect traffic flows. The location and functionality of buildings, its structural flexibility and technological resources, orientation, shape and structure, heating and ventilation characteristics used in the construction materials - all these parameters affect the amount of energy required for the construction, operation and maintenance of the building, and as for transportation, moving to it and from it" [1]. Purpose. The purpose of the study is scientific justification principles of architectural formation decisions of the power-rise energy efficient complexes and developing methods of architectural design of PRBC using wind energy. To develop the science-based principles forming the architectural buildings with the use of alternative energy and determine the specific features of the architectural design of buildings. Conclusion. The principles of architectural forming in the use of wind power and identify possible trends for the development of buildings with integrated wind installations. Polyfunctional wind power plants are in special properties of certain material and structural elements of the building structure, improve aerodynamic performance of the outer shell and therefore wind energy devices. Thus, the power efficiency of energy active building depends on its space solutions.

  4. Study of radionuclides complexes formation by organic compounds in intermediate and low-level radioactive wastes

    International Nuclear Information System (INIS)

    In the general framework of the safety of nuclear wastes of low and intermediate activity, we have studied the effects of organic compounds on the solubilization of metallic cations. Organic compounds originate from the degradation of cellulose in concrete interstitial waters. Degradation reactions generate a number of products, among which carboxylic acids. These acids are known for their chelating properties. We have first analysed the degradation of cellulose in alkaline conditions: we have qualitatively and quantitatively determined the degradation products for various reaction progress indices, including a dozen of carboxylic acids. The principal goal of our work was the prediction of the behaviour of metallic cations in such cellulose degradation solutions. Owing the complexity of the system, a priori theoretical calculation are not possible. We have thus decided to choose tetra hydroxy pentanoic acid as a reference compound in order to simulate as accurately as possible the behaviour of more complex acids which contain similar functional groups. We have experimentally determined the complexing properties of this reference acid toward divalent cobalt and copper, and trivalent samarium and europium. Simple and mixed complex (hydroxyl) have been evidenced in alkaline medium. Their stability constants have been determined and extrapolated at zero ionic strength using the SIT theory. These results allowed us to theoretically predict the behaviour of our four reference cations in cellulose degradation products formed in concrete interstitial waters. In parallel, we have measured their solubility in real cellulose degradation solutions. Solubility predictions are correct for transition metals, but not for rare earth cations. In this case the complexes which have been identified with tetra hydroxy pentanoic acid are not stable enough to dissolve metallic hydroxides. In real degradation solutions, other compounds would account for the enhancement of rare earth

  5. Size exclusion chromatography to gain insight into the complex formation of carrot pectin methylesterase and its inhibitor from kiwi fruit as influenced by thermal and high-pressure processing.

    Science.gov (United States)

    Jolie, Ruben P; Duvetter, Thomas; Verlinde, Philippe H C J; Van Buggenhout, Sandy; Van Loey, Ann M; Hendrickx, Marc E

    2009-12-01

    A size exclusion chromatography (HPSEC) method was implemented to study complex formation between carrot pectin methylesterase (PME) and its inhibitor (PMEI) from kiwi fruit in the context of traditional thermal and novel high-pressure processing. Evidence was gained that both thermal and high-pressure treatments of PME give rise to two distinct enzyme subpopulations: a catalytically active population, eluting from the size exclusion column, and an inactive population, aggregated and excluded from the column. When mixing a partly denatured PME sample with a fixed amount of PMEI, a PME-PMEI complex peak was observed on HPSEC, of which the peak area was highly correlated with the residual enzyme activity of the corresponding PME sample. This observation indicates complex formation to be restricted to the active PME fraction. When an equimolar mixture of PME and PMEI was subjected to either a thermal or a high-pressure treatment, marked differences were observed. At elevated temperature, enzyme and inhibitor remained united and aggregated as a whole, thus gradually disappearing from the elution profile. Conversely, elevated pressure caused the dissociation of the PME-PMEI complexes, followed by a separate action of pressure on enzyme and inhibitor. Remarkably, PMEI appeared to be pressure-resistant when compressed at acidic pH (ca. 4). PMID:19908835

  6. Lipoprotein complex formation

    International Nuclear Information System (INIS)

    Transfers of lipids and proteins between different lipoproteins are known to occur in the course of their metabolism. It is likely that these transfers take place during transient physical associations between lipoprotein particles, but the nature and chemical basis for such interactions are poorly understood. The fact that lipid and apolipoprotein movements are particularly prevalent during the intravascular lipolysis of triglyceride-rich lipoproteins suggested to us that lipolysis products accumulating on these particles might promote physical binding with other lipoproteins. To test this hypothesis, we studied interactions between very low-density, low density, and high-density lipoproteins in the setting of partial lipolysis by bovine milk lipoprotein lipase in the presence of limited unesterified fatty acid acceptor. 2 figs., 1 tab

  7. Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation

    Directory of Open Access Journals (Sweden)

    Lee HY

    2011-11-01

    Full Text Available Hye-Young Lee1,*, Young-IL Jeong2,*, Ki-Choon Choi31Anyang Science University, Anyang, Gyeonggi, South Korea; 2Chonnam National University Hwasun Hospital, Jeonnam, South Korea; 3Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration, Chungnam, South Korea*These authors contributed equally to this work.Background: p-Phenylenediamine (PDA or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair dyes such as PDA are known to have potent contact allergy reactions in humans, and severe allergic reactions are problematic.Methods: PDA-incorporated nanoparticles were prepared based on ion-complex formation between the cationic groups of PDA and the anionic groups of poly(γ-glutamic acid (PGA. To reinforce PDA/PGA ion complexes, glycol chitosan (GC was added. PDA-incorporated nanoparticles were characterized using field-emission scanning electron microscopy, Fourier-transform infrared (FT-IR spectroscopy, dynamic light scattering, and powder X-ray diffractometry (XRD.Results: Nanoparticles were formed by ion-complex formation between the amine groups of PDA and the carboxyl groups of PGA. PDA-incorporated nanoparticles are small in size (<100 nm, and morphological observations showed spherical shapes. FT-IR spectra results showed that the carboxylic acid peak of PGA decreased with increasing PDA content, indicating that the ion complexes were formed between the carboxyl groups of PGA and the amine groups of PDA. Furthermore, the intrinsic peak of the carboxyl groups of PGA was also decreased by the addition of GC. Intrinsic crystalline peaks of PDA were observed by XRD. This crystalline peak of PDA was completely nonexistent when nanoparticles were formed by ion complex between PDA, PGA, and GC, indicating that PDA was complexed with PGA and no free drug existed in the formulation. During the drug-release experiment, an initial burst release of PDA was

  8. Thermodynamics of mixed-ligand complex formation of zinc nitrilotriacetate with amino acids and dipeptides in solution

    International Nuclear Information System (INIS)

    Highlights: • Stable mixed ligand complexes of ZnNta with amino acids and dipeptides. • Histamine-like coordination mode of His in the complex ZnNtaHis. • Glycine-like coordination of Lys and Orn in the complexes ZnNtaL and ZnNtaHL • NH2, CO-coordination mode of GlyGly in the complex ZnNtaGG. • NH2, N− or NH2, N−, COO-coordination modes of GlyGly in the complex ZnNtaGGH−1. - Abstract: The isothermal calorimetry, pH-potentiometric titration and 1H and 13C NMR methods has been used to study the mixed-ligand complex formation in the systems Zn2+–Nta3––L− (L = His, Orn, Lys, GlyGly, AlaAla) in aqueous solution at 298.15 K and the ionic strength of I = 0.5 (KNO3). The thermodynamic parameters of formation of the mixed complexes have been determined. The relationship between the probable coordination modes of the complexone and amino acid or dipeptide molecules in the mixed-ligand complex and the thermodynamic parameters has been discussed

  9. Complex Formation of Adenosine 3',5'-Cyclic Monophosphate with β-Cyclodextrin: Kinetics and Mechanism by Ultrasonic Relaxation

    International Nuclear Information System (INIS)

    Adenosine 3',5'-cyclic monophosphate (cAMP) is a second messenger responsible for a multitude of cellular responses. In this study, we utilized β-cyclodextrin (β-CD) as an artificial receptor with a hydrophobic cavity to elucidate the inclusion kinetics of cAMP in a hydrophobic environment using the ultrasonic relaxation method. The results revealed that the interaction of cAMP with β-CD followed a single relaxation curve as a result of host-guest interactions. The inclusion of cAMP into the β-CD cavity was found to be a diffusion-controlled reaction. The dissociation of cAMP from the β-CD cavity was slower than that of adenosine 5'-monophosphate (AMP). The syn and anti glycosyl conformations of adenine nucleotides are considered to play an important role in formation of the inclusion complex. Taken together, our findings indicate that hydrophobic interactions are involved in the inclusion complex formation of cAMP with β-CD and provide insight into the interactions of cAMP with cAMP-binding proteins

  10. Mixed-ligand complex formation equilibria of CuII with biguanide in presence of glycine as the auxiliary ligand

    Indian Academy of Sciences (India)

    Tannistha Roy Barman; G N Mukherjee

    2006-09-01

    Equilibrium study on the mixed ligand complex formation of CuII with biguanide(Bg) and glycine (HG), indicated the formation of the complexes: Cu(Bg)2+, Cu(Bg)$_{2}^{2+}$, Cu(Bg-H)(Bg)+, Cu(Bg-H)2, Cu(Bg)(OH)+, Cu(Bg-H)(OH); Cu(G)+, Cu(G)(OH), Cu(G)2; Cu(G)(Bg)+, Cu(G)(Bg-H); (G)Cu(Bg)Cu(G)2+, (G)Cu(Bg-H)Cu(G)+, and (G)Cu(Bg-2H)Cu(G). From the deprotonation constants of coordinated biguanide (Bg) in the complexes Cu(Bg)(OH)+, Cu(Bg-H)(Bg)+ and Cu(G)(Bg)+, the Lewis basicities of the coordinated ligand species (Bg-H)-, OH- and glycinate (G-) were found to be of the order: (Bg-H)- >> OH- > G-. Bridging (N1-N4, N2-N5) tetradentate mode of coordination by biguanide species Bg, (Bg-H)- and (Bg-2H)2- was indicated from the occurrence of biguanide-bridged dinuclear mixed ligand complexes (G)Cu(Bg)Cu(G)2+, (G)Cu(Bg-H)Cu(G)+, (G)Cu(Bg-2H)Cu(G) in the complexation equilibria.

  11. Thermodynamics of mixed-ligand complex formation of zinc nitrilotriacetate with amino acids and dipeptides in solution

    Energy Technology Data Exchange (ETDEWEB)

    Pyreu, Dmitrii, E-mail: pyreu@mail.ru [Department of Inorganic and Analytic Chemistry, Ivanovo State UniversityErmak 39, Ivanovo 153025 (Russian Federation); Gruzdev, Matvey; Kumeev, Roman [G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo (Russian Federation); Gridchin, Sergei [Ivanovo State University of Chemistry and Technology, Ivanovo (Russian Federation)

    2014-10-20

    Highlights: • Stable mixed ligand complexes of ZnNta with amino acids and dipeptides. • Histamine-like coordination mode of His in the complex ZnNtaHis. • Glycine-like coordination of Lys and Orn in the complexes ZnNtaL and ZnNtaHL • NH{sub 2}, CO-coordination mode of GlyGly in the complex ZnNtaGG. • NH{sub 2}, N{sup −} or NH2, N{sup −}, COO-coordination modes of GlyGly in the complex ZnNtaGGH{sub −1}. - Abstract: The isothermal calorimetry, pH-potentiometric titration and {sup 1}H and {sup 13}C NMR methods has been used to study the mixed-ligand complex formation in the systems Zn{sup 2+}–Nta{sup 3–}–L{sup −} (L = His, Orn, Lys, GlyGly, AlaAla) in aqueous solution at 298.15 K and the ionic strength of I = 0.5 (KNO{sub 3}). The thermodynamic parameters of formation of the mixed complexes have been determined. The relationship between the probable coordination modes of the complexone and amino acid or dipeptide molecules in the mixed-ligand complex and the thermodynamic parameters has been discussed.

  12. Hydrolysis of (CH{sub 3})Hg{sup +} in different ionic media: Salt effects and complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Robertis, A. de; Foti, C.; Patane, G.; Sammartano, S. [Univ. di Messina, Agata (Italy)

    1998-11-01

    The hydrolysis of monomethylmercury(II) was studied potentiometrically, in NaNO{sub 3}, Na{sub 2}SO{sub 4}, and NaCl aqueous solution, in a wide range of ionic strengths (NaNO{sub 3}, 0 {le} I {le} 1; NaCl, 0 {le} 1 {le} 3 mol/dm{sup 3}) and at t = 25 C. For the reaction (CH{sub 3})Hg{sup +} = (CH{sub 3})Hg(OH){degree} + H{sup +}, the authors found log K{sub 1} = {minus}4.528 (I = 0 mol/dm{sup 3}). The species [(CH{sub 3})Hg]{sub 2}(OH){sup +} was also found, with log {beta}{sub 2} = {minus}2.15. Monomethylmercury(II) forms quite strong complexes with Cl{sup {minus}} (log K = 5.45, I = 0 mol/dm{sup 3}) and SO{sub 4}{sup 2{minus}} (log K = 2.64, I = 0 mol/dm{sup 3}). The dependence on ionic strength of formation constants was considered by using a Debye-Hueckel type equation. Hydrolysis and complex formation constants (at different ionic strengths) obtained were used to calculate the interaction parameters of Pitzer equations.

  13. Spectrophotometric Determination of 6-Propyl-2-Thiouracil in Pharmaceutical Formulations Based on Prussian Blue Complex Formation: An Undergraduate Instrumental Analysis Laboratory Experiment

    Science.gov (United States)

    Zakrzewski, Robert; Skowron, Monika; Ciesielski, Witold; Rembisz, Zaneta

    2016-01-01

    The laboratory experiment challenges students to determine 6-propyl-2-thiouracil (PTU) based on Prussian blue complex formation. Prussian blue is formed by ferricyanide and Fe(II) ions which are generated in situ from Fe(III) ions reduced by PTU. The absorbance of this product was measured at a wavelength of 840 nm, after a reaction time of 30…

  14. Remarkable fluorescence enhancement versus complex formation of cationic porphyrins on the surface of ZnO nanoparticles

    KAUST Repository

    Aly, Shawkat Mohammede

    2014-06-12

    Fluorescence enhancement of organic fluorophores shows tremendous potential to improve image contrast in fluorescence-based bioimaging. Here, we present an experimental study of the interaction of two cationic porphyrins, meso-tetrakis(1-methylpyridinium-4-yl)porphyrin chloride (TMPyP) and meso-tetrakis(4-N,N,N-trimethylanilinium)porphyrin chloride (TMAP), with cationic surfactant-stabilized zinc oxide nanoparticles (ZnO NPs) based on several steady-state and time-resolved techniques. We show the first experimental measurements demonstrating a clear transition from pronounced fluorescence enhancement to charge transfer (CT) complex formation by simply changing the nature and location of the positive charge of the meso substituent of the cationic porphyrins. For TMPyP, we observe a sixfold increase in the fluorescence intensity of TMPyP upon addition of ZnO NPs. Our experimental results indicate that the electrostatic binding of TMPyP with the surface of ZnO NPs increases the symmetry of the porphyrin macrocycle. This electronic communication hinders the rotational relaxation of the meso unit and/or decreases the intramolecular CT character between the cavity and the meso substituent of the porphyrin, resulting in the enhancement of the intensity of the fluorescence. For TMAP, on the other hand, the different type and nature of the positive charge resulting in the development of the CT band arise from the interaction with the surface of ZnO NPs. This observation is confirmed by the femtosecond transient absorption spectroscopy, which provides clear spectroscopic signatures of photoinduced electron transfer from TMAP to ZnO NPs. © 2014 American Chemical Society.

  15. Management of the Pregnant Inflammatory Bowel Disease Patient on Antitumour Necrosis Factor Therapy: State of the Art and Future Directions

    Directory of Open Access Journals (Sweden)

    Yvette PY Leung

    2014-01-01

    Full Text Available Antitumour necrosis factor (anti-TNF therapy has been a major advance in the treatment of inflammatory bowel disease (IBD by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta, recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.

  16. N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells

    Science.gov (United States)

    2012-01-01

    Background Liver cancer is one of the most common malignancies in the world and at the moment, there is no drug intervention effective for the treatment of liver tumours. Investigate the effect of N-acetylcysteine (NAC), which has been studied for its antitumoural properties, on the toxicity of hepatocarcinoma (HCC) cells in vitro when used with the drug interferon alpha-2A (IFN), which is used clinically to treat HCC. Results NAC, IFN and NAC plus IFN reduced cell viability, as determined by MTT assay. More importantly, NAC potentiates the cytotoxic effect of IFN, with the best response achieved with 10 mM of NAC and 2.5 x 104 of IFN. These results were confirmed by Annexin/PI staining through flow cytometry and morphologic analyses. Co-treatment reduced the expression of the nuclear transcription factor kappa-B (NF-kB). In a similar way to NAC, RNAi against p65 potentiated the toxic effect of IFN, suggesting that, indeed, NAC may be enhancing the effect of IFN through inhibition of NF-kB. Conclusions Our results support the notion that NAC may be an important drug for the treatment of liver tumours as primary or adjuvant therapy. IFN has a limited clinical response, and therefore, the anti-proliferative properties of NAC in the liver should be explored further as an alternative for non-responders to IFN treatment. PMID:23206959

  17. AQ4N: a new approach to hypoxia-activated cancer chemotherapy

    OpenAIRE

    Patterson, L. H.; McKeown, S R

    2000-01-01

    Preclinical studies demonstrate that in vivo AQ4N enhances the anti-tumour effects of radiation and chemotherapeutic agents with a dose-modifying factor of approximately 2.0. With careful scheduling no, or very little, additional normal tissue toxicity should be observed. AQ4N is a bioreductive prodrug of a potent, stable, reduction product which binds non-covalently to DNA, facilitating antitumour activity in both hypoxic and proximate oxic tumour cells. AQ4N is clearly different in both its...

  18. Recent developments towards the synthesis of Varitriol: An antitumour agent from marine derived fungus Emericella variecolor.

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Tilvi, S.; Parvatkar, P.T.

    Marine natural products are recognized as a fruitful source of drug development due to their rare structural entities and diverse biological activities, and consequently, publicized number of metabolites as new medicines. Although extensive progress...

  19. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    Science.gov (United States)

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-03-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  20. Development of a Pummerer–type cyclisation for the synthesis of analogues of the anti-tumour natural product ecteinascidin 597

    OpenAIRE

    Smith, Laura Hayley Susan

    2013-01-01

    A connective Pummerer reaction was developed with a view to its use in the synthesis of analogues of ecteinascidin 597, a member of a family of potent anti-tumour natural products. A one-step synthesis of N-benzyl 2-hydroxyamides, involving the reaction of 2,2-dimethyl-1,3-dioxolan-4-one with amines, was investigated and the products were oxidised to give glyoxamides. Reaction conditions were optimised for the cyclisation of electron-rich N-benzyl glyoxamides in the presence of thiols and a L...

  1. Anti-tumour efficacy of mouse spleen cells separated with Dolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells.

    OpenAIRE

    Okada, T.; Higuchi, M.; Takano, M; Maruyama, T.; Imai, Y; Osawa, T

    1990-01-01

    Anti-tumour effector cells were generated through 4 days culture of normal C57BL/6 splenocytes in a medium containing concanavalin A supernatant and then fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (non-agglutinable with DBA) cells. The DBA- cells, infused intravenously into mice together with B16 melanoma cells, or adoptively transferred into mice 3 days after the injection of B16 cells, caused a marked decrease in the number of lung nodules, w...

  2. Identification of genes involved in the sensitivity to antitumour drug 17-allylamino,17-demethoxygeldanamycin (17AAG).

    Science.gov (United States)

    Barresi, Vincenza; Fortuna, Cosimo G; Garozzo, Roberta; Musumarra, Giuseppe; Scirè, Salvatore; Condorelli, Daniele F

    2006-05-01

    In the present study we analysed the gene expression database provided by the National Cancer Institute in an attempt to correlate activity profiles of geldanamycin, 17AAG and 11 other analogues in 60 human tumor cell lines with their gene expression profiles determined by the cDNA microarray technique. On the basis of the activity profiles two classes of geldanamycin analogues could be distinguished, having geldanamycin and 17AAG, respectively, as prototype compounds (denominated as gelda-like and 17AAG-like classes). Application of the "soft" statistical methodology of PLS (partial least squares modelling in latent variables or projections to latent structures) allowed us to evaluate the influence of each gene expression target in determining the therapeutical responses. The transcript encoding the translocating chain-associated membrane protein (TRAM) showed a significant statistical correlation with activity profiles of 17AAG. In order to validate the role of TRAM in determining sensitivity to 17AAG we induced a selective knocking-down of this transcript by the RNA interference methodology in H226 non-small cell lung carcinoma cell line. The efficiency of double-stranded RNA oligonucleotides (short-interfering RNAs, siRNAs) was determined by measuring TRAM mRNA levels by quantitative real-time RT-PCR at different times (24-72 hours) after siRNA lipotransfection. A significant increase in chemosensitivity to 17AAG was observed in siRNA-silenced cells. Although a number of factors may affect tumour sensitivity to 17AAG the present methodology allowed us to dissect out a single parameter which may be partly responsible for its activity. PMID:16880941

  3. The problem of mental disorders and psychological effects of antitumour treatment in children with cancer pathology

    OpenAIRE

    Пионтковская, Оксана Владимировна

    2015-01-01

    Aim – analysis of the problem of psychological and psychiatrical aspects of impact of cancer disease on child and its parents for detection of the main directions of medical and psychological help to this contingent.Results. In the younger age group the most stress factors that provoke the development of psychogenic fears, anxiety states and the derivative mood disorders are the “hospital routine” – limitation of activity (playing, motor), subjectively heavy procedures and manipulations, pain...

  4. Antitumour Metallocenes: Effect of DMSO on the Stability of Cp2TiX2 and Implications for Anticancer Activity

    OpenAIRE

    Mokdsi, George; Harding, Margaret M.

    1998-01-01

    The rate of hydrolysis of the aromatic rings of Cp2TiX2 [X = CI 1, O2CCCl3  8 and O2CCH2NH3Cl  13], in aqueous solutions, 10%DMSO and 100% DMSO have been studied by H1NMR spectroscopy. Rapid hydrolysis of both the carboxylate and cyclopentadienyl ligands in Cp2TiX2[X = O2CCCl3,O2CCH2NH3Cl] occurs in DMSO to give biologically inactive species. The rate of these reactions are concentration dependent as dilution of these samples with saline or water to give the therapeutic conditions of 10%DMSO/...

  5. A Systematic Comparison of the Anti-Tumoural Activity and Toxicity of the Three Adv-TKs

    OpenAIRE

    Gao, Qinglei; Chen, Caihong; Ji, Teng; Wu, Peng; Han, Zhiqiang; Fang, Haiyan; Li, Fei; Liu, Yi; Hu, Wencheng; Gong, Danni; Zhang, Zeyu; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding

    2014-01-01

    Adenovirus 5 vectors, known respectively as, the first generation, second generation and oncolytic adenovirus, have been studied extensively in preclinical and clinical trials. However, hitherto few systemic evaluations of the efficacy and toxicity of these adenoviral vectors that have reflected the vertical history of adenovirus based cancer gene therapy strategies have been undertaken. This study has chosen Adv-TK, the well-established adjuvant treatment in cancer, and compared its efficacy...

  6. Evaluation of antitumour activity and antioxidant status in Dioscorea hispida, Dennst. leaves on Ehrlich Ascites Carcinoma in Swiss Albino Mice

    OpenAIRE

    Punith kumar. T. G; Panduranga Murthy. G; Suresh. A, Suresh. V; Senthil kumar N; Raviashankar. H. G

    2011-01-01

    Cancer’ is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumour, or proliferate throughout the body. Next to heart disease, cancer is a killer of mankind. The present study aims at a preliminary phytochemical analysis and anticancer evaluation of Dioscorea hispida, Dennst. against Ehrlich Ascites Carcinoma in animal model. The results indicate that ethanolic extract of Dioscorea hispida leaves (DhLE)...

  7. NIR and visible investigation of some potential SERS-active substrates for studying antitumour agent all- trans retinoic acid

    Science.gov (United States)

    Beljebbar, A.; Sockalingum, G. D.; Morjani, H.; Angiboust, J. F.; Manfait, M.

    1997-01-01

    Red and near-infrared excited Fourier transform surface-enhanced Raman spectra of an anticancer agent, all- trans retinoic acid (ATRA), adsorbed on gold island films are reported. Best results have been obtained with plates 80 Å and 40 Å thick respectively in the red and near-infrared and at concentrations of 10 -5 and 5 × 10 -6 M with a spinning system. The use of near-infrared laser excitation with low photon energy, allows us to overcome the problems of isomerisation when the sample is exposed for a long time to the laser radiation. Comparison between the Raman and SERS spectra in the visible shows that the adsorption on the surface does not perturb the structure of ATRA and confirms the long range enhancement of the island films with this type of molecule. Spectral data show that while gold island films and colloids are appropriate substrates for use with red excitation, silver and gold colloids as well as gold island films exhibit satisfactory enhancement levels in the near-infrared. This study will in the future allow us to choose the appropriate system that will serve to investigate the interaction of ATRA with its target in vitro and the effect of this differentiating agent in human leukaemia cell lines such as K562 and HL60.

  8. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer

    Czech Academy of Sciences Publication Activity Database

    Ohnmacht, S.A.; Marchetti, C.; Gunaratnam, M.; Besser, R.J.; Haider, S.M.; Di Vita, G.; Lowe, H.L.; Mellinas-Gomez, M.; Diocou, S.; Robson, M.; Šponer, Jiří

    2015-01-01

    Roč. 5, JUN 2015 (2015). ISSN 2045-2322 R&D Projects: GA ČR(CZ) GAP208/11/1822; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081707 Keywords : NAPHTHALENE DIIMIDE LIGANDS * AMBER FORCE-FIELD * DNA G-QUADRUPLEX Subject RIV: BO - Biophysics Impact factor: 5.578, year: 2014

  9. Novel polysaccharide anti-tumour drug delivery system for active targeting and controlled release to breast cancer bone metastases

    OpenAIRE

    Bonzi, Gwénaëlle A.M.

    2014-01-01

    ABSTRACT In the late stage of the disease, breast cancer patients often develop bone metastases, a major cause of cancer-related death among women worldwide. The common treatment currently used clinically includes the anti-neoplastic agent paclitaxel combined with the bisphosphonate alendronate. Paclitaxel is an anti-neoplastic drug which cytotoxic effect is mainly attributed to its ability to promote the assembly of microtubules as well as prevent the depolymerisation of these micro...

  10. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses.

    Science.gov (United States)

    Boks, Martine A; Ambrosini, Martino; Bruijns, Sven C; Kalay, Hakan; van Bloois, Louis; Storm, Gert; Garcia-Vallejo, Juan J; van Kooyk, Yvette

    2015-10-28

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)(X) which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. Le(X)-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro-inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280-288 peptide to CD8(+) T cells compared to non-glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280-288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8(+) T cell responses. These data demonstrate that adjuvant-containing glycoliposome-based vaccines targeting DC-SIGN(+) DC

  11. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response

    Science.gov (United States)

    Li, Haiyan; Li, Yuhuan; Jiao, Jun; Hu, Hong-Ming

    2011-10-01

    Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems. Here we show that α-Al2O3 nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that α-Al2O3 nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with α-Al2O3 nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that α-Al2O3 nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines.

  12. Energetic Mechanism of Cytochrome c-Cytochrome c Oxidase Electron Transfer Complex Formation under Turnover Conditions Revealed by Mutational Effects and Docking Simulation.

    Science.gov (United States)

    Sato, Wataru; Hitaoka, Seiji; Inoue, Kaoru; Imai, Mizue; Saio, Tomohide; Uchida, Takeshi; Shinzawa-Itoh, Kyoko; Yoshikawa, Shinya; Yoshizawa, Kazunari; Ishimori, Koichiro

    2016-07-15

    Based on the mutational effects on the steady-state kinetics of the electron transfer reaction and our NMR analysis of the interaction site (Sakamoto, K., Kamiya, M., Imai, M., Shinzawa-Itoh, K., Uchida, T., Kawano, K., Yoshikawa, S., and Ishimori, K. (2011) Proc. Natl. Acad. Sci. U.S.A. 108, 12271-12276), we determined the structure of the electron transfer complex between cytochrome c (Cyt c) and cytochrome c oxidase (CcO) under turnover conditions and energetically characterized the interactions essential for complex formation. The complex structures predicted by the protein docking simulation were computationally selected and validated by the experimental kinetic data for mutant Cyt c in the electron transfer reaction to CcO. The interaction analysis using the selected Cyt c-CcO complex structure revealed the electrostatic and hydrophobic contributions of each amino acid residue to the free energy required for complex formation. Several charged residues showed large unfavorable (desolvation) electrostatic interactions that were almost cancelled out by large favorable (Columbic) electrostatic interactions but resulted in the destabilization of the complex. The residual destabilizing free energy is compensated by the van der Waals interactions mediated by hydrophobic amino acid residues to give the stabilized complex. Thus, hydrophobic interactions are the primary factors that promote complex formation between Cyt c and CcO under turnover conditions, whereas the change in the electrostatic destabilization free energy provides the variance of the binding free energy in the mutants. The distribution of favorable and unfavorable electrostatic interactions in the interaction site determines the orientation of the binding of Cyt c on CcO. PMID:27226541

  13. Critical solvent thermodynamic effect on molecular recognition: The case of the complex formation of carboxylates and ammonium-squaramido based receptors

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • The enthalpy–entropy compensation in the complex is independent of the spacer used. • The enthalpy–entropy compensation is dependent on the microscopic nature of the binary mixture. • The enthalpy–entropy compensation is dependent on the proportion of the components of the binary mixture. - Abstract: An isothermal titration microcalorimetry (ITC) study on the supramolecular complex formation between carboxylates and ammonium-squaramido based receptors at different ethanol:water proportions is reported. The results obtained show that the formation enthalpy sign of a supramolecular complex in a water–ethanol binary mixture can be influenced by the proportion of the cosolvent. Moreover there is an enthalpy–entropy compensation process in the supramolecular complex formation; in poor water mixtures the process is endothermic, whilst in reach water mixtures the process is exothermic. This behavior is mostly due to the intrinsic nature of the mixture between water and ethanol, and particularly the process of solvation and desolvation of receptor, substrate and complex. When this study is repeated with binary mixtures of water–methanol and water–DMSO it is observed that the nature of the organic solvent affects the results. While the mixture water–methanol has a behavior similar to water–ethanol mixture, the water–DMSO mixture shows clear differences. In order to check this compensation process, △Cp values are calculated at two different proportions water–ethanol, and they are consistent with an enthalpy–entropy compensation process similar to that described by the inclusion process for certain hydrophilic cyclodextrines. The results obtained show that the enthalpy–entropy compensation detected in the supramolecular complex formation between carboxylates and ammonium-squaramido receptors is independent of the spacer used, and more dependent on the microscopic nature and proportion of the binary mixture

  14. Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review

    Science.gov (United States)

    Boland, J W; McWilliams, K; Ahmedzai, S H; Pockley, A G

    2014-01-01

    Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group. PMID:25025960

  15. Complex Formation in a Liquid-Liquid Extraction System Containing Cobalt(II), 4-(2-Pyridylazo)resorcinol, and Nitron

    OpenAIRE

    Petya Vassileva Racheva; Kiril Blazhev Gavazov; Vanya Dimitrova Lekova; Atanas Nikolov Dimitrov

    2013-01-01

    Complex formation and liquid-liquid extraction were studied in a system containing cobalt(II), 4-(2-pyridylazo)resorcinol (PAR), 1,4-diphenyl-3-(phenylamino)-1H-1,2,4-triazole (Nitron, Nt), water, and chloroform. The effect of some experimental parameters (pH, shaking time, concentration of PAR, and concentration of Nt) was systematically investigated, and the optimum conditions for cobalt extraction as an ion-association complex, (NtH+)[Co3+(PAR)2], were found. The following key equilibrium ...

  16. MET is required for the recruitment of anti-tumoural neutrophils.

    Science.gov (United States)

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A A Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-06-18

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  17. Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.

    LENUS (Irish Health Repository)

    McCabe, D J H

    2005-09-01

    The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference.

  18. Crosstalk between Fibroblast Growth Factor (FGF Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation

    Directory of Open Access Journals (Sweden)

    Seiji Mori

    2013-08-01

    Full Text Available Fibroblast growth factors (FGFs play a critical role in diverse physiological processes and the pathogenesis of diseases. Integrins are involved in FGF signaling, since integrin antagonists suppress FGF signaling. This is called integrin-FGF crosstalk, while the specifics of the crosstalk are unclear. This review highlights recent findings that FGF1 directly interacts with integrin αvβ3, and the resulting integrin-FGF-fibroblast growth factor receptor (FGFR ternary complex formation is essential for FGF1-induced cell proliferation, migration and angiogenesis. An integrin-binding defective FGF1 mutant (Arg-50 to Glu, R50E is defective in ternary complex formation and in inducing cell proliferation, migration and angiogenesis, while R50E still binds to the FGF receptor and heparin. In addition, R50E suppressed tumorigenesis in vivo, while wild-type (WT FGF1 enhanced it. Thus, the direct interaction between FGF1 and integrin αvβ3 is a potential therapeutic target, and R50E is a potential therapeutic agent.

  19. Fac-mer equilibria of coordinated iminodiacetate (ida2-) in ternary CuII(ida)(H-1B)- complex formation (B = imidazole, benzimidazole) in aqueous solution

    Indian Academy of Sciences (India)

    Susmita Bandyopadhyay; G N Mukherjee

    2003-08-01

    pH potentiometric and spectrophotometric investigations on the complex formation equilibria of CuII with iminodiacetate (ida2-) and heterocyclic N-bases, viz. imidazole and benzimidazole (B), in aqueous solution in binary and ternary systems using different molar ratios of the reactants indicated the formation of complexes of the types, Cu(ida), Cu(ida)(OH)-, (ida)Cu(OH)Cu(ida)-, Cu(B)2+, Cu(H-1B)+, Cu(ida)(H-1B)-, (ida)Cu(B)Cu(ida) and (ida)Cu(H-1B)Cu(ida)-. Formation constants of the complexes at 25 ± 1° at a fixed ionic strength, = 0.1 mol dm-3 (NaNO3) in aqueous solution were evaluated and the complex formation equilibria were elucidated with the aid of speciation curves. Departure of the experimental values of the reproportionation constants (log Cu) of ternary Cu(ida)(H-1B)- complexes from the statistically expected values, despite their formation in appreciable amounts at equilibrium, were assigned to fac(f)-mer(m) equilibria of the ida2- ligand coordinated to CuII, as the N-heterocyclic donors, (H-1B)-, coordinate trans- to the N-(ida2-) atom in the binary Cu(ida) complex to form the ternary Cu(ida) (H-1B)- complexes.

  20. Complex formation reactions of uranyl(VI) with neutral N-donors in dimethyl sulfoxide. Influence of small amounts of water

    International Nuclear Information System (INIS)

    Quantitative information about the existence and thermodynamic stability of uranyl(VI) ion complexes based solely upon nitrogen coordination has been obtained in the solvent dimethyl sulfoxide. Calorimetric, potentiometric, and FT-IR investigations, under controlled anhydrous conditions, show that the uranyl(VI) ion can form both mono and bis chelates with the ethylenediamine ligand and only a mono chelate of rather low stability with propylenediamine. With the monodentate ligand n-butylamine only a very weak metal-ligand interaction has been detected. The stability constants and the enthalpy and entropy changes have been calculated for the identified coordinated species. All data refer to 25.0 degree C and a tetraethylammonium perchlorate medium of ionic strength 0.1 M. All the complexes are enthalpy stabilized whereas the entropy contributions oppose the complex formation. Calorimetric and FT-IR measurements carried out to investigate the effects of small amounts of water present show that a very low water concentration, comparable to that of the coordinating metal ion, can give rise to hydrolysis reactions that may compete with complex formation. This is due to the combined action of different factors that are discussed. 39 refs., 6 figs., 1 tab

  1. Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex.

    Science.gov (United States)

    Kosmopoulou, Magda N; Leonidas, Demetres D; Chrysina, Evangelia D; Bischler, Nicolas; Eisenbrand, Gerhard; Sakarellos, Constantinos E; Pauptit, Richard; Oikonomakos, Nikos G

    2004-06-01

    The binding of indirubin-5-sulphonate (E226), a potential anti-tumour agent and a potent inhibitor (IC(50) = 35 nm) of cyclin-dependent kinase 2 (CDK2) and glycogen phosphorylase (GP) has been studied by kinetic and crystallographic methods. Kinetic analysis revealed that E226 is a moderate inhibitor of GPb (K(i) = 13.8 +/- 0.2 micro m) and GPa (K(i) = 57.8 +/- 7.1 micro m) and acts synergistically with glucose. To explore the molecular basis of E226 binding we have determined the crystal structure of the GPb/E226 complex at 2.3 A resolution. Structure analysis shows clearly that E226 binds at the purine inhibitor site, where caffeine and flavopiridol also bind [Oikonomakos, N.G., Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E. & Johnson, L.N. (2000) J. Biol. Chem.275, 34566-34573], by intercalating between the two aromatic rings of Phe285 and Tyr613. The mode of binding of E226 to GPb is similar, but not identical, to that of caffeine and flavopiridol. Comparative structural analyses of the GPb-E226, GPb-caffeine and GPb-flavopiridol complex structures reveal the structural basis of the differences in the potencies of the three inhibitors and indicate binding residues in the inhibitor site that can be exploited to obtain more potent inhibitors. Structural comparison of the GPb-E226 complex structure with the active pCDK2-cyclin A-E226 complex structure clearly shows the different binding modes of the ligand to GPb and CDK2; the more extensive interactions of E226 with the active site of CDK2 may explain its higher affinity towards the latter enzyme. PMID:15153119

  2. Nuclear magnetic resonance study of charge transfer complex formation between Silver Nitrate and Benzylcyanide in Solvent Ethylene Glycol

    CERN Document Server

    Modarress, H

    2003-01-01

    The formation constant for charge transfer complexes between electron acceptor (AgNo sub 3) and electron donor benzylcyanide (C sub 6 H sub 5 -CH sub 2 -C ident to N) in solvent ethyleneglycol [(CH sub 2 OH) sub 2] has been evaluated by using the nuclear magnetic resonance chemical shifts of aromatic group of benzylcyanide measured against external references, tetramethylsilane, hexamethyldisilane and cyclohexane at 20 sup d ig sup C. The external referencing procedure eliminated the interference of internal reference in the course of complexation. The necessary bulk magnetic susceptibility corrections on the measured chemical shifts have been made. The solution nationalised and their effects on the formation constant have been considered and a new equation has been suggested to obtain the main ionic activity coefficient of AgNO sub 3 from nuclear magnetic resonance results. The mean ionic activity coefficient has been taken into account in the formation constant calculations. The results indicated that the a...

  3. Selective and non-extractive spectrophotometric determination of cefdinir in formulations based on donor-acceptor complex formation

    Directory of Open Access Journals (Sweden)

    Babita K. Singh

    2010-01-01

    Full Text Available Cefdinir has broad spectrum of activity and high prescription rates, hence its counterfeiting seems imminent. We have proposed a simple, fast, selective and non-extractive spectrophotometric method for the content assay of cefdinir in formulations. The method is based on complexation of cefdinir and Fe under reducing condition in a buffered medium (pH 11 to form a magenta colored donor-acceptor complex (λ max = 550 nm; apparent molar absorptivity = 3720 L mol-1 cm-1. No other cephalosporins, penicillins and common excipients interfere under the test conditions. The Beer's law is followed in the concentration range 8-160 µg mL-1.

  4. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-08-12

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

  5. Inducer effect on the complex formation between rat liver nuclear proteins and cytochrome P450 2B gene regulatory elements.

    Science.gov (United States)

    Duzhak, T G; Schwartz, E I; Gulyaeva, L F; Lyakhovich, V V

    2002-09-01

    DNA gel retardation assay has been applied to the investigation of complexes between rat liver nuclear proteins and Barbie box positive regulatory element of cytochrome P450 2B (CYP2B) genes. The intensities of B1 and B2 bands detected in the absence of an inducer increased after 30 min protein incubation with phenobarbital (PB) or triphenyldioxane (TPD), but not with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOPOB). In addition, a new complex (B3 band) was for the first time detected under induction by PB, TPD, and TCPOPOB. Increase in the incubation time up to 2 h facilitated the formation of other new complexes (B4 and B5 bands), which were detected only in the presence of TPD. The use of [3H]TPD in hybridization experiments revealed that this inducer, capable of binding to Barbie box DNA, is also present in B4 and B5 complexes. It is probable that the investigated compounds activate the same proteins at the initial induction steps, which correlates with the formation of B1, B2, and B3 complexes. The further induction step might be inducer-specific, as indicated by the formation of B4 and B5 complexes in the presence of TPD only. Thus, the present data suggest the possibility of specific gene activation signaling pathways that are dependent on a particular inducer. PMID:12387719

  6. ANTI HYPERGLYCEMIC AND HYPOLIPIDEMIC ACTIVITY OF LEEA INDICA

    OpenAIRE

    Damayanthi Dalu*, Satyavathi Duggirala and Suresh Akarapu

    2014-01-01

    Leea indica (Burm.f) Merr is a well-known traditional Chinese medicine. Leaves of Leea indica have multiple pharmacological activities like Antitumour, Analgesic, Antiviral, Sedative and Anxiolytic and NO inhibitory activities. It has long been used as a folk medicine for the treatment of Cardiac diseases, Diabetes, Fever, headache, dizziness, soreness, eczema, sprain, leprosy, bone fracture, body pain, muscle spasms, diarrhoea and dysentery. Scientific studies are not yet carried out to prov...

  7. Complex formation in molten salts: association constants of cadmium-iodo complexes in molten potassium nitrate-barium nitrate eutectic

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, R.K.; Gaur, H.C. (Delhi Univ. (India). Dept. of Chemistry)

    1981-06-01

    Association constants for the formation of CdI/sup +/ and CdI/sub 2/ in molten KNO/sub 3/-Ba(NO/sub 3/)/sub 2/(87.6:12.4 mol%) eutectic in the temperature range 568.2 - 608.2 K have been evaluated from activity coefficient by measurement of emf of the molten salt concentration cell, Ag, AgI(s)/KNO/sub 3/ -Ba(NO/sub 3/)/sub 2/, KI/KNO/sub 3/ - Ba(NO/sub 3/)/sub 2/, KI, Cd(NO/sub 3/)/sub 2/ or CdI/sub 2//AgI(s), Ag. Data do not suggest the formation of polynuclear species under the experimental conditions employed. The temperature coefficients of the association constants are predictable from equations based on quasi-lattice model.

  8. Thermodynamics of complexes formation by ITC in methanol/water = 9/1 (v/v) solution: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Fisicaro, Emilia, E-mail: emilia.fisicaro@unipr.it [University of Parma, Department of Pharmacy, Parco Area delle Scienze, 27/A, 43124 Parma (Italy); Compari, Carlotta; Bacciottini, Franco; Contardi, Laura [University of Parma, Department of Pharmacy, Parco Area delle Scienze, 27/A, 43124 Parma (Italy); Carcelli, Mauro; Rispoli, Gabriele; Rogolino, Dominga [University of Parma, Department of Chemistry, Parco Area delle Scienze, 17/A, 43124 Parma (Italy)

    2014-06-01

    Graphical abstract: Integrase strand transfert inhibitors chelate the metal ions in the active site of HIV integrase. - Highlights: • Development of inhibitors acting against those viral enzymes operating via a cooperative two-metal ion mechanism, such as HIV integrase (IN), requires optimizing the binding affinity to the target. • We have defined an experimental procedure for obtaining reliable thermodynamic data by ITC in methanol/water = 9/1 (v/v) as solvent. • Formation heats in mixed solvent of the complexes formed by a ligand, model of Raltegravir, with Mg(II), Mn(II), Co(II) and Zn(II) are here reported. - Abstract: Most enzymes that participate in the biochemistry of nucleic acids require divalent metal ion cofactors to promote activity. Development of potent inhibitors, acting against those viral enzymes operating via a cooperative two-metal ion mechanism, such as HIV integrase (IN) and RNase H, hepatitis C virus polymerase and influenza endonuclease, requires optimizing the binding affinity to the target, which is dictated by the binding free energy composed of both enthalpic and entropic contributions. They can be obtained by using isothermal titration microcalorimetry. We have defined an experimental procedure for obtaining reliable thermodynamic data in methanol/water = 9/1 0.1 M KCl as solvent, used to overcome solubility problems. In this way we have measured the heats of formation of the complexes formed by N-(4-fluorobenzyl)-5-hydroxy-2-isopropyl-1-methyl-6-oxo-1, 6-dihydroxypyrimidine-4-carboxylate (HL, a model of Raltegravir, the antiretroviral drug produced by Merck and Co.), and a series of divalent metal ions of biological interest (Mg(II), Mn(II), Co(II) and Zn(II)), whose speciation was previously determined by potentiometry.

  9. Complex Formation in a Liquid-Liquid Extraction System Containing Co(II), 4-(2-Thiazolylazo)resorcinol and Monotetrazolium Salt.

    Science.gov (United States)

    Divarova, Vidka; Stojnova, Kirila; Racheva, Petya; Lekova, Vanya

    2016-01-01

    The ion-associated complex formed between anionic chelate of Co(II)-4-(2-Thiazolylazo)resorcinol (TAR) with the monotetrazolium cation of 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-phenyl-2H-tetrazolium chloride (INT) in the liquid-liquid extraction system Co(II)-TAR-INT-H(2)O-CHCl(3) was studied by the spectrophotometric method. The optimum extraction conditions of Co(II) were found. The extraction equilibria were studied. The equilibrium constants, the recovery factor and some analytical characteristics were calculated. The validity of Beer's law was checked. The molar ratio of the components in the ternary ion-associated complex Co(II)-TAR-INT was determined. The general formula of the complex was suggested. The effect of various foreign ions and reagents on the process of complex formation in the liquid-liquid extraction system was studied. PMID:26970793

  10. Study into the applicability of laboratory data to natural conditions: Laser fluorescence spectroscopy for the analysis of Cm(III) complex formation with humate and fulvate

    International Nuclear Information System (INIS)

    The complex formation of Cm(III) with humic acid or fulvic acid isolated from a Gorleben groundwater is analysed in 0.1 M NaClO4 at pH = 6.0 by means of the time-resolved, laser-induced fluorescence spectroscopy. The humate and fulvate complexes are characterized by their excitation, emission, and life spectra. Complexation constants are derived by way of spectroscopic speciation in the trace concentration range (Cm(III) = 2.1-10.1x10-8 mol L-1). The results obtained for Cm-humate (lg β = 6.22±0.05) and Cm-fulvate (lg β = 6.05±0.11) are in very good agreement with those obtained for Am(III) in the saturation concentration range of the humic acid ([Am(I II) = 10-5 mol L1-1). (orig.)

  11. Cadmium-glutathione complex formation in human t-cell and b-cell lymphocytes after their incubation with organo-cadmium diacetate.

    Science.gov (United States)

    Ullah, Hashmat; Khan, Muhammad Farid; Jan, Syed Umer; Hashmat, Farwa

    2015-11-01

    Cadmium intake is associated with oxidative stress that causes depletion of intracellular as well as extra cellular reduced glutathione. There is strong evidence indicating that reactive oxygen species and reactive nitrogen species generated in the presence of cadmium could be responsible for its toxic effects in many cells and tissues. Depletion of reduced glutathione in various cells, especially in T and B-lymphocytes, causes extreme damage to the antioxidant defense system of body. The aim of this research work was to investigate the metabolic changes that occur in T and B lymphocytes after their incubation with organ cadmium diacetate by using Ellman's spectrophotometric method of thiol quantification. The results of the present study indicate that cadmium depleted T and B lymphocytes GSH to a harmful extent. It is proposed that this depletion is due to the bivalent cadmium glutathione complex formation, oxidation of reduced glutathione (GSH) to its oxidized form, or both. PMID:26639500

  12. Potentiometric studies on stepwise biligand complex formation La(III), Pr(III) or Nd(III)-cyclo hexane-1, 2-diaminotetraacetic acid-hydroxy acid

    International Nuclear Information System (INIS)

    Potentiometric studies of the interaction between 1:1 Ln(III)-CDTA binary chelate (where Ln(III) = La(III), Pr(III) or Nd(III); CDTA = cyclohexane-1,2-diamino-N,N,N',N'-tetracetic acid) with certain hydroxy acids such as glycollic (GA), lactic (LA) and malic (MEA) are described. The nature of the titration curves indicates the stepwise addition of the secondary ligand to the initially formed 1:1, M(III)-CDTA binary complex. Formation constants (Ksub(MAL)) of the resulting biligand chelates have been determined at 30 +- 10 and 35 +- 10C and also thermodynamic functions (viz. ΔG,ΔH and ΔS). The order of stability in terms of metal ions has been found to be La(III) LA > GA. (author)

  13. Nucleoprotein of influenza B virus binds to its type A counterpart and disrupts influenza A viral polymerase complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Jaru-ampornpan, Peera, E-mail: peera.jar@biotec.or.th; Narkpuk, Jaraspim; Wanitchang, Asawin; Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th

    2014-01-03

    Highlights: •FluB nucleoprotein (BNP) can bind to FluA nucleoprotein (ANP). •BNP–ANP interaction inhibits FluA polymerase activity. •BNP binding prevents ANP from forming a functional FluA polymerase complex. •Nuclear localization of BNP is necessary for FluA polymerase inhibition. •Viral RNA is not required for the BNP–ANP interaction. -- Abstract: Upon co-infection with influenza B virus (FluB), influenza A virus (FluA) replication is substantially impaired. Previously, we have shown that the nucleoprotein of FluB (BNP) can inhibit FluA polymerase machinery, retarding the growth of FluA. However, the molecular mechanism underlying this inhibitory action awaited further investigation. Here, we provide evidence that BNP hinders the proper formation of FluA polymerase complex by competitively binding to the nucleoprotein of FluA. To exert this inhibitory effect, BNP must be localized in the nucleus. The interaction does not require the presence of the viral RNA but needs an intact BNP RNA-binding motif. The results highlight the novel role of BNP as an anti-influenza A viral agent and provide insights into the mechanism of intertypic interference.

  14. Nucleoprotein of influenza B virus binds to its type A counterpart and disrupts influenza A viral polymerase complex formation

    International Nuclear Information System (INIS)

    Highlights: •FluB nucleoprotein (BNP) can bind to FluA nucleoprotein (ANP). •BNP–ANP interaction inhibits FluA polymerase activity. •BNP binding prevents ANP from forming a functional FluA polymerase complex. •Nuclear localization of BNP is necessary for FluA polymerase inhibition. •Viral RNA is not required for the BNP–ANP interaction. -- Abstract: Upon co-infection with influenza B virus (FluB), influenza A virus (FluA) replication is substantially impaired. Previously, we have shown that the nucleoprotein of FluB (BNP) can inhibit FluA polymerase machinery, retarding the growth of FluA. However, the molecular mechanism underlying this inhibitory action awaited further investigation. Here, we provide evidence that BNP hinders the proper formation of FluA polymerase complex by competitively binding to the nucleoprotein of FluA. To exert this inhibitory effect, BNP must be localized in the nucleus. The interaction does not require the presence of the viral RNA but needs an intact BNP RNA-binding motif. The results highlight the novel role of BNP as an anti-influenza A viral agent and provide insights into the mechanism of intertypic interference

  15. Molecular Mechanisms of Transcription Initiation-Structure, Function, and Evolution of TFE/TFIIE-Like Factors and Open Complex Formation.

    Science.gov (United States)

    Blombach, Fabian; Smollett, Katherine L; Grohmann, Dina; Werner, Finn

    2016-06-19

    Transcription initiation requires that the promoter DNA is melted and the template strand is loaded into the active site of the RNA polymerase (RNAP), forming the open complex (OC). The archaeal initiation factor TFE and its eukaryotic counterpart TFIIE facilitate this process. Recent structural and biophysical studies have revealed the position of TFE/TFIIE within the pre-initiation complex (PIC) and illuminated its role in OC formation. TFE operates via allosteric and direct mechanisms. Firstly, it interacts with the RNAP and induces the opening of the flexible RNAP clamp domain, concomitant with DNA melting and template loading. Secondly, TFE binds physically to single-stranded DNA in the transcription bubble of the OC and increases its stability. The identification of the β-subunit of archaeal TFE enabled us to reconstruct the evolutionary history of TFE/TFIIE-like factors, which is characterised by winged helix (WH) domain expansion in eukaryotes and loss of metal centres including iron-sulfur clusters and Zinc ribbons. OC formation is an important target for the regulation of transcription in all domains of life. We propose that TFE and the bacterial general transcription factor CarD, although structurally and evolutionary unrelated, show interesting parallels in their mechanism to enhance OC formation. We argue that OC formation is used as a way to regulate transcription in all domains of life, and these regulatory mechanisms coevolved with the basal transcription machinery. PMID:27107643

  16. Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

    Directory of Open Access Journals (Sweden)

    Marriott Susan J

    2007-12-01

    Full Text Available Abstract Background The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS. We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins. Results We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284 within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35. Conclusion This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284

  17. Influence of temperature and crown ether complex formation on the charge partitioning between z and c fragments formed after electron capture by small peptide dications

    Science.gov (United States)

    Ehlerding, Anneli; Jensen, Camilla S.; Wyer, Jean A.; Holm, Anne I. S.; Jørgensen, Palle; Kadhane, Umesh; Larsen, Mikkel K.; Panja, Subhasis; Poully, Jean Christophe; Worm, Esben S.; Zettergren, Henning; Hvelplund, Preben; Brøndsted Nielsen, Steen

    2009-04-01

    Electron capture by peptide dications results in N-C[alpha] bond cleavage to give c+ and z or c and z+ fragments. In this work we have investigated how crown ether (18-crown-6 = CE) complex formation and a change in the internal energy affect the charge division between the z and c fragments. Both complex formation and a high temperature have the effect of breaking internal ionic hydrogen bonds. The crown ether complex also lowers the probability of internal proton transfer between the two fragments, and reduces the recombination energy of the charged group it targets. The systems under study were doubly protonated di- and tripeptides, [AK+2H]2+, [AR+2H]2+, [KK+2H]2+ and [GHK+2H]2+ (A = alanine, K = lysine, R = arginine, G = glycine and H = histidine). For crown ether complexes the formation of z+ ions was always preferred over c+ ions. In the case of [GHK+2H]2+, the bare ion dissociated into z2+ + c1 and z1 + c2+ from cleavage of the first and second N-C[alpha] bond, respectively, whereas z1+ fragment ions had higher yield than c2+ for [GHK+2H]2+(CE). The internal energy of the ions was changed by storing them in a 22-pole ion trap in which they were equilibrated to a temperature between -60 and 90 °C in collisions with helium gas. The average internal energy increased by about 0.4 eV from the lowest to the highest temperature for the dipeptides and 0.6 eV for the tripeptide. More fragmentation occurred at the higher temperature, as observed by an increase in the formation of b+ and y+ ions after breakage of the peptide bond of vibrationally hot even-electron cations and from secondary reactions of z+ radical cations within the time window of the experiment. However, the z+ to c+ partitioning was not found to depend significantly on temperature in the measured range. In addition the decay of [GHK+H]+/[GHK+2H]+ and [AK+H]+ formed after electron capture by [GHK+2H]2+ and [AK+2H]2+ was found to occur on a microsecond to millisecond timescale. The data are well

  18. In vitro complex formation and inhibition of hepatic cytochrome P450 activity by different macrolides and tiamulin in goats and cattle

    NARCIS (Netherlands)

    Zweers-Zeilmaker, W.M.; Miert, A.S.J.P.A.M. van; Horbach, G.J.; Witkamp, R.F.

    1998-01-01

    In humans, clinically relevant drug–drug interactions occur with some macrolide antibiotics via the formation of stable metabolic intermediate (MI) complexes with enzymes of the cytochrome P4503A (CYP3A) subfamily. The formation of such complexes can result in a decreased biotransformation rate of s

  19. Cl-doping of Te-rich CdTe: Complex formation, self-compensation and self-purification from first principles

    Directory of Open Access Journals (Sweden)

    A. Lindström

    2015-08-01

    Full Text Available The coexistence in Te-rich CdTe of substitutional Cl-dopants, ClTe, which act as donors, and Cd vacancies, V C d − 1 , which act as electron traps, was studied from first principles utilising the HSE06 hybrid functional. We find ClTe to preferably bind to V C d − 1 and to form an acceptor complex, (ClTe–VCd−1. The complex has a (0,-1 charge transfer level close to the valence band and shows no trap state (deep level in the band gap. During the complex formation, the defect state of VCd−1 is annihilated and leaves the Cl-doped CdTe bandgap without any trap states (self-purification. We calculate Cl-doped CdTe to be semi-insulating with a Fermi energy close to midgap. We calculate the formation energy of the complex to be sufficiently low to allow for spontanous defect formation upon Cl-doping (self-compensation. In addition, we quantitatively analyse the geometries, DOS, binding energies and formation energies of the (ClTe–VCd complexes.

  20. 试从家庭环境分析自卑感形成的影响因素%Inferiority Complex Formation Factors from the Family Environment

    Institute of Scientific and Technical Information of China (English)

    于见伟

    2012-01-01

    自从阿德勒建立个体心理学以来,其自卑理论流传全球,并对后世心理学理论产生了深远影响。关于自卑形成的内在机制及其影响因素众说纷纭,本文试从家庭微环境来探讨影响自卑形成的内在机制,主要从家庭的经济因素、家庭教育方式、孩子的出生顺序、家庭的和谐程度以及父母子三者的互动关系来探索自卑形成的影响因素。%Since Adler established individual psychology, the self-esteem theory spread to the world, and had a profound im- pact on future generations psychological theory. Divergent views on the inferiority complex formation of the internal mecha- nisms and their influencing factors, this article tries to explore the impact of low self-esteem inherent mechanism from the family microenvironment mainly from the economic factors of the family, family education, the child's birth order, the harmony of the family, and parental sub-interactions among these three relations to explore the impact factor of the inferiority.

  1. α-N-heterocyclic thiosemicarbazone derivatives as potential antitumor agents: A structure-activity relationships approach

    OpenAIRE

    Matesanz, Ana I.; Souza, Pilar

    2009-01-01

    α-N-Heterocyclic thiosemicarbazones, (N)-TSCs, are potent inhibitors of ribonucleotide reductase (RR). This enzyme plays a critical role in DNA synthesis and repair, and is a well-recognized target for cancer chemotherapeutic agents. In this review the structural features of (N)-TSCs, required for maximum antitumour activity have been explored. Special attention is given to the mechanisms of action and structure-activity relationships

  2. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody.

    Science.gov (United States)

    Isaacs, J D; Cutolo, M; Keystone, E C; Park, W; Braun, J

    2016-01-01

    The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of 'biosimilar' drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost-effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the 'switchability' and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT-P13, a biosimilar of the anti-tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed. PMID:26403380

  3. Principle component analysis (PCA) and second-order global hard-modelling for the complete resolution of transition metal ions complex formation with 1,10-phenantroline

    International Nuclear Information System (INIS)

    Second-order global hard-modelling was applied to resolve the complex formation between Co2+, Ni2+, and Cd2+ cations and 1,10-phenantroline. The highly correlated spectral and concentration profiles of the species in these systems and low concentration of some species in the individual collected data matrices prevent the well-resolution of the profiles. Therefore, a collection of six equilibrium data matrices including series of absorption spectra taken with pH changes at different reactant ratios were analyzed. Firstly, a precise principle component analysis (PCA) of different augmented arrangements of the individual data matrices was used to distinguish the number of species involved in the equilibria. Based on the results of PCA, the equilibria included in the data were specified and second-order global hard-modelling of the appropriate arrangement of six collected equilibrium data matrices resulted in well-resolved profiles and equilibrium constants. The protonation constant of the ligand (1,10-phenantroline) and spectral profiles of its protonated and unprotonated forms are the additional information obtained by global analysis. For comparison, multivariate curve resolution-alternating least squares (MCR-ALS) was applied to the same data. The results showed that second-order global hard-modelling is more convenient compared with MCR-ALS especially for systems with completely known model. It can completely resolve the system and the concentration profiles which are closer to correct ones. Moreover, parameters showing the goodness of fit are better with second-order global hard-modelling.

  4. Cytokeratin 8/18 overexpression and complex formation as an indicator of GST-P positive foci transformation into hepatocellular carcinomas

    International Nuclear Information System (INIS)

    Screening of the proteome of microdissected glutathione S-transferase placental form (GST-P) positive foci and normal-appearing liver on anionic (Q10), and cationic (CM10) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip arrays demonstrated significant overexpression of cytokeratin 8 (CK8; m/z 54,020), cytokeratin 18 (CK18; m/z 47,760), microsomal cytochrome 5A (m/z 15,224) and histone type 2 H2aa3 (m/z 15,964) in the livers of rats initiated with diethylnitrosamine (DEN) followed by 10 weeks on phenobarbital (PB) at a dose of 500 ppm. Furthermore, formation of CK8 and CK18 complexes due to CK8 phosphorylation at Ser73 and Ser431 was found to be strongly associated with promotion of hepatocarcinogenesis by PB and the development of hepatocellular carcinomas. The data were confirmed by immunohistochemistry and real-time Q-PCR and profound overexpression of CK8 and CK18 (CK8/18) proteins and mRNAs were detected in several large size GST-P positive foci and liver tumors. A strong correlation between CK8/18 positive foci development and multiplicity of hepatocellular carcinomas was further observed. Moreover, elevation of CK8/18 was strongly associated with induction of cell proliferation in GST-P positive foci and tumors. In conclusion, our data imply that CK8/18 overexpression, those two cytokeratins complex formation associated with histone type 2 H2aa3 up-regulation and intermediate filament reorganization may drive neoplastic transformation of GST-P positive foci during rat hepatocarcinogenesis leading to the formation of hepatocellular carcinomas.

  5. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema.

    Science.gov (United States)

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-10-15

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE. PMID:26371246

  6. A novel signal transduction protein P(II) variant from Synechococcus elongatus PCC 7942 indicates a two-step process for NAGK-P(II) complex formation.

    Science.gov (United States)

    Fokina, Oleksandra; Chellamuthu, Vasuki-Ranjani; Zeth, Kornelius; Forchhammer, Karl

    2010-06-11

    P(II) signal transduction proteins are highly conserved in bacteria, archaea and plants and have key functions in coordination of central metabolism by integrating signals from the carbon, nitrogen and energy status of the cell. In the cyanobacterium Synechococcus elongatus PCC 7942, P(II) binds ATP and 2-oxoglutarate (2-OG) in a synergistic manner, with the ATP binding sites also accepting ADP. Depending on its effector molecule binding status, P(II) (from this cyanobacterium and other oxygenic phototrophs) complexes and regulates the arginine-controlled enzyme of the cyclic ornithine pathway, N-acetyl-l-glutamate kinase (NAGK), to control arginine biosynthesis. To gain deeper insights into the process of P(II) binding to NAGK, we searched for P(II) variants with altered binding characteristics and found P(II) variants I86N and I86T to be able to bind to an NAGK variant (R233A) that was previously shown to be unable to bind wild-type P(II) protein. Analysis of interactions between these P(II) variants and wild-type NAGK as well as with the NAGK R233A variant suggested that the P(II) I86N variant was a superactive NAGK binder. To reveal the structural basis of this property, we solved the crystal structure of the P(II) I86N variant at atomic resolution. The large T-loop, which prevails in most receptor interactions of P(II) proteins, is present in a tightly bended conformation that mimics the T-loop of S. elongatus P(II) after having latched onto NAGK. Moreover, both P(II) I86 variants display a specific defect in 2-OG binding, implying a role of residue I86 in 2-OG binding. We propose a two-step model for the mechanism of P(II)-NAGK complex formation: in an initiating step, a contact between R233 of NAGK and E85 of P(II) initiates the bending of the extended T-loop of P(II), followed by a second step, where a bended T-loop deeply inserts into the NAGK clefts to form the tight complex. PMID:20399792

  7. XI International conference Problems of solvation and complex formation in solutions, and VI Conference of young scientists Theoretical and experimental chemistry of liquid-phase systems (Krestovsky readings). Summary of reports

    International Nuclear Information System (INIS)

    The collection contains materials of plenary, sectional and poster sessions, presented at the XI International conference Problems of solvation and complex formation in solutions, and VI Conference of young scientists Theoretical and experimental chemistry of liquid-phase systems (Krestovsky readings). Theoretical questions and new experimental methods of chemistry of solutions, structure and dynamics of molecular and ion-molecular systems in solution and at the phase boundary; modern aspects of applied chemistry of solutions are discussed

  8. Bioavailability and dose-dependent anti-tumour effects of 9-cis retinoic acid on human neuroblastoma xenografts in rat

    OpenAIRE

    Ponthan, F; Kogner, P; Bjellerup, P; Klevenvall, L; Hassan, M

    2001-01-01

    Neuroblastoma, the most common extracranial solid tumour in children, may undergo spontaneous differentiation or regression, but the majority of metastatic neuroblastomas have poor prognosis despite intensive treatment. Retinoic acid regulates growth and differentiation of neuroblastoma cells in vitro, and has shown activity against human neuroblastomas in vivo. The retinoid 9-cis RA has been reported to induce apoptosis in vitro, and to inhibit the growth of human neuroblastoma xenografts in...

  9. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    International Nuclear Information System (INIS)

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5–7.2) the neutral form of the luotonin derivatives emit in the region of 410–450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pKa⁎ values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pKa⁎ values and the chemical structure was found. The protonation of luotonin A was also studied by 1H-NMR and 13C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: ► This is the first study on the fluorescence properties of luotonin A analogues. ► Fluorescence and NMR experiments

  10. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Ruiz, Victor; Gonzalez-Cuevas, Yamisley; Arunachalam, Sankaralingam [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Martin, M. Antonia, E-mail: mantonia@farm.ucm.es [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Olives, Ana I. [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Ribelles, Pascual; Ramos, M. Teresa; Menendez, J. Carlos [D. Quimica Organica y Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain)

    2012-09-15

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5-7.2) the neutral form of the luotonin derivatives emit in the region of 410-450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pK{sub a}{sup Low-Asterisk} values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pK{sub a}{sup Low-Asterisk} values and the chemical structure was found. The protonation of luotonin A was also studied by {sup 1}H-NMR and {sup 13}C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: Black-Right-Pointing-Pointer This is the first study on the fluorescence

  11. Supramolecular complex formation of β-cyclodextrin polymer with substituted salicylic acid or 3-hydroxy-2-naphthoic acid and their electrorheological behaviors

    Institute of Scientific and Technical Information of China (English)

    GAO; Ziwei; ZHAO; Xiaopeng; SUN; Ping; SI; Gang

    2004-01-01

    supramolecular systems (XXXV) --Synthesis of novel β-cyclodextrin derivative beating pyridinio group and its chiral discrimination of amino acids, Science in China, Ser. B, 2001, 44(3): 260-267.[13]Liu, Y., Yang, Y. W., Cao, R. et al., Thermodynamic origin of molecular selective binding of bile salts by aminated β-cyclodextrins,J. Phys. Chem. B, 2003: 14130-14139.[14]Liu, Y., Chen, G. S., Li, L. et al., Inclusion complexation and solubilization of paclitaxel by bridged bis(β-cyclodextrin)s containing a tetraethylenepentaamino spacer, J. Med. Chem., 2003,46(22): 4634-4637.[15]Yoshida, K., Shimomura, T., Ito, K. et al., Inclusion complex formation of cyclodextrin and polyaniline, Langmuir, 1999, 15(4):910-913.[16]Crini, G., Bertini, S., Torri, G. et al., Sorption of aromatic co-pounds in water using insoluble cyclodextrin polymers, J.Appllied Polymer Science, 1998, 68: 1973-1978.[17]Renard, E., Deratani, A., Volet, G. et al., Preparation and characterization of water soluble high molecular weight β-cyclodextrinepichlorohydrin polymers, Eur. Polym. J., 1997, 33(1): 49-57.[18]Gao, Z. W., Zhao, X. P., Electrorheological properties of inclusive complex of β-cyclodextrin polymer, Materials Letters, 2002, 57:615-618.[19]Gao, Z. W., Zhao, X. P., Enhancing electrorheological behaviors with formation of β-cyclodextrin supramolecular complex, Polymer, 2003, 44:4519-4526.[20]Su, X. D., Liu, L. Z., Shen, H. Y., Study on the absorbing enrichment of trace metals using α-pyridylaxo-β-naphthol inclusion complexes of cyclodextrin polymer resin, Analytical Chemistry (in Chinese), 1995, 23(12): 1361-1366.[21]Catena, G. C., Bright, F. V., Thermodynamic study on the effects of β-cyclodextrin inclusion with anilinonaphthalenesulfonates,Anal. Chem., 1989, 61: 905-909.[22]Kano, K., Tatsumi, M., Hashimoto, S., Cyclodextrin-induced conformational enantiomerism of dinaphthylmethanes, J. Org.Chem., 1991, 56: 6579-6585.

  12. Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

    NARCIS (Netherlands)

    C. van Bree; A.D. Barten-van Rijbroek; R. Leen; H.M. Rodermond; A.B.P. van Kuilenburg; H.B. Kal

    2009-01-01

    Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether OPEC enhances

  13. G9a inhibition potentiates the anti-tumour activity of DNA double-strand break inducing agents by impairing DNA repair independent of p53 status.

    Science.gov (United States)

    Agarwal, Pallavi; Jackson, Stephen P

    2016-10-01

    Cancer cells often exhibit altered epigenetic signatures that can misregulate genes involved in processes such as transcription, proliferation, apoptosis and DNA repair. As regulation of chromatin structure is crucial for DNA repair processes, and both DNA repair and epigenetic controls are deregulated in many cancers, we speculated that simultaneously targeting both might provide new opportunities for cancer therapy. Here, we describe a focused screen that profiled small-molecule inhibitors targeting epigenetic regulators in combination with DNA double-strand break (DSB) inducing agents. We identify UNC0638, a catalytic inhibitor of histone lysine N-methyl-transferase G9a, as hypersensitising tumour cells to low doses of DSB-inducing agents without affecting the growth of the non-tumorigenic cells tested. Similar effects are also observed with another, structurally distinct, G9a inhibitor A-366. We also show that small-molecule inhibition of G9a or siRNA-mediated G9a depletion induces tumour cell death under low DNA damage conditions by impairing DSB repair in a p53 independent manner. Furthermore, we establish that G9a promotes DNA non-homologous end-joining in response to DSB-inducing genotoxic stress. This study thus highlights the potential for using G9a inhibitors as anti-cancer therapeutic agents in combination with DSB-inducing chemotherapeutic drugs such as etoposide. PMID:27431310

  14. Utilization of an Automated Pipetting System in the Cell Line-Based Screening of the Activity of a DNA-Damaging Anti-Tumour Drug

    Czech Academy of Sciences Publication Activity Database

    Suchánková, Tereza; Ovesná, P.; Samadder, P.; Souček, Karel

    2014-01-01

    Roč. 60, č. 1 (2014), s. 50-55. ISSN 0015-5500 R&D Projects: GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : cell line screen * drug treatment * liquid handling station Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

  15. Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid).

    OpenAIRE

    Bibby, M. C.; Double, J A; Phillips, R. M.; Loadman, P.M.

    1987-01-01

    LM985 has been shown previously to hydrolyse to flavone acetic acid (LM975) in mouse plasma and to produce significant anti-tumour effects in transplantable mouse colon tumours (MAC). It has undergone Phase I clinical trials and dose limiting toxicity was acute reversible hypotension. Substantially higher doses of LM975 can be given clinically without dose limiting toxicity. We have investigated the activity of LM975 against a panel of MAC tumours and also the in vitro cytotoxicity of both LM...

  16. Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

    LENUS (Irish Health Repository)

    McCabe, Dominick J H

    2004-06-01

    Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and\\/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P <\\/= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P <\\/= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and\\/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

  17. TBP-TAF Complex SL1 Directs RNA Polymerase I Pre-initiation Complex Formation and Stabilizes Upstream Binding Factor at the rDNA Promoter*||

    OpenAIRE

    Friedrich, J. Karsten; Panov, Kostya I.; Cabart, Pavel; Russell, Jackie; Zomerdijk, Joost C. B. M.

    2005-01-01

    Knowledge of the role of components of the RNA polymerase I transcription machinery is paramount to understanding regulation of rDNA expression. We describe key findings for the roles of essential transcription factor SL1 and activator upstream binding factor (UBF). We demonstrate that human SL1 can direct accurate Pol I transcription in the absence of UBF and can interact with the rDNA promoter independently and stably, consistent with studies of rodent SL1 but contrary to previous reports o...

  18. Direct and allosteric inhibition of the FGF2/HSPGs/FGFR1 ternary complex formation by an antiangiogenic, thrombospondin-1-mimic small molecule.

    Directory of Open Access Journals (Sweden)

    Katiuscia Pagano

    Full Text Available Fibroblast growth factors (FGFs are recognized targets for the development of therapies against angiogenesis-driven diseases, including cancer. The formation of a ternary complex with the transmembrane tyrosine kinase receptors (FGFRs, and heparan sulphate proteoglycans (HSPGs is required for FGF2 pro-angiogenic activity. Here by using a combination of techniques including Nuclear Magnetic Resonance, Molecular Dynamics, Surface Plasmon Resonance and cell-based binding assays we clarify the molecular mechanism of inhibition of an angiostatic small molecule, sm27, mimicking the endogenous inhibitor of angiogenesis, thrombospondin-1. NMR and MD data demonstrate that sm27 engages the heparin-binding site of FGF2 and induces long-range dynamics perturbations along FGF2/FGFR1 interface regions. The functional consequence of the inhibitor binding is an impaired FGF2 interaction with both its receptors, as demonstrated by SPR and cell-based binding assays. We propose that sm27 antiangiogenic activity is based on a twofold-direct and allosteric-mechanism, inhibiting FGF2 binding to both its receptors.

  19. Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.

    Science.gov (United States)

    Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J; Golovanov, Alexander P

    2016-01-01

    The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos. PMID:27412770

  20. An update on PPAR activation by cannabinoids.

    Science.gov (United States)

    O'Sullivan, Saoirse Elizabeth

    2016-06-01

    Some cannabinoids activate the different isoforms of PPARs (α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies. Activation of all isoforms, but primarily PPARα and γ, mediates some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti-inflammatory, metabolic, anti-tumour, gastrointestinal and cardiovascular effects of some cannabinoids, often in conjunction with activation of the more traditional target sites of action such as the cannabinoid CB1 and CB2 receptors and the TRPV1 ion channel. PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport. Cannabinoids may be chaperoned to the PPARs by fatty acid binding proteins. The aims of this review are to update the evidence supporting PPAR activation by cannabinoids and to review the physiological responses to cannabinoids that are mediated, and not mediated, by PPAR activation. PMID:27077495

  1. Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.

    LENUS (Irish Health Repository)

    Li, Chong Hui

    2012-02-03

    Tolerance to bacterial cell-wall components may represent an essential regulatory mechanism during bacterial infection. We have demonstrated previously that the inhibition of nuclear factor (NF)-kappaB and mitogen-activated protein kinase activation was present in bacterial lipoprotein (BLP) self-tolerance and its cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP-induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent upstream signaling pathway for NF-kappaB activation in vitro was examined further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant cells had a significant reduction in tumor necrosis factor alpha (TNF-alpha) production in response to a high-dose BLP (86+\\/-12 vs. 6042+\\/-245 ng\\/ml, P < 0.01) or LPS (341+\\/-36 vs. 7882+\\/-318 ng\\/ml, P < 0.01) stimulation. The expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as confirmed by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant cells, although IRAK-1 mRNA expression remained unchanged as revealed by real-time reverse transcriptase-polymerase chain reaction analysis. Furthermore, decreased MyD88-IRAK immunocomplex formation, as demonstrated by immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total and phosphorylated inhibitor of kappaB-alpha (IkappaB-alpha) expression, which was not up-regulated by subsequent BLP or LPS stimulation. These results demonstrate that in addition to the down-regulation of TLR2 expression, BLP tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK association, and IkappaB-alpha phosphorylation. These

  2. Structural basis of LaDR5, a novel agonistic anti-death receptor 5 (DR5 monoclonal antibody, to inhibit DR5/TRAIL complex formation

    Directory of Open Access Journals (Sweden)

    Qiao Chunxia

    2012-07-01

    Full Text Available Abstract Background As a member of the TNF superfamily, TRAIL could induce human tumor cell apoptosis through its cognate death receptors DR4 or DR5, which can induce formation of the death inducing signaling complex (DISC and activation of the membrane proximal caspases (caspase-8 or caspase-10 and mitochondrial pathway. Some monoclonal antibodies against DR4 or DR5 have been reported to have anti-tumor activity. Results In this study, we reported a novel mouse anti-human DR5 monoclonal antibody, named as LaDR5, which could compete with TRAIL to bind DR5 and induce the apoptosis of Jurkat cells in the absence of second cross-linking in vitro. Using computer-guided molecular modeling method, the 3-D structure of LaDR5 Fv fragment was constructed. According to the crystal structure of DR5, the 3-D complex structure of DR5 and LaDR5 was modeled using molecular docking method. Based on distance geometry method and intermolecular hydrogen bonding analysis, the key functional domain in DR5 was predicted and the DR5 mutants were designed. And then, three mutants of DR5 was expressed in prokaryotic system and purified by affinity chromatograph to determine the epitope of DR5 identified by LaDR5, which was consistent with the theoretical results of computer-aided analysis. Conclusions Our results demonstrated the specific epitope located in DR5 that plays a crucial role in antibody binding and even antineoplastic bioactivity. Meanwhile, revealed structural features of DR5 may be important to design or screen novel drugs agonist DR5.

  3. Multiprotein complex formation at the beta myosin heavy chain distal muscle CAT element correlates with slow muscle expression but not mechanical overload responsiveness.

    Science.gov (United States)

    Vyas, D R; McCarthy, J J; Tsika, G L; Tsika, R W

    2001-01-12

    To examine the role of the beta-myosin heavy chain (betaMyHC) distal muscle CAT (MCAT) element in muscle fiber type-specific expression and mechanical overload (MOV) responsiveness, we conducted transgenic and in vitro experiments. In adult transgenic mice, mutation of the distal MCAT element led to significant reductions in chloramphenicol acetyltransferase (CAT) specific activity measured in control soleus and plantaris muscles when compared with wild type transgene beta293WT but did not abolish MOV-induced CAT specific activity. Electrophoretic mobility shift assay revealed the formation of a specific low migrating nuclear protein complex (LMC) at the betaMyHC MCAT element that was highly enriched only when using either MOV plantaris or control soleus nuclear extract. Scanning mutagenesis of the betaMyHC distal MCAT element revealed that only the nucleotides comprising the core MCAT element were essential for LMC formation. The proteins within the LMC when using either MOV plantaris or control soleus nuclear extracts were antigenically related to nominal transcription enhancer factor 1 (NTEF-1), poly(ADP-ribose) polymerase (PARP), and Max. Only in vitro translated TEF-1 protein bound to the distal MCAT element, suggesting that this multiprotein complex is tethered to the DNA via TEF-1. Protein-protein interaction assays revealed interactions between nominal TEF-1, PARP, and Max. Our studies show that for transgene beta293 the distal MCAT element is not required for MOV responsiveness but suggest that a multiprotein complex likely comprised of nominal TEF-1, PARP, and Max forms at this element to contribute to basal slow fiber expression. PMID:11010974

  4. Kinetic method for the determination of nanogram amounts of cadmium(II) by its catalytic effect on the complex formation of manganese(II) with. cap alpha. ,. beta. ,. gamma. , $delta-tetra-(p-sulfonatophenyl)porphine

    Energy Technology Data Exchange (ETDEWEB)

    Tabata, M. (Saga Univ. (Japan). Faculty of Science and Engineering); Tanaka, M. (Nagoya Univ. (Japan). Faculty of Science)

    1982-01-01

    Cadmium(II) accelerates the complex formation reaction of manganese(II) with ..cap alpha.., ..beta.., ..gamma.., $delta-tetra(p-sulfonatophenyl)porphine (H/sub 2/TPPS/sub 4/). Cadmium(II) concentration as low as 1O/sup -7/ mol dm/sup -3/ can be determined from the decrease in absorbance at 413 nm ($lambdasub(max) H/sub 2/TPPS/sub 4/) at a fixed time after the start of the reaction of manganese(II) with H/sub 2/TPPS/sub 4/. After the separation of lead(II) by coprecipitation of manganese(IV) oxide, the method is highly selective and is free from interference of most substances usually encountered. Sandell's sensitivity calculated from the calibration curve at 30 min after the start of the reaction is 1.43 x 10/sup -/ /sup 1/ ng cm/sup -2/.

  5. Ternary complex formation of Ino2p-Ino4p transcription factors and Apl2p adaptin beta subunit in yeast.

    Science.gov (United States)

    Nikawa, Jun-ichi; Yata, Masako; Motomura, Miki; Miyoshi, Nobutaka; Ueda, Tsuyoshi; Hisada, Daisuke

    2006-11-01

    Yeast Ino2p-Ino4p heterodimeric complex is well known as a transcriptional activator for the genes regulated by inositol and choline, such as the INO1 gene. Apl2p is a large subunit of the yeast adaptin complex, an adaptor complex required for the clathrin coat to bind to the membrane. We found that Ino2p, Ino4p, and Apl2p form a ternary complex. This interaction was initially observed in a yeast two-hybrid study and subsequently verified by co-immunoprecipitation. Ino2p and Ino4p bind to Apl2p in the same region of Apl2p, viz., at the middle part and the C-terminal part. Ino2p and Ino4p bind to Apl2p independently, but more strongly when both are present. Furthermore, a disruption of APL2 together with INO2 or INO4 rendered yeast cells sensitive to oxidative stress. INO2-APL2 double disruptants also showed growth inability in non-fermentable carbon sources, such as glycerol. These results indicate a genetic interaction between APL2, INO2 and INO4 and uncovere novel functions of the Ino2p-Ino4p-Apl2p complex in yeast. PMID:17090927

  6. Interaction between Nbp35 and Cfd1 proteins of cytosolic Fe-S cluster assembly reveals a stable complex formation in Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Shadab Anwar

    Full Text Available Iron-Sulfur (Fe-S proteins are involved in many biological functions such as electron transport, photosynthesis, regulation of gene expression and enzymatic activities. Biosynthesis and transfer of Fe-S clusters depend on Fe-S clusters assembly processes such as ISC, SUF, NIF, and CIA systems. Unlike other eukaryotes which possess ISC and CIA systems, amitochondriate Entamoeba histolytica has retained NIF & CIA systems for Fe-S cluster assembly in the cytosol. In the present study, we have elucidated interaction between two proteins of E. histolytica CIA system, Cytosolic Fe-S cluster deficient 1 (Cfd1 protein and Nucleotide binding protein 35 (Nbp35. In-silico analysis showed that structural regions ranging from amino acid residues (P33-K35, G131-V135 and I147-E151 of Nbp35 and (G5-V6, M34-D39 and G46-A52 of Cfd1 are involved in the formation of protein-protein complex. Furthermore, Molecular dynamic (MD simulations study suggested that hydrophobic forces surpass over hydrophilic forces between Nbp35 and Cfd1 and Van-der-Waal interaction plays crucial role in the formation of stable complex. Both proteins were separately cloned, expressed as recombinant fusion proteins in E. coli and purified to homogeneity by affinity column chromatography. Physical interaction between Nbp35 and Cfd1 proteins was confirmed in vitro by co-purification of recombinant Nbp35 with thrombin digested Cfd1 and in vivo by pull down assay and immunoprecipitation. The insilico, in vitro as well as in vivo results prove a stable interaction between these two proteins, supporting the possibility of its involvement in Fe-S cluster transfer to target apo-proteins through CIA machinery in E. histolytica. Our study indicates that initial synthesis of a Fe-S precursor in mitochondria is not necessary for the formation of Cfd1-Nbp35 complex. Thus, Cfd1 and Nbp35 with the help of cytosolic NifS and NifU proteins can participate in the maturation of non-mitosomal Fe-S proteins

  7. Complex formation ions with macromolecules pectin

    International Nuclear Information System (INIS)

    This article describe the sorption properties of N M pectin from sunflowers. It is shown than calcium ion binding to the pectin carboxylic group differ from that of zinc ions and describe cooperative character -

  8. Complex formation ions calcium with macromolecules pectin

    International Nuclear Information System (INIS)

    In clause the mechanism of sorption of ions of calcium by macromolecules of pectin is opened. Is shown, that the linkage of ions of calcium descends on acid bunches of pectin, and process carries cooperative character

  9. Further Aspects of Ochratoxin A-Cation Interactions: Complex Formation with Zinc Ions and a Novel Analytical Application of Ochratoxin A-Magnesium Interaction in the HPLC-FLD System

    Directory of Open Access Journals (Sweden)

    Miklós Poór

    2014-04-01

    Full Text Available Ochratoxin A (OTA is a mycotoxin produced by different Aspergillus and Penicillium species. Since its mechanism of action is not fully understood yet, it is important to gain further insight into different interactions of OTA at the molecular level. OTA is found worldwide in many foods and drinks. Moreover, it can also be detected in human and animal tissues and body fluids, as well. Therefore, the development of highly sensitive quantitative methods for the determination of OTA is of utmost importance. OTA most likely forms complexes with divalent cations, both in cells and body fluids. In the present study, the OTA-zinc interaction was investigated and compared to OTA-magnesium complex formation using fluorescence spectroscopy and molecular modeling. Our results show that zinc(II ion forms a two-fold higher stable complex with OTA than magnesium(II ion. In addition, based on the enhanced fluorescence emission of OTA in its magnesium-bound form, a novel RP-HPLC-fluorescence detector (FLD method was also established. Our results highlight that the application of magnesium chloride in alkaline eluents results in an approximately two-fold increase in sensitivity using the HPLC-FLD technique.

  10. Adamantyl-group containing mixed-mode acrylamide-based continuous beds for capillary electrochromatography. Part I: study of a synthesis procedure including solubilization of N-adamantyl-acrylamide via complex formation with a water-soluble cyclodextrin.

    Science.gov (United States)

    Al-Massaedh, Ayat Allah; Pyell, Ute

    2013-04-19

    A new synthesis procedure for highly crosslinked macroporous amphiphilic N-adamantyl-functionalized mixed-mode acrylamide-based monolithic stationary phases for capillary electrochromatography (CEC) is investigated employing solubilization of the hydrophobic monomer by complexation with a cyclodextrin. N-(1-adamantyl)acrylamide is synthesized and characterized as a hydrophobic monomer forming a water soluble-inclusion complex with statistically methylated-β-cyclodextrin. The stoichiometry, the complex formation constant and the spatial arrangement of the formed complex are determined. Mixed-mode monolithic stationary phases are synthesized by in situ free radical copolymerization of cyclodextrin-solubilized N-adamantyl acrylamide, a water soluble crosslinker (piperazinediacrylamide), a hydrophilic monomer (methacrylamide), and a negatively charged monomer (vinylsulfonic acid) in aqueous medium in bind silane-pretreated fused silica capillaries. The synthesized monolithic stationary phases are amphiphilic and can be employed in the reversed- and in the normal-phase mode (depending on the composition of the mobile phase), which is demonstrated with polar and non-polar analytes. Observations made with polar analytes and polar mobile phase can only be explained by a mixed-mode retention mechanism. The influence of the total monomer concentration (%T) on the chromatographic properties, the electroosmotic mobility, and on the specific permeability is investigated. With a homologues series of alkylphenones it is confirmed that the hydrophobicity (methylene selectivity) of the stationary phase increases with increasing mass fraction of N-(1-adamantyl)acrylamide in the synthesis mixture. PMID:23489493

  11. Application of soft- and hard-modelling approaches to resolution of kinetics of electron donor-acceptor complex formation of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with imipramine in different solutions

    Energy Technology Data Exchange (ETDEWEB)

    Hasani, Masoumeh [Faculty of Chemistry, Bu-Ali Sina University, Mahdieh, Hamedan, 65174 (Iran, Islamic Republic of)], E-mail: hasani@basu.ac.ir; Shariati-Rad, Masoud [Faculty of Chemistry, Bu-Ali Sina University, Mahdieh, Hamedan, 65174 (Iran, Islamic Republic of); Abdollahi, Hamid [Department of Chemistry, Institute for Advanced Studies in Basic Sciences, Zanjan (Iran, Islamic Republic of)

    2009-03-23

    Kinetics of electron donor-acceptor (EDA) complex formation of imipramine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was investigated spectrophotometrically in acetonitrile, 1,2-dichloroethane, and chloroform solutions using soft- and hard-modelling approaches. From the results of exploratory analysis of kinetic data and the spectral changes by soft-modelling approaches, evolving factor analysis (EFA) and orthogonal projection approach (OPA), a consecutive two-steps reaction with two intermediates was proposed for the process in acetonitrile and 1,2-dichloroethane media and one with a single intermediate in chloroform solution. Secondly, by applying, multivariate nonlinear least squares hard-modelling approach on the collected experimental kinetic data matrix, the nonlinear parameters (rate constants) as well as the linear parameters (spectral profiles) were obtained by fitting the collected experimental kinetic data matrix to the proposed model. Small values of standard deviation in the resulting parameters and sum of squares of the residuals (ssq) obtained showed the proper selection of the model. Furthermore, the values of lack of fit and percent of explained variance confirmed the correct identified models. Identification of the model with the aid of soft-modelling approaches followed by application of the hard-modelling approaches decreases significantly the rotational ambiguity associated with the obtained concentration and spectral profiles. Variations in the kinetic constants were in complete agreement with the model proposed and the solvent polarities.

  12. Imaging protein complex formation in the autophagy pathway: analysis of the interaction of LC3 and Atg4BC74A in live cells using Förster resonance energy transfer and fluorescence recovery after photobleaching

    Science.gov (United States)

    Kraft, Lewis J.; Kenworthy, Anne K.

    2012-01-01

    The protein microtubule-associated protein 1, light chain 3 (LC3) functions in autophagosome formation and plays a central role in the autophagy pathway. Previously, we found LC3 diffuses more slowly in cells than is expected for a freely diffusing monomer, suggesting it may constitutively associate with a macromolecular complex containing other protein components of the pathway. In the current study, we used Förster resonance energy transfer (FRET) microscopy and fluorescence recovery after photobleaching (FRAP) to investigate the interactions of LC3 with Atg4BC74A, a catalytically inactive mutant of the cysteine protease involved in lipidation and de-lipidation of LC3, as a model system to probe protein complex formation in the autophagy pathway. We show Atg4BC74A is in FRET proximity with LC3 in both the cytoplasm and nucleus of living cells, consistent with previous biochemical evidence that suggests these proteins directly interact. In addition, overexpressed Atg4BC74A diffuses significantly more slowly than predicted based on its molecular weight, and its translational diffusion coefficient is significantly slowed upon coexpression with LC3 to match that of LC3 itself. Taken together, these results suggest Atg4BC74A and LC3 are contained within the same multiprotein complex and that this complex exists in both the cytoplasm and nucleoplasm of living cells.

  13. Indirect Voltammetric Sensing Platforms For Fluoride Detection on Boron-Doped Diamond Electrode Mediated via [FeF6]3− and [CeF6]2− Complexes Formation

    International Nuclear Information System (INIS)

    Very simple and sensitive electroanalytical technique based on synergistic combination of reaction electrochemistry (specificity) and bare boron-doped diamond electrode (sensitivity) for the detection of fluorides in drinking water was developed as variant based on dynamic electrochemistry to ISE analysis. It is based on the formation of electroinactive fluoride complexes with Fe(III) and Ce(IV) ions decreasing such diffusion current of free metal on boron-doped diamond electrode. Due to low background signal of boron-doped diamond electrode reasonably low detection limits of the order of 10−6 mol L−1 for linear sweep voltammetric method using formation of [FeF6]3− and 10−7 mol L−1 in a square-wave variant of this technique have been achieved. This is approximately 1–2 orders lower than in the case of platinum comb-shaped interdigitated microelectrode array. Linear sweep voltammetric method based on [CeF6]2− complex formation has lower sensitivity and may be suitable for samples with higher content of fluoride and not to analysis of drinking water

  14. Application of soft- and hard-modelling approaches to resolution of kinetics of electron donor-acceptor complex formation of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with imipramine in different solutions

    International Nuclear Information System (INIS)

    Kinetics of electron donor-acceptor (EDA) complex formation of imipramine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was investigated spectrophotometrically in acetonitrile, 1,2-dichloroethane, and chloroform solutions using soft- and hard-modelling approaches. From the results of exploratory analysis of kinetic data and the spectral changes by soft-modelling approaches, evolving factor analysis (EFA) and orthogonal projection approach (OPA), a consecutive two-steps reaction with two intermediates was proposed for the process in acetonitrile and 1,2-dichloroethane media and one with a single intermediate in chloroform solution. Secondly, by applying, multivariate nonlinear least squares hard-modelling approach on the collected experimental kinetic data matrix, the nonlinear parameters (rate constants) as well as the linear parameters (spectral profiles) were obtained by fitting the collected experimental kinetic data matrix to the proposed model. Small values of standard deviation in the resulting parameters and sum of squares of the residuals (ssq) obtained showed the proper selection of the model. Furthermore, the values of lack of fit and percent of explained variance confirmed the correct identified models. Identification of the model with the aid of soft-modelling approaches followed by application of the hard-modelling approaches decreases significantly the rotational ambiguity associated with the obtained concentration and spectral profiles. Variations in the kinetic constants were in complete agreement with the model proposed and the solvent polarities

  15. Activity and safety of combined rituximab with chlorambucil in patients with mantle cell lymphoma.

    Science.gov (United States)

    Bauwens, Deborah; Maerevoet, Marie; Michaux, Lucienne; Théate, Ivan; Hagemeijer, Anne; Stul, Michel; Danse, Etienne; Costantini, Sabrina; Vannuffel, Pascal; Straetmans, Nicole; Vekemans, Marie-Christiane; Deneys, Véronique; Ferrant, Augustin; Van Den Neste, Eric

    2005-11-01

    We evaluated the combination of rituximab with chlorambucil in patients with mantle cell lymphoma (MCL) not eligible for aggressive therapy. Fourteen patients (male/female: 9/5) were included (two newly diagnosed, 12 relapsed/refractory). The toxicities were neutropenia, thrombopenia and infection. Nine (64%) patients responded; five (36%) achieved complete remission and four (29%) achieved partial remission. The median progression-free survival for responders was 26 months (95% CI, 4-48). Marrow polymerase chain reaction negativity was attained in seven responders. These results suggest that this schedule may have notable antitumour activity in patients with MCL, including patients in relapse after autologous stem cell transplantation. PMID:16225653

  16. The study of anticancer and antifungal activities of Pistacia integerrima extract In vitro

    Directory of Open Access Journals (Sweden)

    Y Bibi

    2012-01-01

    Full Text Available Pistacia integerrima Stew. ex Brand (Anacardiaceae is an ethanobotanically important plant species traditionally used in the treatment of chronic wounds, jaundice, dysentery, etc. The crude extract from Pistacia integerrima and its fractions were tested for cytotoxic activity against Michigan Cancer Foundation-7 human breast cancer cell line. We have also investigated that crude stem extract of this plant also exhibits the antitumour as well as antifungal potential activities. Moreover, we have also studied that the crude extract inhibited Michigan Cancer Foundation-7 cell viability in a dose-dependent manner; the poor toxicity (1.6% at 10 μg/ml to moderate toxicity (55.4% at 100 μg/ml. The IC 50 values calculated were 90.9 μg/ml. The ethyl acetate and chloroform fractions at a concentration of 200 μg/ml showed ~100 and 97.4% inhibition against Michigan Cancer Foundation-7 cell line, respectively. The crude methanol extract also showed good antitumour (IC 50 125 ppm activity, but weak antifungal activity. These findings reveal that the ethyl acetate and chloroform fractions of Pistacia integerrima are potent cytotoxic fractions, and could be an alternate candidate for the development of novel biologically active compounds.

  17. Equilibrium study of the complex formation of some trivalent metal ion chelates of Schiff bases derived from 2-hydroxy-3-phenyl benzaldehyde and evaluation of these reagents from their anticoagulant activity

    International Nuclear Information System (INIS)

    Potentiometric studies have been carried out on metal chelates of La3+, Pr3+, Gd3+, Tb3+, Dy3+, Er3+ and Yb3+ with N-(2-hydroxy-3-phenylbenz ylidene)-aniline and N-(2-hydroxy-3-phenylbenzylidene)-3, 4, 5 trimethoxyaniline. The dissociatio n constants of the reagents and formation constants of their metal chelates have been determine d by Calvin-Bjerrum pH titration technique as adopted by Irving and Rossotti and at 28 ± 0.1degC at ionic strength 0.1 M in 75:25 (v/v) dioxane-water mediium. (author). 7 figs., 5 refs

  18. Coordination equilibria in the complex formation of guanylurea with CuII: Formation and stability of binary CuII-guanylurea and ternary CuII-guanylurea-glycinate complexes

    Indian Academy of Sciences (India)

    Tannistha Roy Barman; G N Mukherjee

    2008-07-01

    Combined pH-metric and spectrophotometric investigations on the complex formation equilibria of CuII with guanylurea (H$_{2}^{1}$NC(=O) 2NH.C(=3NH) 4NH2), hereafter, GuH, in the absence and in the presence of glycine (GlyH), in aqueous solution indicates variety of binary and mixed-ligand complexes: Cu(Gu)+, Cu(Gu)(OH); Cu(Gu)2, Cu(Gu-H)(Gu)-, Cu(Gu-H)$_{2}^{2-}$, Cu(Gu-H)(Gu-2H)3-; Cu(Gly)+, Cu(Gly) (OH); Cu(Gly)(Gu); Cu(Gly)(Gu-H)-, Cu(Gly)(Gu-2H)2-; (Gly)Cu(Gu)Cu(Gly)+, (Gly)Cu(Gu-H)Cu(Gly) and (Gly)Cu(Gu-2H)Cu(Gly)-. At pH < 6, guanylurea anion (Gu-) acts as a [(C=O), 3N-] or [=1NH, 3N-] bidentate ligand and above pH 7 it is transformed through a coordination equilibrium into a (=1N-, =3N-) bidentate ligand, similar to biguanide dianion. Occurrence of dinuclear complex species, (Gly) Cu(Gu)Cu(Gly)+, in the complexation equilibria, indicates bridging double bidentate [(1NH2, 3N-), (C=O, 4NH2)] and/or [(1NH2, 4NH2), (C=O, 3N-)] chelation by Gu- ion in an isomeric equilibrium. Above pH 6.5, the dinuclear complex decomposes mostly to the mononuclear species, Cu(Gly)(OH) and Cu(Gu)(OH) and only partly deprotonates to (Gly)Cu(Gu-H)Cu(Gly) and (Gly)Cu(Gu-2H)Cu(Gly)-. Electronic spectral shifts, with change of pH have been correlated with the possible modes of coordination of guanylurea species.

  19. Antiproliferative activity and apoptotic effects of Filipendula ulmaria pollen against C26 mice colon tumour cells

    Directory of Open Access Journals (Sweden)

    Mărgăoan Rodica

    2016-06-01

    Full Text Available Honeybee collected pollen exhibits high nutritional and pharmaceutical benefits for the human diet and medicine. Pollen’s antioxidant, anti-ageing, anti-inflammatory, anti-atherosclerosis, and cardioprotective activity, depending on the floral origin, are well known. Recent studies proposed that pollen may also be an excellent cancer-fighting candidate, as pollen harbours high amounts of phenolic substances. In our study, Filipendula ulmaria pollen (bee collected was methanol-water extracted and used to verify its in vitro pharmacological activities on C26 mice cancer tumour cells. Three different concentrations of the extract were tested in antitumour assays. Monitoring was done after 6, 12, 24, and 48 hours. Promising results were obtained for antiproliferative and apoptotic activity of the pollen extracts, with high efficiency for the highest concentration (1 mg/mL. For both activities, time and concentration-dependent effects were observed. Pollen extracts or bee collected pollen has a high potential as an antitumour agent for use in human medicine, because they are both rich in bioactive compounds.

  20. BIOLOGICAL ACTIVITIES OF OXAZINE AND ITS DERIVATIVES: A REVIEW

    Directory of Open Access Journals (Sweden)

    SINDHU T J

    2014-12-01

    Full Text Available Oxazine derivatives are an important class of heterocycles, which has attracted much synthetic interest due to their wide range of biological activities. Oxazine is a heterocyclic compound can be formally derived from benzene, and its reduction products, by suitable substitution of carbon (and hydrogen atoms by nitrogen and oxygen. In the last few years oxazine derivatives have proved to be valuable synthetic intermediates and also possess important biological activities like sedative, analgesic, antipyretic, anticonvulsant, antitubercular, antitumour, antimalarial and antimicrobial. In these days, development of drug resistance is a major problem and to overcome this situation, it is necessary to synthesize new classes of compounds. The aim of the article is to review the generalization of the collected data about the synthesis of oxazine derivatives and their activities. We hope that this work will be a definite interest for researchers concerned with azines in generally and oxazines in particular.

  1. A study on the processing method for acoustic slowness logging in complex formations%复杂地层声波测井时差处理方法研究

    Institute of Scientific and Technical Information of China (English)

    苏远大; 庄春喜; 唐晓明; 王易安; 贾向东

    2011-01-01

    During acoustic logging in complex formations, the logging waveforms are often distorted by formation velocity changes and by the interference of acoustic reflections from formation bed boundaries. The waveform distortion causes different receivers in the receiver array to have significantly different amplitudes, and the resulting slowness estimation from the array data suffers from large errors due to poor signal coherence. This wave phenomenon, can be seen from a finite difference simulation of acoustic logging for the thin-bed sand-shale sequence model. To improve the slowness estimation accuracy for this situation, we use a Frequency-Wavenumber Coherence Filtering method to suppress the bed-boundary reflection interference in acoustic data and enhance the coherence of formation compressional (P) waves in array. We have applied the technique to both synthetic modeling and field logging data. The results show that this method effectively suppresses the interference of bed-boundaryreflections and significantly improves the coherence of formation P-waves, allowing forincreasing the resolution of the P-wave slowness log curve and detecting the thin-bedcharacteristics of sand-shale sequences in formation.%在复杂地层(如砂—泥岩薄互层)的声波测井中,由于地层声速变化及界面反射波叠加干扰,导致不同接收器的地层纵波波形幅度差异明显,且相关性很差,使得提取的时差误差较大.这一声场特征可从薄互层声波测井的有限差分数值模拟中看到.针对这一现象,本文利用频率—波数域相关滤波处理技术来消除薄互层声波测井的界面反射干扰,以改善地层纵波波形的相关性.本文给出了砂—泥岩薄互层数字声波测井的现场资料处理实例,处理结果证明了该方法有效地消除了界面反射波的干扰,明显改善了地层纵波的相关性,提高了地层纵波时差曲线的分辨率,清晰地刻画出了薄互层特征.

  2. Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway

    Indian Academy of Sciences (India)

    Zhaocai Li; Yong Huang; Feng Dong; Wei Li; Li Ding; Gaoshui Yu; Dan Xu; Yuanyuan Yang; Xingang Xu; Dewen Tong

    2012-12-01

    Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay. Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, down-regulated Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsonine-treated xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.

  3. Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Luo, Xiang-jian; Li, Li-li; Deng, Qi-pan; Yu, Xin-fang; Yang, Li-fang; Luo, Fei-jun; Xiao, Lan-bo; Chen, Xiao-yan; Ye, Mao; Liu, Ji-kai; Cao, Ya

    2011-01-01

    Grifolin, a secondary metabolite isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, has been shown to inhibit the growth of some cancer cell lines in vitro by induction of apoptosis in previous studies of our group. However, the mechanisms of action are not completely understood. An apoptosis-related gene expression profiling analysis provided a clue that death-associated protein kinase 1 (dapk1) gene was upregulated at least twofold in response to grifolin treatment in nasopharyngeal carcinoma cell CNE1. Here, we further investigated the role of DAPK1 in apoptotic effect induced by grifolin. We observed that protein as well as mRNA level of DAPK1 was induced by grifolin in a dose-dependent manner in nasopharyngeal carcinoma cell CNE1. We found that grifolin increased both Ser392 and Ser20 phosphorylation levels of transcription factor p53 protein, which could promote its transcriptional activity. Moreover, induced by grifolin, the recruitment of p53 to dapk1 gene promoter was confirmed to enhance markedly using EMSA and ChIP assays analysis. The involvement of DAPK1 in grifolin-induced apoptosis was supported by the studies that introducing siRNA targeting DAPK1 to CNE1 cells remarkably interfered grifolin-caused apoptotic effect as well as the activation of caspase-3. Grifolin induced upregulation of DAPK1 via p53 was also observed in tumour cells derived from human breast cancer and human colon cancer. The findings suggest that upregulation of DAPK1 via p53-DAPK1 pathway is an important mechanism of grifolin contributing to its ability to induce apoptotic effect. Since growing evidence found a significant loss of DAPK1 expression in a large variety of tumour types, grifolin may represent a promising candidate in the intervention of cancer via targeting DAPK1. PMID:20943371

  4. Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents.

    Science.gov (United States)

    Senwar, Kishna Ram; Reddy, T Srinivasa; Thummuri, Dinesh; Sharma, Pankaj; Naidu, V G M; Srinivasulu, Gannoju; Shankaraiah, Nagula

    2016-08-01

    A series of new (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 ± 0.6 and 1.94 ± 0.2 μM, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (ΔΨm) was also affected and the levels of intracellular Ca(2+) were raised. PMID:27128173

  5. Activities.

    Science.gov (United States)

    Moody, Mally

    1992-01-01

    A series of four activities are presented to enhance students' abilities to appreciate and use trigonometry as a tool in problem solving. Activities cover problems applying the law of sines, the law of cosines, and matching equivalent trigonometric expressions. A teacher's guide, worksheets, and answers are provided. (MDH)

  6. Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates

    Indian Academy of Sciences (India)

    Palaniyandi Ravanan; Sanjay K Singh; G S R Subba Rao; Paturu Kondaiah

    2011-06-01

    Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, prodifferentiative and anti-tumour triterpenoid compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic activity on a number of cancer cell lines with IC50 ranging from 0.2 to 0.6 M. CEMB inhibits DNA synthesis and induces apoptosis in A549 cell line at 0.25 M and 1 M concentrations, respectively. CEMB induces adipogenic differentiation in 3T3-L1 cells at a concentration of 0.1 M. Finally, administration of CEMB intra-tumourally significantly inhibited the growth of C6 glioma tumour xenograft in immuno-compromised mice. Collectively, these results suggest that CEMB is a very potent anti-tumour compound.

  7. Discovery of a dual-targeting organometallic ruthenium complex with high activity inducing early stage apoptosis of cancer cells.

    Science.gov (United States)

    Du, Jun; Zhang, Erlong; Zhao, Yao; Zheng, Wei; Zhang, Yang; Lin, Yu; Wang, Zhaoying; Luo, Qun; Wu, Kui; Wang, Fuyi

    2015-12-01

    Ruthenium based complexes are promising antitumour candidates due to their lower toxicity and better water-solubility compared to the platinum antitumour complexes. An epidermal growth factor receptor (EGFR) has been found to be overexpressed in a large set of tumour cells. In this work, a series of organoruthenium complexes containing EGFR-inhibiting 4-anilinoquinazoline pharmacophores were synthesised and characterised. These complexes exhibited excellent inhibitory activity against EGFR and high affinity to interact with DNA via minor groove binding, featuring dual-targeting properties. In vitro screening demonstrated that the as-prepared ruthenium complexes are anti-proliferating towards a series of cancer cell lines, in particular the non-small-cell lung cancer cell line A549. Fluorescence-activated cell sorting analysis and fluorescence microscopy revealed that the most active complex 3 induced much more early-stage cell apoptosis than its cytotoxic arene ruthenium analogue and the EGFR-inhibiting 4-anilinoquinazolines, verifying the synergetic effect of the two mono-functional pharmacophores. PMID:26446567

  8. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3

    OpenAIRE

    Todi, Sokol V.; Winborn, Brett J; Scaglione, K Matthew; Blount, Jessica R.; Travis, Sue M.; Paulson, Henry L.

    2009-01-01

    Deubiquitinating enzymes (DUBs) control the ubiquitination status of proteins in various cellular pathways. Regulation of the activity of DUBs, which is critically important to cellular homoeostasis, can be achieved at the level of gene expression, protein complex formation, or degradation. Here, we report that ubiquitination also directly regulates the activity of a DUB, ataxin-3, a polyglutamine disease protein implicated in protein quality control pathways. Ubiquitination enhances ubiquiti...

  9. Polyphenolic Profile and Biological Activity of Chinese Hawthorn (Crataegus pinnatifida BUNGE Fruits

    Directory of Open Access Journals (Sweden)

    Tunde Jurikova

    2012-12-01

    Full Text Available Chinese hawthorn (Crataegus pinnatifida Bge. fruits are rich in polyphenols (e.g., epicatechin, procyanidin B2, procyanidin B5, procyanidin C1, hyperoside, isoquercitrin and chlorogenic acid—active compounds that exert beneficial effects. This review summarizes all information available on polyphenolic content and methods for their quantification in Chinese hawthorn berries and the relationships between individual polyphenolic compounds as well. The influence of species or cultivars, the locality of cultivation, the stage of maturity, and extract preparation conditions on the polyphenolic content were discussed as well. Currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included in the Chinese Pharmacopoeia. Recent trials have demonstrated the efficacy of Chinese hawthorn fruit in lowering blood cholesterol and the risk of cardiovascular diseases. The fruit has also demonstrated anti-inflammatory and anti-tumour activities. This review deals mainly with the biological activity of the fruit related to its antioxidant properties.

  10. Polyphenolic profile and biological activity of Chinese hawthorn (Crataegus pinnatifida BUNGE) fruits.

    Science.gov (United States)

    Jurikova, Tunde; Sochor, Jiri; Rop, Otakar; Mlcek, Jiri; Balla, Stefan; Szekeres, Ladislav; Adam, Vojtech; Kizek, Rene

    2012-01-01

    Chinese hawthorn (Crataegus pinnatifida Bge.) fruits are rich in polyphenols (e.g., epicatechin, procyanidin B2, procyanidin B5, procyanidin C1, hyperoside, isoquercitrin and chlorogenic acid)--active compounds that exert beneficial effects. This review summarizes all information available on polyphenolic content and methods for their quantification in Chinese hawthorn berries and the relationships between individual polyphenolic compounds as well. The influence of species or cultivars, the locality of cultivation, the stage of maturity, and extract preparation conditions on the polyphenolic content were discussed as well. Currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included in the Chinese Pharmacopoeia. Recent trials have demonstrated the efficacy of Chinese hawthorn fruit in lowering blood cholesterol and the risk of cardiovascular diseases. The fruit has also demonstrated anti-inflammatory and anti-tumour activities. This review deals mainly with the biological activity of the fruit related to its antioxidant properties. PMID:23222867

  11. Synthesis, structure, photoluminescence and antitumour activity of zinc complex based on 2-(2-(1H-benzo-[d]imidazol-2-yl)benzyl)-1H-benzo-[d]imidazole

    Science.gov (United States)

    Che, Zhijian; Wang, Shaoxiang; Liu, Shenggui; Li, Guobi; Wu, Qiting; Lin, Chunyu; Kong, Linglang; Wang, Sheng

    2015-01-01

    A new complex [Zn(bbb)Cl2]·DMF, where bbb is 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole, was synthesized and characterized by element analysis, 1H NMR and X-ray single crystal structure analyses. For complex: crystal system, triclinic, space group, P-1, a = 9.4661(13), b = 10.3534(14), c = 13.0025(18) Å, α = 73.477(2), β = 80.743(2), γ = 88.658(2)°, V = 1205.5(3) Å3, Z = 2. In this complex, the Zn2+ distorted tetrahedron geometry is coordinated by two nitrogen atoms from 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole and two Cl-. The complex emits yellow green luminescence with the maximal emission peak at 550 nm in DMF solution. The complex exhibits inhibition on the growth of Eca109 cancer cell with IC50 value of 8.9 ± 1.1 μM, which was lower than that of cisplatin (14.3 ± 1.4 μM). This complex has potential application in treatment of esophageal cancer.

  12. The chemistry and biological activity of herbs used in Flor-Essence herbal tonic and Essiac.

    Science.gov (United States)

    Tamayo, C; Richardson, M A; Diamond, S; Skoda, I

    2000-02-01

    The herbal mixtures, Essiac and Flor-Essence, are sold as nutritional supplements and used by patients to treat chronic conditions, particularly cancer. Evidence of anticancer activity for the herbal teas is limited to anecdotal reports recorded for some 40 years in Canada. Individual case reports suggest that the tea improves quality of life, alleviates pain, and in some cases, impacts cancer progression among cancer patients. Experimental studies with individual herbs have shown evidence of biological activity including antioxidant, antioestrogenic, immunostimulant, antitumour, and antiocholeretic actions. However, research that demonstrates these positive effects in the experimental setting has not been translated to the clinical arena. Currently, no clinical studies of Essiac or Flor-essence are published, but a clinical study is being planned at the British Columbia Cancer Agency by the University of Texas-Center for Alternative Medicine (UT-CAM) and Tzu-Chi Institute for Complementary and Alternative Medicine. PMID:10641040

  13. AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease.

    Science.gov (United States)

    Grahame Hardie, D

    2014-12-01

    The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole-body energy balance. A recently reported crystal structure has illuminated the complex regulatory mechanisms by which AMP and ADP cause activation of AMPK, involving phosphorylation by the upstream kinase LKB1. Once activated by falling cellular energy status, AMPK activates catabolic pathways that generate ATP whilst inhibiting anabolic pathways and other cellular processes that consume ATP. A role of AMPK is implicated in many human diseases. Mutations in the γ2 subunit cause heart disease due to excessive glycogen storage in cardiac myocytes, leading to ventricular pre-excitation. AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK. The upstream kinase LKB1 is a tumour suppressor, and AMPK may exert many of its antitumour effects. AMPK activation promotes the oxidative metabolism typical of quiescent cells, rather than the aerobic glycolysis observed in tumour cells and cells involved in inflammation, explaining in part why AMPK activators have both antitumour and anti-inflammatory effects. Salicylate (the major in vivo metabolite of aspirin) activates AMPK, and this could be responsible for at least some of the anticancer and anti-inflammatory effects of aspirin. In addition to metformin and salicylates, novel drugs that modulate AMPK are likely to enter clinical trials soon. Finally, AMPK may be involved in viral infection: downregulation of AMPK during hepatitis C virus infection appears to be essential for efficient viral replication. PMID:24824502

  14. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke;

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a...... subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the......) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the...

  15. Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Na Song

    2014-04-01

    Full Text Available Aberrant MET expression and hepatocyte growth factor (HGF signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.

  16. Synthesis of Novel Biologically Active s-Triazolo[3,4-b]-1,3,4-thiadiazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    SUN,Yi-Feng

    2004-01-01

    @@ Heterocycles bearing a symmetrical triazole or 1,3,4-thiadiazole ring system are reported to show a broad spectrum of biological activities.[1,2] The 1,2,4-triazole nucleus has been recently incorporated into a wide variety of therapeutically interesting drugs including H1/H2 histamine receptor blockers, cholinesterase active agents, CNS stimulants, antianxiety and sedatives[3] Coumarins are nowadays an important group of organic compounds that used as bactericides, fungicides,anti-inflammatory, anticoagulant, anti-HIV and antitumour agents.[4,5] Keeping in view the biological importance of the above mentioned heterocyclic compounds and in continuation of our search for biologically active nitrogen and sulphur heterocycles, a series of s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives was synthesized.

  17. Crustal structure of a rifted oceanic core complex and its conjugate side at the MAR at 5°S: implications for melt extraction during detachment faulting and core complex formation

    OpenAIRE

    L. Planert; E. R. Flueh; Frederik Tilmann; I. Grevemeyer; Reston, T.J.;  

    2010-01-01

    We present results of a seismic refraction experiment which determines the crustal and uppermantle structure of an oceanic core complex (OCC) and its conjugate side located south of the 5◦S ridge–transform intersection at the Mid-Atlantic Ridge. The core complex with a corrugated surface has been split by a change in location of active seafloor spreading, resulting in two massifs on either side of the current spreading axis. We applied a joint tomographic inversion of wide-angle reflected and...

  18. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke Hansen;

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a...... subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the...... presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted in...

  19. 内酯型荧光黄与β-环糊精的包合作用研究%Study of inclusion complex formation between the lactonic structure of fluorescein and β-cyclodextrin

    Institute of Scientific and Technical Information of China (English)

    刘奇; 魏静娟; 孟芹红; 王爱军

    2011-01-01

    A Cu-Ni hydroxid / overoxidized polypynole composite film modified electrode was fabricated by using cyclic voltammetry and characterized by electrochemistry and XRD techniques. The electrochemical behavior of glucose on the modified electrode was investigated by cyclic voltammetry and amperometry. The results showed that the resulting modified electrode exhibited high electrocatalytic activity for the oxidation of glucose. Based on this, an amperometric techniques for the determination of glucose was established. Under the optimal conditions, the oxidation peak current has linear relationship with concentration of glucose over the ranges of 5. 0 ×10-7 to 1.1 × 10~3 mol/L (r = 0.9992) and 1.1 × 10 3 mol/L to 5. 8 x× 10 3 mol/L(r = 0.9977), with sensitivities of 1069.3 μA/mmol/L · cm-2 and 505.7 μA/mmol/L · cm-2, respectively. The detection limit (3sb) was 2.0 × 10-7 mol/L. The RSD (n = 10) for the determination of 1.0 × 10-4 mol/L glucose was 3. 2 % and the recoveries were 96. 4 % ~ 100. 8%. The proposed method was applied to the determination of glucose in the serum.%在pH 4的缓冲溶液中,内酯型荧光黄与β-环糊精形成1∶1包合物,其紫外-可见吸光变和荧光强度均下降.考察了pH,离子强度及有机溶剂对包合物稳定性的影响;采用热力学法分析了温度和包合常数的关系,计算了包合过程的焓变,熵变及自由能变化;并通过分子模拟和红外光谱法对包合物的包合形式进行理论探讨和研究.

  20. Gambogic acid covalently modifies IkappaB kinase-beta subunit to mediate suppression of lipopolysaccharide-induced activation of NF-kappaB in macrophages.

    Science.gov (United States)

    Palempalli, Umamaheshwari D; Gandhi, Ujjawal; Kalantari, Parisa; Vunta, Hema; Arner, Ryan J; Narayan, Vivek; Ravindran, Anand; Prabhu, K Sandeep

    2009-04-15

    GA (gambogic acid) is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi with a long history of use as a complementary and alternative medicine. The antitumour activity of GA has been well demonstrated and is thought to arise partly from the associated anti-inflammatory activity. Recent studies have indicated that the antitumour activity of GA is mediated by its ligation of TfR1 (transferrin receptor-1). Since the cellular expression of TfR1 is down-regulated by LPS (lipopolysaccharide), we hypothesized that an alternative pathway exists in immune cells, such as macrophages, where GA could mitigate the expression of pro-inflammatory genes. Here we demonstrate that GA inhibits the LPS-dependent expression of NF-kappaB (nuclear factor kappaB) target pro-inflammatory genes in macrophages. Western immunoblot, NF-kappaB-luciferase reporter and gel-shift analyses revealed that GA strongly blocked the activation of NF-kappaB induced by LPS, whereas 9,10-dihydro-GA, which lacks the reactive alpha,beta-unsaturated carbonyl group, was ineffective. Moreover, GA was able to decrease nuclear p65 levels in RAW264.7 macrophages, where the expression of TfR1 was down-regulated by RNA interference. in vitro kinase assays coupled with interaction studies using biotinylated GA as well as proteomic analysis demonstrated that IKKbeta [IkappaB (inhibitory kappaB) kinase-beta], a key kinase of the NF-kappaB signalling axis, was covalently modified by GA at Cys-179, causing significant inhibition of its kinase activity. Taken together, these results demonstrate the potent anti-inflammatory activity of GA. PMID:19140805

  1. Complex formation of Np(V) with various carboxylates

    International Nuclear Information System (INIS)

    The stability constants of Np(V) complexes with a series of aliphatic and aromatic carboxylates, including hydroxycarboxylates, hydroxydicarboxylates, dicarboxylates and pyridinecarboxylates have been obtained in 1.0 M NaClO4 by a solvent extraction method using thenoyltrifluoroacetone and 1,10- phenanthroline in isoamyl alcohol. Stabilities of these complexes are discussed in terms of their structures and ligand basicities. (orig.)

  2. Complex formation of calcium with humic acid and polyacrylic acid

    International Nuclear Information System (INIS)

    In order to understand the migration behavior of radionuclides in the underground, it is also important to estimate the effect of the competing cations originally present in the groundwater. In this connection, the complexation of Ca(II) with Aldrich humic acid has been examined. For the study at trace concentrations (∝ 10-10 M) of Ca(II), the solvent extraction of 45Ca with TTA and TOPO in cyclohexane has been used. At macro concentrations (10-4 M) of Ca(II), the measurement of the free Ca2+ ion concentration with a calcium selective electrode has been conducted. To estimate the polyelectrolyte effect of humic acid separately from its heterogeneous composition effect, polyacrylic acid ([-CH2CH(COOH)-]n) has been selected as a representative of the homogeneous polymeric weak acids and its complexation with Ca(II) has also been examined. The values of log βα have been obtained at pH 5 ∝ 7 in 0.1, 0.4 and 1.0 M NaCl, where βα is the apparent formation constants defined by βα = [ML]/([M][R]). In this definition, [ML] and [M] are the concentrations of bound and free Ca2+ respectively, [R] is the concentration of dissociated proton exchanging sites. log βα of humate decreases from 2.19 ∝ 2.92 (depending on pH and ionic strength 1.0 α of polyacrylate (1.36 ∝ 3.24 for I = 0.1 ∝ 1.0). For both humate and polyacrylate, log βα decreases linearly with log[Na+], where [Na+] is the bulk concentration of sodium ion. Their dependences of log βα on ionic strength are stronger than those of log β of monomeric carboxylates such as oxalate and EDTA, indicating the large electrostatic effect of crowded negative charges on the macromolecules of humic or polyacrylic acid. (orig.)

  3. Enhancing the Reduction Potential of Quinones via Complex Formation.

    Science.gov (United States)

    Nepal, Binod; Scheiner, Steve

    2016-05-20

    Quantum calculations are used to study the manner in which quinones interact with proton-donating molecules. For neutral donors, a stacked geometry is favored over a H-bond structure. The former is stabilized by charge transfers from the N or O lone pairs to the quinone's π* orbitals. Following the addition of an electron to the quinone, the radical anion forms strong H-bonded complexes with the various donors. The presence of the donor enhances the electron affinity of the quinone. This enhancement is on the order of 15 kcal/mol for neutral donors, but up to as much as 85 kcal/mol for a cationic donor. The increase in electron affinity is larger for electron-rich quinones than for their electron-deficient counterparts, containing halogen substituents. Similar trends are in evidence when the systems are immersed in aqueous solvent. PMID:27135719

  4. Mechanisms Underlying Methamphetamine-Induced Dopamine Transporter Complex Formation

    OpenAIRE

    Hadlock, Gregory C.; Baucum, Anthony J.; King, Jill L.; Horner, Kristen A.; Cook, Glen A.; Gibb, James W.; Wilkins, Diana G; Hanson, Glen R.; Fleckenstein, Annette E.

    2009-01-01

    Repeated, high-dose methamphetamine (METH) administrations cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. In rats, this treatment also causes the formation of high-molecular mass (greater than approximately 120 kDa) dopamine transporter (DAT)-associated complexes, the loss of DAT monomer immunoreactivity, and a decrease in DAT function, as assessed in striatal synaptosomes prepared 24 h after METH treatment. The present study extends ...

  5. Thermodynamic incompatibility and complex formation in pectin/caseinate mixtures

    OpenAIRE

    Rediguieri, Camila F; de Freitas, Osvaldo; Lettinga, Pavlik; Tuinier, Remco

    2007-01-01

    The instability of polysaccharide/protein mixtures occurs because of either thermodynamic incompatibility or complexation. We studied which instability mechanism dominated given the external conditions. Therefore the effect of temperature, pH, and biopolymer concentration on the phase separation of pectin/caseinate mixtures was investigated. At pH > 6, thermodynamic incompatibility with spinodal decomposition was observed in pectin/caseinate mixtures resulting in the formation of water-in-wat...

  6. The imidazole role in strontium beta-diketonate complexes formation.

    Science.gov (United States)

    Marchetti, Fabio; Pettinari, Claudio; Pettinari, Riccardo; Cingolani, Augusto; Gobetto, Roberto; Chierotti, Michele R; Drozdov, Andrei; Troyanov, Sergey I

    2006-04-01

    A selection of new strontium beta-diketonate derivatives (imH2)2[Sr2(beta-dike)6] [where imH = imidazole and beta-dike = tfac (tfacH = 1,1,1-trifluoro-2,4-pentanedione), tfbz (tfbzH = 1,1,1-trifluoro-4-phenyl-2,4-butanedione), or hfac (hfacH = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione)], [Sr2(tfac)4(Meim)2(H2O)2], (MeimH)2[Sr(beta-dike)4] (where Meim = 1-methylimidazole and beta-dike = tfbz or hfac), [Sr2(thd)4(imH)2(EtOH)], and [Sr2(thd)4(Meim)2(EtOH)] (where thdH = 2,2,6,6-tetramethyl-3,5-heptanedione) have been synthesized and fully characterized. (imH2)2[Sr2(beta-dike)6] and (MeimH)2[Sr(beta-dike)4] are di- and mononuclear Sr anionic complexes, respectively, while [Sr2(tfac)4(Meim)2(H2O)2], [Sr2(thd)4(imH)2(EtOH)], and [Sr2(thd)4(Meim)2(EtOH)] are neutral dinuclear molecular derivatives. The derivative (imH2)2[Sr2(hfac)6] slowly decomposes in solution under aerobic conditions, giving (imH2)2[Sr(H2O)2(tfa)3](tfa) (tfaH = trifluoroacetic acid), which is an ionic compound containing polynuclear anionic chains composed of Sr(H2O)2(tfa)3 units. When a deficiency of imH is employed, the thdH proligand forms not only the dinuclear derivative [Sr2(thd)4(imH)2(EtOH)] but also an additional product with the formula [Sr(thd)2(H2O)2(EtOH)], in which the Sr atom is seven-coordinated. A complete solid-state characterization has been accomplished by comparing X-ray and solid-state 13C NMR data. Elucidation of the H-bond interaction between the heterocyclic rings and metal complexes by cross-polarization magic-angle-spinning 15N NMR is also reported. PMID:16562964

  7. Impurity complex formation in ultra-pure germanium

    International Nuclear Information System (INIS)

    Several unknown, hydrogenic acceptors and donors were recently discovered in ultra-pure germanium by photoelectric spectroscopy. These centers are not created by elemental impurities. Comparative analysis of a large number of crystals grown under various conditions lead to the conclusion that copper, a fast diffusing multivalent acceptor, together with lithium and/or hydrogen, is responsible for several of the unknown centers. This is the first time that hydrogen has been recognized as playing the role of a donor pairing with an acceptor. Hall effect measurements complementing the photoelectric spectroscopy results lead to a tentative assignment of the following energy levels: (Cu, Li) complexes: E/sub V/ + 20.5 meV/super */, E/sub V/ + 25.0 meV/super */, E/sub V/ + 275 meV(/super */hydrogenic acceptor); (Cu, H) complexes: E/sub V/ + 17.0 meV/super */, E/sub V/ + 17.5 meV/super */, E/sub V/ + 175 meV. Experiments which may help determine the structure of the complexes are proposed

  8. Excretion technique of radioactive materials in vivo by complex formation

    International Nuclear Information System (INIS)

    To establish an excretion technique of RI metals (63Ni, 109Cd and 210Pb) in vivo, many kinds of complexing agents were developed. The performance evaluation of these agents was carried out by mouse in vivo. They are various kinds of carbohydrate formazan derivatives with deduced uni-saccharide (D-glucose, D-mannose and D-galactose) or disaccharide (maltose) and functional group (-COOH, -NH, -OH, -N=N- and pyridyl group). For example of synthesis method of, formazan derivative with maltose was described. 100 mouse with 8 to 10 g were classified to four groups. 1 group get 0.1 ml of nickel ion hemoperitoneum injection once (control). 2 group had 0.1 ml nickel ion hemoperitoneum injection at one time a day and then 0.1 ml eccritic hypodermic injection during 5 days. 3 group get 0.1 ml cadmium ion hemoperitoneum injection once (control). 4 group had 0.1 ml cadmium ion hemoperitoneum injection and then 0.1 ml eccritic hypodermic injection at one time a day for 5 days. Decay of residue was measured. PCF-maltose showed the best chemical protector against radiation in these agents. Especially, this eccritic can excrete 63Ni and 109Cd without effect on the essential metals such as calcium, magnesium and iron. (S.Y.)

  9. Peptide-Phospholipid Complex Formation at Liquid-Liquid Interfaces

    OpenAIRE

    Mendez, M A; Prudent, M.; Su, B; Girault, H. H.

    2008-01-01

    Two peptides known to interact with receptors embedded in cell membranes, angiotensin III (AngIII) and Leuenkephalin(LeuEnk), were studied electrochemically at the interface formed between two immiscible electrolyte solutions modified by an adsorbed monolayer of dipalmitoylphosphatidylcholine(DPPC). The results indicate thatcationic angiotensin III transfer can be facilitated by the interfacial formation of a complex with DPPC. The complexation constant was determined by voltammetry and found...

  10. Complex Formation History of Highly Evolved Basaltic Shergottite, Zagami

    Science.gov (United States)

    Niihara, T.; Misawa, K.; Mikouchi, T.; Nyquist, L. E.; Park, J.; Hirata, D.

    2012-01-01

    Zagami, a basaltic shergottite, contains several kinds of lithologies such as Normal Zagami consisting of Fine-grained (FG) and Coarse-grained (CG), Dark Mottled lithology (DML), and Olivine-rich late-stage melt pocket (DN). Treiman and Sutton concluded that Zagami (Normal Zagami) is a fractional crystallization product from a single magma. It has been suggested that there were two igneous stages (deep magma chamber and shallow magma chamber or surface lava flow) on the basis of chemical zoning features of pyroxenes which have homogeneous Mg-rich cores and FeO, CaO zoning at the rims. Nyquist et al. reported that FG has a different initial Sr isotopic ratio than CG and DML, and suggested the possibility of magma mixing on Mars. Here we report new results of petrology and mineralogy for DML and the Olivine-rich lithology (we do not use DN here), the most evolved lithology in this rock, to understand the relationship among lithologies and reveal Zagami s formation history

  11. Complement activation by Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, E T; Kharazmi, A; Garred, P;

    1993-01-01

    In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...

  12. Study of complex formation of 5,5'-(2 E, 2' E)-2,2'-(ethane-1,2-diylidene)bis(hydrazine-1-yl-2-ylidene)bis(4-amino-4H-1,2,4-triazole-3-thiol) (HYT) macrocyclic ligand with Cd2+ cation in non-aqueous solution by spectroscopic and conductometric methods

    Science.gov (United States)

    Mallaekeh, Hassan; Shams, Alireza; Shaker, Mohammad; Bahramzadeh, Ehsan; Arefi, Donya

    2014-12-01

    In this paper the complexation reaction of the 5,5'-(2 E,2' E)-2,2'-(ethane-1,2-diylidene)bis(hydrazine-1-yl-2-ylidene)bis(4-amino-4H-1,2,4-triazole-3-thiol) ligand (HYT) with Cd2+ education was studied in some binary mixtures of methanol (MeOH), n-propanol (PrOH) and dimethyl-formamide (DMF) at different temperatures using the conductometry and spectrophotometry. The stability constants of the complex was determined using a GENPLOT computer program. The conductance data and absorbance-mole ratio plots show that in all solvent systems, the stoichiometry of the complex formed between (HYT) and Cd2+ cation is 1: 1. The obtained results show that the stability of (HYT)-Cd complex is sensitive to the mixed solvents composition. The values of thermodynamic parameters (Δ G ∘, Δ H ∘, and Δ S ∘) for formation of (HYT)-Cd complex were obtained from temperature dependence of the stability constant using the van't Hoff plots. The results show that in most cases, the complex are enthalpy destabilized but entropy stabilized and the complex formation is affected by pH, time, temperature and the nature of the solvent.

  13. Copper-containing polyvinyl alcohol composite systems: Preparation, characterization and biological activity

    Science.gov (United States)

    Reza Hajipour, Abdol; Mohammadsaleh, Fatemeh; Reza Sabzalian, Mohammad

    2015-08-01

    The present investigation reports, the complex formation of Cu(II) with polyvinyl alcohol (PVA) and the synthesis of PVA-stabilized Cu2O particles. This PVA-Cu2O composite has been prepared via chemical reduction method using PVA-Cu(II) complex as precursor. At first, Cu(II) ions were stabilized in PVA matrix via complex formation with OH groups; subsequently, this PVA-Cu(II) macromolecular complex as precursor reacted with ascorbic acid as reducing agent at pH=12 to prepare PVA-Cu2O composite. The products were characterized by FTIR, XRD, FE-SEM, HRTEM, Visible Spectroscopy and atomic absorption. In the following, the antibacterial properties of as-prepared composites were examined against Gram-positive (Bacillus thuringiensis) and Gram-negative bacteria (Escherichia coli), and the results showed excellent antibacterial activity of these materials.

  14. Assembly of the eukaryotic PLP-synthase complex from plasmodium and activation of the Pdx1 enzyme

    OpenAIRE

    Guedez, Gabriela; Hipp, Katharina; Windeisen, Volker; Derrer, Bianca; Gengenbacher, Martin; Boettcher, Bettina; Sinning, Irmgard; Kappes, Barbara; Tews, Ivo

    2012-01-01

    Biosynthesis of vitamins is fundamental to malaria parasites. Plasmodia synthesize the active form of vitamin B6 (pyridoxal 5-phosphate, PLP) using a PLP synthase complex. The EM analysis shown here reveals a random association pattern of up to 12 Pdx2 glutaminase subunits to the dodecameric Pdx1 core complex. Interestingly, Plasmodium falciparum PLP synthase organizes in fibers. The crystal structure shows differences in complex formation to bacterial orthologs as interface variations. Alter...

  15. (24S)-ergostane-3β,5α,6β-triol from Hedyotis chrysotricha with inhibitory activity on migration of SK-HEP-1 human hepatocarcinoma cells.

    Science.gov (United States)

    Ye, Miao; Su, Jing-Jing; Liu, Shu-Ting; Cao, Lei; Xiong, Juan; Zhao, Yun; Fan, Hui; Yang, Guo-Xun; Xia, Gang; Hu, Jin-Feng

    2013-01-01

    The methanol extract of the whole plant of Hedyotis chrysotricha demonstrated cytotoxicity against SK-HEP-1 human hepatocarcinoma cells in a primary screening for novel antitumour agents. Bioassay-guided fractionation and purification led to an active principle (24S)-ergostane-3β,5α,6β-triol (1) along with four inactive compounds (2-5). The in vitro transwell migration assay showed that compound 1 remarkably reduced the migration of SK-HEP-1 cells by 78.9% at a dose of 30 µM, without any apoptotic effect on this cell line. Moreover, all the isolated compounds were further evaluated for their cytotoxicities against another four human cancer cell lines (MCF-7, NUGC3, SH-SY5Y and PC-3). PMID:22889249

  16. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry

    DEFF Research Database (Denmark)

    Glintborg, Bente; Østergaard, Mikkel; Krogh, Niels Steen; Dreyer, Lene; Kristensen, Hanne Lene; Hetland, Merete Lund

    2010-01-01

    To use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual patients maintained treatment) and clinical response among patients ...... with ankylosing spondylitis (AS) receiving their first treatment series with a tumour necrosis factor α (TNFα) inhibitor....

  17. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry

    DEFF Research Database (Denmark)

    Glintborg, Bente; Østergaard, Mikkel; Krogh, Niels Steen; Kristensen, Hanne Lene; Hetland, Merete Lund; Dreyer, Lene

    2010-01-01

    To use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual patients maintained treatment) and clinical response among patients ...... with ankylosing spondylitis (AS) receiving their first treatment series with a tumour necrosis factor a (TNFa) inhibitor....

  18. Mitogen-activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells.

    Science.gov (United States)

    Brown, Gabriella K; Tovar, Cesar; Cooray, Anne A; Kreiss, Alexandre; Darby, Jocelyn; Murphy, James M; Corcoran, Lynn M; Bettiol, Silvana S; Lyons, A Bruce; Woods, Gregory M

    2016-08-01

    Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8(+) T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll-like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo. PMID:27089941

  19. Disruption of cell-cell contact maximally but transiently activates AhR-mediated transcription in 10T1/2 fibroblasts

    International Nuclear Information System (INIS)

    The aryl hydrocarbon receptor (AhR) is activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but activation without an exogenous ligand also occurs when normal cell-cell contact is prevented. Suspension of several C3H10T1/2 fibroblast clonal sub-lines that contain an integrated AhR-responsive reporter produced a time course and level of reporter activation and CYP1B1 induction that paralleled TCDD stimulation in confluent monolayer culture. Suspension activation was, however, more transient. Loss of cell-cell contact at low density also activated these reporters independent of cell cycle changes to levels comparable to TCDD stimulation of confluent cells. Loss of cell-cell contact may, therefore, activate AhR. Suspension and TCDD activations exhibited comparable nuclear translocation of AhR and then AhR/ARNT complex formation. Each AhR activation process was equally attenuated by inhibition of, respectively, HSP90 ATPase, the 26S proteosome, and by depletion of intracellular Ca2+. By contrast, the AhR antagonist α-naphthoflavone (αNF) blocked ligand-stimulated AhR activity, but not activation through loss of cell-cell contact. Suspension-induced reporter activation was selectively enhanced by LiCl, which prevented GSK-3β effects on the simultaneously released β-catenin. The effects of suspension and LiCl on reporters were reversed by Ro-31-8220, which did not affect β-catenin, TCDD-activation processes, or AhR turnover. Neither LiCl nor Ro-31-8220 altered suspension-induced AhR/ARNT complex formation. Loss of cell-cell contact permits nuclear translocation and AhR activation that is largely replicated after TCDD binding, but with activity differences due to contact-sensitive factors functioning after AhR/ARNT complex formation

  20. Synthesis, Structure and Antitumor Activity of Dibutyltin Oxide Complexes with 5-Fluorouracil Derivatives. Crystal Structure of [(5-Fluorouracil-1-CH2CH2COOSn(n-Bu 2]4O2

    Directory of Open Access Journals (Sweden)

    Zhan Shi

    2001-07-01

    Full Text Available Dibutyltin (IV oxide complex reacts with the fluorouracil compounds 5-fluorouracil-1-propanonic or 5-fluorouracil-1-acetic acid (Fu to give the complexes [(5-Fu-1-(CH2nCOOSn(n-Bu2]4O2 (I, n=2; II, n=1 which were characterized by IR and 1H-NMR. The crystal structure of complex I shows that the molecular is a dimer, in which two [(5-Fu-1-CH2CH2COOSn(n-Bu2]2O units are linked by a bridging oxygen atom, and the tin atoms adopt distorted trigonal bipyramids via two carbons from a dibutyl moiety and three oxygen atoms from 5-Fu and bridging oxygen. These complexes have potential anti-tumour activity: in vitro tests showed that complexes I and II exhibit high cytotoxicity against OVCAR-3 and PC-14.

  1. MalT, the regulatory protein of the Escherichia coli maltose system, is an ATP-dependent transcriptional activator.

    OpenAIRE

    Richet, E; Raibaud, O

    1989-01-01

    We show that MalT, the transcriptional activator of the Escherichia coli maltose regulon, specifically binds ATP and dATP with a high affinity (Kd = 0.4 microM) and exhibits a weak ATPase activity. Using an abortive initiation assay, we further show that activation of open complex formation by MalT depends on the presence of ATP in addition to that of maltotriose, the inducer of the maltose system. Similar experiments in which ATP was replaced by ADP or AMP-PNP, a non-hydrolysable analogue of...

  2. Mutant Forms of the Azotobacter vinelandii Transcriptional Activator NifA Resistant to Inhibition by the NifL Regulatory Protein

    OpenAIRE

    Reyes-Ramirez, Francisca; Little, Richard; Dixon, Ray

    2002-01-01

    The Azotobacter vinelandii σ54-dependent transcriptional activator protein NifA is regulated by the NifL protein in response to redox, carbon, and nitrogen status. Under conditions inappropriate for nitrogen fixation, NifL inhibits transcription activation by NifA through the formation of the NifL-NifA protein complex. NifL inhibits the ATPase activity of the central AAA+ domain of NifA required to drive open complex formation by σ54-RNA polymerase and may also inhibit the activator-polymeras...

  3. Nutritional, antioxidant and antitumour properties of Leccinum vulpinum Watling

    OpenAIRE

    Reis, Filipa S.; Sousa, Diana; Barros, Lillian; Martins, Anabela; Morales, Patricia; Vasconcelos, M. Helena; Ferreira, Isabel C. F. R.

    2014-01-01

    Mushrooms are widely appreciated all over the world for their nutritional [1] and bioactive properties [2, 3]. This work characterizes Leccinum vulpinum Watling, an edible mushroom harvested in Bragan

  4. The transcriptional activator GAL4-VP16 regulates the intra-molecular interactions of the TATA-binding protein

    Indian Academy of Sciences (India)

    Anurag Kumar Mishra; Perumal Vanathi; Purnima Bhargava

    2003-06-01

    Binding characteristics of yeast TATA-binding protein (yTBP) over five oligomers having different TATA variants and lacking a UASGAL, showed that TATA-binding protein (TBP)-TATA complex gets stabilized in the presence of the acidic activator GAL4-VP16. Activator also greatly suppressed the non-specific TBP-DNA complex formation. The effects were more pronounced over weaker TATA boxes. Activator also reduced the TBP dimer levels both in vitro and in vivo, suggesting the dimer may be a direct target of transcriptional activators. The transcriptional activator facilitated the dimer to monomer transition and activated monomers further to help TBP bind even the weaker TATA boxes stably. The overall stimulatory effect of the GAL4-VP16 on the TBP-TATA complex formation resembles the known effects of removal of the N-terminus of TBP on its activity, suggesting that the activator directly targets the N-terminus of TBP and facilitates its binding to the TATA box.

  5. Study on HepG-2 apoptosis induced by saponins isolated from Asparagus and the effects on the activities of caspase-3,8,9

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; XU He; JI Chen-feng

    2008-01-01

    Objective To study the effect of saponins of asparagus on apoptosis and the variations of caspaseS, caspase-9 and caspase-3 activity in the process of asparagus induced apoptosis in HepG-2, to investigate the apoptosis mechanism further. Methods Asparagus on apoptosis effects on tumor cells cultured-HepG-2 with different concentrations at different time, IC50 value was measured by MTT assay, the apoptosis rate was determined by FCM with AnnexinV/PI staining, their apoptotic morphology were observed by electron microscopy and Colorimetric method was used to measure caspase-8,9 and caspase-3 activities. Results Experiments of antitumour in vivo showed that saponins of asparagus can inhibit the growth of tumor cell of HepG-2 in evidence, IC50 was 101.15 mg·L-1. Cultured for 72 h, the apoptosis rate had positive increased with concentrations. Apoptotic morphology was observed by electron microscopy. The activities of caspase-8, easpase-9 and caspase-3 had positive increased with concentrations. And have significant difference compared with negative control group(P<0.01). The activities of caspase-8 were high at 24 h, but the activities of caspase-9 and caspase-3 is high at 48 h. Conclusions Aaponins of asparagus can inhibit the growth of tumor cell of HepG2, and the underlying mechanism might be related to up regulation of caspase-8, 9 activity which subsequently transforms caspase-3 into its active form.

  6. Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

    Science.gov (United States)

    Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

    2016-03-23

    Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. PMID:26854381

  7. Further in vitro biological activity evaluation of amino-, thio- and ester-derivatives of avarol.

    Science.gov (United States)

    Tommonaro, Giuseppina; Pejin, Boris; Iodice, Carmine; Tafuto, Antonietta; De Rosa, Salvatore

    2016-08-01

    The acetylcholinesterase inhibitory and/or antitumour activities of amino-, thio- and ester-derivatives of avarol selected were evaluated for the first time at in vitro conditions. Avarol-3',4'-dithioglycol (1) and avarol-4'-(3)mercaptopropionic acid (3) were shown to be the best inhibitors of the enzyme tested (0.50 µg and IC50 0.05 mM and 0.50 µg and IC50 0.12 mM, respectively), while 4'-tryptamine-avarone (9) and avarol-3'-(3)mercaptopropionic acid (2) exhibited the highest cytotoxicity against the human breast T-47D cancer cell line (IC50 0.66 µg/mL and 1.25 µg/mL, respectively). According to experimental data obtained, the sesquiterpenoid hydroquinone structure of bioactive avarol derivatives may inspire development of new pharmacologically useful substances to be used in the treatment of Alzheimer's disease and/or human breast tumour. PMID:26114310

  8. Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models.

    Science.gov (United States)

    Tsimafeyeu, Ilya; Ludes-Meyers, John; Stepanova, Evgenia; Daeyaert, Frits; Kochenkov, Dmitry; Joose, Jean-Baptiste; Solomko, Eliso; Van Akene, Koen; Peretolchina, Nina; Yin, Wei; Ryabaya, Oxana; Byakhov, Mikhail; Tjulandin, Sergei

    2016-07-01

    Alofanib (RPT835) is a novel selective allosteric inhibitor of fibroblast growth factor receptor 2 (FGFR2). We showed previously that alofanib could bind to the extracellular domain of FGFR2 and has an inhibitory effect on FGF2-induced phoshphorylation of FRS2α. In the present study, we further showed that alofanib inhibited phosphorylation of FRS2α with the half maximal inhibitory concentration (IC50) values of 7 and 9 nmol/l in cancer cells expressing different FGFR2 isoforms. In a panel of four cell lines representing several tumour types (triple-negative breast cancer, melanoma, and ovarian cancer), alofanib inhibited FGF-mediated proliferation with 50% growth inhibition (GI50) values of 16-370 nmol/l. Alofanib dose dependently inhibited the proliferation and migration of human and mouse endothelial cells (GI50 11-58 nmol/l) compared with brivanib and bevacizumab. Treatment with alofanib ablated experimental FGF-induced angiogenesis in vivo. In a FGFR-driven human tumour xenograft model, oral administration of alofanib was well tolerated and resulted in potent antitumour activity. Importantly, alofanib was effective in FGFR2-expressing models. These results show that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. PMID:27136102

  9. Poly(ADP-ribose) polymerase-1-induced NAD+ depletion promotes nuclear factor-κB transcriptional activity by preventing p65 de-acetylation

    OpenAIRE

    Kauppinen, Tiina M; Gan, Li; Swanson, Raymond A.

    2013-01-01

    NF-κB is a transcription factor that integrates pro-inflammatory and pro-survival responses in diverse cell types. The activity of NF-κB is regulated in part by acetylation of its p65 subunit at lysine 310,which is required for transcription complex formation. De-acetylation at this site is performed by sirtuin 1(SIRT1) and possibly other sirtuins in an NAD+ dependent manner, such that SIRT1 inhibition promotes NF-κB transcriptional activity. It is unknown, however, whether changes in NAD+ le...

  10. Using molecular docking to investigate the anti-breast cancer activity of low molecular weight compounds present on wild mushrooms.

    Science.gov (United States)

    Froufe, H J C; Abreu, R M V; Ferreira, I C F R

    2011-06-01

    Mushrooms represent an unlimited source of compounds with anti-tumour and immunostimulating properties, and their intake has been shown to reduce the risk of breast cancer. A large number of low molecular weight (LMW) compounds present in mushrooms have been identified, including phenolic acids, flavonoids, tocopherols, carotenoids, sugars and fatty acids. In order to evaluate which wild mushroom LMW compounds may be involved in anti-breast cancer activity we selected a representative dataset of 43 LMW compounds and performed molecular docking against three known protein targets involved in breast cancer (aromatase, estrone sulfatase and 17β-HSD-1) using AutoDock4 as docking software. The estimated inhibition constants for all LMW compounds were determined, and the potential structure-activity relationships for the compounds with the best estimated inhibition constants are discussed for each compound family. 4-O-caffeoylquinic, naringin and lycopene stand out as the top-ranked potential inhibitors for aromatase, estrone sulfatase and 17β-HSD1, respectively, and the 3-D docked conformations for these compounds are discussed in detail. This information provides several interesting starting points for further development of aromatase, estrone sulfatase and 17β-HSD1 inhibitors. PMID:21598196

  11. Evaluation of Antiproliferative Activity of Red Sorghum Bran Anthocyanin on a Human Breast Cancer Cell Line (MCF-7)

    International Nuclear Information System (INIS)

    Breast cancer is a leading cause of death in women worldwide both in the developed and developing countries. Thus effective treatment of breast cancer with potential antitumour drugs is important. In this paper, human breast cancer cell line MCF-7 has been employed to evaluate the antiproliferative activity of red sorghum bran anthocyanin. The present investigation showed that red sorghum bran anthocyanin induced growth inhibition of MCF-7 cells at significant level. The growth inhibition is dose dependent and irreversible in nature. When MCF-7 cells were treated with red sorghum bran anthocyanins due to activity of anthocyanin morphological changes were observed. The morphological changes were identified through the formation of apoptopic bodies. The fragmentation by these anthocyanins on DNA to oligonuleosomal-sized fragments, is a characteristic of apoptosis, and it was observed as concentration-dependent. Thus, this paper clearly demonstrates that human breast cancer cell MCF-7 is highly responsive by red sorghum bran anthocyanins result from the induction of apoptosis in MCF-7 cells.

  12. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.

    Science.gov (United States)

    Estañ, María Cristina; Calviño, Eva; Calvo, Susana; Guillén-Guío, Beatriz; Boyano-Adánez, María Del Carmen; de Blas, Elena; Rial, Eduardo; Aller, Patricio

    2014-01-01

    Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic

  13. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.

    Directory of Open Access Journals (Sweden)

    María Cristina Estañ

    Full Text Available Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox, and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin, in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content, as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the

  14. Creative elements: network-based predictions of active centres in proteins, cellular and social networks

    CERN Document Server

    Csermely, Peter

    2008-01-01

    Active centres and hot spots of proteins have a paramount importance in enzyme action, protein complex formation and drug design. Recently a number of publications successfully applied the analysis of residue networks to predict active centres in proteins. Most real-world networks show a number of properties, such as small-worldness or scale-free degree distribution, which are rather general features of networks from molecules to the society. Based on extensive analogies I propose that the existing findings and methodology enable us to detect active centres in cells, social networks and ecosystems. Members of these active centres are creative elements of the respective networks, which may help them to survive unprecedented, novel challenges, and play a key role in the development, survival and evolvability of complex systems.

  15. Polymeric Switch on Lysozyme Activity: Role of Hydrophobic and Electrostatic Interactions

    Directory of Open Access Journals (Sweden)

    Dr. Sumon Ganguli

    2013-07-01

    Full Text Available Enzymes have attracted potential applications in both medicine and biotechnology. In our present study, we show a strategy for switching the enzymatic activity of lysozyme by the complex formation with a cationic smart copolymer. PAMA-g-PEG graft copolymers suppressed the enzymatic activity of lysozyme without any conformational change, indicating the formation of complex and covering the active site of lysozyme by copolymers. The addition of polyanion, poly(acrylic acid (PAAc, recovered the suppressed enzymatic activity of the lysozyme/polymer complex efficiently. These finding suggest that that hydrophobic interaction coupled with electrostatic interactions has a great role for the complexation and decomplexation of the lysozyme/polymer complex. Circular dichroism (CD spectral analysis indicated that the conformation of the enzymes maintained largely during the course of the complexation.

  16. [Structure and Activity of Fungal Lipases in Bile Salt Solutions].

    Science.gov (United States)

    Bogdanova, L R; Bakirova, D R; Valiullina, Yu A; Idiyatullin, B Z; Faizullin, D A; Zueva, O S; Zuev, Yu F

    2016-01-01

    The changes in structure and catalytic properties of fungal lipases (Candida rugosa, Rhizomucor miehei, Mucor javanicus) were investigated in micellar solutions of bile salts that differ in hydrophilic-lypophilic balance and reaction medium properties. The methods of circular dichroism and tryptophan fluorescence were applied to estimate the changes in peptide structure within complexes with bile salt micelles. Bile salts do not exert a significant influence on the structure of the enzymes under study: in Rh. miehei and M. javanicus lipases the alpha helix content slightly decreased, the influence of bile salts on the C. rugosa structure was not revealed. Despite negligible structural modifications in the enzymes, in bile salt solutions a considerable change in their catalytic properties was observed: an abrupt decrease in catalytic effectiveness. Substrate-bile salts micelles complex formation was demonstrated by the NMR self-diffusion method. The model of a regulation of fungal lipase activity was proposed. PMID:27192825

  17. Kinetics and mechanism of interaction of some bioactive ligands with cis-diaqua(cis-1,2-diaminocyclohexane)platinum(II) in aqueous medium

    Indian Academy of Sciences (India)

    P Karmakar; S Ray; S Mallick; B K Bera; A Mandal; S Mondal; A K Ghosh

    2013-09-01

    The substitution reaction of cis-[Pt(cis-dach)(H2O)2]2+ (where `dach’ is cis-1,2-diaminocyclohexane) with 2-thiouracil (S, N), 1,2-cyclohexanedionedioxime (N, N) and acetylacetone (O, O) were studied in aqueous solution in 0.10 M NaClO4 under pseudo-first order conditions as a functions of concentration, pH and temperature using UV-Vis spectrophotometry. The substitution reaction proceeds via rapid outer sphere association complex formation, followed by two slow consecutive steps. The first of these involves ligand-assisted deaquation, while second involves chelation as the second aqua ligand is displaced. The association equilibrium constant (KE) for the outer sphere complex formation has been evaluated together with rate constants for the two subsequent steps. The rate constants increase with increasing ligand concentration and the evaluated activation parameters for all reactions suggest an associative substitution mechanism for both the aqua ligand substitution processes. The product of the reaction has been characterized by IR, NMR and ESI-MS spectral analysis; which throws more light on the mechanistic behaviour of platinum(II) antitumour complexes.

  18. In search of uracil derivatives as bioactive agents. Uracils and fused uracils: Synthesis, biological activity and applications.

    Science.gov (United States)

    Pałasz, Aleksandra; Cież, Dariusz

    2015-06-01

    This review article is an effort to summarize recent developments in researches providing uracil derivatives with promising biological potential. This article also aims to discuss potential future directions on the development of more potent and specific uracil analogues for various biological targets. Uracils are considered as privileged structures in drug discovery with a wide array of biological activities and synthetic accessibility. Antiviral and anti-tumour are the two most widely reported activities of uracil analogues however they also possess herbicidal, insecticidal and bactericidal activities. Their antiviral potential is based on the inhibition of key step in viral replication pathway resulting in potent activities against HIV, hepatitis B and C, the herpes viruses etc. Uracil derivatives such as 5-fluorouracil or 5-chlorouracil were the first pharmacological active derivatives to be generated. Poor selectivity limits its therapeutic application, resulting in high incidences of gastrointestinal tract or central nervous toxicity. Numerous modifications of uracil structure have been performed to tackle these problems resulting in the development of derivatives exhibiting better pharmacological and pharmacokinetic properties including increased bioactivity, selectivity, metabolic stability, absorption and lower toxicity. Researches of new uracils and fused uracil derivatives as bioactive agents are related with modifications of substituents at N(1), N(3), C(5) and C(6) positions of pyrimidine ring. This review is an endeavour to highlight the progress in the chemistry and biological activity of the uracils, predominately after the year 2000. In particular are presented synthetic methods and biological study for such analogues as: 5-fluorouracil or 5-chlorouracil derivatives, tegafur analogues, arabinopyranonucleosides of uracil, glucopyranonucleosides of uracil, liposidomycins, caprazamycins or tunicamycins, tritylated uridine analogues, nitro or cyano

  19. Kinetics and mechanism of reductive elimination of dimethyl Pt(4) complex in aqueous solutions. Decomposition of Cs2Pt(CH3)2Cl4 as the independent route of generation of intermediates of alkane activation by Pt(2)

    International Nuclear Information System (INIS)

    Unconventional method for formation of ethane during decomposition of Pt(4)(CH3)2 in aqueous solutions is revealed: the breaking of C-H bond is prefixed to the reducing elimination of C2H6. The intermediates of dimethylplatinum(4) decomposition was demonstrated to be identical to the intermediates formed during activation of alkanes (ethane) of Pt(2). The activation mechanism involving oxidizing addition of the alkanes to Pt(2) with Pt(4) alkylhydride complexes formation was suggested. 24 refs., 3 figs., 2 tabs

  20. Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity.

    Science.gov (United States)

    Kathum, Omer Abid; Schräder, Tobias; Anhlan, Darisuren; Nordhoff, Carolin; Liedmann, Swantje; Pande, Amit; Mellmann, Alexander; Ehrhardt, Christina; Wixler, Viktor; Ludwig, Stephan

    2016-06-01

    Phosphorylation and dephosphorylation acts as a fundamental molecular switch that alters protein function and thereby regulates many cellular processes. The non-structural protein 1 (NS1) of influenza A virus is an important factor regulating virulence by counteracting cellular immune responses against viral infection. NS1 was shown to be phosphorylated at several sites; however, so far, no function has been conclusively assigned to these post-translational events yet. Here, we show that the newly identified phospho-site threonine 49 of NS1 is differentially phosphorylated in the viral replication cycle. Phosphorylation impairs binding of NS1 to double-stranded RNA and TRIM25 as well as complex formation with RIG-I, thereby switching off its interferon antagonistic activity. Because phosphorylation was shown to occur at later stages of infection, we hypothesize that at this stage other functions of the multifunctional NS1 beyond its interferon-antagonistic activity are needed. PMID:26687707

  1. LPS induces pulp progenitor cell recruitment via complement activation.

    Science.gov (United States)

    Chmilewsky, F; Jeanneau, C; Laurent, P; About, I

    2015-01-01

    Complement system, a major component of the natural immunity, has been recently identified as an important mediator of the dentin-pulp regeneration process through STRO-1 pulp cell recruitment by the C5a active fragment. Moreover, it has been shown recently that under stimulation with lipoteichoic acid, a complex component of the Gram-positive bacteria cell wall, human pulp fibroblasts are able to synthesize all proteins required for complement activation. However, Gram-negative bacteria, which are also involved in tooth decay, are known as powerful activators of complement system and inflammation. Here, we investigated the role of Gram-negative bacteria-induced complement activation on the pulp progenitor cell recruitment using lipopolysaccharide (LPS), a major component of all Gram-negative bacteria. Our results show that incubating pulp fibroblasts with LPS induced membrane attack complex formation and C5a release in serum-free fibroblast cultures. The produced C5a binds to the pulp progenitor cells' membrane and induces their migration toward the LPS stimulation chamber, as revealed by the dynamic transwell migration assays. The inhibition of this migration by the C5aR-specific antagonist W54011 indicates that the pulp progenitor migration is mediated by the interaction between C5a and C5aR. Our findings demonstrate, for the first time, a direct interaction between the recruitment of progenitor pulp cells and the activation of complement system generated by pulp fibroblast stimulation with LPS. PMID:25359783

  2. Polycyclic Xanthone Natural Products: Structure, Biological Activity and Chemical Synthesis

    OpenAIRE

    Winter, Dana K.; Sloman, David L.; Porco, John A.

    2013-01-01

    Polycyclic xanthone natural products are a family of polyketides which are characterized by highly oxygenated, angular hexacyclic frameworks. In the last decade, this novel class of molecules has attracted noticeable attention from the synthetic and biological communities due to emerging reports of their potential use as antitumour agents. The aim of this article is to highlight the most recent developments of this subset of the xanthone family by detailing the innate challenges of the constr...

  3. Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL.

    Science.gov (United States)

    Eydmann, T; Söderbäck, E; Jones, T; Hill, S; Austin, S; Dixon, R

    1995-03-01

    The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch. PMID:7868590

  4. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    International Nuclear Information System (INIS)

    Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells

  5. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Garrido Federico

    2008-03-01

    Full Text Available Abstract Background Protein-bound polysaccharide (PSK is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

  6. Complex formation in the Ru(3)-HCl-DMSO-sorbent system as determined by EPR

    International Nuclear Information System (INIS)

    The Ru(3) compounds, formed in hydrochloric solutions in the presence of dimethylsulphoxide (DMSO), are studied by the EPR method. It is established that depending on the HCl concentration the [Ru(DMSO)Cl5]2-, trans-[Ru(DMSO)3Cl3] complexes are formed. Ruthenium (3) is extracted from the HCl-DMSO solutions through AB-14 anionite and complex-forming sorbent POLYORGS-4 primarily in the [(R)nNH3O+]2[Ru(DMSO)Cl5] and [CR)nNH+]2[Ru(DMSO)Cl5] forms depending on the sorbent moisture content and initial solution acidity. The ligands crystal field parameters are calculated for all complexes and it is shown that the DMSO ligand, coordinated through sulphur, is characterized by high acceptor capacity

  7. The Effect of Complex Formation upon the Redox Potentials of Metallic Ions. Cyclic Voltammetry Experiments.

    Science.gov (United States)

    Ibanez, Jorge G.; And Others

    1988-01-01

    Describes experiments in which students prepare in situ soluble complexes of metal ions with different ligands and observe and estimate the change in formal potential that the ion undergoes upon complexation. Discusses student formation and analysis of soluble complexes of two different metal ions with the same ligand. (CW)

  8. EFFECT OF COMPLEX FORMATION ON ELECTROCHEMICAL BEHAVIOUR OF METAL-CONTAINING WASTE WATERS

    OpenAIRE

    Olga Covaliova

    2009-01-01

    The problem of preventing the heavy metals and other toxic substances release in environment due to the discharges of untreated plating and rinsing solutions is actual from both ecologic and economic point of view. It is crucial to prevent the environmental pollution and uncontrolled losses of resources (metals and other substances). The treatment technologies used today are not always efficient and cost saving and in some cases they may even provoke the secondary pollution of environment....

  9. Calculating the contribution of different binding modes to Quinacrine - DNA complex formation from polarized fluorescence data

    CERN Document Server

    Voloshin, Igor; Karachevtsev, Victor; Zozulya, Victor

    2013-01-01

    Binding of acridine derivative quinacrine (QA) to chicken erythrocyte DNA was studied by methods of absorption and polarized fluorescent spectroscopy. Measurements were carried out in aqueous buffered solutions (pH 6.9) of different dye concentrations (QA concentration range from $10^{-6}$ till $10^{-4}$ M) and ionic strengths ($Na^{+}$ concentration rang from $10^{-3}$ till 0.15 M) in a wide range of phosphate-to-dye molar ratios ($P/D$). It is established that the minimum of fluorescent titration curve plotted as relative fluorescence intensity $vs$ $P/D$ is conditioned by the competition between the two types of QA binding to DNA which posses by different emission parameters: (i) intercalative one dominating under high $P/D$ values, and (ii) outside electrostatic binding dominating under low $P/D$ values, which is accompanied by the formation of non-fluorescent dye associates on the DNA backbone. Absorption and fluorescent characteristics of complexes formed were determined. The method of calculation of di...

  10. Ganglioside-magnetosome complex formation enhances uptake of gangliosides by cells

    Directory of Open Access Journals (Sweden)

    Guan F

    2015-11-01

    Full Text Available Feng Guan,1 Xiang Li,1 Jia Guo,1 Ganglong Yang,1 Xiang Li2 1The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, 2Wuxi Medical School, Jiangnan University, Wuxi, People’s Republic of China Abstract: Bacterial magnetosomes, because of their nano-scale size, have a large surface-to-volume ratio and are able to carry large quantities of bioactive substances such as enzymes, antibodies, and genes. Gangliosides, a family of sialic acid-containing glycosphingolipids, function as distinctive cell surface markers and as specific determinants in cellular recognition and cell-to-cell communication. Exogenously added gangliosides are often used to study biological functions, transport mechanisms, and metabolism of their endogenous counterparts. Absorption of gangliosides into cells is typically limited by their tendency to aggregate into micelles in aqueous media. We describe here a simple strategy to remove proteins from the magnetosome membrane by sodium dodecyl sulfate treatment, and efficiently immobilize a ganglioside (GM1 or GM3 on the magnetosome by mild ultrasonic treatment. The maximum of 11.7±1.2 µg GM1 and 11.6±1.5 µg GM3 was loaded onto 1 mg magnetosome, respectively. Complexes of ganglioside-magnetosomes stored at 4°C for certain days presented the consistent stability. The use of GM1-magnetosome complex resulted in the greatest enhancement of ganglioside incorporation by cells. GM3-magnetosome complex significantly inhibited EGF-induced phosphorylation of the epidermal growth factor receptor. Both of these effects were further enhanced by the presence of a magnetic field. Keywords: bacterial magnetosome, nanoparticle, cellular uptake, ganglioside, inhibition

  11. Influence of complex formation on extraction of some fission products by sorption on inorganic sorbents

    International Nuclear Information System (INIS)

    Sorption of fission products of radionuclides 137Cs, 89,90Sr, 90,91Y, 86Rb, 133Ba, 95Zr+95Nb, 95Nb, 103,106Ru, 141,144Ce, 115mCd, 113Sn, 125Sb by hydroxides Fe(III), Mn(IV) on the background of 1 mol/l of NaNO3 at the pretense of ions SO42-, C2O42- at a wide ph range (1+14) is studied in present work. Optimal conditions of extraction of each radionuclide by sorption on inorganic sorbents are defined.

  12. Ligand Conformational and Solvation/Desolvation Free Energy in Protein-Ligand Complex Formation

    Czech Academy of Sciences Publication Activity Database

    Kolář, Michal; Fanfrlík, Jindřich; Hobza, Pavel

    2011-01-01

    Roč. 115, č. 16 (2011), s. 4718-4724. ISSN 1520-6106 R&D Projects: GA MŠk LC512; GA ČR GAP208/11/0295 Grant ostatní: Korea Science and Engineering Foundation(KR) R32-2008-000-10180-0; European Science Fund(XE) CZ.1.05/2.1.00/03.0058 Institutional research plan: CEZ:AV0Z40550506 Keywords : solvation free energy * SMD * HIV protease inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.696, year: 2011

  13. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis.

    Directory of Open Access Journals (Sweden)

    Yong-Hyun Shin

    2010-11-01

    Full Text Available Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1(-/ (- testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1(-/ (- testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/ (- ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1(-/ (- oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

  14. Influence of the Hydrophobicity of Polyelectrolytes on Polyelectrolyte Complex Formation and Complex Particle Structure and Shape

    OpenAIRE

    Gudrun Petzold; Andreas Janke; Stefan Zschoche; Simona Schwarz; Mandy Mende

    2011-01-01

    Polyelectrolyte complexes (PECs) were prepared by structural uniform and strongly charged cationic and anionic modified alternating maleic anhydride copolymers. The hydrophobicity of the polyelectrolytes was changed by the comonomers (ethylene, isobutylene and styrene). Additionally, the n−/n+ ratio of the molar charges of the polyelectrolytes and the procedure of formation were varied. The colloidal stability of the systems and the size, shape, and structure of the PEC particles were investi...

  15. Mechanisms of defect complex formation and environmental-assisted fracture behavior of iron aluminides

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, B.R.; Muratov, L.S.; Kang, B.S.J.; Li, K.Z. [West Virginia Univ., Morgantown, WV (United States)

    1997-12-01

    Iron aluminide has excellent corrosion resistance in high-temperature oxidizing-sulfidizing environments; however, there are problems at room and medium temperature with hydrogen embrittlement as related to exposure to moisture. In this research, a coordinated computational modeling/experimental study of mechanisms related to environmental-assisted fracture behavior of selected iron aluminides is being undertaken. The modeling and the experimental work will connect at the level of coordinated understanding of the mechanisms for hydrogen penetration and for loss of strength and susceptibility to fracture. The focus of the modeling component at this point is on the challenging question of accurately predicting the iron vacancy formation energy in Fe{sub 3}A{ell} and the subsequent tendency, if present, for vacancy clustering. The authors have successfully performed, on an ab initio basis, the first calculation of the vacancy formation energy in Fe{sub 3}A{ell}. These calculations include lattice relaxation effects which are quite large. This has significant implications for vacancy clustering effects with consequences to be explored for hydrogen diffusion. The experimental work at this stage has focused on the relationship of the choice and concentration of additives to the improvement of resistance to hydrogen embrittlement and hence to the fracture behavior. For this reason, comparative crack growth tests of FA-186, FA-187, and FA-189 iron aluminides (all with basic composition of Fe-28A{ell}-5Cr, at % with micro-alloying additives of Zr, C or B) under, air, oxygen, or water environment have been performed. These tests showed that the alloys are susceptible to room temperature hydrogen embrittlement in both B2 and DO{sub 3} conditions. Test results indicated that FA-187, and FA-189 are intrinsically more brittle than FA-186.

  16. SOHLH2 is essential for synaptonemal complex formation during spermatogenesis in early postnatal mouse testes

    OpenAIRE

    Miree Park; Youngeun Lee; Hoon Jang; Ok-Hee Lee; Sung-Won Park; Jae-Hwan Kim; Kwonho Hong; Hyuk Song; Se-Pill Park; Yun-Yong Park; Jung Jae Ko; Youngsok Choi

    2016-01-01

    Spermatogenesis- and oogenesis-specific helix-loop-helix transcription factor 2 (SOHLH2) is exclusively expressed in germ cells of the gonads. Previous studies show that SOHLH2 is critical for spermatogenesis in mouse. However, the regulatory mechanism of SOHLH2 during early spermatogenesis is poorly understood. In the present study, we analyzed the gene expression profile of the Sohlh2-deficient testis and examined the role of SOHLH2 during spermatogenesis. We found 513 genes increased in ab...

  17. Spectrophotometric determination of terbutaline sulphate and tetracycline hydrochloride via ion pair complex formation using eosin y

    International Nuclear Information System (INIS)

    A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of terbutaline sulphate and tetracycline hydrochloride drugs in pure form and pharmaceutical formulations. The proposed method is based on the formation of binary complexes between these drugs and eosin Y in aqueous acetate buffered medium. Under the optimum conditions, the binary complexes showed absorption maxima at 545 nm. Beer's law was rectilinear over concentration range of 0.5-10 and 5-45 micro g/mL, R/sub 2/ were 0.9984 and 0.9988, RSD were 0.72 and 0.19 (n=5) with average recovery 101.42 % and 100.08 % and the average recovery values of pharmaceutical formulations 101.48 and 98.01 for above drugs respectively. The limit of detection (LOD) were 0.030 and 0.613 micro g/mL and limit of quantitation (LOQ) were 0.103 and 2.00 micro g/mL with molar absorptivity values 3.169 10/sup 3/ and 6.347 10/sup 3/l. mol/sup -1/. Cm/sup -1/ and the relative standard deviation values 0.720 and 0.19 for both drugs respectively. No interference was observed from the excipients that are commonly present in pharmaceutical formulations. The proposed method was successfully applied to the analysis of terbutaline sulphate tablet and tetracycline hydrochloride capsule in their dosage forms. (author)

  18. Complex formation of uranyl acetate with tetracycline and its utilization for their microdetermination

    International Nuclear Information System (INIS)

    Conductometric and spectrophotometric (covering the visible, uv, and ir ranges) studies as well as microanalyses of uranyl complexes with tetracycline revealed the existence of the 1:1 complex species. The mean stability constant of the 1:1 complex, as determined spectrophotometrically, amounted to 1.2 x 105. This finding permits the use of the procedure for the microdetermination of tetracycline using UO2+2 ion or vice versa. (U.S.)

  19. Thermodynamics of Zn2+ ions complex formation with single-stranded polyi in neutral solution

    Czech Academy of Sciences Publication Activity Database

    Usenko, E. L.; Valeev, V. A.; Andrushchenko, Valery; Sorokin, V. A.

    Kharkiv : National Academy of Sciences of Ukraine, 2014. [Kharkiv Young Scientists Confernce on Radiophysics, Electronics, Photonics and Biophysics /14./. 14.10.2014-17.10.2014, Kharkiv] Institutional support: RVO:61388963 Keywords : nucleic acid metallization * zinc ion * differential UV spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry

  20. Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

    Directory of Open Access Journals (Sweden)

    Zong Guan

    2014-04-01

    Full Text Available Deprotonation of indazolium salts at low temperatures gives N-heterocyclic carbenes of indazoles (indazol-3-ylidenes which can be trapped as rhodium complexes (X-ray analysis. In the absence of Rh, the indazol-3-ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis. Results of DFT calculations are presented.

  1. Complexometric determination: Part I - EDTA and complex formation with the Cu2+ ion

    OpenAIRE

    Rajković Miloš B.

    2002-01-01

    Compounds forming very stable complexes - chelates, have a wide field of application in analytical chemistry. The most famous group of these compounds are complexons. Complexons represent organic polyaminocarbonic acids as for example ethylenediaminetetraacetic acid (EDTA) and its salts. The EDTA molecule has six coordinative sites. It is a hexadentate ligands i.e. it has two binding nitrogen atoms and four oxygen atoms from carboxyl groups and it forms complexes with almost all metal ions. E...

  2. Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

    DEFF Research Database (Denmark)

    Peters, C; Bayer, M J; Bühler, S;

    2001-01-01

    SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodu......SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2......+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans...

  3. Multicomponent complex formation between pyrimethamine, cyclodextrins and water-soluble polymers

    Directory of Open Access Journals (Sweden)

    Leticia Norma Carpentieri Rodrigues

    2011-10-01

    Full Text Available The combined effect of hydroxypropyl-β-cyclodextrin (HPβCD and polyvinylpyrrolidone (PVP or sodium carboxymethylcellulose (CMC on the solubility of pyrimethamine (PYR was studied. Equimolar PYR-HPβCD solid systems, in the presence or the absence of 0.25% (w/v PVP or 0.10% (w/v CMC were prepared by coevaporation or freeze-drying, and characterized by differential scanning calorimetry, X-ray diffraction analysis and dissolution profile. Phase-solubility analysis was used to investigate the interactions in aqueous solution between PYR and HPβCD, in the absence or presence of polymers, which showed a linear increase of PYR solubility depending on the concentration of HPβCD. The presence of polymer did not alter the stoichiometry of the complexes. DSC results were indicative of complexation, due to the loss of the characteristic endothermic peak of PYR. X-ray diffraction analysis confirmed the DSC results. Binary and ternary complexes showed higher dissolution rate when compared with the pure drug.

  4. Protein Complex Formation: Computational Clarification of the Sequential versus Probabilistic Recruitment Puzzle

    OpenAIRE

    Schölling, Manuel; Thurner, Stefan; Hanel, Rudolf

    2013-01-01

    Our current view on how protein complexes assemble and disassemble at promoter sites is based on experimental data. For instance this data is provided by biochemical methods (e.g. ChIP-on-chip assays) or GFP-based assays. These two approaches suggest very different characteristics for protein recruitment processes that regulate and initiate gene transcription. Biochemical methods suggest a strictly ordered and consecutive protein recruitment while GFP-based assays draw a picture much closer t...

  5. Thermoacoustical analysis of solutions of poly(ethylene glycol) 200 through H-bond complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Yasmin, Maimoona, E-mail: myasmin908@gmail.com [Department of Physics, University of Lucknow, Lucknow 226007 (India); Gupta, Manisha, E-mail: guptagm@rediffmail.com [Department of Physics, University of Lucknow, Lucknow 226007 (India)

    2011-05-10

    Research highlights: {yields} The presence of two electronegative elements viz. nitrogen and oxygen in its molecular architecture, ethanolamine has greater extent of interaction with PEG. {yields} Ethanolamine and m-cresol may be involved in a complex type of network of hydrogen bonding. {yields} Ethanolamine has greater extent of interaction with PEG than m-cresol and aniline particularly with least magnitude from aniline, where electron availability is least because of delocalization. {yields} The difference in molar volume between the components of the mixture control the mixture properties. - Abstract: Densities ({rho}) and ultrasonic velocities (u) of binary mixtures of poly(ethylene glycol) 200, PEG, with ethanolamine, m-cresol and aniline have been measured at various concentrations at 293.15, 303.15 and 313.15 K and have been fitted by third order polynomial equations at each temperature. The calculated values of isentropic compressibility (k{sub s}), free volume (V{sub f}), internal pressure ({pi}{sub i}), relaxation time ({tau}) and surface tension ({sigma}) at different mole fractions of PEG have been used to explain the hydrogen bonding and intermolecular interactions present in the mixture. Using these data, excess molar volume (V{sup E}), excess intermolecular free length (L{sub f}{sup E}), excess acoustic impedance (Z{sup E}) and excess pseudo-Grueneisen parameter ({Gamma}{sup E}) have been calculated and the results have been fitted to Redlich-Kister polynomial equation. All the results support each other and help in understanding the interactions in the mixture. Various models and mixing rules have been applied to evaluate the ultrasonic velocity data and have been compared with the experimental results.

  6. The complex formation of selected actinides (U, Np, Cm) with microbial ligands

    International Nuclear Information System (INIS)

    One of the urgent tasks in the field of nuclear technology is the final storage of radioactive substances. As a part of the safety requirements the protection of humans and the environment from the danger of radioactive substances in case of the release from the final storage is essential. For performing long-term safety calculations the detailed understanding of the physico-chemical effects and influences which cause the mobilisation and transport of actinides are necessary. The presented work was a discrete part of a project, which was focused on the clarification of the influence of microorganisms on the migration of actinides in case of the release of actinides from a final storage. The influence of microbial produced substances on the mobilisation of selected actinides was studied thereby. The microbial produced substances studied in this project were synthesized by bacteria from the Pseudomonas genus under special conditions. Fluorescent Pseudomonads secrete bacterial pyoverdin-type siderophores with a high potential to complex and transport metals, especially iron(III). The aim of the project was to determine how and under which conditions the bioligands are able to complex also radioactive substances and therefore to transport them. For this work the alpha-emitting actinides uranium, curium and neptunium were chosen because their long-life cycle and their radiotoxicity are a matter of particular interest. This work dealed with the interaction of the actinides U(VI), Np(V) and Cm(III) with model ligands simulating the functionality of the pyoverdins. So, such bioligands can essentially influence the behaviour of actinides in the environment. The results of this work contribute to a better understanding and assessment of the influence of the microbial ligands to the mobilisation and migration of the radionuclides. The outcomes could be used to quantify the actinide-mobilising effect of the bioligands, which are released, for example, in the vicinity of a nuclear waste disposal site.

  7. Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation

    DEFF Research Database (Denmark)

    Liu, Wei; Kavaliauskas, Darius; Schrader, Jared;

    2014-01-01

    The universally conserved translation elongation factor EF-Tu delivers aminoacyl(aa)-tRNA in the form of an aa-tRNA·EF-Tu·GTP ternary complex (TC) to the ribosome where it binds to the cognate mRNA codon within the ribosomal A-site, leading to formation of a pretranslocation (PRE) complex. Here w...... screening of ribosomal antibiotics...... effects of the misreading-inducing antibiotics streptomycin and paromomycin on tRNA selection at the A-site, and (iii) how strengthening the binding of aa-tRNA to EF-Tu affects the rate of EF-Tu movement away from L11 on the ribosome. These FRET assays have the potential to be adapted for high throughput...

  8. Polyphenol-aluminum complex formation: Implications for aluminum tolerance in plants

    Science.gov (United States)

    Natural polyphenols may play an important role in aluminum detoxification in some plants. We examined the interaction between Al3+ and the purified high molecular weight polyphenols pentagalloyl glucose (940 Da) and oenothein B (1568 Da), and the related compound methyl gallate (184 Da) at pH 4 and ...

  9. Spectroscopic studies on U(VI)-salicylate complex formation with multiple equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Cha, W.; Cho, H.R.; Jung, E.C.; Park, K.K.; Kim, W.H.; Song, K. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of). Nuclear Chemistry Research Div.

    2012-07-01

    This study investigates multiple equilibria related to the formation of the U(VI)-salicylate complex in a pH range of 3.0-5.5 using UV-Vis absorption and fluorescence measurement techniques. The absorbance changes at the characteristic charge-transfer bands of the complex were monitored, and the results indicated the presence of multiple equilibria and the formation of both 1:1 and 1:2 (U(VI):salicylate) complexes possessing bi-dentate chelate structures. The determined step-wise formation constants (log K{sub 1:1} and log K{sub 1:2}) are as follows: 12.5 {+-} 0.1 and 11.4 {+-} 0.2 for salicylate, 11.2 {+-} 0.1 and 10.1 {+-} 0.2 for 5-sulfosalicylate, and 12.4 {+-} 0.1 and 11.4 {+-} 0.1 for 2,6-dihydroxybenzoate, respectively. The molar absorptivities of the complexes are also provided. Furthermore, time-resolved laser-induced luminescence spectra of U(VI) species demonstrate the presence of both a dynamic and static quenching process upon the addition of a salicylate ligand. Particularly for the luminescent hydroxouranyl species, a strong static quenching effect is observed. The results suggest that both the UO{sub 2}(HSal){sup +} and the U(VI)-Sal chelate complexes serve as ground-state complexes that induce static quenching. The Stern-Volmer parameters were derived based on the measured luminescent intensity and lifetime data. The static quenching constants (log K{sub S}) obtained are 3.3 {+-} 0.1, 4.9 {+-} 0.1, and 4.4 {+-} 0.1 for UO{sub 2}{sup 2+}, (UO{sub 2}){sub 2}(OH){sub 2}{sup 2+} and (UO{sub 2}){sub 3}(OH){sub 5}{sup +}, respectively. (orig.)

  10. Complex formation of Cm(III) with formate studied by time-resolved laser fluorescence spectroscopy

    International Nuclear Information System (INIS)

    Highlights: • Cm(III) complexation with formate is investigated at T = 20–90 °C. • The impact of formate on Cm(III) speciation increases with increasing temperature. • The complexation reactions of Cm(III) with formate are endothermic/entropy-driven. - Abstract: Pore waters of natural clays, which are investigated as potential host rock formations for high-level nuclear waste, are known to contain large amounts of low-molecular weight organic compounds. These small organic ligands might impact the aqueous geochemistry of the stored radionuclides and, thus, their migration behavior. In the present work, the complexation of Cm(III) with formate in aqueous NaCl solution is investigated by time-resolved laser fluorescence spectroscopy (TRLFS) as a function of the ionic strength (0.5–3.0 mol/kg), the ligand concentration (0–0.2 mol/kg) and the temperature (20–90 °C). The Cm(III) speciation is determined by deconvolution of the emission spectra. The obtained distribution of Cm(III) species is used to calculate the conditional stability constants (log K′(T)) at a given temperature and ionic strength which are extrapolated to zero ionic strength by using the specific ion interaction theory (SIT). Thus, the thermodynamic log K0n(T) values for the formation of [Cm(Form)n](3−n)+ (n = 1, 2) and the ion interaction coefficients (ε(i,k)) for [Cm(Form)n](3−n)+ (n = 1, 2) with Cl− are obtained. The log K01(T) (2.11 (20 °C)–2.49 (90 °C)) and log K02(T) values (1.17 (30 °C–2.01 (90 °C)) increase continuously with increasing temperature. The log K0n(T) values are used to derive the standard reaction enthalpies and entropies (ΔrH0m, ΔrS0m) of the respective complexation reactions according to the Van’t Hoff equation. In all cases, positive ΔrH0m and ΔrS0m values are obtained. Thus, both complexation steps are endothermic and entropy-driven

  11. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    International Nuclear Information System (INIS)

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates

  12. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    Energy Technology Data Exchange (ETDEWEB)

    Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Ionov, Maksim [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 Route de Narbonne, F-31077 Toulouse cedex 4 (France); Muñoz-Fernández, Maria Angeles [Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Bryszewska, Maria [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland)

    2014-04-15

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates.

  13. Conformational Heterogeneity in Antibody-Protein Antigen Recognition IMPLICATIONS FOR HIGH AFFINITY PROTEIN COMPLEX FORMATION

    Czech Academy of Sciences Publication Activity Database

    Addis, P. W.; Hall, c. J.; Bruton, S.; Veverka, Václav; Wilkinson, I. C.; Muskett, F. W.; Renshaw, P. S.; Prosser, C. E.; Carrington, B.; Lawson, A. D. G.; Griffin, R.; Taylor, R. J.; Waters, L. C.; Henry, A. J.; Carr, M. D.

    2014-01-01

    Roč. 289, č. 10 (2014), s. 7200-7210. ISSN 0021-9258 Institutional support: RVO:61388963 Keywords : NMR * antibody * protein-protein interaction * protein conformation Subject RIV: CE - Biochemistry Impact factor: 4.573, year: 2014

  14. Lattice constant variation and complex formation in zincblende gallium manganese arsenide

    Science.gov (United States)

    Schott, G. M.; Faschinger, W.; Molenkamp, L. W.

    2001-09-01

    We perform high resolution x-ray diffraction on GaMnAs mixed crystals as well as on GaMnAs/GaAs and GaAs/MnAs superlattices for samples grown by low-temperature molecular-beam epitaxy under different growth conditions. Although all samples are of high crystalline quality and show narrow rocking curve widths and pronounced finite thickness fringes, the lattice constant variation with increasing manganese concentration depends strongly on the growth conditions: For samples grown at substrate temperatures of 220 and 270 °C, the extrapolated relaxed lattice constant of Zincblende MnAs is 0.590 nm and 0.598 nm, respectively. This is in contrast to low-temperature GaAs, for which the lattice constant decreases with increasing substrate temperature.

  15. Lattice constant variation and complex formation in zincblende Gallium Manganese Arsenide

    OpenAIRE

    Schott, G. M.; Faschinger, W.; Molenkamp, L.W.

    2001-01-01

    We perform high resolution X-ray diffraction on GaMnAs mixed crystals as well as on GaMnAs/GaAs and GaAs/MnAs superlattices for samples grown by low temperature molecular beam epitaxy under different growth conditions. Although all samples are of high crystalline quality and show narrow rocking curve widths and pronounced finite thickness fringes, the lattice constant variation with increasing manganese concentration depends strongly on the growth conditions: For samples grown at substrate te...

  16. Imaging inclusion complex formation in starch granules using confocal laser scanning microscopy

    NARCIS (Netherlands)

    Manca, Marianna; Woortman, Albert J. J.; Loos, Katja; Loi, Maria A.

    2015-01-01

    The tendency of amylose to form inclusion complexes with guest molecules has been an object of wide interest due to its fundamental role in food processing. Here we investigated the features of starch granules from several botanical sources using confocal laser scanning microscopy (CLSM) and uncover

  17. Encapsulation of nabumetone by means of -drug: (β-cyclodextrin)2:polyvinylpyrrolidone ternary complex formation

    International Nuclear Information System (INIS)

    The aim of the present study was to investigate the effect of the presence of the water-soluble polymer polyvinylpyrrolidone (PVP) MW=24,000 g/mol, on the complexing of the anti-inflammatory drug nabumetone, with β-cyclodextrin (β-CD). The data show that the polymer interacts with the free nabumetone and with the nabumetone:β-CD inclusion complex, in both cases with a stoichiometry of 1:1. The interaction constants are 1.3x104 M-1 and 1.6x104 M-1, respectively. The presence of PVP, changes the drug:cyclodextrin interaction, a nabumetone:(β-CD)2:PVP complex being formed. In addition, the presence of PVP, produces a strong increase in the global binding constant, β 2=(22.12±0.22)x106 M-2 at 1% PVP. In the ternary complex, the nabumetone is wrapped at both ends for the β-CD. In this complex the polymer seems to act as a bridge between both β-CD molecules that bind the nabumetone

  18. [The study of complex-formation of DNA with the antimicrobial drug decamethoxine].

    Science.gov (United States)

    Sorokin, V A; Blagoĭ, Iu P; Valeev, V A; Gladchenko, G O; Sukhodub, L F; Volianskiĭ, Iu L

    1990-01-01

    The interaction of effective antibacterial drug decametoxyn with natural DNA was studied by UV-spectroscopy. Decametoxyn shows a specificity to nucleotides: it decreases the cooperativity of melting and the thermal stability of DNA parts enriched by AT pairs. The characteristics of the helix-coil transition on the DNA parts enriched by GC-pairs are invariable. Interaction with AT-pairs results in their partial or complete melting at room temperature, followed by intermolecule aggregation. Interacting with phosphates decametoxyn manifests itself not as a dication but as two single-charged ions. PMID:2348822

  19. Diffusion NMR study of complex formation in membrane-associated peptides

    OpenAIRE

    Barhoum, Suliman; Booth, Valerie; Yethiraj, Anand

    2012-01-01

    Pulsed-field-gradient nuclear magnetic resonance (PFG-NMR) is used to obtain the true hydrodynamic size of complexes of peptides with sodium dodecyl sulfate SDS micelles. The peptide used in this study is a 19-residue antimicrobial peptide, GAD-2. Two smaller dipeptides, alanine-glycine (Ala-Gly) and tyrosine-leucine (Tyr-Leu), are used for comparison. We use PFG-NMR to simultaneously measure diffusion coefficients of both peptide and surfactant. These two inputs, as a function of SDS concent...

  20. Voltammetric investigation of avidin-biotin complex formation using an electroactive bisbiotinyl compound

    International Nuclear Information System (INIS)

    Formation of avidin-biotin complex was investigated using bisbiotinyl thionine (BBT) by means of voltammetric techniques. Thionine is an electroactive compound and has two amino groups that are necessary for the reaction with a biotinylation reagent. The biotinylation of thionine produces a new reagent with two biotin moieties at each end of thionine. Three BBTs of different lengths of the spacer that connects the biotin moiety to the thionine moiety were prepared. The avidin-biotin binding assay was achieved by measuring the electrode response of the thionine moiety in BBT. The binding affinity and the conformation of complex, which depended on the length of spacer, are discussed. BBT in which the spacer is shortest (BBT-S, distance between carbonyl group of the two biotin moieties: 11 A) binds with only one avidin molecule. BBT with medium length of spacer (BBT-M, 28.8 A) forms the complex with two avidin molecules. BBT with the longest spacer (BBT-L, 46.6 A) allows binding with two avidin molecules as well as intramolecular binding within one avidin molecule. The affinity constants of BBT-S, BBT-M and BBT-L for avidin were estimated to be 7.0 x 1012 M-1, 3.2 x 1012 M-1 and 4.0 x 1012 M-1, respectively

  1. Spectrophotometric Determination of Terbutaline Sulphate and Tetracycline Hydrochloride via ion pair Complex Formation Using Eosin Y

    Directory of Open Access Journals (Sweden)

    Mohamed Y. Dhamra

    2014-06-01

    Full Text Available A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of terbutaline sulphate and tetracycline hydrochloride drugs in pure form and pharmaceutical formulations. The proposed method is based on the formation of binary complexes between these drugs and eosin Y in aqueous acetate buffered medium. Under the optimum conditions, the binary complexes showed absorption maxima at 545 nm. Beer's law was rectilinear over concentration range of 0.5-10 and 5-45 μg/mL, R2 were 0.9984 and 0.9988, RSD were ≤ 0.72 and ≤ 0.19 (n=5 with average recovery % 101.42 % and 100.08 % and the average recovery values of pharmaceutical formulations 101.48 and 98.01 for above drugs respectively. The limit of detection (LOD were 0.030 and 0.613 μg/mL and limit of quantitation (LOQ were 0.103 and 2.00 μg/mL with molar absorptivity values 3.169  103 and 6.347  103 l. mol-1. cm-1 and the relative standard deviation values ≤0.720 and ≤ 0.19 for both drugs respectively. No interference was observed from the excipients that are commonly present in pharmaceutical formulations. The proposed method was successfully applied to the analysis of terbutaline sulphate tablet and tetracycline hydrochloride capsule in their dosage forms.

  2. Ternary complex formation and competition quench fluorescence of ZnAF family zinc sensors.

    Science.gov (United States)

    Staszewska, Anna; Kurowska, Ewa; Bal, Wojciech

    2013-11-01

    Our current understanding of the intracellular thermodynamics and kinetics of Zn(ii) ions is largely based on the application of fluorescent sensor molecules, used to study and visualize the concentration, distribution and transport of Zn(ii) ions in real time. Such agents are designed for high selectivity for zinc in respect to other biological metal ions. However, the issue of their sensitivity to physiological levels of low molecular weight Zn(ii) ligands (LMWLs) has not been addressed. We followed the effects of eight such compounds on the fluorescence of ZnAF-1 and ZnAF-2F, two representatives of the ZnAF family of fluorescein-based zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine chelating unit. Fluorescence titrations of equimolar Zn(ii)-ZnAF-1 and Zn(ii)-ZnAF-2F solutions with acetate, phosphate, citrate, glycine, glutamic acid, histidine, ATP and GSH demonstrated strong fluorescence quenching. These results are interpreted in terms of an interplay of the formation of the [ZnAF-Zn(ii)-LMWL] ternary complexes and the competition for Zn(ii) between ZnAF and LMWLs. UV-vis spectroscopic titrations revealed the existence of supramolecular interactions between the fluorescein moiety of ZnAF-1 and ATP and His, which, however, did not contribute to fluorescence quenching. Therefore, the obtained results show that the ZnAF sensors, other currently used zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine unit, and, in general, all sensors that do not saturate the Zn(ii) coordination sphere may co-report cellular metabolites and Zn(ii) ions, leading to misrepresentations of the concentrations and fluxes of biological zinc. PMID:23939683

  3. Floatation-spectrophotometric Determination of Thorium, Using Complex Formation with Eriochrome Cyanine R

    Science.gov (United States)

    Shiri, Sabah; Delpisheh, Ali; Haeri, Ali; Poornajaf, Abdolhossein; Khezeli, Tahereh; Badkiu, Nadie

    2011-01-01

    A novel and sensitive floatation-spectrophotometric method is presented for determination of trace amounts of thorium in water samples. The method is based on the ion-associated formation between thorium, Eriochrome cyanine R and Brij-35 at pH = 4 media. The complex was floated in the interface of the aqueous phase and n-hexane by vigorous shaking. After removing the aqueous phase the floated particles were dissolved in methanol and the absorbance was measured at 607 nm. The influence of different important parameters such as Eriochrome cyanine R and surfactants concentration, pH, volume of n-hexane, standing time and interfering ions were evaluated. Under optimized conditions the calibration graph was linear in the range of 6–230 ng mL−1 of thorium with a correlation coefficient of 0.9985. The limit of detections (LOD), based on signal to noise ratio (S/N) of 3 was 1.7 ng mL−1. The relative standard deviations for determination of 150 and 30 ng ml−1 of thorium were 3.26 and 4.41%, respectively (n = 10). The method showed a good linearity, recoveries, as well as some advantages such as sensitivity, simplicity, affordability and a high feasibility. The method was successfully applied to determine thorium in different water and urine samples. PMID:21340019

  4. Complex formation of cadmium with sugar residues, nucleobases, phosphates, nucleotides, and nucleic acids.

    Science.gov (United States)

    Sigel, Roland K O; Skilandat, Miriam; Sigel, Astrid; Operschall, Bert P; Sigel, Helmut

    2013-01-01

    Cadmium(II), commonly classified as a relatively soft metal ion, prefers indeed aromatic-nitrogen sites (e.g., N7 of purines) over oxygen sites (like sugar-hydroxyl groups). However, matters are not that simple, though it is true that the affinity of Cd(2+) towards ribose-hydroxyl groups is very small; yet, a correct orientation brought about by a suitable primary binding site and a reduced solvent polarity, as it is expected to occur in a folded nucleic acid, may facilitate metal ion-hydroxyl group binding very effectively. Cd(2+) prefers the guanine(N7) over the adenine(N7), mainly because of the steric hindrance of the (C6)NH(2) group in the adenine residue. This Cd(2+)-(N7) interaction in a guanine moiety leads to a significant acidification of the (N1)H meaning that the deprotonation reaction occurs now in the physiological pH range. N3 of the cytosine residue, together with the neighboring (C2)O, is also a remarkable Cd(2+) binding site, though replacement of (C2)O by (C2)S enhances the affinity towards Cd(2+) dramatically, giving in addition rise to the deprotonation of the (C4)NH(2) group. The phosphodiester bridge is only a weak binding site but the affinity increases further from the mono- to the di- and the triphosphate. The same also holds for the corresponding nucleotides. Complex stability of the pyrimidine-nucleotides is solely determined by the coordination tendency of the phosphate group(s), whereas in the case of purine-nucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Cd(2+) with N7. The extents of the formation degrees of these chelates are summarized and the effect of a non-bridging sulfur atom in a thiophosphate group (versus a normal phosphate group) is considered. Mixed ligand complexes containing a nucleotide and a further mono- or bidentate ligand are covered and it is concluded that in these species N7 is released from the coordination sphere of Cd(2+). In the case that the other ligand contains an aromatic residue (e.g., 2,2'-bipyridine or the indole ring of tryptophanate) intramolecular stack formation takes place. With buffers like Tris or Bistris mixed ligand complexes are formed. Cd(2+) coordination to dinucleotides and to dinucleoside monophosphates provides some insights regarding the interaction between Cd(2+) and nucleic acids. Cd(2+) binding to oligonucleotides follows the principles of coordination to its units. The available crystal studies reveal that N7 of purines is the prominent binding site followed by phosphate oxygens and other heteroatoms in nucleic acids. Due to its high thiophilicity, Cd(2+) is regularly used in so-called thiorescue experiments, which lead to the identification of a direct involvement of divalent metal ions in ribozyme catalysis. PMID:23430775

  5. Complex formation in molten salts : thermodynamic association constants of cadmium-chloro complexes in molten nitrates

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, R.K.; Verma, K.W.D.; Gauer, H.C. (Delhi Univ. (India). Dept. of Chemistry)

    1981-09-01

    Thermodynamic association constants for the formation of CdCl/sup +/ and CdCl/sub 2/ species in molten KNO/sub 2/-Ba(NO/sub 3/)/sub 2/ (87.6:12.4 mol percent) eutectic in the temperature range 568.2-628.2 K have been determined by the emf method using Pd-PdO-CdO as the indicator electrode. The temperature coefficients of the association constants were predictable from equations based on quasi-lattice model.

  6. Influence of the Hydrophobicity of Polyelectrolytes on Polyelectrolyte Complex Formation and Complex Particle Structure and Shape

    Directory of Open Access Journals (Sweden)

    Gudrun Petzold

    2011-08-01

    Full Text Available Polyelectrolyte complexes (PECs were prepared by structural uniform and strongly charged cationic and anionic modified alternating maleic anhydride copolymers. The hydrophobicity of the polyelectrolytes was changed by the comonomers (ethylene, isobutylene and styrene. Additionally, the n−/n+ ratio of the molar charges of the polyelectrolytes and the procedure of formation were varied. The colloidal stability of the systems and the size, shape, and structure of the PEC particles were investigated by turbidimetry, dynamic light scattering (DLS and atomic force microscopy (AFM. Dynamic light scattering indicates that beside large PEC particle aggregates distinct smaller particles were formed by the copolymers which have the highest hydrophobicity (styrene. These findings could be proved by AFM. Fractal dimension (D, root mean square (RMS roughness and the surface profiles of the PEC particles adsorbed on mica allow the following conclusions: the higher the hydrophobicity of the polyelectrolytes, the broader is the particle size distribution and the minor is the swelling of the PEC particles. Hence, the most compact particles are formed with the very hydrophobic copolymer.

  7. Effect of fat type in baked bread on amylose-lipid complex formation and glycaemic response.

    Science.gov (United States)

    Lau, Evelyn; Zhou, Weibiao; Henry, Christiani Jeyakumar

    2016-06-01

    The formation of amylose-lipid complexes (ALC) had been associated with reduced starch digestibility. A few studies have directly characterised the extent of ALC formation with glycaemic response. The objectives of this study were to investigate the effect of using fats with varying degree of saturation and chain length on ALC formation as well as glycaemic and insulinaemic responses after consumption of bread. Healthy men consumed five test breads in a random order: control bread without any added fats (CTR) and breads baked with butter (BTR), coconut oil (COC), grapeseed oil (GRP) or olive oil (OLV). There was a significant difference in glycaemic response between the different test breads (P=0·002), primarily due to COC having a lower response than CTR (P=0·016), but no significant differences between fat types were observed. Insulinaemic response was not altered by the addition of fats/oils. Although BTR was more insulinotropic than GRP (Pcoconut oil showing the greatest attenuation of glycaemic response. PMID:27102847

  8. Complex formation of the lanthanides and actinides in lower oxidation states

    International Nuclear Information System (INIS)

    The coordination chemistry of the lanthanides (ln) and actinides (An) in lower oxidation states is discussed, including the hydration-solvation properties of Ln2+ and An2+ in aqueous and aqueous-ethanolic solutions and the formation of complexes with the tetraphenylborate ion and crown ethers. Some physicochemical properties of a number of novel compounds with crown ethers are reported. In this paper the difference in the properties of Ln2+ and An2+ with an fnd0 and fn-1d1 configuration and the ability of the fn-1 d1 compounds to form mixed condensed clusters with Gd2Cl3 are discussed. The properties of Ln and An elements in various oxidation states are compared with those of elements of other groups in the periodic table

  9. Cerimetric determination of simvastatin in pharmaceuticals based on redox and complex formation reactions

    International Nuclear Information System (INIS)

    Two sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods are based on the oxidation of SMT by a measured excess of cerium (IV) in acid medium followed by determination of unreacted oxidant by two different reaction schemes. In one procedure (method A), the residual cerium (IV) is reacted with a fixed concentration of ferroin and the increase in absorbance is measured at 510 nm. The second approach (method B) involves the reduction of the unreacted cerium (IV) with a fixed quantity of iron (II), and the resulting iron (III) is complexed with thiocyanate and the absorbance measured at 470 nm. In both methods, the amount of cerium (IV) reacted corresponds to SMT concentration. The experimental conditions for both methods were optimized. In method A, the absorbance is found to increase linearly with SMT concentration (r = 0.9995) whereas in method B, the same decreased (r = -0.9943). The systems obey Beer's law for 0.6-7.5 and 0.5-5.0 μg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 2.7 X 104 and 1.06 X 105 Lmol-1 cm-1, respectively; and the corresponding sandel sensitivity values are 0.0153 and 0.0039 μg cm-2, respectively. The limit of detection (LOD) and quantification (LOQ) are reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of SMT in tablets and the results were statistically compared with those of the reference method by applying the Student's t-test and F-test. No interference was observed from the common excipients added to tablets. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard addition procedure. (author)

  10. Complex formation in the ternary U(VI)-F-L system (L = carbonate, oxalate and picolinate)

    International Nuclear Information System (INIS)

    The formation of ternary complexes and their equilibrium constants, in the system U(VI)-F--L, where L is one of the ligands picolinate, oxalate or carbonate have been investigated by potentiometric titrations using both F- and H- selective electrodes. The experimental results indicated that very stable ternary complexes are formed with the composition UO2LFq, q = 1 to 3, and UO2L2F for L = picolinate and oxalate. These complexes have a pentagonal bipyramid coordination geometry, with the five exchangeable donor atoms in a plane perpendicular to the linear UO2-group. The equilibrium constants have been determined at 25 C in a 1.00 M NaClO4 ionic medium. The equilibrium constants for the stepwise addition of F- to UO2L to form UO2LFq, q = 1 to 3, and to UO2L2 to form UO2L2F indicates that the prior coordination of L to U(VI) has a fairly small effect on the subsequent bonding of fluoride, except for a statistical effect determined by the number of available coordination sites. These results indicates that ternary complexes might be important for the speciation and transport of hexavalent actinides in ground and surface water systems. (orig.)

  11. Substitutional solute atom-vacancy complex formation in proton-irradiated Zirlo

    International Nuclear Information System (INIS)

    The role of substitutional alloying elements on the recovery processes associated with proton-induced defects in a new zirconium-based alloy (known as Zirlo) is investigated by positron annihilation studies. We observed that the atoms of the alloying elements when knocked out by protons from complexes with the vacancies generated by the removal of host Zr atoms. The formation of the solute atom-vacancy complexes is favoured by the fact that these atoms can migrate only substitutionally in the close-packed crystal structure. With increasing dose of irradiation, the usual defect agglomeration dominates but the growth of vacancy clusters is restricted by the octahedral oxygen atoms which diffuse to an appreciable number of Zr vacancies. Isochronal annealing of the defects took place in three stages and are respectively identified as the annealing of dislocation/vacancy loops, an antirecovery stage due to the dissociation of the solute atom-vacancy complexes and the final annealing of vacancy clusters. (author)

  12. Sorption and complex formation studies of some radioisotopes in the terrestrial environment of inshas area

    International Nuclear Information System (INIS)

    Shallow burial of radioactive wastes has become the most viable disposal option that is receiving a greater attention nowadays to provide the radiological safety in low level waste management processes. The migration behavior of radionuclides in the terrestrial environment of the repository have a predominant role in confirming the suitability of the disposal site. This migration behavior is almostly affected by the presence of dissolved organic compounds, such as humic acid, that have a substantial chelation properties to metal ions

  13. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation

    Science.gov (United States)

    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-01-01

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein–protein or protein–ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. PMID:27288028

  14. Complex formation of trivalent americium with salicylic acid at very low concentrations

    International Nuclear Information System (INIS)

    For the first time, the complexation of americium(III) with salicylic acid was studied at trace metal concentrations using a 2.0 m Long Path Flow Cell for UV-vis spectroscopy. The detection limit of Am(III) in aqueous solution at pH 3.0 was found to be 5 x 10-9 M. Two Am(III)-salicylate complexes were formed at pH 5.0 in 0.1 M NaClO4, indicated by a clear red shift of the absorption maximum. The absorption spectra obtained from spectrophotometric titration were analyzed by means of factor analysis and complex stabilities were calculated to be log β110 = 2.56 ± 0.08 and log β120 = 3.93 ± 0.19. (author)

  15. Complex formation between UO22+ and CO32-: studied by laser-induced photoacoustic spectroscopy (LIPAS)

    International Nuclear Information System (INIS)

    The formation constant log β = 21.57 ± 0.70 of the uranyl triscarbonato complex, UO2(CO3)34-, was determined for the first time by laser-induced photoacoustic spectroscopy at uranium concentrations from 5 x 10-4 to 10-5 M. The photoacoustic absorption spectra from pH 5 to 10 were recorded in the UV-vis range using a continous scan mode from 380 nm to 480 nm. Furthermore, a mill tailing water from Helmsdorf in Saxony, Germany, with uranium concentration of 2.5 x 10-5 M was measured by LIPAS. By comparing this spectrum with the spectrum of pure uranyl tris carbonate, the main species in the mill tailing water was identified as the uranyl triscarbonato complex. This finding agrees with speciation calculations. (orig.)

  16. Complex formation of U(VI) with Bacillus-isolates from a uranium mining waste pile

    International Nuclear Information System (INIS)

    Accumulation studies with vegetative cells and spores of three Bacillus isolates (JG-A 30, JG-A 12, JG-A 22, classified as Bacillus cereus, Bacillus sphaericus, Bacillus megaterium) from a uranium mining waste pile (Johanngeorgenstadt, Saxony) and their corresponding reference strains have shown that Bacilli accumulate high amounts of U(VI) in the concentration range examined (11-214 mg/L). Information on the binding strength and the reversibility were obtained from extraction studies with different extractants. With 0.01 M EDTA solution the uranium bound to the biomass was released almost quantitatively. The characterization of the bacterial-UO22+-complexes by time-resolved laser fluorescence spectroscopy (TRLFS) showed the formation of inner-sphere complexes with phosphate groups of the biomass. The results lead to the conclusion that the cell wall components with phosphate residues e.g., polysaccharides, teichoic and teichuroic acids or phospholipide layers of the membranes are responsible for the uranium binding. The spectroscopic studies of the U(VI)-complexes with isolated bacterial cell walls and isolated surface-layer proteins of the strain Bacillus sphaericus NCTC 9602 after cell fractionation have shown that the complexation of U(VI) with intact cells (vegetative cells or spores) is different from the coordination with isolated cell wall components, especially with the S-layer proteins. For all Bacillus strains studied in this work, a significant contribution of the S-layer proteins to the binding of uranyl to living cells can be excluded. (orig.)

  17. The interaction of streptococcal enolase with canine plasminogen: the role of surfaces in complex formation.

    Directory of Open Access Journals (Sweden)

    Vinod Balhara

    Full Text Available The enolase from Streptococcus pyogenes (Str enolase F137L/E363G is a homo-octamer shaped like a donut. Plasminogen (Pgn is a monomeric protein composed of seven discrete separated domains organized into a lock washer. The enolase is known to bind Pgn. In past work we searched for conditions in which the two proteins would bind to one another. The two native proteins in solution would not bind under any of the tried conditions. We found that if the structures were perturbed binding would occur. We stated that only the non-native Str enolase or Pgn would interact such that we could detect binding. We report here the results of a series of dual polarization interferometry (DPI experiments coupled with atomic force microscopy (AFM, isothermal titration calorimetry (ITC, dynamic light scattering (DLS, and fluorescence. We show that the critical condition for forming stable complexes of the two native proteins involves Str enolase binding to a surface. Surfaces that attract Str enolase are a sufficient condition for binding Pgn. Under certain conditions, Pgn adsorbed to a surface will bind Str enolase.

  18. Capping complex formation at the slow-growing end of the actin filament.

    Science.gov (United States)

    Kostyukova, A S

    2008-12-01

    Actin filaments are polar; their barbed (fast-growing) and pointed (slow-growing) ends differ in structure and dynamic properties. The slow-growing end is regulated by tropomodulins, a family of capping proteins that require tropomyosins for optimal function. There are four tropomodulin isoforms; their distributions vary depending on tissue type and change during development. The C-terminal half of tropomodulin contains one compact domain represented by alternating alpha-helices and beta-structures. The tropomyosin-independent actin-capping site is located at the C-terminus. The N-terminal half has no regular structure; however, it contains a tropomyosin-dependent actin-capping site and two tropomyosin-binding sites. One tropomodulin molecule can bind two tropomyosin molecules. Effectiveness of tropomodulin binding to tropomyosin depends on the tropomyosin isoform. Regulation of tropomodulin binding at the pointed end as well as capping effectiveness in the presence of specific tropomyosins may affect formation of local cytoskeleton and dynamics of actin filaments in cells. PMID:19216712

  19. Thermoacoustical analysis of solutions of poly(ethylene glycol) 200 through H-bond complex formation

    International Nuclear Information System (INIS)

    Research highlights: → The presence of two electronegative elements viz. nitrogen and oxygen in its molecular architecture, ethanolamine has greater extent of interaction with PEG. → Ethanolamine and m-cresol may be involved in a complex type of network of hydrogen bonding. → Ethanolamine has greater extent of interaction with PEG than m-cresol and aniline particularly with least magnitude from aniline, where electron availability is least because of delocalization. → The difference in molar volume between the components of the mixture control the mixture properties. - Abstract: Densities (ρ) and ultrasonic velocities (u) of binary mixtures of poly(ethylene glycol) 200, PEG, with ethanolamine, m-cresol and aniline have been measured at various concentrations at 293.15, 303.15 and 313.15 K and have been fitted by third order polynomial equations at each temperature. The calculated values of isentropic compressibility (ks), free volume (Vf), internal pressure (πi), relaxation time (τ) and surface tension (σ) at different mole fractions of PEG have been used to explain the hydrogen bonding and intermolecular interactions present in the mixture. Using these data, excess molar volume (VE), excess intermolecular free length (LfE), excess acoustic impedance (ZE) and excess pseudo-Grueneisen parameter (ΓE) have been calculated and the results have been fitted to Redlich-Kister polynomial equation. All the results support each other and help in understanding the interactions in the mixture. Various models and mixing rules have been applied to evaluate the ultrasonic velocity data and have been compared with the experimental results.

  20. Diazomethyl ketone substrate derivatives as active-site-directed inhibitors of thiol proteases. Papain

    Energy Technology Data Exchange (ETDEWEB)

    Leary, R.; Larsen, D.; Watanabe, H.; Shaw, E.

    1977-12-27

    The diazomethyl ketones of z-Phe and z-Phe-Phe inactivate papain by a stoichiometric reaction at the active-center thiol. Since the reagents are stable in mercaptoethanol, their reaction with papain is judged to be the result of complex formation characteristic of affinity-labeling reagents. The diazomethyl ketones react by a mechanism different from that of chloromethyl ketones, since the pH dependence of their inactivation of papain is different, the rate increasing with decreasing pH. This relationship has been observed in other cases, such as the reaction of azaserine with glutamine amidotransferases (Buchanan, J. M. (1973), Adv. Enzmol. Relat. Areas Mol. Biol. 39, 91), and is interpreted as an indication of reaction with a thiol group in its protonated form.

  1. Chlorine ions effect on photochemical activity of alcoholate complexes of vanadium

    International Nuclear Information System (INIS)

    Photochemical activity of vanadium complexes during alcogolate ion substitution by chlorine is studied. Using the method of electron spectroscopy and ESR photochemical transformations in alcohol solutions, containing alkoxides VO(OR)3, VO(OR)2Cl, VO(OR)Cl2 as well as VOCl3 with additions of HCl and LiCl, are investigated. It is shown that with the increase of chloride-ion concentration in solution the rate of all the stages of photochemical reduction of vanadium increases considerably. It is also found that photoreduction of vanadium (5) in the case of absence of chlorine ions ends at the stage of vanadium (3) complex formation, whereas when chlorine ions are present in solution the process proceeds further to the formation of divalent vanadium complexes

  2. Cobalt substituted thiosemicarbazone metal complex induced apoptosis in cancer cells via activation of mitochondrial pathway

    International Nuclear Information System (INIS)

    Thiosemicarbazone (TSC) and their transition metal complexes are broad class of biologically active small molecules and present a great variety of biological activity ranging from antitumour, fungicide, bacteriocide, anti inflammatory and antiviral activities. These characteristics render the whole class of compounds very interesting. In the present study, we sought to examine cytotoxic activity of thiosemicarbazone cobalt complex on various cancer cell lines along with the possible mechanism through which the compound induce apoptosis in these cell lines. Cytotoxicity of TSC cobalt complex was studied by performing standard MTT drug sensitivity assay and determining its IC50 value on various leukemic and solid cancer cell lines like HL-60, MOLT-4, K-562 and COLO-205. Cellular damage upon the treatment of test molecule was analyzed by conducting LDH release assay. DNA fragmentation and morphology of apoptotic cells were assessed respectively by performing ladder assay and acridine orange/ethidium bromide staining. Role of mitochondria in the induction of cell death was studied by measuring mitochondrial membrane potential (ΔΨm) using JC-1 probe. The cytotoxicity studies confirms that TSC cobalt complex is having potent anticancer activity on HL-60, K-562, MOLT-4 and COLO-205 cell lines with the IC50 value in the range 0.225-29.00 μM. Dose dependent increase in the LDH release into the surrounding media depicts the cell membrane disintegrity. DNA fragmentation on treated cells revealed the cell death, which is commonly associated with apoptosis. Fluorescence microscopic imaging of treated cells confirms that the mode of cell death was through apoptosis. Loss of the ΔΨm in treated cells explicates the involvement of mitochondria in the cell death induction. Further increase in caspase-3 activity upon treatment corroborates that molecule induces apoptosis. Taken together, this exploratory study revealed that TSC cobalt complex possesses potent cytotoxic and

  3. Physical activity

    Science.gov (United States)

    Physical activity -- which includes an active lifestyle and routine exercise -- plus eating well, is the best way to ... shortness of breath when you are active Build physical activity into your regular routine Simple lifestyle changes can ...

  4. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug

    Directory of Open Access Journals (Sweden)

    Gullbo Joachim

    2009-06-01

    Full Text Available Abstract Background N-(6-(4-chlorophenoxyhexyl-N'-cyano-N''-4-pyridyl guanidine (CHS 828 is the first candidate drug from a novel group of anti-tumour agents – the pyridyl cyanoguanidines, shown to be potent compounds interfering with cellular metabolism (inhibition of nicotinamide phosphoribosyl transferase and NF-κB signalling. Substituted cyanoguanidines are also found in anti-hypertensive agents such as the potassium channel opener pinacidil (N-cyano-N'-(4-pyridyl-N''-(1,2,2-trimethylpropylguanidine and histamine-II receptor antagonists (e.g. cimetidine, N-cyano-N'-methyl-N''-[2-[[(5-methylimidazol-4-yl]methyl]thio]ethylguanidine. In animal studies, CHS 828 has shown very promising activity, and phase I and II studies resulted in further development of a with a water soluble prodrug. Findings To study the structural requirements for cyanoguanidine cytotoxicity a set of 19 analogues were synthesized. The cytotoxic effects were then studied in ten cell lines selected for different origins and mechanisms of resistance, using the fluorometric microculture cytotoxicity assay (FMCA. The compounds showed varying cytotoxic activity even though the dose-response curves for some analogues were very shallow. Pinacidil and cimetidine were found to be non-toxic in all ten cell lines. Starting with cyanoguanidine as the crucial core it was shown that 4-pyridyl substitution was more efficient than was 3-pyridyl substitution. The 4-pyridyl cyanoguanidine moiety should be linked by an alkyl chain, optimally a hexyl, heptyl or octyl chain, to a bulky end group. The exact composition of this end group did not seem to be of crucial importance; when the end group was a mono-substituted phenyl ring it was shown that the preferred position was 4-substitution, followed by 3- and, finally, 2-substitution as the least active. Whether the substituent was a chloro, nitro or methoxy substituent seemed to be of minor importance. Finally, the activity patterns in the

  5. Comparative study on the immunocompetent activity of three different kinds of Peh-Hue-Juwa-Chi-Cao, Hedyotis diffusa, H. corymbosa and Mollugo pentaphylla after sublethal whole body X-irradiation

    International Nuclear Information System (INIS)

    This brief communication describes the immunocompetent activity of the Chinese folk-medicinal herbs, Hedyotis corymbosa, H. diffusa and Mollugo pentaphylla in mice after moderate whole body x-irradiation. These antitumour drugs, given at doses of 500 and 1000 mg/kg/day for 7 consecutive days before x-irradiation protected ICR strain mice from the sublethal effects of radiation at a dose of 4 Gy, especially for the dose at 1000 mg/kg. Prior administration of H. corymbosa and H. diffusa ameliorated the leukopenia and splenic cellular decrease induced by sublethal irradiation, and slightly increased the immunocompetence of splenic cells after being stimulated by mitogens. However, administration of M. pentaphylla before x-irradiation exerted a less protective effect on ameliorating leukopenia and on splenic cellular immunocompetence. These findings suggest that some types of Peh-Hue-Juwa-Chi-Caoi (PHJCC) may also be effective in the prevention of haematopoietic damage when used in combination with radiotherapy. (author)

  6. Physical activity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001941.htm Physical activity To use the sharing features on this page, please enable JavaScript. Physical activity -- which includes an active lifestyle and routine exercise -- ...

  7. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

    NARCIS (Netherlands)

    C.M.L. Herpen, C.M.L. (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I. Desar; L. Hooftman (Leon); E. Bone (Elisabeth); J.N.H. Timmerbonte (Johanna); J. Verweij (Jaap)

    2010-01-01

    textabstractBackground: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxe

  8. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.

    NARCIS (Netherlands)

    Herpen, C.M.L. van; Eskens, F.A.; Jonge, M. de; Desar, I.M.E.; Hooftman, L.; Bone, E.A.; Timmer-Bonte, J.N.H.; Verweij, J.

    2010-01-01

    BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:

  9. Tumour cell growth inhibitory potential of mushroom extracts from the genus Suillus

    OpenAIRE

    Vaz, Josiana A.; Santos, Tiago; Tavares, Catarina; Almeida, Gabriela M.; Ferreira, Isabel C. F. R.; Vasconcelos, M. Helena

    2012-01-01

    Mushrooms are a source of compounds with promising antitumour activity [1]. We have been working on the identification of wild mushrooms with promising antitumour activity and a Clitocybe alexandri extract which induces cell cycle arrest and apoptosis in a lung cancer cell line has been previously identified by part of the team [2]. The objective of this work was to continue the identification of mushrooms from the Northeast of Portugal with tumour cell growth inhibitory potential. Thirty...

  10. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Molife, L R; Sorensen, Janice Marie;

    2010-01-01

    This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours.......This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours....

  11. Solid-State Synthesis, Characterization, and Biological Activity of the Bioinorganic Complex of Aspartic Acid and Arsenic Triiodide

    Directory of Open Access Journals (Sweden)

    Guo-Qing Zhong

    2013-01-01

    Full Text Available The bioinorganic complex of aspartic acid and arsenic triiodide was synthesized by a solid-state reaction at room temperature. The formula of the complex is AsI3[HOOCCH2CH(NH2COOH]2.5. The crystal structure of the complex belongs to monoclinic system with lattice parameters: a=1.0019 nm, b=1.5118 nm, c=2.1971 nm, and β=100.28°. The infrared spectra can demonstrate the complex formation between the arsenic ion and aspartic acid, and the complex may be a dimer with bridge structure. The result of primary biological test indicates that the complex possesses better biological activity for the HL-60 cells of the leukemia than arsenic triiodide.

  12. Get Active

    Science.gov (United States)

    ... feeling the benefits of getting active, such as sleeping better or getting toned. Here are 2 ways to add more activity to your life. Be active for longer each time. If you are walking 3 days a week for 30 minutes, try ...

  13. Pharmacokinetics of activated protein C in guinea pigs

    International Nuclear Information System (INIS)

    Protein C is a vitamin K-dependent zymogen of the serine protease, activated protein C (APC), an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the pharmacokinetics and tissue distribution of APC were studied in guinea pigs. The plasma elimination of a trace dose of 125I-APC was biphasic following an initial rapid elimination of approximately 15% of the injected dose within 1 to 2 minutes. This rapid removal of 125I-APC from the circulation was found to be a result of an association with the liver regardless of the route of injection. Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association. Accumulation of all three forms of APC in the liver peaked at 30 minutes and then declined as increasing amounts of degraded radiolabeled material appeared in the gastrointestinal tract and urine. Removal of the gamma-carboxyglutamic acid (gla) domain of diisopropylphosphoryl-APC resulted in a 50% reduction in the association with liver and an accumulation in the kidneys. Protein C and protein S were cleared from the circulation at rates approximately one-half and one-fourth, respectively, that of APC. Both in vitro and in vivo, APC was found to form complexes with protease inhibitors present in guinea pig plasma. Complex formation resulted in a more rapid disappearance of the enzymatic activity of APC than elimination of the protein moiety. These findings indicate two distinct mechanisms for the elimination of APC. One mechanism involves reaction with plasma protease inhibitors and subsequent elimination by specific hepatic receptors. (Abstract Truncated)

  14. Effects of milk fermented by Lactobacillus helveticus R389 on a murine breast cancer model

    OpenAIRE

    de Moreno de LeBlanc, Alejandra; Matar, Chantal; LeBlanc, Nicole; Perdigón, Gabriela

    2005-01-01

    Introduction Antitumour activity is one of the health-promoting effects attributed to the lactic acid bacteria and their products of fermentation. Previous studies in mice demonstrated that bioactive compounds released in milk fermented by Lactobacillus helveticus R389 contribute to its immunoenhancing and antitumour properties. The aim of the present work was to study the effects of the consumption of milk fermented by L. helveticus R389 or its proteolytic-deficient variant, L. helveticus L8...

  15. Regulation of activity of the yeast TATA-binding protein through intra-molecular interactions

    Indian Academy of Sciences (India)

    Perumal Vanathi; Anurag Kumar Mishra; Purnima Bhargava

    2003-06-01

    Dimerization is proposed to be a regulatory mechanism for TATA-binding protein (TBP) activity both in vitro and in vivo. The reversible dimer-monomer transition of TBP is influenced by the buffer conditions in vitro. Using in vitro chemical cross-linking, we found yeast TBP (yTBP) to be largely monomeric in the presence of the divalent cation Mg2+, even at high salt concentrations. Apparent molecular mass of yTBP at high salt with Mg2+, run through a gel filtration column, was close to that of monomeric yTBP. Lowering the monovalent ionic concentration in the absence of Mg2+, resulted in dimerization of TBP. Effect of Mg2+ was seen at two different levels: at higher TBP concentrations, it suppressed the TBP dimerization and at lower TBP levels, it helped keep TBP monomers in active conformation (competent for binding TATA box), resulting in enhanced TBP-TATA complex formation in the presence of increasing Mg2+. At both the levels, activity of the full-length TBP in the presence of Mg2+ was like that reported for the truncated C-terminal domain of TBP from which the N-terminus is removed. Therefore for full-length TBP, intra-molecular interactions can regulate its activity via a similar mechanism.

  16. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-11-29

    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  17. Antioxidant activities of Indigofera cassioides Rottl. Ex. DC. using various in vitro assay models

    Institute of Scientific and Technical Information of China (English)

    R Senthil Kumar; B Rajkapoor; P Perumal

    2012-01-01

    Objective: To evaluate the antioxidant potential of methanolic leaf extract of Indigoferacassioides (MEIC) using various in vitro antioxidant assay systems. Methods: Antioxidant and free radical scavenging activity of MEIC was assayed by using different in vitro models like ABTS, DPPH, nitric oxide, superoxide, hydrogen peroxide and hydroxyl radical. Reductive ability of the extract was tested by the complex formation with potassium ferricyanide. Further total phenol and flavonoid contents of the crude extract were also determined. Rutin and ascorbic acid were used as standards. Results: MEIC exhibited potent and concentration dependent free radical scavenging activity in all the tested models. Reductive ability was also found to increase with increase in MEIC concentration. Total phenol and flavonoid content determination showed that the extract is rich in phenols and flavonoids. Conclusions: All the results of the in vitro antioxidant assays reveal potent antioxidant and free radical scavenging activity of the leaves of Indigofera cassioides, equivalent to that of standard ascorbic acid and rutin. This potent antioxidant activity may be attributed to its high phenolic and flavonoid contents

  18. Mutations that alter the ability of the Escherichia coli cyclic AMP receptor protein to activate transcription.

    Science.gov (United States)

    Bell, A; Gaston, K; Williams, R; Chapman, K; Kolb, A; Buc, H; Minchin, S; Williams, J; Busby, S

    1990-12-25

    The effects of a number of mutations in the E. coli cyclic AMP receptor protein (CRP) have been determined by monitoring the in vivo expression and in vitro open complex formation at two semi-synthetic promoters that are totally CRP-dependent. At one promoter the CRP-binding site is centered around 41.5 base pairs upstream from the transcription start whilst at the other promoter it is 61.5 base pairs upstream. The CRP mutation E171K reduces expression from both promoters whilst H159L renders CRP totally inactive: neither mutation stops CRP binding at either promoter. The mutations K52N and K52Q reverse the effect of H159L and 'reeducate' CRP to activate transcription. CRP carrying both H159L and K52N activates transcription from the promoter with the CRP site at -41.5 better than wild type CRP. In sharp contrast, this doubly changed CRP is totally inactive with respect to the activation of transcription from the promoter carrying the CRP site at -61.5. Our results suggest that CRP can use different contacts and/or conformations during transcription activation at promoters with different architectures. PMID:2259621

  19. Chemical composition and antimicrobial activity of the essential oil of Plectranthus mollis (Lamiaceae) from Western Ghats Region, Karnataka, India.

    Science.gov (United States)

    Joshi, Rajesh K

    2014-06-01

    Plectranthus is a large and widespread genus with a diversity of ethnobotanical uses. In traditional medicine P. mollis has been used against snakebites, respiratory stimulant and vasoconstrictor, cardiac depressant, cure for haemorrahage, treatment of mental retardation and rheumatism. P. mollis is reported to exhibit relaxant activity on smooth and skeletal muscles, and has cytotoxic and anti-tumour promoting activity, and can be used in the treatment of cancer. The aim of the present study was to identify chemical composition of the essential oil of P. mollis and to evaluate antimicrobial efficacy of the oil. The essential oil of the flowering aerial parts of P. mollis was obtained by hydro-distillation and analyzed by gas chromatography equipped with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). Twenty-seven compounds were identified, which comprised 98.6% of the total constituents. The main compound was identified as fenchone (32.3%), followed by alpha-humulene (17.3%), piperitenone oxide (8.5%), cis-piperitone oxide (6.0%) and E-beta-farnesene (5.9%). The oil was found rich in oxygenated monoterpenes type constituents (52.0%), followed by sesquiterpene hydrocarbons (40.2%), oxygenated sesquiterpenes (4.9%), and monoterpene hydrocarbons (1.5%). Antimicrobial activity of the essential oil of P. mollis was tested against six Gram-positive and eight Gram-negative bacteria, and three fungi, by using the tube dilution method. The oil was active against the tested Gram-positive and Gram-negative bacteria, and fungi at a concentration range of 0.065 +/- 0.008-0.937 +/- 0.139 mg/mL, 0.468 +/- 0.069-3.333 +/- 0.527 mg/mL and 0.117 +/- 0.017-0.338 +/- 0.062 mg/mL, respectively. The present study revealed that the oil constituents somehow were qualitatively similar and quantitatively different than earlier reports from different parts of the world. The essential oil of P. mollis has found to be antimicrobial activity

  20. Monocytes and the 38kDa-antigen of mycobacterium tuberculosis modulate natural killer cell activity and their cytolysis directed against ovarian cancer cell lines

    International Nuclear Information System (INIS)

    Despite strong efforts to improve clinical outcome of ovarian cancer patients by conventional and targeted immuno-based therapies, the prognosis of advanced ovarian cancer is still poor. Natural killer (NK) cells mediate antibody-dependent cellular cytotoxicity (ADCC), release immunostimulatory cytokines and thus function as potent anti-tumour effector cells. However, tumour cells developed mechanisms to escape from an effective immune response. So highly immunogenic substances, like the 38 kDa-preparation of M. tuberculosis, PstS-1, are explored for their potential to enhance cancer-targeted immune responses. In this study we examined the modulation of different NK cell functions by accessory monocytes and PstS-1. We focussed on NK cell activation as well as natural and antibody-dependent cellular cytotoxicity directed against epidermal-growth-factor-receptor (EGFR)-positive ovarian cancer cell lines. Activation, cytokine release and cytotoxicity of NK cells stimulated by monocytes and PstS-1 were determined by FACS-analysis, ELISA, Bioplex assay and quantitative polymerase-chain reaction (qPCR). Transwell assays were used to discriminate cell-cell contact-dependent from contact-independent mechanisms. Five ovarian cancer cell lines (A2780, IGROV-1, OVCAR-3, OVCAR-4 and SKOV-3) with different EGFR-expression were used as target cells for natural and antibody-dependent cellular cytotoxicity assays. Cetuximab (anti-EGFR-antibody) was used for ADCC studies. Our data show that monocytes effectively enhance activation as well natural and antibody-dependent cytolytic activity of NK cells. PstS-1 directly stimulated monocytes and further activated monocyte-NK-co-cultures. However, PstS-1 did not directly influence purified NK cells and did also not affect natural and antibody-dependent cellular cytotoxicity directed against EGFR-positive ovarian cancer cells, even in presence of monocytes. Direct cell-cell contact between NK cells and monocytes was required for NK

  1. Activation analysis

    International Nuclear Information System (INIS)

    The neutron activation analysis, which appears to be in limits for further advance, is the most suitable for providing information on the principal as well as the microcomponents in any sample of solid form. Then, instrumental activation analysis is capable of determination of far many elements in various samples. Principally on the neutron activation analysis, the following are described in literature survey from 1982 to middle 1984: bibliography, review, data collection, etc.; problems in spectral analysis and measurement; activation analysis with neutrons; charged particle and photo-nucleus reactions; chemical separation, isotopic dilution activation analysis; molecular activation analysis; standard materials; life and its relation samples; environmental, food, court trial and archaeological samples; space and earth sciences. (Mori, K.)

  2. Active ratchets

    Science.gov (United States)

    Angelani, L.; Costanzo, A.; Di Leonardo, R.

    2011-12-01

    We analyze self-propelling organisms, or active particles, in a periodic asymmetric potential. Unlike standard ratchet effect for Brownian particles requiring external forcing, in the case of active particles asymmetric potential alone produces a net drift speed (active ratchet effect). By using theoretical models and numerical simulations we demonstrate the emergence of the rectification process in the presence of an asymmetric piecewise periodic potential. The broken spatial symmetry (external potential) and time symmetry (active particles) are sufficient ingredients to sustain unidirectional transport. Our findings open the way to new mechanisms to move in directional manner motile organisms by using external periodic static fields.

  3. Physical Activity

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Anderssen, Sigmund Alfred; Wisløff, Ulrik;

    2014-01-01

    Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers.......Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers....

  4. Manipulation of P450 gene expression in tumours; a novel approach for targeted activation of bioreductive prodrugs

    International Nuclear Information System (INIS)

    We are developing a gene-directed enzyme prodrug therapy (GDEPT) strategy to enhance the metabolism of a novel bioreductive drug, AQ4N. Bioreductive drugs are metabolically activated in the hypoxic cell environment allowing effective targeting of hypoxic radioresistant tumour regions. We aim to achieve additional layers of selectivity by using an X-ray inducible promoter linked to our therapeutic gene (cytochrome P450s). This strategy would enhance metabolism of the drug only within the radiation field. Furthermore, normal tissue would be unaffected as the bioreductive drug is only activated in hypoxic conditions. We have identified several human cytochrome P450s which are important for AQ4N prodrug activation, these include CYP3A4, 1A1 and 2B6. RIF1 murine tumour cells transfected with cDNA from any one of these CYPs displayed increased DNA damage and clonogenic cell kill following treatment with AQ4N under hypoxia compared to controls. We are presently testing the ability of these transfectants to enhance anti-tumour effectiveness of AQ4N in combination with radiation in vivo. We have shown that a single CYP3A4 injection using a simple non-optimized approach can increase metabolism of AQ4N and when used in combination with radiation 3 out of 4 tumours are locally controlled for > 60 days (McCarthy et al., 2002). This result is remarkable considering the large enhancement of the radiation effect achieved by adding AQ4N alone. This implies that the bioreduction of AQ4N by CYPs in this tumour system is sub-optimal and this strategy could therefore be very promising for clinical use where CYP levels are known to be variable. We are now exploring the CYP/AQ4N GDEPT strategy in combination with cyclophosphamide, which is also metabolised by CYPs and aim to link these CYPs to the radiation and hypoxia inducible WAF1 promoter for selective activation in vivo

  5. Activity report

    International Nuclear Information System (INIS)

    The Department of Physics and Measurement Technology, Biology and Chemistry (IFM) presents every year a progress report containing a brief description of activities in research and education within the department. The report is intended as an information for colleagues and institutions. The present report contains activities for the academic year July 1989 to June 1990

  6. Indoor Activities

    Science.gov (United States)

    ... so you can do some lifting while you watch TV. Walk around the house when you talk on the phone. Make an extra trip up and down the stairs when you do the laundry. Download the Tip Sheet Indoor Activities (PDF, 739.53 KB) You Might Also Like Sun Safety Have Fun. Be Active with Your Dog! ...

  7. Chiral copper(II) complex based on natural product rosin derivative as promising antitumour agent.

    Science.gov (United States)

    Fei, Bao-Li; Huang, Zhi-Xiang; Xu, Wu-Shuang; Li, Dong-Dong; Lu, Yang; Gao, Wei-Lin; Zhao, Yue; Zhang, Yu; Liu, Qing-Bo

    2016-07-01

    To evaluate the biological preference of chiral drug candidates for molecular target DNA, the synthesis and characterization of a chiral copper(II) complex (2) of a chiral ligand N,N'-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral, emission spectral and viscosity analysis reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. In the absence/presence of ascorbic acid, 1 and 2 cleaved supercoiled pBR322 DNA by single-strand and 2 displayed stronger DNA cleavage ability. In addition, in vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines study show that they exhibited effective cytotoxicity against the tested cell lines, notably, 2 showed a superior cytotoxicity than the widely used drug cisplatin under identical conditions, indicating it has the potential to act as effective anticancer drug. Flow cytometry analysis indicates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis demonstrates that 2 mainly arrested HeLa cells at the S phase. The study represents the first step towards understanding the mode of the promising chiral rosin-derivative based copper complexes as chemotherapeutics. PMID:27088508

  8. Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization.

    Science.gov (United States)

    Mahale, S; Bharate, S B; Manda, S; Joshi, P; Jenkins, P R; Vishwakarma, R A; Chaudhuri, B

    2015-01-01

    The marine natural product fascaplysin (1) is a potent Cdk4 (cyclin-dependent kinase 4)-specific inhibitor, but is toxic to all cell types possibly because of its DNA-intercalating properties. Through the design and synthesis of numerous fascaplysin analogues, we intended to identify inhibitors of cancer cell growth with good therapeutic window with respect to normal cells. Among various non-planar tryptoline analogues prepared, N-(biphenyl-2-yl) tryptoline (BPT, 6) was identified as a potent inhibitor of cancer cell growth and free from DNA-binding properties owing to its non-planar structure. This compound was tested in over 60 protein kinase assays. It displayed inhibition of Cdk4-cyclin D1 enzyme in vitro far more potently than many other kinases including Cdk family members. Although it blocks growth of cancer cells deficient in the mitotic-spindle checkpoint at the G0/G1 phase of the cell cycle, the block occurs primarily at the G2/M phase. BPT inhibits tubulin polymerization in vitro and acts as an enhancer of tubulin depolymerization of paclitaxel-stabilized tubulin in live cells. Western blot analyses indicated that, in p53-positive cells, BPT upregulates the expression of p53, p21 and p27 proteins, whereas it downregulates the expression of cyclin B1 and Cdk1. BPT selectively kills SV40-transformed mouse embryonic hepatic cells and human fibroblasts rather than untransformed cells. BPT inhibited the growth of several human cancer cells with an IC50anticancer agent than fascaplysin with an unusual ability to block two overlapping yet crucial phases of the cell cycle, mitosis and G0/G1. Its ability to effectively halt tumour growth in human tumour-bearing mice would suggest that BPT has the potential to be a candidate for further clinical development. PMID:25950473

  9. Regression of Sweet's syndrome associated with Crohn's disease after anti-Tumour Necrosis Factor therapy.

    Science.gov (United States)

    Rahier, J F; Lion, L; Dewit, O; Lambert, M

    2005-01-01

    The association of inflammatory bowel disease and acute febrile neutrophilic dermatitis (Sweet's syndrome) has infrequently been reported in the literature. We describe the case of a 41-year-old Caucasian woman with ileo- anal Crohn's disease who presented simultaneously an erythema nodosum and a Sweet's syndrome. A dramatic regression of the cutaneous lesions was observed after infliximab treatment, indicating that this therapy might be useful for both Crohn's disease and Sweet's syndrome. PMID:16268426

  10. Antitumour effects of combined radio- and parvovirotherapy in N-Ras-positive tumour cells

    International Nuclear Information System (INIS)

    Many innovative approaches have attempted to challenge the dominant position of surgery, chemotherapy and radiotherapy as the major therapeutic modalities to treat cancer. However, only recently some new agents have appeared that achieve effects comparable to the ones of these established treatments. A novel class of such therapeutics consists of oncolytic viruses with several main representatives, namely adeno-, herpes, reo- and parvovirus. The latter class of anticancer agents has proven to be quite effective in many preclinical models and is now considered for a phase I clinical trial in patients with glioma and pancreatic cancer. An important question to be answered is whether virotherapy can be combined with standard treatments to achieve an enhanced antitumor effect still at a low level of toxicity. Here we present data concerning the application of irradiation together with H-1PV parvovirus infection comparing their toxic effects on normal and Ras -transformed fibroblasts. This proved to be a potent combination achieving high level of synergistic toxicity on transformed cells at doses, which did not affect the viability of normal human fibroblasts. This strategy holds promise to become a part of the clinical treatment of radioresistant tumours. (authors)

  11. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

    NARCIS (Netherlands)

    Boks, Martine A.; Ambrosini, Martino; Bruijns, Sven C.; Kalay, Hakan; Van Bloois, Louis; Storm, G; Garcia-Vallejo, Juan J.; Van Kooyk, Yvette

    2015-01-01

    Abstract Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhance

  12. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

    NARCIS (Netherlands)

    Boks, M.A.; Ambrosini, Martino; Bruijns, Sven C.M.; Kalay, Hakan; Bloois, van Louis; Storm, G.; Garcia-Vallejo, Juan J.; Kooyk, van Y.

    2015-01-01

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with st

  13. Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin.

    Science.gov (United States)

    Gajski, Goran; Čimbora-Zovko, Tamara; Rak, Sanjica; Osmak, Maja; Garaj-Vrhovac, Vera

    2016-08-01

    Cisplatin (cDDP) is one of the most widely used anticancer-drugs in both therapy and research. However, cDDP-resistance is the greatest obstacle for the successful treatment of cancer patients. In the present study, the possible joint anticancer effect of bee venom (BV), as a natural toxin, and cDDP towards human glioblastoma A1235 cells was evaluated. Treatment with BV alone in concentrations of 2.5-30 μg/ml displayed dose-dependent cytotoxicity towards A1235 cells, as evaluated with different cytotoxicity assays (MTT, Cristal violet and Trypan blue exclusion assay), with an IC50 value of 22.57 μg/ml based on the MTT results. Furthermore, BV treatment induced necrosis, which was confirmed by typical morphological features and fast staining with ethidium-bromide dye. Pre-treatment with BV induced cell sensitization to cDDP, indicating that BV could improve the killing effect of selected cells when combined with cDDP. The isobologram method used to determine the extent of synergism in combining two agents to examine their possible therapeutic effect showed that combined treatment induced an additive and/or synergistic effect towards selected cells depending on the concentration of both. Hence, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. The obtained results indicate that joint treatment with BV could be useful from the point of minimizing the cDDP concentration during chemotherapy, thus reducing and/or postponing the development of drug resistance. Our data, in accordance with previously reported results, suggests that BV could be used in the development of a new strategy for cancer treatment. PMID:25916941

  14. Mitochondria and Nuclear changes in postimplanted mice embryos After treatment with Cisplatim antitumour drugs

    Directory of Open Access Journals (Sweden)

    Hassan M.El Ashmaoui

    2004-12-01

    Full Text Available To evaluate a possible relationship of maternal exposure to capsulation during postimp-lantation embryotoxicity, SWR pregnant female mice were injected intraperitoneally on day 4 of gestation with 7mg/kg cisplatin or with saline (0.4 ml for the control group. Embryos were collected after 24h 48h, 72h, after injection. ultrastructural sections were used to investigate the mitochondria and the nuclear changes Both the mitochondria and the nuclei were damaged specially 48h and 72 h after injection they may be related to cytotoxicity of the drug

  15. SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice

    OpenAIRE

    Neesse, A.; Frese, K K; Chan, D. S.; Bapiro, T. E.; Howat, W J; Richards, F. M.; Ellenrieder, V; Jodrell, D I; Tuveson, D A

    2013-01-01

    Design Pharmacokinetic and pharmacodynamic parameters of cremophor-paclitaxel, nab-paclitaxel (human-albumin-bound paclitaxel, Abraxane) and a novel mouse-albumin-bound paclitaxel (m-nab-paclitaxel) were evaluated in genetically engineered mouse models (GEMMs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), histological and biochemical analysis. Preclinical evaluation of m-nab-paclitaxel included assessment by three-dimensional high-resolution ultrasound and molecular analysis i...

  16. Topological estimation of proton-ligand formation constants of potential antitumour agents: Salicylhydroxamic acids

    Indian Academy of Sciences (India)

    Sneha Karmarkar; P V Khadikar; Vijay K Agrawal; Keshav C Mathur; Manorama Mandloi; Shobha Joshi

    2000-02-01

    Proton-ligand formation constants of salicylhydroxamic acids (SHA) and their nuclear substituted derivatives have been estimated topologically using the normalized Wiener index, referred to as mean square Wiener index (Wms). Regression analysis of the data indicates that Wms can be used successfully for estimating and monitoring proton-ligand formation constants.

  17. Cell-mediated anti-tumour immunity induced by devitalization in porcine malignant melanoma model

    Czech Academy of Sciences Publication Activity Database

    Horák, Vratislav; Soukupová, Pavla; Šinkora, J.; Řeháková, Z.; Málek, Ondřej; Hradecký, Jan; Klaudy, Jiří

    Praha: European School of Hematology, 2003. s. 1. [Euroconference on Animal Models of Human Diseases/3./. 16.05.2003-18.05.2003, Praha] R&D Projects: GA ČR GA524/01/0162; GA AV ČR IBS5045113 Institutional research plan: CEZ:AV0Z5045916 Keywords : devitalization Subject RIV: ED - Physiology

  18. Melanoma devitalization indfuces T cell anti-tumour immunity in the melim miniature pigs

    Czech Academy of Sciences Publication Activity Database

    Horák, V.; Soukupová, P.; Šinkora, Jiří; Řeháková, Zuzana; Veselský, Leopold; Málek, O.; Hradecký, J.; Klaudy, J.

    Gent, 2003, s. 583. [Meeting of the European Society for Pigmečnt Cell Research /11./. Gent (BE), 17.09.2003-20.09.2003] R&D Projects: GA ČR GA524/01/0162; GA AV ČR IBS5045113 Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z5020903 Keywords : hsp70 * til Subject RIV: EE - Microbiology, Virology

  19. Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents.

    Science.gov (United States)

    Le Gresley, A; Gudivaka, V; Carrington, S; Sinclair, A; Brown, J E

    2016-03-21

    A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar-phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents. PMID:26893255

  20. Versatile strategy for controlling the specificity and activity of engineered T cells.

    Science.gov (United States)

    Ma, Jennifer S Y; Kim, Ji Young; Kazane, Stephanie A; Choi, Sei-Hyun; Yun, Hwa Young; Kim, Min Soo; Rodgers, David T; Pugh, Holly M; Singer, Oded; Sun, Sophie B; Fonslow, Bryan R; Kochenderfer, James N; Wright, Timothy M; Schultz, Peter G; Young, Travis S; Kim, Chan Hyuk; Cao, Yu

    2016-01-26

    The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general application of current CAR-T--cell therapy is limited by serious treatment-related toxicities. One approach to improve the safety of CAR-T cells involves making their activation and proliferation dependent upon adaptor molecules that mediate formation of the immunological synapse between the target cancer cell and T-cell. Here, we describe the design and synthesis of structurally defined semisynthetic adaptors we refer to as "switch" molecules, in which anti-CD19 and anti-CD22 antibody fragments are site-specifically modified with FITC using genetically encoded noncanonical amino acids. This approach allows the precise control over the geometry and stoichiometry of complex formation between CD19- or CD22-expressing cancer cells and a "universal" anti-FITC-directed CAR-T cell. Optimization of this CAR-switch combination results in potent, dose-dependent in vivo antitumor activity in xenograft models. The advantage of being able to titrate CAR-T-cell in vivo activity was further evidenced by reduced in vivo toxicity and the elimination of persistent B-cell aplasia in immune-competent mice. The ability to control CAR-T cell and cancer cell interactions using intermediate switch molecules may expand the scope of engineered T-cell therapy to solid tumors, as well as indications beyond cancer therapy. PMID:26759368

  1. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    Energy Technology Data Exchange (ETDEWEB)

    Aquino, B.; Stefanello, A.A.; Oliveira, M.A.S.; Pedrosa, F.O.; Souza, E.M.; Monteiro, R.A.; Chubatsu, L.S. [Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2015-07-10

    NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain.

  2. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    International Nuclear Information System (INIS)

    NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain

  3. Activated Charcoal

    Science.gov (United States)

    ... reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile flow problems (cholestasis) during pregnancy. ... pregnancy, according to some early research reports. Preventing hangover. Activated charcoal is included in some hangover remedies, ...

  4. Active Galaxies

    DEFF Research Database (Denmark)

    Kilerci Eser, Ece

    Galaxy formation and evolution is one of the main research themes of modern astronomy. Active galaxies such as Active Galactic Nuclei (AGN) and Ultraluminous Infrared Galaxies (ULIRGs) are important evolutionary stages of galaxies. The ULIRG stage is mostly associated with galaxy mergers and...... interactions. During the interactions of gas-rich galaxies, the gas inflows towards the centers of the galaxies and can trigger both star formation and AGN activity. The ULIRG stage includes rapid star formation activity and fast black hole growth that is enshrouded by dust. Once the AGN emission is...... one is related to the mass estimates of supermassive black holes (SMBHs). Mass estimates of SMBHs are important to understand the formation and evolution of SMBHs and their host galaxies. Black hole masses in Type 1 AGN are measured with the reverberation mapping (RM) technique. Reverberation mapping...

  5. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    OpenAIRE

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F.I.; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L. J. M.

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposur...

  6. Active colloids

    Science.gov (United States)

    Aranson, Igor S.

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior.

  7. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial.

    Science.gov (United States)

    Robertson, K D; Hayward, S D; Ling, P D; Samid, D; Ambinder, R F

    1995-01-01

    The Epstein-Barr Virus (EBV) latency C promoter (Cp) is the origin of transcripts for six viral proteins. The promoter is active in lymphoblastoid B-cell lines but silent in many EBV-associated tumors and tumor cell lines. In these latter cell lines, the viral episome is hypermethylated in the vicinity of this promoter. We show that in such a cell line (Rael, a Burkitt's lymphoma line), 5-azacytidine inhibits DNA methyltransferase, brings about demethylation of EBV genomes, activates Cp transcription, and induces the expression of EBNA-2. Investigation of the phenomenon demonstrates the importance of the methylation status of a particular CpG site for the regulation of the Cp: (i) genomic sequencing shows that this site is methylated when the Cp is inactive and is not methylated when the promoter is active; (ii) methylation or transition mutation at this site abolishes complex formation with a cellular binding activity (CBF2) as determined by electrophoretic mobility shift analyses, competition binding analyses, and DNase I footprinting; and (iii) a single C --> T transition mutation at this site is associated with a marked reduction (> 50-fold) of transcriptional activity in a reporter plasmid. Thus, the CBF2 binding activity is shown to be methylation sensitive and crucial to EBNA-2-mediated activation of the Cp. PMID:7565767

  8. Physics activities

    International Nuclear Information System (INIS)

    As we move into the 21st Century, nuclear technology is on the verge of rejuvenation in advanced Member States and of expansion in developing Member States. The principal responsibilities of the IAEA are transferring technologies, co-ordinating scientific research, managing specialized projects and maintaining analytical quality control. The IAEA physics activities provide assistance with nuclear instrumentation, promote more effective utilization of research reactors and accelerators, and facilitate global co-operation in nuclear fusion research. These activities will help Member States improve their standards of living through the benefits of nuclear technology. This booklet presents a brief profile on the physics activities and involvement in these fields of the Physics Section, IAEA

  9. Regulatory activities

    International Nuclear Information System (INIS)

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  10. Lignin binding to pancreatic lipase and its influence on enzymatic activity.

    Science.gov (United States)

    Zhang, Juan; Xiao, Lin; Yang, Yucai; Wang, Zhaoxia; Li, Genxi

    2014-04-15

    In this paper, we find that the effect of lignin on pancreatic lipase (PL) is dependent on reaction medium and substrate used. Experimental results reveal that lignin can gradually bind to PL to form a PL-lignin complex, resulting in an increased activity of the enzyme. The binding process is spontaneous and the PL-lignin complex formation is an endothermic reaction induced by hydrophobic and electrostatic interaction. There is a non-radiation energy transfer from PL to lignin during the binding process, and the binding of lignin to PL conforms to a secondary exponential decay function. Moreover, the α-helix content of the enzyme will be changed and the rigidity of its side chain will be enhanced due to the formation of lignin-PL complex. This study has not only provided the activation effect of lignin on PL, but also given an insight into the interaction between lignin and the enzyme, which would benefit the application of lignin in the pharmacy and food industry, as well as other fields. PMID:24295682

  11. E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Pruneda, Jonathan N. [Department of Biochemistry, University of Washington, Seattle WA USA; Smith, F. Donelson [Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle WA USA; Daurie, Angela [Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada; Swaney, Danielle L. [Department of Genome Sciences, University of Washington, Seattle WA USA; Villén, Judit [Department of Genome Sciences, University of Washington, Seattle WA USA; Scott, John D. [Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle WA USA; Stadnyk, Andrew W. [Department of Pediatrics, Dalhousie University, Halifax NS Canada; Le Trong, Isolde [Department of Biological Structure, University of Washington, Seattle WA USA; Stenkamp, Ronald E. [Department of Biochemistry, University of Washington, Seattle WA USA; Department of Biological Structure, University of Washington, Seattle WA USA; Klevit, Rachel E. [Department of Biochemistry, University of Washington, Seattle WA USA; Rohde, John R. [Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada; Brzovic, Peter S. [Department of Biochemistry, University of Washington, Seattle WA USA

    2014-01-20

    Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.

  12. Active house

    DEFF Research Database (Denmark)

    Eriksen, Kurt Emil; Olesen, Gitte Gylling Hammershøj

    2010-01-01

    Formålet med dette abstrakt er at illustrere, at huse kan være konstrueret til at basere sig udelukkende på vedvarende energikilder og samtidig være CO2-neutrale og producere mere energi end de forbruger. Active House Visionen undersøger disse muligheder i otte demonstration huse i fem forskellige...

  13. Activated Sludge.

    Science.gov (United States)

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  14. Surface charge-transfer complex formation of catechol on titanium(IV) oxide and the application to bio-sensing.

    Science.gov (United States)

    Murata, Yusuke; Hori, Hiroshige; Taga, Atsushi; Tada, Hiroaki

    2015-11-15

    Adsorption properties of 2-hydroxyphenol (catechol) on TiO2 particles has been studied at 298K. The adsorption proceeds from the aqueous solution with the Langmuir type behavior. Diffuse reflectance infrared spectra of the catechol-adsorbed TiO2 suggested that catechol is adsorbed on TiO2 solution via the chelation to the surface Ti ions. The adsorption induces a strong absorption in the whole visible region, of which intensity increases with an increase in the adsorption amount. Photoelectrochemical experiments and molecular orbital calculations indicate that the absorption stems from the charge-transfer (CT) transition from the HOMO of catechol to the conduction band of TiO2. Time courses for the adsorption of catechol on mesoporous TiO2 nanocrystalline film-coated glass was traced by measuring the change in the absorbance of the CT band, and analyzed on the basis of the Langmuir model. This study would present a new simple technique for sensing of important biomolecules bearing the catechol moiety. PMID:26247381

  15. Studies on U(VI)-salicylate Charge Transfer Complex Formation by Using Time-resolved Laser Fluorescence Spectroscopy

    International Nuclear Information System (INIS)

    Organic ligands, such as humic and fulvic acids, play important roles in dissolution and migration of actinide radionuclide species. They can form stable actinide complexes in the presence of inorganic ions like hydroxides and carbonates. Therefore, the structural mimics of such ligands containing carboxylic and phenolic functional groups have been targets of studies to understand their chemical behaviors migrating actinides under geological groundwater conditions. Among many carboxylic ligands salycylate (SA) is useful to examine the role of phenolic groups on humic substances. Salicylate ion can form ligand-to-metal chargetransfer (LMCT) complexes with various metal ions. It has been shown that the fluorescence of SA is suppressed in the presence of Cu(II) or Eu(III) at pH 4 by forming ground state complexes. While uranyl ions also can form complex with SA, the dominant species at pH 4-7 region is known to be an 1:1 complex. However, the chemical structures reported on this 1:1 species are different among [UO2SA]0, [UO2(OH)SAH]0 and [UO2(OH)SA]-. For α- hydroxycarboxylates cyclic chelate structures were suggested where both carboxylate and phenolate groups simultaneously bind to uranyl ion. In the present study we investigate aqueous U(VI)- SA complex systems by using UV-Vis absorbance measurement and highly sensitive time-resolved laserinduced fluorescence spectroscopic (TRLFS) technique. The U(VI)-SA complex shows two characteristic charge-transfer (CT) bands at higher pH (> 4), which we found useful to examine the complexation equilibrium. Further, the TRLFS method is used to study the fluorescence (FL) quenching of U(VI) species, particularly for hydroxouranyl species at pH 4.5 of which FL is significantly suppressed as SA concentration elevates in aqueous solution. Fluorescence quenching mechanism in conjunction with the formation of U(VI)-SA CT complex is discussed

  16. Naturally occurring autologous anti-idiotypic antibodies. Participation in immune complex formation in selective IgA deficiency

    OpenAIRE

    1982-01-01

    50% of individuals of selective IgA deficiency have high serum titers of antibody to bovine proteins, and high levels of circulating immune complexes that contain bovine antigens. Because in animal studies, immunization with antigen-antibody complexes is a very effective means of producing anti-idiotypic antibodies, we sought such autoantibodies in two sera known to have large amounts of anticasein. After IgG isolation and two-stage affinity chromatography, IgG-like material (molecular weight...

  17. Inclusion complex formation of ionic liquids with 4-sulfonatocalixarenes studied by competitive binding of berberine alkaloid fluorescent probe

    Science.gov (United States)

    Miskolczy, Zsombor; Biczók, László

    2009-07-01

    A clinically important natural isoquinoline alkaloid, berberine, was used as a fluorescent probe to study the encapsulation of 1-alkyl-3-methylimidazolium (C nMIm +) type ionic liquids in 4-sulfonato-substituted calix[4]arene (SCX4) and calix[6]arene (SCX6) at pH 2. Addition of ionic liquids to the aqueous solution of berberine-SCXn inclusion complexes brought about considerable fluorescence intensity diminution due to the extrusion of berberine from the macrocycle into the aqueous phase by the competitive inclusion of C nMIm + cation. The lengthening of the aliphatic side chain of the imidazolium moiety diminished the equilibrium constant of complexation with SCX4, but enhanced the stability of SCX6 complexes. Larger binding strength was found for SCX4.

  18. Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation

    OpenAIRE

    Choi, Ki-Choon

    2011-01-01

    Hye-Young Lee1,*, Young-IL Jeong2,*, Ki-Choon Choi31Anyang Science University, Anyang, Gyeonggi, South Korea; 2Chonnam National University Hwasun Hospital, Jeonnam, South Korea; 3Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration, Chungnam, South Korea*These authors contributed equally to this work.Background: p-Phenylenediamine (PDA) or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair ...

  19. Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation

    OpenAIRE

    Lee HY; Jeong YI; Choi KC

    2011-01-01

    Hye-Young Lee1,*, Young-IL Jeong2,*, Ki-Choon Choi31Anyang Science University, Anyang, Gyeonggi, South Korea; 2Chonnam National University Hwasun Hospital, Jeonnam, South Korea; 3Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration, Chungnam, South Korea*These authors contributed equally to this work.Background: p-Phenylenediamine (PDA) or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair ...

  20. The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic.

    Science.gov (United States)

    Kala, S V; Neely, M W; Kala, G; Prater, C I; Atwood, D W; Rice, J S; Lieberman, M W

    2000-10-27

    Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 microg/liter by as much as 50-300-fold, yet little is known about the molecular basis for arsenic excretion. Here we show that transport of arsenic into bile depends on the MRP2/cMOAT transporter and that glutathione is obligatory for such transport. Using reversed phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic-glutathione complexes not previously identified in vivo, arsenic triglutathione and methylarsenic diglutathione, account for most of the arsenic in the bile. The structure of the compounds was also confirmed by nuclear magnetic resonance spectroscopy. Our findings may help explain the increased susceptibility of malnourished human populations to arsenic. PMID:10938093

  1. Effect of mixed-ligand complex formation on the volatility of alkaline-earth element β-diketonates

    International Nuclear Information System (INIS)

    Some aspects of effect of heteroligand complexing on structure, thermal stability and volatility of β-diketonates of alkaline earth elements are considered using own and literature data. Radius of M2+ ion increases from 0.99 up to 1.34 A in the Ca-Sr-Ba row and strength and coordination numbers of forming associates increase. The strength of molecular associates decreases and volatility increases when degree of branching and degree of fluorination of alkyl radicals in β-diketonate ligands increase

  2. Host-Guest Chemistry in the Gas Phase: Complex Formation of Cucurbit[6]uril with Proton-bound Water Dimer

    Science.gov (United States)

    Noh, Dong Hun; Lee, Shin Jung C.; Lee, Jong Wha; Kim, Hugh I.

    2014-03-01

    The hydration of cucurbit[6]uril (CB[6]) in the gas phase is investigated using electrospray ionization traveling wave ion mobility mass spectrometry (ESI-TWIM-MS). Highly abundant dihydrated and tetrahydrated species of diprotonated CB[6] are found in the ESI-TWIM-MS spectrum. The hydration patterns of the CB[6] ion and the dissociation patterns of the hydrated CB[6] ion indicate that two water molecules are bound to each other, forming a water dimer in the CB[6] complex. Ion mobility studies combined with the structures calculated by density functional theory suggest that the proton-bound water dimer is present as a Zundel-like structure in the CB[6] portal, forming a hydrogen bond network with carbonyl groups of the CB[6]. When a large guest molecule is bound to a CB[6] portal, water molecules cannot bind to the portal. In addition, the strong binding energy of the water dimer blocks the portal, hindering the insertion of the long alkyl chain of the guest molecule into the CB[6] cavity. With small alkali metal cations, such as Li+ and Na+, a single water molecule interacts with the CB[6] portal, forming hydrogen bonds with the carbonyl groups of CB[6]. A highly stable Zundel-like structure of the proton-bound water dimer or a metal-bound water molecule at the CB[6] portal is suggested as an initial hydration process for CB[6], which is only dissolved in aqueous solution with acid or alkali metal ions.

  3. DNA Condensation by Partially Acetylated Poly(amido amine Dendrimers: Effects of Dendrimer Charge Density on Complex Formation

    Directory of Open Access Journals (Sweden)

    Ronald G. Larson

    2013-09-01

    Full Text Available The ability of poly(amido amine (or PAMAM dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5 dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA.

  4. Temperature and dose dependence of defect complex formation with ion implanted Mn/Fe in ZnO

    CERN Document Server

    Mølholt, T E; Gunnlaugsson, H P; Bharuth-Ram, K; Fanciulli, M; Gíslason, H P; Johnston, K; Kobayashi, Y; Langouche, G; Masenda, H; Naidoo, D; Ólafsson, S; Sielemann, R; Weyer, G

    2009-01-01

    57Fe Mössbauer spectroscopy following ion implantation of radioactive 57Mn+ ( T1/2=85.4 s) has been applied to study the formation of Fe/Mn implantation-induced defects in ZnO at temperatures between 319 and 390 K. The formation of ferric iron–vacancy complexes is found to depend strongly on the implanted dose and to be faster and more efficient at higher temperatures. The results at these temperatures suggest the mobility of the Zn vacancy, together with vacancy trapping at the substitutional Mn/Fe impurities are responsible for the formation of Fe–VZn complexes

  5. The reaction of iodoplatination of triple bond by platinum(4) complexes: formation of σ-vinyl derivatives

    International Nuclear Information System (INIS)

    According to IR and 1H NMR data, propargyl alcohol reacts with platinum(4) iodide complexes in aqueous solution at 10-15 deg C to yield the product of the addition of platinum(4) and iodine to the triple bond, which has been isolated in the form of Pt(CH=CI-CH2OH)2I2(CH3OH). The σ-vinyl ligands in the complex are situated in cis-position. The complex obtained decomposed at 80 deg C to form products of reductive elimination - E,E-2,5-diiodo-1,6-diolhexadiene-2,4 and PtI2. 3 refs

  6. Fundamental Differences between Group 8 Metals: Unexpected Oxidation State Preferences and Mechanisms in Ruthenium Borylene Complex Formation.

    Science.gov (United States)

    Braunschweig, Holger; Damme, Alexander; Dewhurst, Rian D; Radacki, Krzysztof; Weißenberger, Felix; Wennemann, Benedikt; Ye, Qing

    2016-06-13

    The reaction of the salts K[Ru(CO)3 (PMe3 )(SiR3 )] (R=Me, Et) with Br2 BDur or Cl2 BDur (Dur=2,3,5,6-Me4 C6 H) leads to both boryl and borylene complexes of divalent ruthenium, the former through simple salt elimination and the latter through subsequent CO loss and 1,2-halide shift. The balance of products can be altered by varying the reaction conditions; boryl complexes can be favored by the addition of CO, and borylene complexes by removal of CO under vacuum. All of these products are in competition with the corresponding (aryl)(halo)(trialkylsilyl)borane, a reductive elimination product. The Ru(II) borylene products and the mechanisms that form them are distinctly different from the analogous reactions with iron, which lead to low-valent borylene complexes, highlighting fundamental differences in oxidation state preferences between iron and ruthenium. PMID:27124888

  7. Complex formation by the Drosophila MSL proteins: role of the MSL2 RING finger in protein complex assembly.

    OpenAIRE

    Copps, K.; Richman, R.; Lyman, L M; Chang, K A; Rampersad-Ammons, J; Kuroda, M I

    1998-01-01

    Drosophila MSL proteins are thought to act within a complex to elevate transcription from the male X chromosome. We found that the MSL1, MSL2 and MSL3 proteins are associated in immunoprecipitations, chromatographic steps and in the yeast two-hybrid system, but that the MLE protein is not tightly complexed in these assays. We focused our analysis on the MSL2-MSL1 interaction, which is postulated to play a critical role in MSL complex association with the X chromosome. Using a modified two-hyb...

  8. From PII Signaling to Metabolite Sensing: A Novel 2-Oxoglutarate Sensor That Details PII - NAGK Complex Formation

    OpenAIRE

    Lüddecke, Jan; Forchhammer, Karl

    2013-01-01

    The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specific...

  9. Actinide oxalate complexes formation as a function of temperature by capillary electrophoresis coupled with inductively coupled plasma mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Brunel, Benoit; Mendes, Mickael; Aupiais, Jean [CEA, DAM, DIF, Arpajon (France); Philippini, Violaine [Nice Univ. Sophia Antipolis (France). Inst. de Chimie de Nice

    2015-05-01

    Complexation of various actinides (U(VI), Np(V), Pu(V), Am(III)) by oxalato ligand was studied by capillary electrophoresis (ICPMS detection) in 0.1 mol L{sup -1} NaClO{sub 4} ionic strength solutions at various temperatures (15, 25, 35, 45 and 55 C). For each solution a unique peak was observed as a result of a fast equilibrium between the free ions and the complexes (labile systems). The results confirmed the formation of the 1:1, 1:2 and 1:3 complexes for U(VI) and Am(III); the formation of the 1:1 and 1:2 complexes for Np(V) and the formation of only 1 complex for Pu(V). For each complex, the thermodynamic parameters (the Gibbs energy Δ{sub r}G(T), the molar entropy change Δ{sub r}S(T) and the molar enthalpy change Δ{sub r}H(T{sup 0})) were fitted to the experimental data. The effect of the ionic medium was treated using the specific ion interaction theory and the thermodynamic parameters at zero ionic strength were compared to previously published data.

  10. Internalization of nucleoside phosphates into live cells by complex formation with different CPPs and JBS-nucleoducin.

    Science.gov (United States)

    Mussbach, Franziska; Pietrucha, Regina; Schaefer, Buerk; Reissmann, Siegmund

    2011-01-01

    Nucleoside phosphates can bind to many functional proteins like G-proteins or other GTP-binding proteins in signal transduction or translation processes. Till now internalization of nucleoside phosphates into live cells remains a challenge. We study the internalization of a fluorescent-labelled deoxyuridine triphosphate into HeLa cells and other adhesion and suspension cells. We use different cell-penetrating peptides and a cocktail suitable for formation of non-covalent complexes with the nucleotide. Internalization is observed by fluorescence microscopy, and the uptake efficiency is quantitatively estimated by fluorescence spectroscopy. The applied concentrations of CPPs and the cocktail were checked on cell viability (MTT test) and membrane integrity (bioluminescence test with peptidyl-luciferin), indicating that the CPPs and the complexes with the nucleotide are cytotoxic above certain concentrations. These concentrations depend on CPP and cell type and are the limiting factors for the cargo uptake. PMID:21053144

  11. Atomic absorption spectroscopic, conductometric and colorimetric methods for determination of fluoroquinolone antibiotics using ammonium reineckate ion-pair complex formation

    Science.gov (United States)

    Ragab, Gamal H.; Amin, Alaa S.

    2004-03-01

    Three accurate, rapid and simple atomic absorption spectrometric, conductometric and colorimetric methods were developed for the determination of norfloxacin (NRF), ciprofloxacin (CIP), ofloxacin (OFL) and enrofloxacin (ENF). The proposed methods depend upon the reaction of ammonium reineckate with the studied drugs to form stable precipitate of ion-pair complexes, which was dissolved in acetone. The pink coloured complexes were determined either by AAS or colorimetrically at λmax 525 nm directly using the dissolved complex. Using conductometric titration, the studied drugs could be evaluated in 50% (v/v) acetone in the range 5.0-65, 4.0-48, 5.0-56 and 6.0-72 μg ml -1 of NRF, CPF, OFL and ENF, respectively. The optimizations of various experimental conditions were described. The results obtained showed good recoveries of 99.15±1.15, 99.30±1.40, 99.60±1.50, and 99.00±1.25% with relative standard deviations of 0.81, 1.06, 0.97, and 0.69% for NRF, CPF, OFL, and ENF, respectively. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented.

  12. Tissues development in stems of Aristolochia clematitis L. in the point of view of multicellular complexes formation

    Directory of Open Access Journals (Sweden)

    Zofia Puławska

    2014-02-01

    Full Text Available After cytokinesis the cells do not separate but remain within the wall of the mother cell. After a series of divisions a multicellular complex arises. In the stems of Aristolochia clematitis procambium is closer related to protoxylem than to protophloem, and metaphloem is closer related to metaxylem than to protophloem. Since protophloem has a closer common origin with fibre primordia than with the remaining tissues, it cannot be decided unequivocally what is the origin of the fibres or when procambium differentiates. The common origin of the primary vascular tissues is visible in the pattern of the multicellular complexes, whereas the common origin of the secondary vascular tissue developing in the underground several-year-old parts of the stem can be traced in the arrangement of the single radial tiers. Some characteristics of symplastic growth are discussed.

  13. Amino-terminal domains of the bovine papillomavirus type 1 E1 and E2 proteins participate in complex formation.

    OpenAIRE

    Benson, J D; Howley, P M

    1995-01-01

    Interaction between the E1 and E2 papillomavirus proteins appear to play an important role in viral DNA replication, although the exact domains of each protein involved in this interaction have not been identified. Using bovine papillomavirus type 1 (BPV-1) as a model for examining interactions between E1 and E2, we have used the two-hybrid and glutathione S-transferase (GST) fusion systems to map domains of BPV-1 E1 and E2 that interact in vivo and in vitro. In the two-hybrid system experime...

  14. STUDY OF THERMODYNAMICS OF COMPLEX FORMATION OF FLAVONOIDS OF STEVIА (STEVіA REBAUDіANABERTONі) LEAVES

    OpenAIRE

    Kuznetsova, I.

    2014-01-01

    Изучен механизм образования комплекса флаваноидов с ионами алюминия. На основе отрицательных низких значений энергии Гиббса установлено,что комплексообразование является природным явлением. Впервые определены термодинамические свойства флаваноидов листьев стевии (Stevіa rebaudіana Bertonі) сушенных и разработана номограмма зависимости содержания флаваноидов от возможности комплексообразования. В результате проведённых иследований определена антиоксидантная способность флаваноидов, которые сод...

  15. Confirmation of vanadium complex formation using electrospray mass spectrometry and determination of vanadium speciation by sample stacking capillary electrophoresis

    International Nuclear Information System (INIS)

    Capillary zone electrophoresis (CZE) with UV detection was used to determine vanadium species. Nitrilotriacetic acid (NTA), hydroxyethylethylenediaminetriacetic acid (HEDTA), ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), ethylene glycol-bis(2-aminoethylether)-tetraacetic acid (EGTA) and 2,6-pyridinedicarboxylic acid (PDCA) were investigated to determine whether these ligands formed stable anionic complexes with vanadium. Of all the ligands studied HEDTA was the most suitable ligand because it gave the largest UV response with reasonable migration time. Electrospray mass spectrometry (ES-MS) was used to confirm the formation of [VO2(HEDTA)]2- and [VO(HEDTA)]1- in solution. An electrolyte containing 25 mM phosphate, 0.25 mM tetradecyltrimethylammonium bromide (TTAB) at pH 5.5 was optimum for the separation of these anionic vanadium complexes. Sample stacking techniques, including large-volume sample stacking (LVSS) and field-amplified sample injection (FASI), were tested to improve the sensitivity. Best sensitivity was obtained using FASI, with detection limits of 0.001 μM, equivalent to 0.4 μg L-1, for [VO2(HEDTA)]2- and 0.01 μM, equivalent to 3.4 μg L-1 for [VO(HEDTA)]1-. The utility of the method for the speciation of V(IV) and V(V) was demonstrated using ground water samples

  16. Electrochemical deposition of cadmium sulfide thin films from organic solution I. Sulfur reduction and cadmium-polysulfide complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Mondon, F.

    1985-02-01

    The reduction of sulfur in an aprotic solvent (DMSO) is known to be a two-stage process; each stage involves a bielectronic electrochemical step followed by a chemical dismutation reaction. When reduction is performed at a rotating electrode, it is shown that the electrochemical steps alone are involved in the electrode process. The voltammetric waves then correspond to the simple scheme 1st wave: S/sub 8/ + 2e/sup -/ ..-->.. S/sub 8//sup 2 -/ 2nd wave: S/sub 8//sup 2 -/ + 2e/sup -/ ..-->.. 2S/sub 4//sup 2 -/ The slower dismutation reactions appear only in the bulk of solution. They lead to electron number which differ from 2 when S/sub 8/ is electrolyzed. The addition of Cd/sup 2 -/ ions to a polysulfide ion solution yields soluble polysulfide-cadmium 2:1 complexes (Cd(S /SUB x/ )/sub 2/)/sup 2 -/ with /chi/ = 8, 6, and 4. The stability of the complex is increased when /chi/ decreases from 8 to 4, which leads to dismutation and exchange reactions between complexes, polysulfide ions, and sulfur.

  17. Cadmium(II) complex formation with selenourea and thiourea in solution: an XAS and 113Cd NMR study.

    Science.gov (United States)

    Jalilehvand, Farideh; Amini, Zahra; Parmar, Karnjit

    2012-10-15

    The complexes formed in methanol solutions of Cd(CF(3)SO(3))(2) with selenourea (SeU) or thiourea (TU), for thiourea also in aqueous solution, were studied by combining (113)Cd NMR and X-ray absorption spectroscopy. At low temperature (~200 K), distinct (113)Cd NMR signals were observed, corresponding to CdL(n)(2+) species (n = 0-4, L = TU or SeU) in slow ligand exchange. Peak integrals were used to obtain the speciation in the methanol solutions, allowing stability constants to be estimated. For cadmium(II) complexes with thione (C═S) or selone (C═Se) groups coordinated in Cd(S/Se)O(5) or Cd(S/Se)(2)O(4) (O from MeOH or CF(3)SO(3)(-)) environments, the (113)Cd chemical shifts were quite similar, within 93-97 ppm and 189-193 ppm, respectively. However, the difference in the chemical shift for the Cd(SeU)(4)(2+) (578 pm) and Cd(TU)(4)(2+) (526 ppm) species, with CdSe(4) and CdS(4) coordination, respectively, shows less chemical shielding for the coordinated Se atoms than for S, in contrast to the common trend with increasing shielding in the following order: O > N > Se > S. In solutions dominated by mono- and tetra-thiourea/selenourea complexes, their coordination and bond distances could be evaluated by Cd K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy. At ~200 K and high excess of thiourea, a minor amount (up to ~30%) of [Cd(TU)(5-6)](2+) species was detected by an upfield shift of the (113)Cd NMR signal (up to 423 ppm) and an amplitude reduction of the EXAFS oscillation. The amount was estimated by fitting linear combinations of simulated EXAFS spectra for [Cd(TU)(4)](2+) and [Cd(TU)(6)](2+) complexes. At room temperature, [Cd(TU)(4)](2+) was the highest complex formed, also in aqueous solution. Cd L(3)-edge X-ray absorption near edge structure (XANES) spectra of cadmium(II) thiourea solutions in methanol were used to follow changes in the CdS(x)O(y) coordination. The correlations found from the current and previous studies between (113)Cd NMR chemical shifts and different Cd(II) coordination environments are generally useful for evaluating cadmium coordination to thione-containing or Se-donor ligands in biochemical systems or for monitoring speciation in solution. PMID:23016594

  18. Study on complex formation of cadmium (II) ions, 9. Formation constants on cadmium (II) complexes with dicarboxylic acids

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Haruo (Government Industrial Research Inst., Nagoya (Japan))

    1984-03-01

    Formation constants of cadmium (11) complexes with dicarboxylic acids such as oxalic, malonic, methylmalonic, succinic, and glutaric acids were determined in aqueous solutions containing 3 mol.dm/sup -3/ LiClO/sub 4/ as a constant ionic medium at 25/sup 0/C by potentiometric titrations. It was reported in the previous works that cadmium (11)- aspartic acid complexes contained two chelate rings. However, a problem remained whether the second chelate ring could be formed by six membered-ring containing -O-Cd-N- bond or by seven membered-ring containing -O-Cd-O- bond. The results of the present work suggested that it would be formed by a six membered ring. Cadmium (11) ions were coordinated with a carboxylic group of the dicarboxylic acids studied, and formed no chelate ring within the complexes. The white precipitate appeared in the solution containing cadmium (11) ion and oxalic acid, in the pH range below 3.0, therefore, the chelate formation was not ascertained in this case. The formation constants, log ..beta..sub(pr)= log((Cdsub(p)Lsub(r)sup((2p-2r)+))/((Cd/sup 2 +/)sup(p)(L/sup 2 -/)sup(r))), of the complexes were: log ..beta../sub 11/ = 1.98, log ..beta../sub 12/ = 3.05 for cadmium (11)-malonic acid; log ..beta../sub 11/ = 2.28, log ..beta../sub 12/ = 3.06 for cadmium (11)-methylmalonic acid; log ..beta../sub 11/ = 1.78, log ..beta../sub 12/ = 3.08 for cadmium (11)-succinic acid; log ..beta../sub 11/ = 1.85, log ..beta../sub 12/ = 3.28 for cadmium (11)-glutaric acid complexes.

  19. Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Schmiedeke, T.M.; Stoeckl, F.W.W.; Weber, R.; Sugisaki, Y.; Batsford, S.R.; Vogt, A.

    1989-06-01

    An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns, have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of /sup 125/I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary.

  20. Spectrophotometric determination of Mercury (II by simultaneous micelle mediated extraction through ternary complex formation in water samples

    Directory of Open Access Journals (Sweden)

    Farzin Nekouei

    2014-06-01

    Full Text Available In this study, a micelle mediated extraction procedure for preconcentration of trace quantities of Hg(II as a prior step to its simultaneous spectrophotometric determination has been developed. The method is based on a ternary ion-association of Hg(II, Xylidyl Blue (XB and cationic surfactant (CTAB. Major factors affecting the efficiency of the method has been studied. The limit of detection (LOD under optimum conditions based on 3Sb was 4.65 ng mL-1. The proposed method has been applied for determination of trace amount of mercury in water samples with satisfactory results.