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Sample records for synthetic trihydroxilated chalcones

  1. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    PubMed Central

    Echeverria, Cesar; Santibañez, Juan Francisco; Donoso-Tauda, Oscar; Escobar, Carlos A.; Ramirez-Tagle, Rodrigo

    2009-01-01

    Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series. PMID:19333443

  2. A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

    PubMed Central

    Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

    2014-01-01

    Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2′,5′-dihydroxychalcone (2′,5′-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4′,6′-dimethoxy-2′-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements. PMID:22239485

  3. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    PubMed Central

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

  4. Experimental and quantum chemical studies of a novel synthetic prenylated chalcone

    PubMed Central

    2013-01-01

    Background Chalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra. Results A novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical 1H-NMR and 13C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry. Conclusion Considering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of 1H-NMR and 13C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones

  5. Differential Effects of Structural Modifications on the Competition of Chalcones for the PIB Amyloid Imaging Ligand-Binding Site in Alzheimer's Disease Brain and Synthetic Aβ Fibrils.

    PubMed

    Fosso, Marina Y; McCarty, Katie; Head, Elizabeth; Garneau-Tsodikova, Sylvie; LeVine, Harry

    2016-02-17

    Alzheimer's disease (AD) is a complex brain disorder that still remains ill defined. In order to understand the significance of binding of different clinical in vivo imaging ligands to the polymorphic pathological features of AD brain, the molecular characteristics of the ligand interacting with its specific binding site need to be defined. Herein, we observed that tritiated Pittsburgh Compound B ((3)H-PIB) can be displaced from synthetic Aβ(1-40) and Aβ(1-42) fibrils and from the PIB binding complex purified from human AD brain (ADPBC) by molecules containing a chalcone structural scaffold. We evaluated how substitution on the chalcone scaffold alters its ability to displace (3)H-PIB from the synthetic fibrils and ADPBC. By comparing unsubstituted core chalcone scaffolds along with the effects of bromine and methyl substitution at various positions, we found that attaching a hydroxyl group on the ring adjacent to the carbonyl group (ring I) of the parent member of the chalcone family generally improved the binding affinity of chalcones toward ADPBC and synthetic fibrils F40 and F42. Furthermore, any substitution on ring I at the ortho-position of the carbonyl group greatly decreases the binding affinity of the chalcones, potentially as a result of steric hindrance. Together with the finding that neither our chalcones nor PIB interact with the Congo Red/X-34 binding site, these molecules provide new tools to selectively probe the PIB binding site that is found in human AD brain, but not in brains of AD pathology animal models. Our chalcone derivatives also provide important information on the effects of fibril polymorphism on ligand binding.

  6. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

    PubMed Central

    de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Sechini Cordeiro, Marlon Norberto; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

    2015-01-01

    Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID:26366075

  7. Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation.

    PubMed

    Ramalho, Suelem Demuner; Bernades, Aline; Demetrius, Giulio; Noda-Perez, Caridad; Vieira, Paulo Cezar; Dos Santos, Caio Yu; da Silva, James Almada; de Moraes, Manoel Odorico; Mousinho, Kristiana Cerqueira

    2013-11-01

    A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one (12), (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (13), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (14), and (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (15) showed significant cytotoxicities. The most effective compound was 15, which showed high cytotoxic activity with an IC50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.

  8. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

    PubMed Central

    Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

    2009-01-01

    Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

  9. Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in inhibiting the properties of CD133+ sphere-forming cells in liver stem cells

    PubMed Central

    Lin, Rui-Xin; Gong, Lu-Lu; Fan, Li-Mei; Zhao, Zhong-Kai; Yang, Shu-Li

    2015-01-01

    The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133+ hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133+ in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 μM and on day 8. The percentage of CD133+ cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, β-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133+ HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC. PMID:25973027

  10. Development of a stability-indicating LC method for determination of a synthetic chalcone derivative in a nanoemulsion dosage form and identification of the main photodegradation product by LC-MS.

    PubMed

    Mattos, Cristiane B; Deponti, Vânia B; Barreto, Fabiano; Simões, Cláudia M O; Andrighetti-Frohner, Carla R; Nunes, Ricardo J; Steindel, Mário; Teixeira, Helder F; Koester, Letícia S

    2012-11-01

    This study aimed to develop and validate a stability indicating LC for the determination of 5-(2-benzoylethenyl)-N-benzyl-2 methoxybenzenesulfonamide (SCD - a synthetic chalcone derivative), and evaluate the degradation profile of the compound under different stress conditions recommended by International Conference on Harmonization (ICH). Chromatographic separation was performed on a silica C18 column, methanol-water mobile phase 70:30 (v:v), pH 5.0 adjusted with the addition of trifluoroacetic acid (TFA) at a flow rate of 1.0 mL min(-1); detection by UV absorption at 330 nm. The method was validated for linearity, precision, accuracy, robustness and specificity. The SCD was subjected to forced degradation and peak photodegradation product was well separated from the pure substance, with retention times significantly different, indicating the specificity of the method. Second-order degradation kinetics of SCD was observed under photodegradation and base-induced degradation. In order to identify the product formed under photodegradation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed. These results indicate that the method can be successfully used in order to assay SCD in a nanoemulsion dosage form, and that this formulation has a protective effect over SCD degradation.

  11. A chalcone with potent inhibiting activity against biofilm formation by nontypeable Haemophilus influenzae.

    PubMed

    Kunthalert, Duangkamol; Baothong, Sudarat; Khetkam, Pichit; Chokchaisiri, Suwadee; Suksamrarn, Apichart

    2014-10-01

    Nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, frequently causes biofilm infections. Currently, resistance of bacteria within the biofilm to conventional antimicrobials poses a major obstacle to effective medical treatment on a global scale. Novel agents that are effective against NTHi biofilm are therefore urgently required. In this study, a series of natural and synthetic chalcones with various chemical substituents were evaluated in vitro for their antibiofilm activities against strong biofilm-forming strains of NTHi. Of the test chalcones, 3-hydroxychalcone (chalcone 8) exhibited the most potent inhibitory activity, its mean minimum biofilm inhibitory concentration (MBIC50 ) being 16 μg/mL (71.35 μM), or approximately sixfold more active than the reference drug, azithromycin (MBIC50 419.68 μM). The inhibitory activity of chalcone 8, which is a chemically modified chalcone, appeared to be superior to those of the natural chalcones tested. Significantly, chalcone 8 inhibited biofilm formation by all studied NTHi strains, indicating that the antibiofilm activities of this compound occur across multiple strong-biofilm forming NTHi isolates of different clinical origins. According to antimicrobial and growth curve assays, chalcone 8 at concentrations that decreased biofilm formation did not affect growth of NTHi, suggesting the biofilm inhibitory effect of chalcone 8 is non-antimicrobial. In terms of structure-activity relationship, the possible substituent on the chalcone backbone required for antibiofilm activity is discussed. These findings indicate that 3-hydroxychalcone (chalcone 8) has powerful antibiofilm activity and suggest the potential application of chalcone 8 as a new therapeutic agent for control of NTHi biofilm-associated infections.

  12. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    PubMed

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-02-22

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  13. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    PubMed Central

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A.; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

  14. Chemical reactivity and biological activity of chalcones and other α,β-unsaturated carbonyl compounds.

    PubMed

    Maydt, Daniela; De Spirt, Silke; Muschelknautz, Christian; Stahl, Wilhelm; Müller, Thomas J J

    2013-08-01

    Abstract 1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction. 2. The present study used a model system estimating the reactivity of different synthetic chalcones and other α,β-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts. 3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5'-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure-reactivity relationship. Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ((2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one) and chalcone 7 (1,3-diphenylprop-2-yn-1-one). This result demonstrates that α,β-unsaturated carbonyl derivatives react with thiols differently. All compounds were also biologically active; however, expression of HO-1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake. Most efficient inducers of HO-1 expression were BAP, 4-hydroxynonenal and chalcone 1 (4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile), chalcone 5 ((2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one) and chalcone 7.

  15. Advances in chalcones with anticancer activities.

    PubMed

    Karthikeyan, Chandrabose; Moorthy, Narayana S H Narayana; Ramasamy, Sakthivel; Vanam, Uma; Manivannan, Elangovan; Karunagaran, Devarajan; Trivedi, Piyush

    2015-01-01

    Chalcones are naturally occurring compounds exhibiting broad spectrum biological activities including anticancer activity through multiple mechanisms. Literature on anticancer chalcones highlights the employment of three pronged strategies, namely; structural manipulation of both aryl rings, replacement of aryl rings with heteroaryl scaffolds, molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of anticancer properties. Methoxy substitutions on both the aryl rings (A and B) of the chalcones, depending upon their positions in the aryl rings appear to influence anticancer and other activities. Similarly, heterocyclic rings either as ring A or B in chalcones, also influence the anticancer activity shown by this class of compounds. Hybrid chalcones formulated by chemically linking chalcones to other prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines, benzothiazoles, imidazolones have demonstrated synergistic or additive pharmacological activities. The successful application of these three pronged strategies for discovering novel anticancer agents based on chalcone scaffold has resulted in many novel and chemically diverse chalcones with potential therapeutic application for many types of cancer. This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and also provides an overview of the patents published in this area between 2007 and 2014 (WO2013022951, WO201201745 & US2012029489).

  16. Anti-cancer chalcones: Structural and molecular target perspectives.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

    2015-06-15

    Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold remained a fascination among researchers in the 21st century due to its simple chemistry, ease of synthesis and a wide variety of promising biological activities. Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ABCG2/P-gp/BCRP, 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, HDAC/Situin-1, proteasome, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, cathepsin-K, topoisomerase-II, Wnt, NF-κB, B-Raf and mTOR etc. In this review, a comprehensive study on molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), structure activity relationships (SARs) and patents granted have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer chalcones.

  17. Chalcone and curcumin derivatives: a way ahead for malarial treatment.

    PubMed

    Kumar, Dileep; Kumar, Manish; Kumar, Ashok; Singh, Sushil Kumar

    2013-12-01

    Malaria has been a major cause of morbidity and mortality in developing countries, particularly in Sub-Saharan Africa and South Asia. The global malaria situation is increasingly being challenging owing to lack of credible malaria vaccine and the emergence of drug resistance to most of the available antimalarials. They demand search for novel generation of drugs. Versatility and flexibility for structural modification of natural and synthetic analogues of curcumin and chalcone have been explored extensively for designing new antimalarial agent. Recent advances to our knowledge of parasite biology as well as the availability of the genome sequence, have opened up new vista in the firmament of antimalarial drug designing for identifying novel molecular targets. Curcumin and chalcones has been reported to exert anti-malarial effect by binding directly to numerous signaling molecules, such as histone acetyltransferase, histone deacetylase, sarco (endo) plasmic reticulum Ca(2+)-ATPase, cysteine proteases etc. This review highlights insights the more recent antimalarial activities of these compounds, their mechanisms of action, molecular targets and relevant structureactivity relationship studies. Natural lead compounds like chalcone and curcumin have shown good and optimal binding to many enzymes present in parasite and can be explored as molecular targets for in silico studies to develop new, affordable and effective antimalarial drugs. With no credible malaria vaccine in sight, there is an imperative need to develop new drugs with different mechanisms of action to help preclude issues of cross-resistance.

  18. Diverse Molecular Targets for Chalcones with Varied Bioactivities

    PubMed Central

    Zhou, Bo; Xing, Chengguo

    2015-01-01

    Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities. PMID:26798565

  19. Chalcones as Promising Lead Compounds on Cancer Therapy.

    PubMed

    León-González, Antonio J; Acero, Nuria; Muñoz-Mingarro, Dolores; Navarro, Inmaculada; Martín-Cordero, Carmen

    2015-01-01

    Chalcones constitute a group of phenolic compounds that command an increasing interest on cancer research. Natural chalcones are widespread through the plant kingdom. The most abundant and investigated chalcones are isoliquiritigenin, flavokawain and xanthohumol, which are present in the Fabaceae, Piperaceae, Cannabaceae, and Moraceae families. These chalcones have been shown to be promising lead antitumor-chemopreventive drugs by three different activities: antioxidants, cytotoxic and apoptosis inducers. In the recent years, SAR (structure-activity relationship) has contributed towards the improvement of anticancer properties of chalcones by substituting aryl rings and introducing heterocyclic moieties. This review summarizes the anticancer activities shown by natural chalcones and the SAR and describes how different chemical moiety modifications could lead them to be therapeutically useful in the treatment of cancer.

  20. Benzylidenetetralones, cyclic chalcone analogues, induce cell cycle arrest and apoptosis in HCT116 colorectal cancer cells.

    PubMed

    Drutovic, David; Chripkova, Martina; Pilatova, Martina; Kruzliak, Peter; Perjesi, Pal; Sarissky, Marek; Lupi, Monica; Damia, Giovanna; Broggini, Massimo; Mojzis, Jan

    2014-10-01

    Colorectal cancer is the third most common cancer in the world, with 1.2 million new cancer cases annually. Chalcones are secondary metabolite precursors of flavonoids that exhibit diverse biological activities, including antioxidant and antitumor activities. The aim of this study was to investigate the antiproliferative effect of new synthetic chalcone derivatives on HCT116 cells. (E)-2-(2',4'-dimethoxybenzylidene)-1-tetralone (Q705) was found to be the most active (IC50 = 3.44 ± 0.25 μM). Based on these results, this compound was chosen for further analysis of its biochemical and molecular mechanisms. Our results showed that Q705 inhibited the growth and clonogenicity of HCT116 cells. The results of a flow cytometric analyses suggested that this compound caused a significant cell cycle arrest in G2/M phase and increased the proportion of cells in the subG0/G1 phase, marker of apoptosis. Q705-induced apoptosis was confirmed by TdT-mediated dUTP nick end labelling (TUNEL) assay. Treatment of HCT116 cells with this chalcone significantly increased the caspase-3,-7 activity and resulted in cleavage of poly-ADP-ribose polymerase (PARP). Changes in the nuclear morphology such as chromatin condensation were also observed. These effects were associated with a decreased expression of bcl-xL and increased overall ratio of bax/bcl-xL mRNA levels. Immunofluorescence and qRT-PCR analysis revealed that Q705 induced H2AX histone modifications characteristic of DNA damage, disruption of microtubule organization and downregulation of tubulins. In summary, these results suggest that the cyclic chalcone analogue Q705 has potential as a new compound for colorectal cancer therapy.

  1. Structural Elucidation of Chalcone Reductase and Implications for Deoxychalcone Biosynthesis

    PubMed Central

    Bomati, Erin K.; Austin, Michael B.; Bowman, Marianne E.; Dixon, Richard A.; Noel, Joseph P.

    2010-01-01

    4,2′,4′,6′-tetrahydroxychalcone (chalcone) and 4,2′,4′-trihydroxychalcone (deoxychalcone) serve as precursors of ecologically important flavonoids and isoflavonoids. Deoxychalcone formation depends on chalcone synthase and chalcone reductase; however, the identity of the chalcone reductase substrate out of the possible substrates formed during the multistep reaction catalyzed by chalcone synthase remains experimentally elusive. We report here the three-dimensional structure of alfalfa chalcone reductase bound to the NADP+ cofactor and propose the identity and binding mode of its substrate, namely the non-aromatized coumaryl-trione intermediate of the chalcone synthase-catalyzed cyclization of the fully extended coumaryl-tetraketide thioester intermediate. In the absence of a ternary complex, the quality of the refined NADP+-bound chalcone reductase structure serves as a template for computer-assisted docking to evaluate the likelihood of possible substrates. Interestingly, chalcone reductase adopts the three-dimensional structure of the aldo/keto reductase superfamily. The aldo/keto reductase fold is structurally distinct from all known ketoreductases of fatty acid biosynthesis, which instead belong to the short-chain dehydrogenase/reductase superfamily. The results presented here provide structural support for convergent functional evolution of these two ketoreductases that share similar roles in the biosynthesis of fatty acids/polyketides. In addition, the chalcone reductase structure represents the first protein structure of a member of the aldo/ketoreductase 4 family. Therefore, the chalcone reductase structure serves as a template for the homology modeling of other aldo/ketoreductase 4 family members, including the reductase involved in morphine biosynthesis, namely codeinone reductase. PMID:15970585

  2. Induction of chalcone isomerase in elicitor-treated bean cells. Comparison of rates of synthesis and appearance of immunodetectable enzyme.

    PubMed

    Robbins, M P; Dixon, R A

    1984-11-15

    Chalcone isomerase, an enzyme involved in the formation of flavonoid-derived compounds in plants, has been purified nearly 600-fold from cell suspension cultures of dwarf French bean (Phaseolus vulgaris L.). Chromatofocussing yielded a single form of the enzyme of apparent pI 5.0. This preparation was used to raise rabbit anti-(chalcone isomerase) serum. Changes in the rate of synthesis of chalcone isomerase have been investigated by indirect immunoprecipitation of enzyme labelled in vivo with [35S]methionine in elicitor-treated cultures of P. vulgaris. Elicitor, heat-released from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum, the causal agent of anthracnose disease of bean, causes increased synthesis of the isomerase, with maximum synthetic rate occurring 11-12 h after exposure to elicitor. Immune blotting studies indicate that the elicitor-mediated increase in extractable activity of the isomerase is associated with increased appearance of immunodetactable isomerase protein of Mr 27 000. However, the maximum level of immunodetectable isomerase was attained approximately 6 h earlier than maximum extractable activity. Furthermore, a 2.8-fold increase in enzyme activity above basal levels at 12 h after elicitor-treatment was associated with a corresponding 5.8-fold increase in immunodetectable enzyme. It is concluded that elicitor induces the synthesis of both active and inactive chalcone isomerase of Mr 27 000, and that some activation of inactive enzyme occurs during the elicitor-mediated increase in isomerase activity. The presence of a pool of inactive chalcone isomerase in bean cell cultures has recently been suggested on the basis of density labelling experiments utilising 2H from 2H2O [Dixon et al. (1983) Planta (Berl.) 159, 561-569].

  3. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    PubMed Central

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  4. Chalcone scaffolds as anti-infective agents: structural and molecular target perspectives.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

    2015-08-28

    In recent years, widespread outbreak of numerous infectious diseases across the globe has created havoc among the population. Particularly, the inhabitants of tropical and sub-tropical regions are mainly affected by these pathogens. Several natural and (semi) synthetic chalcones deserve the credit of being potential anti-infective candidates that inhibit various parasitic, malarial, bacterial, viral, and fungal targets like cruzain-1/2, trypanopain-Tb, trans-sialidase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, falcipain-1/2, β-hematin, topoisomerase-II, plasmepsin-II, lactate dehydrogenase, protein kinases (Pfmrk and PfPK5), and sorbitol-induced hemolysis, DEN-1 NS3, H1N1, HIV (Integrase/Protease), protein tyrosine phosphatase A/B (Ptp-A/B), FtsZ, FAS-II, lactate/isocitrate dehydrogenase, NorA efflux pump, DNA gyrase, fatty acid synthase, chitin synthase, and β-(1,3)-glucan synthase. In this review, a comprehensive study (from Jan. 1982 to May 2015) of the structural features of anti-infective chalcones, their mechanism of actions (MOAs) and structure activity relationships (SARs) have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-infective agents.

  5. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect.

    PubMed

    Vogel, Susanne; Barbic, Matej; Jürgenliemk, Guido; Heilmann, Jörg

    2010-06-01

    Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'-dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'-trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3+/-0.4 microM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7+/-0.3 and 6.0+/-1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 microM the TNFalpha induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.

  6. Synthesis and Biological Evaluation of Retinoid-Chalcones as Inhibitors of Colon Cancer Cell Growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids were designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer ce...

  7. Bis-chalcones and flavones: synthesis and antimicrobial activity.

    PubMed

    Husain, Asif; Rashid, Mohd; Mishra, Ravinesh; Kumar, Deepak

    2013-01-01

    A series of bis-chalcones (3a-g) and their flavones derivatives (4a-g) were synthesized and evaluated for their antimicrobial activity. Bis-chalcones were prepared by condensing 1,1'-(4,6-dihydroxy-1,3-phenylene)diethanone (2) with appropriate aryl aldehydes following Claisen-Schmidt reaction conditions. Oxidative cyclization of bis-chalcones (3a-g) in DMSO in the presence of iodine furnished flavones (4a-g). The synthesized compounds were evaluated for their antibacterial and antifungal actions against some selected microbes. The results of antimicrobial evaluation showed that some of the synthesized compounds were good in their antibacterial and antifungal actions.

  8. 4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

    SciTech Connect

    Ku, Bo Mi; Ryu, Hyung Won; Lee, Yeon Kyung; Ryu, Jinhyun; Jeong, Joo Yeon; Choi, Jungil; Cho, Hee Jun; Park, Ki Hun; Kang, Sang Soo

    2010-11-19

    Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, and tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.

  9. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed Central

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  10. Chromene chalcones from Tephrosia carrollii and the revised structure of Oaracacin.

    PubMed

    Gómez-Garibay, F; Arciniega, M D; Céspedes, C L; Taboada, J; Calderón, J S

    2001-01-01

    The aerial parts of Tephrosia carrollii afforded two chromene chalcones. Their structures and stereochemistry were established by spectroscopic methods. The structure of oaxacacin was revised and confirmed by X-ray diffraction. In this paper, we describe the isolation of the chalcone known as "oaxacacin" and the new chalcone named epoxyobovatachalcone. The compound der. oaxacacin was found to be identical with obovatachalcone based on spectroscopic evidence and X-ray diffraction.

  11. Enzymatic reactions by five chalcone synthase homologs from hop (Humulus lupulus L.).

    PubMed

    Okada, Yukio; Sano, Yukie; Kaneko, Takafumi; Abe, Ikuro; Noguchi, Hiroshi; Ito, Kazutoshi

    2004-05-01

    The enzyme activities encoded in five cDNAs for chalcone synthase (CHS) homologs from hop were investigated. Only valerophenone synthase (VPS) and CHS_H1 showed both naringenin-chalcone and phlorisovalerophenone forming activity. Narigenin-chalcone production by VPS was much lower than by CHS_H1. Therefore, it is highly possible that flavonoid depends mainly on CHS_H1, while bitter acid biosynthesis depends mainly on VPS and CHS_H1.

  12. Novel prenylated bichalcone and chalcone from Humulus lupulus and their quinone reductase induction activities.

    PubMed

    Yu, Liyan; Zhang, Fuxian; Hu, Zhijuan; Ding, Hui; Tang, Huifang; Ma, Zhongjun; Zhao, Xiaofeng

    2014-03-01

    A new prenylated chalcone xanthohumol M (1), a novel prenylated bichalcone humulusol (2) and six known chalcones (3-8) were found from Humulus lupulus. Their structures were determined by spectroscopic methods. All the chalcones' electrophilic abilities were assessed by GSH (glutathione) rapid screening, and their QR (quinone reductase) induction activities were evaluated using hepa 1c1c7 cells. The results of electrophilic assay and QR induction activity assay were quite well. New compounds 1 and 2, along with some known prenylated chalcones, displayed certain QR induction activity.

  13. Molecular evolution and sequence divergence of plant chalcone synthase and chalcone synthase-Like genes.

    PubMed

    Han, Yingying; Zhao, Wenwen; Wang, Zhicui; Zhu, Jingying; Liu, Qisong

    2014-06-01

    Plant chalcone synthase (CHS) and CHS-Like (CHSL) proteins are polyketide synthases. In this study, we evaluated the molecular evolution of this gene family using representative types of CHSL genes, including stilbene synthase (STS), 2-pyrone synthase (2-PS), bibenzyl synthase (BBS), acridone synthase (ACS), biphenyl synthase (BIS), benzalacetone synthase, coumaroyl triacetic acid synthase (CTAS), and benzophenone synthase (BPS), along with their CHS homologs from the same species of both angiosperms and gymnosperms. A cDNA-based phylogeny indicated that CHSLs had diverse evolutionary patterns. STS, ACS, and 2-PS clustered with CHSs from the same species (late diverged pattern), while CTAS, BBS, BPS, and BIS were distant from their CHS homologs (early diverged pattern). The amino-acid phylogeny suggested that CHS and CHSL proteins formed clades according to enzyme function. The CHSs and CHSLs from Polygonaceae and Arachis had unique evolutionary histories. Synonymous mutation rates were lower in late diverged CHSLs than in early diverged ones, indicating that gene duplications occurred more recently in late diverged CHSLs than in early diverged ones. Relative rate tests proved that late diverged CHSLs had unequal rates to CHSs from the same species when using fatty acid synthase, which evolved from the common ancestor with the CHS superfamily, as the outgroup, while the early diverged lineages had equal rates. This indicated that late diverged CHSLs experienced more frequent mutation than early diverged CHSLs after gene duplication, allowing obtaining new functions in relatively short period of time.

  14. Design of potent fluoro-substituted chalcones as antimicrobial agents.

    PubMed

    Burmaoglu, Serdar; Algul, Oztekin; Gobek, Arzu; Aktas Anil, Derya; Ulger, Mahmut; Erturk, Busra Gul; Kaplan, Engin; Dogen, Aylin; Aslan, Gönül

    2017-12-01

    Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9-15, and 20-23) using a structure-activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and three common fungal strains. Three derivatives (3, 9, and 10) displayed significant antitubercular activity with IC50 values of ≤16,760. Compounds derived from trimethoxy substituent scaffolds with monofluoro substitution on the B ring of the chalcone structure exhibited superior inhibition activity compared to corresponding hydroxy analogs. In terms of antimicrobial activity, most compounds (3, 9, 12-14, and 23) exhibited moderate to potent activity against the bacteria, and the antifungal activities of compounds 3, 13, 15, 20, and 22 were comparable to those of reference drugs ampicillin and fluconazole.

  15. [Cloning, expression and charaterization of chalcone synthase from Saussurea medusa].

    PubMed

    Xia, Fang; Li, Houhua; Fu, Chunxiang; Yu, Zhenzhen; Xu, Yanjun; Zhao, Dexiu

    2011-09-01

    A fragment of chalcone synthase gene (SmCHS) was cloned from the cDNA library constructed in Saussurea medusa. The full-length cDNA sequence of SmCHS was obtained by RT-PCR. Sequence analysis showed that the full length of SmCHS was 1313 bp, containing an open reading frame (1170 bp) encoding 389 amino acids. The molecular weight of the protein was estimated to be 43 kDa. The prokaryotic expression plasmids pET28a(+)-SmCHS was constructed and transformed into Escherichia coli BL21(DE3) for expression. SDS-PAGE indicated that the fusion protein was expressed partially in soluble form after induction by IPTG. The recombinant protein was collected and purified by Ni-NTA affinity column. The enzymatic activity assay of the purified recombinant protein showed that the fusion protein had chalcone synthase activity. It could catalyze the condensation of a 4-coumaroyl-CoA with three malonyl-CoAs to produce naringenin chalcone.

  16. Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i) and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthes...

  17. Green synthesis of chalcones derivatives as intermediate of flavones and their antibacterial activities

    NASA Astrophysics Data System (ADS)

    VH, Elfi Susanti; Matsjeh, Sabirin; Wahyuningsih, Tutik Dwi; Mustofa, Redjeki, Tri

    2016-02-01

    Four chalcones derivatives have been synthesized from 3,4-dimethoxybenzaldehyde and acetophenone derivatives (2-hydroxy acetophenone, 2,4-dihydroxy acetophenone, 2,5-dihydroxy acetophenone and 2,6-dihydroxy acetophenone). The synthesis of these chalcones were conducted by Claisen-Schmidt condensation using grinding techniques at room temperature in the absence of solvents. The chalcones were prepared by grinding together equivalent amount of the approriate hydroxyacetophenone and 3,4-dimethoxybenzaldehyde in the presence of solid sodium hydroxide. Grinding techniques for synthesis of the chalcones derivatives is simple, efficient and environmentally benign compared to conventional methods. Then, the four chalcones derivatives undergo cyclization reactions to produce four flavones after reacted with iodine. The synthesized compounds were characterized by spectrometry (IR, 1H-NMR, 13C-NMR and MS).

  18. Green synthesis of chalcones derivatives as intermediate of flavones and their antibacterial activities

    SciTech Connect

    VH, Elfi Susanti Redjeki, Tri; Matsjeh, Sabirin Wahyuningsih, Tutik Dwi; Mustofa

    2016-02-08

    Four chalcones derivatives have been synthesized from 3,4-dimethoxybenzaldehyde and acetophenone derivatives (2-hydroxy acetophenone, 2,4-dihydroxy acetophenone, 2,5-dihydroxy acetophenone and 2,6-dihydroxy acetophenone). The synthesis of these chalcones were conducted by Claisen-Schmidt condensation using grinding techniques at room temperature in the absence of solvents. The chalcones were prepared by grinding together equivalent amount of the approriate hydroxyacetophenone and 3,4-dimethoxybenzaldehyde in the presence of solid sodium hydroxide. Grinding techniques for synthesis of the chalcones derivatives is simple, efficient and environmentally benign compared to conventional methods. Then, the four chalcones derivatives undergo cyclization reactions to produce four flavones after reacted with iodine. The synthesized compounds were characterized by spectrometry (IR, {sup 1}H-NMR, {sup 13}C-NMR and MS)

  19. Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents.

    PubMed

    Vijaya Bhaskar Reddy, Mopur; Hung, Hsin-Yi; Kuo, Ping-Chung; Huang, Guan-Jhong; Chan, Yu-Yi; Huang, Shiow-Chyn; Wu, Shwu-Jen; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Wu, Tian-Shung

    2017-04-01

    Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in LPS-activated mouse peritoneal macrophages. Among the tested compounds, a 1,3-diarylpropane analog, 2-(3-(3,4-dimethoxyphenyl)propyl)-5-methoxyphenol (3p), displayed the most significant inhibitory effects against NO production. To investigate the mechanism of action, the effects of 3p on iNOS and COX-2 protein expression were studied by immunoblot. The results concluded that 3p is capable of inhibiting iNOS expression in LPS-induced RAW264.7 cells via attenuation of NF-κB signaling by ERK, p38, and JNK.

  20. Quantitative analysis of flavanones and chalcones from willow bark.

    PubMed

    Freischmidt, A; Untergehrer, M; Ziegler, J; Knuth, S; Okpanyi, S; Müller, J; Kelber, O; Weiser, D; Jürgenliemk, G

    2015-09-01

    Willow bark extracts are used for the treatment of fever, pain and inflammation. Recent clinical and pharmacological research revealed that not only the salicylic alcohol derivatives, but also the polyphenols significantly contribute to these effects. Quantitative analysis of the European Pharmacopoeia still focuses on the determination of the salicylic alcohol derivatives. The objective of the present study was the development of an effective quantification method for the determination of as many flavanone and chalcone glycosides as possible in Salix purpurea and other Salix species as well as commercial preparations thereof. As Salix species contain a diverse spectrum of the glycosidated flavanones naringenin, eriodictyol, and the chalcone chalconaringenin, a subsequent acidic and enzymatic hydrolysis was developed to yield naringenin and eriodictyol as aglycones, which were quantified by HPLC. The 5-O-glucosides were cleaved with 11.5% TFA before subsequent hydrolysis of the 7-O-glucosides with an almond β-glucosidase at pH 6-7. The method was validated with regard to LOD, LOQ, intraday and interday precision, accuracy, stability, recovery, time of hydrolysis, robustness and applicability to extracts. All 5-O- and 7-O-glucosides of naringenin, eriodictyol and chalconaringenin were completely hydrolysed and converted to naringenin and eriodictyol. The LOD of the HPLC method was 0.77 μM of naringenin and 0.45 μM of eriodictyol. The LOQ was 2.34 μM of naringenin and 1.35 μM for eriodictyol. The method is robust with regard to sample weight, but susceptible concerning enzyme deterioration. The developed method is applicable to the determination of flavanone and chalcone glycosides in willow bark and corresponding preparations.

  1. Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase.

    PubMed

    Abe, Ikuro; Watanabe, Tatsuya; Morita, Hiroyuki; Kohno, Toshiyuki; Noguchi, Hiroshi

    2006-02-02

    [reaction: see text]. Chalcone synthase (CHS) is a plant-specific type III polyketide synthase catalyzing condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA. Surprisingly, it was demonstrated that S338V mutant of Scutellaria baicalensis CHS produced octaketides SEK4/SEK4b from eight molecules of malonyl-CoA. Further, the octaketides-forming activity was dramatically increased in a CHS triple mutant (T197G/G256L/S338T). The functional conversion is based on the simple steric modulation of a chemically inert residue lining the active-site cavity.

  2. Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents.

    PubMed

    Cole, Amy L; Hossain, Sandra; Cole, Alex M; Phanstiel, Otto

    2016-06-15

    A series of chalcone, flavone, coumaranone and other flavonoid compounds were screened for their anti HIV-1 activity in two cell culture models using TZM-bl and PM1 cells. Within the systems evaluated, the most promising compounds contained either an α- or β-hydroxy-carbonyl motif within their structure (e.g., 8 and 9). Efficacious substituents were identified and used to design new HIV inhibitors with increased potency and lower cytotoxicity. Of the scaffolds evaluated, specific chalcones were found to provide the best balance between anti-HIV potency and low host cell toxicity. Chalcone 8l was shown to inhibit different clinical isolates of HIV in a dose-dependent manner (e.g., IC50 typically⩽5μM). Inhibition of HIV infection experiments using TZM-bl cells demonstrated that chalcone 8l and flavonol 9c had IC50 values of 4.7μM and 10.4μM, respectively. These insights were used to design new chalcones 8o and 8p. Rewardingly, chalcones 8o and 8p (at 10μM) each gave >92% inhibition of viral propagation without impacting PM1 host cell viability. Inhibition of viral propagation significantly increased (60-90%) when PM1 cells were pre-incubated with chalcone 8o, but not with the related flavonol 9c. These results suggested that chalcone 8o may be of value as both a HIV prophylactic and therapy. In summary, O-benzyl-substituted chalcones were identified as promising anti-HIV agents for future investigation.

  3. Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists.

    PubMed

    Zhang, Guoning; Liu, Shuainan; Tan, Wenjuan; Verma, Ruchi; Chen, Yuan; Sun, Deyang; Huan, Yi; Jiang, Qian; Wang, Xing; Wang, Na; Xu, Yang; Wong, Chiwai; Shen, Zhufang; Deng, Ruitang; Liu, Jinsong; Zhang, Yanqiao; Fang, Weishuo

    2017-03-31

    Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy. Many chalcones and four chromenes were identified as microM potent FXR antagonists, among which chromene 11c significantly decreased the plasma and hepatic triglyceride level in KKay mice.

  4. Effects of chalcone derivatives on players of the immune system.

    PubMed

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.

  5. Effects of chalcone derivatives on players of the immune system

    PubMed Central

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

  6. Xanthohumol, a prenylated chalcone from Humulus lupulus L., inhibits cholesteryl ester transfer protein.

    PubMed

    Hirata, Hiroshi; Takazumi, Koji; Segawa, Shuichi; Okada, Yukio; Kobayashi, Naoyuki; Shigyo, Tatsuro; Chiba, Hitoshi

    2012-10-01

    High density lipoprotein (HDL)-cholesterol levels are correlated with a low risk of atherosclerosis. The inhibition of cholesteryl ester transfer protein (CETP), which catalyses cholesterol transfer between lipoproteins, leads to an increase in HDL-cholesterol and is expected to be the next anti-atherogenic target. This study revealed that xanthohumol, a prenylated chalcone, showed the highest inhibition against CETP from screening of natural products in various plants. We investigated the inhibitory activity of some chalcones and flavanones. Naringenin chalcone showed weak CETP inhibition compared with xanthohumol. In addition, isoxanthohumol and naringenin drastically decreased the inhibitory activity. These results suggest that the prenyl group and chalcone structure of xanthohumol were responsible for the CETP inhibitory activity.

  7. Novel Chalcone-Based Fluorescent Human Histamine H3 Receptor Ligands as Pharmacological Tools

    PubMed Central

    Tomasch, Miriam; Schwed, J. Stephan; Weizel, Lilia; Stark, Holger

    2012-01-01

    Novel fluorescent chalcone-based ligands at human histamine H3 receptors (hH3R) have been designed, synthesized, and characterized. Compounds described are non-imidazole analogs of ciproxifan with a tetralone motif. Tetralones as chemical precursors and related fluorescent chalcones exhibit affinities at hH3R in the same concentration range like the reference antagonist ciproxifan (hH3R pKi value of 7.2). Fluorescence characterization of our novel ligands shows emission maxima about 570 nm for yellow fluorescent chalcones and ≥600 nm for the red fluorescent derivatives. Interferences to cellular autofluorescence could be excluded. All synthesized chalcone compounds could be used to visualize hH3R proteins in stably transfected HEK-293 cells using confocal laser scanning fluorescence microscopy. These novel fluorescent ligands possess high potential to be used as pharmacological tools for hH3R visualization in different tissues. PMID:22470321

  8. Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages.

    PubMed

    Hirai, Shizuka; Kim, Young-Il; Goto, Tsuyoshi; Kang, Min-Sook; Yoshimura, Mineka; Obata, Akio; Yu, Rina; Kawada, Teruo

    2007-09-29

    Obese adipose tissue is characterized by an enhanced infiltration of macrophages. It is considered that the paracrine loop involving monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha between adipocytes and macrophages establishes a vicious cycle that augments the inflammatory changes and insulin resistance in obese adipose tissue. Polyphenols, which are widely distributed in fruit and vegetables, can act as antioxidants and some of them are also reported to have anti-inflammatory properties. Tomato is one of the most popular and extensively consumed vegetable crops worldwide, which also contains many flavonoids, mainly naringenin chalcone. We investigated the effect of flavonoids, including naringenin chalcone, on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages and in the interaction between adipocytes and macrophages. Naringenin chalcone inhibited the production of TNF-alpha, MCP-1, and nitric oxide (NO) by LPS-stimulated RAW 264 macrophages in a dose-dependent manner. Coculture of 3T3-L1 adipocytes and RAW 264 macrophages markedly enhanced the production of TNF-alpha, MCP-1, and NO compared with the control cultures; however, treatment with naringenin chalcone dose-dependently inhibited the production of these proinflammatory mediators. These results indicate that naringenin chalcone exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages. Naringenin chalcone may be useful for ameliorating the inflammatory changes in obese adipose tissue.

  9. Cloning, functional expression, and characterization of a chalcone 3-hydroxylase from Cosmos sulphureus.

    PubMed

    Schlangen, Karin; Miosic, Silvija; Thill, Jana; Halbwirth, Heidi

    2010-07-01

    A chalcone 3-hydroxylase (CH3H) cDNA clone was isolated and characterized from Cosmos sulphureus petals accumulating butein (2',3,4,4'-tetrahydroxychalcone) derivatives as yellow flower pigments. The recombinant protein catalyses the introduction of an additional hydroxyl group in the B-ring of chalcones, a reaction with high similarity to the hydroxylation of flavonoids catalysed by the well-studied flavonoid 3'-hydroxylase (F3'H). CH3H shows high specificity for chalcones, but a low F3'H activity was also detected. By contrast, the common F3'H from C. sulphureus does not accept chalcones as substrates and is therefore unlikely to be involved in the creation of the B-ring hydroxylation pattern of the yellow flower pigments. CH3H was primarily expressed in young buds, the main tissue for chalcone pigment formation. Expression levels in open flowers and 3-d-old seedlings were lower and almost no CH3H expression was observed in leaves. F3'H, in contrast, showed the highest expression also in buds, but comparable expression rates in all other tissues tested. Recombinant hybrid proteins constructed from CH3H and F3'H fragments demonstrated that amino acid residues at a substrate recognition site and an insertion of four amino acid residues in a putative loop region have an impact on chalcone acceptance. This is the first identification of a CH3H cDNA from any plant species.

  10. Cationic chalcone antibiotics. Design, synthesis, and mechanism of action.

    PubMed

    Nielsen, Simon F; Larsen, Mogens; Boesen, Thomas; Schønning, Kristian; Kromann, Hasse

    2005-04-07

    This paper describes how the introduction of "cationic" aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the B-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the A-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 muM against methicillin resistant Staphylococus aureus.

  11. Enzymes do what is expected (chalcone isomerase versus chorismate mutase).

    PubMed

    Hur, Sun; Bruice, Thomas C

    2003-02-12

    Madicago sativa chalcone isomerase (CI) catalyzes the isomerization of chalcone to flavanone, whereas E. coli chorismate mutase (CM) catalyzes the pericyclic rearrangement of chorismate to prephenate. Covalent intermediates are not formed in either of the enzyme-catalyzed reactions, K(M) and k(cat) are virtually the same for both enzymes, and the rate constants (k(o)) for the noncatalyzed reactions in water are also the same. This kinetic identity of both the enzymatic and the nonenzymatic reactions is not shared by a similarity in driving forces. The efficiency (DeltaG(o)() - DeltaG(cat)()) for the CI mechanism involves transition-state stabilization through general-acid catalysis and freeing of three water molecules trapped in the E.S species. The contribution to lowering DeltaG(cat)() by an increase in near attack conformer (NAC) formation in E.S as compared to S in water is not so important. In the CM reaction, the standard free energy for NAC formation in water is 8.4 kcal/mol as compared to 0.6 kcal/mol in E.S. Because the value of (DeltaG(o)() - DeltaG(cat)()) is 9 kcal/mol, the greater percentage of NACs accounts for approximately 90% of the kinetic advantage of the CM reaction. There is no discernible transition-state stabilization in the CM reaction. These results are discussed. In anthropomorphic terms, each enzyme has had to do what it must to have a biologically relevant rate of reaction.

  12. Effects of two 6-quinolinyl chalcones on the integrity of plasma membrane of Paracoccidioides brasiliensis.

    PubMed

    de Sá, Nívea P; Cisalpino, Patrícia S; Tavares, Luciana C; Espíndola, Leandro; Borelli, Beatriz M; Barbeira, Paulo Js; Cardoso Perdigão, Gabriele de Matos; Souza-Fagundes, Elaine M; Rosa, Carlos A; Pizzolatti, Moacir G; Johann, Susana

    2017-03-01

    Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, yet few therapeutic options exist. Our aim was to search for new compounds with high efficacy, low toxicity, shorter treatment time and affordable cost. We studied two synthetic 6-quinolinyl chalcones, 3b and 3e, to determine their effects on VERO cells, antifungal activity, survival curve, interaction with other drugs and phenotypic effects against several isolates of Paracoccidioides spp. In this study, we verified that the compounds were not toxic, exhibited superior in vitro activity compared with that shown by trimethoprim-sulfamethoxazole, and after 5 days of treatment, decreased the fungal cell viability by approximately 70%. Additionally, no interactions were observed between the tested compounds and other drugs. We also found that these compounds induced morphological changes, such as shriveling of cells, fragmentation of the plasma membrane and cytoplasmic disorganization in vitro. The changes observed by microscopy assays corroborate the observation made with propidium iodide, where the number of cells stained with the compounds was higher than that observed after amphotericin B treatment. We observed an increase in the efflux of K(+) and a loss of intracellular contents in cells treated with 3b and 3e, confirming their effects on fungal membranes. However, damage to the membrane was not associated with a decrease in membrane ergosterol levels. The experimental evidences showed no direct indications of cellular wall damage caused by these compounds. Thus, these results confirm the antifungal potential of 3b and 3e against Paracoccidioides spp. with possible action on the membrane.

  13. Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

    PubMed

    Kil, Yun-Seo; Choi, Seul-Ki; Lee, Yun-Sil; Jafari, Mahtab; Seo, Eun-Kyoung

    2015-10-23

    Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

  14. SYNTHETIC OIL,

    DTIC Science & Technology

    The patent concerns a dicarboxylate-base synthetic oil with antiwear and antioxidation additives. The oil is prepared from the esterification of 2- or 3-methylcyclohexanol and 2-ethylhexanol with adipic acid. (Author)

  15. Synthetic oils

    NASA Technical Reports Server (NTRS)

    Hatton, R. E.

    1973-01-01

    Synthetic lubricants are discussed by chemical class and their general strengths and weaknesses in terms of lubrication properties are analyzed. Comparative ratings are given for 14 chemical classes and are used as a guide for lubricant selection. The effects of chemical structure on the properties of the lubricant are described with special emphasis on thermal stability. The diversity of synthetic lubricants which is provided by the wide range of properties permits many applications, some of which are reported.

  16. Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers.

    PubMed

    Hofmann, Emily; Webster, Jonathan; Do, Thuy; Kline, Reid; Snider, Lindsey; Hauser, Quintin; Higginbottom, Grace; Campbell, Austin; Ma, Lili; Paula, Stefan

    2016-02-15

    In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones' effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class.

  17. Influence of industrial processing on orange juice flavanone solubility and transformation to chalcones under gastrointestinal conditions.

    PubMed

    Gil-Izquierdo, Angel; Gil, María Isabel; Tomas-Barberan, Francisco Abraham; Ferreres, Federico

    2003-05-07

    Orange juice manufactured at industrial scale was subjected to digestion under in vitro gastrointestinal conditions (pH, temperature, and enzyme and chemical conditions) to evaluate the influence of individual industrial processing treatments on flavanone solubility, stability, and ability to permeate through a membrane under simulated physiological conditions. Four industrial processes including squeezing, standard pasteurization, concentration, and freezing were evaluated. Hand squeezing was compared with industrial squeezing. After in vitro gastrointestinal digestion of the orange juices, the flavanones able to permeate through a dialysis membrane, and those remaining in the retentate were evaluated by HPLC as were those present in the insoluble fraction. In all of the assayed orange juices, a high content of precipitated chalcones ( approximately 70% of the total flavanones) was formed under the physiological conditions of the gastrointestinal tract. Hand squeezing provided a higher concentration of flavanones in the permeated fraction and lower transformation to chalcones than industrial squeezing. Standard pasteurization did not influence the solubility and permeability of the orange juice flavanones and chalcones. Industrial concentration did not affect the amount of flavanones able to permeate but decreased the chalcones produced. Juices produced from frozen orange juice contained considerably smaller amounts of both soluble flavanones and insoluble chalcones.

  18. In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells.

    PubMed

    Zenger, Katharina; Dutta, Subhajit; Wolff, Horst; Genton, Marc G; Kraus, Birgit

    2015-10-02

    Xanthohumol (XN), the major prenylated chalcone from hops (Humulus lupulus L.), has received much attention within the last years, due to its multiple pharmacological activities including anti-proliferative, anti-inflammatory, antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However, there exists a huge number of metabolites and structurally-related chalcones, which can be expected, or are already known, to exhibit various effects on cells. We have therefore analyzed the effects of XN and 18 other chalcones in a panel, consisting of multiple cell-based assays. Readouts of these assays addressed distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell cycle and other cellular features. Besides known active structural elements of chalcones, like the Michael system, we have identified several moieties that seem to have an impact on specific effects and toxicity in human liver cells in vitro. Based on these observations, we present a structure-toxicity model, which will be crucial to understand the molecular mechanisms of wanted effects and unwanted side-effects of chalcones.

  19. Antioxidant activities of [60]fullerene derivatives from chalcone, flavone and flavanone: A ONIOM approach via H-atom and electron transfer mechanism

    NASA Astrophysics Data System (ADS)

    Thong, Nguyen Minh; Dao, Duy Quang; Ngo, Thi Chinh; Huyen, Trinh Le; Nam, Pham Cam

    2016-05-01

    Antioxidant properties of C60 flavonoid conjugates were computationally examined via their O-H bond dissociation enthalpies (BDEs) and ionization energies (IEs) using two-layer ONIOM and PM6 methods, respectively. Eight ONIOM((RO)B3LYP/6-311++G(2df,2p):PM6) models were evaluated by computing BDE(O-H)s of a series of polyphenol. Synthetic mechanism of C60 flavonoid conjugates was also explored via the potential energy surfaces of reaction between C60 and malonate flavonoid derivatives (chalcone, flavone and flavanone) at the B3LYP/6-31G(d)//PM6. Antioxidant activities of C60 flavonoid conjugates were discussed via hydrogen atom transfer, single electron transfer mechanisms and the effect of C60 on the BDE(O-H)s and IEs of these compounds.

  20. Synthesis, growth, structure determination and optical properties of chalcone derivative single crystal

    SciTech Connect

    Karthi, S. Girija, E. K.

    2014-04-24

    Acquiring large nonlinear optical (NLO) efficient organic material is essential for the development of optoelectronics and photonic devices. Chalcone is the donor - Π - acceptor - Π - donor (D-Π-A-Π-D) type conjugated molecule with appreciable hyperpolarizability of potential interest in NLO applications. The addition of vinyl and electron donor groups in the chalcone molecule may enhance the second harmonic generation (SHG) efficiency. Here we report the synthesis, crystal growth and characterization of a chalcone derivative 1-(4-methylphenyl)-5-(4-methoxyphenyl)-penta-2,4-dien-1-one (MPMPP). The MPMPP crystal was grown by slow evaporation solution growth technique from acetone. The grown crystal structure was studied by single crystal X-ray diffraction. The SHG efficiency of the grown crystal was determined by Kurtz and Perry method.

  1. Organocatalytic regioselective asymmetric Michael addition of azlactones to o-hydroxy chalcone derivatives.

    PubMed

    Zhang, Shao-Yun; Ruan, Gui-Yu; Geng, Zhi-Cong; Li, Nai-Kai; Lv, Ming; Wang, Yong; Wang, Xing-Wang

    2015-05-28

    The regioselective and enantioselective Michael addition between azlactones and o-hydroxy chalcone derivatives is reported. Enantiomerically enriched N,O-aminals with two continuous stereogenic centers are exclusively obtained in moderate to good yields with excellent diastereoselectivities and good to excellent enantioselectivities. The experimental results show that an o-hydroxy group on the cinnamenyl motif of chalcone derivatives plays a crucial role at the reaction sites for the regioselective Michael addition. In addition, circular dichroism (CD) spectroscopy and density functional theory (DFT) are used to investigate the absolute configuration of N,O-aminals and the corresponding transition-state structures.

  2. Studies on the chalcone synthase gene of two higher plants: petroselinum hortense and matthiola incana

    SciTech Connect

    Hemleben, V.; Frey, M.; Rall, S.; Koch, M.; Kittel, M.; Kreuzaler, F.; Ragg, H.; Fautz, E.; Hahlbrock, K.

    1982-01-01

    Two higher plant systems are presented which allow to study coordinated gene expression of the light-induced metabolic pathway of flavonoid biosynthesis: tissue culture cells of Petroselinum hortense (Apiaceae) and different developmental stages of various genotypes of Matthiola incana (Brassicaceae). The gene structure of the chalcone synthase is mainly studied. A cDNA clone (pLF56) of parsley has been constructed and characterized conferring the chalcone synthase gene sequence. Strong cross hybridization between the parsley cDNA and Matthiola DNA allowed to identify a HindIII fragment (6000 bp) identical in size for parsley and different Matthiola wild type lines and a mutant line.

  3. Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones from Humulus lupulus.

    PubMed

    Vogel, Susanne; Heilmann, Jörg

    2008-07-01

    The minor hop ( Humulus lupulus) chalcones 3'-geranylchalconaringenin (3), 5'-prenylxanthohumol (4), flavokawin (5), xanthohumol H (8), xanthohumol C (9), and 1'',2''-dihydroxanthohumol C (10) were synthesized. The non-natural chalcones 3'-geranyl-6'-O-methylchalconaringenin (2), 3'-methylflavokawin (6), and 2'-O-methyl-3'-prenylchalconaringenin (7) were also synthesized. Cytotoxicity was investigated in HeLa cells, and these compounds all had IC 50 values comparable to xanthohumol (8.2-19.2 microM). The ORAC-fluorescein assay revealed potent antioxidative activity for 7 and 8 with 5.2 and 4.8 Trolox equivalents, respectively.

  4. Free Volume Related Fluorescence Properties of Electron Irradiated Chalcone Doped PMMA Films

    SciTech Connect

    Ravindrachary, Ismayil V.; Bhajantri, R. F.; Harisha, A.; Praveena, S. D.

    2011-07-15

    Effect of electron irradiation on free volume related fluorescence properties of chalcone doped Poly(methyl methacrylate)(PMMA) composite films have been studied using Positron Annihilation and Fluorescence spectroscopic techniques. In this polymer composite, enhancement of fluorescence at lower doses and reduction at higher doses has been observed under electron irradiation. From Positron annihilation studies suggests that at lower doses of irradiation induced crosslinking which affect the free volume properties and inturn hinders the chalcone molecular rotation. At higher doses chain scission process affect matrix relaxation. Under the restricted condition the chromophore molecules likely to emit enhanced fluorescence and its mobility is directly related to the free volume around it.

  5. Further studies on anti-invasive chemotypes: An excursion from chalcones to curcuminoids.

    PubMed

    Roman, Bart I; De Ryck, Tine; Verhasselt, Sigrid; Bracke, Marc E; Stevens, Christian V

    2015-03-01

    In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1,ω-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart invasion assay. Unfortunately, these compounds proved less potent and more toxic than earlier evaluated chemotypes. In the 1,3-diarylpenta-2,4-dien-1-one series, fluoro and/or trimethoxy substitution caused an increase in potency. This agrees with observations made earlier for the chalcone class.

  6. Tetramethoxychalcone, a Chalcone Derivative, Suppresses Proliferation, Blocks Cell Cycle Progression, and Induces Apoptosis of Human Ovarian Cancer Cells

    PubMed Central

    Liu, Yang; Zhang, Meiqin; Yang, Gong

    2014-01-01

    In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3′,4′,5′- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer. PMID:25180593

  7. Synthetic multicellularity.

    PubMed

    Maharbiz, Michel M

    2012-12-01

    The ability to synthesize biological constructs on the scale of the organisms we observe unaided is probably one of the more outlandish, yet recurring, dreams humans have had since they began to modify genes. This review brings together recent developments in synthetic biology, cell and developmental biology, computation, and technological development to provide context and direction for the engineering of rudimentary, autonomous multicellular ensembles.

  8. Synthetic DNA

    PubMed Central

    O’ Driscoll, Aisling; Sleator, Roy D.

    2013-01-01

    With world wide data predicted to exceed 40 trillion gigabytes by 2020, big data storage is a very real and escalating problem. Herein, we discuss the utility of synthetic DNA as a robust and eco-friendly archival data storage solution of the future. PMID:23514938

  9. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2015-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  10. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2016-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  11. Synthetic chromosomes.

    PubMed

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes.

  12. SYNTHETIC LUBRICANTS

    DTIC Science & Technology

    of synthetic lubricants for use at low and high temperatures. The diesters of straight-chain dibasic acids lead the field of esters mutable as...lubricants for use at both low and high temperatures, because of their desirable combinations of properties and potentially good availability. Adipic ...azelaic, and sebacic acids are the most readily available dibasic acids suitable for ester lubricant production, while the petroleum derived Oxo alcohols

  13. Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates.

    PubMed

    Raj, Raghu; Saini, Anu; Gut, Jiri; Rosenthal, Philip J; Kumar, Vipan

    2015-05-05

    The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates. The presence of a methoxy substituent at para position of ring B on chalcones and longer alkyl chain length markedly improved the antiplasmodial profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC50 value of 17.8 nM.

  14. Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV.

    PubMed

    Park, Ji-Young; Ko, Jin-A; Kim, Dae Wook; Kim, Young Min; Kwon, Hyung-Jun; Jeong, Hyung Jae; Kim, Cha Young; Park, Ki Hun; Lee, Woo Song; Ryu, Young Bae

    2016-01-01

    Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).

  15. A chiral benzoylthiourea-pyrrolidine catalyst for the highly enantioselective Michael addition of ketones to chalcones.

    PubMed

    Ban, Shu-Rong; Zhu, Xi-Xia; Zhang, Zhi-Ping; Li, Qing-Shan

    2014-06-01

    A benzoylthiourea-pyrrolidine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding products were obtained in high yields with high level of diastereoselectivities (up to 99:1 dr) and high level of enantioselectivities (up to 94% ee) under mild conditions.

  16. Hydroxylated chalcones with dual properties: xanthine oxidase inhibitors and radical scavengers

    PubMed Central

    Hofmann, Emily; Webster, Jonathan; Do, Thuy; Kline, Reid; Snider, Lindsey; Hauser, Quintin; Higginbottom, Grace; Campbell, Austin; Ma, Lili; Paula, Stefan

    2016-01-01

    In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones’ effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class. PMID:26762836

  17. Semi-synthesis and NMR spectral assignments of flavonoid and chalcone derivatives.

    PubMed

    Kumar, Rohitesh; Lu, Yuting; Elliott, Alysha G; Kavanagh, Angela M; Cooper, Matthew A; Davis, Rohan A

    2016-11-01

    Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin (4) and 2',6'-dihydroxy-4'-methoxy-3',5'-dimethyl chalcone (7), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4'-triacetoxy jaceosidin (10), 5,7,4'-tripivaloyloxy jaceosidin (11), 5,7,4'-trimethoxy jaceosidin (12), 2',6'-diacetoxy-4'-methoxy-3',5'-dimethyl chalcone (13), 2'-hydroxy-4'-methoxy-6'-pivaloyloxy-3',5'-dimethyl chalcone (14), and 2'-hydroxy-4',6'-dimethoxy-3',5'-dimethyl chalcone (15) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14. The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin (4) and the acetylated derivative, 5,7,4'-triacetoxy jaceosidin (10), showed modest antibacterial activity (32-128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Chemistry of isoflavone heteroanalogs. 11. Benzodioxane analogs of chalcone, flavone, and isoflavone

    SciTech Connect

    Khilya, V.P.; Aitmambetov, A.; Turov, A.V.; Kornilov, A.M.; Litkei, D.; Patonai, T.

    1986-08-01

    Benzodioxane analogs of chalcones and their epoxides have been prepared. Different types of analogs of natural flavonolignan - silibin - have been synthesized from these compounds. The PMR spectra of the new compounds and the results of the preliminary biological testings are reported and discussed.

  19. Synthesis and Hydrogenation of Disubstituted Chalcones: A Guided-Inquiry Organic Chemistry Project

    ERIC Educational Resources Information Center

    Mohrig, Jerry R.; Hammond, Christina Noring; Schatz, Paul F.; Davidson, Tammy A.

    2009-01-01

    Guided-inquiry experiments offer the same opportunities to participate in the process of science as classical organic qualitative analysis used to do. This three-week guided-inquiry project involves an aldol-dehydration synthesis of a chalcone chosen from a set of nine, followed by a catalytic transfer hydrogenation reaction using ammonium formate…

  20. Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

    PubMed

    Wang, R K; Zhan, S F; Zhao, T J; Zhou, X L; Wang, C E

    2015-03-20

    Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

  1. 2-Methoxy-2',4'-dichloro chalcone as an antimicrofoulant against marine bacterial biofilm.

    PubMed

    Sivakumar, P M; Prabhawathi, V; Doble, Mukesh

    2010-12-01

    Marine paint mixed with 2-methoxy-2',4'-dichloro chalcone is able to considerably reduce the formation of biofilm by Vibrio natriegens, a marine bacterium, on polycarbonate (PC), polymethylmethacrylate (PMMA) and glass fiber reinforced plastic (GFRP). These polymers have been selected for the study, since they have wide marine applications. Surfaces coated with dichloro chalcone containing marine paint had the lowest number of colony forming units (CFU) (1-5×10(6)), proteins (20-30 μg/cm2) and carbohydrates (5-10 μg/cm2) attached to them after 28 days of exposure to the organism when compared to surfaces coated with CuSO4 mixed paint (20-40×10(6) CFU/ml, proteins of 50-60 μg/cm2 and carbohydrates of 40-50 μg/cm2) or plain marine paint (30-40×10(6) CFU/ml, proteins of 120-150 μg/cm2 and carbohydrates of 40-60 μg/cm2). At the end of the study period, the biofilm on PMMA was 7, 10 and 12 μm thick on chalcone, copper and plain paint coated surfaces, respectively. The first two paints increased the surface roughness but decreased the surface hydrophobicity when compared to the plain paint. Large number of dead cells was found on the chalcone mixed and predominantly live cells were found on plain paint coated surfaces. 15% of dichloro chalcone had leached out of PMMA surface after 28 days. The low amount of biofilm formed in the presence of dichlorochalcone can be associated to its antibacterial and slimicidal activity and also its ability to reduce the hydrophobicity of the surface. This dichlorochalcone appears to be a novel agent for decreasing the formation of marine biofilm.

  2. Synthetic wisdom.

    PubMed

    Kitcher, Philip

    2016-11-01

    Wisdom is a special kind of virtue. It is not to be identified with any outstanding cognitive ability-like having a prodigious memory or knowing a lot. Rather it consists in seeing what is most important and most valuable, either within a particular domain or in life as a whole. In the life of a wise person, that insight should be accompanied by traits of character, enabling the person to pursue what is seen as valuable. Viewing wisdom as a capacity for synthetic understanding, I argue for the need for philosophy, even at a time when all of us have much to learn from the sciences.

  3. Isolation, sequence identification and tissue expression profile of two novel soybean (glycine max) genes-vestitone reductase and chalcone reductase.

    PubMed

    Liu, G Y

    2009-09-01

    The complete mRNA sequences of two soybean (glycine max) genes-vestitone reductase and chalcone reductase, were amplified using the rapid amplification of cDNA ends methods. The sequence analysis of these two genes revealed that soybean vestitone reductase gene encodes a protein of 327 amino acids which has high homology with the vestitone reductase of Medicago sativa (77%). The soybean chalcone reductase gene encodes a protein of 314 amino acids that has high homology with the chalcone reductase of kudzu vine (88%) and medicago sativa (83%). The expression profiles of the soybean vestitone reductase and chalcone reductase genes were studied and the results indicated that these two soybean genes were differentially expressed in detected soybean tissues including leaves, stems, roots, inflorescences, embryos and endosperm. Our experiment established the foundation for further research on these two soybean genes.

  4. Synthetic chloroplasts

    SciTech Connect

    Calvin, M.

    1980-06-01

    The principal function of the chloroplast is to capture solar quanta and to store them in some stable form. We are in the process of trying to construct a totally synthetic system that would simulate some of the reactions of the two photosystems which occur in natural chloroplasts. Toward this end, we have demonstrated a number of the reactions required in separated systems. We have shown that it is possible to transfer electrons across an insulating membrane barrier with a surfactant photosensitizer. Others have shown, and we have confirmed, that it is possible to collect the two electrons necessary for the generation of molecular hydrogen on a heterogeneous catalyst suspended in water and similarly to collect the four holes on another heterogeneous catalyst suspended in water for the generation of molecular oxygen. A synthesis of some of these molecular catalysts for both these purposes is underway, with some partial success. When these partial reactions are assembled in a system, the resulting synthetic chloroplasts will not resemble the natural entity in detailed construction as they will contain no protein.

  5. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    PubMed Central

    Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

    2014-01-01

    Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

  6. Synthetic Brainbows

    PubMed Central

    Wan, Y.; Otsuna, H.; Hansen, C.

    2014-01-01

    Brainbow is a genetic engineering technique that randomly colorizes cells. Biological samples processed with this technique and imaged with confocal microscopy have distinctive colors for individual cells. Complex cellular structures can then be easily visualized. However, the complexity of the Brainbow technique limits its applications. In practice, most confocal microscopy scans use different florescence staining with typically at most three distinct cellular structures. These structures are often packed and obscure each other in rendered images making analysis difficult. In this paper, we leverage a process known as GPU framebuffer feedback loops to synthesize Brainbow-like images. In addition, we incorporate ID shuffing and Monte-Carlo sampling into our technique, so that it can be applied to single-channel confocal microscopy data. The synthesized Brainbow images are presented to domain experts with positive feedback. A user survey demonstrates that our synthetic Brainbow technique improves visualizations of volume data with complex structures for biologists. PMID:25018576

  7. Synthetic Botany.

    PubMed

    Boehm, Christian R; Pollak, Bernardo; Purswani, Nuri; Patron, Nicola; Haseloff, Jim

    2017-02-28

    Plants are attractive platforms for synthetic biology and metabolic engineering. Plants' modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. However, efforts in this area have been constrained by slow growth, long life cycles, the requirement for specialized facilities, a paucity of efficient tools for genetic manipulation, and the complexity of multicellularity. There is a need for better experimental and theoretical frameworks to understand the way genetic networks, cellular populations, and tissue-wide physical processes interact at different scales. We highlight new approaches to the DNA-based manipulation of plants and the use of advanced quantitative imaging techniques in simple plant models such as Marchantia polymorpha. These offer the prospects of improved understanding of plant dynamics and new approaches to rational engineering of plant traits.

  8. Studies on chalcone derivatives: Complex formation, thermal behavior, stability constant and antioxidant activity

    NASA Astrophysics Data System (ADS)

    El-Sayed, Yusif S.; Gaber, M.

    2015-02-01

    The chalcone 3-[4‧-dimethylaminophenyl]-1-(2-pyridyl) prop-2-en-1-one (DMAPP) and 3-(4‧-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPP have been synthesized and characterized with IR, 1H NMR, 13C NMR spectroscopic techniques as described previously (El-Daly et al., 2008; Gaber et al., 2009; El-Sayed, 2013). By using UV visible spectroscopy method the mole fraction ratio for copper with DMAPP and DEAPP complexes were determined and it was found to be 1:1. The stability constants of this complex have been determined by Job's method. The stability constant (Kf) of copper with DMAPP and DEAPP complexes in universal buffer pH = 3.2 was determined to be 9.9 × 104 and 5.2 × 104 respectively. The effect of Cu(II) ion on the emission spectrum of the free chalcone is also assigned. Adherence to Beer's law and Ringbom optimum concentration ranges are determined. The thermal decomposition of the metal complexes is studied by TGA technique. The kinetic parameters like activation energy, pre-exponential factor and entropy of activation are estimated. The structure of complexes was energetically optimized through molecular mechanics applying MM+ force field coupled with molecular dynamics simulation. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the chalcone to copper nanoparticles was studied. The apparent association constants of the colloidal copper nanoparticles:chalcone complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) chalcone complexes. Antioxidant activity of these chalcones was evaluated by using 1,1‧-diphenyl-2-picrylhydrazyl (DPPHrad) radicals scavenging method, which showed that the antioxidant activity of DMAPP has higher value than the DEAPP. Semi-empirical study results showed that DMAPP have higher dipole moment than DEAPP [1].

  9. Determination of absorptivity and formation constant of a chalcone association complex.

    PubMed

    Blanco, S E; Ferretti, F H

    1998-04-01

    A UV spectrometric method was developed to determine the molar absorptivity (epsilon(C)) and formation constant (K(c)) of the association complex of unsubstituted chalcone in cyclohexane, in the concentration range from 4.00.10(-4) to 2.00.10(-2) mol dm(-3). The thermodynamic and spectroscopic magnitudes such as K(c) and epsilon(C) contribute to the understanding of the physicochemical behavior of several alpha,beta-unsaturated carbonylic compounds, of low solubility in water, as it is the case of numerous flavonoids of chemical and biological importance. The studied association complex, formed by two chalcone molecules, is characterized by the constants epsilon(C) (300.8 nm)=4.98.10(4) dm(3) mol(-1) cm(-1) and K(c)=5.58.10(3). The method proposed is convenient for the study of solute-solute molecular associations particularly those due to dipole-dipole interactions.

  10. Coumarin-Chalcone Hybrids as Peroxyl Radical Scavengers: Kinetics and Mechanisms.

    PubMed

    Mazzone, Gloria; Galano, Annia; Alvarez-Idaboy, Juan R; Russo, Nino

    2016-04-25

    The primary antioxidant activity of coumarin-chalcone hybrids has been investigated using the density functional and the conventional transition state theories. Their peroxyl radical scavenging ability was studied in solvents of different polarity and taking into account different reaction mechanisms. It was found that the activity of the hybrids increases with the polarity of the environment and the number of phenolic sites. In addition, their peroxyl radical scavenging activity is larger than those of the corresponding nonhybrid coumarin and chalcone molecules. This finding is in line with previous experimental evidence. All the investigated molecules were found to react faster than Trolox with (•)OOH, regardless of the polarity of the environment. The role of deprotonation on the overall activity of the studied compounds was assessed. The rate constants and branching ratios for the reactions of all the studied compounds with (•)OOH are reported for the first time.

  11. Flemingin-Type Prenylated Chalcones from the Sarawak Rainforest Plant Desmodium congestum.

    PubMed

    Rees, Karlee A; Bermudez, Cindy; Edwards, David J; Elliott, Alysha G; Ripen, Jovita E; Seta, Cynthia; Huang, Johnny X; Cooper, Matthew A; Fraser, James A; Yeo, Tiong Chia; Butler, Mark S

    2015-08-28

    In an ongoing program to identify new anti-infective leads, an extract derived from whole plant material of Desmodium congestum collected in the Sarawak rainforest was found to have anti-MRSA activity. Bioassay-guided isolation led to the isolation of two new prenylated chalcones, 5'-O-methyl-3-hydroxyflemingin A (1) and 5'-O-methylflemingin C (2), which were closely related to the flemingins previously isolated from various Flemingia species. Chalcones 1 and 2, which were determined to be 4:6 enantiomeric mixtures by chiral HPLC, exhibited moderate activity against a panel of Gram-positive bacteria and were also cytotoxic to the HEK293 human embryonic kidney cell line.

  12. 4-Hydroxy-2-pyrone formation by chalcone and stilbene synthase with nonphysiological substrates.

    PubMed

    Zuurbier, K W; Leser, J; Berger, T; Hofte, A J; Schröder, G; Verpoorte, R; Schröder, J

    1998-12-01

    Valerophenone synthase (VPS) is a polyketide synthase that catalyzes the formation of the phloroglucinol derivatives in the synthesis of the bitter acids in hop (Humulus lupulus). The reaction uses isovaleryl-CoA or isobutyryl-CoA, but otherwise it is identical to that of the chalcone synthase in flavonoid biosynthesis. Our study showed that chalcone synthase can perform the function of VPS, but not perfectly, because the majority of the reactions terminated after two condensation reactions (products: 4-hydroxy-2-pyrone derivatives). The same experiments with stilbene synthase yielded exclusively the 4-hydroxy-2-pyrone derivatives, not the products expected from three condensation reactions. The results are discussed in the context of the functional diversity and evolution in the family of CHS-related polyketide synthases.

  13. Cloning and functional characterization of a chalcone isomerase from Trigonella foenum-graecum L.

    PubMed

    Qin, Jian-chun; Zhu, Lin; Gao, Ming-jun; Wu, Xian; Pan, Hong-yu; Zhang, Yan-sheng; Li, Xiang

    2011-05-01

    Flavonoids belong to a group of plant natural products with variable phenolic structures and play important roles in protection against biotic and abiotic stress. Fenugreek (Trigonella foenum-graecum L.) seeds and stems contain flavonol glycosides and isoflavone derivatives. Up to now, the molecular features of fenugreek flavonoid biosynthesis have not been characterized. Here we present cloning of a cDNA encoding a chalcone isomerase (namely TFGCHI-1) from the leaves of T. foenum-graecum which convert chalcones to flavanones in vitro. Transformation of Arabidopsis loss-of-function TT5 (CHI) mutant with a TFGCHI-1 cDNA complemented TT5 and produced higher levels of flavonol glycosides than wild-type Col-0.

  14. A quantitative analysis of weak intermolecular interactions & quantum chemical calculations (DFT) of novel chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Chavda, Bhavin R.; Gandhi, Sahaj A.; Dubey, Rahul P.; Patel, Urmila H.; Barot, Vijay M.

    2016-05-01

    The novel chalcone derivatives have widespread applications in material science and medicinal industries. The density functional theory (DFT) is used to optimized the molecular structure of the three chalcone derivatives (M-I, II, III). The observed discrepancies between the theoretical and experimental (X-ray data) results attributed to different environments of the molecules, the experimental values are of the molecule in solid state there by subjected to the intermolecular forces, like non-bonded hydrogen bond interactions, where as isolated state in gas phase for theoretical studies. The lattice energy of all the molecules have been calculated using PIXELC module in Coulomb -London -Pauli (CLP) package and is partitioned into corresponding coulombic, polarization, dispersion and repulsion contributions. Lattice energy data confirm and strengthen the finding of the X-ray results that the weak but significant intermolecular interactions like C-H…O, Π- Π and C-H… Π plays an important role in the stabilization of crystal packing.

  15. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2017-01-01

    "Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids.

  16. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2015-01-01

    'Are we alone?' is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids.

  17. Development of fluorescent lead II sensor based on an anthracene derived chalcone.

    PubMed

    Prabhu, J; Velmurugan, K; Nandhakumar, R

    2015-06-05

    A simple anthracene based chalcone as a fluorescent chemosensor 1, capable of detecting Pb(2+) in aqueous media, has been synthesized by the reaction between pyridine 2-carboxaldehyde and 9-acetyl anthracene. The Pb(2+) recognition processes follows a photo induced electron transfer (PET) mechanism and are scarcely influenced by other coexisting metal ions. In addition, determination of lead in a variety of samples was also determined.

  18. Highly enantioselective Michael addition of nitroalkanes to chalcones using chiral squaramides as hydrogen bonding organocatalysts.

    PubMed

    Yang, Wen; Du, Da-Ming

    2010-12-03

    A series of squaramide-based organocatalysts were facilely synthesized and applied as hydrogen bonding organocatalysts in the enantioselective Michael addition of nitroalkanes to chalcones. These organocatalysts promoted the Michael addition with low catalyst loading under high temperature (80 °C), affording the desired R or S enantiomers of the products flexibly in high yields with excellent enantioselectivities (93-96% ee) by the appropriate choice of organocatalysts.

  19. Study of DNA interactions with cyclic chalcone derivatives by spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Štefanišinová, M.; Tomečková, V.; Kožurková, M.; Ostró, A.; Mareková, M.

    2011-10-01

    A series of chalcone derivatives ( 1- 4) were studied. The interaction between these ligands and calf thymus DNA was studied with UV-vis spectrophotometry, fluorescence and circular dichroism spectroscopy. The binding constants K were estimated at 0.5-4.6 × 10 5 M -1. All these measurements indicated that the compounds behave as effective DNA-intercalating agents. Electrophoretic separation proved that ligands inhibited topoisomerase I at a concentration of 60 μM.

  20. Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes.

    PubMed

    Issaenko, Olga A; Amerik, Alexander Yu

    2012-05-01

    The ubiquitin-proteasome system (UPS) is usurped by many if not all cancers to regulate their survival, proliferation, invasion, angiogenesis and metastasis. Bioflavonoids curcumin and chalcones exhibit anti-neoplastic selectivity through inhibition of the 26S proteasome-activity within the UPS. Here, we provide evidence for a novel mechanism of action of chalcone-based derivatives AM146, RA-9 and RA-14, which exert anticancer activity by targeting deubiquitinating enzymes (DUB) without affecting 20S proteasome catalytic-core activity. The presence of the α,β-unsaturated carbonyl group susceptible to nucleophilic attack from the sulfhydryl of cysteines in the active sites of DUB determines the capacity of novel small-molecules to act as cell-permeable, partly selective DUB inhibitors and induce rapid accumulation of polyubiquitinated proteins and deplete the pool of free ubiquitin. These chalcone-derivatives directly suppress activity of DUB UCH-L1, UCH-L3, USP2, USP5 and USP8, which are known to regulate the turnover and stability of key regulators of cell survival and proliferation. Inhibition of DUB-activity mediated by these compounds downregulates cell-cycle promoters, e.g., cyclin D1 and upregulates tumor suppressors p53, p27(Kip1) and p16(Ink4A). These changes are associated with arrest in S-G 2/M, abrogated anchorage-dependent growth and onset of apoptosis in breast, ovarian and cervical cancer cells without noticeable alterations in primary human cells. Altogether, this work provides evidence of antitumor activity of novel chalcone-based derivatives mediated by their DUB-targeting capacity; supports the development of pharmaceuticals to directly target DUB as a most efficient strategy compared with proteasome inhibition and also provides a clear rationale for the clinical evaluation of these novel small-molecule DUB inhibitors.

  1. In silico analysis reveals the anti-malarial potential of quinolinyl chalcone derivatives.

    PubMed

    Thillainayagam, Mahalakshmi; Pandian, Lavanya; Murugan, Kumar Kalavathy; Vijayaparthasarathi, Vijayakumar; Sundaramoorthy, Sarveswari; Anbarasu, Anand; Ramaiah, Sudha

    2015-01-01

    In this study, the correlation between chemical structures and various parameters such as steric effects and electrostatic interactions to the inhibitory activities of quinolinyl chalcone derivatives is derived to identify the key structural elements required in the rational design of potent and novel anti-malarial compounds. The molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex-dock is used to determine the probable binding conformations of all the compounds at the active site of pfLDH and to identify the hydrogen bonding interactions which could be used to alter the inhibitory activities. The CoMFA model has provided statistically significant results with the cross-validated correlation coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number of component is five. The predictive ability of the resultant model is evaluated using a test set comprising of 13 molecules and the predicted r(2) value is .885. The results provide valuable insight for optimization of quinolinyl chalcone derivatives for better anti-malarial therapy.

  2. Cloning and Functional Analysis of Three Chalcone Synthases from the Flowers of Safflowers Carthamus tinctorius.

    PubMed

    Shinozaki, Junichi; Kenmoku, Hiromichi; Nihei, Kenichi; Masuda, Kazuo; Noji, Masaaki; Konno, Katsuhiro; Asakawa, Yoshinori; Kazuma, Kohei

    2016-06-01

    The flowers of safflowers (Carthamus tinctorius L.) are very important as they are the sole source of their distinct pigments, i.e. carthamus-red and -yellows, and have historically had strong connections to the cultural side of human activities such as natural dyes, rouge, and traditional medicines. The distinct pigments are quinochalcone C-glucosides, which are found specifically in the flowers of C. tinctorius. To investigate the biosynthetic pathways of quinochalcone C-glucosides, de novo assembly of the transcriptome was performed on the flowers using an Illumina sequencing platform to obtain 69,312 annotated coding DNA sequences. Three chalcone synthase like genes, CtCHS1, 2 and 3 were focused on and cloned, which might be involved in quinochalcone C-glucosides biosynthesis by establishing the C6-C3-C6 chalcone skeleton. It was demonstrated that all the recombinant CtCHSs could recognize p-coumaroyl-CoA, caffeoyl-CoA, feruloyl-CoA, and sinapoyl-CoA as starter substrates. This is the first report on the cloning and functional analysis of the three chalcone synthase genes from the flowers of C. tinctorius.

  3. DNA-targeting pyrroloquinoline-linked butenone and chalcones: synthesis and biological evaluation.

    PubMed

    Dalla Via, Lisa; Gia, Ornella; Chiarelotto, Gianfranco; Ferlin, Maria Grazia

    2009-07-01

    A series of conjugates of alpha,beta-unsaturated ketone systems, phenyl-butenone and diaryl-propenones (chalcones), with the tricyclic planar pyrroloquinoline nucleus were synthesised and evaluated for their anticancer properties. The aim was to target DNA by butenone and chalcones, and determine the occurrence of interactions with the macromolecule or related functional enzymes. The ability to inhibit cell growth was assayed on three human tumor cell lines, and the capacity to form molecular complexes with DNA was studied by linear flow dichroism (LD). The effect on the activity of the nuclear enzyme DNA topoisomerase II was also investigated. A noticeable cytotoxic effect was observed for all pyrroloquinoline-conjugated compounds 5 and 7a-c, particularly against human melanoma cell line JR8 (IC(50) 1.2-3.3 microM); the unconjugated chalcones (8a-c) and butenone had a lower or no effect at the tested concentrations. LD experiments confirmed the pyrroloquinoline nucleus as an efficacious carrier for intercalative complexation with DNA. The ability of pyrroloquinoline derivatives to intercalate between base pairs appears to inhibit the relaxation of supercoiled DNA by topoisomerase II, while they induce no significant DNA cleavage. Since the concentrations inhibiting the enzyme appear relatively high with respect to cytotoxicity, the effective intercalation could affect the activity of more DNA processing enzymes and these overall nuclear effects may induce cell death.

  4. Ferrocenyl-cymantrenyl hetero-bimetallic chalcones: Synthesis, structure and biological properties

    NASA Astrophysics Data System (ADS)

    Mishra, Sasmita; Tirkey, Vijaylakshmi; Ghosh, Avishek; Dash, Hirak R.; Das, Surajit; Shukla, Madhulata; Saha, Satyen; Mobin, Sheikh M.; Chatterjee, Saurav

    2015-04-01

    Two new ferrocenyl-cymantrenyl bimetallic chalcones, [(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)Fe(η5-C5H5)] (1) and [{(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)}2Fe] (2) have been synthesized. Their reactivity study with triphenylphosphine and bis-(diphenylphosphino)ferrocene led to the isolation of phosphine substituted bimetallic chalcones (3-6). Single crystal X-ray structural characterization for 1 and its phosphine analogue (3) reveals their different conformational identity with anti-conformation for 1, while syn-conformation for 3. Investigation of antimalarial and antibacterial activities was carried out for compounds 1 and 2 against two strains of Plasmodium falciparum (3D7, K1) and four bacterial strains. TD-DFT calculation was performed for compound 1 and electrochemical properties were studied for bimetallic chalcone compounds by cyclic voltammetric technique.

  5. Targeting Death Receptor TRAIL-R2 by Chalcones for TRAIL-Induced Apoptosis in Cancer Cells

    PubMed Central

    Szliszka, Ewelina; Jaworska, Dagmara; Kłósek, Małgorzata; Czuba, Zenon P.; Król, Wojciech

    2012-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties. PMID:23203129

  6. Effects of a herbal gel containing carvacrol and chalcones on alveolar bone resorption in rats on experimental periodontitis.

    PubMed

    Botelho, Marco Antonio; Rao, Vietla Satyanarayana; Montenegro, Danusa; Bandeira, Mary Anne Menezes; Fonseca, Said Gonçalves Cruz; Nogueira, Nadia Accioly Pinto; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne Castro

    2008-04-01

    Carvacrol and dimeric chalcones are the respective bioactive components of Lippia sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern Brazil with proven antimicrobial and antiinflammatory properties. Periodontal disease is associated with inflammation and microbiological proliferation, thus the study aimed to investigate the effect of a topical gel based on carvacrol and chalcones in the experimental periodontal disease (EPD) in rats. Animals were treated with carvacrol and/or chalcones gel, immediately after EPD induction, three times a day for 11 days. Appropriate controls were included in the study. Animals were weighed daily. They were killed on day 11, the mandibles dissected and alveolar bone loss was measured. The periodontium were examined at histopathology and the neutrophil influx into the gingiva was assayed using myeloperoxidase activity. The bacterial flora were assessed through culture of the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by combined carvacrol and chalcones gel, compared with the vehicle and non-treated groups. The treatment with the combined gel reduced tissue lesion at histopathology, decreased myeloperoxidase activity in gingival tissue and inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol and chalcones combination gel has a beneficial effect upon EPD in this model.

  7. Effect of diethylcarbamazine, butylated hydroxy anisole and methyl substituted chalcone on filarial parasite Setaria cervi: proteomic and biochemical approaches.

    PubMed

    Rathaur, Sushma; Yadav, Marshleen; Singh, Neetu; Singh, Alka

    2011-08-24

    For survival, parasite exerts several lines of defense of which drug neutralization is one of the major phenomena. Lack of phase I cytochrome P450 in some of the nematode render them depend on the phase II detoxification system involving GST as a major detoxifying enzymes. In present study, the antifilarial DEC, phenolic compound BHA and methyl chalcone have been evaluated for proteomic and biochemical studies in Setaria cervi. BHA and methyl chalcone showed cytotoxic effect leading to irreversible inhibition in motility and viability of parasites. These drugs showed marked alteration in proteomic profile of S. cervi at 100 μM concentration with 10.82, 8.52 and 6.75% downregulated (<0.5) and 7.64, 31.78 and 24.32% upregulated (>1.5) in DEC, BHA and methyl chalcone treatment respectively. Significant depletion in GSH level with increase in NO production was observed. Amongst these compounds, methyl chalcone demonstrated significant inhibitory effect (p<0.05) on GST, PGHS and PTP activity leading to loss of metabolic homeostasis and parasite death. The cytotoxic response and altered expression profile of major enzymes under drug exposure suggested the oxidative stress induced apoptosis as a major cause of parasite killing which was further supported by DNA fragmentation in BHA and methyl chalcone.

  8. Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: a new target for a privileged structure.

    PubMed

    Balsera, Beatriz; Mulet, José; Fernández-Carvajal, Asia; de la Torre-Martínez, Roberto; Ferrer-Montiel, Antonio; Hernández-Jiménez, José G; Estévez-Herrera, Judith; Borges, Ricardo; Freitas, Andiara E; López, Manuela G; García-López, M Teresa; González-Muñiz, Rosario; Pérez de Vega, María Jesús; Valor, Luis M; Svobodová, Lucie; Sala, Salvador; Sala, Francisco; Criado, Manuel

    2014-10-30

    The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α7 nicotinic function. The most potent compound (2,4,2',5'-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.

  9. Exploration of the SAR of anti-invasive chalcones: synthesis and biological evaluation of conformationally restricted analogues.

    PubMed

    Roman, Bart I; Ryck, Tine De; Dierickx, Laura; Vanhoecke, Barbara W A; Katritzky, Alan R; Bracke, Marc; Stevens, Christian V

    2012-08-01

    In order to get a clearer view on the active geometry of anti-invasive chalcones, we have prepared a number of isoxazoles and related substances as conformationally restrained mimics of 1,3-diarylpropenones, and also of (Z)-stilbenes. In vitro anti-invasive activity data for 3,5-isoxazoles and 4,5-isoxazoles, together with an in silico geometrical comparison, point towards an active conformation for chalcones more resembling their s-trans geometry than the s-cis counterpart.

  10. Some ferrocenyl chalcones as useful candidates for cancer treatment.

    PubMed

    Janka, Vašková; Žatko, Daniel; Ladislav, Vaško; Pál, Perjési; Janka, Poráčová; Gabriela, Mojžišová

    2015-10-01

    Although knowledge of cancer management is extensive, mortality is not currently declining in this area. It is therefore important to implement a long-term strategy that would aim to prevent these serious diseases. Ferrocene-related organometallic compounds are promising candidates for design of new drugs since they can exhibit much greater biological activity than their phenyl analogs. In our work, we focused on investigating the cytotoxic and antiproliferative effects of five ferrocenyl derivatives toward selected tumor cell lines. We found that some of these substances significantly reduced Jurkat cell survival and, to a lesser extent, that of the HeLa, MCF7, A549, and MDA cells. Long-term treatment of HeLa cell cultures with these agents resulted in a significant blockade of formation of tumor cell colonies. We found that one of the mechanisms of action of the compounds is likely to display an effect on the redox state of the mitochondria at a final concentration of 10(-4) and 10(-5) mol l(-1). Of the compounds tested, the indanonyl ferrocene derivative (C) was the most effective, especially via glutathione depletion. Based on the obtained results, it can be concluded that synthetic substances containing iron have potential antitumor activity.

  11. In vitro and in vivo anti-glioma activity of a chalcone-quinoxaline hybrid.

    PubMed

    Loch-Neckel, Gecioni; Bicca, Maíra Assunção; Leal, Paulo César; Mascarello, Alessandra; Siqueira, Jarbas Mota; Calixto, João B

    2015-01-27

    Chalcones are important compounds that exhibit multiple biological activities, including anti-inflammatory, antimitotic and antibacterial properties. In the present study, we have analyzed the potential anti-cancer activity of a chalcone named N9 (a hybrid chalcone-quinoxaline compound) using in vitro and in vivo experimental glioma models. Here, we report N9-induced inhibition of cell proliferation and also N9-induced cell death in a concentration-dependent manner in U87-MG glioma cells. These effects of N9 appear to be associated with its ability to inhibit the expression of cell cycle-associated proteins, and also the augmentation in the expression of the p21 (p21/Cip1) protein, a cyclin-dependent kinase inhibitor. Additionally, N9 also potentiates the production of the pro-apoptotic markers Bax and p53 via inhibition of MDM2. Moreover, our results show that N9 also significantly enhanced apoptosis of U87-MG cells with disruption of mitochondrial membrane potential, generation of ROS and caspase-9 activation. In vivo experiments carried out in a murine xenograft model of U87-MG revealed that N9 produced a significant reduction of tumors volume when compared to vehicle treated mice. Collectively, data demonstrate that N9 possess in vitro and in vivo anti-cancer activity, an effect that seems to involve the induction of p53 and p21 proteins, as well as, the activation of mitochondrial apoptosis pathway associated with the inhibition of protein MDM2. Overall, this study suggests N9 is affecting a variety of intracellular pathways related to tumor apoptosis. Perhaps N9 or derivate molecules could represent new potential drugs for cancer therapeutics.

  12. Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

    NASA Astrophysics Data System (ADS)

    Baskar, R.; Baby, C.; Moni, M. S.; Subramanian, K.

    2013-05-01

    The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using a two step protocol is reported. The compound is characterized by FTIR, GC-MS and FTNMR spectroscopy techniques. Advanced 2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to establish through-bond and through-space correlations. Dynamic NMR measurements were carried out to obtain the energy barrier to ring inversion of the morpholine moiety.

  13. Synthetic biology, inspired by synthetic chemistry.

    PubMed

    Malinova, V; Nallani, M; Meier, W P; Sinner, E K

    2012-07-16

    The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell.

  14. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    PubMed

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  15. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    NASA Astrophysics Data System (ADS)

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-06-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2‧,3‧,4‧,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2‧,3‧,4‧-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

  16. Design, synthesis, and biological evaluation of chalcone oxime derivatives as potential immunosuppressive agents.

    PubMed

    Luo, Yin; Song, Ran; Li, Yao; Zhang, Shuai; Liu, Zhi-Jun; Fu, Jie; Zhu, Hai-Liang

    2012-05-01

    A series of deoxybenzoin oximes were recently reported as potent immunosuppressive agents by our group. In order to continue the original research for potential immunosuppressive agents with high efficacy and low toxicity, we synthesized a series of new chalcone oximes and evaluated them for their cytotoxicities and immunosuppressive activities. Among the synthesized compounds, chalcone oximes 25 and 27 exhibited lower cytotoxicities and higher inhibitory activities on anti-CD3/anti-CD28 co-stimulated lymph node cells than other compounds. Specially, compound 27 displayed 200-fold lower cytotoxicity (CC(50)=2174.39 μM) than cyclosporin A (CC(50)=10.10 μM) and showed SI value (SI=176.69) close to cyclosporin A (SI=154.13). Besides, the preliminary mechanism of inhibition effect of compounds 25 and 27 was also detected by flow cytometry, and the compounds exerted immunosuppressive activities via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Also, the deep mechanism of apoptosis was detected by Western blot analysis.

  17. Prenylated chalcones and flavonoids for the prevention and treatment of cancer.

    PubMed

    Venturelli, Sascha; Burkard, Markus; Biendl, Martin; Lauer, Ulrich M; Frank, Jan; Busch, Christian

    2016-01-01

    Prenylated chalcones and flavonoids gained increasing attention not only in nutrition but also in cancer prevention because of their biological and molecular activities in humans, which have been extensively investigated in vitro or in preclinical studies. These naturally occurring compounds exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display antiinflammatory properties. In particular, their potential to prevent proliferation of tumor cells is noteworthy. Some representatives of this subclass of secondary plant compounds exert pronounced anti-tumor-initiating capacities and directly inhibit growth of cancer cells, whereas their toxic effects on healthy tissues are remarkably low. These promising pharmacologic characteristics are countered by low ingestion, low bioavailability, and little knowledge of their metabolism. This review focuses on the great potential of these plant- and nutrient-derived compounds for cancer prevention and therapy. Provided here is a comprehensive summary of the current knowledge and inherent modes of action, focusing on the prenylated chalcones xanthohumol, desmethylxanthohumol, and xanthogalenol, as well as the prenylated flavonoids isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin, 6-geranylnaringenin, 8-geranylnaringenin, and pomiferin.

  18. A mutation in the rice chalcone isomerase gene causes the golden hull and internode 1 phenotype.

    PubMed

    Hong, Lilan; Qian, Qian; Tang, Ding; Wang, Kejian; Li, Ming; Cheng, Zhukuan

    2012-07-01

    The biosynthesis of flavonoids, important secondary plant metabolites, has been investigated extensively, but few mutants of genes in this pathway have been identified in rice (Oryza sativa). The rice gold hull and internode (gh) mutants exhibit a reddish-brown pigmentation in the hull and internode and their phenotype has long been used as a morphological marker trait for breeding and genetic study. Here, we characterized that the gh1 mutant was a mutant of the rice chalcone isomerase gene (OsCHI). The result showed that gh1 had a Dasheng retrotransposon inserted in the 5′ UTR of the OsCHI gene, which resulted in the complete loss of OsCHI expression. gh1 exhibited golden pigmentation in hulls and internodes once the panicles were exposed to light. The total flavonoid content in gh1 hulls was increased threefold compared to wild type. Consistent with the gh1 phenotype, OsCHI transcripts were expressed in most tissues of rice and most abundantly in internodes. It was also expressed at high levels in panicles before heading, distributed mainly in lemmas and paleae, but its expression decreased substantially after the panicles emerged from the sheath. OsCHI encodes a protein functionally and structurally conserved to chalcone isomerases in other species. Our findings demonstrated that the OsCHI gene was indispensable for flux of the flavonoid pathway in rice.

  19. Enzymatic properties and mutational studies of chalcone synthase from Physcomitrella patens.

    PubMed

    Rahman, Raja Noor Zaliha Raja Abdul; Zakaria, Iffah Izzati; Salleh, Abu Bakar; Basri, Mahiran

    2012-01-01

    PpCHS is a member of the type III polyketide synthase family and catalyses the synthesis of the flavonoid precursor naringenin chalcone from p-coumaroyl-CoA. Recent research reports the production of pyrone derivatives using either hexanoyl-CoA or butyryl-CoA as starter molecule. The Cys-His-Asn catalytic triad found in other plant chalcone synthase predicted polypeptides is conserved in PpCHS. Site directed mutagenesis involving these amino acids residing in the active-site cavity revealed that the cavity volume of the active-site plays a significant role in the selection of starter molecules as well as product formation. Substitutions of Cys 170 with Arg and Ser amino acids decreased the ability of the PpCHS to utilize hexanoyl-CoA as a starter molecule, which directly effected the production of pyrone derivatives (products). These substitutions are believed to have a restricted number of elongations of the growing polypeptide chain due to the smaller cavity volume of the mutant's active site.

  20. Role of a chalcone isomerase-like protein in flavonoid biosynthesis in Arabidopsis thaliana.

    PubMed

    Jiang, Wenbo; Yin, Qinggang; Wu, Ranran; Zheng, Guangshun; Liu, Jinyue; Dixon, Richard A; Pang, Yongzhen

    2015-12-01

    Flavonoids are important natural products for plant defence and human health. Although almost all the flavonoid pathway genes have been well-documented by biochemical and/or genetic approaches, the role of the Arabidopsis chalcone isomerase-like (CHIL) gene remains unclear. Two chil mutants with a seed colour similar to that of wild-type Arabidopsis have been identified here, but in sharp contrast to the characteristic transparent testa seed phenotype associated with other known flavonoid pathway genes. CHIL loss-of-function mutations led to a strong reduction in the proanthocyanidin and flavonol levels in seeds, but not in the anthocyanin levels in leaves. CHIL over-expression could partially recover the mutant phenotype of the chil mutant and increased both proanthocyanidin and flavonol accumulation in wild-type Arabidopsis. However, the CHIL gene could not rescue the mutant phenotype of TT5 that encodes the intrinsic chalcone isomerase in Arabidopsis. Parallel phenotypical and metabolic analyses of the chil, tt5, chs, and f3h mutants revealed that, genetically, CHIL functions at the same step as TT5. Moreover, it is demonstrated that CHIL co-expresses, co-localizes, and interacts with TT5 in Arabidopsis for flavonoid production. Based on these genetic and metabolic studies, it is concluded that CHIL functions with TT5 to promote flavonoid production, which is a unique enhancer in the flavonoid pathway.

  1. Enzymatic Properties and Mutational Studies of Chalcone Synthase from Physcomitrella patens

    PubMed Central

    Rahman, Raja Noor Zaliha Raja Abdul; Zakaria, Iffah Izzati; Salleh, Abu Bakar; Basri, Mahiran

    2012-01-01

    PpCHS is a member of the type III polyketide synthase family and catalyses the synthesis of the flavonoid precursor naringenin chalcone from p-coumaroyl-CoA. Recent research reports the production of pyrone derivatives using either hexanoyl-CoA or butyryl-CoA as starter molecule. The Cys-His-Asn catalytic triad found in other plant chalcone synthase predicted polypeptides is conserved in PpCHS. Site directed mutagenesis involving these amino acids residing in the active-site cavity revealed that the cavity volume of the active-site plays a significant role in the selection of starter molecules as well as product formation. Substitutions of Cys 170 with Arg and Ser amino acids decreased the ability of the PpCHS to utilize hexanoyl-CoA as a starter molecule, which directly effected the production of pyrone derivatives (products). These substitutions are believed to have a restricted number of elongations of the growing polypeptide chain due to the smaller cavity volume of the mutant’s active site. PMID:22949824

  2. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    PubMed Central

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-01-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2′,3′,4′,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2′,3′,4′-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID:27263468

  3. Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes.

    PubMed

    Zenger, Katharina; Agnolet, Sara; Schneider, Bernd; Kraus, Birgit

    2015-07-22

    The in vitro metabolism of flavokawains A, B, and C (FKA, FKB, FKC), methoxylated chalcones from Piper methysticum, was examined using human liver microsomes. Phase I metabolism and phase II metabolism (glucuronidation) as well as combined phase I+II metabolism were studied. For identification and structure elucidation of microsomal metabolites, LC-HRESIMS and NMR techniques were applied. Major phase I metabolites were generated by demethylation in position C-4 or C-4' and hydroxylation predominantly in position C-4, yielding FKC as phase I metabolite of FKA and FKB, helichrysetin as metabolite of FKA and FKC, and cardamonin as metabolite of FKC. To an even greater extent, flavokawains were metabolized in the presence of uridine diphosphate (UDP) glucuronic acid by microsomal UDP-glucuronosyl transferases. For all flavokawains, monoglucuronides (FKA-2'-O-glucuronide, FKB-2'-O-glucuronide, FKC-2'-O-glucuronide, FKC-4-O-glucuronide) were found as major phase II metabolites. The dominance of generated glucuronides suggests a role of conjugated chalcones as potential active compounds in vivo.

  4. Altered sterol profile induced in Leishmania amazonensis by a natural dihydroxymethoxylated chalcone

    PubMed Central

    Torres-Santos, Eduardo Caio; Sampaio-Santos, Maria Isabel; Buckner, Frederick S.; Yokoyama, Kohei; Gelb, Michael; Urbina, Julio A.; Rossi-Bergmann, Bartira

    2009-01-01

    Objectives The effects of the antileishmanial chalcone 2′,6′-dihydroxy-4′-methoxychalcone (DMC) on Leishmania amazonensis sterol composition and biosynthesis were investigated to obtain information about the mechanism of growth inhibition by DMC on this parasite. Methods The interference of sterol biosynthesis by DMC was studied in drug-treated promastigotes by two different methods. (i) Newly synthesized sterols from parasites grown in the presence of [3H]mevalonate were analysed by thin layer chromatography (TLC)/fluorography. (ii) Total sterols extracted from the parasites grown with or without DMC were characterized by gas chromatography coupled to mass spectroscopy (GC/MS). Results TLC and GC/MS analyses of sterols extracted from DMC-treated promastigotes revealed the accumulation of early precursors and a reduction in the levels of C-14 demethylated and C-24 alkylated sterols, as well as a reduction in exogenous cholesterol uptake. Conclusions This study demonstrates that the natural chalcone DMC alters the sterol composition of L. amazonensis and suggests that the parasite target is different from other known sterol inhibitors. PMID:19176591

  5. Nonlinear optical studies on 1,3-disubstituent chalcones doped polymer films

    NASA Astrophysics Data System (ADS)

    Poornesh, P.; Shettigar, Seetharam; Umesh, G.; Manjunatha, K. B.; Prakash Kamath, K.; Sarojini, B. K.; Narayana, B.

    2009-04-01

    We report the measurements of the third-order nonlinear optical properties of recently synthesized and characterized two different 1,3-disubstituent chalcones doped PMMA films, with the prospective of reaching a good compromise between processability and high nonlinear optical properties. The measurements were done using nanosecond Z-scan at 532 nm. The Z-scan spectra reveal a large negative nonlinear refraction coefficient n2 of the order 10 -11 esu and the molecular two photon absorption cross section is 10 -46 cm 4 s/photon. The doped films exhibit good optical power limiting property under nanosecond regime and the two photon absorption (TPA) is the dominating process leading to the nonlinear behavior. The improvement in the nonlinear properties has been observed when methylenedioxy group is replaced by dimethoxy group due to increase in conjugation length. The observed nonlinear parameters of chalcone derivatives doped PMMA film is comparable with stilbazolieum derivatives, a well-known class of optical materials for photonics and biophotonics applications, which suggests that, these moieties have potential for the application of all-optical limiting and switching devices.

  6. The flavonoid biosynthetic enzyme chalcone isomerase modulates terpenoid production in glandular trichomes of tomato.

    PubMed

    Kang, Jin-Ho; McRoberts, John; Shi, Feng; Moreno, Javier E; Jones, A Daniel; Howe, Gregg A

    2014-03-01

    Flavonoids and terpenoids are derived from distinct metabolic pathways but nevertheless serve complementary roles in mediating plant interactions with the environment. Here, we show that glandular trichomes of the anthocyanin free (af) mutant of cultivated tomato (Solanum lycopersicum) fail to accumulate both flavonoids and terpenoids. This pleiotropic metabolic deficiency was associated with loss of resistance to native populations of coleopteran herbivores under field conditions. We demonstrate that Af encodes an isoform (SlCHI1) of the flavonoid biosynthetic enzyme chalcone isomerase (CHI), which catalyzes the conversion of naringenin chalcone to naringenin and is strictly required for flavonoid production in multiple tissues of tomato. Expression of the wild-type SlCHI1 gene from its native promoter complemented the anthocyanin deficiency in af. Unexpectedly, the SlCHI1 transgene also complemented the defect in terpenoid production in glandular trichomes. Our results establish a key role for SlCHI1 in flavonoid production in tomato and reveal a link between CHI1 and terpenoid production. Metabolic coordination of the flavonoid and terpenoid pathways may serve to optimize the function of trichome glands in dynamic environments.

  7. Plant synthetic biology.

    PubMed

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants.

  8. Chalcones from Angelica keiskei attenuate the inflammatory responses by suppressing nuclear translocation of NF-κB.

    PubMed

    Chang, Hee Ryun; Lee, Hwa Jin; Ryu, Jae-Ha

    2014-12-01

    The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones (1-7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine (1), xanthoangelol E (2), xanthokeismin A (4), and xanthoangelol B (5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory-κBα (I-κBα) and the translocation of nuclear factor κB (NF-κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones (1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I-κBα and nuclear translocation of NF-κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents.

  9. Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus

    PubMed Central

    Bozic, Dragana D.; Milenkovic, Marina; Ivkovic, Branka; Cirkovic, Ivana

    2014-01-01

    Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA). The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3- Bis-(2-hydroxy-phenyl)-propenone, 3-(3-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300). Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3- Bis-(2-hydroxy-phenyl)-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy. PMID:24948943

  10. HIGHLY DIASTEREOSELECTIVE MICHAEL ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES

    EPA Science Inventory

    Substituted 2'-hydroxychalcones were found to give an equilibrium mixture of the starting chalcone and the corresponding flavanone in 4:6 - 1:3 ratio in the presence of various supports and MW irradiation. MW irradiation of 2'-hydroxychalcones in the presence of DBU gave two hit...

  11. A disulfide-linked conjugate of ferrocenyl chalcone and silicon(IV) phthalocyanine as an activatable photosensitiser.

    PubMed

    Lau, Janet T F; Jiang, Xiong-Jie; Ng, Dennis K P; Lo, Pui-Chi

    2013-05-14

    A novel bis(ferrocenyl chalcone) silicon(IV) phthalocyanine has been prepared in which the disulfide linker can be cleaved by dithiothreitol. The separation of the ferrocenyl quencher and the phthalocyanine core greatly enhances the fluorescence emission, singlet oxygen production and in vitro photocytotoxicity.

  12. [SYNTHETIC PEPTIDE VACCINES].

    PubMed

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  13. [From synthetic biology to synthetic humankind].

    PubMed

    Nouvel, Pascal

    2015-01-01

    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed.

  14. Synthesis and Evaluation of Novel Chalcone Derivatives with 99mTc/Re Complexes as Potential Probes for Detection of β-Amyloid Plaques

    PubMed Central

    2010-01-01

    Four 99mTc-labeled chalcone derivatives and their corresponding rhenium analogues were tested as potential probes for imaging β-amyloid plaques. The chalcones showed higher affinity for Aβ(1−42) aggregates than did 99mTc complexes. In sections of brain tissue from an animal model of AD, the four Re chalcones intensely stained β-amyloid plaques. In biodistribution experiments using normal mice, 99mTc-BAT-chalcone ([99mTc]17) displayed high uptake in the brain (1.48% ID/g) at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.17% ID/g at 60 min), a highly desirable feature for an imaging agent. [99mTc]17 may be a potential probe for imaging β-amyloid plaques in Alzheimer’s brains. PMID:22778849

  15. Separation of two major chalcones from Angelica keiskei by high-speed counter-current chromatography.

    PubMed

    Kil, Yun-Seo; Nam, Joo-Won; Lee, Jun; Seo, Eun Kyoung

    2015-08-01

    Angelica keiskei (Shin-sun cho) is an edible higher plant with the beneficial preventive effects on cancer, hypertension, and coronary heart disease. Two bioactive chalcones of Shin-sun cho, xanthoangelol (1) and 4-hydroxyderricin (2), were separated simultaneously by using high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-EtOAc-MeOH-H2O (9:5:9:4). Only nonconsuming processes, solvent fractionations and Sephadex LH-20 column chromatography, were conducted as presteps. Xanthoangelol (1, 35.9 mg, 99.9 % purity at 254 and 365 nm) and 4-hydroxyderricin (2, 4.4 mg, 98.7 % purity at 254 nm and 98.8 % purity at 365 nm) were successfully purified from 70 mg of the processed extract from A. keiskei. The structures of two compounds were confirmed by (1)H- and (13)C-NMR analysis.

  16. Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

    PubMed

    Li, Haoxin; Jean, Stéphanie; Webster, Duncan; Robichaud, Gilles A; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2015-11-25

    Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively).

  17. Xanthohumol, a chalcon derived from hops, inhibits hepatic inflammation and fibrosis.

    PubMed

    Dorn, Christoph; Kraus, Birgit; Motyl, Magdalena; Weiss, Thomas S; Gehrig, Manfred; Schölmerich, Jürgen; Heilmann, Jörg; Hellerbrand, Claus

    2010-07-01

    Xanthohumol (XN) is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. In this study, we first investigated the effects of XN on hepatocytes and hepatic stellate cells (HSC), the central mediators of liver fibrogenesis. XN inhibited the activation of primary human HSC and induced apoptosis in activated HSC in vitro in a dose dependent manner (0-20 microM). In contrast, XN doses as high as 50 microM did not impair viability of primary human hepatocytes. However, in both cell types XN inhibited activation of the transcription factor NFkappaB and expression of NFkappaB dependent proinflammatory genes. In vivo, feeding of XN reduced hepatic inflammation and expression of profibrogenic genes in a murine model of non-alcoholic steatohepatitis. These data indicate that XN has the potential as functional nutrient for the prevention or treatment of non-alcoholic steatohepatitis or other chronic liver disease.

  18. Synthesis and electrochemical and biological studies of novel coumarin-chalcone hybrid compounds.

    PubMed

    Pérez-Cruz, Fernanda; Vazquez-Rodriguez, Saleta; Matos, Maria João; Herrera-Morales, Alejandra; Villamena, Frederick A; Das, Amlan; Gopalakrishnan, Bhavani; Olea-Azar, Claudio; Santana, Lourdes; Uriarte, Eugenio

    2013-08-08

    A series of novel hydroxy-coumarin-chalcone hybrid compounds 2a-i has been synthesized by employing a simple and efficient methodology. An electrochemical characterization using cyclic voltammetry and ESR spectroscopy were carried out to characterize the oxidation mechanism for the target compounds. The antioxidant capacity and reactivity were determined by ORAC and ESR assays, respectively. Biological assays were assessed to evaluate the cytotoxicity and cytoprotection capacity against ROS/RNS on BAEC. The results revealed that all tested compounds present ORAC values that are much higher than other well-known antioxidant compounds such as quercetin and catechin. Compound 2e showed the highest ORAC value (14.1) and also presented a low oxidation potential, good scavenging capacity against hydroxyl radicals, low cytotoxicity, and high cytoprotective activity.

  19. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    PubMed

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound.

  20. Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

    NASA Astrophysics Data System (ADS)

    Prasath, R.; Bhavana, P.; Sarveswari, S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2015-02-01

    Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, 1H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the Cdbnd C ethylene bond has been established via 1H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

  1. Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis.

    PubMed

    Bajgai, Santi Prasad; Prachyawarakorn, Vilailak; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2011-11-01

    Hybrid flavan-chalcones, desmosflavans A (1) and B (2), together with three known compounds, cardamonin (3), pinocembrin (4) and chrysin (5), were isolated from leaves of Desmos cochinchinensis. Cardamonin (3) and chrysin (5) exhibited potent antioxidant activity with 15.0 and 12.2 ORAC units. Desmosflavans A (1) and B (2), pinocembrin (4), and chrysin (5) were found to be inhibitors of aromatase with respective IC50 values of 1.8, 3.3, 0.9, and 0.8 μM. Desmosflavan A (1) inhibited lipoxygenase with the IC50 value of 4.4 μM. Desmosflavan A (1) exhibited cytotoxic activity with IC50 values of 0.29-3.75 μg/mL, while desmosflavan B (2) showed IC50 values of 1.71-27.0 μg/mL.

  2. Cloning and characterization of chalcone synthase from the moss, Physcomitrella patens.

    PubMed

    Jiang, Chenguang; Schommer, Clark K; Kim, Sun Young; Suh, Dae-Yeon

    2006-12-01

    Since the early evolution of land plants from primitive green algae, flavonoids have played an important role as UV protective pigments in plants. Flavonoids occur in liverworts and mosses, and the first committed step in the flavonoid biosynthesis is catalyzed by chalcone synthase (CHS). Although higher plant CHSs have been extensively studied, little information is available on the enzymes from bryophytes. Here we report the cloning and characterization of CHS from the moss, Physcomitrella patens. Taking advantage of the available P. patens EST sequences, a CHS (PpCHS) was cloned from the gametophores of P. patens, and heterologously expressed in Escherichia coli. PpCHS exhibited similar kinetic properties and substrate preference profile to those of higher plant CHS. p-Coumaroyl-CoA was the most preferred substrate, suggesting that PpCHS is a naringenin chalcone producing CHS. Consistent with the evolutionary position of the moss, phylogenetic analysis placed PpCHS at the base of the plant CHS clade, next to the microorganism CHS-like gene products. Therefore, PpCHS likely represents a modern day version of one of the oldest CHSs that appeared on earth. Further, sequence analysis of the P. patens EST and genome databases revealed the presence of a CHS multigene family in the moss as well as the 3'-end heterogeneity of a CHS gene. Of the 19 putative CHS genes, 10 genes are expressed and have corresponding ESTs in the databases. A possibility of the functional divergence of the multiple CHS genes in the moss is discussed.

  3. Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols.

    PubMed

    Braune, Annett; Engst, Wolfram; Elsinghorst, Paul W; Furtmann, Norbert; Bajorath, Jürgen; Gütschow, Michael; Blaut, Michael

    2016-11-01

    The enzyme catalyzing the ring-contracting conversion of the flavanonol taxifolin to the auronol alphitonin in the course of flavonoid degradation by the human intestinal anaerobe Eubacterium ramulus was purified and characterized. It stereospecifically catalyzed the isomerization of (+)-taxifolin but not that of (-)-taxifolin. The Km for (+)-taxifolin was 6.4 ± 0.8 μM, and the Vmax was 108 ± 4 μmol min(-1) (mg protein)(-1) The enzyme also isomerized (+)-dihydrokaempferol, another flavanonol, to maesopsin. Inspection of the encoding gene revealed its complete identity to that of the gene encoding chalcone isomerase (CHI) from E. ramulus Based on the reported X-ray crystal structure of CHI (M. Gall et al., Angew Chem Int Ed 53:1439-1442, 2014, http://dx.doi.org/10.1002/anie.201306952), docking experiments suggest the substrate binding mode of flavanonols and their stereospecific conversion. Mutation of the active-site histidine (His33) to alanine led to a complete loss of flavanonol isomerization by CHI, which indicates that His33 is also essential for this activity. His33 is proposed to mediate the stereospecific abstraction of a proton from the hydroxymethylene carbon of the flavanonol C-ring followed by ring opening and recyclization. A flavanonol-isomerizing enzyme was also identified in the flavonoid-converting bacterium Flavonifractor plautii based on its 50% sequence identity to the CHI from E. ramulus IMPORTANCE: Chalcone isomerase was known to be involved in flavone/flavanone conversion by the human intestinal bacterium E. ramulus Here we demonstrate that this enzyme moreover catalyzes a key step in the breakdown of flavonols/flavanonols. Thus, a single isomerase plays a dual role in the bacterial conversion of dietary bioactive flavonoids. The identification of a corresponding enzyme in the human intestinal bacterium F. plautii suggests a more widespread occurrence of this isomerase in flavonoid-degrading bacteria.

  4. Evolvable synthetic neural system

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  5. Synthetic cathinone abuse

    PubMed Central

    Capriola, Michael

    2013-01-01

    The abuse of synthetic cathinones, widely known as bath salts, has been increasing since the mid-2000s. These substances are derivatives of the naturally occurring compound cathinone, which is the primary psychoactive component of khat. The toxicity of synthetic cathinones includes significant sympathomimetic effects, as well as psychosis, agitation, aggression, and sometimes violent and bizarre behavior. Mephedrone and methylenedioxypyrovalerone are currently the predominantly abused synthetic cathinones. PMID:23869180

  6. Theoretical and Experimental Study of Inclusion Complexes of β-Cyclodextrins with Chalcone and 2',4'-Dihydroxychalcone.

    PubMed

    Sancho, Matias I; Andujar, Sebastian; Porasso, Rodolfo D; Enriz, Ricardo D

    2016-03-31

    The inclusion complexes formed by chalcone and 2',4'-dihydroxychalcone with β-cyclodextrin have been studied combining experimental (phase solubility diagrams, Fourier transform infrared spectroscopy) and molecular modeling (molecular dynamics, quantum mechanics/molecular mechanics calculations) techniques. The formation constants of the complexes were determined at different temperatures, and the thermodynamic parameters of the process were obtained. The inclusion of chalcone in β-cyclodextrin is an exothermic process, while the inclusion of 2',4'-dihydroxychalcone is endothermic. Free energy profiles, derived from umbrella sampling using molecular dynamics simulations, were constructed to analyze the binding affinity and the complexation reaction at a molecular level. Hybrid QM/MM calculations were also employed to obtain a better description of the energetic and structural aspects of the complexes. The intermolecular interactions that stabilize both inclusion complexes were characterized by means of quantum atoms in molecules theory and reduce density gradient method. The calculated interactions were experimentally observed using FTIR.

  7. Designing synthetic biology.

    PubMed

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  8. New eco-friendly animal bone meal catalysts for preparation of chalcones and aza-Michael adducts

    PubMed Central

    2012-01-01

    Abstract Two efficient reactions were successfully carried out using Animal Bone Meal (ABM) and potassium fluoride or sodium nitrate doped ABMs as new heterogeneous catalysts under very mild conditions. After preparation and characterization of the catalysts, we first report their use in a simple and convenient synthesis of various chalcones by Claisen–Schmidt condensation and then in an aza-Michael addition involving several synthesized chalcones with aromatic amines. All the reactions were carried out at room temperature in methanol; the chalcone synthesis was also achieved in water environment under microwave irradiation. Doping ABM enhances the rate and yield at each reaction. Catalytic activities are discussed and the ability to re-use the ABM is demonstrated. Results For Claisen–Schmidt the use of ABM alone, yields never exceeded 17%. In each entry, KF/ABM and NaNO3/ABM (79-97%) gave higher yields than using ABM alone under thermic condition. Also the reaction proceeded under microwave irradiation in good yields (72-94% for KF/ABM and 81-97% for NaNO3/ABM) and high purity. For aza-Michael addition the use of ABM doped with KF or NaNO3 increased the catalytic activity remarkably. The very high yields could be noted (84-95% for KF/ABM and 81-94% for NaNO3/ABM). Conclusion The present method is an efficient and selective procedure for the synthesis of chalcones an aza-Michael adducts. The ABM and doped ABMs are a new, inexpensive and attractive solid supports which can contribute to the development of catalytic processes and reduced environmental problems. PMID:22721409

  9. Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.

    PubMed

    Meng, Charles Q; Zheng, X Sharon; Ni, Liming; Ye, Zhihong; Simpson, Jacob E; Worsencroft, Kimberly J; Hotema, Martha R; Weingarten, M David; Skudlarek, Jason W; Gilmore, Joshua M; Hoong, Lee K; Hill, Russell R; Marino, Elaine M; Suen, Ki-Ling; Kunsch, Charles; Wasserman, Martin A; Sikorski, James A

    2004-03-22

    Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.

  10. Theoretical investigation on mechanism of asymmetric Michael addition of malononitrile to chalcones catalyzed by Cinchona alkaloid aluminium(III) complex.

    PubMed

    Su, Zhishan; Lee, Hai Whang; Kim, Chan Kyung

    2011-09-21

    The mechanism of Michael addition of malononitrile to chalcones catalyzed by Cinchona alkaloid aluminium(III) complex has been investigated by DFT and ONIOM methods. Calculations indicate that the reaction proceeds through a dual activation mechanism, in which Al(III) acts as a Lewis acid to activate the electrophile α,β-unsaturated carbonyl substrate while the tertiary amine in the Cinchona alkaloid works as a Lewis base to promote the activation of the malononitrile and deprotonation. A stepwise pathway involving C-C bond formation followed by proton transfer from the catalyst to the carbonyl substrate is adopted, and latter step is predicted to be the rate-determining-step in the reaction with an energy barrier of 12.4 kcal mol(-1). In the absence of the Al(III)-complex, a Cinchona alkaloid activates the carbonyl substrate by a hydrogen bonding of the hydroxyl group, involving a higher energy barrier of 30.4 kcal mol(-1). The steric repulsion between the phenyl group attached to the carbonyl group in the chalcone and isopropoxyl groups of the Al(III)-complex may play an important role in the control of stereoselectivity. The π-π stacking effect between the quinuclidine ring of the quinine and the phenyl group of the chalcones may also help the stabilization of the preferred molecular complex. These results are in agreement with experimental observations.

  11. Studies of manufacturing controlled-release graphene acid and catalyzing synthesis of chalcone with Claisen-Schmidt condensation reaction

    NASA Astrophysics Data System (ADS)

    Li, Jihui; Feng, Jia; Li, Mei; Wang, Qiaolian; Su, Yumin; Jia, Zhixin

    2013-07-01

    In the paper, graphene acid (GA) was manufactured, using flake graphite as raw material, and the acidity and the structure of GA were characterized as well as. Then, chalcone was synthesized in the presence of GA, using acetophenone and benzaldehyde as the reactant. The results showed that the acidity of GA was for pH = 1.12 in aqueous solution, and it was structured by the graphene sheets with the spaces between the graphene sheet and the graphene sheet and sulfuric acid (H2SO4) and acetic acid (CH3CO2H) inside the spaces. At the same time, the results also exhibited that the chalcone yield was able to reach 60.36% when GA dosage was 5 g, and the chalcone yields could attain apart 60.36, 52.05 and 31.16% when 5 g of GA was used thrice. This shows that GA is not only a high-performance catalyst, but also a controlled-release catalyst.

  12. Chemoprotective potentials of homoisoflavonoids and chalcones of Dracaena cinnabari: modulations of drug-metabolizing enzymes and antioxidant activity.

    PubMed

    Machala, M; Kubínová, R; Horavová, P; Suchý, V

    2001-03-01

    A series of homoisoflavonoids and chalcones, isolated from the endemic tropical plant Dracaena cinnabari Balf. (Agavaceae), were tested for their potential to inhibit cytochrome P4501A (CYP1A) enzymes and Fe-enhanced in vitro peroxidation of microsomal lipids in C57B1/6 mouse liver. The effects of the polyphenolic compounds were compared with those of prototypal flavonoid modulators of CYP1A and the well-known antioxidant, butylated hydroxytoluene. 2-Hydroxychalcone and partly 4,6-dihydroxychalcone were found to be strong inhibitors of CYP1A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity in vitro comparable to the effects of quercetin and chrysin. The first screening of flavonoids and chalcones of Dracaena cinnabari for antioxidant activity was done in an in vitro microsomal peroxidation assay. While chalcones were shown to be poor antioxidants, 7,8-methylenedioxy-3(4-hydroxybenzyl) chromane, as one of the tested homoisoflavonoids, exhibited a strong antioxidant activity comparable to that of the strongest flavonol antioxidant, quercetin.

  13. Antitumor effects of the flavone chalcone: inhibition of invasion and migration through the FAK/JNK signaling pathway in human gastric adenocarcinoma AGS cells.

    PubMed

    Lin, Su-Hsuan; Shih, Yuan-Wei

    2014-06-01

    Chalcones (benzylideneacetophenone) are cancer-preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in human gastric adenocarcinoma cell lines: AGS. The results showed that chalcone could inhibit the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, Boyden chamber invasion/migration assay, and wound-healing assay. Molecular data showed that the effect of chalcone in AGS cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) and c-Jun N-terminal kinase 1 and 2 (JNK1/2) signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Next, chalcone-treated AGS cells showed tremendous decrease in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, treating FAK small interfering RNA (FAK siRNA) and specific inhibitor for JNK (SP600125) to AGS cells could reduce the phosphorylation of JNK1/2 and the activity of MMP-2 and MMP-9. Our results revealed that chalcone significantly inhibited the metastatic ability of AGS cells by reducing MMP-2 and MMP-9 expressions concomitantly with a marked reduction on cell invasion and migration through suppressing and JNK signaling pathways. We suggest that chalcone may offer the application in clinical medicine.

  14. Synthetic biological networks

    NASA Astrophysics Data System (ADS)

    Archer, Eric; Süel, Gürol M.

    2013-09-01

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics.

  15. Molecular structures of chalcone podands: A prognosis of photoinduced transformations in the crystals

    SciTech Connect

    Ovchinnikova, I. G. Fedorova, O. V.; Slepukhin, P. A.; Litvinov, I. A.; Rusinov, G. L.

    2009-01-15

    A series of chalcone podands with the propenone group in the ortho position of the bridging aryl substituent with respect to the oxyethylene fragment is synthesized. The influence of the preorganization of the chalcone podand molecules in crystals on their ability to participate in topochemical reactions is investigated. From analyzing the X-ray structural data, the highest probability of the solid-state photochemical [2 + 2]cycloaddition is predicted for podands with phenyl substituents and the oxyethylene fragment containing two or three oxygen atoms. The X-ray structural data for the chalcone podand C{sub 32}H{sub 26}O{sub 4} (3a) are as follows: a = 7.904(9) A, b = 14.92(2) A, c = 21.30(3) A, {beta} = 91.7(1){sup o}, monoclinic system, space group P2{sub 1}/c, Z = 4, V = 2510(5) A{sup 3}, {rho} = 1.26 g/cm{sup 3}, and R = 0.046; C{sub 34}H{sub 30}O{sub 5} (3b): a = 15.738(9) A, b = 11.889(2) A, c = 15.0830(15) A, {beta} = 105.47(14){sup o}, monoclinic system, space group C2/c, Z = 4, V = 2720.0(9) A{sup 3}, {rho} = 1.266 g/cm{sup 3}, and R = 0.0418; C{sub 32}H{sub 24}N{sub 2}O{sub 8} (4a): a = 17.9416(18) A, b = 10.9703(8) A, c = 41.699(2) A, {beta} = 105.970(11){sup o}, monoclinic system, space group P2{sub 1}/c, Z = 4, V = 2781.4(5) A{sup 3}, {rho} = 1.348 g/cm{sup 3}, and R = 0.0426; C{sub 36}H{sub 32}N{sub 2}O{sub 10} (4c): a = 7.6286(5)A, b = 17.9398(10) A, c = 11.5890(3)A, {beta} = 95.287(4){sup o}, monoclinic system, space group P2{sub 1}/n, Z = 2, V = 1579.27(14) A{sup 3}, {rho} = 1.372 g/cm{sup 3}, and R = 0.0377; and C{sub 28}H{sub 22}O{sub 6} (5a): a = 15.6032(10) A, b = 8.1131(5) A, c = 17.7334(11) A, {beta} = 91.381(5){sup o}, monoclinic system, space group C2/c, Z = 4, V = 2244.2(2) A{sup 3}, {rho} = 1.345 g/cm{sup 3}, and R = 0.0309.

  16. Identification of Chalcones as Fasciola hepatica Cathepsin L Inhibitors Using a Comprehensive Experimental and Computational Approach

    PubMed Central

    Ferraro, Florencia; Merlino, Alicia; dell´Oca, Nicolás; Gil, Jorge; Tort, José F.; Gonzalez, Mercedes; Cerecetto, Hugo; Cabrera, Mauricio

    2016-01-01

    Background Increased reports of human infections have led fasciolosis, a widespread disease of cattle and sheep caused by the liver flukes Fasciola hepatica and Fasciola gigantica, to be considered an emerging zoonotic disease. Chemotherapy is the main control measure available, and triclabendazole is the preferred drug since is effective against both juvenile and mature parasites. However, resistance to triclabendazole has been reported in several countries urging the search of new chemical entities and target molecules to control fluke infections. Methodology/Principle Findings We searched a library of forty flavonoid derivatives for inhibitors of key stage specific Fasciola hepatica cysteine proteases (FhCL3 and FhCL1). Chalcones substituted with phenyl and naphtyl groups emerged as good cathepsin L inhibitors, interacting more frequently with two putative binding sites within the active site cleft of the enzymes. One of the compounds, C34, tightly bounds to juvenile specific FhCL3 with an IC50 of 5.6 μM. We demonstrated that C34 is a slow-reversible inhibitor that interacts with the Cys-His catalytic dyad and key S2 and S3 pocket residues, determinants of the substrate specificity of this family of cysteine proteases. Interestingly, C34 induces a reduction in NEJ ability to migrate through the gut wall and a loss of motility phenotype that leads to NEJ death within a week in vitro, while it is not cytotoxic to bovine cells. Conclusions/Significance Up to date there are no reports of in vitro screening for non-peptidic inhibitors of Fasciola hepatica cathepsins, while in general these are considered as the best strategy for in vivo inhibition. We have identified chalcones as novel inhibitors of the two main Cathepsins secreted by juvenile and adult liver flukes. Interestingly, one compound (C34) is highly active towards the juvenile enzyme reducing larval ability to penetrate the gut wall and decreasing NEJ´s viability in vitro. These findings open new avenues

  17. What Are Synthetic Cannabinoids?

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... they are related to chemicals found in the marijuana plant. Because of this similarity, synthetic cannabinoids are ...

  18. Synthetic Vision Systems

    NASA Technical Reports Server (NTRS)

    Prinzel, L.J.; Kramer, L.J.

    2009-01-01

    A synthetic vision system is an aircraft cockpit display technology that presents the visual environment external to the aircraft using computer-generated imagery in a manner analogous to how it would appear to the pilot if forward visibility were not restricted. The purpose of this chapter is to review the state of synthetic vision systems, and discuss selected human factors issues that should be considered when designing such displays.

  19. Active synthetic soil

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W. (Inventor); Henninger, Donald L. (Inventor); Allen, Earl R. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic soil/fertilizer for horticultural application having all the agronutrients essential for plant growth is disclosed. The soil comprises a synthetic apatite fertilizer having sulfur, magnesium and micronutrients dispersed in a calcium phosphate matrix, a zeolite cation exchange medium saturated with a charge of potassium and nitrogen cations, and an optional pH buffer. Moisture dissolves the apatite and mobilizes the nutrient elements from the apatite matrix and the zeolite charge sites.

  20. Active synthetic soil

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W. (Inventor); Henninger, Donald L. (Inventor); Allen, Earl R. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic soil/fertilizer for horticultural application having all the agronutrients essential for plant growth is disclosed. The soil comprises a synthetic apatite fertilizer having sulfur, magnesium, and micronutrients dispersed in a calcium phosphate matrix, a zeolite cation exchange medium saturated with a charge of potassium and nitrogen cations, and an optional pH buffer. Moisture dissolves the apatite and mobilizes the nutrient elements from the apatite matrix and the zeolite charge sites.

  1. Silybin content and overexpression of chalcone synthase genes in Silybum marianum L. plants under abiotic elicitation.

    PubMed

    El-Garhy, Hoda A S; Khattab, Salah; Moustafa, Mahmoud M A; Abou Ali, Rania; Abdel Azeiz, Ahmed Z; Elhalwagi, Abeer; El Sherif, Fadia

    2016-11-01

    Silymarin, a Silybum marianum seed extract containing a mixture of flavonolignans including silybin, is being used as an antihepatotoxic therapy for liver diseases. In this study, the enhancing effect of gamma irradiation on plant growth parameters of S. marianum under salt stress was investigated. The effect of gamma irradiation, either as a single elicitor or coupled with salinity, on chalcone synthase (CHS) gene expression and silybin A + B yield was also evaluated. The silybin A + B content in S. marianum fruits was estimated by liquid chromatography-mass spectrometry (LC-MS/MS). An increase in silybin content was accompanied by up-regulation of the CHS1, CHS2 and CHS3 genes, which are involved in the silybin biosynthetic pathway. The highest silybin A + B production (0.77 g/100 g plant DW) and transcript levels of the three studied genes (100.2-, 91.9-, and 24.3-fold increase, respectively) were obtained with 100GY gamma irradiation and 4000 ppm salty water. The CHS2 and CHS3 genes were partially sequenced and submitted to the NCBI database under the accession numbers KT252908.1 and KT252909.1, respectively. Developing new approaches to stimulate silybin biosynthetic pathways could be a useful tool to potentiate the use of plants as renewable resources of medicinal compounds.

  2. Molecular evolution and functional specialization of chalcone synthase superfamily from Phalaenopsis orchid.

    PubMed

    Han, Ying-Ying; Ming, Feng; Wang, Wei; Wang, Jing-Wen; Ye, Ming-Ming; Shen, Da-Leng

    2006-01-01

    Plant genomes appear to exploit the process of gene duplication as a primary means of acquiring biochemical and developmental flexibility. The best example is the gene encoding chalcone synthase (CHS, EC2.3.1.74), the first committed step in flavonoid biosynthesis. In this study, we examined the molecular evolution of three CHS family members of Phalaenopsis including a novel chs gene (phchs5), which is slowly evolved. The inferred phylogeny of the chs genes of Phalaenopsis with other two orchid plants, Bromoheadia finlaysoniana and Dendrobium hybrid, suggested that gene duplication and divergence have occurred before divergence of these three genera. Relatively quantitative RT-PCR analysis identified expression patterns of these three chs genes in different floral tissues at different developmental stages. Phchs5 was the most abundantly expressed chs gene in floral organs and it was specifically transcribed in petal and lip at the stages when anthocyanin accumulated (stage1-4). Phchs3 and phchs4 were expressed at much lower levels than phchs5. Phchs3 was expressed in pigmented tissue (including lip, petal and sepal) at middle stages (stages 2-4) and in colorless reproductive tissue at late stage (stage 5). Phchs4 was only expressed in petal at earlier stages (stage 1-3) and in lip at middle stage (stage 4). These results present new data on differentiation of gene expression among duplicate copies of chs genes in Phalaenopsis.

  3. Structural, electrochemical and theoretical study of a new chalcone derivative containing 3-thiophene rings

    NASA Astrophysics Data System (ADS)

    Baggio, Ricardo; Brovelli, Francisco; Moreno, Yanko; Pinto, Marcela; Soto-Delgado, Jorge

    2016-11-01

    The title chalcone, 1,3-di(thiophene-3-yl)prop-2-en-1-one (C11H8OS2) is an essentially planar molecular with its terminal thiophene rings subtending an angle of 8.9°. The crystal structure consists in the π··π stacking of molecules defining columns along [010], further linked along c by non conventional Csbnd H⋯O bonds, thus determining broad planar arrays parallel to (100). In addition, there are weak S⋯S contacts connecting these weakly interacting 2D substructures. The experimental results obtained from single crystal X-ray diffraction data and the theoretical geometry calculated by molecular mechanics are in good agreement. Electrochemical records reveal an anodic profile with an unsymmetrical irreversible peak at 1.77 V and a shoulder at 1.62 V vs SCE, a behavior interpretable as due to the oxidation of reactive sites present in the molecule. On the other hand, the electrochemical reduction shows a narrow peak at -1.58 V vs SCE, a fact attributable to the carbonyl group. Finally, the values for the energy involved in the departure/arrival of electrons from border orbitals, as calculated using DFT, is compared with experimental data from cyclic voltammetry.

  4. Enhancement of flavone levels through overexpression of chalcone isomerase in hairy root cultures of Scutellaria baicalensis.

    PubMed

    Park, Nam Il; Xu, Hui; Li, Xiaohua; Kim, Sun-Ju; Park, Sang Un

    2011-09-01

    A complementary DNA (cDNA) encoding Scutellaria baicalensis chalcone isomerase (SbCHI) was isolated using rapid amplification of cDNA ends polymerase chain reaction. After the treatment of wounding or methyl jasmonate, SbCHI transcripts were increased in S. baicalensis cell suspensions. SbCHI-overexpressed and SbCH-silenced transgenic hairy root lines were established by using an Agrobacterium rhizogenes-mediated system. SbCHI-overexpressed hairy root lines not only enhanced SbCHI gene expression but also produced more flavones (i.e., baicalin, baicalein, and wogonin) than the control hairy root line. In contrast, SbCHI-silenced hairy root lines reduced SbCHI transcripts and flavone production compared to those of the control hairy roots. In addition, the amount of wogonin in all hairy root cultures was increased compared to that of wild-type roots of S. baicalensis. Finally, this study showed the importance of CHI in flavone biosynthesis and the efficiency of metabolic engineering in S. baicalensis hairy roots.

  5. Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in Flavonoid Biosynthetic Pathway

    PubMed Central

    Sun, Wei; Meng, Xiangyu; Liang, Lingjie; Jiang, Wangshu; Huang, Yafei; He, Jing; Hu, Haiyan; Almqvist, Jonas; Gao, Xiang; Wang, Li

    2015-01-01

    Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants. PMID:25742495

  6. Molecular cloning and sequence analysis of a novel chalcone synthase cDNA from Ginkgo biloba.

    PubMed

    Pang, Yongzhen; Shen, Guo-An; Liu, Chenghong; Liu, Xiaojun; Tan, Feng; Sun, Xiaofen; Tang, Kexuan

    2004-08-01

    A chalcone synthase (CHS) gene was cloned from Ginkgo biloba for the first time and it was also the first cloned gene involved in flavonoids metabolic pathway in G. biloba. The full-length cDNA of G. biloba CHS (designated as Gbchs) was 1608bp with poly(A) tailing and it contained a 1173bp open reading frame (ORF) encoding a 391 amino acid protein. Gbchs was found to have extensive homology with those of other plant chs genes via multiple alignments. The active sites of the CoA binding, coumaroyl pocket and cyclization pocket in CHS protein of Medicago sativa were also found in GbCHS. Molecular modeling of GbCHS indicated that the three-dimensional structure of GbCHS strongly resembled that of M. sativa (MsCHS2), implying GbCHS may have similar functions with MsCHS2. Phylogenetic tree analysis revealed that GbCHS had closer relationship with CHSs from gymnosperm plants than from other plants. Gbchs is a useful tool to study the regulation of flavonoids metabolism in G. biloba.

  7. Genome-Wide Identification, Characterization and Expression Analysis of the Chalcone Synthase Family in Maize

    PubMed Central

    Han, Yahui; Ding, Ting; Su, Bo; Jiang, Haiyang

    2016-01-01

    Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01–14) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I–IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family. PMID:26828478

  8. Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines.

    PubMed

    Sakai, Toshinori; Eskander, Ramez N; Guo, Yi; Kim, Kap Jung; Mefford, Jason; Hopkins, Justin; Bhatia, Nitin N; Zi, Xiaolin; Hoang, Bang H

    2012-07-01

    Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis. Treatment with FKB increased caspase 8, 9, and 3/7 activity compared to vehicle-treated controls, indicating that both extrinsic and intrinsic apoptotic pathways were activated. Furthermore, FKB treatment of both cell lines resulted in increased mRNA and protein expression of death receptor-5 and the mitochondrial pro-apoptotic proteins Bim and Puma, while down-regulating the expression of an inhibitor of apoptosis, survivin in a dose-dependent manner. Our results suggest the natural compound FKB has a pro-apoptotic effect on SS cell lines. FKB may be a new chemotherapeutic strategy for patients with SS and deserves further investigation as a potential agent in the treatment of this malignancy.

  9. Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica).

    PubMed

    Dare, Andrew P; Tomes, Sumathi; Jones, Midori; McGhie, Tony K; Stevenson, David E; Johnson, Ross A; Greenwood, David R; Hellens, Roger P

    2013-05-01

    We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids. Surprisingly, down-regulation of CHS also led to major changes in plant development, resulting in plants with shortened internode lengths, smaller leaves and a greatly reduced growth rate. Microscopic analysis revealed that these phenotypic changes extended down to the cellular level, with CHS-silenced lines showing aberrant cellular organisation in the leaves. Fruit collected from one CHS-silenced line was smaller than the 'Royal Gala' controls, lacked flavonoids in the skin and flesh and also had changes in cell morphology. Auxin transport experiments showed increased rates of auxin transport in a CHS-silenced line compared with the 'Royal Gala' control. As flavonoids are well known to be key modulators of auxin transport, we hypothesise that the removal of almost all flavonoids from the plant by CHS silencing creates a vastly altered environment for auxin transport to occur and results in the observed changes in growth and development.

  10. Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship

    NASA Astrophysics Data System (ADS)

    Akhtar, Muhammad Nadeem; Sakeh, Nurshafika M.; Zareen, Seema; Gul, Sana; Lo, Kong Mun; Ul-Haq, Zaheer; Shah, Syed Adnan Ali; Ahmad, Syahida

    2015-04-01

    Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.

  11. Synthesis, fluorescence, TGA and crystal structure of thiazolyl-pyrazolines derived from chalcones

    NASA Astrophysics Data System (ADS)

    Suwunwong, T.; Chantrapromma, S.; Fun, H.-K.

    2015-04-01

    Thiazolyl-pyrazolines 3a-3d were synthesized in a three step procedure using chalcones as starting materials and characterized by FT-IR, UV-Vis, and 1H NMR techniques. The crystal structure of compound 3a was also determined by X-ray diffraction analysis. Compound 3a crystallized out in the orthorhombic P212121 space group with the unit cell dimensions: a = 5.2106(2) Å, b = 12.4341(5) Å, c = 33.3254(13) Å, α = β = γ = 90°, V = 2159.12(15) Å3, Z = 4, D cald = 1.372 M gm-3 and F(000) = 928. Fluorescence of 3a-3d were studied in solid state and acetonitrile solution. It was found that, these compounds exhibit the green fluorescence light (506-508 nm) in both solid and solution states. The pH stability on fluorescence property and the thermal gravimetric analysis of compound 3a were specifically carried out. It was revealed that 3a shows high thermal stability up to around 250°C and presenting high stability in various pH ranges in the acetonitrilewater matrix.

  12. Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

    PubMed

    Anthwal, Amit; Rajesh, U Chinna; Rawat, M S M; Kushwaha, Bhavana; Maikhuri, Jagdamba P; Sharma, Vishnu L; Gupta, Gopal; Rawat, Diwan S

    2014-05-22

    Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 μg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

  13. Spectral, biological screening of metal chelates of chalcone based Schiff bases of N-(3-aminopropyl) imidazole

    NASA Astrophysics Data System (ADS)

    Kalanithi, M.; Rajarajan, M.; Tharmaraj, P.; Sheela, C. D.

    2012-02-01

    Tridentate chelate complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized from the chalcone based ligands 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-(phenylallyl)]phenol( HL1), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-p-tolylallyl]phenol( HL2), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-4-nitrophenylallyl]phenol( HL3). Microanalytical data, UV-vis spectrophotometric method, magnetic susceptibility measurements, IR, 1H NMR, Mass, and EPR techniques were used to characterize the structure of chelates. The electronic absorption spectra and magnetic susceptibility measurements suggest a distorted square planar geometry for the copper(II) ion. The other metal complexes show distorted tetrahedral geometry. The coordination of the ligands with metal(II) ions was further confirmed by solution fluorescence spectrum. The antimicrobial activity of the ligands and metal(II) complexes against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger has been carried out and compared. The electrochemical behavior of copper(II) complex is studied by cyclic voltammetry.

  14. Antibacterial activity and QSAR of chalcones against biofilm-producing bacteria isolated from marine waters.

    PubMed

    Sivakumar, P M; Prabhawathi, V; Doble, M

    2010-04-01

    Biofouling in the marine environment is a major problem. In this study, three marine organisms, namely Bacillus flexus (LD1), Pseudomonas fluorescens (MD3) and Vibrio natriegens (MD6), were isolated from biofilms formed on polymer and metal surfaces immersed in ocean water. Phylogenetic analysis of these three organisms indicated that they were good model systems for studying marine biofouling. The in vitro antifouling activity of 47 synthesized chalcone derivatives was investigated by estimating the minimum inhibitory concentration against these organisms using a twofold dilution technique. Compounds C-5, C-16, C-24, C-33, C-34 and C-37 were found to be the most active. In the majority of the cases it was found that these active compounds had hydroxyl substitutions. A quantitative structure-activity relationship (QSAR) was developed after dividing the total data into training and test sets. The statistical measures r(2), [image omitted] (>0.6) q(2) (>0.5) and the F-ratio were found to be satisfactory. Spatial, structural and electronic descriptors were found to be predominantly affecting the antibiofouling activity of these compounds. Among the spatial descriptors, Jurs descriptors showed their contribution in all the three antibacterial QSARs.

  15. Synthesis, growth, structure and characterization of chalcone crystal: A novel organic NLO material

    NASA Astrophysics Data System (ADS)

    Agilandeshwari, R.; Meenatchi, V.; Meenakshisundaram, S. P.

    2016-08-01

    Single crystals of a chalcone, (E)-3-(4-bromophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (BHP), were grown by the slow evaporation solution growth technique. The structure is elucidated by single-crystal X-ray diffraction analysis and the crystal belongs to the monoclinic system with noncentrosymmetric space group P21. Optical studies reveal that the absorption is minimum in the visible region and the cut-off wavelength is at ∼468 nm. The band-gap energy was estimated by the application of the Kubelka-Munk algorithm. The powder X-ray diffraction pattern reveals the good crystallinity of the as-grown specimen. The vibrational patterns in FT-IR are used to identify the functional groups and thermal studies indicate the stability of the material. The second harmonic generation efficiency (SHG), as estimated by Kurtz and Perry powder technique, reveals the superior nonlinear optical character of this material. Hirshfeld surface analysis is done to quantify the intermolecular interactions, responsible for developing a nonlinear atmosphere. As-grown crystals were further characterized by SEM, NMR, mass spectrometry and elemental analysis.

  16. Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer.

    PubMed

    Vanhoecke, Barbara; Derycke, Lara; Van Marck, Veerle; Depypere, Herman; De Keukeleire, Denis; Bracke, Marc

    2005-12-20

    The female inflorescences of the hop plant (Humulus lupulus L.) are essential during brewing to add taste and flavor to beer and to stabilize beer foam. Xanthohumol, the main prenylated chalcone in hops, was investigated for its antiinvasive activity on human breast cancer cell lines (MCF-7 and T47-D) in vitro. Xanthohumol was able to inhibit the invasion of MCF-7/6 cells at 5 microM in the chick heart invasion assay and of T47-D cells in the collagen invasion assay. Xanthohumol inhibited growth of MCF-7/6 and T47-D cells, but not of chick heart cells. Moreover, it induced apoptosis of these tumor cells as demonstrated by the cleavage of nuclear PARP after 48 hr treatment. To probe the mechanism of the antiinvasive effect of xanthohumol, involvement of the E-cadherin/catenin invasion-suppressor complex was investigated. An aggregation assay demonstrated stimulation of aggregation of MCF-7/6 cells in the presence of 5 microM xanthohumol and this could be completely inhibited by an antibody against E-cadherin. Xanthohumol upregulates the function of the E-cadherin/catenin complex and inhibits invasion in vitro, indicating a possible role as an antiinvasive agent in vivo as well.

  17. Transient silencing of CHALCONE SYNTHASE during fruit ripening modifies tomato epidermal cells and cuticle properties.

    PubMed

    España, Laura; Heredia-Guerrero, José A; Reina-Pinto, José J; Fernández-Muñoz, Rafael; Heredia, Antonio; Domínguez, Eva

    2014-11-01

    Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids.

  18. Cytotoxic chalcones and antioxidants from the fruits of a Syzygium samarangense (Wax Jambu)

    PubMed Central

    Simirgiotis, Mario J.; Adachi, Seiji; To, Satoshi; Yang, Hui; Reynertson, Kurt A.; Basile, Margaret J.; Gil, Roberto R.; Weinstein, I. Bernard; Kennelly, Edward J.

    2011-01-01

    Bioassay-guided fractionation of the methanolic extracts of the pulp and seeds of the fruits of Syzygium samarangense Merr. & Perry (Blume) led to the identification of four cytotoxic compounds and eight antioxidants on the basis of HPLC-PDA analysis, MS, and various NMR spectroscopic techniques. Three C-methylated chalcones, 2′,4′-dihydroxy-3′,5′-dimethyl-6′-methoxychalcone (1), 2′,4′-dihydroxy-3′-methyl-6′-methoxychalcone (stercurensin, 2), and 2′,4′-dihydroxy-6′-methoxychalcone (cardamonin, 3), were isolated and displayed cytotoxic activity (IC50 = 10, 35, and 35 μM, respectively) against the SW-480 human colon cancer cell line. Also a number of known antioxidants were obtained including six quercetin glycosides: reynoutrin (4), hyperin (5), myricitrin (6), quercitrin (7), quercetin (9), and guaijaverin (10), one flavanone: (S)-pinocembrin (8), and two phenolic acids: gallic acid (11) and ellagic acid (12). PMID:22359426

  19. The Synthetic Cannabinoids Phenomenon.

    PubMed

    Karila, Laurent; Benyamina, Amine; Blecha, Lisa; Cottencin, Olivier; Billieux, Joël

    2016-01-01

    « Spice » is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at

  20. Differential Synthetic Aperture Ladar

    SciTech Connect

    Stappaerts, E A; Scharlemann, E

    2005-02-07

    We report a differential synthetic aperture ladar (DSAL) concept that relaxes platform and laser requirements compared to conventional SAL. Line-of-sight translation/vibration constraints are reduced by several orders of magnitude, while laser frequency stability is typically relaxed by an order of magnitude. The technique is most advantageous for shorter laser wavelengths, ultraviolet to mid-infrared. Analytical and modeling results, including the effect of speckle and atmospheric turbulence, are presented. Synthetic aperture ladars are of growing interest, and several theoretical and experimental papers have been published on the subject. Compared to RF synthetic aperture radar (SAR), platform/ladar motion and transmitter bandwidth constraints are especially demanding at optical wavelengths. For mid-IR and shorter wavelengths, deviations from a linear trajectory along the synthetic aperture length have to be submicron, or their magnitude must be measured to that precision for compensation. The laser coherence time has to be the synthetic aperture transit time, or transmitter phase has to be recorded and a correction applied on detection.

  1. Excision of transposable elements from the chalcone isomerase and dihydroflavonol 4-reductase genes may contribute to the variegation of the yellow-flowered carnation (Dianthus caryophyllus).

    PubMed

    Itoh, Yoshio; Higeta, Daisuke; Suzuki, Akane; Yoshida, Hiroyuki; Ozeki, Yoshihiro

    2002-05-01

    In the "Rhapsody" cultivar of the carnation, which bears white flowers variegated with red flecks and sectors, a transposable element, dTdic1, belonging to the Ac/Ds superfamily, was found within the dihydroflavonol 4-reductase (DFR) gene. The red flecks and sectors of "Rhapsody" may be attributable to a reversion to DFR activity after the excision of dTdic1. The yellow color of the carnation petals is attributed to the synthesis and accumulation of chalcone 2'-glucoside. In several of the carnation cultivars that bear yellow flowers variegated with white flecks and sectors, both the chalcone isomerase (CHI) and DFR genes are disrupted by dTdic1.

  2. Synthetic carbon precursor materials

    SciTech Connect

    Frame, B.J.

    1986-03-01

    Synthetic carbon precursor systems offer advantages over natural petroleum and coal-tar pitch precursors in that they can reproducibly provide a material with a known and uniform composition. They also permit controlled modifications of the derived carbon's properties through variations in the precursor's properties and processing conditions. Extensive research efforts at Oak Ridge have been directed toward the production and characterization of synthetic carbon precursors and the correlations that exist between carbon precursor properties and the properties of the ultimate carbon. This report describes how synthetic carbon precursors can be used to tailor and develop reproducible carbon structures for advanced materials applications. The potential and capability for performing carbon material development at Oak Ridge is also described.

  3. Gamma synthetic hydrographs

    NASA Astrophysics Data System (ADS)

    Croley, Thomas E.

    1980-05-01

    The two-parameter Gamma distribution is presented as a basis for synthetic hydrographs with a review of existing applications and non-feasible applications are identified. Several approaches for fitting this function to practical boundary condition parameters are identified and presented in a unified treatment. They are especially designed for use on small programmable calculators since the synthetic hydrograph is extremely sensitive to the Gamma distribution parameters. Nomographs would give large errors in the fit for small errors in the boundary condition parameters. Although non-dimensionalization of the synthetic hydrograph is possible with the Gamma distribution, it is shown to be unnecessary. Current uses of "standard" non-dimensional hydrographs are shown to be in error.

  4. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test

    PubMed Central

    Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo e

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties. PMID:26335560

  5. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

    PubMed

    Silva, Carolina Ribeiro E; Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo E; Chen-Chen, Lee

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

  6. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A [Castro Valley, CA; Page, Ralph H [Castro Valley, CA; Ebbers, Christopher A [Livermore, CA; Beach, Raymond J [Livermore, CA

    2008-06-10

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  7. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A.; Page, Ralph H.; Ebbers, Christopher A.; Beach, Raymond J.

    2004-03-09

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  8. Synthesis, α-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones.

    PubMed

    Sun, Hua; Li, Yashan; Zhang, Xiaoting; Lei, Yanan; Ding, Weina; Zhao, Xue; Wang, Haomeng; Song, Xiaotong; Yao, Qingwei; Zhang, Yongmin; Ma, Ying; Wang, Runling; Zhu, Tao; Yu, Peng

    2015-10-15

    Three series of prenylated and/or geranylated flavonoids were synthesized and evaluated for their α-glucosidase inhibitory activity. The 3',5'-digeranylated chalcone (16) was identified as a new α-glucosidase inhibitor whose activity (IC50=0.90 μM) was 50-fold more than that of acarbose (IC50=51.32 μM). Molecular docking studies revealed the existence of strong hydrophobic interaction and H-bonding between compound 16 and α-glucosidase's active site. The inhibitory mode analysis showed that 16 exhibited a competitive inhibitory mode.

  9. Biodegradable synthetic bone composites

    SciTech Connect

    Liu, Gao; Zhao, Dacheng; Saiz, Eduardo; Tomsia, Antoni P.

    2013-01-01

    The invention provides for a biodegradable synthetic bone composition comprising a biodegradable hydrogel polymer scaffold comprising a plurality of hydrolytically unstable linkages, and an inorganic component; such as a biodegradable poly(hydroxyethylmethacrylate)/hydroxyapatite (pHEMA/HA) hydrogel composite possessing mineral content approximately that of human bone.

  10. Synthetic Bursae for Robots

    NASA Technical Reports Server (NTRS)

    Lovchik, Christopher S.

    2005-01-01

    Synthetic bursae are under development for incorporation into robot joints that are actuated by motor-driven cables in a manner similar to that of arthropod joints actuated by muscle-driven tendons. Like natural bursae, the synthetic bursae would serve as cushions and friction reducers. A natural bursa is a thin bladder filled with synovial fluid, which serves to reduce friction and provide a cushion between a bone and a muscle or a tendon. A synthetic bursa would be similar in form and function: It would be, essentially, a compact, soft roller consisting of a bladder filled with a non-Newtonian fluid. The bladder would be constrained to approximately constant volume. The synthetic bursa would cushion an actuator cable against one of the members of a robot joint and would reduce the friction between the cable and the member. Under load, the pressure in the bladder would hold the opposite walls of the bladder apart, making it possible for them to move freely past each other without rubbing.

  11. Synthetic Aperture Radar Interferometry

    NASA Technical Reports Server (NTRS)

    Rosen, P. A.; Hensley, S.; Joughin, I. R.; Li, F.; Madsen, S. N.; Rodriguez, E.; Goldstein, R. M.

    1998-01-01

    Synthetic aperture radar interferometry is an imaging technique for measuring the topography of a surface, its changes over time, and other changes in the detailed characteristics of the surface. This paper reviews the techniques of interferometry, systems and limitations, and applications in a rapidly growing area of science and engineering.

  12. Synthetic Cathinones ("Bath Salts")

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... europa.eu/publications/drug-profiles/synthetic-cathinones www.justice.gov/archive/ndic/pubs44/44571/44571p.pdf For ...

  13. Synthetic Confrontation Therapy.

    ERIC Educational Resources Information Center

    Gilliam, Larry

    After initially dispelling predictable fears that his paper might suggest that computers can be equated with man, the author states the problem: what part, if any, might computers play in counseling. Specifically, the possibilities for therapeutic synthetic (artificial) counseling encounters are discussed. Two propositions are significant: (1) the…

  14. Adaptive synthetic vision

    NASA Astrophysics Data System (ADS)

    Julier, Simon J.; Brown, Dennis; Livingston, Mark A.; Thomas, Justin

    2006-05-01

    Through their ability to safely collect video and imagery from remote and potentially dangerous locations, UAVs have already transformed the battlespace. The effectiveness of this information can be greatly enhanced through synthetic vision. Given knowledge of the extrinsic and intrinsic parameters of the camera, synthetic vision superimposes spatially-registered computer graphics over the video feed from the UAV. This technique can be used to show many types of data such as landmarks, air corridors, and the locations of friendly and enemy forces. However, the effectiveness of a synthetic vision system strongly depends on the accuracy of the registration - if the graphics are poorly aligned with the real world they can be confusing, annoying, and even misleading. In this paper, we describe an adaptive approach to synthetic vision that modifies the way in which information is displayed depending upon the registration error. We describe an integrated software architecture that has two main components. The first component automatically calculates registration error based on information about the uncertainty in the camera parameters. The second component uses this information to modify, aggregate, and label annotations to make their interpretation as clear as possible. We demonstrate the use of this approach on some sample datasets.

  15. Synthetic hydrophilic polymers

    NASA Astrophysics Data System (ADS)

    Rajasekharan Pillai, V. N.; Mutter, Manfred

    1981-11-01

    Synthetic hydrophilic polymers find promising applications in pharmacology, biotechnology and chemistry. The biocompatibility, biodegradability and pharmacological activity of these polymers depend much on their hydrophilic nature. This article summarizes the recent developments in the utilization of the different classes of these hydrophilic polymers as pharmacologically active agents, for enzyme modification and as catalysts and supports for chemical reactions.

  16. Synthetic Vision Workshop 2

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J. (Compiler)

    1999-01-01

    The second NASA sponsored Workshop on Synthetic/Enhanced Vision (S/EV) Display Systems was conducted January 27-29, 1998 at the NASA Langley Research Center. The purpose of this workshop was to provide a forum for interested parties to discuss topics in the Synthetic Vision (SV) element of the NASA Aviation Safety Program and to encourage those interested parties to participate in the development, prototyping, and implementation of S/EV systems that enhance aviation safety. The SV element addresses the potential safety benefits of synthetic/enhanced vision display systems for low-end general aviation aircraft, high-end general aviation aircraft (business jets), and commercial transports. Attendance at this workshop consisted of about 112 persons including representatives from industry, the FAA, and other government organizations (NOAA, NIMA, etc.). The workshop provided opportunities for interested individuals to give presentations on the state of the art in potentially applicable systems, as well as to discuss areas of research that might be considered for inclusion within the Synthetic Vision Element program to contribute to the reduction of the fatal aircraft accident rate. Panel discussions on topical areas such as databases, displays, certification issues, and sensors were conducted, with time allowed for audience participation.

  17. Synthesis, X-ray crystal structures and catecholase activity investigation of new chalcone ligands

    NASA Astrophysics Data System (ADS)

    Thabti, Salima; Djedouani, Amel; Rahmouni, Samra; Touzani, Rachid; Bendaas, Abderrahmen; Mousser, Hénia; Mousser, Abdelhamid

    2015-12-01

    The reaction of dehydroacetic acid DHA carboxaldehyde and RCHO derivatives (R = quinoleine-8-; indole-3-; pyrrol-2- and 4-(dimethylamino)phenyl - afforded four new chalcone ligands (4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one) L1, (4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one) L2, (4-hydroxy-6-methyl-3-[(2E)-3-(1H-pyrrol-2-yl)prop-2-enoyl]-2H-pyran-2-one) L3, and (3-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl}-4-hydroxy-6-methyl-2H-pyran-2-one) L4. L3 and L4 were characterized by X-ray crystallography. Molecules crystallize with four and two molecules in the asymmetric unit, respectively and adopt an E conformation about the Cdbnd C bond. Both structures are stabilized by an extended network O-H … O. Furthermore, N-H … O and C-H … O hydrogen bonds are observed in L3 and L4 structures, respectively. The in situ generated copper (II) complexes of the four compounds L1, L2, L3 and L4 were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The rates of this oxidation depend on three parameters: ligand, ion salts and solvent nature and the combination L2[Cu (CH3COO)2] leads to the faster catalytic process.

  18. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    SciTech Connect

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  19. A Malus crabapple chalcone synthase gene, McCHS, regulates red petal color and flavonoid biosynthesis.

    PubMed

    Tai, Deqiang; Tian, Ji; Zhang, Jie; Song, Tingting; Yao, Yuncong

    2014-01-01

    Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, 'Royalty' and 'Flame', have dark red and white petals respectively, while the intermediate cultivar 'Radiant' has pink petals. We detected the flavoniods accumulation and the expression levels of McCHS during petals expansion process in different cultivars. The results showed McCHS have their special expression patterns in each tested cultivars, and is responsible for the red coloration and color variation in crabapple petals, especially for color fade process in 'Radiant'. Furthermore, tobacco plants constitutively expressing McCHS displayed a higher anthocyanins accumulation and a deeper red petal color compared with control untransformed lines. Moreover, the expression levels of several anthocyanin biosynthetic genes were higher in the transgenic McCHS overexpressing tobacco lines than in the control plants. A close relationship was observed between the expression of McCHS and the transcription factors McMYB4 and McMYB5 during petals development in different crabapple cultivars, suggesting that the expression of McCHS was regulated by these transcription factors. We conclude that the endogenous McCHS gene is a critical factor in the regulation of anthocyanin biosynthesis during petal coloration in Malus crabapple.

  20. A Malus Crabapple Chalcone Synthase Gene, McCHS, Regulates Red Petal Color and Flavonoid Biosynthesis

    PubMed Central

    Song, Tingting; Yao, Yuncong

    2014-01-01

    Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, ‘Royalty’ and ‘Flame’, have dark red and white petals respectively, while the intermediate cultivar ‘Radiant’ has pink petals. We detected the flavoniods accumulation and the expression levels of McCHS during petals expansion process in different cultivars. The results showed McCHS have their special expression patterns in each tested cultivars, and is responsible for the red coloration and color variation in crabapple petals, especially for color fade process in ‘Radiant’. Furthermore, tobacco plants constitutively expressing McCHS displayed a higher anthocyanins accumulation and a deeper red petal color compared with control untransformed lines. Moreover, the expression levels of several anthocyanin biosynthetic genes were higher in the transgenic McCHS overexpressing tobacco lines than in the control plants. A close relationship was observed between the expression of McCHS and the transcription factors McMYB4 and McMYB5 during petals development in different crabapple cultivars, suggesting that the expression of McCHS was regulated by these transcription factors. We conclude that the endogenous McCHS gene is a critical factor in the regulation of anthocyanin biosynthesis during petal coloration in Malus crabapple. PMID:25357207

  1. A chalcone isomerase-like protein enhances flavonoid production and flower pigmentation.

    PubMed

    Morita, Yasumasa; Takagi, Kyoko; Fukuchi-Mizutani, Masako; Ishiguro, Kanako; Tanaka, Yoshikazu; Nitasaka, Eiji; Nakayama, Masayoshi; Saito, Norio; Kagami, Takashi; Hoshino, Atsushi; Iida, Shigeru

    2014-04-01

    Flavonoids are major pigments in plants, and their biosynthetic pathway is one of the best-studied metabolic pathways. Here we have identified three mutations within a gene that result in pale-colored flowers in the Japanese morning glory (Ipomoea nil). As the mutations lead to a reduction of the colorless flavonoid compound flavonol as well as of anthocyanins in the flower petal, the identified gene was designated enhancer of flavonoid production (EFP). EFP encodes a chalcone isomerase (CHI)-related protein classified as a type IV CHI protein. CHI is the second committed enzyme of the flavonoid biosynthetic pathway, but type IV CHI proteins are thought to lack CHI enzymatic activity, and their functions remain unknown. The spatio-temporal expression of EFP and structural genes encoding enzymes that produce flavonoids is very similar. Expression of both EFP and the structural genes is coordinately promoted by genes encoding R2R3-MYB and WD40 family proteins. The EFP gene is widely distributed in land plants, and RNAi knockdown mutants of the EFP homologs in petunia (Petunia hybrida) and torenia (Torenia hybrida) had pale-colored flowers and low amounts of anthocyanins. The flavonol and flavone contents in the knockdown petunia and torenia flowers, respectively, were also significantly decreased, suggesting that the EFP protein contributes in early step(s) of the flavonoid biosynthetic pathway to ensure production of flavonoid compounds. From these results, we conclude that EFP is an enhancer of flavonoid production and flower pigmentation, and its function is conserved among diverse land plant species.

  2. Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

    SciTech Connect

    Wu, Yang-Chang; Sureshbabu, Munisamy; Fang, Yao-Ching; Wu, Yi-Hsiu; Lan, Yu-Hsuan; Chang, Fang-Rong; Chang, Ya-Wen; Hwang, Tsong-Long

    2013-02-01

    Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.

  3. Antigiardial activity of novel triazolyl-quinolone-based chalcone derivatives: when oxygen makes the difference

    PubMed Central

    Bahadur, Vijay; Mastronicola, Daniela; Singh, Amit K.; Tiwari, Hemandra K.; Pucillo, Leopoldo P.; Sarti, Paolo; Singh, Brajendra K.; Giuffrè, Alessandro

    2015-01-01

    Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an ‘anaerobic pathogen,’ G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100-fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds. PMID:25904901

  4. Cyclooxygenase-2 knockdown using retinoic acid chalcone (RAC), a promising therapeutic strategy for colon cancer

    PubMed Central

    Jiang, Chao; Wang, Qiong; Xu, Zhe; Li, Wei-Su; Chen, Che; Yao, Xue-Quan; Liu, Fu-Kun

    2015-01-01

    Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 ± 3, 45.0 ± 3 to 72.6 ± 5% respectively at 10, 15 and 20 μg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 ± 3, 41.2 ± 3 to 65.4 ± 5% on treatment with 10, 15 and 20 μg/mL concentrations of RAC after 72 h compared to 2.9 ± 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors. PMID:26269760

  5. Synthetic River Valleys

    NASA Astrophysics Data System (ADS)

    Brown, R.; Pasternack, G. B.

    2011-12-01

    The description of fluvial form has evolved from anecdotal descriptions to artistic renderings to 2D plots of cross section or longitudinal profiles and more recently 3D digital models. Synthetic river valleys, artificial 3D topographic models of river topography, have a plethora of potential applications in fluvial geomorphology, and the earth sciences in general, as well as in computer science and ecology. Synthetic river channels have existed implicitly since approximately the 1970s and can be simulated from a variety of approaches spanning the artistic and numerical. An objective method of synthesizing 3D stream topography based on reach scale attributes would be valuable for sizing 3D flumes in the physical and numerical realms, as initial input topography for morphodynamic models, stream restoration design, historical reconstruction, and mechanistic testing of interactions of channel geometric elements. Quite simply - simulation of synthetic channel geometry of prescribed conditions can allow systematic evaluation of the dominant relationships between river flow and geometry. A new model, the control curve method, is presented that uses hierarchically scaled parametric curves in over-lapping 2D planes to create synthetic river valleys. The approach is able to simulate 3D stream geometry from paired 2D descriptions and can allow experimental insight into form-process relationships in addition to visualizing past measurements of channel form that are limited to two dimension descriptions. Results are presented that illustrate the models ability to simulate fluvial topography representative of real world rivers as well as how channel geometric elements can be adjusted. The testing of synthetic river valleys would open up a wealth of knowledge as to why some 3D attributes of river channels are more prevalent than others as well as bridging the gap between the 2D descriptions that have dominated fluvial geomorphology the past century and modern, more complete, 3D

  6. Synthetic plant defense elicitors

    PubMed Central

    Bektas, Yasemin; Eulgem, Thomas

    2015-01-01

    To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection. PMID:25674095

  7. Synthetic plant defense elicitors.

    PubMed

    Bektas, Yasemin; Eulgem, Thomas

    2014-01-01

    To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection.

  8. Overexpression of the Saussurea medusa chalcone isomerase gene in S. involucrata hairy root cultures enhances their biosynthesis of apigenin.

    PubMed

    Li, Feng-Xia; Jin, Zhi-Ping; Zhao, De-Xiu; Cheng, Li-Qin; Fu, Chun-Xiang; Ma, Fengshan

    2006-03-01

    Saussurea involucrata is a medicinal plant well known for its flavonoids, including apigenin, which has been shown to significantly inhibit tumorigenesis. Since naturally occurring apigenin is in very low abundance, we took a transgenic approach to increase apigenin production by engineering the flavonoid pathway. A construct was made to contain the complete cDNA sequence of the Saussurea medusa chalcone isomerase (CHI) gene under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Using an Agrobacterium rhizogenes-mediated transformation system, the chi overexpression cassette was incorporated into the genome of S. involucrata, and transgenic hairy root lines were established. CHI converts naringenin chalcone into naringenin that is the precursor of apigenin. We observed that transgenic hairy root lines grew faster and produced higher levels of apigenin and total flavonoids than wild-type hairy roots did. Over a culture period of 5 weeks, the best-performing line (C46) accumulated 32.1 mgL(-1) apigenin and 647.8 mgL(-1) total flavonoids, or 12 and 4 times, respectively, higher than wild-type hairy roots did. The enhanced productivity corresponded to elevated CHI activity, confirming the key role that CHI played for total flavonoids and apigenin synthesis and the efficiency of the current metabolic engineering strategy.

  9. Binding of the hop (Humulus lupulus L.) chalcone xanthohumol to cytosolic proteins in Caco-2 intestinal epithelial cells.

    PubMed

    Pang, Yan; Nikolic, Dejan; Zhu, Dongwei; Chadwick, Lucas R; Pauli, Guido F; Farnsworth, Norman R; van Breemen, Richard B

    2007-07-01

    Used in the brewing of beer, hops (Humulus lupulus L.) contain the prenylated chalcone xanthohumol, which is under investigation as a cancer chemoprevention agent and as a precursor for the estrogenic flavanones isoxanthohumol and 8-prenylnaringenin. The uptake, transport and accumulation of xanthohumol were studied using the human intestinal epithelial cell line Caco-2 to help understand the poor bioavailability of this chalcone. Studies were carried out using Caco-2 cell monolayers 18-21 days after seeding. The apparent K(m) and V(max) values of xanthohumol accumulation in Caco-2 cells were determined, and the protein binding of xanthohumol in sub-cellular fractions of Caco-2 cells was investigated. Approximately 70% of xanthohumol added to the apical side of Caco-2 cells accumulated inside the cells, while 93% of the intracellular xanthohumol was localized in the cytosol. Xanthohumol accumulation was temperature dependent and saturable with an apparent K(m )value of 26.5 +/- 4.66 muM and an apparent V(max) of 0.215 +/- 0.018 nmol/mg protein/min. Facilitated transport was not responsible for the uptake of xanthohumol, instead, accumulation inside the Caco-2 cells was apparently the result of specific binding to cytosolic proteins. These data suggest that specific binding of xanthohumol to cytosolic proteins in intestinal epithelial cells contributes to the poor oral bioavailability observed previously in vivo.

  10. Differential modification of flavonoid and isoflavonoid biosynthesis with an antisense chalcone synthase construct in transgenic Lotus corniculatus.

    PubMed

    Colliver, S P; Morris, P; Robbins, M P

    1997-11-01

    Three clonal genotypes of Lotus corniculatus L. (bird's foot trefoil) were transformed with an antisense chalcone synthase (CHS) gene construct made using a stress induced CHS17 cDNA from Phaseolus vulgaris under the control of the constitutive CaMV 35S promoter and Nos terminator via Agrobacterium rhizogenes. After initial screening, ten antisense and five control co-transformation events from each recipient clonal genotype were analysed. After elicitation with glutathione, the level of tannin accumulation was found to be increased in a number of antisense root cultures derived from the low (S33) and moderate (S50) tannin recipient genotypes. Six antisense and four control transformed lines from genotype S50 were selected for more detailed study. The antisense CHS construct was found to be integrated into the genome, with a copy number ranging from 1 to 5 and antisense orientation was confirmed by PCR. In transformed root cultures, increased CHS transcript levels were noted in a number of antisense lines. Biochemical analyses of glutathione-elicited-root cultures indicated a significant increase in tannin accumulation in antisense CHS lines and mean vestitol levels were reduced. These results show that the introduction of a heterologous antisense chalcone synthase construct into L. corniculatus resulted in an unpredicted molecular and biochemical phenotype. Such findings are discussed in relation to manipulation of this complex multigene family.

  11. Effect of position of nitrogen in pyridine ring on structural, optical and thermal properties of chalcone single crystals

    NASA Astrophysics Data System (ADS)

    Menezes, Anthoni Praveen; Jayarama, A.

    2015-06-01

    Crystals are unacknowledged pillars of the world of contemporary technology. Single crystals of a set of three chalcone derivatives, 1-(pyridin-2-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C1), 1-(pyridin-3-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C2) and 1-(pyridin-4-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C3) were grown by slow evaporation technique. The thermal analysis reveals that the chalcone derivatives possess good thermal and chemical stability. Crystal C1 is nonlinear optically (NLO) active with SHG efficiency of 0.7 times that of KDP. The position of nitrogen in the pyridine ring has a significant effect on thermal, structural and NLO properties of these materials. The UV-Visible spectrum discloses that the crystals have adequate transmission in the entire visible region. Due to good thermal stability, optical transparency and SHG response, crystal C1 is an useful candidate for NLO applications such as frequency doubling down to 433 nm.

  12. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents.

    PubMed

    Pingaew, Ratchanok; Saekee, Amporn; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2014-10-06

    A new series of chalcone-coumarin derivatives (9-19) linked by the 1,2,3-triazole ring were synthesized through the azide/alkyne dipolar cycloaddition. Hybrid molecules were evaluated for their cytotoxic activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) and antimalarial activity toward Plasmodium falciparum. Most of the synthesized hybrids, except for analogs 10 and 16, displayed cytotoxicity against MOLT-3 cell line without affecting normal cells. Analogs (10, 11, 16 and 18) exhibited higher inhibitory efficacy than the control drug, etoposide, in HepG2 cells. Significantly, the high cytotoxic potency of the hybrid 11 was shown to be non-toxic to normal cells. Interestingly, the chalcone-coumarin 18 was the most potent antimalarial compound affording IC50 value of 1.60 μM. Molecular docking suggested that the cytotoxicity of reported hybrids could be possibly due to their dual inhibition of α- and β-tubulins at GTP and colchicine binding sites, respectively. Furthermore, falcipain-2 was identified to be a plausible target site of the hybrids given their antimalarial potency.

  13. The Flavonoid Biosynthetic Enzyme Chalcone Isomerase Modulates Terpenoid Production in Glandular Trichomes of Tomato1[C][W][OPEN

    PubMed Central

    Kang, Jin-Ho; McRoberts, John; Shi, Feng; Moreno, Javier E.; Jones, A. Daniel; Howe, Gregg A.

    2014-01-01

    Flavonoids and terpenoids are derived from distinct metabolic pathways but nevertheless serve complementary roles in mediating plant interactions with the environment. Here, we show that glandular trichomes of the anthocyanin free (af) mutant of cultivated tomato (Solanum lycopersicum) fail to accumulate both flavonoids and terpenoids. This pleiotropic metabolic deficiency was associated with loss of resistance to native populations of coleopteran herbivores under field conditions. We demonstrate that Af encodes an isoform (SlCHI1) of the flavonoid biosynthetic enzyme chalcone isomerase (CHI), which catalyzes the conversion of naringenin chalcone to naringenin and is strictly required for flavonoid production in multiple tissues of tomato. Expression of the wild-type SlCHI1 gene from its native promoter complemented the anthocyanin deficiency in af. Unexpectedly, the SlCHI1 transgene also complemented the defect in terpenoid production in glandular trichomes. Our results establish a key role for SlCHI1 in flavonoid production in tomato and reveal a link between CHI1 and terpenoid production. Metabolic coordination of the flavonoid and terpenoid pathways may serve to optimize the function of trichome glands in dynamic environments. PMID:24424324

  14. "N"-Heterocyclic Carbene-Catalyzed Reaction of Chalcone and Cinnamaldehyde to Give 1,3,4-Triphenylcyclopentene Using Organocatalysis to Form a Homoenolate Equivalent

    ERIC Educational Resources Information Center

    Snider, Barry B.

    2015-01-01

    In this experiment, students carry out a modern organocatalytic reaction using IMes·HCl and NaOH to catalyze the formation of 1,3,4-triphenylcyclopentene from cinnamaldehyde and chalcone in water. Deprotonation of IMes·HCl with NaOH forms the "N"-heterocyclic carbene IMes that reacts with cinnamaldehyde to form a homoenolate equivalent…

  15. Green Synthesis, Spectrofluorometric Characterization and Antibacterial Activity of Heterocyclic Compound from Chalcone on the Basis of in Vitro and Quantum Chemistry Calculation.

    PubMed

    Khan, Salman A

    2017-02-08

    2-amino-4-(4-bromophenyl)-8-methoxy-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (ABDC) was synthesized by the reaction of (2E)-2-(4 bromobenzylidene) - 6 -methoxy-3,4-dihydronaphthalen-1(2H)-one (Chalcone) with malononitrile and ammonium acetate under microwave irradiation. Chalcone was synthesised by the reaction 4-bromobenzaldehyd, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one under the same condition. Structure of ABDC was conformed by (1)H and (13)C NMR, FT-IR, EI-MS spectral studies and elemental analysis. The electronic absorption and fluorescence spectra of ABDC have been studied in solvents of different polarities, and the data were used to study the solvatochromic properties such as excitation coefficient, stokes shift, oscillator strength, transition dipole moment and fluorescence quantum yield. The absorption maximum and fluorescence emission maximum was observed red shift when increase solvent polarity n-Hexane to DMSO. ABDC undergoes solubilization in different micelles and may be used as a probe and quencher to determine the critical micelle concentration (CMC) of CTAB and SDS. The anti-bacterial activity of chalcone and its cyclized product ABDC was tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria was determined with the reference of standard drug Tetracycline. Results showed that the ABDC is better anti-bacterial agent as compared to chalcone. The anti-bacterial activity was further supported by the quantum chemistry calculation.

  16. EXPEDITIOUS SYNTHETIC TRANSFORMATIONS USING MICROWAVES

    EPA Science Inventory

    Microwave-expedited solvent-free synthetic processes will be described for the synthesis of a variety of industrially significant compounds and intermediates namely, enamines, nitroalkenes, enones, oxidized sulfur compounds and ionic liquids. This solvent-free synthetic methodolo...

  17. Synthetic Foveal Imaging Technology

    NASA Technical Reports Server (NTRS)

    Monacos, Steve P. (Inventor); Hoenk, Michael E. (Inventor); Nikzad, Shouleh (Inventor)

    2013-01-01

    Apparatuses and methods are disclosed that create a synthetic fovea in order to identify and highlight interesting portions of an image for further processing and rapid response. Synthetic foveal imaging implements a parallel processing architecture that uses reprogrammable logic to implement embedded, distributed, real-time foveal image processing from different sensor types while simultaneously allowing for lossless storage and retrieval of raw image data. Real-time, distributed, adaptive processing of multi-tap image sensors with coordinated processing hardware used for each output tap is enabled. In mosaic focal planes, a parallel-processing network can be implemented that treats the mosaic focal plane as a single ensemble rather than a set of isolated sensors. Various applications are enabled for imaging and robotic vision where processing and responding to enormous amounts of data quickly and efficiently is important.

  18. Synthetic Porphyrins and Metalloporphyrins

    DTIC Science & Technology

    1976-12-10

    last type of complexes to be considered are the sterically hindered macrocycles . Examples of this class of complexes exe the capped" or "crow henhe...group IV metalloporphyrins, phthalocyanines and correspond- log Ru"l and Reol complexes induce smaller shifts than the lanthanides (about 8 ppm vs 25...ROLE W1r ROLE wTr ROLE Wt * ~Synthe tic Porphyrins Synthetic lMetalloporphyrinsj tetrapyrrole macrocycles "Inatural" porphyrins * j meso

  19. Synthetic Biological Engineering of Photosynthesis

    DTIC Science & Technology

    2015-11-16

    SECURITY CLASSIFICATION OF: The overall goal of the grant is to create a synthetic biology platform based on solar energy that can be used on a local...Research Triangle Park, NC 27709-2211 Synthetic biology , photosynthesis, solar energy, biofuels REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S...Synthetic Biological Engineering of Photosynthesis Report Title The overall goal of the grant is to create a synthetic biology platform based on solar

  20. Synthetic biology in plastids.

    PubMed

    Scharff, Lars B; Bock, Ralph

    2014-06-01

    Plastids (chloroplasts) harbor a small gene-dense genome that is amenable to genetic manipulation by transformation. During 1 billion years of evolution from the cyanobacterial endosymbiont to present-day chloroplasts, the plastid genome has undergone a dramatic size reduction, mainly as a result of gene losses and the large-scale transfer of genes to the nuclear genome. Thus the plastid genome can be regarded as a naturally evolved miniature genome, the gradual size reduction and compaction of which has provided a blueprint for the design of minimum genomes. Furthermore, because of the largely prokaryotic genome structure and gene expression machinery, the high transgene expression levels attainable in transgenic chloroplasts and the very low production costs in plant systems, the chloroplast lends itself to synthetic biology applications that are directed towards the efficient synthesis of green chemicals, biopharmaceuticals and other metabolites of commercial interest. This review describes recent progress with the engineering of plastid genomes with large constructs of foreign or synthetic DNA, and highlights the potential of the chloroplast as a model system in bottom-up and top-down synthetic biology approaches.

  1. Opportunities in plant synthetic biology.

    PubMed

    Cook, Charis; Martin, Lisa; Bastow, Ruth

    2014-05-01

    Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology.

  2. Synthetic passive margin stratigraphy

    SciTech Connect

    Turcotte, D.L.; Kenyon, P.M.

    1984-06-01

    Synthetic stratigraphic cross sections are derived mathematically for a variety of simple conditions. The variables considered in the mathematical model include variations in sea level, rate of tectonic subsidence, rate of sedimentation, and rate of erosion. Derived stratigraphic relationships include unconformities, correlative conformities and disconformities, coastal onlap, coastal toplap, erosional truncation, pinch-out, and sigmoidal progradational clinoforms. An important conclusion is that the rate of erosion is a dominant variable in determining the type of stratigraphic section observed. The proposed approach may provide the basis for either a forward or inverse modeling of seismic stratigraphic sections.

  3. Synthetic Fence Jets

    NASA Astrophysics Data System (ADS)

    Sigurdson, Lorenz; Apps, Christopher

    2000-11-01

    "Synthetic Jets" have previously been produced where an oscillating flow with zero net mass flux acts on the edges of an orifice. The resulting flow is similar to a normal jet. We have proposed and verified that another type of jet called a "Synthetic Fence Jet" (SFJ or "fe-je") can also be created. We introduced a fence perpendicular to both a wall and an oscillating velocity field. Under certain conditions a jet was formed by vortices of alternating sign. The vortices were shed from the fence and they induced each other away from it. This phenomenon could be used as a method of flow control. The objective of this project was to use flow visualization to prove the existence of and characterize this jet. A test rig was used which incorporates smoke-wire flow visualization; independent oscillation level and frequency control; and computer- controlled data acquisition. It has been discovered that the jet direction can be vectored by altering the forcing waveform shape. To explain this a theory was developed that is based on the Biot-Savart law of vortex dynamics.

  4. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  5. Synthetic collective intelligence.

    PubMed

    Solé, Ricard; Amor, Daniel R; Duran-Nebreda, Salva; Conde-Pueyo, Núria; Carbonell-Ballestero, Max; Montañez, Raúl

    2016-10-01

    Intelligent systems have emerged in our biosphere in different contexts and achieving different levels of complexity. The requirement of communication in a social context has been in all cases a determinant. The human brain, probably co-evolving with language, is an exceedingly successful example. Similarly, social insects complex collective decisions emerge from information exchanges between many agents. The difference is that such processing is obtained out of a limited individual cognitive power. Computational models and embodied versions using non-living systems, particularly involving robot swarms, have been used to explore the potentiality of collective intelligence. Here we suggest a novel approach to the problem grounded in the genetic engineering of unicellular systems, which can be modified in order to interact, store memories or adapt to external stimuli in collective ways. What we label as Synthetic Swarm Intelligence defines a parallel approach to the evolution of computation and swarm intelligence and allows to explore potential embodied scenarios for decision making at the microscale. Here, we consider several relevant examples of collective intelligence and their synthetic organism counterparts.

  6. Benzophenone Synthase and Chalcone Synthase Accumulate in the Mesophyll of Hypericum perforatum Leaves at Different Developmental Stages.

    PubMed

    Belkheir, Asma K; Gaid, Mariam; Liu, Benye; Hänsch, Robert; Beerhues, Ludger

    2016-01-01

    The active medicinal constituents in Hypericum perforatum, used to treat depression and skin irritation, include flavonoids and xanthones. The carbon skeletons of these compounds are formed by chalcone synthase (CHS) and benzophenone synthase (BPS), respectively. Polyclonal antisera were raised against the polyketide synthases from Hypericum androsaemum and their IgG fractions were isolated. Immunoblotting and immunotitration were used to test the IgGs for crossreactivity and monospecificity in H. perforatum leaf protein extract. Immunofluorescence localization revealed that both CHS and BPS are located in the mesophyll. The maximum fluorescence levels were observed in approx. 0.5 and 1 cm long leaves, respectively. The fluorescence intensity observed for CHS significantly exceeded that for BPS. Using histochemical staining, flavonoids were detected in the mesophyll, indicating that the sites of biosynthesis and accumulation coincide. Our results help understand the biosynthesis and underlying regulation of active H. perforatum constituents.

  7. Design, synthesis, characterization and in vitro and in vivo anti-inflammatory evaluation of novel pyrazole-based chalcones.

    PubMed

    Chavan, Hemant V; Adsul, Laxman K; Kotmale, Amol S; Dhakane, Valmik D; Thakare, Vishnu N; Bandgar, Babasaheb P

    2015-02-01

    Abstract A series of novel pyrazole-based chalcones have been designed, synthesized from 1-methyl-5-(2,4,6-trimethoxyphenyl)-1H-pyrazole (6). The structures of regioisomers 6 and 7 were determined by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were tested for their inhibitory activity against COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Moreover, they were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model for acute inflammation and cotton pellet-induced granuloma model for chronic inflammation. All the synthesized compounds showed potential to demonstrate anti-inflammatory activities, of particular interest compounds 10i, 10e, 10f, and 10h were found to be potent anti-inflammatory agents.

  8. Xanthohumol, a prenylated chalcone derived from hops, inhibits proliferation, migration and interleukin-8 expression of hepatocellular carcinoma cells.

    PubMed

    Dorn, Christoph; Weiss, Thomas S; Heilmann, Jörg; Hellerbrand, Claus

    2010-02-01

    Xanthohumol, the major prenylated chalcone found in hops, is well known to exert anti-cancer effects, but information regarding the impact on hepatocellular carcinoma (HCC) cells and potential adverse effects on non-tumorous hepatocytes is limited. Here, we show that xanthohumol at a concentration of 25 microM induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore, xanthohumol repressed proliferation and migration, as well as TNF induced NF-kappaB activity and interleukin-8 expression in both cell lines at even lower concentrations. In contrast, xanthohumol concentrations up to 100 microM did not affect viability of primary human hepatocytes in vitro. In summary, our data showed that xanthohumol can ameliorate different pro-tumorigenic mechanisms known to promote HCC progression, indicating its potential as promising therapeutic agent that selectively affects cancer cells.

  9. The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops, on cell growth and tumorigenesis in human pancreatic cancer.

    PubMed

    Jiang, Weiliang; Zhao, Senlin; Xu, Ling; Lu, Yingying; Lu, Zhanjun; Chen, Congying; Ni, Jianbo; Wan, Rong; Yang, Lijuan

    2015-07-01

    Pancreatic cancer (PC) is one of the most lethal human malignancies worldwide. Here, we demonstrated that xanthohumol (XN), the most abundant prenylated chalcone isolated from hops, inhibited the growth of cultured PC cells and their subcutaneous xenograft tumors. XN treatment was found to induce cell cycle arrest and apoptosis of PC cells (PANC-1, BxPC-3) by inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of its downstream targeted genes cyclinD1, survivin, and Bcl-xL at the messenger RNA level, which involved in regulation of apoptosis and the cell cycle. Overall, our results suggested that XN presents a promising candidate therapeutic agent against human PC and the STAT3 signaling pathway is its key molecular target.

  10. Patterning of Virus-Infected Glycine max Seed Coat Is Associated with Suppression of Endogenous Silencing of Chalcone Synthase Genes

    PubMed Central

    Senda, Mineo; Masuta, Chikara; Ohnishi, Shizen; Goto, Kazunori; Kasai, Atsushi; Sano, Teruo; Hong, Jin-Sung; MacFarlane, Stuart

    2004-01-01

    Most commercial Glycine max (soybean) varieties have yellow seeds because of loss of pigmentation in the seed coat. It has been suggested that inhibition of seed coat pigmentation in yellow G. max may be controlled by homology-dependent silencing of chalcone synthase (CHS) genes. Our analysis of CHS mRNA and short-interfering RNAs provide clear evidence that the inhibition of seed coat pigmentation in yellow G. max results from posttranscriptional rather than transcriptional silencing of the CHS genes. Furthermore, we show that mottling symptoms present on the seed coat of G. max plants infected with some viruses can be caused by suppression of CHS posttranscriptional gene silencing (PTGS) by a viral silencing suppressor protein. These results demonstrate that naturally occurring PTGS plays a key role in expression of a distinctive phenotype in plants and present a simple clear example of the elucidation of the molecular mechanism for viral symptom induction. PMID:15037735

  11. Patterning of virus-infected Glycine max seed coat is associated with suppression of endogenous silencing of chalcone synthase genes.

    PubMed

    Senda, Mineo; Masuta, Chikara; Ohnishi, Shizen; Goto, Kazunori; Kasai, Atsushi; Sano, Teruo; Hong, Jin-Sung; MacFarlane, Stuart

    2004-04-01

    Most commercial Glycine max (soybean) varieties have yellow seeds because of loss of pigmentation in the seed coat. It has been suggested that inhibition of seed coat pigmentation in yellow G. max may be controlled by homology-dependent silencing of chalcone synthase (CHS) genes. Our analysis of CHS mRNA and short-interfering RNAs provide clear evidence that the inhibition of seed coat pigmentation in yellow G. max results from posttranscriptional rather than transcriptional silencing of the CHS genes. Furthermore, we show that mottling symptoms present on the seed coat of G. max plants infected with some viruses can be caused by suppression of CHS posttranscriptional gene silencing (PTGS) by a viral silencing suppressor protein. These results demonstrate that naturally occurring PTGS plays a key role in expression of a distinctive phenotype in plants and present a simple clear example of the elucidation of the molecular mechanism for viral symptom induction.

  12. One type of chalcone synthase gene expressed during embryogenesis regulates the flavonoid accumulation in citrus cell cultures.

    PubMed

    Moriguchi, T; Kita, M; Tomono, Y; EndoInagaki, T; Omura, M

    1999-06-01

    To elucidate the relationship between the expression of chalcone synthase (CHS) genes and the production of flavonoid in citrus cell cultures, two cDNA clones encoding CHS were isolated (CitCHS1 and CitCHS2) from the citrus. The accumulation of CitCHS2 mRNA was notably induced by embryogenesis but CitCHS1 mRNA was not. There was no detectable accumulation of flavonoid in the undifferentiated calli, but flavonoid accumulated after the morphological changes to embryoids. These results indicate that two CHS genes differentially expressed during citrus somatic embryogenesis and CitCHS2 may regulate the accumulation of flavonoid in citrus cell cultures.

  13. Benzophenone Synthase and Chalcone Synthase Accumulate in the Mesophyll of Hypericum perforatum Leaves at Different Developmental Stages

    PubMed Central

    Belkheir, Asma K.; Gaid, Mariam; Liu, Benye; Hänsch, Robert; Beerhues, Ludger

    2016-01-01

    The active medicinal constituents in Hypericum perforatum, used to treat depression and skin irritation, include flavonoids and xanthones. The carbon skeletons of these compounds are formed by chalcone synthase (CHS) and benzophenone synthase (BPS), respectively. Polyclonal antisera were raised against the polyketide synthases from Hypericum androsaemum and their IgG fractions were isolated. Immunoblotting and immunotitration were used to test the IgGs for crossreactivity and monospecificity in H. perforatum leaf protein extract. Immunofluorescence localization revealed that both CHS and BPS are located in the mesophyll. The maximum fluorescence levels were observed in approx. 0.5 and 1 cm long leaves, respectively. The fluorescence intensity observed for CHS significantly exceeded that for BPS. Using histochemical staining, flavonoids were detected in the mesophyll, indicating that the sites of biosynthesis and accumulation coincide. Our results help understand the biosynthesis and underlying regulation of active H. perforatum constituents. PMID:27446151

  14. Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.

    PubMed

    Kumar, Himank; Chattopadhyay, Anjan; Prasath, R; Devaraji, Vinod; Joshi, Ritika; Bhavana, P; Saini, Praveen; Ghosh, Sujit Kumar

    2014-07-03

    The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a β-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research.

  15. Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells.

    PubMed

    Fang, Song-Chwan; Hsu, Chin-Lin; Yu, Yu-Shen; Yen, Gow-Chin

    2008-10-08

    Breadfruit (Artocarpus communis Moraceae) is cultivated in tropical and subtropical regions as a traditional starch crop and also has potential medicinal properties. The aim of this work was to study the in vitro anticancer activity of compounds isolated from the leaves of Artocarpus communis. Three new geranyl chalcone derivatives including isolespeol (1), 5'-geranyl-2',4',4-trihydroxychalcone (2), and 3,4,2',4'-tetrahydroxy-3'-geranyldihydrochalcone (3), together with two known compounds lespeol (4) and xanthoangelol (5), were isolated from the leaves of Artocarpus communis. The structures of 1- 5 were elucidated by spectroscopy and through comparison with data reported in the literature. The effects of geranyl chalcone derivatives (1- 5) on the viability of human cancer cells (including SW 872, HT-29, COLO 205, Hep3B, PLC5, Huh7, and HepG2 cells) were investigated. The results indicate that isolespeol (1) showed the highest inhibitory activity with an IC 50 value of 3.8 muM in SW 872 human liposarcoma cells. Treatment of SW 872 human liposarcoma cells with isolespeol (1) caused the loss of mitochondrial membrane potential (DeltaPsim). Western blotting revealed that isolespeol (1) stimulated increased protein expression of Fas, FasL, and p53. The expression ratios of pro- and antiapoptotic Bcl-2 family members were also changed by isolespeol (1) treatment to subsequently induce the activation of caspase-9 and caspase-3, which was followed by cleavage of poly (ADP-ribose) polymerase (PARP). These results demonstrate that isolespeol (1) induces apoptosis in SW 872 cells through Fas- and mitochondria-mediated pathways.

  16. Synergistic combination of fluoro chalcone and doxorubicin on HeLa cervical cancer cells by inducing apoptosis

    NASA Astrophysics Data System (ADS)

    Arianingrum, Retno; Arty, Indyah Sulistyo; Atun, Sri

    2017-03-01

    Doxorubicin (Dox), a primary chemotherapeutic agent used for cancer treatment is known to have various side effect included multidrug resistance (MDR) phenomenon. Combination chemotherapy is one of some approaches to reduce Dox side effect. Chalcones have been reported to reduce the proliferation of many cancer cells. The research were conducted to investigate the cytotoxic activity and apoptosis induction of a chalcone derivate which is containing fluoro substituent [1 - (4" - fluorophenyl) -3 - (4' - hydroxy - 3' - methoxyphenyl) - 2 - propene - 1 -on] (FHM) and its combination with Dox on HeLa cells line. The observation of the cytotoxic activity was conducted using MTT [3 - (4, 5 - dimethyl thiazol - 2 - y1) - 2.5 - diphenyltetrazolium bromide] assay. Apoptosis induction was determined by flow cytometric. The changes of cell morphology were observed using phase contrast microscopy. The combination index (CI) was used to determine the effect of the combination. The study showed that FHM inhibited the HeLa cell growth with IC50 of 34 μM, while the IC50 of Dox was 1 μM. The combination had a higher inhibitory effect on cell growth compare to the single treatment of FHM and Dox. All of the combination doses under IC50 of FHM and Dox gave synergistic (CI: - 0.7) up to strong synergistic effect (CI: 0.l - 0.3). The synergistic effects of the combination were due to their ability to induce apoptosis in the HeLa cells. According to the result, FHM was potential to be developed as a co-chemotherapeutic agent with Dox for cervical cancer.

  17. Tissue-specific gene silencing mediated by a naturally occurring chalcone synthase gene cluster in Glycine max.

    PubMed

    Tuteja, Jigyasa H; Clough, Steven J; Chan, Wan-Ching; Vodkin, Lila O

    2004-04-01

    Chalcone synthase, a key regulatory enzyme in the flavonoid pathway, constitutes an eight-member gene family in Glycine max (soybean). Three of the chalcone synthase (CHS) gene family members are arranged as inverted repeats in a 10-kb region, corresponding to the I locus (inhibitor). Spontaneous mutations of a dominant allele (I or i(i)) to a recessive allele (i) have been shown to delete promoter sequences, paradoxically increasing total CHS transcript levels and resulting in black seed coats. However, it is not known which of the gene family members contribute toward pigmentation and how this locus affects CHS expression in other tissues. We investigated the unusual nature of the I locus using four pairs of isogenic lines differing with respect to alleles of the I locus. RNA gel blots using a generic open reading frame CHS probe detected similar CHS transcript levels in stems, roots, leaves, young pods, and cotyledons of the yellow and black isolines but not in the seed coats, which is consistent with the dominant I and i(i) alleles mediating CHS gene silencing in a tissue-specific manner. Using real-time RT-PCR, a variable pattern of expression of CHS genes in different tissues was demonstrated. However, increase in pigmentation in the black seed coats was associated with release of the silencing effect specifically on CHS7/CHS8, which occurred at all stages of seed coat development. These expression changes were linked to structural changes taking place at the I locus, shown to encompass a much wider region of at least 27 kb, comprising two identical 10.91-kb stretches of CHS gene duplications. The suppressive effect of this 27-kb I locus in a specific tissue of the G. max plant represents a unique endogenous gene silencing mechanism.

  18. Tissue-Specific Gene Silencing Mediated by a Naturally Occurring Chalcone Synthase Gene Cluster in Glycine maxW⃞

    PubMed Central

    Tuteja, Jigyasa H.; Clough, Steven J.; Chan, Wan-Ching; Vodkin, Lila O.

    2004-01-01

    Chalcone synthase, a key regulatory enzyme in the flavonoid pathway, constitutes an eight-member gene family in Glycine max (soybean). Three of the chalcone synthase (CHS) gene family members are arranged as inverted repeats in a 10-kb region, corresponding to the I locus (inhibitor). Spontaneous mutations of a dominant allele (I or ii) to a recessive allele (i) have been shown to delete promoter sequences, paradoxically increasing total CHS transcript levels and resulting in black seed coats. However, it is not known which of the gene family members contribute toward pigmentation and how this locus affects CHS expression in other tissues. We investigated the unusual nature of the I locus using four pairs of isogenic lines differing with respect to alleles of the I locus. RNA gel blots using a generic open reading frame CHS probe detected similar CHS transcript levels in stems, roots, leaves, young pods, and cotyledons of the yellow and black isolines but not in the seed coats, which is consistent with the dominant I and ii alleles mediating CHS gene silencing in a tissue-specific manner. Using real-time RT-PCR, a variable pattern of expression of CHS genes in different tissues was demonstrated. However, increase in pigmentation in the black seed coats was associated with release of the silencing effect specifically on CHS7/CHS8, which occurred at all stages of seed coat development. These expression changes were linked to structural changes taking place at the I locus, shown to encompass a much wider region of at least 27 kb, comprising two identical 10.91-kb stretches of CHS gene duplications. The suppressive effect of this 27-kb I locus in a specific tissue of the G. max plant represents a unique endogenous gene silencing mechanism. PMID:15064367

  19. Synthetic biology and genetic causation.

    PubMed

    Oftedal, Gry; Parkkinen, Veli-Pekka

    2013-06-01

    Synthetic biology research is often described in terms of programming cells through the introduction of synthetic genes. Genetic material is seemingly attributed with a high level of causal responsibility. We discuss genetic causation in synthetic biology and distinguish three gene concepts differing in their assumptions of genetic control. We argue that synthetic biology generally employs a difference-making approach to establishing genetic causes, and that this approach does not commit to a specific notion of genetic program or genetic control. Still, we suggest that a strong program concept of genetic material can be used as a successful heuristic in certain areas of synthetic biology. Its application requires control of causal context, and may stand in need of a modular decomposition of the target system. We relate different modularity concepts to the discussion of genetic causation and point to possible advantages of and important limitations to seeking modularity in synthetic biology systems.

  20. Synthetic and Alternate Fuels Characterization

    DTIC Science & Technology

    1988-02-01

    e-e AD-A197 531 AD_ m iI ORNL/TM-10706 OAK RIDGE NATIONAL Synthetic and Alternate LABORATORY Fuels Characterization •_ _ __ _ _Final Report February...21701-5012 62787A 2787A878 CA 294 11 TITLE (Include Security Classification) Synthetic and Alternate Fuels Characterization 12 PERSONAL AUTHOR(S) W. H...results suggest that highly refined and finished mobility fuels from synthetic or alternate sources will not pose a significantly greater toxicological

  1. Entraining synthetic genetic oscillators

    NASA Astrophysics Data System (ADS)

    Wagemakers, Alexandre; Buldú, Javier M.; Sanjuán, Miguel A. F.; de Luis, Oscar; Izquierdo, Adriana; Coloma, Antonio

    2009-09-01

    We propose a new approach for synchronizing a population of synthetic genetic oscillators, which consists in the entrainment of a colony of repressilators by external modulation. We present a model where the repressilator dynamics is affected by periodic changes in temperature. We introduce an additional plasmid in the bacteria in order to correlate the temperature variations with the enhancement of the transcription rate of a certain gene. This can be done by introducing a promoter that is related to the heat shock response. This way, the expression of that gene results in a protein that enhances the overall oscillations. Numerical results show coherent oscillations of the population for a certain range of the external frequency, which is in turn related to the natural oscillation frequency of the modified repressilator. Finally we study the transient times related with the loss of synchronization and we discuss possible applications in biotechnology of large-scale production coupled to synchronization events induced by heat shock.

  2. Synthetic quantum systems

    NASA Astrophysics Data System (ADS)

    Cahill, Reginald T.

    2002-10-01

    So far proposed quantum computers use fragile and environmentally sensitive natural quantum systems. Here we explore the new notion that synthetic quantum systems suitable for quantum computation may be fabricated from smart nanostructures using topological excitations of a stochastic neural-type network that can mimic natural quantum systems. These developments are a technological application of process physics which is an information theory of reality in which space and quantum phenomena are emergent, and so indicates the deep origins of quantum phenomena. Analogous complex stochastic dynamical systems have recently been proposed within neurobiology to deal with the emergent complexity of biosystems, particularly the biodynamics of higher brain function. The reasons for analogous discoveries in fundamental physics and neurobiology are discussed.

  3. Evolutionary synthetic biology.

    PubMed

    Peisajovich, Sergio G

    2012-06-15

    Signaling networks process vast amounts of environmental information to generate specific cellular responses. As cellular environments change, signaling networks adapt accordingly. Here, I will discuss how the integration of synthetic biology and directed evolution approaches is shedding light on the molecular mechanisms that guide the evolution of signaling networks. In particular, I will review studies that demonstrate how different types of mutations, from the replacement of individual amino acids to the shuffling of modular domains, lead to markedly different evolutionary trajectories and consequently to diverse network rewiring. Moreover, I will argue that intrinsic evolutionary properties of signaling proteins, such as the robustness of wild type functions, the promiscuous nature of evolutionary intermediates, and the modular decoupling between binding and catalysis, play important roles in the evolution of signaling networks. Finally, I will argue that rapid advances in our ability to synthesize DNA will radically alter how we study signaling network evolution at the genome-wide level.

  4. Synthetic biology and occupational risk.

    PubMed

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

    Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

  5. Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

    PubMed Central

    König, Harald; Frank, Daniel; Heil, Reinhard; Coenen, Christopher

    2013-01-01

    New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications. PMID:23997647

  6. Synthetic genomics and synthetic biology applications between hopes and concerns.

    PubMed

    König, Harald; Frank, Daniel; Heil, Reinhard; Coenen, Christopher

    2013-03-01

    New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks - stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications.

  7. SNP in Chalcone Synthase gene is associated with variation of 6-gingerol content in contrasting landraces of Zingiber officinale.Roscoe.

    PubMed

    Ghosh, Subhabrata; Mandi, Swati Sen

    2015-07-25

    Zingiber officinale, medicinally the most important species within Zingiber genus, contains 6-gingerol as the active principle. This compound obtained from rhizomes of Z.officinale, has immense medicinal importance and is used in various herbal drug formulations. Our record of variation in content of this active principle, viz. 6-gingerol, in land races of this drug plant collected from different locations correlated with our Gene expression studies exhibiting high Chalcone Synthase gene (Chalcone Synthase is the rate limiting enzyme of 6-gingerol biosynthesis pathway) expression in high 6-gingerol containing landraces than in the low 6-gingerol containing landraces. Sequencing of Chalcone Synthase cDNA and subsequent multiple sequence alignment revealed seven SNPs between these contrasting genotypes. Converting this nucleotide sequence to amino acid sequence, alteration of two amino acids becomes evident; one amino acid change (asparagine to serine at position 336) is associated with base change (A→G) and another change (serine to leucine at position 142) is associated with the base change (C→T). Since asparagine at position 336 is one of the critical amino acids of the catalytic triad of Chalcone Synthase enzyme, responsible for substrate binding, our study suggests that landraces with a specific amino acid change viz. Asparagine (found in high 6-gingerol containing landraces) to serine causes low 6-gingerol content. This is probably due to a weak enzyme substrate association caused by the absence of asparagine in the catalytic triad. Detailed study of this finding could also help to understand molecular mechanism associated with variation in 6-gingerol content in Z.officinale genotypes and thereby strategies for developing elite genotypes containing high 6-gingerol content.

  8. Holographically Correcting Synthetic Aperture Aberrations.

    DTIC Science & Technology

    1987-12-01

    Malacara (20:105-148). The synthetic aperture was aligned in accordance with the synthetic-aperture alignment technique of Gill (8:61-64). The...1987. 20. Malacara , Daniel, ed. Optical Shop Testing. New York: John Wiley & Sons, 1978. 21. Marciniak, Capt Michael. Tutorial Presentation of mV

  9. Synthetic biology and metabolic engineering.

    PubMed

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  10. Binary classification of chalcone derivatives with LDA or KNN based on their antileishmanial activity and molecular descriptors selected using the Successive Projections Algorithm feature-selection technique.

    PubMed

    Goodarzi, Mohammad; Saeys, Wouter; de Araujo, Mario Cesar Ugulino; Galvão, Roberto Kawakami Harrop; Vander Heyden, Yvan

    2014-01-23

    Chalcones are naturally occurring aromatic ketones, which consist of an α-, β-unsaturated carbonyl system joining two aryl rings. These compounds are reported to exhibit several pharmacological activities, including antiparasitic, antibacterial, antifungal, anticancer, immunomodulatory, nitric oxide inhibition and anti-inflammatory effects. In the present work, a Quantitative Structure-Activity Relationship (QSAR) study is carried out to classify chalcone derivatives with respect to their antileishmanial activity (active/inactive) on the basis of molecular descriptors. For this purpose, two techniques to select descriptors are employed, the Successive Projections Algorithm (SPA) and the Genetic Algorithm (GA). The selected descriptors are initially employed to build Linear Discriminant Analysis (LDA) models. An additional investigation is then carried out to determine whether the results can be improved by using a non-parametric classification technique (One Nearest Neighbour, 1NN). In a case study involving 100 chalcone derivatives, the 1NN models were found to provide better rates of correct classification than LDA, both in the training and test sets. The best result was achieved by a SPA-1NN model with six molecular descriptors, which provided correct classification rates of 97% and 84% for the training and test sets, respectively.

  11. Synthetic Foveal Imaging Technology

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael; Monacos, Steve; Nikzad, Shouleh

    2009-01-01

    Synthetic Foveal imaging Technology (SyFT) is an emerging discipline of image capture and image-data processing that offers the prospect of greatly increased capabilities for real-time processing of large, high-resolution images (including mosaic images) for such purposes as automated recognition and tracking of moving objects of interest. SyFT offers a solution to the image-data processing problem arising from the proposed development of gigapixel mosaic focal-plane image-detector assemblies for very wide field-of-view imaging with high resolution for detecting and tracking sparse objects or events within narrow subfields of view. In order to identify and track the objects or events without the means of dynamic adaptation to be afforded by SyFT, it would be necessary to post-process data from an image-data space consisting of terabytes of data. Such post-processing would be time-consuming and, as a consequence, could result in missing significant events that could not be observed at all due to the time evolution of such events or could not be observed at required levels of fidelity without such real-time adaptations as adjusting focal-plane operating conditions or aiming of the focal plane in different directions to track such events. The basic concept of foveal imaging is straightforward: In imitation of a natural eye, a foveal-vision image sensor is designed to offer higher resolution in a small region of interest (ROI) within its field of view. Foveal vision reduces the amount of unwanted information that must be transferred from the image sensor to external image-data-processing circuitry. The aforementioned basic concept is not new in itself: indeed, image sensors based on these concepts have been described in several previous NASA Tech Briefs articles. Active-pixel integrated-circuit image sensors that can be programmed in real time to effect foveal artificial vision on demand are one such example. What is new in SyFT is a synergistic combination of recent

  12. Recent advances in synthetic biosafety

    PubMed Central

    Simon, Anna J.; Ellington, Andrew D.

    2016-01-01

    Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment. PMID:27635235

  13. Synthetic retinoids in dermatology

    PubMed Central

    Heller, Elizabeth H.; Shiffman, Norman J.

    1985-01-01

    The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited. ImagesFig. 3 PMID:3158386

  14. Synthetic aperture hitchhiker imaging.

    PubMed

    Yarman, Can Evren; Yazici, Birsen

    2008-11-01

    We introduce a novel synthetic-aperture imaging method for radar systems that rely on sources of opportunity. We consider receivers that fly along arbitrary, but known, flight trajectories and develop a spatio-temporal correlation-based filtered-backprojection-type image reconstruction method. The method involves first correlating the measurements from two different receiver locations. This leads to a forward model where the radiance of the target scene is projected onto the intersection of certain hyperboloids with the surface topography. We next use microlocal techniques to develop a filtered-backprojection-type inversion method to recover the scene radiance. The method is applicable to both stationary and mobile, and cooperative and noncooperative sources of opportunity. Additionally, it is applicable to nonideal imaging scenarios such as those involving arbitrary flight trajectories, and has the desirable property of preserving the visible edges of the scene radiance. We present an analysis of the computational complexity of the image reconstruction method and demonstrate its performance in numerical simulations for single and multiple transmitters of opportunity.

  15. Synthetic carriers of oxygen.

    PubMed

    Dellacherie, E; Labrude, P; Vigneron, C; Riess, J G

    1987-01-01

    During the last decade, construction of artificial carriers of oxygen for transfusion purposes has evolved in three main directions, which can be reviewed as follows. The first approach consists of modifying hemoglobin (Hb), the natural oxygen carrier, in order to lower its oxygen affinity and increase its intravascular persistence. To achieve this aim, two basic procedures have been used: molecular and environmental modification. In the first case, Hb is modified with chemical reagents; the second requires encapsulation of Hb to obtain artificial erythrocytes. The second approach is based on the use of synthetic oxygen-carrying chelates that mimic the oxygenation function of Hb. The main products in this class are metalloporphyrins, whose chemical environment is designed to render them efficient as reversible carriers of oxygen in vivo. Finally, the third approach deals with the perfluorochemicals used in emulsified form. Perfluorochemical liquids are excellent gas solvents, but some problems remain unsolved with regard to their development as oxygen carriers in vivo: low O2 dissolving capacity, toxicity, and excretion.

  16. Computing with synthetic protocells.

    PubMed

    Courbet, Alexis; Molina, Franck; Amar, Patrick

    2015-09-01

    In this article we present a new kind of computing device that uses biochemical reactions networks as building blocks to implement logic gates. The architecture of a computing machine relies on these generic and composable building blocks, computation units, that can be used in multiple instances to perform complex boolean functions. Standard logical operations are implemented by biochemical networks, encapsulated and insulated within synthetic vesicles called protocells. These protocells are capable of exchanging energy and information with each other through transmembrane electron transfer. In the paradigm of computation we propose, protoputing, a machine can solve only one problem and therefore has to be built specifically. Thus, the programming phase in the standard computing paradigm is represented in our approach by the set of assembly instructions (specific attachments) that directs the wiring of the protocells that constitute the machine itself. To demonstrate the computing power of protocellular machines, we apply it to solve a NP-complete problem, known to be very demanding in computing power, the 3-SAT problem. We show how to program the assembly of a machine that can verify the satisfiability of a given boolean formula. Then we show how to use the massive parallelism of these machines to verify in less than 20 min all the valuations of the input variables and output a fluorescent signal when the formula is satisfiable or no signal at all otherwise.

  17. Synthesis of some novel chalcones, flavanones and flavones and evaluation of their anti-inflammatory activity.

    PubMed

    Bano, Sameena; Javed, Kalim; Ahmad, Shamim; Rathish, I G; Singh, Surender; Chaitanya, M; Arunasree, K M; Alam, M S

    2013-07-01

    A novel series of synthetic 2'-hydroxychalcones (1a-h), 2'-methoxychalcones (2a-l), flavanones (3a-k) and flavones (4a-f) have been synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw oedema model. Compounds 1a, 1e-g, 2e-g, 3j, and 4f showed potent anti-inflammatory activity comparable to the reference drug indomethacin with insignificant ulceration. Compound 1f showed mild inhibition against the enzymatic activity of ovine COX-1 and COX-2 (in-vitro). Compound 1f also exhibited inhibitory activity in LPS induced TNF-α production.

  18. Synthetic biology: Understanding biological design from synthetic circuits

    PubMed Central

    Mukherji, Shankar; van Oudenaarden, Alexander

    2011-01-01

    An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to intuitively grasp the ranges of behavior generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes such as gene expression and population dynamics. PMID:19898500

  19. Spicing thing up: Synthetic cannabinoids

    PubMed Central

    Spaderna, Max; Addy, Peter H; D’Souza, Deepak Cyril

    2013-01-01

    Rationale Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. Objectives The availability, acute subjective effects—including self-reports posted on Erowid—laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Results Spice is sold under the guise of potpourri or incense. Unlike THC, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid-receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned. Conclusions There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug-detection tests for synthetic cannabinoids need to become clinically available. PMID:23836028

  20. Synthetic biology and personalized medicine.

    PubMed

    Jain, K K

    2013-01-01

    Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task.

  1. Distributed and collaborative synthetic environments

    NASA Technical Reports Server (NTRS)

    Bajaj, Chandrajit L.; Bernardini, Fausto

    1995-01-01

    Fast graphics workstations and increased computing power, together with improved interface technologies, have created new and diverse possibilities for developing and interacting with synthetic environments. A synthetic environment system is generally characterized by input/output devices that constitute the interface between the human senses and the synthetic environment generated by the computer; and a computation system running a real-time simulation of the environment. A basic need of a synthetic environment system is that of giving the user a plausible reproduction of the visual aspect of the objects with which he is interacting. The goal of our Shastra research project is to provide a substrate of geometric data structures and algorithms which allow the distributed construction and modification of the environment, efficient querying of objects attributes, collaborative interaction with the environment, fast computation of collision detection and visibility information for efficient dynamic simulation and real-time scene display. In particular, we address the following issues: (1) A geometric framework for modeling and visualizing synthetic environments and interacting with them. We highlight the functions required for the geometric engine of a synthetic environment system. (2) A distribution and collaboration substrate that supports construction, modification, and interaction with synthetic environments on networked desktop machines.

  2. Bistatic synthetic aperture radar

    NASA Astrophysics Data System (ADS)

    Yates, Gillian

    Synthetic aperture radar (SAR) allows all-weather, day and night, surface surveillance and has the ability to detect, classify and geolocate objects at long stand-off ranges. Bistatic SAR, where the transmitter and the receiver are on separate platforms, is seen as a potential means of countering the vulnerability of conventional monostatic SAR to electronic countermeasures, particularly directional jamming, and avoiding physical attack of the imaging platform. As the receiving platform can be totally passive, it does not advertise its position by RF emissions. The transmitter is not susceptible to jamming and can, for example, operate at long stand-off ranges to reduce its vulnerability to physical attack. This thesis examines some of the complications involved in producing high-resolution bistatic SAR imagery. The effect of bistatic operation on resolution is examined from a theoretical viewpoint and analytical expressions for resolution are developed. These expressions are verified by simulation work using a simple 'point by point' processor. This work is extended to look at using modern practical processing engines for bistatic geometries. Adaptations of the polar format algorithm and range migration algorithm are considered. The principal achievement of this work is a fully airborne demonstration of bistatic SAR. The route taken in reaching this is given, along with some results. The bistatic SAR imagery is analysed and compared to the monostatic imagery collected at the same time. Demonstrating high-resolution bistatic SAR imagery using two airborne platforms represents what I believe to be a European first and is likely to be the first time that this has been achieved outside the US (the UK has very little insight into US work on this topic). Bistatic target characteristics are examined through the use of simulations. This also compares bistatic imagery with monostatic and gives further insight into the utility of bistatic SAR.

  3. Synthetic biology for therapeutic applications.

    PubMed

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2015-02-02

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  4. Synthetic Biology for Therapeutic Applications

    PubMed Central

    2015-01-01

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders. PMID:25098838

  5. Synthetic Turf Multiplies Stadium Use.

    ERIC Educational Resources Information Center

    Leach, Richard

    1979-01-01

    The high school stadium in Flint, Michigan, once was used only for varsity football games. After the installation of synthetic turf, an average of 332 events have been staged there each year. (Author/MLF)

  6. A Course on Synthetic Fuels.

    ERIC Educational Resources Information Center

    Kimmel, Howard S.; Tomkins, Reginald P. T.

    1985-01-01

    A senior-level, elective course on synthetic fuels was developed for chemistry and chemical engineering majors. The topics covered in this course, instructional strategies used, and independent student projects are described. (JN)

  7. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  8. Toward Engineering Synthetic Microbial Metabolism

    PubMed Central

    McArthur, George H.; Fong, Stephen S.

    2010-01-01

    The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel function. Further development of analytical and computer-aided design tools should accelerate the forward engineering of precisely regulated synthetic pathways by providing a standard framework for the predictable design of biological systems from well-characterized parts. In this review we discuss the current state of synthetic biology within a four-stage framework (design, modeling, synthesis, analysis) and highlight areas requiring further advancement to facilitate true engineering of synthetic microbial metabolism. PMID:20037734

  9. Synthetic Biology for Specialty Chemicals.

    PubMed

    Markham, Kelly A; Alper, Hal S

    2015-01-01

    In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

  10. Approaches to chemical synthetic biology.

    PubMed

    Chiarabelli, Cristiano; Stano, Pasquale; Anella, Fabrizio; Carrara, Paolo; Luisi, Pier Luigi

    2012-07-16

    Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology.

  11. Programming languages for synthetic biology.

    PubMed

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

    2010-12-01

    In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

  12. Synthetic biology as red herring.

    PubMed

    Preston, Beth

    2013-12-01

    It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy.

  13. Design and synthesis of imidazo[2,1-b]thiazole-chalcone conjugates: microtubule-destabilizing agents.

    PubMed

    Kamal, Ahmed; Balakrishna, Moku; Nayak, V Lakshma; Shaik, Thokhir Basha; Faazil, Shaikh; Nimbarte, Vijaykumar D

    2014-12-01

    A series of chalcone conjugates featuring the imidazo[2,1-b]thiazole scaffold was designed, synthesized, and evaluated for their cytotoxic activity against five human cancer cell lines (MCF-7, A549, HeLa, DU-145 and HT-29). These new hybrid molecules have shown promising cytotoxic activity with IC50 values ranging from 0.64 to 30.9 μM. Among them, (E)-3-(6-(4-fluorophenyl)-2,3-bis(4-methoxyphenyl)imidazo[2,1-b]thiazol-5-yl)-1-(pyridin-2-yl)prop-2-en-1-one (11 x) showed potent antiproliferative activity with IC50 values ranging from 0.64 to 1.44 μM in all tested cell lines. To investigate the mechanism of action, the detailed biological aspects of this promising conjugate (11 x) were carried out on the A549 lung cancer cell line. The tubulin polymerization assay and immunofluoresence analysis results suggest that this conjugate effectively inhibits microtubule assembly in A549 cells. Flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase and leads to apoptotic cell death. This was further confirmed by Hoechst staining, activation of caspase-3, DNA fragmentation analysis, and Annexin V-FITC assay. Moreover, molecular docking studies indicated that this conjugate (11 x) interacts and binds efficiently with the tubulin protein.

  14. Design, synthesis and antibacterial study of new potent and selective coumarin-chalcone derivatives for the treatment of tenacibaculosis.

    PubMed

    Vazquez-Rodriguez, Saleta; Lama López, Raquel; Matos, Maria João; Armesto-Quintas, Gabriel; Serra, Silvia; Uriarte, Eugenio; Santana, Lourdes; Borges, Fernanda; Muñoz Crego, Angeles; Santos, Ysabel

    2015-11-01

    With the aim of finding new chemical entities selective for fish pathogens to avoid drug resistance in humans, a series of coumarin-chalcone hybrid compounds with different patterns of substitution were designed and synthesized. Their antibacterial activity was evaluated against important types of human bacteria strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and against a fourteen strains of the marine pathogen Tenacibaculum maritimum, responsible for tenacibaculosis in fish, which is an important disease that causes great economical loss in the aquaculture industry. All the amino derivatives 5-12 presented high activity against different strains of T. maritimum, no activity against any of the three human pathogenic bacteria strains and no toxicity. Compounds 6, 7 and 11 were the most promising molecules. The most sensitive strains to these compounds were LL01 8.3.8 and LL01 8.3.1, being compound 11 up to 20 times more active than enrofloxacin. Therefore these scaffolds are good candidates for aquaculture treatments, avoiding possible drug resistance problems in humans.

  15. Coumarin-chalcone hybrid instigates DNA damage by minor groove binding and stabilizes p53 through post translational modifications

    PubMed Central

    Ashraf, Raghib; Hamidullah; Hasanain, Mohammad; Pandey, Praveen; Maheshwari, Mayank; Singh, L. Ravithej; Siddiqui, M. Quadir; Konwar, Rituraj; Sashidhara, Koneni V.; Sarkar, Jayanta

    2017-01-01

    S009-131, a coumarin-chalcone hybrid, had been shown to possess anti-proliferative and anti-tumour effect by triggering apoptosis. In this report, we investigated role of DNA damage signalling pathway in S009-131 induced cancer cell death. Here we show that S009-131 causes DNA damage by potential binding to the minor groove which led to the phosphorylation and activation of ATM and DNA-PK, but not ATR, at earlier time points in order to initiate repair process. S009-131 induced DNA damage response triggered activation of p53 through phosphorylation at its key residues. Pharmacological inhibition of PIKKs abrogated S009-131 induced phosphorylation of p53 at Ser 15. DNA damage induced phosphorylation resulted in reduced proteasomal degradation of p53 by disrupting p53-MDM2 interaction. Additionally, our docking studies revealed that S009-131 might also contribute to increased cellular p53 level by occupying p53 binding pocket of MDM2. Posttranslational modifications of p53 upon S009-131 treatment led to enhanced affinity of p53 towards responsive elements (p53-RE) in the promoter regions of target genes and increased transcriptional efficiency. Together, the results suggest that S009-131 cleaves DNA through minor groove binding and eventually activates PIKKs associated DNA damage response signalling to promote stabilization and enhanced transcriptional activity of p53 through posttranslational modifications at key residues. PMID:28349922

  16. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-01

    Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.

  17. Novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids: synthesis, physicochemical properties, anticancer and topoisomerase I and II inhibitory activity.

    PubMed

    Abdel-Aziz, Mohamed; Park, So-Eun; Abuo-Rahma, Gamal El-Din A A; Sayed, Mohamed A; Kwon, Youngjoo

    2013-11-01

    A group of novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids was prepared. One-dose anticancer test results indicated that compounds 3a and 3g exhibited the highest ability to inhibit the proliferation of different cancer cell lines. Compound 3a exhibited a broad-spectrum of anti-tumor activity without pronounced selectivity while compound 3g revealed high selectivity toward the leukemia subpanel with selectivity ratio of 6.71 at GI₅₀ level. Moreover, compounds 3e and 3j have shown remarkable topo II inhibitory activity compared to etoposide at 100 μM and 20 μM concentrations. Compounds 3e and 3j exhibited comparably potent topo I inhibitory activity at 20 μM concentration compared to camptothecin. Compounds 3e and 3j exhibited strong topo II inhibitory activities compared to topo I at 20 μM concentration. Studying of the solubility and partition coefficient revealed higher lipophilicity of the hybrids 3a-j compared to the parent ciprofloxacin.

  18. Silencing CHALCONE SYNTHASE in Maize Impedes the Incorporation of Tricin into Lignin and Increases Lignin Content1[OPEN

    PubMed Central

    2017-01-01

    Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant produces highly reduced levels of apigenin- and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in β-β and β-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production. PMID:27940492

  19. Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents.

    PubMed

    Bhale, Pravin S; Chavan, Hemant V; Dongare, Sakharam B; Shringare, Sadanand N; Mule, Yoginath B; Nagane, Samadhan S; Bandgar, Babasaheb P

    2017-04-01

    In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a-p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI50 <0.1 and 4μM respectively) as good as adriamycin (GI50 <0.1μM). The compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells. The effect of extended conjugation on activity authenticated by comparing activity profile of compound 5a, 5i and 5m with their simple analogues. Among the synthesized compounds, 5i and 5l were found to be active anti-inflammatory agents in addition to having noteworthy antioxidant potential. These results suggest the possible use of these compounds for the design and development of novel anti-breast cancer agents.

  20. Likelihood analysis of the chalcone synthase genes suggests the role of positive selection in morning glories (Ipomoea).

    PubMed

    Yang, Ji; Gu, Hongya; Yang, Ziheng

    2004-01-01

    Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoides, which are important for the pigmentation of flowers and act as attractants to pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. In morning glories (Ipomoea), five functional CHS genes (A-E) have been described. Phylogenetic analysis of the Ipomoea CHS gene family revealed that CHS A, B, and C experienced accelerated rates of amino acid substitution relative to CHS D and E. To examine whether the CHS genes of the morning glories underwent adaptive evolution, maximum-likelihood models of codon substitution were used to analyze the functional sequences in the Ipomoea CHS gene family. These models used the nonsynonymous/synonymous rate ratio (omega = d(N)/ d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio test suggested significant variation in selection pressure among amino acid sites, with a small proportion of them detected to be under positive selection along the branches ancestral to CHS A, B, and C. Positive Darwinian selection appears to have promoted the divergence of subfamily ABC and subfamily DE and is at least partially responsible for a rate increase following gene duplication.

  1. Crystal structure and nonlinear optical absorption of a new chalcone derivative: a promising candidate for optical switching

    NASA Astrophysics Data System (ADS)

    Chandra Shekhara Shetty, T.; Raghavendra, S.; Chidan Kumar, C. S.; Dharmaprakash, S. M.

    2016-07-01

    A new nonlinear optical material, 4-[(2 E)-3-(3-fluorophenyl) prop-2-enoyl] benzonitrile (3FPB), belonging to chalcone family was synthesized and characterized by FTIR and linear absorption spectroscopy. Single-crystal X-ray diffraction reveals that the new material crystallizes in monoclinic system with P21/c space group and lattice parameters a = 6.4841(2) Å, b = 13.6038(5) Å, c = 14.6418(6) Å, α = 90.00°, β = 94.552(2)° and γ = 90°. The crystallographic perfection of the synthesized material has been analyzed by X-ray powder diffraction. The X-ray powder diffraction peaks of the sample were indexed with hkl values. The UV-visible spectrum for 3FPB crystals showed the optical transmittance window and a lower cutoff wavelength of absorption at 343 nm. The direct transition band gap energy and indirect transition energy gap were determined using Tauc's plots. The thermal stability and melting point of the material have been investigated by thermogravimetric analysis/differential thermal analysis (TGA/DTA). The Thermogravimetric curve showed the absence of any phase transition before melting point. Third-order nonlinear absorption and optical limiting experiment were carried out using open-aperture Z-scan experiment with Nd:YAG laser nanosecond pulses at a wavelength of 532 nm.

  2. Transient Silencing of CHALCONE SYNTHASE during Fruit Ripening Modifies Tomato Epidermal Cells and Cuticle Properties1[C][W

    PubMed Central

    España, Laura; Heredia-Guerrero, José A.; Reina-Pinto, José J.; Fernández-Muñoz, Rafael; Heredia, Antonio; Domínguez, Eva

    2014-01-01

    Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids. PMID:25277718

  3. Imbalance in expression of hop (Humulus lupulus) chalcone synthase H1 and its regulators during hop stunt viroid pathogenesis.

    PubMed

    Füssy, Zoltán; Patzak, Josef; Stehlík, Jan; Matoušek, Jaroslav

    2013-05-01

    Viroid-derived small RNAs generated during hop stunt viroid (HSVd) pathogenesis may induce the symptoms found in the hop cultivar "Admiral", including observed shifts in phenylpropanoid metabolites and changes in petiole coloration. Using quantitative RT-PCR, we examined hop lupulin gland-specific genes that have been shown to be involved in phenylpropanoid metabolism, for altered expression in response to infection with two HSVd isolates, HSVd-g and CPFVd. Most notably, the expression of a gene encoding a key enzyme for phenylpropanoid synthesis, naringenin-chalcone synthase H1 (chs_H1), decreased up to 40-fold in infected samples. In addition, a marked decrease in the expression of HlbHLH2 and an increase in the expression of HlMyb3 were observed. These two genes encode transcription factors that form a ternary complex with HlWDR1 for chs_H1 promoter activation. In a transient expression assay, a decrease in the ternary complex potential to activate the chs_H1 promoter was observed upon the decrease of HlbHLH2 expression. In addition, targeting of the chs_H1 transcript by vd-sRNAs may contribute to these expression changes. Our data show that HSVd infection causes a significant imbalance in the expression of phenylpropanoid metabolite-affecting genes via a complex mechanism, possibly involving regulatory disorders and direct targeting by vd-sRNA.

  4. Catechol-based substrates of chalcone synthase as a scaffold for novel inhibitors of PqsD.

    PubMed

    Allegretta, Giuseppe; Weidel, Elisabeth; Empting, Martin; Hartmann, Rolf W

    2015-01-27

    A new strategy for treating Pseudomonas aeruginosa infections could be disrupting the Pseudomonas Quinolone Signal (PQS) quorum sensing (QS) system. The goal is to impair communication among the cells and, hence, reduce the expression of virulence factors and the formation of biofilms. PqsD is an essential enzyme for the synthesis of PQS and shares some features with chalcone synthase (CHS2), an enzyme expressed in Medicago sativa. Both proteins are quite similar concerning the size of the active site, the catalytic residues and the electrostatic surface potential at the entrance of the substrate tunnel. Hence, we evaluated selected substrates of the vegetable enzyme as potential inhibitors of the bacterial protein. This similarity-guided approach led to the identification of a new class of PqsD inhibitors having a catechol structure as an essential feature for activity, a saturated linker with two or more carbons and an ester moiety bearing bulky substituents. The developed compounds showed PqsD inhibition with IC50 values in the single-digit micromolar range. The binding mode of these compounds was investigated by Surface Plasmon Resonance (SPR) experiments revealing that their interaction with the protein is not influenced by the presence of the anthranilic acid bound to active site cysteine. Importantly, some compounds reduced the signal molecule production in cellulo.

  5. Synthesis, leishmanicidal and cytotoxic activity of triclosan-chalcone, triclosan-chromone and triclosan-coumarin hybrids.

    PubMed

    Otero, Elver; Vergara, Sebastián; Robledo, Sara M; Cardona, Wilson; Carda, Miguel; Vélez, Ivan D; Rojas, Carlos; Otálvaro, Felipe

    2014-08-28

    Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC50=9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.

  6. Electrosynthesis, spectral and structural studies of a semi-conducting oligomer deriving from a methoxy-substituted chalcone

    NASA Astrophysics Data System (ADS)

    Aribi, Imen; Ghomrasni, Saber; Ayachi, Sahbi; Alimi, Kamel; Roudesli, Sadok; Said, Ayoub Haj

    2016-11-01

    The anodic oxidation of a substituted chalcone namely the (E)-1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl) prop-2-enone (TMC) was investigated by different electrochemical techniques using a platinum working electrode in acetonitrile. On the cyclic voltammetry time scale, the TMC exhibited a single irreversible anodic peak around 1.4 V vs. Ag/AgCl and the coupling of the radical cations, issued from the first electron transfer, was the governing reaction near the electrode. Electrolysis at a constant potential revealed that an oligo o-phenylenevinylene was the main product of the anodic oxidation of TMC. The chemical structure of the isolated oligomer was elucidated by 1H, 13C NMR, and IR spectroscopy. Gel permeation chromatography indicated that the average chain length was about 5 units. In addition, the obtained oligomer was thermally stable up to 220 °C and exhibited a light emission in the indigo-blue region. Finally, a mechanism for the TMC electro-oligomerization was proposed on the basis of the electrochemical data and the theoretical calculation of the spin densities distribution for the TMC radical cation.

  7. Synthetic Eelgrass Oil Barrier

    NASA Astrophysics Data System (ADS)

    Curtis, T. G.

    2013-05-01

    Although surviving in situ micro-organisms eventually consume spilled oil, extensive inundation of shore biota by oil requires cleanup to enable ecological recovery within normal time scales. Although effective in calm seas and quiet waters, oil is advected over and under conventional curtain oil booms by wave actions and currents when seas are running. Most sorbent booms are not reusable, and are usually disposed of in landfills, creating excessive waste. A new concept is proposed for a floating oil barrier, to be positioned off vulnerable coasts, to interdict, contain, and sequester spilled oil, which can then be recovered and the barrier reused. While conventional oil boom designs rely principally on the immiscibility of oil in water and its relative buoyancy, the new concept barrier avoids the pitfalls of the former by taking advantage of the synergistic benefits of numerous fluid and material properties, including: density, buoyancy, elasticity, polarity, and surface area to volume ratio. Modeled after Zostera marina, commonly called eelgrass, the new barrier, referred to as synthetic eelgrass (SE), behaves analogously. Eelgrass has very long narrow, ribbon-like, leaves which support periphyton, a complex matrix of algae and heterotrophic microbes, which position themselves there to extract nutrients from the seawater flowing past them. In an analogous fashion, oil on, or in, seawater, which comes in contact with SE, is adsorbed on the surface and sequestered there. Secured to the bottom, in shoal waters, SE rises to the surface, and, if the tide is low enough, floats on the sea surface down wind, or down current to snare floating oil. The leaves of SE, called filaments, consist of intrinsically buoyant strips of ethylene methyl acrylate, aka EMA. EMA, made of long chain, saturated, hydrocarbon molecules with nearly homogeneous electron charge distributions, is a non-polar material which is oleophilic and hydrophobic. Oil must be in close proximity to the

  8. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

    PubMed Central

    Sliva, Anna; Yang, Huanming; Boeke, Jef D.; Mathews, Debra J. H.

    2015-01-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 Project: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. PMID:26272997

  9. Synthetic genomics and the construction of a synthetic bacterial cell.

    PubMed

    Glass, John I

    2012-01-01

    The first synthetic cellular organism was created in 2010 and based on a very small, very simple bacterium called Mycoplasma mycoides. The bacterium was called synthetic because its DNA genome was chemically synthesized rather than replicated from an existing template DNA, as occurs in all other known cellular life on Earth. The experiment was undertaken in order to develop a system that would allow creation of a minimal bacterial cell that could lead to a better understand of the first principles of cellular life. The effort resulted in new synthetic genomics techniques called genome assembly and genome transplantation. The ability of scientists to design and build bacteria opens new possibilities for creating microbes to solve human problems.

  10. Epi-cinchona based thiourea organocatalyst family as an efficient asymmetric Michael addition promoter: enantioselective conjugate addition of nitroalkanes to chalcones and alpha,beta-unsaturated N-acylpyrroles.

    PubMed

    Vakulya, Benedek; Varga, Szilárd; Soós, Tibor

    2008-05-02

    A small set of easily available epi-cinchona based thiourea organocatalysts have been synthesized and tested in enantioselective Michael addition of nitroalkanes to chalcones. These bifunctional catalyst systems promoted the conjugate additions with high enantioselectivities and chemical yields. The extension of this methodology was further explored to encompass alpha,beta-unsaturated N-acylpyrroles, as a chalcone mimic. Functionally, the N-acylpyrrole moiety in the adduct acts as an ester surrogate; therefore, it can easily be transformed to various valuable and biologically relevant compounds. This approach allowed the concise stereoselective synthesis of (R)-rolipram.

  11. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    ERIC Educational Resources Information Center

    Campbell, A. Malcolm

    2005-01-01

    The field of synthetic biology (the name is derived from an analogy to synthetic chemistry) has recognized itself as a "field" only since about 2002. Synthetic biology has gotten some high-profile attention recently, but most people are not aware the field even exists. Synthetic biologists apply engineering principles to genomic circuits to…

  12. Synthesis, characterization and crystal structure of 4‧-ethynylflavanone and its chalcone precursor

    NASA Astrophysics Data System (ADS)

    Salinas-Ortega, Ismael; Ocayo, Fernanda; Santos, Juan C.; Trujillo, Alexander; Escobar, Carlos A.

    2017-01-01

    The synthesis of (E)-4-ethynyl-2‧-hydroxychalcone (7) and the 4‧-ethynylflavanone (8), it's spectroscopic and X-ray characterization are described for both compounds. Products were prepared by reacting 4-bromobenzaldehyde (1) under Sonogashira coupling reaction conditions, in order to obtain the key intermediary 4-ethynylbenzaldehyde (3). Then, this intermediary was reacted with 2‧-hydroxyacetophenone (4) under Claisen-Shchmidt conditions to render a mixture of (E)-4-ethynyl-2‧-hydroxychalcone (7) and 4‧-ethynylflavanone (8). Compounds were separated by column chromatography, and spectroscopically characterized. Also, an alternative synthetic route to 4‧-ethynylflavanone (8) was tested; the known 4‧-bromoflavanone (6) was reacted under Sonogashira coupling conditions, in order to obtain the intermediary 4‧-(trimethylsilylethynyl)-flavanone (9), which under deprotection afforded the desired 4‧-ethynylflavanone (8). The Synthesis of (E)-4-bromo-2‧-hydroxychalcone (5) and 4‧-bromoflavanone (6), used as precursors, is also described. The X-ray structure of (E)-4-bromo-2‧-hydroxychalcone (5) is presented as well.

  13. Control theory meets synthetic biology.

    PubMed

    Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

  14. Control theory meets synthetic biology

    PubMed Central

    2016-01-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. PMID:27440256

  15. Synthetic Peptides as Protein Mimics

    PubMed Central

    Groß, Andrea; Hashimoto, Chie; Sticht, Heinrich; Eichler, Jutta

    2016-01-01

    The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non-proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology. PMID:26835447

  16. Designer Drugs: A Synthetic Catastrophe.

    PubMed

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are "Not for Human Consumption", therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants.

  17. Synthetic neurosteroids on brain protection

    PubMed Central

    Rey, Mariana; Coirini, Héctor

    2015-01-01

    Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids administration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute promising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions. PMID:25788907

  18. Differential Optical Synthetic Aperture Radar

    DOEpatents

    Stappaerts, Eddy A.

    2005-04-12

    A new differential technique for forming optical images using a synthetic aperture is introduced. This differential technique utilizes a single aperture to obtain unique (N) phases that can be processed to produce a synthetic aperture image at points along a trajectory. This is accomplished by dividing the aperture into two equal "subapertures", each having a width that is less than the actual aperture, along the direction of flight. As the platform flies along a given trajectory, a source illuminates objects and the two subapertures are configured to collect return signals. The techniques of the invention is designed to cancel common-mode errors, trajectory deviations from a straight line, and laser phase noise to provide the set of resultant (N) phases that can produce an image having a spatial resolution corresponding to a synthetic aperture.

  19. Designer Drugs: A Synthetic Catastrophe

    PubMed Central

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    2016-01-01

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are “Not for Human Consumption”, therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants. PMID:27617301

  20. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    NASA Astrophysics Data System (ADS)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  1. US Competitiveness in Synthetic Biology.

    PubMed

    Gronvall, Gigi Kwik

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

  2. US Competitiveness in Synthetic Biology

    PubMed Central

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative—additional investments will expand markets—but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized. PMID:26690379

  3. Design Automation in Synthetic Biology.

    PubMed

    Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

    2017-04-03

    Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks.

  4. Synthetic Aperture Radar Oceanographic Investigations.

    DTIC Science & Technology

    1987-03-01

    Shuchman, P.G. Teleki, S.V. Hsiao, O.H. Shemdin , and W.E. Brown, Synthetic Aperture Radar Imaging of Ocean Waves : Comparison with Wave Measurements, J... Shemdin , Synthetic Aperture Radar Imaging of Ocean Waves during the Marineland Experiment, IEEE J. Oceanic Eg., OE-8, pp. 83-90, 1983. 12. R.A...If the surface reflectivity is assumed to be spatially un- section. are computed from the wave height spectrum as correlated, i.e. follows . (x. Y. t

  5. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  6. Kava chalcone, flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T transgenic mouse model.

    PubMed

    Liu, Zhongbo; Xu, Xia; Li, Xuesen; Liu, Shuman; Simoneau, Anne R; He, Feng; Wu, Xue-Ru; Zi, Xiaolin

    2013-12-01

    Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously shown that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here, we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (P = 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1 ± 69.4 mg (P = 0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4 μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non-muscle-invasive UCC.

  7. Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53.

    PubMed

    Tang, Yaxiong; Simoneau, Anne R; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin

    2008-11-01

    Flavokawain A is the predominant chalcone from kava extract. We have assessed the mechanisms of flavokawain A's action on cell cycle regulation. In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G(1) arrest. The increase of p21/WAF1 protein corresponded to an increased mRNA level, whereas p27/KIP1 accumulation was associated with the down-regulation of SKP2, which then increased the stability of the p27/KIP1 protein. The accumulation of p21/WAF1 and p27/KIP1 was independent of cell cycle position and thus not a result of the cell cycle arrest. In contrast, flavokawain A induced a G(2)-M arrest in six p53 mutant-type, high-grade bladder cancer cell lines (T24, UMUC3, TCCSUP, 5637, HT1376, and HT1197). Flavokawain A significantly reduced the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and caused cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. Suppression of p53 expression by small interfering RNA in RT4 cells restored Cdc25C expression and down-regulated p21/WAF1 expression, which allowed Cdc25C and CDK1 activation, which then led to a G(2)-M arrest and an enhanced growth-inhibitory effect by flavokawain A. Consistently, flavokawain A also caused a pronounced CDK1 activation and G(2)-M arrest in p53 knockout but not in p53 wild-type HCT116 cells. This selectivity of flavokawain A for inducing a G(2)-M arrest in p53-defective cells deserves further investigation as a new mechanism for the prevention and treatment of bladder cancer.

  8. Cloning of a cDNA encoding the Saussurea medusa chalcone isomerase and its expression in transgenic tobacco.

    PubMed

    Li, F; Jin, Z; Qu, W; Zhao, D; Ma, F

    2006-01-01

    Chalcone isomerase (CHI; EC 5.5.1.6) is a key enzyme in the flavonoid biosynthesis pathway. We isolated a CHI gene (SmCHI) from a cDNA library derived from Saussurea medusa (Asteraceae) cell cultures. The cDNA and genomic sequences of SmCHI are the same; in other words, this gene is intronless. The coding region of the gene is 699 bp long, and its deduced protein consists of 232 amino acids with a predicted molecular mass of 24 kDa and a pI of 4.7. The deduced amino acid sequence of SmCHI shares 79.3% identity with CHI from Callistephus chinensis, a familial relative to S. medusa; this homology is higher than those with CHI's from any other plant species. A functional bioassay for SmCHI was performed by transforming Nicotiana tabacum plants in the sense or antisense orientation under the regulation of the cauliflower mosaic virus (CaMV) 35S promoter. Transgenic tobacco plants overexpressing sense SmCHI produced up to fivefold total flavonoids over wild-type tobacco plants, mainly due to an enhanced accumulation of rutin. Transgenic tobacco plants with antisense SmCHI accumulated smaller amounts of flavonoids; this is apparently brought about by suppressed expression of the endogenous CHI gene. CHI activities also positively correlated with the amounts of total flavonoids accumulated in the transgenic plants. It is concluded that overexpression of SmCHI can be used as a useful approach to increase flavonoid production in transgenic plants.

  9. Effects of the Kava Chalcone Flavokawain A Differ in Bladder Cancer Cells with Wild-type versus Mutant p53

    PubMed Central

    Tang, Yaxiong; Simoneau, Anne R.; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin

    2010-01-01

    Flavokawain A is the predominant chalcone from kava extract. We have assessed the mechanisms of flavokawain A's action on cell cycle regulation. In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G1 arrest. The increase of p21/WAF1 protein corresponded to an increased mRNA level, whereas p27/KIP1 accumulation was associated with the down-regulation of SKP2 and then increased the stability of the p27/KIP1 protein. The accumulation of p21/WAF1 and p27/KIP1 was independent of cell cycle position and thus not a result of the cell cycle arrest. In contrast, flavokawain A induced a G2-M arrest in six p53 mutant-type, high-grade bladder cancer cell lines (T24, UMUC3, TCCSUP, 5637, HT1376, and HT1197). Flavokawain A significantly reduced the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and caused cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. Suppression of p53 expression by small interfering RNA in RT4 cells restored Cdc25C expression and down-regulated p21/WAF1 expression, which allowed Cdc25C and CDK1 activation and then led to a G2-M arrest and an enhanced growth-inhibitory effect by flavokawain A. Consistently, flavokawain A also caused a pronounced CDK1 activation and G2-M arrest in p53 knockout but not in p53 wild-type HCT116 cells. This selectivity of flavokawain A for inducing a G2-M arrest in p53-defective cells deserves further investigation as a new mechanism for the prevention and treatment of bladder cancer. PMID:19138991

  10. (68)Ga based probe for Alzheimer's disease: synthesis and preclinical evaluation of homodimeric chalcone in β-amyloid imaging.

    PubMed

    Chauhan, Kanchan; Datta, Anupama; Adhikari, Anupriya; Chuttani, Krishna; Kumar Singh, Ajai; Mishra, Anil K

    2014-10-07

    In an attempt to explore use of PET radioisotope, (68)Ga, in the diagnosis of Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity towards Aβ aggregates was designed by conjugating two chalcone units with the chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8-bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)-2-(2-(2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)ethylamino)-2-oxoethyl)-10-oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)2 was synthesized in 95% yield with high purity. It was radiolabelled with (68)Ga under mild conditions with 85.4% efficiency and 9.5-10 MBq nmol(-1) specific activity. An in vitro binding assay on Aβ42 aggregates displayed high binding affinity of (68)Ga-DT(Ch)2 and inhibition constant of 4.18 ± 0.62 nM. The fluorescent properties of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue shift with 5.5-fold increase in emission intensity on binding with Aβ aggregates. Blood kinetics of the complex performed on normal rabbit exhibited fast clearance (t1/2(F) = 24 ± 0.08 min; t1/2(S) = 2 h 40 ± 0.04 min). Ex vivo biodistribution analysis demonstrated blood-brain barrier penetration with brain uptake of 1.24 ± 0.31% ID g(-1) at 2 min p.i. and rapid washout with negligible activity (0.36% ID g(-1)) left at 30 min p.i. These preliminary studies reveal that the bivalent approach of synthesis had minimal effect on binding affinity, signifying that the developed (68)Ga-complex, (68)Ga-DT(Ch)2, may offer a new perspective in generator produced PET imaging probes for Alzheimer's disease.

  11. In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot)

    PubMed Central

    Isa, N.M.; Abdelwahab, S.I.; Mohan, S.; Abdul, A.B.; Sukari, M.A.; Taha, M.M.E.; Syam, S.; Narrima, P.; Cheah, S.Ch.; Ahmad, S.; Mustafa, M.R.

    2012-01-01

    The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µg/mL and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µg/mL. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract. PMID:22358425

  12. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

    1983-01-01

    Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

  13. Synthetic stellar libraries for Gaia

    NASA Astrophysics Data System (ADS)

    Sordo, R.

    A large database of synthetic stellar libraries has been collected for the Gaia mission. I will present the libraries in the context of their usage in APSIS, the system of algorithms developed to deal with the automated classification and parameter determination of the observed sources.

  14. Synthetic biology meets tissue engineering

    PubMed Central

    Davies, Jamie A.; Cachat, Elise

    2016-01-01

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the ‘embryological cycle’ of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. PMID:27284030

  15. Modeling Transport Through Synthetic Nanopores

    PubMed Central

    Aksimentiev, Aleksei; Brunner, Robert K.; Cruz-Chú, Eduardo; Comer, Jeffrey; Schulten, Klaus

    2011-01-01

    Nanopores in thin synthetic membranes have emerged as convenient tools for high-throughput single-molecule manipulation and analysis. Because of their small sizes and their ability to selectively transport solutes through otherwise impermeable membranes, nanopores have numerous potential applications in nanobiotechnology. For most applications, properties of the nanopore systems have to be characterize at the atomic level, which is currently beyond the limit of experimental methods. Molecular dynamics (MD) simulations can provide the desired information, however several technical challenges have to be met before this method can be applied to synthetic nanopore systems. Here, we highlight our recent work on modeling synthetic nanopores of the most common types. First, we describe a novel graphical tool for setting up all-atom systems incorporating inorganic materials and biomolecules. Next, we illustrate the application of the MD method for silica, silicon nitride, and polyethylene terephthalate nanopores. Following that, we describe a method for modeling synthetic surfaces using a bias potential. Future directions for tool development and nanopore modeling are briefly discussed at the end of this article. PMID:21909347

  16. Where Synthetic Biology Meets ET

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2016-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  17. SEASAT Synthetic Aperture Radar Data

    NASA Technical Reports Server (NTRS)

    Henderson, F. M.

    1981-01-01

    The potential of radar imagery from space altitudes is discussed and the advantages of radar over passive sensor systems are outlined. Specific reference is made to the SEASAT synthetic aperture radar. Possible applications include oil spill monitoring, snow and ice reconnaissance, mineral exploration, and monitoring phenomena in the urban environment.

  18. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

    1983-06-14

    Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

  19. Leaching behaviour of synthetic aggregates.

    PubMed

    van der Sloot, H A; Hoede, D; Cresswell, D J; Barton, J R

    2001-01-01

    In the framework of EU project "Utilising innovative kiln technology to recycle waste into synthetic aggregate" (BRST-CT98-5234), the leaching behaviour of synthetic aggregates has been studied to assess its environmental compatibility in the various stages of its use. Since the conditions are very different for the different uses, the assessment calls for a variety of different leaching conditions. The pH dependence test is used to cover important differences in pH environment to which the materials are exposed to as well as for an assessment of the buffering capacity of the material. Synthetic aggregate features a low buffer capacity, which makes it sensitive to externally imposed pH conditions. Utilisation and storage exposed to acidic conditions needs to be avoided. The results of the pH dependence test and column leaching test are mutually consistent. The CEN TC 154 method appears to provide systematically low values due to the arbitrary selection of test conditions. Synthetic aggregate studied to date will not adversely affect the concrete in its service life. The main issue for aggregate use is the recycling and the "end of life" condition, when the material becomes construction debris. Not metals, but oxyanions, such as Cr VI and Mo are most relevant under these conditions. A concise test has been applied to assess crucial aspects of leaching for different production mixes.

  20. Future of synthetic aperture radar

    NASA Technical Reports Server (NTRS)

    Barath, F. T.

    1978-01-01

    The present status of the applications of Synthetic Aperture Radars (SARs) is reviewed, and the technology state-of-the art as represented by the Seasat-A and SIR-A SARs examined. The potential of SAR applications, and the near- and longer-term technology trends are assessed.

  1. The synthetic biology open language.

    PubMed

    Myers, Chris; Clancy, Kevin; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline; Roehner, Nicholas; Sauro, Herbert M

    2015-01-01

    The design and construction of engineered organisms is an emerging new discipline called synthetic biology and holds considerable promise as a new technological platform. The design of biologically engineered systems is however nontrivial, requiring contributions from a wide array of disciplines. One particular issue that confronts synthetic biologists is the ability to unambiguously describe novel designs such that they can be reengineered by a third-party. For this reason, the synthetic biology open language (SBOL) was developed as a community wide standard for formally representing biological designs. A design created by one engineering team can be transmitted electronically to another who can then use this design to reproduce the experimental results. The development and the community of the SBOL standard started in 2008 and has since grown in use with now over 80 participants, including international, academic, and industrial interests. SBOL has stimulated the development of repositories and software tools to help synthetic biologists in their design efforts. This chapter summarizes the latest developments and future of the SBOL standard and its supporting infrastructure.

  2. Stereoscopy in cinematographic synthetic imagery

    NASA Astrophysics Data System (ADS)

    Eisenmann, Jonathan; Parent, Rick

    2009-02-01

    In this paper we present experiments and results pertaining to the perception of depth in stereoscopic viewing of synthetic imagery. In computer animation, typical synthetic imagery is highly textured and uses stylized illumination of abstracted material models by abstracted light source models. While there have been numerous studies concerning stereoscopic capabilities, conventions for staging and cinematography in stereoscopic movies have not yet been well-established. Our long-term goal is to measure the effectiveness of various cinematography techniques on the human visual system in a theatrical viewing environment. We would like to identify the elements of stereoscopic cinema that are important in terms of enhancing the viewer's understanding of a scene as well as providing guidelines for the cinematographer relating to storytelling. In these experiments we isolated stereoscopic effects by eliminating as many other visual cues as is reasonable. In particular, we aim to empirically determine what types of movement in synthetic imagery affect the perceptual depth sensing capabilities of our viewers. Using synthetic imagery, we created several viewing scenarios in which the viewer is asked to locate a target object's depth in a simple environment. The scenarios were specifically designed to compare the effectiveness of stereo viewing, camera movement, and object motion in aiding depth perception. Data were collected showing the error between the choice of the user and the actual depth value, and patterns were identified that relate the test variables to the viewer's perceptual depth accuracy in our theatrical viewing environment.

  3. Analysis of the relationship between Chalcone Isomerase gene expression level and rutin production in Ficus deltoidea var. deltoidea and F. deltoidea var. angustifolia

    NASA Astrophysics Data System (ADS)

    Najid, Najihah Mohd; Zain, Che Radziah Che Mohd; Zainal, Zamri

    2016-11-01

    Ficus deltoidea (moraceae) is a herbal plant with medicinal values. Previous studies reported that the F. deltoidea contains a high level of bioactive compounds such as flavonoids. A cDNA encodes for chalcone isomerase was identified from F. deltoidea, designated as FdCHI, which involved in the isomerization of naringenin chalcone to naringenin. Naringenin is a key branch point for the synthesis of rutin, which is believed involved in defense mechanism in the plant. Therefore, we hypothesized that there might be a direct relationship between FdCHI expression level and rutin production in leaves of F. deltoidea var. deltoidea (FDD) and F. deltoidea var. angustifolia (FDA). Our result showed that expression level of FdCHI in leaves FDD was greater than FDA. Analysis of High Performance Liquid Chromatography (HPLC) revealed that rutin was only detected in FDA leaves. Based on the results between FdCHI expression and rutin production, this study concluded that there is no relationship between FdCHI expression and rutin production in leaves of FDA and FDD.

  4. Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

    PubMed

    Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

    2016-08-21

    The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds.

  5. LAP5 and LAP6 Encode Anther-Specific Proteins with Similarity to Chalcone Synthase Essential for Pollen Exine Development in Arabidopsis1[W][OA

    PubMed Central

    Dobritsa, Anna A.; Lei, Zhentian; Nishikawa, Shuh-ichi; Urbanczyk-Wochniak, Ewa; Huhman, David V.; Preuss, Daphne; Sumner, Lloyd W.

    2010-01-01

    Pollen grains of land plants have evolved remarkably strong outer walls referred to as exine that protect pollen and interact with female stigma cells. Exine is composed of sporopollenin, and while the composition and synthesis of this biopolymer are not well understood, both fatty acids and phenolics are likely components. Here, we describe mutations in the Arabidopsis (Arabidopsis thaliana) LESS ADHESIVE POLLEN (LAP5) and LAP6 that affect exine development. Mutation of either gene results in abnormal exine patterning, whereas pollen of double mutants lacked exine deposition and subsequently collapsed, causing male sterility. LAP5 and LAP6 encode anther-specific proteins with homology to chalcone synthase, a key flavonoid biosynthesis enzyme. lap5 and lap6 mutations reduced the accumulation of flavonoid precursors and flavonoids in developing anthers, suggesting a role in the synthesis of phenolic constituents of sporopollenin. Our in vitro functional analysis of LAP5 and LAP6 using 4-coumaroyl-coenzyme A yielded bis-noryangonin (a commonly reported derailment product of chalcone synthase), while similar in vitro analyses using fatty acyl-coenzyme A as the substrate yielded medium-chain alkyl pyrones. Thus, in vitro assays indicate that LAP5 and LAP6 are multifunctional enzymes and may play a role in both the synthesis of pollen fatty acids and phenolics found in exine. Finally, the genetic interaction between LAP5 and an anther gene involved in fatty acid hydroxylation (CYP703A2) demonstrated that they act synergistically in exine production. PMID:20442277

  6. Hiding and unveiling trans-chalcone in a constrained derivative of 4',7-dihydroxyflavylium in water: a versatile photochromic system.

    PubMed

    Pessêgo, Márcia; Gago, Sandra; Basílio, Nuno; Laia, César A T; Jorge Parola, A; Lima, João C; Pina, Fernando

    2017-01-04

    A structurally constrained derivative of 4',7-dihydroxyflavylium was studied in aqueous solution and in CTAB micelles by pH jumps, flash photolysis and continuous irradiation with spectroscopic details assessed as well by theoretical calculations. In water, up to pH = 8, the compound shows only acid base chemistry with deprotonation of the flavylium cation to form a quinoidal base that further deprotonates with pKas of 4.8 and 7.4. In the basic region, unprotonated trans-chalcones are formed. No neutral trans-chalcone (Ct) is formed in water preventing the establishment of the well-known photochromism involving photoisomerization of this species with subsequent formation of the flavylium cation. Addition of 0.02 M CTAB drastically changes the mole fraction distribution of species, leading to the formation of Ct (χCt = 1 at pH = 5) and unveiling a photochromic behavior with a pH-tunable colour contrast in a large pH range (2 < pH < 8). The Ct species can be hidden again (irreversibly) upon addition of α-cyclodextrin that disrupts the CTAB micelles, reverting the system to its initial mole fraction distribution of species. These supramolecular inputs work atop the molecular reaction networks by modifying their species' mole fraction distribution.

  7. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

    PubMed Central

    Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

    2016-01-01

    Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

  8. Designing synthetic vaccines for HIV

    PubMed Central

    2015-01-01

    Summary Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies (BnAbs) has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope (Env) glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines. PMID:25824661

  9. Synthetic microbial ecosystems for biotechnology.

    PubMed

    Pandhal, Jagroop; Noirel, Josselin

    2014-06-01

    Most highly controlled and specific applications of microorganisms in biotechnology involve pure cultures. Maintaining single strain cultures is important for industry as contaminants can reduce productivity and lead to longer "down-times" during sterilisation. However, microbes working together provide distinct advantages over pure cultures. They can undertake more metabolically complex tasks, improve efficiency and even expand applications to open systems. By combining rapidly advancing technologies with ecological theory, the use of microbial ecosystems in biotechnology will inevitably increase. This review provides insight into the use of synthetic microbial communities in biotechnology by applying the engineering paradigm of measure, model, manipulate and manufacture, and illustrate the emerging wider potential of the synthetic ecology field. Systems to improve biofuel production using microalgae are also discussed.

  10. Developing technologies for synthetic fuels

    NASA Astrophysics Data System (ADS)

    Sprow, F. B.

    1981-05-01

    After consideration of a likely timetable for the development of a synthetic fuels industry and its necessary supporting technology, the large variety of such fuels and their potential roles is assessed along with their commercialization outlook. Among the fuel production methods considered are: (1) above-ground retorting of oil shale; (2) in-situ shale retorting; (3) open pit mining of tar sands; (4) in-situ steam stimulation of tar sands; (5) coal gasification; (6) methanol synthesis from carbon monoxide and hydrogen; and (7) direct coal liquefaction by the hydrogenation of coal. It is shown that while the U.S. has very limited resource bases for tar sands and heavy crudes, the abundance of shale in the western states and the abundance and greater geographical dispersion of coal will make these the two most important resources of a future synthetic fuels industry.

  11. Designing synthetic vaccines for HIV.

    PubMed

    Fernández-Tejada, Alberto; Haynes, Barton F; Danishefsky, Samuel J

    2015-06-01

    Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines.

  12. Synthetic approaches to multifunctional indenes

    PubMed Central

    López-Pérez, Sara; Dinarès, Immaculada

    2011-01-01

    Summary The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones. PMID:22238553

  13. Engineering Ecosystems and Synthetic Ecologies#

    PubMed Central

    Mee, Michael T; Wang, Harris H

    2012-01-01

    Microbial ecosystems play an important role in nature. Engineering these systems for industrial, medical, or biotechnological purposes are important pursuits for synthetic biologists and biological engineers moving forward. Here, we provide a review of recent progress in engineering natural and synthetic microbial ecosystems. We highlight important forward engineering design principles, theoretical and quantitative models, new experimental and manipulation tools, and possible applications of microbial ecosystem engineering. We argue that simply engineering individual microbes will lead to fragile homogenous populations that are difficult to sustain, especially in highly heterogeneous and unpredictable environments. Instead, engineered microbial ecosystems are likely to be more robust and able to achieve complex tasks at the spatial and temporal resolution needed for truly programmable biology. PMID:22722235

  14. Synthetic cannabinoids: analysis and metabolites.

    PubMed

    Elsohly, Mahmoud A; Gul, Waseem; Wanas, Amira S; Radwan, Mohamed M

    2014-02-27

    Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.

  15. Synthetic Aperture Radar Simulation Study

    DTIC Science & Technology

    1984-03-01

    multilook are discussed. A chapter is devoted to elevation and planimetric data bases. In addition, six- teen pictures of SAR images from Hughes Aircraft, as...scans. Figure 5.4-1 is a photograph ot two SAR displays. The tirst display is made up ot six subscans and has a multilook ot one. Note that tading is...dentfi by block number) * Synthetic Aperture Radar ( SAR ) Simulation Study Radar Simulation Data Bases 5/~t. 4th.- Computer Image Generation Display 20

  16. Synthetic LDL as targeted drug delivery vehicle

    SciTech Connect

    Forte, Trudy M; Nikanjam, Mina

    2012-08-28

    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  17. Cell microencapsulation with synthetic polymers

    PubMed Central

    Olabisi, Ronke M

    2015-01-01

    The encapsulation of cells into polymeric microspheres or microcapsules has permitted the transplantation of cells into human and animal subjects without the need for immunosuppressants. Cell-based therapies use donor cells to provide sustained release of a therapeutic product, such as insulin, and have shown promise in treating a variety of diseases. Immunoisolation of these cells via microencapsulation is a hotly investigated field, and the preferred material of choice has been alginate, a natural polymer derived from seaweed due to its gelling conditions. Although many natural polymers tend to gel in conditions favorable to mammalian cell encapsulation, there remain challenges such as batch to batch variability and residual components from the original source that can lead to an immune response when implanted into a recipient. Synthetic materials have the potential to avoid these issues; however, historically they have required harsh polymerization conditions that are not favorable to mammalian cells. As research into microencapsulation grows, more investigators are exploring methods to microencapsulate cells into synthetic polymers. This review describes a variety of synthetic polymers used to microencapsulate cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 846–859, 2015. PMID:24771675

  18. Hydrogen speciation in synthetic quartz

    USGS Publications Warehouse

    Aines, R.D.; Kirby, S.H.; Rossman, G.R.

    1984-01-01

    The dominant hydrogen impurity in synthetic quartz is molecular H2O. H-OH groups also occur, but there is no direct evidence for the hydrolysis of Si-O-Si bonds to yield Si-OH HO-Si groups. Molecular H2O concentrations in the synthetic quartz crystals studied range from less than 10 to 3,300 ppm (H/Si), and decrease smoothly by up to an order of magnitude with distance away from the seed. OH- concentrations range from 96 to 715 ppm, and rise smoothly with distance away from the seed by up to a factor of three. The observed OH- is probably all associated with cationic impurities, as in natural quartz. Molecular H2O is the dominant initial hydrogen impurity in weak quartz. The hydrolytic weakening of quartz may be caused by the transformation H2O + Si-O-Si ??? 2SiOH, but this may be a transitory change with the SiOH groups recombining to form H2O, and the average SiOH concentration remaining very low. Synthetic quartz is strengthened when the H2O is accumulated into fluid inclusions and cannot react with the quartz framework. ?? 1984 Springer-Verlag.

  19. Strategies for protein synthetic biology

    PubMed Central

    Grünberg, Raik; Serrano, Luis

    2010-01-01

    Proteins are the most versatile among the various biological building blocks and a mature field of protein engineering has lead to many industrial and biomedical applications. But the strength of proteins—their versatility, dynamics and interactions—also complicates and hinders systems engineering. Therefore, the design of more sophisticated, multi-component protein systems appears to lag behind, in particular, when compared to the engineering of gene regulatory networks. Yet, synthetic biologists have started to tinker with the information flow through natural signaling networks or integrated protein switches. A successful strategy common to most of these experiments is their focus on modular interactions between protein domains or domains and peptide motifs. Such modular interaction swapping has rewired signaling in yeast, put mammalian cell morphology under the control of light, or increased the flux through a synthetic metabolic pathway. Based on this experience, we outline an engineering framework for the connection of reusable protein interaction devices into self-sufficient circuits. Such a framework should help to ‘refacture’ protein complexity into well-defined exchangeable devices for predictive engineering. We review the foundations and initial success stories of protein synthetic biology and discuss the challenges and promises on the way from protein- to protein systems design. PMID:20385577

  20. Synthetic-aperture chirp confocal imaging.

    PubMed

    Chien, Wei-Chen; Dilworth, D S; Liu, Elson; Leith, E N

    2006-01-20

    An imaging system that combines synthetic-aperture imaging, holography, and an optical chirp with confocal imaging is described and analyzed. Comparisons are made with synthetic-aperture radar systems. Adaptation of several synthetic-aperture radar techniques to the optical counterparts is suggested.

  1. Synthetic Cannabinoids and Cathinones: Prevalence and Markets.

    PubMed

    Bretteville-Jensen, A L; Tuv, S S; Bilgrei, O R; Fjeld, B; Bachs, L

    2013-03-01

    Over the past few years, the phenomenon of new designer drugs has attracted much attention. Synthetic cannabinoids and cathinones are the two main classes of these drugs. Both are potent drugs of abuse, and several cases of severe toxicity and deaths are reported. The present work is based on a systematic review of studies that have assessed the market and prevalence of synthetic cannabinoids and cathinones, and integrates pharmacological, sociological, and epidemiological aspects of these two groups of emerging synthetic drugs. The review reflects that the Internet has made synthetic cannabinoids and cathinones widely available. Furthermore, aggressive and widespread marketing, as well as the low price level of these drugs, their juridical status and their lack of detection on standard drug tests may serve as major motivations for drug use. The number of prevalence studies is small and derived from a limited number of countries. In spite of the many methodological shortcomings, some conclusions may be cautiously drawn. Taken together, the results point toward higher prevalence of use for synthetic cathinones than for synthetic cannabinoids. In the general population, the prevalence of use of synthetic cathinones is reported to be around 4% compared to figures lower than 1% for synthetic cannabinoids. Among students, the prevalence varies from 1-20% for synthetic cathinones and 2-10% for synthetic cannabinoids. Among groups with high rates of drug use, the prevalence varies between 4% to more than 60% for synthetic cathinones and around 10% for synthetic cannabinoids.

  2. 63 FR 41290 - Synthetic Methionine From Japan

    Federal Register 2010, 2011, 2012, 2013, 2014

    1998-08-03

    ... COMMISSION Synthetic Methionine From Japan AGENCY: United States International Trade Commission. ACTION: Institution of a five-year review concerning the antidumping duty order on synthetic methionine from Japan... antidumping duty order on synthetic methionine from Japan would be likely to lead to continuation...

  3. Synthetic thermoelectric materials comprising phononic crystals

    DOEpatents

    El-Kady, Ihab F; Olsson, Roy H; Hopkins, Patrick; Reinke, Charles; Kim, Bongsang

    2013-08-13

    Synthetic thermoelectric materials comprising phononic crystals can simultaneously have a large Seebeck coefficient, high electrical conductivity, and low thermal conductivity. Such synthetic thermoelectric materials can enable improved thermoelectric devices, such as thermoelectric generators and coolers, with improved performance. Such synthetic thermoelectric materials and devices can be fabricated using techniques that are compatible with standard microelectronics.

  4. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells

    PubMed Central

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3’,4’,5’-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development. PMID:27525972

  5. Synthetic cornea: biocompatibility and optics

    NASA Astrophysics Data System (ADS)

    Parel, Jean-Marie A.; Kaminski, Stefan; Fernandez, Viviana; Alfonso, E.; Lamar, Peggy; Lacombe, Emmanuel; Duchesne, Bernard; Dubovy, Sander; Manns, Fabrice; Rol, Pascal O.

    2002-06-01

    Purpose. Experimentally find a method to provide a safe surgical technique and an inexpensive and long lasting mesoplant for the restoration of vision in patients with bilateral corneal blindness due to ocular surface and stromal diseases. Methods. Identify the least invasive and the safest surgical technique for synthetic cornea implantation. Identify the most compatible biomaterials and the optimal shape a synthetic cornea must have to last a long time when implanted in vivo. Results. Penetrating procedures were deemed too invasive, time consuming, difficult and prone to long term complications. Therefore a non-penetrating delamination technique with central trephination was developed to preserve the integrity of Descemet's membrane and the anterior segment. Even though this approach limits the number of indications, it is acceptable since the majority of patients only have opacities in the stroma. The prosthesis was designed to fit in the removed tissue plane with its skirt fitted under the delaminated stroma. To improve retention, the trephination wall was made conical with the smallest opening on the anterior surface and a hat-shaped mesoplant was made to fit. The skirt was perforated in its perimeter to allow passage of nutrients and tissues ingrowths. To simplify the fabrication procedure, the haptic and optic were made of the same polymer. The intrastromal biocompatibility of several hydrogels was found superior to current clinically used PMMA and PTFE materials. Monobloc mesoplants made of 4 different materials were implanted in rabbits and followed weekly until extrusion occurred. Some remained optically clear allowing for fundus photography. Conclusions. Hydrogel synthetic corneas can be made to survive for periods longer than 1 year. ArF excimer laser photoablation studies are needed to determine the refractive correction potential of these mesoplants. A pilot FDA clinical trial is needed to assess the mesoplant efficacy and very long-term stability.

  6. Synthetic networks in microbial communities

    NASA Astrophysics Data System (ADS)

    Suel, Gurol

    2015-03-01

    While bacteria are single celled organisms, they predominantly reside in structured communities known as biofilms. Cells in biofilms are encapsulated and protected by the extracellular matrix (ECM), which also confines cells in space. During biofilm development, microbial cells are organized in space and over time. Little is known regarding the processes that drive the spatio-temporal organization of microbial communities. Here I will present our latest efforts that utilize synthetic biology approaches to uncover the organizational principles that drive biofilm development. I will also discuss the possible implications of our recent findings in terms of the cost and benefit to biofilm cells.

  7. Synthetic carbonaceous fuels and feedstocks

    DOEpatents

    Steinberg, Meyer

    1980-01-01

    This invention relates to the use of a three compartment electrolytic cell in the production of synthetic carbonaceous fuels and chemical feedstocks such as gasoline, methane and methanol by electrolyzing an aqueous sodium carbonate/bicarbonate solution, obtained from scrubbing atmospheric carbon dioxide with an aqueous sodium hydroxide solution, whereby the hydrogen generated at the cathode and the carbon dioxide liberated in the center compartment are combined thermocatalytically into methanol and gasoline blends. The oxygen generated at the anode is preferably vented into the atmosphere, and the regenerated sodium hydroxide produced at the cathode is reused for scrubbing the CO.sub.2 from the atmosphere.

  8. Synthetic Fourier transform light scattering.

    PubMed

    Lee, Kyeoreh; Kim, Hyeon-Don; Kim, Kyoohyun; Kim, Youngchan; Hillman, Timothy R; Min, Bumki; Park, Yongkeun

    2013-09-23

    We present synthetic Fourier transform light scattering, a method for measuring extended angle-resolved light scattering (ARLS) from individual microscopic samples. By measuring the light fields scattered from the sample plane and numerically synthesizing them in Fourier space, the angle range of the ARLS patterns is extended up to twice the numerical aperture of the imaging system with unprecedented sensitivity and precision. Extended ARLS patterns of individual microscopic polystyrene beads, healthy human red blood cells (RBCs), and Plasmodium falciparum-parasitized RBCs are presented.

  9. Clustered Carbohydrates in Synthetic Vaccines†

    PubMed Central

    Peri, Francesco

    2013-01-01

    Are there general rules to achieve efficient immunization against carbohydrate antigens? Thanks to technological advances in glycobiology and glycochemistry we entered in a new era in which the rational design of carbohydrate vaccines has become an achievable goal. Aim of this Tutorial Review is to present the most recent achievements in the field of semi and fully synthetic carbohydrate vaccines against viruses, bacteria and cancer. It is also pointed out that the understanding of the chemical and biochemical processes related to immunization allows the modern chemist to rationally design carbohydrate vaccines with improved efficiency. PMID:23250562

  10. Synthetic Studies in Phytochrome Chemistry

    PubMed Central

    Jacobi, Peter A.; Adel Odeh, Imad M.; Buddhu, Subhas C.; Cai, Guolin; Rajeswari, Sundaramoorthi; Fry, Douglas; Zheng, Wanjun; DeSimone, Robert W.; Guo, Jiasheng; Coutts, Lisa D.; Hauck, Sheila I.; Leung, Sam H.; Ghosh, Indranath; Pippin., Douglas

    2008-01-01

    An account is given of the author’s several approaches to the synthesis of the parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole derivative that controls photomorphogenesis in higher plants. These studies culminated in enantioselective syntheses of both 2R- and 2S-phytochromobilin (4), as well as several 13C-labeled derivatives designed to probe the site of Z,E-isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and recombinant-derived phytochrome apoprotein N-C produced a protein-bound chromophore with identical difference spectra to naturally occurring 1. PMID:18633455

  11. Dynamic microcompartmentation in synthetic cells

    PubMed Central

    Long, M. Scott; Jones, Clinton D.; Helfrich, Marcus R.; Mangeney-Slavin, Lauren K.; Keating, Christine D.

    2005-01-01

    An experimental model for cytoplasmic organization is presented. We demonstrate dynamic control over protein distribution within synthetic cells comprising a lipid bilayer membrane surrounding an aqueous polymer solution. This polymer solution generally exists as two immiscible aqueous phases. Protein partitioning between these phases leads to microcompartmentation, or heterogeneous protein distribution within the “cell” interior. This model cytoplasm can be reversibly converted to a single phase by slight changes in temperature or osmolarity, such that local protein concentrations can be manipulated within the vesicle interior. PMID:15788532

  12. Synthetic Biology Guides Biofuel Production

    PubMed Central

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  13. Designing, synthesis of selective and high-affinity chalcone-benzothiazole hybrids as Brugia malayi thymidylate kinase inhibitors: In vitro validation and docking studies.

    PubMed

    Sashidhara, Koneni V; Avula, Srinivasa Rao; Doharey, Pawan Kumar; Singh, L Ravithej; Balaramnavar, Vishal M; Gupta, Jyoti; Misra-Bhattacharya, Shailja; Rathaur, Sushma; Saxena, Anil K; Saxena, Jitendra Kumar

    2015-10-20

    In our continuing search for safe and efficacious antifilarials, a series of novel chalcone-benzothiazole hybrids have been synthesized and evaluated for their Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition activity. Their selectivity towards BmTMK was studied and compared to the human TMK (HsTMK) by an in silico method. Out of seventeen derivatives, compounds 34 and 42 showed higher interactions with the BmTMK active site. MolDock docking model revealed the interactions of these two derivatives and the results corroborated well with their in vitro antifilarial activities. Our studies suggest that these hybrids are selective towards the BmTMK enzyme and may serve as potential therapeutic agents against filariasis.

  14. Asymmetric Michael Addition of Aldimino Esters with Chalcones Catalyzed by Silver/Xing-Phos: Mechanism-Oriented Divergent Synthesis of Chiral Pyrrolines.

    PubMed

    Bai, Xing-Feng; Li, Li; Xu, Zheng; Zheng, Zhan-Jiang; Xia, Chun-Gu; Cui, Yu-Ming; Xu, Li-Wen

    2016-07-18

    The mechanism-oriented reaction design for the divergent synthesis of chiral molecules from simple starting materials is highly desirable. In this work, aromatic amide-derived nonbiarylatropisomer/silver (silver/Xing-Phos) complex was used to catalyze the Michael addition of glycine aldimino esters to chalcones and successfully applied to the subsequent cyclocondensation to afford substituted cis-Δ(1)-pyrroline derivatives with up to 98 % ee. Besides the inherent performance of the chiral Ag/Xing-Phos catalyst system, it was found that the workup of such reactions played an important role for the stereoselective construction of stereodivergent Δ(1)-pyrrolines, in which an epimerization of the cis-Δ(1)-pyrrolines to the trans-isomers during was revealed.

  15. Synthesis of novel analogs of 2-pyrazoline obtained from [(7-chloroquinolin-4-yl)amino]chalcones and hydrazine as potential antitumor and antimalarial agents.

    PubMed

    Insuasty, Braulio; Montoya, Alba; Becerra, Diana; Quiroga, Jairo; Abonia, Rodrigo; Robledo, Sara; Vélez, Ivan Darío; Upegui, Yulieth; Nogueras, Manuel; Cobo, Justo

    2013-09-01

    A new series of N-acetyl and N-formyl-pyrazoline derivatives 6 and 7-8 were synthesized by cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones with hydrazine hydrate in acetic acid and hydrazine hydrate in formic acid respectively. These compounds were evaluated in vitro as antitumor and as antimalarial agents. Compounds 7b and 8b-e showed remarkable antitumor activity against cancer cell lines, with the most important GI50 values ranging from 0.13 to 0.99 μM. The best antimalarial response was observed for compound 7a with an inhibition percentage of 50.8% for Plasmodium falciparum, a hemolytic capacity of 3.2% and an IC50 of 14.1 μg/mL.

  16. Enzymatic biotransformation of synthetic dyes.

    PubMed

    Rodríguez-Couto, S

    2009-11-01

    Environmental pollution by discharge of dye-containing effluents represents a serious ecological concern in many countries. Public demands for colour-free discharges to receiving waters have made decolouration of a variety of industrial wastewater a top priority. The current existing techniques for dye removal have several drawbacks such as high cost, low efficiency, use of large amounts of chemicals and formation of toxic sub-products. This has impelled the search for alternative methods such as those based on oxidative enzymes. This approach is believed to be a promising technology since it is cost-effective, environmentally friendly and does not produce sludge. Enzymatic transformation of synthetic dyes can be described as the conversion of dye molecules by enzymes into simpler and generally colourless molecules. Detailed characterisation of the metabolites produced during enzymatic transformation of synthetic dyes as well as ecotoxicity studies is of great importance to assess the effectiveness of the biodegradation process. However, most reports on the biotreatment of dyes mainly deal with decolouration and there are few reports on the reduction in toxicity or on the identification of the biodegradation products. This implies a limitation to assess their true technical potential.

  17. Synthetic population system user guide

    SciTech Connect

    Roberts, D.J.

    1998-03-01

    The Los Alamos National Laboratory (LANL) TRansportation Analysis SIMulatiuon System (TRANSIMS) synthetic population system (SYN) is designed to produce populations (family households, non-family households, and group quarters) that are statistically equivalent to actual populations when compared at the level of block group or higher. The methodology used by this system is described in a report entitled Creating Synthetic Baseline Populations. The inputs to the system are US Census Bureau data (STF3A and PUMS) and MABLE/GEOCORR data. Census Bureau STF3A and PUMS data formats are commonly used and are available on CD-ROM from the Census Bureau. These data inputs will not be described in any detail in this guide. The primary function of MABLE/GEOCORR data is to cross-reference STF3 block group data to PUMS areas. The outputs of the system are files that contain family household, non-family household, and group quarters data in the form of household and person records. SYN will run on a variety of Unix platforms.

  18. Synthetic vision display evaluation studies

    NASA Technical Reports Server (NTRS)

    Regal, David M.; Whittington, David H.

    1994-01-01

    The goal of this research was to help us understand the display requirements for a synthetic vision system for the High Speed Civil Transport (HSCT). Four experiments were conducted to examine the effects of different levels of perceptual cue complexity in displays used by pilots in a flare and landing task. Increased levels of texture mapping of terrain and runway produced mixed results, including harder but shorter landings and a lower flare initiation altitude. Under higher workload conditions, increased texture resulted in an improvement in performance. An increase in familiar size cues did not result in improved performance. Only a small difference was found between displays using two patterns of high resolution texture mapping. The effects of increased perceptual cue complexity on performance was not as strong as would be predicted from the pilot's subjective reports or from related literature. A description of the role of a synthetic vision system in the High Speed Civil Transport is provide along with a literature review covering applied research related to perceptual cue usage in aircraft displays.

  19. Multiple arrested synthetic aperture radar

    NASA Astrophysics Data System (ADS)

    Shuster, J. S.

    1981-05-01

    This report contains the formulation and analysis of an airborne synthetic aperture rate scheme which employs a multiplicity of antennas with the displaced phase center antenna technique to detect slowly moving targets embedded in a severe clutter environment. The radar is evaluated using the target to clutter power ratio as the measure of performance. Noise is ignored in the analysis. An optimization scheme which maximizes this ratio is employed to obtain the optimum processor weighting. The performance of the MASAR processor with optimum weights is compared against that using target weights (composed of the target signal) and that using binomial weights (which, effectively, form an n-pulse canceller). Both the target and the clutter are modeled with the electric field backscattering coefficient. The target is modeled simply as a deterministically moving point scatterer with the same albedo as a point of clutter. The clutter is modeled as a homogeneous, isotropic, two dimensional, spatiotemporal random field for which only the correlation properties are required. The analysis shows that this radar, with its optimum weighting scheme, is a promising synthetic aperture concept for the detection of slowly moving targets immersed in strong clutter environments.

  20. CFIT Prevention Using Synthetic Vision

    NASA Technical Reports Server (NTRS)

    Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.; Parrish, Russell V.

    2003-01-01

    In commercial aviation, over 30-percent of all fatal accidents worldwide are categorized as Controlled Flight Into Terrain (CFIT) accidents where a fully functioning airplane is inadvertently flown into the ground, water, or an obstacle. An experiment was conducted at NASA Langley Research Center investigating the presentation of a synthetic terrain database scene to the pilot on a Primary Flight Display (PFD). The major hypothesis for the experiment is that a synthetic vision system (SVS) will improve the pilot s ability to detect and avoid a potential CFIT compared to conventional flight instrumentation. All display conditions, including the baseline, contained a Terrain Awareness and Warning System (TAWS) and Vertical Situation Display (VSD) enhanced Navigation Display (ND). Sixteen pilots each flew 22 approach - departure maneuvers in Instrument Meteorological Conditions (IMC) to the terrain challenged Eagle County Regional Airport (EGE) in Colorado. For the final run, the flight guidance cues were altered such that the departure path went into the terrain. All pilots with a SVS enhanced PFD (12 of 16 pilots) noticed and avoided the potential CFIT situation. All of the pilots who flew the anomaly with the baseline display configuration (which included a TAWS and VSD enhanced ND) had a CFIT event.

  1. Development of Leishmania donovani stably expressing DsRed for flow cytometry-based drug screening using chalcone thiazolyl-hydrazone as a new antileishmanial target.

    PubMed

    Jaiswal, Anil Kumar; Rao, K Bhaskara; Kushwaha, Pragati; Rawat, Keerti; Modukuri, Ram K; Khare, Prashant; Joshi, Sumit; Mishra, Shikha; Rai, Ambak; Sashidhara, Koneni V; Dube, Anuradha

    2016-12-01

    Green fluorescent protein produces significant fluorescence and is extremely stable, however its excitation maximum is close to the ultraviolet range and thus can damage living cells. Hence, Leishmania donovani stably expressing DsRed were developed and their suitability for flow cytometry-based antileishmanial screening was assessed by evaluating the efficacies of standard drugs as well as newly synthesised chalcone thiazolyl-hydrazone compounds. The DsRed gene was successfully integrated at the 18S rRNA locus of L. donovani and transfectants (LdDsRed) were selected using hygromycin B. Enhanced expression of DsRed and a high level of infectivity to J774A.1 macrophages were achieved, which was confirmed by fluorescence microscopy and flow cytometry. Furthermore, these LdDsRed transfectants were utilised for development of an in vitro screening assay using the standard antileishmanial drugs miltefosine, amphotericin B, pentamidine and paromomycin. The response of transfectants to standard drugs correlated well with previous reports. Subsequently, the suitability of this system was further assessed by screening a series of 18 newly synthesised chalcone thiazolyl-hydrazone compounds in vitro for their antileishmanial activity, wherein 8 compounds showed moderate antileishmanial activity. The most active compound 5g, with ca. 73% splenic parasite reduction, exerted its activity via generating nitric oxide and reactive oxygen species and inducing apoptosis in LdDsRed-infected macrophages. Thus, these observations established the applicability of LdDsRed transfectants for flow cytometry-based antileishmanial screening. Further efforts aimed at establishing a high-throughput screening assay and determining the in vivo screening of potential antileishmanial leads are required.

  2. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    SciTech Connect

    Fang, Qilu; Zhao, Leping; Wang, Yi; Zhang, Yali; Li, Zhaoyu; Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao; Li, Dan; Liang, Guang

    2015-01-15

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

  3. Microbial synthetic biology for human therapeutics.

    PubMed

    Jain, Aastha; Bhatia, Pooja; Chugh, Archana

    2012-06-01

    The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products. It is expected that the construction of novel microbial genetic circuitry for human therapeutics will greatly benefit from the data generated by 'omics' approaches and multidisciplinary nature of synthetic biology. Development of novel antimicrobial drugs and vaccines by engineering microbial systems are a promising area of research in the field of synthetic biology for human theragnostics. Expression of plant based medicinal compounds in the microbial system using synthetic biology tools is another avenue dealt in the present study. Additionally, the study suggest that the traditional medicinal knowledge can do value addition for developing novel drugs in the microbial systems using synthetic biology tools. The presented work envisions the success of synthetic biology for human therapeutics via microbial approach in a holistic manner. Keeping this in view, various legal and socio-ethical concerns emerging from the use of synthetic biology via microbial approach such as patenting, biosafety and biosecurity issues have been touched upon in the later sections.

  4. Word selection affects perceptions of synthetic biology.

    PubMed

    Pearson, Brianna; Snell, Sam; Bye-Nagel, Kyri; Tonidandel, Scott; Heyer, Laurie J; Campbell, A Malcolm

    2011-07-21

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  5. Creating biological nanomaterials using synthetic biology

    NASA Astrophysics Data System (ADS)

    Rice, MaryJoe K.; Ruder, Warren C.

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  6. Nature's chemicals and synthetic chemicals: comparative toxicology.

    PubMed Central

    Ames, B N; Profet, M; Gold, L S

    1990-01-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50% for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests. PMID:2217211

  7. Word selection affects perceptions of synthetic biology

    PubMed Central

    2011-01-01

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create". PMID:21777466

  8. Creating biological nanomaterials using synthetic biology.

    PubMed

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  9. Nature's chemicals and synthetic chemicals: Comparative toxicology

    SciTech Connect

    Ames, B.N.; Profet, M.; Gold, L.S. )

    1990-10-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50{percent} for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests.

  10. Synthetic biology - the state of play.

    PubMed

    Kitney, Richard; Freemont, Paul

    2012-07-16

    Just over two years ago there was an article in Nature entitled "Five Hard Truths for Synthetic Biology". Since then, the field has moved on considerably. A number of economic commentators have shown that synthetic biology very significant industrial potential. This paper addresses key issues in relation to the state of play regarding synthetic biology. It first considers the current background to synthetic biology, whether it is a legitimate field and how it relates to foundational biological sciences. The fact that synthetic biology is a translational field is discussed and placed in the context of the industrial translation process. An important aspect of synthetic biology is platform technology, this topic is also discussed in some detail. Finally, examples of application areas are described.

  11. A synthetic zero air standard

    NASA Astrophysics Data System (ADS)

    Pearce, Ruth

    2016-04-01

    A Synthetic Zero Air Standard R. E. Hill-Pearce, K. V. Resner, D. R. Worton, P. J. Brewer The National Physical Laboratory Teddington, Middlesex TW11 0LW UK We present work towards providing traceability for measurements of high impact greenhouse gases identified by the World Meteorological Organisation (WMO) as critical for global monitoring. Standards for these components are required with challengingly low uncertainties to improve the quality assurance and control processes used for the global networks to better assess climate trends. Currently the WMO compatibility goals require reference standards with uncertainties of < 100 nmolmol-1 for CO2 (northern hemisphere) and < 2 nmolmol-1 for CH4 and CO. High purity zero gas is required for both the balance gas in the preparation of reference standards and for baseline calibrations of instrumentation. Quantification of the amount fraction of the target components in the zero gas is a significant contributor to the uncertainty and is challenging due to limited availability of reference standard at the amount fraction of the measurand and limited analytical techniques with sufficient detection limits. A novel dilutor was used to blend NPL Primary Reference Gas Mixtures containing CO2, CH4 and CO at atmospheric amount fractions with a zero gas under test. Several mixtures were generated with nominal dilution ratios ranging from 2000:1 to 350:1. The baseline of two cavity ring down spectrometers was calibrated using the zero gas under test after purification by oxidative removal of CO and hydrocarbons to < 1 nmolmol-1 (SAES PS15-GC50) followed by the removal of CO2 and water vapour to < 100 pmolmol-1 (SAES MC190). Using the standard addition method.[1] we have quantified the amount fraction of CO, CO2, and CH4 in scrubbed whole air (Scott Marrin) and NPL synthetic zero air. This is the first synthetic zero air standard with a matrix of N2, O2 and Ar closely matching ambient composition with gravimetrically assigned

  12. Broadband synthetic aperture geoacoustic inversion.

    PubMed

    Tan, Bien Aik; Gerstoft, Peter; Yardim, Caglar; Hodgkiss, William S

    2013-07-01

    A typical geoacoustic inversion procedure involves powerful source transmissions received on a large-aperture receiver array. A more practical approach is to use a single moving source and/or receiver in a low signal to noise ratio (SNR) setting. This paper uses single-receiver, broadband, frequency coherent matched-field inversion and exploits coherently repeated transmissions to improve estimation of the geoacoustic parameters. The long observation time creates a synthetic aperture due to relative source-receiver motion. This approach is illustrated by studying the transmission of multiple linear frequency modulated (LFM) pulses which results in a multi-tonal comb spectrum that is Doppler sensitive. To correlate well with the measured field across a receiver trajectory and to incorporate transmission from a source trajectory, waveguide Doppler and normal mode theory is applied. The method is demonstrated with low SNR, 100-900 Hz LFM pulse data from the Shallow Water 2006 experiment.

  13. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  14. Synthetic Jets in Quiescent Air

    NASA Technical Reports Server (NTRS)

    Yao, C. S.; Chen, F. J.; Neuhart, D.; Harris, J.

    2007-01-01

    An oscillatory jet with zero net mass flow is generated by a cavity-pumping actuator. Among the three test cases selected for the Langley CFD validation workshop to assess the current CFD capabilities to predict unsteady flow fields, this basic oscillating jet flow field is the least complex and is selected as the first test case. Increasing in complexity, two more cases studied include jet in cross flow boundary layer and unsteady flow induced by suction and oscillatory blowing with separation control geometries. In this experiment, velocity measurements from three different techniques, hot-wire anemometry, Laser Doppler Velocimetry (LDV) and Particle Image Velocimetry (PIV), documented the synthetic jet flow field. To provide boundary conditions for computations, the experiment also monitored the actuator operating parameters including diaphragm displacement, internal cavity pressure, and internal cavity temperature.

  15. Synthetically simple, highly resilient hydrogels.

    PubMed

    Cui, Jun; Lackey, Melissa A; Madkour, Ahmad E; Saffer, Erika M; Griffin, David M; Bhatia, Surita R; Crosby, Alfred J; Tew, Gregory N

    2012-03-12

    Highly resilient synthetic hydrogels were synthesized by using the efficient thiol-norbornene chemistry to cross-link hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) polymer chains. The swelling and mechanical properties of the hydrogels were controlled by the relative amounts of PEG and PDMS. The fracture toughness (G(c)) was increased to 80 J/m(2) as the water content of the hydrogel decreased from 95% to 82%. In addition, the mechanical energy storage efficiency (resilience) was more than 97% at strains up to 300%. This is comparable with one of the most resilient materials known: natural resilin, an elastic protein found in many insects, such as in the tendons of fleas and the wings of dragonflies. The high resilience of these hydrogels can be attributed to the well-defined network structure provided by the versatile chemistry, low cross-link density, and lack of secondary structure in the polymer chains.

  16. Synthetic CA II Triplet Lines

    NASA Astrophysics Data System (ADS)

    Erdelyi, M. M.; Barbuy, B.

    1990-11-01

    RESUMEN. Se hicieron calculos de sintesis del espectro en el ititervalo de longitud de onda - 8700 A, ara ? oder verificar el comporta- mien to de diferentes lineas moleculares y at5micas como funci5n de los parametros esteldres de temperatura, gravedad y metalicidad. El espec- tro sintetico ha sido generado para:(a) todas las , (b) solamente de CN, (c) solamente de TiO, y (d) solamente lineas at6micas. Abstract. Spectrum synthesis calculations are carried out in the wavelength interval X 8300 - 8700 A, in order to verify the behaviour of different molecular and atomic lines as a function of the stellar para meters temperature, gravity and metallicity. Synthetic spectra were ge nerated for: (a) all lines, (b) only CN lines, (c) only TiO lines, and (d) only atomic lines Key `td6: LINE-PROFILE - ST S-AThOSPHERES

  17. Nanostructures from Synthetic Genetic Polymers.

    PubMed

    Taylor, Alexander I; Beuron, Fabienne; Peak-Chew, Sew-Yeu; Morris, Edward P; Herdewijn, Piet; Holliger, Philipp

    2016-06-16

    Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. Here, we explore the construction of nano-objects made entirely from alternative building blocks: synthetic genetic polymers not found in nature, also called xeno nucleic acids (XNAs). Specifically, we describe assembly of 70 kDa tetrahedra elaborated in four different XNA chemistries (2'-fluro-2'-deoxy-ribofuranose nucleic acid (2'F-RNA), 2'-fluoroarabino nucleic acids (FANA), hexitol nucleic acids (HNA), and cyclohexene nucleic acids (CeNA)), as well as mixed designs, and a ∼600 kDa all-FANA octahedron, visualised by electron microscopy. Our results extend the chemical scope for programmable nanostructure assembly, with implications for the design of nano-objects and materials with an expanded range of structural and physicochemical properties, including enhanced biostability.

  18. Multifocal interferometric synthetic aperture microscopy

    PubMed Central

    Xu, Yang; Chng, Xiong Kai Benjamin; Adie, Steven G.; Boppart, Stephen A.; Scott Carney, P.

    2014-01-01

    There is an inherent trade-off between transverse resolution and depth of field (DOF) in optical coherence tomography (OCT) which becomes a limiting factor for certain applications. Multifocal OCT and interferometric synthetic aperture microscopy (ISAM) each provide a distinct solution to the trade-off through modification to the experiment or via post-processing, respectively. In this paper, we have solved the inverse problem of multifocal OCT and present a general algorithm for combining multiple ISAM datasets. Multifocal ISAM (MISAM) uses a regularized combination of the resampled datasets to bring advantages of both multifocal OCT and ISAM to achieve optimal transverse resolution, extended effective DOF and improved signal-to-noise ratio. We present theory, simulation and experimental results. PMID:24977909

  19. Jet fuels from synthetic crudes

    NASA Technical Reports Server (NTRS)

    Antoine, A. C.; Gallagher, J. P.

    1977-01-01

    An investigation was conducted to determine the technical problems in the conversion of a significant portion of a barrel of either a shale oil or a coal synthetic crude oil into a suitable aviation turbine fuel. Three syncrudes were used, one from shale and two from coal, chosen as representative of typical crudes from future commercial production. The material was used to produce jet fuels of varying specifications by distillation, hydrotreating, and hydrocracking. Attention is given to process requirements, hydrotreating process conditions, the methods used to analyze the final products, the conditions for shale oil processing, and the coal liquid processing conditions. The results of the investigation show that jet fuels of defined specifications can be made from oil shale and coal syncrudes using readily available commercial processes.

  20. Synthetically Simple, Highly Resilient Hydrogels

    PubMed Central

    Cui, Jun; Lackey, Melissa A.; Madkour, Ahmad E.; Saffer, Erika M.; Griffin, David M.; Bhatia, Surita R.; Crosby, Alfred J.; Tew, Gregory N.

    2014-01-01

    Highly resilient synthetic hydrogels were synthesized by using the efficient thiol-norbornene chemistry to cross-link hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) polymer chains. The swelling and mechanical properties of the hydrogels were well-controlled by the relative amounts of PEG and PDMS. In addition, the mechanical energy storage efficiency (resilience) was more than 97% at strains up to 300%. This is comparable with one of the most resilient materials known: natural resilin, an elastic protein found in many insects, such as in the tendons of fleas and the wings of dragonflies. The high resilience of these hydrogels can be attributed to the well-defined network structure provided by the versatile chemistry, low cross-link density, and lack of secondary structure in the polymer chains. PMID:22372639

  1. Microorganism Utilization for Synthetic Milk

    NASA Technical Reports Server (NTRS)

    Morford, Megan A.; Khodadad, Christina L.; Caro, Janicce I.; Spencer, LaShelle E.; Richards, Jeffery T.; Strayer, Richard F.; Birmele, Michele N.; Wheeler, Raymond M.

    2014-01-01

    A desired architecture for long duration spaceflight, like aboard the International Space Station or for future missions to Mars, is to provide a supply of fresh food crops for the astronauts. However, some crops can create a high proportion of inedible plant waste. The main goal of the Synthetic Biology project, Cow in a Column, was to produce the components of milk (sugar, lipid, protein) from inedible plant waste by utilizing microorganisms (fungi, yeast, bacteria). Of particular interest was utilizing the valuable polysaccharide, cellulose, found in plant waste, to naturally fuel-through microorganism cellular metabolism- the creation of sugar (glucose), lipid (milk fat), and protein (casein) in order to produce a synthetic edible food product. Environmental conditions such as pH, temperature, carbon source, aeration, and choice microorganisms were optimized in the laboratory and the desired end-products, sugars and lipids, were analyzed. Trichoderma reesei, a known cellulolytic fungus, was utilized to drive the production of glucose, with the intent that the produced glucose would serve as the carbon source for milk fat production and be a substitute for the milk sugar lactose. Lipid production would be carried out by Rhodosporidium toruloides, yeast known to accumulate those lipids that are typically found in milk fat. Results showed that glucose and total lipid content were below what was expected during this phase of experimentation. In addition, individual analysis of six fatty acids revealed that the percentage of each fatty acid was lower than naturally produced bovine milk. Overall, this research indicates that microorganisms could be utilized to breakdown inedible solid waste to produce useable products. For future work, the production of the casein protein for milk would require the development of a genetically modified organism, which was beyond the scope of the original project. Additional trials would be needed to further refine the required

  2. The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology from the Laboratory to the Field

    DTIC Science & Technology

    2016-09-26

    ARL-RP-0579 ● OCT 2016 US Army Research Laboratory The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology ...Do not return it to the originator. ARL-RP-0579 ● OCT 2016 US Army Research Laboratory The Next Generation of Synthetic Biology ...Chassis: Moving Synthetic Biology from the Laboratory to the Field by Bryn L Adams Sensors and Electron Devices Directorate, ARL A

  3. World synthetic rubber consumption is growing

    SciTech Connect

    Not Available

    1987-03-04

    Worldwide consumption of new rubber, both synthetic and natural, has increased. This report includes a prediction of even more growth in the rubber market which was made by the International Institute of Synthetic Rubber Producers (IISRP), based in Houston. Figures are given for worldwide consumption.

  4. Opportunities for microfluidic technologies in synthetic biology

    PubMed Central

    Gulati, Shelly; Rouilly, Vincent; Niu, Xize; Chappell, James; Kitney, Richard I.; Edel, Joshua B.; Freemont, Paul S.; deMello, Andrew J.

    2009-01-01

    We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed. PMID:19474079

  5. 78 FR 22209 - Additional Synthetic Drug Testing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... COMMISSION 10 CFR Part 26 Additional Synthetic Drug Testing AGENCY: Nuclear Regulatory Commission. ACTION... NRC amend its Fitness for Duty program regulations to amend drug testing requirements to test for additional synthetic drugs currently not included in the regulations. The NRC determined that the...

  6. Synthetic biology: programming cells for biomedical applications.

    PubMed

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

    2012-01-01

    The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

  7. Synergistic Synthetic Biology: Units in Concert.

    PubMed

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  8. Synthetic biology: from mainstream to counterculture.

    PubMed

    Sleator, Roy D

    2016-09-01

    Existing at the interface of science and engineering, synthetic biology represents a new and emerging field of mainstream biology. However, there also exists a counterculture of Do-It-Yourself biologists, citizen scientists, who have made significant inroads, particularly in the design and development of new tools and techniques. Herein, I review the development and convergence of synthetic biology's mainstream and countercultures.

  9. [Preparation technique of Cremastra appendiculata synthetic seed].

    PubMed

    Zhang, Mingsheng; Peng, Siwen; Yang, Xiaorui; Xu, Li

    2009-08-01

    The protocorm-suspension-system of Cremastra appendiculata was founded by liquid-suspension culture. The factors to effect germination rate and seedling conversion rate of C. appendiculata synthetic seeds, such as synthetic coating materials, synthetic endosperm components, storing conditions and germination materials, etc. were studied. The result showed that the germination rate and seedling conversion rate of synthetic seeds were the highest on the MS solid-medium while using 4% sodium alginate + 2% CaCl2 + 2% chitosan as synthetic coating materials, with 1/2 MS liquid-medium + 0.2 mg x L(-1) NAA + 0.1 mg x L(-1) GA3 + 0.5 mg L(-1) BA + 0.4 mg x L(-1) penicillin + 10.0 mg x L(-1) endophyte extract +0.3% carbendazim powder + 0.2% sodium benzoate + 1.0% sucrose as synthetic endosperm. And the germination rate and seedling conversion rate of synthetic seeds could attain to 68% and 65% after 20 days storing at 4 degrees C. The germination rate and seedling conversion rate of synthetic seeds decreased to a great extent with increasing the storing temperature and prolonging storing time.

  10. Synthetic diagnostics platform for fusion plasmas (invited)

    DOE PAGES

    Shi, L.; Valeo, E. J.; Tobias, B. J.; ...

    2016-08-26

    A Synthetic Diagnostics Platform (SDP) for fusion plasmas has been developed which provides state of the art synthetic reflectometry, beam emission spectroscopy, and Electron Cyclotron Emission (ECE) diagnostics. Interfaces to the plasma simulation codes GTC, XGC-1, GTS, and M3D-C-1 are provided, enabling detailed validation of these codes. In this paper, we give an overview of SDP's capabilities, and introduce the synthetic diagnostic modules. A recently developed synthetic ECE Imaging module which self-consistently includes refraction, diffraction, emission, and absorption effects is discussed in detail. Its capabilities are demonstrated on two model plasmas. Finally, the importance of synthetic diagnostics in validation ismore » shown by applying the SDP to M3D-C1 output and comparing it with measurements from an edge harmonic oscillation mode on DIII-D.« less

  11. Development of synthetic lethality anticancer therapeutics.

    PubMed

    Fang, Bingliang

    2014-10-09

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy.

  12. Synthetic diagnostics platform for fusion plasmas (invited)

    SciTech Connect

    Shi, L.; Valeo, E. J.; Tobias, B. J.; Kramer, G. J.; Hausammann, L.; Tang, W. M.; Chen, M.

    2016-08-26

    A Synthetic Diagnostics Platform (SDP) for fusion plasmas has been developed which provides state of the art synthetic reflectometry, beam emission spectroscopy, and Electron Cyclotron Emission (ECE) diagnostics. Interfaces to the plasma simulation codes GTC, XGC-1, GTS, and M3D-C-1 are provided, enabling detailed validation of these codes. In this paper, we give an overview of SDP's capabilities, and introduce the synthetic diagnostic modules. A recently developed synthetic ECE Imaging module which self-consistently includes refraction, diffraction, emission, and absorption effects is discussed in detail. Its capabilities are demonstrated on two model plasmas. Finally, the importance of synthetic diagnostics in validation is shown by applying the SDP to M3D-C1 output and comparing it with measurements from an edge harmonic oscillation mode on DIII-D.

  13. Mammalian synthetic biology: emerging medical applications.

    PubMed

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

  14. Applications of synthetic carbohydrates to chemical biology.

    PubMed

    Lepenies, Bernd; Yin, Jian; Seeberger, Peter H

    2010-06-01

    Access to synthetic carbohydrates is an urgent need for the development of carbohydrate-based drugs, vaccines, adjuvants as well as novel drug delivery systems. Besides traditional synthesis in solution, synthetic carbohydrates have been generated by chemoenzymatic methods as well as automated solid-phase synthesis. Synthetic oligosaccharides have proven to be useful for identifying ligands of carbohydrate-binding proteins such as C-type lectins and siglecs using glycan arrays. Furthermore, glyconanoparticles and glycodendrimers have been used for specific targeting of lectins of the immune system such as selectins, DC-SIGN, and CD22. This review focuses on how diverse carbohydrate structures can be synthetically derived and highlights the benefit of synthetic carbohydrates for glycobiology.

  15. Synthetic diagnostics platform for fusion plasmas (invited)

    NASA Astrophysics Data System (ADS)

    Shi, L.; Valeo, E. J.; Tobias, B. J.; Kramer, G. J.; Hausammann, L.; Tang, W. M.; Chen, M.

    2016-11-01

    A Synthetic Diagnostics Platform (SDP) for fusion plasmas has been developed which provides state of the art synthetic reflectometry, beam emission spectroscopy, and Electron Cyclotron Emission (ECE) diagnostics. Interfaces to the plasma simulation codes GTC, XGC-1, GTS, and M3D-C1 are provided, enabling detailed validation of these codes. In this paper, we give an overview of SDP's capabilities, and introduce the synthetic diagnostic modules. A recently developed synthetic ECE Imaging module which self-consistently includes refraction, diffraction, emission, and absorption effects is discussed in detail. Its capabilities are demonstrated on two model plasmas. The importance of synthetic diagnostics in validation is shown by applying the SDP to M3D-C1 output and comparing it with measurements from an edge harmonic oscillation mode on DIII-D.

  16. Mammalian synthetic biology: emerging medical applications

    PubMed Central

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  17. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  18. Synthetic Landau levels for photons

    NASA Astrophysics Data System (ADS)

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-06-01

    Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock-Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen-Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.

  19. MONITORING SYNTHETIC MUSK COMPOUNDS IN ...

    EPA Pesticide Factsheets

    Synthetic musk compounds are manufactured as fragrance materials for consumer products and are consumed in very large quantities worldwide. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for media, responding to public inquiries. Subtask 3: To apply state-of-the-art envir

  20. Electrospun Synthetic Polypeptide Nanofibrous Biomaterials

    NASA Astrophysics Data System (ADS)

    Khadka, Dhan; Haynie, Donald

    2011-03-01

    Water-insoluble nanofiber mats of synthetic polypeptides of defined composition have been prepared from fibers electrospun from aqueous solution in the absence of organic co-solvents. 20-50 kDa poly(L-glutamate, L-tyrosine) 4:1 (PLGY) but not 15-50 kDa or 50-100 kDa poly(L-glutamate) was spinnable at 20-55% (w/v) polymer in water. Applied voltage and needle-collector distance were crucial for spinnability. Attractive fibers were obtained at 50% polymer. Fiber diameter and mat morphology have been characterized by electron microscopy. Exposure of spun fiber mats to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), which reacts with carboxylate, decreased fiber solubility. Fluorescein-conjugated poly(L-lysine) (FITC-PLL) but not the fluorophore alone was able bind PLGY fiber mats electrostatically, judging by fluorescence microscopy. Key advances of this work are the avoidance of an animal source of peptides and of an inorganic co-solvent to achieve polypeptide spinnability. Polypeptide fiber mats are a promising type of nano-structured biomaterial for applications in biomedicine and biotechnology.

  1. The major synthetic evolutionary transitions

    PubMed Central

    Solé, Ricard

    2016-01-01

    Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431528

  2. Involvement of Salicylic Acid on Antioxidant and Anticancer Properties, Anthocyanin Production and Chalcone Synthase Activity in Ginger (Zingiber officinale Roscoe) Varieties

    PubMed Central

    Ghasemzadeh, Ali; Jaafar, Hawa Z. E.; Karimi, Ehsan

    2012-01-01

    The effect of foliar application of salicylic acid (SA) at different concentrations (10−3 M and 10−5 M) was investigated on the production of secondary metabolites (flavonoids), chalcone synthase (CHS) activity, antioxidant activity and anticancer activity (against breast cancer cell lines MCF-7 and MDA-MB-231) in two varieties of Malaysian ginger, namely Halia Bentong and Halia Bara. The results of high performance liquid chromatography (HPLC) analysis showed that application of SA induced the synthesis of anthocyanin and fisetin in both varieties. Anthocyanin and fisetin were not detected in the control plants. Accordingly, the concentrations of some flavonoids (rutin and apigenin) decreased significantly in plants treated with different concentrations of SA. The present study showed that SA enhanced the chalcone synthase (CHS) enzyme activity (involving flavonoid synthesis) and recorded the highest activity value of 5.77 nkat /mg protein in Halia Bara with the 10−5 M SA treatment. As the SA concentration was decreased from 10−3 M to 10−5 M, the free radical scavenging power (FRAP) increased about 23% in Halia Bentong and 10.6% in Halia Bara. At a concentration of 350 μg mL−1, the DPPH antioxidant activity recorded the highest value of 58.30%–72.90% with the 10−5 M SA treatment followed by the 10−3 M SA (52.14%–63.66%) treatment. The lowest value was recorded in the untreated control plants (42.5%–46.7%). These results indicate that SA can act not only as an inducer but also as an inhibitor of secondary metabolites. Meanwhile, the highest anticancer activity against MCF-7 and MDA-MB-231 cell lines was observed for H. Bara extracts treated with 10−5 M SA with values of 61.53 and 59.88%, respectively. The results suggest that the high anticancer activity in these varieties may be related to the high concentration of potent anticancer components including fisetin and anthocyanin. The results thus indicate that the synthesis of flavonoids in

  3. Synthetic biology: mapping the scientific landscape.

    PubMed

    Oldham, Paul; Hall, Stephen; Burton, Geoff

    2012-01-01

    This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.

  4. Synthetic Biology: Mapping the Scientific Landscape

    PubMed Central

    Oldham, Paul; Hall, Stephen; Burton, Geoff

    2012-01-01

    This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves. PMID:22539946

  5. Effects of the Synthetic Neurosteroid

    PubMed Central

    Parésys, Lucie; Hoffmann, Kerstin; Bianchi, Massimiliano; Villey, Isabelle; Baulieu, Etienne-Emile; Fuchs, Eberhard

    2016-01-01

    Background: Most currently available active antidepressant drugs are selective serotonin/noradrenaline reuptake inhibitors. However, as their clinical efficacy is not immediate, long-term administration is often accompanied by substantial side effects, and numerous patients remain non- or partial responders. We have recently found that the synthetic neurosteroid derivative 3β-methoxypregnenolone, which binds to the microtubule-associated protein-2, can provide a novel therapeutic approach in experimental model of depressive disorders in rats. To further validate the antidepressant-like efficacy of 3β-methoxypregnenolone, we investigated effects of a longer treatment (4-week oral administration; 50mg/kg/d) in a nonrodent species, the tree shrew, exposed to psychosocial stress that elicits close-to-human alterations observed in patients with depressive disorders. Methods: During the experimental period, physiological parameters were registered, including core body temperature and electroencephalogram, while animals were videotaped to analyze their avoidance behavior. Morning urine samples were collected for measurements of cortisol and noradrenaline levels. Results: We found that treatment with 3β-methoxypregnenolone abolished stress-triggered avoidance behavior and prevented hormone hypersecretion, hypothermia, and sleep disturbances, further suggesting its antidepressant-like efficacy. Comparative treatment with fluoxetine also prevented some of the physiological alterations, while the hypersecretion of cortisol and sleep disturbances were not or partially restored by fluoxetine, suggesting a better efficacy of 3β-methoxypregnenolone. Alpha-tubulin isoforms were measured in hippocampi: we found that 3β-methoxypregnenolone reversed the specific decrease in acetylation of α-tubulin induced by psychosocial stress, while it did not modify the psychosocial stress-elicited reduction of tyrosinated α-tubulin. Conclusions: Taken together, these data strongly suggest

  6. Evaluating and Regulating Lead in Synthetic Turf

    PubMed Central

    Van Ulirsch, Gregory; Gleason, Kevin; Gerstenberger, Shawn; Moffett, Daphne B.; Pulliam, Glenn; Ahmed, Tariq; Fagliano, Jerald

    2010-01-01

    Background In 2007, a synthetic turf recreational field in Newark, New Jersey, was closed because lead was found in synthetic turf fibers and in surface dust at concentrations exceeding hazard criteria. Consequently, public health professionals across the country began testing synthetic turf to determine whether it represented a lead hazard. Currently, no standardized methods exist to test for lead in synthetic turf or to assess lead hazards. Objectives Our objectives were to increase awareness of potential lead exposure from synthetic turf by presenting data showing elevated lead in fibers and turf-derived dust; identify risk assessment uncertainties; recommend that federal and/or state agencies determine appropriate methodologies for assessing lead in synthetic turf; and recommend an interim standardized approach for sampling, interpreting results, and taking health-protective actions. Discussion Data collected from recreational fields and child care centers indicate lead in synthetic turf fibers and dust at concentrations exceeding the Consumer Product Safety Improvement Act of 2008 statutory lead limit of 300 mg/kg for consumer products intended for use by children, and the U.S. Environmental Protection Agency’s lead-dust hazard standard of 40 μg/ft2 for floors. Conclusions Synthetic turf can deteriorate to form dust containing lead at levels that may pose a risk to children. Given elevated lead levels in turf and dust on recreational fields and in child care settings, it is imperative that a consistent, nationwide approach for sampling, assessment, and action be developed. In the absence of a standardized approach, we offer an interim approach to assess potential lead hazards when evaluating synthetic turf. PMID:20884393

  7. Grand challenges in space synthetic biology

    PubMed Central

    Montague, Michael G.; Cumbers, John; Hogan, John A.

    2015-01-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  8. Grand challenges in space synthetic biology.

    PubMed

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-06

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth.

  9. Synthetic cathinones: chemical phylogeny, physiology, and neuropharmacology.

    PubMed

    De Felice, Louis J; Glennon, Richard A; Negus, Sidney S

    2014-02-27

    This mini-review summarizes the history of cathinone and its synthesized derivatives from early records to the present day, including the appearance of synthetic cathinones in the drug combination known as bath salts. Bath salts may consist of one compound (MDPV) or combinations of MDPV and one or more other synthetic cathinones, which may also appear alone without MDPV. We briefly review recent in vitro studies of bath salts components alone or in combination, focusing on pharmacological and biophysical studies. Finally we summarize new data from in vivo procedures that characterize the abuse-related neurochemical and behavioral effects of synthetic cathinones in rats.

  10. Synthetic promoter design for new microbial chassis

    PubMed Central

    Gilman, James; Love, John

    2016-01-01

    The judicious choice of promoter to drive gene expression remains one of the most important considerations for synthetic biology applications. Constitutive promoter sequences isolated from nature are often used in laboratory settings or small-scale commercial production streams, but unconventional microbial chassis for new synthetic biology applications require well-characterized, robust and orthogonal promoters. This review provides an overview of the opportunities and challenges for synthetic promoter discovery and design, including molecular methodologies, such as saturation mutagenesis of flanking regions and mutagenesis by error-prone PCR, as well as the less familiar use of computational and statistical analyses for de novo promoter design. PMID:27284035

  11. Enabling plant synthetic biology through genome engineering.

    PubMed

    Baltes, Nicholas J; Voytas, Daniel F

    2015-02-01

    Synthetic biology seeks to create new biological systems, including user-designed plants and plant cells. These systems can be employed for a variety of purposes, ranging from producing compounds of industrial or therapeutic value, to reducing crop losses by altering cellular responses to pathogens or climate change. To realize the full potential of plant synthetic biology, techniques are required that provide control over the genetic code - enabling targeted modifications to DNA sequences within living plant cells. Such control is now within reach owing to recent advances in the use of sequence-specific nucleases to precisely engineer genomes. We discuss here the enormous potential provided by genome engineering for plant synthetic biology.

  12. Synthetic Cathinones: Chemical Phylogeny, Physiology, and Neuropharmacology

    PubMed Central

    De Felice, Louis J; Glennon, Richard A; Negus, Sidney S

    2014-01-01

    This mini-review summarizes the history of cathinone and its synthesized derivatives from early records to the present day, including the appearance of synthetic cathinones in the drug combination known as bath salts. Bath salts may consist of one compound (MDPV) or combinations of MDPV and one or more other synthetic cathinones, which may also appear alone without MDPV. We briefly review recent in vitro studies of bath salts components alone or in combination, focusing on pharmacological and biophysical studies. Finally we summarize new data from in vivo procedures that characterize the abuse-related neurochemical and behavioral effects of synthetic cathinones in rats. PMID:24231923

  13. [Progress in synthetic biology of "973 Funding Program" in China].

    PubMed

    Chen, Guoqiang; Wang, Ying

    2015-06-01

    This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems.

  14. Directional synthetic aperture flow imaging.

    PubMed

    Jensen, Jørgen Arendt; Nikolov, Svetoslav Ivanov

    2004-09-01

    A method for flow estimation using synthetic aperture imaging and focusing along the flow direction is presented. The method can find the correct velocity magnitude for any flow angle, and full color flow images can be measured using only 32 to 128 pulse emissions. The approach uses spherical wave emissions with a number of defocused elements and a linear frequency-modulated pulse (chirp) to improve the signal-to-noise ratio. The received signals are dynamically focused along the flow direction and these signals are used in a cross-correlation estimator for finding the velocity magnitude. The flow angle is manually determined from the B-mode image. The approach can be used for both tissue and blood velocity determination. The approach was investigated using both simulations and a flow system with a laminar flow. The flow profile was measured with a commercial 7.5 MHz linear array transducer. A plastic tube with an internal diameter of 17 mm was used with an EcoWatt 1 pump generating a laminar, stationary flow. The velocity profile was measured for flow angles of 90 and 60 degrees. The RASMUS research scanner was used for acquiring radio frequency (RF) data from 128 elements of the array, using 8 emissions with 11 elements in each emission. A 20-micros chirp was used during emission. The RF data were subsequently beamformed off-line and stationary echo canceling was performed. The 60-degree flow with a peak velocity of 0.15 m/s was determined using 16 groups of 8 emissions, and the relative standard deviation was 0.36% (0.65 mm/s). Using the same setup for purely transverse flow gave a standard deviation of 1.2% (2.1 mm/s). Variation of the different parameters revealed the sensitivity to number of lines, angle deviations, length of correlation interval, and sampling interval. An in vivo image of the carotid artery and jugular vein of a healthy 29-year-old volunteer was acquired. A full color flow image using only 128 emissions could be made with a high

  15. Synthetic Aperture Radar Missions Study Report

    NASA Technical Reports Server (NTRS)

    Bard, S.

    2000-01-01

    This report reviews the history of the LightSAR project and summarizes actions the agency can undertake to support industry-led efforts to develop an operational synthetic aperture radar (SAR) capability in the United States.

  16. Synthetic biology between technoscience and thing knowledge.

    PubMed

    Gelfert, Axel

    2013-06-01

    Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation.

  17. Thermodynamic Analysis of Ionic Compounds: Synthetic Applications.

    ERIC Educational Resources Information Center

    Yoder, Claude H.

    1986-01-01

    Shows how thermodynamic cycles can be used to understand trends in heats of formation and aqueous solubilities and, most importantly, how they may be used to choose synthetic routes to new ionic compounds. (JN)

  18. Validation and acceptance of synthetic infrared imagery

    NASA Astrophysics Data System (ADS)

    Smith, Moira I.; Bernhardt, Mark; Angell, Christopher R.; Hickman, Duncan; Whitehead, Philip; Patel, Dilip

    2004-08-01

    This paper describes the use of an image query database (IQ-DB) tool as a means of implementing a validation strategy for synthetic long-wave infrared images of sea clutter. Specifically it was required to determine the validity of the synthetic imagery for use in developing and testing automatic target detection algorithms. The strategy adopted for exploiting synthetic imagery is outlined and the key issues of validation and acceptance are discussed in detail. A wide range of image metrics has been developed to achieve pre-defined validation criteria. A number of these metrics, which include post processing algorithms, are presented. Furthermore, the IQ-DB provides a robust mechanism for configuration management and control of the large volume of data used. The implementation of the IQ-DB is reviewed in terms of its cardinal point specification and its central role in synthetic imagery validation and EOSS progressive acceptance.

  19. Contour-Mapping Synthetic-Aperture Radar

    NASA Technical Reports Server (NTRS)

    Goldstein, R. M.; Caro, E. R.; Wu, C.

    1985-01-01

    Airborne two-antenna synthetic-aperture-radar (SAR) interferometric system provides data processed to yield terrain elevation as well as reflectedintensity information. Relative altitudes of terrain points measured to within error of approximately 25 m.

  20. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

    2013-01-08

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  1. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi; Ganguly, Kumkum; Silks, Louis A

    2011-12-06

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  2. Convergent Replication of Mouse Synthetic Prion Strains

    PubMed Central

    Ghaemmaghami, Sina; Colby, David W.; Nguyen, Hoang-Oanh B.; Hayashi, Shigenari; Oehler, Abby; DeArmond, Stephen J.; Prusiner, Stanley B.

    2014-01-01

    Prion diseases are neurodegenerative disorders characterized by the aberrant folding of endogenous proteins into self-propagating pathogenic conformers. Prion disease can be initiated in animal models by inoculation with amyloid fibrils formed from bacterially derived recombinant prion protein. The synthetic prions that accumulated in infected organisms are structurally distinct from the amyloid preparations used to initiate their formation and change conformationally on repeated passage. To investigate the nature of synthetic prion transformation, we infected mice with a conformationally diverse set of amyloids and serially passaged the resulting prion strains. At each passage, we monitored changes in the biochemical and biological properties of the adapting strain. The physicochemical properties of each synthetic prion strain gradually changed on serial propagation until attaining a common adapted state with shared physicochemical characteristics. These results indicate that synthetic prions can assume multiple intermediate conformations before converging into one conformation optimized for in vivo propagation. PMID:23438476

  3. Synthetic biology platform technologies for antimicrobial applications.

    PubMed

    Braff, Dana; Shis, David; Collins, James J

    2016-10-01

    The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels.

  4. The emerging world of synthetic genetics.

    PubMed

    Chaput, John C; Yu, Hanyang; Zhang, Su

    2012-11-21

    For over 20 years, laboratories around the world have been applying the principles of Darwinian evolution to isolate DNA and RNA molecules with specific ligand-binding or catalytic activities. This area of synthetic biology, commonly referred to as in vitro genetics, is made possible by the availability of natural polymerases that can replicate genetic information in the laboratory. Moving beyond natural nucleic acids requires organic chemistry to synthesize unnatural analogues and polymerase engineering to create enzymes that recognize artificial substrates. Progress in both of these areas has led to the emerging field of synthetic genetics, which explores the structural and functional properties of synthetic genetic polymers by in vitro evolution. This review examines recent advances in the Darwinian evolution of artificial genetic polymers and their potential downstream applications in exobiology, molecular medicine, and synthetic biology.

  5. Synthetic Core Promoters for Pichia pastoris

    PubMed Central

    2013-01-01

    Synthetic promoters are commonly used tools for circuit design or high level protein production. Promoter engineering efforts in yeasts, such as Saccharomyces cerevisiae and Pichia pastoris have mostly been focused on altering upstream regulatory sequences such as transcription factor binding sites. In higher eukaryotes synthetic core promoters, directly needed for transcription initiation by RNA Polymerase II, have been successfully designed. Here we report the first synthetic yeast core promoter for P. pastoris, based on natural yeast core promoters. Furthermore we used this synthetic core promoter sequence to engineer the core promoter of the natural AOX1 promoter, thereby creating a set of core promoters providing a range of different expression levels. As opposed to engineering strategies of the significantly longer entire promoter, such short core promoters can directly be added on a PCR primer facilitating library generation and are sufficient to obtain variable expression yields. PMID:24187969

  6. Microfluidic technologies for studying synthetic circuits.

    PubMed

    Lin, Benjamin; Levchenko, Andre

    2012-08-01

    Advances in synthetic biology have augmented the available toolkit of biomolecular modules, allowing engineering and manipulation of signaling in a variety of organisms, ranging in complexity from single bacteria and eukaryotic cells to multi-cellular systems. The richness of synthetic circuit outputs can be dramatically enhanced by sophisticated environmental control systems designed to precisely pattern spatial-temporally heterogeneous environmental stimuli controlling these circuits. Moreover, the performance of the synthetic modules and 'blocks' needed to assemble more complicated networks requires more complete characterization as a function of arbitrarily complex environmental inputs. Microfluidic technologies are poised to meet these needs through a variety of innovative designs capitalizing on the unique benefits of manipulating fluids on the micro-scales and nano-scales. This review discusses the utility of microfluidics for the study of synthetic circuits and highlights recent work in the area.

  7. Elevated gene expression in chalcone synthase enzyme suggests an increased production of flavonoids in skin and synchronized red cell cultures of North American native grape berries.

    PubMed

    Davis, Gina; Ananga, Anthony; Krastanova, Stoyanka; Sutton, Safira; Ochieng, Joel W; Leong, Stephen; Tsolova, Violetka

    2012-06-01

    Anthocyanins are antioxidants and are among the natural products synthesized via the flavonoid biosynthesis pathway. Anthocyanins have been recommended for dietary intake in the prevention of cardiovascular diseases, cancer, and age-related conditions such as Alzheimer's disease or dementia. With an increasingly aging population in many parts of the world, strategies for the commercial production of in vitro synchronized red cell cultures as natural antioxidants will be a significant contribution to human medicine. Red pigmented fruits such as grapes (Vitis sp.) are a major source of bioavailable anthocyanins and other polyphenols. Since the level of antioxidants varies among cultivars, this study is the first one that phytochemically and genetically characterizes native grape cultivars of North America to determine the optimal cultivar and berry cells for the production of anthocyanins as antioxidants. Using real-time PCR and bioinformatics approaches, we tested for the transcript expression of the chalcone synthase (CHS) gene, an enzyme involved in the flavonoid and anthocyanin biosynthesis pathway, in different parts of physiologically mature grape berries and in vitro synchronized red cells. A low level of expression was recorded in berry flesh, compared with an elevated expression in berry skins and in vitro synchronized red cells, suggesting increased production of flavonoids in skin and cell cultures. This preliminary study demonstrates the potential of functional genomics in natural products research as well as in systematic studies of North American native grapes, specifically in muscadine (Vitis rotundifolia).

  8. Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri.

    PubMed

    Yang, Mingbo; Li, Na; Li, Fang; Zhu, Qianqian; Liu, Xi; Han, Qunying; Wang, Yawen; Chen, Yanping; Zeng, Xiaoyan; Lv, Yi; Zhang, Pingping; Yang, Cuiling; Liu, Zhengwen

    2013-08-01

    Hepatitis C virus (HCV) infection in Tupaia belangeri (Tupaia) represents an important model of HCV infection. Xanthohumol (XN), a major prenylated chalcone from hops, has various biological activities including hepatopreventive and anti-viral activities. In this study, Tupaias infected with HCV RNA positive serum were used to evaluate the effects of XN on liver damage, oxidative reaction, apoptosis and viral protein expression in liver tissues. The Tupaias inoculated with HCV positive serum had elevated serum aminotransferase levels and inflammation, especially hepatic steatosis, and HCV core protein expression in liver tissue. In the animals inoculated with HCV positive serum, XN significantly decreased aminotransferase levels, histological activity index, hepatic steatosis score and transforming growth factor β1 expression in liver tissue compared with the animals without XN intervention. XN reduced HCV core protein expression in liver tissue compared with those without XN intervention but the difference was not significant. XN significantly decreased malondialdehyde, potentiated superoxide dismutase and glutathione peroxidase, reduced Bax expression, promoted Bcl-xL and inhibited caspase 3 activity in liver tissues compared with the animals without XN intervention. These results indicate that XN may effectively improve hepatic inflammation, steatosis and fibrosis induced by HCV in Tupaias primarily through inhibition of oxidative reaction and regulation of apoptosis and possible suppression of hepatic stellate cell activation. The anti-HCV potential of XN needs further investigation.

  9. Synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities.

    PubMed

    Kant, Rama; Kumar, Dharmendra; Agarwal, Drishti; Gupta, Rinkoo Devi; Tilak, Ragini; Awasthi, Satish Kumar; Agarwal, Alka

    2016-05-04

    The present study was carried out in an attempt to synthesize a new class of antimicrobial and antiplasmodial agents by copper catalyzed click chemistry to afford 25 compounds 10-14(a-e) of 1,4-disubstituted-1,2,3-triazole derivatives of chalcones and flavones. The structures of the newly synthesized compounds were established by elemental analysis, IR, (1)H NMR, (13)C NMR and Mass spectral data. The newly synthesized compounds were evaluated for their antibacterial activity against Gram positive bacteria (Staphylococcus aureus, Enterococcus faecalis), Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Shigella boydii, Klebsiella pneumoniae) and antifungal activity against (Candida albicans, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Dermatophyte) as well as molds (Aspergillus niger, Aspergillus fumigatus). The antiplasmodial and cytotoxic activities of these compounds were also evaluated against human malaria parasite Plasmodium falciparum strain 3D7 and human hepato-cellular carcinoma cells (Huh-7), respectively. Compounds 10a, 10c, 10d, 12c and 14e showed promising antibacterial activity while compounds 10e, 11d, 11e, 12c, 13a, 13b, 13e, 14a and 14d showed good antifungal activity as compared to the corresponding standard drugs. Compound 10b was found to be the most active against Plasmodium falciparum while the remaining compounds showed moderate to weak antiplasmodial activity. However, cytotoxic activities of all compounds were found ineffective against Huh-7 cells.

  10. PpASCL, a moss ortholog of anther-specific chalcone synthase-like enzymes, is a hydroxyalkylpyrone synthase involved in an evolutionarily conserved sporopollenin biosynthesis pathway.

    PubMed

    Colpitts, Che C; Kim, Sung Soo; Posehn, Sarah E; Jepson, Christina; Kim, Sun Young; Wiedemann, Gertrud; Reski, Ralf; Wee, Andrew G H; Douglas, Carl J; Suh, Dae-Yeon

    2011-12-01

    Sporopollenin is the main constituent of the exine layer of spore and pollen walls. Recently, several Arabidopsis genes, including polyketide synthase A (PKSA), which encodes an anther-specific chalcone synthase-like enzyme (ASCL), have been shown to be involved in sporopollenin biosynthesis. The genome of the moss Physcomitrella patens contains putative orthologs of the Arabidopsis sporopollenin biosynthesis genes. We analyzed available P.patens expressed sequence tag (EST) data for putative moss orthologs of the Arabidopsis genes of sporopollenin biosynthesis and studied the enzymatic properties and reaction mechanism of recombinant PpASCL, the P.patens ortholog of Arabidopsis PKSA. We also generated structure models of PpASCL and Arabidopsis PKSA to study their substrate specificity. Physcomitrella patens orthologs of Arabidopsis genes for sporopollenin biosynthesis were found to be expressed in the sporophyte generation. Similarly to Arabidopsis PKSA, PpASCL condenses hydroxy fatty acyl-CoA esters with malonyl-CoA and produces hydroxyalkyl α-pyrones that probably serve as building blocks of sporopollenin. The ASCL-specific set of Gly-Gly-Ala residues predicted by the models to be located at the floor of the putative active site is proposed to serve as the opening of an acyl-binding tunnel in ASCL. These results suggest that ASCL functions together with other sporophyte-specific enzymes to provide polyhydroxylated precursors of sporopollenin in a pathway common to land plants.

  11. Synthesis, spectral behaviour and photophysics of donor-acceptor kind of chalcones: Excited state intramolecular charge transfer and fluorescence quenching studies

    NASA Astrophysics Data System (ADS)

    Pannipara, Mehboobali; Asiri, Abdullah M.; Alamry, Khalid A.; Arshad, Muhammad N.; El-Daly, Samy A.

    2015-02-01

    The spectral and photophysical properties of two chalcones containing electron donating and accepting groups with intramolecular charge transfer characteristics were synthesized and characterized by 1H NMR, 13C NMR and X-ray crystallography. Both compounds show very strong solvent polarity dependent changes in their photophysical characteristics, namely, remarkable red shift in the emission spectra with increasing solvent polarity, large change in Stokes shift, significant reduction in the fluorescence quantum yield; indicating that the fluorescence states of these compounds are of intramolecular charge transfer (ICT) character. The solvent effect on the photophysical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment, fluorescence spectra, and fluorescence quantum yield of both compounds have been investigated comprehensively. For both dyes, Lippert-Mataga and Reichardt's correlations were used to estimate the difference between the excited and ground state dipole moments (Δμ). The interactions of dyes with colloidal silver nanoparticles (Ag NPs) were also studied in ethanol using steady state fluorescence quenching measurements. The fluorescence quenching data reveal that dynamic quenching and energy transfer play a major role in the fluorescence quenching of dyes by Ag NPs.

  12. Benzophenone synthase and chalcone synthase from Hypericum androsaemum cell cultures: cDNA cloning, functional expression, and site-directed mutagenesis of two polyketide synthases.

    PubMed

    Liu, Benye; Falkenstein-Paul, Hildegard; Schmidt, Werner; Beerhues, Ludger

    2003-06-01

    Benzophenone derivatives, such as polyprenylated benzoylphloroglucinols and xanthones, are biologically active secondary metabolites. The formation of their C13 skeleton is catalyzed by benzophenone synthase (BPS; EC 2.3.1.151) that has been cloned from cell cultures of Hypericum androsaemum. BPS is a novel member of the superfamily of plant polyketide synthases (PKSs), also termed type III PKSs, with 53-63% amino acid sequence identity. Heterologously expressed BPS was a homodimer with a subunit molecular mass of 42.8 kDa. Its preferred starter substrate was benzoyl-CoA that was stepwise condensed with three malonyl-CoAs to give 2,4,6-trihydroxybenzophenone. BPS did not accept activated cinnamic acids as starter molecules. In contrast, recombinant chalcone synthase (CHS; EC 2.3.1.74) from the same cell cultures preferentially used 4-coumaroyl-CoA and also converted CoA esters of benzoic acids. The enzyme shared 60.1% amino acid sequence identity with BPS. In a phylogenetic tree, the two PKSs occurred in different clusters. One cluster was formed by CHSs including the one from H. androsaemum. BPS grouped together with the PKSs that functionally differ from CHS. Site-directed mutagenesis of amino acids shaping the initiation/elongation cavity of CHS yielded a triple mutant (L263M/F265Y/S338G) that preferred benzoyl-CoA over 4-coumaroyl-CoA.

  13. Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives

    PubMed Central

    2015-01-01

    On the basis of recently reported abyssinone II and olympicin A, a series of chemically modified flavonoid phytochemicals were synthesized and evaluated against Mycobacterium tuberculosis and a panel of Gram-positive and -negative bacterial pathogens. Some of the synthesized compounds exhibited good antibacterial activities against Gram-positive pathogens including methicillin resistant Staphylococcus aureus with minimum inhibitory concentration as low as 0.39 μg/mL. SAR analysis revealed that the 2-hydrophobic substituent and the 4-hydrogen bond donor/acceptor of the 4-chromanone scaffold together with the hydroxy groups at 5- and 7-positions enhanced antibacterial activities; the 2′,4′-dihydroxylated A ring and the lipophilic substituted B ring of chalcone derivatives were pharmacophoric elements for antibacterial activities. Mode of action studies performed on selected compounds revealed that they dissipated the bacterial membrane potential, resulting in the inhibition of macromolecular biosynthesis; further studies showed that selected compounds inhibited DNA topoisomerase IV, suggesting complex mechanisms of actions for compounds in this series. PMID:25238443

  14. Synthesis, characterization and biological activities of some Ru(II) complexes with substituted chalcones and their applications as chemotherapeutics against breast cancer

    NASA Astrophysics Data System (ADS)

    Singh, Ashok K.; Saxena, Gunjan; Dixit, Shivani; Hamidullah; Singh, Sachin K.; Singh, Sudheer K.; Arshad, M.; Konwar, Rituraj

    2016-05-01

    Four new Ru(II) DMSO complexes with substituted chalcone ligands viz. (E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (HL1), (E)-1-(2-hydroxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HL2), (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (HL3) and (E)-1-(2-hydroxyphenyl)-3-(4-Chlorophenyl)prop-2-en-1-one (HL4) have been synthesized, and characterized by micro-analyses, IR, 1H NMR, UV-Vis and ESI-MS and screened for anti-cancer activity against breast cancer cell lines (MCF-7 and MDA MB-231). Compounds HL4 and [Ru(HL1) (O-DMSO)3(S-DMSO)]Cl (M1R) showed significant anti-breast cancer activity as evident from cytotoxicity, morphological and nuclear changes, DNA fragmentation and cell cycle arrest in breast cancer cells. UV-Vis and CD-spectra analysis showed HL4 and M1R interfered with DNA absorption spectra possibly due to DNA binding whereas these compounds were devoid of DNA topoisomerase inhibiting activity. Thus, these Ru(II) compounds have been established as new leads for future optimization by improving anti-cancer potency and safety.

  15. Chalcone Synthase (CHS) Gene Suppression in Flax Leads to Changes in Wall Synthesis and Sensing Genes, Cell Wall Chemistry and Stem Morphology Parameters

    PubMed Central

    Zuk, Magdalena; Działo, Magdalena; Richter, Dorota; Dymińska, Lucyna; Matuła, Jan; Kotecki, Andrzej; Hanuza, Jerzy; Szopa, Jan

    2016-01-01

    The chalcone synthase (CHS) gene controls the first step in the flavonoid biosynthesis. In flax, CHS down-regulation resulted in tannin accumulation and reduction in lignin synthesis, but plant growth was not affected. This suggests that lignin content and thus cell wall characteristics might be modulated through CHS activity. This study investigated the possibility that CHS affects cell wall sensing as well as polymer content and arrangement. CHS-suppressed and thus lignin-reduced plants showed significant changes in expression of genes involved in both synthesis of components and cell wall sensing. This was accompanied by increased levels of cellulose and hemicellulose. CHS-reduced flax also showed significant changes in morphology and arrangement of the cell wall. The stem tissue layers were enlarged averagely twofold compared to the control, and the number of fiber cells more than doubled. The stem morphology changes were accompanied by reduction of the crystallinity index of the cell wall. CHS silencing induces a signal transduction cascade that leads to modification of plant metabolism in a wide range and thus cell wall structure. PMID:27446124

  16. What's so Hot About Formulated Synthetics?

    NASA Technical Reports Server (NTRS)

    Beerbower, A.

    1984-01-01

    The development of synthetic automotive engine oil is discussed. The history of synthetic lubricants, and of the additives required to compete in a market which developed by and for petroleum oils. Some examples of real data, and enlarged using heat transfer properties obtained by chemical engineering thermodynamic methods are shown. The prospects for future successes and ideas on the additives that would most help to bring them about are also presented.

  17. Synthetic antiferromagnetic nanoparticles with tunable susceptibilities

    PubMed Central

    Hu, Wei; Wilson, Robert J.; Earhart, Christopher M.; Koh, Ai Leen; Sinclair, Robert; Wang, Shan X.

    2009-01-01

    High-moment monodisperse disk-shaped Co–Fe magnetic nanoparticles, stable in aqueous solution, were physically fabricated by using nanoimprinted templates and vacuum deposition techniques. These multilayer synthetic antiferromagnetic nanoparticles exhibit nearly zero magnetic remanence and coercivity, and susceptibilities which can be tuned by exploiting interlayer magnetic interactions. In addition, a low cost method of scaling up the production of sub-100 nm synthetic antiferromagnetic nanoparticles is demonstrated. PMID:19529797

  18. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  19. Synthetic CO.sub.2 acceptor

    DOEpatents

    Lancet, Michael S.; Curran, George P.

    1981-08-18

    A synthetic CO.sub.2 acceptor consisting essentially of at least one compound selected from the group consisting of calcium oxide and calcium carbonate supported in a refractory carrier matrix, the carrier having the general formula Ca.sub.5 (SiO.sub.4).sub.2 CO.sub.3. A method for producing the synthetic CO.sub.2 acceptor is also disclosed.

  20. Synthetic Sling Failure - Evaluations and Recommendations

    SciTech Connect

    Henderson, C. S.; Mackey, Thomas C.

    2009-10-26

    The information and evaluations provided in this report were compiled to address the recurring problem of synthetic sling failure. As safety is the number one priority in all work aspects, a solution must be devised to prevent accidents from occurring. A total of thirteen cases regarding synthetic sling failure were evaluated in order to determine their causes, effects, and preventative measures. From the collected data, it was found that all cases in which the synthetic sling contacted the edge of its load resulted in sling failure. It is required that adequate synthetic sling protection devices be used to protect slings in any lift where the sling comes in direct contact with the edge or corner of its load. However, there are no consensus codes or standards stating the type, material, or purpose of the type of protective device used to protect the sling from being cut. Numerous industry standards and codes provide vague descriptions on how to protect synthetic slings. Without a clear, concise statement of how to protect synthetic slings, it is common for inadequate materials and sling protection devices to be used in an attempt to meet the intent of these requirements. The use of an inadequate sling protection device is the main cause of synthetic sling failure in all researched cases. Commercial sling protection devices come in many shapes and sizes, and have a variety of names, as well as advertised uses. 'Abrasion pads' and 'wear protectors' are two different names for products with the same intended purpose. There is no distinguishable way to determine the extent of sling protection which these devices will provide, or what specific scenarios they are made for. This creates room for error in a field where error is unacceptable. This report provides a recommended action for hoisting and rigging activities which require synthetic slings to contact a load, as well as recommended changes to industry standards which will benefit overall industry safety.

  1. [On health regulation of synthetic detergents].

    PubMed

    Frolova, A D; Sidorin, G I; Lukovnikova, L V; Skhodkina, N I; D'iakova, L I; Shaposhnikova, E S

    1999-01-01

    The authors present materials on hygienic regulation of such synthetic detergents as "Losk", "Dixan" in air of workplace and populated area, demonstrate results concerning evaluation of "Losk" effects. Discussion covers ways to evaluate chemical load caused by simultaneous emission of synthetic detergents from various environmental objects. For testing reliability of hygienic regulation for complex emission exemplified by "Losk", the authors suggest a model for express evaluation of complex exposure to chemicals.

  2. Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry

    PubMed Central

    Harris, D. Calvin; Jewett, Michael C.

    2014-01-01

    Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology for synthetic chemistry and using synthetic chemistry to reprogram or mimic biology. In the coming years, the impact of advances inspired by these approaches will make possible the synthesis of non-biological polymers having new backbone compositions, new chemical properties, new structures, and new functions. PMID:22483202

  3. The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

    PubMed

    Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

    2014-06-01

    The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

  4. Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry.

    PubMed

    Harris, D Calvin; Jewett, Michael C

    2012-10-01

    Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology for synthetic chemistry and using synthetic chemistry to reprogram or mimic biology. In the coming years, the impact of advances inspired by these approaches will make possible the synthesis of nonbiological polymers having new backbone compositions, new chemical properties, new structures, and new functions.

  5. Synthetic cannabinoids and potential reproductive consequences.

    PubMed

    Sun, Xiaofei; Dey, Sudhansu K

    2014-02-27

    Increases in emergency room visits due to abuse of designer drugs, popularly known by the street names "K2" and "Spice," are a cause for social, judicial, and clinical concerns. The psychoactive components in these herbal drugs mainly consist of different synthetic cannabinoids, and users of these street drugs are primarily within the age group of 12 to 20years old. The abusive use of synthetic cannabinoids results in anxiety, nausea, vomiting, tachycardia, elevated blood pressure, tremors, seizures, hallucinations, and paranoid behavior, but the effects of maternal use of synthetic cannabinoids during pregnancy are ambiguous due to limited studies in humans and a relative short history of the drugs. In this review, we discuss the known and potential adverse effects of synthetic cannabinoids on human pregnancy using knowledge gathered from studies in mice and limited studies in humans. In mice, multiple sites and stages of pregnancy are potential targets of synthetic cannabinoids, including preimplantation embryo development, oviductal embryo transport, implantation, placentation, and parturition. It is anticipated that maternal use of synthetic cannabinoids would result in severely compromised female fertility and pregnancy outcome.

  6. How to make a synthetic multicellular computer.

    PubMed

    Macia, Javier; Sole, Ricard

    2014-01-01

    Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined.

  7. Biomedical synthetic biology: an overview for physicians.

    PubMed

    Keret, Ophir

    2013-06-01

    Synthetic bioiogy is a ,relatively new fieild of bologlcal research and development that focases on the engineering of genetic molecular machlnes wIth a specific predefined function. Plainly put the newly engineered organism functions as a machine. It can process information. manufature, heal and even diagnose. We just have to engineer It to do so. The famous quote "Biology Is the nanotechnology that works" is currently being put to the test on a worldwide scale. The application of these machines Is theoretically boundless. In laboratories worldwide synthetic biology technologies are being rationally designed to assist in diagnosis or disrupt disease mechnisms. In the not too distant future they are expected to reach the clinical setting. This new field should be distinguished from classic genetic engineering. The latter researches naturalfy found DNA segments via cloning. It is weakly associated with engineering. Synthetic biology focuses on the engineering of molecular biological machines for the benefit of mankind. This is done via synthetic (computer printed) DNA sequences, man-designed or altered in silico. In this article I will briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an independent fast-growing synthetic biology-sharing movement, and report on selected developing applications for medicine.

  8. Synthetic biology era: Improving antibiotic's world.

    PubMed

    Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

    2017-01-31

    The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge.

  9. Synthetic jet actuation for load control

    NASA Astrophysics Data System (ADS)

    de Vries, H.; van der Weide, E. T. A.; Hoeijmakers, H. W. M.

    2014-12-01

    The reduction of wind turbine blade loads is an important issue in the reduction of the costs of energy production. Reduction of the loads of a non-cyclic nature requires so-called smart rotor control, which involves the application of distributed actuators and sensors to provide fast and local changes in aerodynamic performance. This paper investigates the use of synthetic jets for smart rotor control. Synthetic jets are formed by ingesting low-momentum fluid from the boundary layer along the blade into a cavity and subsequently ejecting this fluid with a higher momentum. We focus on the observed flow phenomena and the ability to use these to obtain the desired changes of the aerodynamic properties of a blade section. To this end, numerical simulations and wind tunnel experiments of synthetic jet actuation on a non-rotating NACA0018 airfoil have been performed. The synthetic jets are long spanwise slits, located close to the trailing edge and directed perpendicularly to the surface of the airfoil. Due to limitations of the present experimental setup in terms of performance of the synthetic jets, the main focus is on the numerical flow simulations. The present results show that high-frequency synthetic jet actuation close to the trailing edge can induce changes in the effective angle of attack up to approximately 2.9°.

  10. The Fifth Annual Sc2.0 and Synthetic Genomes Conference: Synthetic Genomes in High Gear.

    PubMed

    Walker, Roy S K; Cai, Yizhi

    2016-09-16

    The Sc2.0 project is perhaps the largest synthetic biology project in the public domain, and ultimately aims to construct a new version of the humble brewer's yeast, Saccharomyces cerevisiae. Each year, the Sc2.0 consortium gather to discuss progress in this ambitious project and highlight new developments at the forefront of synthetic genome engineering. This viewpoint summarizes some of the key moments of the 2016 conference, including updates on the Sc2.0 project itself, mammalian synthetic biology, DNA assembly automation, HGP-Write and a panel discussion on the social and ethical perspectives of synthetic biology.

  11. 21 CFR 73.1200 - Synthetic iron oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  12. 21 CFR 73.1200 - Synthetic iron oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  13. 21 CFR 73.200 - Synthetic iron oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Synthetic iron oxide. 73.200 Section 73.200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  14. 21 CFR 73.1200 - Synthetic iron oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  15. 21 CFR 73.1200 - Synthetic iron oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  16. 21 CFR 73.1200 - Synthetic iron oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  17. 21 CFR 73.200 - Synthetic iron oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.200 Section 73.200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically...

  18. 21 CFR 172.888 - Synthetic petroleum wax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Synthetic petroleum wax. 172.888 Section 172.888... Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is a mixture of solid hydrocarbons, paraffinic in...

  19. 21 CFR 172.888 - Synthetic petroleum wax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is...

  20. 21 CFR 172.888 - Synthetic petroleum wax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is...

  1. 21 CFR 172.888 - Synthetic petroleum wax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is...

  2. 21 CFR 172.888 - Synthetic petroleum wax.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is...

  3. WISB: Warwick Integrative Synthetic Biology Centre

    PubMed Central

    McCarthy, John

    2016-01-01

    Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary ‘build to apply’ and ‘build to understand’ approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia. PMID:27284024

  4. Synthetic biology and the technicity of biofuels.

    PubMed

    Mackenzie, Adrian

    2013-06-01

    The principal existing real-world application of synthetic biology is biofuels. Several 'next generation biofuel' companies-Synthetic Genomics, Amyris and Joule Unlimited Technologies-claim to be using synthetic biology to make biofuels. The irony of this is that highly advanced science and engineering serves the very mundane and familiar realm of transport. Despite their rather prosaic nature, biofuels could offer an interesting way to highlight the novelty of synthetic biology from several angles at once. Drawing on the French philosopher of technology and biology Gilbert Simondon, we can understand biofuels as technical objects whose genesis involves processes of concretisation that negotiate between heterogeneous geographical, biological, technical, scientific and commercial realities. Simondon's notion of technicity, the degree of concretisation of a technical object, usefully conceptualises this relationality. Viewed in terms of technicity, we might understand better how technical entities, elements, and ensembles are coming into being in the name of synthetic biology. The broader argument here is that when we seek to identify the newness of disciplines, their newness might be less epistemic and more logistic.

  5. Synthetic cathinones: a new public health problem.

    PubMed

    Karila, Laurent; Megarbane, Bruno; Cottencin, Olivier; Lejoyeux, Michel

    2015-01-01

    New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "mephedrone", "methylone", "MDPV", "4-MEC", "addiction", and "substance use disorder".

  6. [Treatment approaches for synthetic drug addiction].

    PubMed

    Kobayashi, Ohji

    2015-09-01

    In Japan, synthetic drugs have emerged since late 2000s, and cases of emergency visits and fatal traffic accidents due to acute intoxication have rapidly increased. The synthetic drugs gained popularity mainly because they were cheap and thought to be "legal". The Japanese government restricted not only production and distribution, but also its possession and use in April 2014. As the synthetic drug dependent patients have better social profiles compared to methamphetamine abusers, this legal sanction may have triggered the decrease in the number of synthetic drug dependent patient visits observed at Kanagawa Psychiatric Center since July 2014. Treatment of the synthetic drug dependent patients should begin with empathic inquiry into the motives and positive psychological effects of the drug use. In the maintenance phase, training patients to trust others and express their hidden negative emotions through verbal communications is essential. The recovery is a process of understanding the relationship between psychological isolation and drug abuse, and gaining trust in others to cope with negative emotions that the patients inevitably would face in their subsequent lives.

  7. Is It Time for Synthetic Biodiversity Conservation?

    PubMed

    Piaggio, Antoinette J; Segelbacher, Gernot; Seddon, Philip J; Alphey, Luke; Bennett, Elizabeth L; Carlson, Robert H; Friedman, Robert M; Kanavy, Dona; Phelan, Ryan; Redford, Kent H; Rosales, Marina; Slobodian, Lydia; Wheeler, Keith

    2017-02-01

    Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.

  8. Parity-Time Synthetic Phononic Media

    NASA Astrophysics Data System (ADS)

    Christensen, J.; Willatzen, M.; Velasco, V. R.; Lu, M.-H.

    2016-05-01

    Classical systems containing cleverly devised combinations of loss and gain elements constitute extremely rich building units that can mimic non-Hermitian properties, which conventionally are attainable in quantum mechanics only. Parity-time (P T ) symmetric media, also referred to as synthetic media, have been devised in many optical systems with the ground breaking potential to create nonreciprocal structures and one-way cloaks of invisibility. Here we demonstrate a feasible approach for the case of sound where the most important ingredients within synthetic materials, loss and gain, are achieved through electrically biased piezoelectric semiconductors. We study first how wave attenuation and amplification can be tuned, and when combined, can give rise to a phononic P T synthetic media with unidirectional suppressed reflectance, a feature directly applicable to evading sonar detection.

  9. Light-activated communication in synthetic tissues

    PubMed Central

    Booth, Michael J.; Schild, Vanessa Restrepo; Graham, Alexander D.; Olof, Sam N.; Bayley, Hagan

    2016-01-01

    We have previously used three-dimensional (3D) printing to prepare tissue-like materials in which picoliter aqueous compartments are separated by lipid bilayers. These printed droplets are elaborated into synthetic cells by using a tightly regulated in vitro transcription/translation system. A light-activated DNA promoter has been developed that can be used to turn on the expression of any gene within the synthetic cells. We used light activation to express protein pores in 3D-printed patterns within synthetic tissues. The pores are incorporated into specific bilayer interfaces and thereby mediate rapid, directional electrical communication between subsets of cells. Accordingly, we have developed a functional mimic of neuronal transmission that can be controlled in a precise way. PMID:27051884

  10. Sustainability, synthetic chemicals, and human exposure.

    PubMed

    Podein, Rian J; Hernke, Michael T; Fortney, Luke W; Rakel, David P

    2010-01-01

    Public concerns regarding exposures to synthetic chemicals are increasing. Globally, there are increasing concentrations of many synthetic chemicals within the environment. The ubiquitous extent of some chemicals makes human exposure unavoidable. Biomonitoring has emerged as the optimal method for assessing exposures. The extent of human exposure and contamination occurs throughout the life cycle and is widespread. Although there is limited information on health risks for the majority of chemicals within our environment, and those identified with biomonitoring, many are known or suspected to cause human harm. Continued global and national unsustainable development regarding synthetic chemicals will increase the extent of environmental and human contamination unless precautionary action is implemented. Precautionary legislation may protect ecological and public health until societal sustainability is achieved.

  11. Network Reverse Engineering Approach in Synthetic Biology

    NASA Astrophysics Data System (ADS)

    Zhang, Haoqian; Liu, Ao; Lu, Yuheng; Sheng, Ying; Wu, Qianzhu; Yin, Zhenzhen; Chen, Yiwei; Liu, Zairan; Pan, Heng; Ouyang, Qi

    2013-12-01

    Synthetic biology is a new branch of interdisciplinary science that has been developed in recent years. The main purpose of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to develop basic biological functional modules, and through rational design, develop man-made biological systems that have predicted useful functions. Here, we discuss an important principle in rational design of functional biological circuits: the reverse engineering design. We will use a research project that was conducted at Peking University for the International Genetic Engineering Machine Competition (iGEM) to illustrate the principle: synthesis a cell which has a semi-log dose-response to the environment. Through this work we try to demonstrate the potential application of network engineering in synthetic biology.

  12. Computational Modeling And Analysis Of Synthetic Jets

    NASA Technical Reports Server (NTRS)

    Mittal, Rajat; Cattafesta, Lou

    2005-01-01

    In the last report we focused on the study of 3D synthetic jets of moderate jet aspect-ratio. Jets in quiescent and cross-flow cases were investigated. Since most of the synthetic jets in practical applications are found to be of large aspect ratio, the focus was shifted to studying synthetic jets of large aspect ratio. In the current year, further progress has been made by studying jets of aspect ratio 8 and infinity. Some other aspects of the jet, like the vorticity flux is looked into apart from analyzing the vortex dynamics, velocity profiles and the other dynamical characteristics of the jet which allows us to extract some insight into the effect of these modifications on the jet performance. Also, efforts were made to qualitatively validate the simulated results with the NASA Langley test cases at higher jet Reynolds number for the quiescent jet case.

  13. Parity-Time Synthetic Phononic Media.

    PubMed

    Christensen, J; Willatzen, M; Velasco, V R; Lu, M-H

    2016-05-20

    Classical systems containing cleverly devised combinations of loss and gain elements constitute extremely rich building units that can mimic non-Hermitian properties, which conventionally are attainable in quantum mechanics only. Parity-time (PT) symmetric media, also referred to as synthetic media, have been devised in many optical systems with the ground breaking potential to create nonreciprocal structures and one-way cloaks of invisibility. Here we demonstrate a feasible approach for the case of sound where the most important ingredients within synthetic materials, loss and gain, are achieved through electrically biased piezoelectric semiconductors. We study first how wave attenuation and amplification can be tuned, and when combined, can give rise to a phononic PT synthetic media with unidirectional suppressed reflectance, a feature directly applicable to evading sonar detection.

  14. Synthetic polymer-layer silicate clay composites

    SciTech Connect

    Carrado, K.A.; Elder, D.L.; Thiyagarajan, P.

    1995-07-01

    Synthetic hectorites were hydrothermally crystallized with direct incorporation of water-soluble polyvinyl alcohol (PVA), a cationic polymer poly(dimethyl diallyl ammonium chloride) (PDDA), and two cellulosic polymers: hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC). The molecular weight of polyvinyl alcohols had little effect on the success of hydrothermal hectorite synthesis, d-spacing, or amount of polymer incorporated; the basal spacings range from 19.5 {angstrom} to 20.8 {angstrom} and the percent of polymer incorporated ranges from 20.4 wt% to 23.0 wt%. Synthetic PDDA-hectorite displays the lowest d-spacing at 15.8 {angstrom}, and less cationic PDDA is incorporated into hectorite (7.8 wt% organic) than the other neutral polymers (17.8-23.0 wt% organic). The basal spacing for synthetic HPMC-hectorite is the largest at 25.2 {angstrom}. Small angle neutron scattering was used to further examine the PVA-clay systems.

  15. Agent-based modelling in synthetic biology

    PubMed Central

    2016-01-01

    Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. PMID:27903820

  16. Synthetic biology through biomolecular design and engineering.

    PubMed

    Channon, Kevin; Bromley, Elizabeth H C; Woolfson, Derek N

    2008-08-01

    Synthetic biology is a rapidly growing field that has emerged in a global, multidisciplinary effort among biologists, chemists, engineers, physicists, and mathematicians. Broadly, the field has two complementary goals: To improve understanding of biological systems through mimicry and to produce bio-orthogonal systems with new functions. Here we review the area specifically with reference to the concept of synthetic biology space, that is, a hierarchy of components for, and approaches to generating new synthetic and functional systems to test, advance, and apply our understanding of biological systems. In keeping with this issue of Current Opinion in Structural Biology, we focus largely on the design and engineering of biomolecule-based components and systems.

  17. The conception of life in synthetic biology.

    PubMed

    Deplazes-Zemp, Anna

    2012-12-01

    The phrase 'synthetic biology' is used to describe a set of different scientific and technological disciplines, which share the objective to design and produce new life forms. This essay addresses the following questions: What conception of life stands behind this ambitious objective? In what relation does this conception of life stand to that of traditional biology and biotechnology? And, could such a conception of life raise ethical concerns? Three different observations that provide useful indications for the conception of life in synthetic biology will be discussed in detail: 1. Synthetic biologists focus on different features of living organisms in order to design new life forms, 2. Synthetic biologists want to contribute to the understanding of life, and 3. Synthetic biologists want to modify life through a rational design, which implies the notions of utilising, minimising/optimising, varying and overcoming life. These observations indicate a tight connection between science and technology, a focus on selected aspects of life, a production-oriented approach to life, and a design-oriented understanding of life. It will be argued that through this conception of life synthetic biologists present life in a different light. This conception of life will be illustrated by the metaphor of a toolbox. According to the notion of life as a toolbox, the different features of living organisms are perceived as various rationally designed instruments that can be used for the production of the living organism itself or secondary products made by the organism. According to certain ethical positions this conception of life might raise ethical concerns related to the status of the organism, the motives of the scientists and the role of technology in our society.

  18. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice.

    PubMed

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Lin, Kai-Yuan; Way, Tzong-Der; Korivi, Mallikarjuna; Liao, Jiuun-Wang; Yang, Hsin-Ling

    2017-04-03

    Flavokawain B (FKB), a naturally occurring chalcone in kava extracts, has been reported to possess anticancer activity. However, the effect of FKB on gastric cancer remains unclear. We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage. FKB further caused p62/SQSTM1 activation, mTOR downregulation, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Silencing autophagy inhibitors CQ/3-MA and LC3 (shRNA) significantly reversed the FKB-induced cell death of AGS cells. FKB-triggered ROS generation and ROS inhibition by NAC pre-treatment diminished FKB-induced cell death, LC3 conversion, AVO formation, p62/SQSTM1 activation, ATG4B inhibition and Beclin-1/Bcl-2 dysregulation, which indicated ROS-mediated autophagy in AGS cells. Furthermore, FKB induces G2/M arrest and alters cell-cycle proteins through ROS-JNK signaling. Interestingly, FKB-induced autophagy is associated with the suppression of HER-2 and PI3K/AKT/mTOR signaling cascades. FKB inhibits apoptotic Bax expression, and Bax-transfected AGS cells exhibit both apoptosis and autophagy; thus, FKB-inactivated Bax results in apoptosis inhibition. In vivo data demonstrated that FKB effectively inhibited tumor growth, prolonged the survival rate, and induced autophagy in AGS-xenografted mice. Notably, silencing of LC3 attenuated FKB-induced autophagy in AGS-xenografted tumors. FKB may be a potential chemopreventive agent in the activation of ROS-mediated autophagy of gastric cancer cells.

  19. Expression of genes encoding chalcone synthase, flavanone 3-hydroxylase and dihydroflavonol 4-reductase correlates with flavanol accumulation during heartwood formation in Juglans nigra.

    PubMed

    Beritognolo, Isacco; Magel, Elisabeth; Abdel-Latif, Amani; Charpentier, Jean-Paul; Jay-Allemand, Christian; Breton, Christian

    2002-04-01

    Heartwood formation is generally characterized by the accumulation of phenolic substances that increase the natural color and durability of wood. Although there is evidence that these substances are synthesized in aging sapwood cells, little is known about heartwood formation at the molecular level. We monitored seasonal changes in flavanol concentration across the stems of 23-year-old Juglans nigra L. trees by sampling growth rings extending from the differentiating xylem to the heartwood. We also analyzed expression of phenylpropanoid and flavonoid structural genes in these samples. In the sapwood-heartwood transition zone, flavanol accumulation was correlated with the transcription levels of the chalcone synthase (CHS) and flavanone 3-hydroxylase (F3H) genes. We also observed correlations between flavanol accumulation and the amount of dihydroflavonol 4-reductase (DFR) gene transcript in October, January and May. Although transcription of phenylalanine ammonia-lyase (PAL) and 4-coumarate:CoA ligase (4CL) genes did not correlate with flavanol accumulation, PAL genes were strongly expressed in the transition zone of samples collected in autumn, suggesting that their transcription in these tissues contributes to phenolic biosynthesis. Western immunoblotting showed that accumulation of CHS protein correlated with the amount of CHS gene transcript, whereas accumulation of PAL protein did not correlate with the the transcription levels PAL genes. Preliminary analyses revealed that PAL and CHS activities were higher in the transition zone than in the inner sapwood in autumn, winter, and spring. Thus, CHS activity could be regulated mainly at the transcriptional level, whereas post-translational modifications could modulate PAL activity. We conclude that flavanols are synthesized de novo in J. nigra sapwood cells that are undergoing transformation to heartwood.

  20. Structure, expression profile and phylogenetic inference of chalcone isomerase-like genes from the narrow-leafed lupin (Lupinus angustifolius L.) genome

    PubMed Central

    Przysiecka, Łucja; Książkiewicz, Michał; Wolko, Bogdan; Naganowska, Barbara

    2015-01-01

    Lupins, like other legumes, have a unique biosynthesis scheme of 5-deoxy-type flavonoids and isoflavonoids. A key enzyme in this pathway is chalcone isomerase (CHI), a member of CHI-fold protein family, encompassing subfamilies of CHI1, CHI2, CHI-like (CHIL), and fatty acid-binding (FAP) proteins. Here, two Lupinus angustifolius (narrow-leafed lupin) CHILs, LangCHIL1 and LangCHIL2, were identified and characterized using DNA fingerprinting, cytogenetic and linkage mapping, sequencing and expression profiling. Clones carrying CHIL sequences were assembled into two contigs. Full gene sequences were obtained from these contigs, and mapped in two L. angustifolius linkage groups by gene-specific markers. Bacterial artificial chromosome fluorescence in situ hybridization approach confirmed the localization of two LangCHIL genes in distinct chromosomes. The expression profiles of both LangCHIL isoforms were very similar. The highest level of transcription was in the roots of the third week of plant growth; thereafter, expression declined. The expression of both LangCHIL genes in leaves and stems was similar and low. Comparative mapping to reference legume genome sequences revealed strong syntenic links; however, LangCHIL2 contig had a much more conserved structure than LangCHIL1. LangCHIL2 is assumed to be an ancestor gene, whereas LangCHIL1 probably appeared as a result of duplication. As both copies are transcriptionally active, questions arise concerning their hypothetical functional divergence. Screening of the narrow-leafed lupin genome and transcriptome with CHI-fold protein sequences, followed by Bayesian inference of phylogeny and cross-genera synteny survey, identified representatives of all but one (CHI1) main subfamilies. They are as follows: two copies of CHI2, FAPa2 and CHIL, and single copies of FAPb and FAPa1. Duplicated genes are remnants of whole genome duplication which is assumed to have occurred after the divergence of Lupinus, Arachis, and Glycine

  1. Differential inductions of phenylalanine ammonia-lyase and chalcone synthase during wounding, salicylic acid treatment, and salinity stress in safflower, Carthamus tinctorius.

    PubMed

    Dehghan, Sara; Sadeghi, Mahnaz; Pöppel, Anne; Fischer, Rainer; Lakes-Harlan, Reinhard; Kavousi, Hamid Reza; Vilcinskas, Andreas; Rahnamaeian, Mohammad

    2014-06-25

    Safflower (Carthamus tinctorius L.) serves as a reference dicot for investigation of defence mechanisms in Asteraceae due to abundant secondary metabolites and high resistance/tolerance to environmental stresses. In plants, phenylpropanoid and flavonoid pathways are considered as two central defence signalling cascades in stress conditions. Here, we describe the isolation of two major genes in these pathways, CtPAL (phenylalanine ammonia-lyase) and CtCHS (chalcone synthase) in safflower along with monitoring their expression profiles in different stress circumstances. The aa (amino acid) sequence of isolated region of CtPAL possesses the maximum identity up to 96% to its orthologue in Cynara scolymus, while that of CtCHS retains the highest identity to its orthologue in Callistephus chinensis up to 96%. Experiments for gene expression profiling of CtPAL and CtCHS were performed after the treatment of seedlings with 0.1 and 1 mM SA (salicylic acid), wounding and salinity stress. The results of semi-quantitative RT-PCR revealed that both CtPAL and CtCHS genes are further responsive to higher concentration of SA with dissimilar patterns. Regarding wounding stress, CtPAL gets slightly induced upon injury at 3 hat (hours after treatment) (hat), whereas CtCHS gets greatly induced at 3 hat and levels off gradually afterward. Upon salinity stress, CtPAL displays a similar expression pattern by getting slightly induced at 3 hat, but CtCHS exhibits a biphasic expression profile with two prominent peaks at 3 and 24 hat. These results substantiate the involvement of phenylpropanoid and particularly flavonoid pathways in safflower during wounding and especially salinity stress.

  2. Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells.

    PubMed

    Gao, Suyu; Sun, Dejuan; Wang, Guan; Zhang, Jin; Jiang, Yingnan; Li, Guoyu; Zhang, Ke; Wang, Lei; Huang, Jian; Chen, Lixia

    2016-12-01

    Five flavones, including four flavonoids and one prenylated chalcone (paratocarpin E), were isolated from E. humifusa. and their chemical structures were established by spectroscopic analyses. We assessed the efficacy of these compounds against the growth of human breast cancer, leukemic, kidney cancer cell lines. Among them, paratocarpin E showed significant cytotoxicity against these cancer cell lines with an IC50 of 19.6μM on the growth of MCF-7 cells. Paratocarpin E treatment of MCF-7 cells resulted in typical apoptotic features via increasing expression of activated caspase-8 and -9 and PARP cleavage. Moreover, paratocarpin E altered the expression of Bax and Bcl-2, leading to the release of cytochrome c from the mitochondria into the cytosol, suggesting that the mitochondria-mediated apoptosis was initiated. In addition, paratocarpin E increased the MDC-positive autophagic vacuoles, the ratio of LC3-II/LC3-I protein levels of Beclin-1, but decreased p62 expression, indicating the potent pro-autophagic effects of paratocarpin E in MCF-7 cells. Mechanistically, cell death induced by paratocarpin E is able to induce apoptosis of MCF-7 cells by activating p38 and JNK signaling pathway while inhibiting Erk pathway. Furthermore, paratocarpin E promotes the activation and nuclear translocation of NF-κB, which plays an important role in balancing paratocarpin E-mediated apoptosis and autophagy. The molecular docking study also revealed that paratocarpin E bound to Fas and NF-κB complex. These findings provide initial evidences that paratocarpin E can be used as a potential anti-cancer drug in future for breast cancer therapy.

  3. Simultaneous post-transcriptional gene silencing of two different chalcone synthase genes resulting in pure white flowers in the octoploid dahlia.

    PubMed

    Ohno, Sho; Hosokawa, Munetaka; Kojima, Misa; Kitamura, Yoshikuni; Hoshino, Atsushi; Tatsuzawa, Fumi; Doi, Motoaki; Yazawa, Susumu

    2011-11-01

    Garden dahlias (Dahlia variabilis) are autoallooctoploids with redundant genes producing wide color variations in flowers. There are no pure white dahlia cultivars, despite its long breeding history. However, the white areas of bicolor flower petals appear to be pure white. The objective of this experiment was to elucidate the mechanism by which the pure white color is expressed in the petals of some bicolor cultivars. A pigment analysis showed that no flavonoid derivatives were detected in the white areas of petals in a star-type cultivar 'Yuino' and the two seedling cultivars 'OriW1' and 'OriW2' borne from a red-white bicolor cultivar, 'Orihime', indicating that their white areas are pure white. Semi-quantitative RT-PCR showed that in the pure white areas, transcripts of two chalcone synthases (CHS), DvCHS1 and DvCHS2 which share 69% nucleotide similarity with each other, were barely detected. Premature mRNA of DvCHS1 and DvCHS2 were detected, indicating that these two CHS genes are silenced post-transcriptionally. RNA gel blot analysis revealed that small interfering RNAs (siRNAs) derived from CHSs were produced in these pure white areas. By high-throughput sequence analysis of small RNAs in the pure white areas with no mismatch acceptance, small RNAs were mapped to two alleles of DvCHS1 and two alleles of DvCHS2 expressed in 'Yuino' petals. Therefore, we concluded that simultaneous siRNA-mediated post-transcriptional gene silencing of redundant CHS genes results in the appearance of pure white color in dahlias.

  4. Quartz: Anomalous Weakness of Synthetic Crystals.

    PubMed

    Griggs, D T; Blacic, J D

    1965-01-15

    The strength of a synthetic quartz crystal drops rapidly at 400 degrees C, and at 600 degrees C is a hundredfold lower than at 300 degrees C. Large plastic deformations can be produced without fracture. The predominant mechanism of deformation is translation gliding. The preferred explanation for this anomalous weakness is that this synthetic quartz contains water which has hydrolyzed the silicon-oxygen bonds. The silanol groups so formed are presumed to be rendered sufficiently mobile by elevating the temperature to 400 degrees C so that they align themselves in dislocation lines and move through the crystal with the dislocation under the small applied shear stress.

  5. [Dangerous drugs: products containing synthetic chemicals].

    PubMed

    Kamijo, Yoshito

    2016-02-01

    When the patients poisoned with "dangerous drugs", that is, products containing synthetic chemicals such as synthetic cannabinoids and cathinones, are transferred to the emergency facilities, the chemicals really consumed cannot be determined there. So, supportive care may be the most important strategy for treating them. For example, those with serious consciousness disturbance should be supported with ventilator after intubation. Those with remarkable excitatory CNS or sympathetic symptoms, benzodiazepines such as diazepam and midazolam, should be administered. Those with hallucination or delusion, antipsychotics such as haloperidol or risperidone should be administered. Those with rhabdomyolysis, hypermyoglobinemia and acute kidney injury, intravenous fluids and hemodialysis should be introduced.

  6. Synthetic biology and the ethics of knowledge

    PubMed Central

    Douglas, Thomas; Savulescu, Julian

    2011-01-01

    Synthetic biologists aim to generate biological organisms according to rational design principles. Their work may have many beneficial applications, but it also raises potentially serious ethical concerns. In this article, we consider what attention the discipline demands from bioethicists. We argue that the most important issue for ethicists to examine is the risk that knowledge from synthetic biology will be misused, for example, in biological terrorism or warfare. To adequately address this concern, bioethics will need to broaden its scope, contemplating not just the means by which scientific knowledge is produced, but also what kinds of knowledge should be sought and disseminated. PMID:20935316

  7. Synthetic biology approaches to engineer T cells.

    PubMed

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

    2015-08-01

    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics.

  8. New Synthetic Methods for Hypericum Natural Products

    SciTech Connect

    Jeon, Insik

    2006-01-01

    Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

  9. Synthetic aperture radar capabilities in development

    SciTech Connect

    Miller, M.

    1994-11-15

    The Imaging and Detection Program (IDP) within the Laser Program is currently developing an X-band Synthetic Aperture Radar (SAR) to support the Joint US/UK Radar Ocean Imaging Program. The radar system will be mounted in the program`s Airborne Experimental Test-Bed (AETB), where the initial mission is to image ocean surfaces and better understand the physics of low grazing angle backscatter. The Synthetic Aperture Radar presentation will discuss its overall functionality and a brief discussion on the AETB`s capabilities. Vital subsystems including radar, computer, navigation, antenna stabilization, and SAR focusing algorithms will be examined in more detail.

  10. Realizing the potential of synthetic biology.

    PubMed

    Church, George M; Elowitz, Michael B; Smolke, Christina D; Voigt, Christopher A; Weiss, Ron

    2014-04-01

    Synthetic biology, despite still being in its infancy, is increasingly providing valuable information for applications in the clinic, the biotechnology industry and in basic molecular research. Both its unique potential and the challenges it presents have brought together the expertise of an eclectic group of scientists, from cell biologists to engineers. In this Viewpoint article, five experts discuss their views on the future of synthetic biology, on its main achievements in basic and applied science, and on the bioethical issues that are associated with the design of new biological systems.

  11. [Salem witches, flying brooms, and synthetic drugs].

    PubMed

    Castellanos Tejero, Manuel; Castellanos Tejero, M de los Angeles

    2002-10-01

    As supplementary material to Health Education programs about synthetic drugs, the authors present a historical summary on LSD, stramonium and khat. "Tripis", Special K and other synthetic pills contain these substances and are being widely used by youths. The history of these main hallucinogenic active ingredients has a strong tie to the mythology of witchcraft and witches: a historically interesting time period bearing a large amount of religious intolerance. The objective of this review is to end the belief today's youth have that they are taking new substances which have no risks.

  12. Synthetic heparin-binding factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  13. Synthetic biology advances for pharmaceutical production

    PubMed Central

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  14. Flight Testing an Integrated Synthetic Vision System

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Arthur, Jarvis J., III; Bailey, Randall E.; Prinzel, Lawrence J., III

    2005-01-01

    NASA's Synthetic Vision Systems (SVS) project is developing technologies with practical applications to eliminate low visibility conditions as a causal factor to civil aircraft accidents while replicating the operational benefits of clear day flight operations, regardless of the actual outside visibility condition. A major thrust of the SVS project involves the development/demonstration of affordable, certifiable display configurations that provide intuitive out-the-window terrain and obstacle information with advanced pathway guidance for transport aircraft. The SVS concept being developed at NASA encompasses the integration of tactical and strategic Synthetic Vision Display Concepts (SVDC) with Runway Incursion Prevention System (RIPS) alerting and display concepts, real-time terrain database integrity monitoring equipment (DIME), and Enhanced Vision Systems (EVS) and/or improved Weather Radar for real-time object detection and database integrity monitoring. A flight test evaluation was jointly conducted (in July and August 2004) by NASA Langley Research Center and an industry partner team under NASA's Aviation Safety and Security, Synthetic Vision System project. A Gulfstream GV aircraft was flown over a 3-week period in the Reno/Tahoe International Airport (NV) local area and an additional 3-week period in the Wallops Flight Facility (VA) local area to evaluate integrated Synthetic Vision System concepts. The enabling technologies (RIPS, EVS and DIME) were integrated into the larger SVS concept design. This paper presents experimental methods and the high level results of this flight test.

  15. Methods of characterization of synthetic opal films

    NASA Astrophysics Data System (ADS)

    Koryukin, A. V.; Akhmadeev, A. A.; Salakhov, M. Kh

    2013-12-01

    We developed methods for determination of thickness, number of layers and filling fraction of silica particles for synthetic opals. We show that the filling fraction is considerably less than for ideal close-packed structure, which is important for practical and theoretical applications.

  16. Interferometric Synthetic Aperture Microwave Radiometers : an Overview

    NASA Technical Reports Server (NTRS)

    Colliander, Andreas; McKague, Darren

    2011-01-01

    This paper describes 1) the progress of the work of the IEEE Geoscience and Remote Sensing Society (GRSS) Instrumentation and Future Technologies Technical Committee (IFT-TC) Microwave Radiometer Working Group and 2) an overview of the development of interferometric synthetic aperture microwave radiometers as an introduction to a dedicated session.

  17. Coal conversion and synthetic-fuel production

    NASA Technical Reports Server (NTRS)

    Bradford, R.; Atkins, W. T.; Bass, R. M.; Dascher, R.; Dunkin, J.; Luce, N.; Seward, W.; Warren, D.

    1980-01-01

    Report evaluates potential coal gasification and synthetic-fuel production technologies for 1985 to 1990. Book includes overview of present and future technical and economic potential, ways of evaluating gasification facility designs, discussion of promising processes, characterization of potential markets, and list of available gasification systems.

  18. 21 CFR 178.3500 - Glycerin, synthetic.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glycerin, synthetic. 178.3500 Section 178.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production...

  19. 21 CFR 178.3500 - Glycerin, synthetic.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glycerin, synthetic. 178.3500 Section 178.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  20. 21 CFR 178.3500 - Glycerin, synthetic.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glycerin, synthetic. 178.3500 Section 178.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...