Seed-mediated synthesis of ultra-long copper nanowires and their application as transparent conducting electrodes

NASA Astrophysics Data System (ADS)

Kim, Hyunhong; Choi, Seong-Hyeon; Kim, Mijung; Park, Jang-Ung; Bae, Joonwon; Park, Jongnam

2017-11-01

Owing to a recent push toward one-dimensional nanomaterials, in this study, we report a seed-mediated synthetic strategy for copper nanowires (Cu NWs) production involving thermal decomposition of metal-surfactant complexes in an organic medium. Ultra-long Cu NWs with a high aspect ratio and uniform diameter were obtained by separating nucleation and growth steps. The underlying mechanism for nanowire formation was investigated, in addition, properties of the obtained Cu NWs were also characterized using diverse analysis techniques. The performance of resulting Cu NWs as transparent electrodes was demonstrated for potential application. This article can provide information on both new synthetic pathway and potential use of Cu NWs.

Shedding Light on the Formation of Gold Nanorods

NASA Astrophysics Data System (ADS)

Lopez, Orlando; Hudry, Damien; Nykypanchuk, Dmytro

A significant interest in the study and synthesis of one-dimensional materials such as nanorods or nanowires is sparked by their potential application in electronics, photonics and biodetection. However, the synthesis of these low dimensional materials is not always reliable due to kinetic effects in symmetry breaking and high sensitivity to impurities. In this work we discuss the synthesis of gold nanorods and new ways to achieve symmetry breaking during the growth from seed solution, hence maximizing the yield of nanorods. We discuss the mechanism involved in symmetry breaking and general strategies to improve the nanorod morphology and synthetic yield. This work can serve as a starting point to design reproducible synthetic strategies for preparing high quality gold nanorods. This project was supported by the U.S. Department of Energy, Office of Science, under the Science Undergraduate Laboratory Internships Program and used resources of the C.F.N., which is a U.S. DOE Facility, at B.N.L., Contract No. DE-SC0012704.

Establishment of a Charge Reversal Derivatization Strategy to Improve the Ionization Efficiency of Limaprost and Investigation of the Fragmentation Patterns of Limaprost Derivatives Via Exclusive Neutral Loss and Survival Yield Method

NASA Astrophysics Data System (ADS)

Sun, Dong; Meng, Xiangjun; Ren, Tianming; Fawcett, John Paul; Wang, Hualu; Gu, Jingkai

2018-04-01

Sensitivity is generally an issue in bioassays of prostaglandins and their synthetic analogs due to their extremely low concentration in vivo. To improve the ionization efficiency of limaprost, an oral prostaglandin E1 (PGE1) synthetic analog, we investigated a charge reversal derivatization strategy in electrospray ionization mass spectrometry (ESI-MS). We established that the cholamine derivative exhibits much greater signal intensity in the positive-ion mode compared with limaprost in the negative ion mode. Collision-induced dissociation (CID) involved exclusive neutral mass loss and positive charge migration to form stable cationic product ions with the positive charge on the limaprost residue rather than on the modifying group. This has the effect of maintaining the efficiency and specificity of multiple reaction monitoring (MRM) and avoiding cross talk. CID fragmentation patterns of other limaprost derivatives allowed us to relate the dissociation tendency of different neutral leaving groups to an internal energy distribution scale based on the survival yield method. Knowledge of the energy involved in the production of stabilized positive ions will potentially assist the selection of suitable derivatization reagents for the analysis of a wide variety of lipid acids. [Figure not available: see fulltext.

Chemically tunable mucin chimeras assembled on living cells

DOE PAGES

Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos; ...

2015-09-29

Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solvingmore » a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.« less

Chemically tunable mucin chimeras assembled on living cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos

Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solvingmore » a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.« less

Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

PubMed

Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

2015-02-01

Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

Postgenomic strategies in antibacterial drug discovery.

PubMed

Brötz-Oesterhelt, Heike; Sass, Peter

2010-10-01

During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned refer to characteristics of targets, screening libraries and screening strategies. The 'genomics' approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product leads among previously abandoned compounds or new microbial sources, screening for synthetic inhibitors by targeted approaches including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established classes. Furthermore, alternative treatment options are being pursued including anti-virulence strategies and immunotherapeutic approaches. This article summarizes the lessons learned from the genomics era and describes discovery strategies resulting from that knowledge.

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.

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

PubMed

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

[Application of synthetic biology to sustainable utilization of Chinese materia medica resources].

PubMed

Huang, Lu-Qi; Gao, Wei; Zhou, Yong-Jin

2014-01-01

Bioactive natural products are the material bases of Chinese materia medica resources. With successful applications of synthetic biology strategies to the researches and productions of taxol, artemisinin and tanshinone, etc, the potential ability of synthetic biology in the sustainable utilization of Chinese materia medica resources has been attracted by many researchers. This paper reviews the development of synthetic biology, the opportunities of sustainable utilization of Chinese materia medica resources, and the progress of synthetic biology applied to the researches of bioactive natural products. Furthermore, this paper also analyzes how to apply synthetic biology to sustainable utilization of Chinese materia medica resources and what the crucial factors are. Production of bioactive natural products with synthetic biology strategies will become a significant approach for the sustainable utilization of Chinese materia medica resources.

Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route.

PubMed

Mirabella, S; Fibbi, G; Matassini, C; Faggi, C; Goti, A; Cardona, F

2017-11-07

A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

PubMed Central

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-01-01

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses—the so-called transfer function—and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. PMID:25404136

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties

PubMed Central

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-01-01

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials. PMID:26198844

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties.

PubMed

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-07-22

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials.

Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014.

PubMed

Gladden, R Matthew; Martinez, Pedro; Seth, Puja

2016-08-26

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(†) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in synthetic opioid deaths among high-burden states disproportionately involved persons aged 15-44 years and males, a pattern consistent with previously documented IMF-involved deaths (5). These findings, combined with the approximate doubling in fentanyl submissions during 2014-2015 (from 5,343 to 13,882) (6), underscore the urgent need for a collaborative public health and law enforcement response.

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet.

PubMed

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining; Li, Man; Wang, Xin; Hu, Cheng; Gorman, Connor; Dai, Susie Y; Ding, Shi-You; Yuan, Joshua S

2018-03-16

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalene at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.

Chemistry of Amadori rearrangement products: analysis, synthesis, kinetics, reactions, and spectroscopic properties.

PubMed

Yaylayan, V A; Huyghues-Despointes, A

1994-01-01

The chemistry of the key intermediate in the Maillard reaction, the Amadori rearrangements product, is reviewed covering the areas of synthesis, chromatographic analyses, chemical and spectroscopic methods of characterization, reactions, and kinetics. Synthetic strategies involving free and protected sugars are described in detail with specific synthetic procedures. GC- and HPLC-based separations of Amadori products are discussed in relation to the type of columns employed and methods of detection. Applications of infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy for structural elucidation of Amadori products are also reviewed. In addition, mass spectrometry of free, protected, and protein-bound Amadori products under different ionization conditions are presented. The mechanism of acid/base catalyzed thermal degradation reactions of Amadori compounds, as well as their kinetics of formation, are critically evaluated.

Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds with Hypervalent Iodine Reagents.

PubMed

Hari, Durga Prasad; Waser, Jerome

2016-02-24

Alkynes have found widespread applications in synthetic chemistry, biology, and materials sciences. In recent years, methods based on electrophilic alkynylation with hypervalent iodine reagents have made acetylene synthesis more flexible and efficient, but they lead to the formation of one equivalent of an iodoarene as side-product. Herein, a more efficient strategy involving a copper-catalyzed oxy-alkynylation of diazo compounds with ethynylbenziodoxol(on)e (EBX) reagents is described, which proceeds with generation of nitrogen gas as the only waste. This reaction is remarkable for its broad scope in both EBX reagents and diazo compounds. In addition, vinyl diazo compounds gave enynes selectively as single geometric isomers. The functional groups introduced during the transformation served as easy handles to access useful building blocks for synthetic and medicinal chemistry.

Facile synthesis of hierarchical Ag3PO4/TiO2 nanofiber heterostructures with highly enhanced visible light photocatalytic properties

NASA Astrophysics Data System (ADS)

Xie, Jinlei; Yang, Yefeng; He, Haiping; Cheng, Ding; Mao, Minmin; Jiang, Qinxu; Song, Lixin; Xiong, Jie

2015-11-01

Heterostructured semiconductor nanostructures have provoked great interest in the areas of energy, environment and catalysis. Herein, we report a novel hierarchical Ag3PO4/TiO2 heterostructure consisting of nearly spherical Ag3PO4 particles firmly coupled on the surface of TiO2 nanofibers (NFs). The construction of Ag3PO4/TiO2 heterostructure with tailored morphologies, compositions and optical properties was simply achieved via a facile and green synthetic strategy involving the electrospinning and solution-based processes. Owing to the synergetic effects of the components, the resulting hybrid heterostructures exhibited much improved visible light photocatalytic performance, which could degrade the RhB dye completely in 7.5 min. In addition, the coupling of Ag3PO4 particles with UV-light-sensitive TiO2 NFs enabled full utilization of solar energy and less consumption of noble metals, significantly appealing for their practical use in new energy sources and environmental issues. The developed synthetic strategy was considered to be applicable for the rational design and construction of other heterostructured catalysts.

Review of synthetic approaches toward maoecrystal V.

PubMed

Smith, Brandon R; Njardarson, Jon T

2018-05-18

Synthetic approaches toward the complex natural product diterpenoid maoecrystal V are reviewed, including successful total syntheses, published synthetic efforts, and efforts compiled from dissertations. The review focuses on general synthetic strategies and chronicles efforts toward the molecule since its isolation in 2004, summarizing key contributions of these efforts to the broader synthetic community.

Facet‐Controlled Synthetic Strategy of Cu2O‐Based Crystals for Catalysis and Sensing

PubMed Central

Shang, Yang

2015-01-01

Shape‐dependent catalysis and sensing behaviours are primarily focused on nanocrystals enclosed by low‐index facets, especially the three basic facets ({100}, {111}, and {110}). Several novel strategies have recently exploded by tailoring the original nanocrystals to greatly improve the catalysis and sensing performances. In this Review, we firstly introduce the synthesis of a variety of Cu2O nanocrystals, including the three basic Cu2O nanocrystals (cubes, octahedra and rhombic dodecahedra, enclosed by the {100}, {111}, and {110} facets, respectively), and Cu2O nanocrystals enclosed by high‐index planes. We then discuss in detail the three main facet‐controlled synthetic strategies (deposition, etching and templating) to fabricate Cu2O‐based nanocrystals with heterogeneous, etched, or hollow structures, including a number of important concepts involved in those facet‐controlled routes, such as the selective adsorption of capping agents for protecting special facets, and the impacts of surface energy and active sites on reaction activity trends. Finally, we highlight the facet‐dependent properties of the Cu2O and Cu2O‐based nanocrystals for applications in photocatalysis, gas catalysis, organocatalysis and sensing, as well as the relationship between their structures and properties. We also summarize and comment upon future facet‐related directions. PMID:27980909

Facet-Controlled Synthetic Strategy of Cu2O-Based Crystals for Catalysis and Sensing.

PubMed

Shang, Yang; Guo, Lin

2015-10-01

Shape-dependent catalysis and sensing behaviours are primarily focused on nanocrystals enclosed by low-index facets, especially the three basic facets ({100}, {111}, and {110}). Several novel strategies have recently exploded by tailoring the original nanocrystals to greatly improve the catalysis and sensing performances. In this Review, we firstly introduce the synthesis of a variety of Cu 2 O nanocrystals, including the three basic Cu 2 O nanocrystals (cubes, octahedra and rhombic dodecahedra, enclosed by the {100}, {111}, and {110} facets, respectively), and Cu 2 O nanocrystals enclosed by high-index planes. We then discuss in detail the three main facet-controlled synthetic strategies (deposition, etching and templating) to fabricate Cu 2 O-based nanocrystals with heterogeneous, etched, or hollow structures, including a number of important concepts involved in those facet-controlled routes, such as the selective adsorption of capping agents for protecting special facets, and the impacts of surface energy and active sites on reaction activity trends. Finally, we highlight the facet-dependent properties of the Cu 2 O and Cu 2 O-based nanocrystals for applications in photocatalysis, gas catalysis, organocatalysis and sensing, as well as the relationship between their structures and properties. We also summarize and comment upon future facet-related directions.

RNA self-assembly and RNA nanotechnology.

PubMed

Grabow, Wade W; Jaeger, Luc

2014-06-17

CONSPECTUS: Nanotechnology's central goal involves the direct control of matter at the molecular nanometer scale to build nanofactories, nanomachines, and other devices for potential applications including electronics, alternative fuels, and medicine. In this regard, the nascent use of nucleic acids as a material to coordinate the precise arrangements of specific molecules marked an important milestone in the relatively recent history of nanotechnology. While DNA served as the pioneer building material in nucleic acid nanotechnology, RNA continues to emerge as viable alternative material with its own distinct advantages for nanoconstruction. Several complementary assembly strategies have been used to build a diverse set of RNA nanostructures having unique structural attributes and the ability to self-assemble in a highly programmable and controlled manner. Of the different strategies, the architectonics approach uniquely endeavors to understand integrated structural RNA architectures through the arrangement of their characteristic structural building blocks. Viewed through this lens, it becomes apparent that nature routinely uses thermodynamically stable, recurrent modular motifs from natural RNA molecules to generate unique and more complex programmable structures. With the design principles found in natural structures, a number of synthetic RNAs have been constructed. The synthetic nanostructures constructed to date have provided, in addition to affording essential insights into RNA design, important platforms to characterize and validate the structural self-folding and assembly properties of RNA modules or building blocks. Furthermore, RNA nanoparticles have shown great promise for applications in nanomedicine and RNA-based therapeutics. Nevertheless, the synthetic RNA architectures achieved thus far consist largely of static, rigid particles that are still far from matching the structural and functional complexity of natural responsive structural elements such as the ribosome, large ribozymes, and riboswitches. Thus, the next step in synthetic RNA design will involve new ways to implement these same types of dynamic and responsive architectures into nanostructures functioning as real nanomachines in and outside the cell. RNA nanotechnology will likely garner broader utility and influence with a greater focus on the interplay between thermodynamic and kinetic influences on RNA self-assembly and using natural RNAs as guiding principles.

Synthetic bedding and wheeze in childhood.

PubMed

Ponsonby, Anne-Louise; Dwyer, Terence; Kemp, Andrew; Cochrane, Jennifer; Couper, David; Carmichael, Allan

2003-01-01

The reasons for the increase in childhood asthma over time are unclear. The indoor environment is of particular concern. An adverse role for synthetic bedding on asthma development in childhood has been suggested by cross-sectional studies that have found an association between synthetic pillow use and childhood wheeze. Prospective data on infant bedding have not been available. Bedding data at 1 month of age were available from an infant survey for children who were participating in a 1995 follow-up study (N = 863; 78% traced). The 1995 follow-up was embedded in a larger cross-sectional survey involving 6,378 seven year olds in Tasmania (N = 92% of eligible). Outcome measures included respiratory symptoms as defined in the International Study of Asthma and Allergies in Childhood protocol. Frequent wheeze was defined as more than 12 wheeze episodes over the past year compared with no wheeze. Synthetic pillow use at 1 month of age was associated with frequent wheeze at age 7 (adjusted relative risk [aRR] = 2.5; 95% confidence interval [CI] = 1.2-5.5) independent of childhood exposure. Current synthetic pillow and quilt use was strongly associated with frequent wheeze (aRR = 5.2; CI = 1.3-20.6). Substantial trends were evident for an association of increasing number of synthetic bedding items with frequent wheeze and with increasing wheeze frequency. Among children with asthma, the age of onset of asthma occurred earlier if synthetic bedding was used in infancy. In this cohort, synthetic bedding was strongly and consistently associated with frequent childhood wheeze. The association did not appear to be attributable to bedding choice as part of an asthma management strategy.

Supervised nonlinear spectral unmixing using a postnonlinear mixing model for hyperspectral imagery.

PubMed

Altmann, Yoann; Halimi, Abderrahim; Dobigeon, Nicolas; Tourneret, Jean-Yves

2012-06-01

This paper presents a nonlinear mixing model for hyperspectral image unmixing. The proposed model assumes that the pixel reflectances are nonlinear functions of pure spectral components contaminated by an additive white Gaussian noise. These nonlinear functions are approximated using polynomial functions leading to a polynomial postnonlinear mixing model. A Bayesian algorithm and optimization methods are proposed to estimate the parameters involved in the model. The performance of the unmixing strategies is evaluated by simulations conducted on synthetic and real data.

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489.

PubMed

Geddis, Stephen M; Carro, Laura; Hodgkinson, James T; Spring, David R

2016-12-01

Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald-Hartwig amination and a final acid-catalysed 1,3-allylic-alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modular strategy enables an improved synthesis towards two natural products previously reported.

Triple Nucleophilic Attack of Nitromethane on (2-Iminoaryl)divinyl Ketones: A Domino Synthetic Strategy for Hexahydrophenanthridinones.

PubMed

Feng, Chengjie; Li, Yifei; Xu, Qi; Pan, Ling; Liu, Qun; Xu, Xianxiu

2018-02-02

A novel domino reaction of (2-iminoaryl)divinyl ketones with nitromethane was developed for the efficient synthesis of hexahydrophenanthridin-9(5H)-ones. The reaction proceeded smoothly from readily available starting materials under mild reaction conditions to construct three new bonds and two rings with high diastereoselectivities in good to excellent yields in a single step. A mechanism is proposed, involving a stepwise double Michael addition/aza-Henry reaction cascade, and in this transformation, nitromethane acts as a trinucleophile.

High-Valent Organometallic Copper and Palladium in Catalysis

PubMed Central

Hickman, Amanda J.; Sanford, Melanie S.

2015-01-01

Preface Copper and palladium catalysts are critically important for numerous commercial chemical processes. Improvements in the activity, selectivity, and scope of these catalysts have the potential to dramatically reduce the environmental impact and increase the sustainability of chemical reactions. One rapidly emerging strategy to achieve these goals is to exploit “high-valent” copper and palladium intermediates in catalysis. This review describes exciting recent advances involving both the fundamental chemistry and the applications of these high-valent metal complexes in numerous synthetically useful catalytic transformations. PMID:22498623

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalenemore » at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.« less

Large scale fabrication of highly monodispersed rattle-type TiO2@void@SiO2 spheres via synthesis-cum-organization process.

PubMed

Wu, Liangzhuan; Yu, Yuan; Zhang, Yuan; Li, Yuzhen; Zhang, Yang; Zhi, Jinfang

2012-03-01

Architected nanostructures with interior space have attracted enormous attention due to both their esthetic beauty and their potential applications. It is a current dream to develop a template-free, one-pot and low-temperature synthetic routes for hetero-architecture in liquid media. In this manuscript, we develop a kind of template-free, low-temperature, and one-pot total synthetic strategy for synthesis of inorganic multi-component hetero-architecture. This synthetic strategy analogous to standard organic reactions used in total synthesis is an important breakthrough in inorganic chemical synthesis. We can achieve 1 kilogram (kg) yield of the TiO(2)@void@SiO(2) core-shell sphere one time by using this synthetic strategy, which may lead to practical applications of the sample. By embodying the new reaction and concept into future investigation, a more mature research field in synthetic architecture of nanomaterials can be anticipated. Copyright © 2011 Elsevier Inc. All rights reserved.

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet

DOE PAGES

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining; ...

2018-02-13

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalenemore » at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.« less

Retroactivity in the Context of Modularly Structured Biomolecular Systems

PubMed Central

Pantoja-Hernández, Libertad; Martínez-García, Juan Carlos

2015-01-01

Synthetic biology has intensively promoted the technical implementation of modular strategies in the fabrication of biological devices. Modules are considered as networks of reactions. The behavior displayed by biomolecular systems results from the information processes carried out by the interconnection of the involved modules. However, in natural systems, module wiring is not a free-of-charge process; as a consequence of interconnection, a reactive phenomenon called retroactivity emerges. This phenomenon is characterized by signals that propagate from downstream modules (the modules that receive the incoming signals upon interconnection) to upstream ones (the modules that send the signals upon interconnection). Such retroactivity signals, depending of their strength, may change and sometimes even disrupt the behavior of modular biomolecular systems. Thus, analysis of retroactivity effects in natural biological and biosynthetic systems is crucial to achieve a deeper understanding of how this interconnection between functionally characterized modules takes place and how it impacts the overall behavior of the involved cell. By discussing the modules interconnection in natural and synthetic biomolecular systems, we propose that such systems should be considered as quasi-modular. PMID:26137457

Effects of synthetic and natural toxicants on livestock.

PubMed

Shull, L R; Cheeke, P R

1983-07-01

Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

Design and synthesis of inositolphosphoglycan putative insulin mediators.

PubMed

López-Prados, Javier; Cuevas, Félix; Reichardt, Niels-Christian; de Paz, José-Luis; Morales, Ezequiel Q; Martín-Lomas, Manuel

2005-03-07

The binding modes of a series of molecules, containing the glucosamine (1-->6) myo-inositol structural motif, into the ATP binding site of the catalytic subunit of cAMP-dependent protein kinase (PKA) have been analysed using molecular docking. These calculations predict that the presence of a phosphate group at the non-reducing end in pseudodisaccharide and pseudotrisaccharide structures properly orientate the molecule into the binding site and that pseudotrisaccharide structures present the best shape complementarity. Therefore, pseudodisaccharides and pseudotrisaccharides have been synthesised from common intermediates using effective synthetic strategies. On the basis of this synthetic chemistry, the feasibility of constructing small pseudotrisaccharide libraries on solid-phase using the same intermediates has been explored. The results from the biological evaluation of these molecules provide additional support to an insulin-mediated signalling system which involves the intermediacy of inositolphosphoglycans as putative insulin mediators.

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.

PubMed

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-12-16

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

PubMed

Pidgeon, Sean E; Pires, Marcos M

2017-07-21

Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

A systems-level approach for metabolic engineering of yeast cell factories.

PubMed

Kim, Il-Kwon; Roldão, António; Siewers, Verena; Nielsen, Jens

2012-03-01

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Tillage and Composting Strategies to Maximize Potentially Mineralizable Nitrogen in Maize-based Cropping Systems

USDA-ARS?s Scientific Manuscript database

Cereal crop yields vary drastically between developed and developing nations. In developing nations, a lack of synthetic nitrogen (N) fertilizer often limits yields. Low-cost soil management strategies that increase biologically available soil organic matter can reduce farmer reliance on synthetic N...

Indole diterpenoid natural products as the inspiration for new synthetic methods and strategies.

PubMed

Corsello, Michael A; Kim, Junyong; Garg, Neil K

2017-09-01

Indole terpenoids comprise a large class of natural products with diverse structural topologies and a broad range of biological activities. Accordingly, indole terpenoids have and continue to serve as attractive targets for chemical synthesis. Many synthetic efforts over the past few years have focused on a subclass of this family, the indole diterpenoids. This minireview showcases the role indole diterpenoids have played in inspiring the recent development of clever synthetic strategies, and new chemical reactions.

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory.

PubMed

Jakobson, Christopher M; Tullman-Ercek, Danielle; Mangan, Niall M

2018-05-29

Natural biochemical systems are ubiquitously organized both in space and time. Engineering the spatial organization of biochemistry has emerged as a key theme of synthetic biology, with numerous technologies promising improved biosynthetic pathway performance. One strategy, however, may produce disparate results for different biosynthetic pathways. We use a spatially resolved kinetic model to explore this fundamental design choice in systems and synthetic biology. We predict that two example biosynthetic pathways have distinct optimal organization strategies that vary based on pathway-dependent and cell-extrinsic factors. Moreover, we demonstrate that the optimal design varies as a function of kinetic and biophysical properties, as well as culture conditions. Our results suggest that organizing biosynthesis has the potential to substantially improve performance, but that choosing the appropriate strategy is key. The flexible design-space analysis we propose can be adapted to diverse biosynthetic pathways, and lays a foundation to rationally choose organization strategies for biosynthesis.

Recent Advances in Hydrogel-Based Drug Delivery for Melanoma Cancer Therapy: A Mini Review

PubMed Central

Elupula, Ravinder

2017-01-01

The purpose of this study is to describe some of the latest advances in using hydrogels for cancer melanoma therapy. Hydrogel formulations of polymeric material from natural or synthetic sources combined with therapeutic agents have gained great attention in the recent years for treating various maladies. These formulations can be categorized according to the strategies that induce cancer cell death in melanoma. First of all, we should note that these formulations can only play a supporting role that releases bioactive agents against cancer cells rather than the main role. This strategy involves delivering the drug via transdermal pathways, resulting in the death of cancerous cells. Another strategy utilizes magnetic gel composites to combat melanoma via hyperthermia therapy. This review discusses both transdermal and hyperthermia therapies and the recent advances that have occurred in the field. PMID:28852576

Studies of a Diazo Cyclopropanation Strategy for the Total Synthesis of (-)-Lundurine A.

PubMed

Huang, Hong-Xiu; Jin, Shuai-Jiang; Gong, Jin; Zhang, Dan; Song, Hao; Qin, Yong

2015-09-14

The bioactive Kopsia alkaloids lundurines A-D are the only natural products known to contain indolylcyclopropane. Achieving their syntheses can provide important insights into their biogenesis, as well as novel synthetic routes for complex natural products. Asymmetric total synthesis of (-)-lundurine A has previously been achieved through a Simmons-Smith cyclopropanation strategy. Here, the total synthesis of (-)-lundurine A was carried out using a metal-catalyzed diazo cyclopropanation strategy. In order to avoid a carbene CH insertion side reaction during cyclopropanation of α-diazo- carboxylates or cyanides, a one-pot, copper-catalyzed Bamford-Stevens diazotization/diazo decomposition/cyclopropanation cascade was developed, involving hydrazone. This approach simultaneously generates the C/D/E ring system and the two chiral quaternary centers at C2 and C7. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

Fracture healing is a complex physiological process, which involves a well-orchestrated series of biological events. Repair of large bone defects resulting from trauma, tumours, osteitis, delayed unions, non-unions, osteotomies, arthrodesis and multifragmentary fractures is a current challenge of surgeons and investigators. Different therapeutic modalities have been developed to enhance the healing response and fill the bone defects. Different types of growth factors, stem cells, natural grafts (autografts, allografts or xenografts) and biologic- and synthetic-based tissue-engineered scaffolds are some of the examples. Nevertheless, these organic and synthetic materials and therapeutic agents have some significant limitations, and there are still no well-approved treatment modalities to meet all the expected requirements. Bone tissue engineering is a newer option than the traditional grafts and may overcome many limitations of the bone graft. To select an appropriate treatment strategy in achieving a successful and secure healing, more information concerning injuries of bones, their healing process and knowledge of the factors involved are required. The main goals of this work are to present different treatment modalities of the fractured bones and to explain how fractures normally heal and what factors interfere with fracture healing. This study provides an overview of the processes of fracture healing and discusses the current therapeutic strategies that have been claimed to be effective in accelerating fracture healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Assembly of Terpenoid Cores by a Simple, Tunable Strategy.

PubMed

Lahtigui, Ouidad; Emmetiere, Fabien; Zhang, Wei; Jirmo, Liban; Toledo-Roy, Samira; Hershberger, John C; Macho, Jocelyn M; Grenning, Alexander J

2016-12-19

Oxygenated, polycyclic terpenoid natural products have important biological activities. Although total synthesis of such terpenes is widely studied, synthetic strategies that allow for controlled placement of oxygen atoms and other functionality remains a challenge. Herein, we present a simple, scalable, and tunable synthetic strategy to assemble terpenoid-like polycycloalkanes from cycloalkanones, malononitrile, and allylic electrophiles, abundantly available reagent classes. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis

PubMed Central

Nagib, David A.; MacMillan, David W. C.

2012-01-01

Modern drug discovery relies on the continual development of synthetic methodology to address the many challenges associated with the design of new pharmaceutical agents1. One such challenge arises from the enzymatic metabolism of drugs in vivo by cytochrome P450 oxidases, which use single-electron oxidative mechanisms to rapidly modify small molecules to facilitate their excretion2. A commonly used synthetic strategy to protect against in vivo metabolism involves the incorporation of electron-withdrawing functionality, such as the trifluoromethyl (CF3) group, into drug candidates3. The CF3 group enjoys a privileged role in the realm of medicinal chemistry because its incorporation into small molecules often enhances efficacy by promoting electrostatic interactions with targets, improving cellular membrane permeability, and increasing robustness towards oxidative metabolism of the drug4–6. Although common pharmacophores often bear CF3 motifs in an aromatic system, access to such analogues typically requires the incorporation of the CF3 group, or a surrogate moiety, at the start of a multi-step synthetic sequence. Here we report a mild, operationally simple strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes through a radical-mediated mechanism using commercial photocatalysts and a household light bulb. We demonstrate the broad utility of this transformation through addition of CF3 to a number of heteroaromatic and aromatic systems. The benefit to medicinal chemistry and applicability to late-stage drug development is also shown through examples of the direct trifluoromethylation of widely prescribed pharmaceutical agents. PMID:22158245

Synthetic Strategies to Terpene Quinones/Hydroquinones

PubMed Central

Gordaliza, Marina

2012-01-01

The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described. PMID:22412807

Perchlorate and Halogen-Free High Energy Dense Oxidizers (HEDO)

DTIC Science & Technology

2011-06-01

nitric acid indicate that the covalent oxalic acid dinitrate ester should be more stable than the ionic dinitronium oxalate . The following three...synthetic strategies were developed to generate compound 11 (Scheme 17). Strategy I is the nitration of anhydrous oxalic acid with nitric acid (100...temperatures (25 to –30 °C) and in all dry solvents used. Scheme 17: Synthetic strategies for the production of oxalic acid dinitrate ester (11

Rate-dependent inverse-addition beta-selective mannosylation and contiguous sequential glycosylation involving beta-mannosidic bond formation.

PubMed

Chang, Shih-Sheng; Shih, Che-Hao; Lai, Kwun-Cheng; Mong, Kwok-Kong Tony

2010-05-03

The beta-selectivity of mannosylation has been found to be dependent on the addition rate of the mannosyl trichloroacetimidate donor in an inverse-addition (I-A) procedure. This rate dependent I-A procedure can improve the selectivity of direct beta-mannosylation and is applicable to orthogonal glycosylations of thioglycoside acceptors. Further elaboration of this novel procedure enables the development of the contiguous sequential glycosylation strategy, which streamlines the preparation of oligosaccharides invoking beta-mannosidic bond formation. The synthetic utility of the contiguous glycosylation strategy was demonstrated by the preparation of the trisaccharide core of human N-linked glycoproteins and the trisaccharide repeating unit of the O-specific polysaccharide found in the cellular capsule of Salmonelle bacteria.

Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

PubMed Central

2009-01-01

Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. PMID:19939265

"Bath salts" intoxication: a new recreational drug that presents with a familiar toxidrome.

PubMed

Hall, Christine; Heyd, Christopher; Butler, Chris; Yarema, Mark

2014-03-01

It is important for emergency physicians to be aware of new psychoactive agents being used as recreational drugs. "Bath salts," which include 3,4-methylenedioxypyrovalerone (MDPV), mephedrone, and methylone, are the newest recreational stimulants to appear in Canada. There are currently more than 12 synthetic cathinones marketed as bath salts and used with increasing frequency recreationally. Although these drugs are now illegal in Canada, they are widely available online. We present a case report and discuss bath salts intoxication and its anticipated sympathomimetic toxidrome, treatment strategies, and toxicologic analysis, Treatment should not rely on laboratory confirmation. Since the laboratory identification of such drugs varies by institution and toxicologic assay, physicians should not misconstrue a negative toxicology screen as evidence of no exposure to synthetic cathinones. Illicit bath salts represent an increasing public health concern that involves risk to the user, prehospital personnel, and health care providers.

Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation.

PubMed

Borrego, Belén; Rodríguez-Pulido, Miguel; Revilla, Concepción; Álvarez, Belén; Sobrino, Francisco; Domínguez, Javier; Sáiz, Margarita

2015-07-17

The innate immune system is the first line of defense against viral infections. Exploiting innate responses for antiviral, therapeutic and vaccine adjuvation strategies is being extensively explored. We have previously described, the ability of small in vitro RNA transcripts, mimicking the sequence and structure of different domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs), to trigger a potent and rapid innate immune response. These synthetic non-infectious molecules have proved to have a broad-range antiviral activity and to enhance the immunogenicity of an FMD inactivated vaccine in mice. Here, we have studied the involvement of pattern-recognition receptors (PRRs) in the ncRNA-induced innate response and analyzed the antiviral and cytokine profiles elicited in swine cultured cells, as well as peripheral blood mononuclear cells (PBMCs).

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489

PubMed Central

Geddis, Stephen M.; Carro, Laura; Hodgkinson, James T.

2016-01-01

Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald–Hartwig amination and a final acid‐catalysed 1,3‐allylic‐alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modular strategy enables an improved synthesis towards two natural products previously reported. PMID:28111524

SVM-Based Synthetic Fingerprint Discrimination Algorithm and Quantitative Optimization Strategy

PubMed Central

Chen, Suhang; Chang, Sheng; Huang, Qijun; He, Jin; Wang, Hao; Huang, Qiangui

2014-01-01

Synthetic fingerprints are a potential threat to automatic fingerprint identification systems (AFISs). In this paper, we propose an algorithm to discriminate synthetic fingerprints from real ones. First, four typical characteristic factors—the ridge distance features, global gray features, frequency feature and Harris Corner feature—are extracted. Then, a support vector machine (SVM) is used to distinguish synthetic fingerprints from real fingerprints. The experiments demonstrate that this method can achieve a recognition accuracy rate of over 98% for two discrete synthetic fingerprint databases as well as a mixed database. Furthermore, a performance factor that can evaluate the SVM's accuracy and efficiency is presented, and a quantitative optimization strategy is established for the first time. After the optimization of our synthetic fingerprint discrimination task, the polynomial kernel with a training sample proportion of 5% is the optimized value when the minimum accuracy requirement is 95%. The radial basis function (RBF) kernel with a training sample proportion of 15% is a more suitable choice when the minimum accuracy requirement is 98%. PMID:25347063

Site-Specific Protein Labeling via Sortase-Mediated Transpeptidation

PubMed Central

Antos, John M.; Ingram, Jessica; Fang, Tao; Pishesha, Novalia; Truttmann, Matthias C.; Ploegh, Hidde L.

2017-01-01

Strategies for site-specific protein modification are highly desirable for the construction of conjugates containing non-genetically encoded functional groups. Ideally, these strategies should proceed under mild conditions, and be compatible with a wide range of protein targets and non-natural moieties. The transpeptidation reaction catalyzed by bacterial sortases is a prominent strategy for protein derivatization that possesses these features. Naturally occurring or engineered variants of sortase A from Staphylococcus aureus catalyze a ligation reaction between a five amino acid substrate motif (LPXTG) and oligoglycine nucleophiles. By pairing proteins and synthetic peptides that possess these ligation handles, it is possible to install modifications onto the protein N- or C-terminus in site-specific fashion. As described in this unit, the successful implementation of sortase-mediated labeling involves straightforward solid-phase synthesis and molecular biology techniques, and this method is compatible with proteins in solution or on the surface of live cells. PMID:19365788

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks

PubMed Central

Krüger, Antje; Csibra, Eszter; Gianni, Edoardo

2016-01-01

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. PMID:27903826

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks.

PubMed

Torres, Leticia; Krüger, Antje; Csibra, Eszter; Gianni, Edoardo; Pinheiro, Vitor B

2016-11-30

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. © 2016 The Author(s).

Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B.

PubMed

Shiozaki, Hiroki; Miyahara, Masayoshi; Otsuka, Kazunori; Miyako, Kei; Honda, Akito; Takasaki, Yuichi; Takamizawa, Satoshi; Tukada, Hideyuki; Ishikawa, Yuichi; Sakai, Ryuichi; Oikawa, Masato

2018-05-23

A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.

Assessing synthetic strategies: total syntheses of (+/-)-neodolabellane-type diterpenoids.

PubMed

Valente, Cory; Organ, Michael G

2008-01-01

Two strategies, namely a cross-metathesis/ring-closing metathesis and Pd-catalyzed Stille allylation/Nozaki-Hiyama-Kishi coupling, are examined for the preparation of neodolabellane-type diterpenoids 1 and 2. Whereas the first approach possessed synthetic limitations, the latter was successfully employed to provide compounds 1 and 2 in 8.8% (14 steps) and 8% (15 steps) overall yields, respectively.

Multiple imputation as one tool to provide longitudinal databases for modelling human height and weight development.

PubMed

Aßmann, C

2016-06-01

Besides large efforts regarding field work, provision of valid databases requires statistical and informational infrastructure to enable long-term access to longitudinal data sets on height, weight and related issues. To foster use of longitudinal data sets within the scientific community, provision of valid databases has to address data-protection regulations. It is, therefore, of major importance to hinder identifiability of individuals from publicly available databases. To reach this goal, one possible strategy is to provide a synthetic database to the public allowing for pretesting strategies for data analysis. The synthetic databases can be established using multiple imputation tools. Given the approval of the strategy, verification is based on the original data. Multiple imputation by chained equations is illustrated to facilitate provision of synthetic databases as it allows for capturing a wide range of statistical interdependencies. Also missing values, typically occurring within longitudinal databases for reasons of item non-response, can be addressed via multiple imputation when providing databases. The provision of synthetic databases using multiple imputation techniques is one possible strategy to ensure data protection, increase visibility of longitudinal databases and enhance the analytical potential.

Prediction of novel synthetic pathways for the production of desired chemicals.

PubMed

Cho, Ayoun; Yun, Hongseok; Park, Jin Hwan; Lee, Sang Yup; Park, Sunwon

2010-03-28

There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism. In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates. It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.

ENHANCED BIOACCUMULATION OF HEAVY METAL BY BACTERIA CELLS DISPLAYING SYNTHETIC PHYTOCHELATINS. (R827227)

EPA Science Inventory

A novel strategy using synthetic phytochelatins is described for the purpose of developing microbial agents for enhanced bioaccumulation of toxic metals. Synthetic genes encoding for several metal-chelating phytochelatin analogs (Glu-Cys)_nGly (EC8 (n = 8), EC11 (n = 11...

Neurotoxicity by synthetic androgen steroids: oxidative stress, apoptosis, and neuropathology: A review.

PubMed

Pomara, Cristoforo; Neri, Margherita; Bello, Stefania; Fiore, Carmela; Riezzo, Irene; Turillazzi, Emanuela

2015-01-01

Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS - induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.

Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review

PubMed Central

Pomara, Cristoforo; Neri, Margherita; Bello, Stefania; Fiore, Carmela; Riezzo, Irene; Turillazzi, Emanuela

2015-01-01

Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future. PMID:26074748

Uncertainty Assessment of Synthetic Design Hydrographs for Gauged and Ungauged Catchments

NASA Astrophysics Data System (ADS)

Brunner, Manuela I.; Sikorska, Anna E.; Furrer, Reinhard; Favre, Anne-Catherine

2018-03-01

Design hydrographs described by peak discharge, hydrograph volume, and hydrograph shape are essential for engineering tasks involving storage. Such design hydrographs are inherently uncertain as are classical flood estimates focusing on peak discharge only. Various sources of uncertainty contribute to the total uncertainty of synthetic design hydrographs for gauged and ungauged catchments. These comprise model uncertainties, sampling uncertainty, and uncertainty due to the choice of a regionalization method. A quantification of the uncertainties associated with flood estimates is essential for reliable decision making and allows for the identification of important uncertainty sources. We therefore propose an uncertainty assessment framework for the quantification of the uncertainty associated with synthetic design hydrographs. The framework is based on bootstrap simulations and consists of three levels of complexity. On the first level, we assess the uncertainty due to individual uncertainty sources. On the second level, we quantify the total uncertainty of design hydrographs for gauged catchments and the total uncertainty of regionalizing them to ungauged catchments but independently from the construction uncertainty. On the third level, we assess the coupled uncertainty of synthetic design hydrographs in ungauged catchments, jointly considering construction and regionalization uncertainty. We find that the most important sources of uncertainty in design hydrograph construction are the record length and the choice of the flood sampling strategy. The total uncertainty of design hydrographs in ungauged catchments depends on the catchment properties and is not negligible in our case.

Degradation and metabolism of synthetic plastics and associated products by Pseudomonas sp.: capabilities and challenges.

PubMed

Wilkes, R A; Aristilde, L

2017-09-01

Synthetic plastics, which are widely present in materials of everyday use, are ubiquitous and slowly-degrading polymers in environmental wastes. Of special interest are the capabilities of microorganisms to accelerate their degradation. Members of the metabolically diverse genus Pseudomonas are of particular interest due to their capabilities to degrade and metabolize synthetic plastics. Pseudomonas species isolated from environmental matrices have been identified to degrade polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyurethane, polyethylene terephthalate, polyethylene succinate, polyethylene glycol and polyvinyl alcohol at varying degrees of efficiency. Here, we present a review of the current knowledge on the factors that control the ability of Pseudomonas sp. to process these different plastic polymers and their by-products. These factors include cell surface attachment within biofilms, catalytic enzymes involved in oxidation or hydrolysis of the plastic polymer, metabolic pathways responsible for uptake and assimilation of plastic fragments and chemical factors that are advantageous or inhibitory to the biodegradation process. We also highlight future research directions required in order to harness fully the capabilities of Pseudomonas sp. in bioremediation strategies towards eliminating plastic wastes. © 2017 The Society for Applied Microbiology.

Anti-EGFR Agents: Current Status, Forecasts and Future Directions.

PubMed

Kwapiszewski, Radoslaw; Pawlak, Sebastian D; Adamkiewicz, Karolina

2016-12-01

The epidermal growth factor receptor (EGFR) is one of the most important and attractive targets for specific anticancer therapies. It is a robust regulator of pathways involved in cancer pathogenesis and progression. Thus far, clinical trials have demonstrated the benefits of monoclonal antibodies and synthetic tyrosine kinase inhibitors in targeting this receptor; however, novel strategies are still being developed. This article reviews the current state of efforts in targeting the EGFR in cancer therapy. Following a brief characterization of EGFR, we will present a complete list of anti-EGFR agents that are already approved, and available in clinical practice. Aside from the indications, we will present the sales forecasts and expiry dates of product patents for the selected agents. Finally, we discuss the novel anti-EGFR strategies that are currently in preclinical development.

A Post-synthetic Modification of II–VI Nanoparticles to Create Tb3+ and Eu3+ Luminophores

PubMed Central

Mukherjee, Prasun; Sloan, Robin F.; Shade, Chad M.; Waldeck, David H.; Petoud, Stéphane

2013-01-01

We describe a novel method for creating luminescent lanthanide-containing nanoparticles in which the lanthanide cations are sensitized by the semiconductor nanoparticle’s electronic excitation. In contrast to previous strategies, this new approach creates such materials by addition of external salt to a solution of fully formed nanoparticles. We demonstrate this post-synthetic modification for the lanthanide luminescence sensitization of two visible emitting lanthanides (Ln), Tb3+ and Eu3+ ions, through ZnS nanoparticles in which the cations were added post-synthetically as external Ln(NO3)3·xH2O salt to solutions of ZnS nanoparticles. The post-synthetically treated ZnS nanoparticle systems display Tb3+ and Eu3+ luminescence intensities that are comparable to those of doped Zn(Ln)S nanoparticles, which we reported previously (J. Phys. Chem. A, 2011, 115, 4031–4041). A comparison with the synthetically doped systems is used to contrast the spatial distribution of the lanthanide ions, bulk versus surface localized. The post-synthetic strategy described in this work is fundamentally different from the synthetic incorporation (doping) approach and offers a rapid and less synthetically demanding protocol for Tb3+:ZnS and Eu3+:ZnS luminophores, thereby facilitating their use in a broad range of applications. PMID:23997842

Synergistic Catalysis: A Powerful Synthetic Strategy for New Reaction Development

PubMed Central

Allen, Anna E.; MacMillan, David W. C.

2012-01-01

Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature. PMID:22518271

A C–H oxidation approach for streamlining synthesis of chiral polyoxygenated motifs

PubMed Central

Covell, Dustin J.; White, M. Christina

2013-01-01

Chiral oxygenated molecules are pervasive in natural products and medicinal agents; however, their chemical syntheses often necessitate numerous, wasteful steps involving functional group and oxidation state manipulations. Herein a strategy for synthesizing a readily diversifiable class of chiral building blocks, allylic alcohols, through sequential asymmetric C—H activation/resolution is evaluated against the state-of-the-art. The C—H oxidation routes’ capacity to strategically introduce oxygen into a sequence and thereby minimize non-productive manipulations is demonstrated to effect significant decreases in overall step-count and increases in yield and synthetic flexibility. PMID:25013239

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

PubMed

Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

2011-06-01

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

Engineering novel synthetic strategy to develop mesocarbon microbeads for multi-functional applications

NASA Astrophysics Data System (ADS)

Chaudhary, Anisha; Teotia, Satish; Kumar, Rajeev; Ramesha, K.; Dhakate, Sanjay R.; Kumari, Saroj

2018-04-01

To assess the challenge of affordable technology, present synthetic strategies can be extended to new low-cost synthesis and processing methods that have potential to tailor the properties of the materials. Here we report, a novel method for the synthesis of mesocarbon microbeads (MCMB) through a pre-processing involved pyrolysis technique. The resulting MCMB is compressed into a product and effects of heat treatment temperature on different properties of MCMB is studied. The use of MCMB for the electromagnetic interference (EMI) shielding is new and hence, the effect of heat treatment temperature on EMI shielding effectiveness is studied in X-band. It is observed that EMI shielding effectiveness increases to ‑39.6 dB on increasing the heat treatment temperature. The high conductivity of MCMB plate heat treated upto 2500 °C contributes to highly conducting networks. Additionally, to investigate the electrochemical performance of MCMB as an anode material for lithium ion batteries, 2500 °C heat treated MCMB powder is used to fabricate the electrode. The MCMB electrode exhibits high discharge capacity of 345 mAh g‑1 with a stable capacity for over 50 cycles and good rate capability. Thus, MCMB synthesized by this novel approach can be used for the development of high performance anode materials for Li-ion batteries.

Dual genetic selection of synthetic riboswitches in Escherichia coli.

PubMed

Nomura, Yoko; Yokobayashi, Yohei

2014-01-01

This chapter describes a genetic selection strategy to engineer synthetic riboswitches that can chemically regulate gene expression in Escherichia coli. Riboswitch libraries are constructed by randomizing the nucleotides that potentially comprise an expression platform and fused to the hybrid selection/screening marker tetA-gfpuv. Iterative ON and OFF selections are performed under appropriate conditions that favor the survival or the growth of the cells harboring the desired riboswitches. After the selection, rapid screening of individual riboswitch clones is performed by measuring GFPuv fluorescence without subcloning. This optimized dual genetic selection strategy can be used to rapidly develop synthetic riboswitches without detailed computational design or structural knowledge.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

PubMed Central

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

Erythrocytes-based synthetic delivery systems: transition from conventional to novel engineering strategies.

PubMed

Bhateria, Manisha; Rachumallu, Ramakrishna; Singh, Rajbir; Bhatta, Rabi Sankar

2014-08-01

Erythrocytes (red blood cells [RBCs]) and artificial or synthetic delivery systems such as liposomes, nanoparticles (NPs) are the most investigated carrier systems. Herein, progress made from conventional approach of using RBC as delivery systems to novel approach of using synthetic delivery systems based on RBC properties will be reviewed. We aim to highlight both conventional and novel approaches of using RBCs as potential carrier system. Conventional approaches which include two main strategies are: i) directly loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas novel approaches exploit structural, mechanical and biological properties of RBCs to design synthetic delivery systems through various engineering strategies. Initial attempts included coupling of antibodies to liposomes to specifically target RBCs. Knowledge obtained from several studies led to the development of RBC membrane derived liposomes (nanoerythrosomes), inspiring future application of RBC or its structural features in other attractive delivery systems (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater potential. In conclusion, this review dwells upon comparative analysis of various conventional and novel engineering strategies in developing RBC based drug delivery systems, diversifying their applications in arena of drug delivery. Regardless of the challenges in front of us, RBC based delivery systems offer an exciting approach of exploiting biological entities in a multitude of medical applications.

Emerging synthetic strategies for core cross-linked star (CCS) polymers and applications as interfacial stabilizers: bridging linear polymers and nanoparticles.

PubMed

Chen, Qijing; Cao, Xueteng; Xu, Yuanyuan; An, Zesheng

2013-10-01

Core cross-linked star (CCS) polymers become increasingly important in polymer science and are evaluated in many value-added applications. However, limitations exist to varied degrees for different synthetic methods. It is clear that improvement in synthetic efficiency is fundamental in driving this field moving even further. Here, the most recent advances are highlighted in synthetic strategies, including cross-linking with cross-linkers of low solubility, polymerization-induced self-assembly in aqueous-based heterogeneous media, and cross-linking via dynamic covalent bonds. The understanding of CCS polymers is also further refined to advocate their role as an intermediate between linear polymers and polymeric nanoparticles, and their use as interfacial stabilizers is rationalized within this context. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of line-specific strategies for improving carotenoid production in synthetic maize through data-driven mathematical modeling.

PubMed

Comas, Jorge; Benfeitas, Rui; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc; Farré, Gemma; Berman, Judit; Zorrilla, Uxue; Capell, Teresa; Sandmann, Gerhard; Zhu, Changfu; Christou, Paul; Alves, Rui

2016-09-01

Plant synthetic biology is still in its infancy. However, synthetic biology approaches have been used to manipulate and improve the nutritional and health value of staple food crops such as rice, potato and maize. With current technologies, production yields of the synthetic nutrients are a result of trial and error, and systematic rational strategies to optimize those yields are still lacking. Here, we present a workflow that combines gene expression and quantitative metabolomics with mathematical modeling to identify strategies for increasing production yields of nutritionally important carotenoids in the seed endosperm synthesized through alternative biosynthetic pathways in synthetic lines of white maize, which is normally devoid of carotenoids. Quantitative metabolomics and gene expression data are used to create and fit parameters of mathematical models that are specific to four independent maize lines. Sensitivity analysis and simulation of each model is used to predict which gene activities should be further engineered in order to increase production yields for carotenoid accumulation in each line. Some of these predictions (e.g. increasing Zmlycb/Gllycb will increase accumulated β-carotenes) are valid across the four maize lines and consistent with experimental observations in other systems. Other predictions are line specific. The workflow is adaptable to any other biological system for which appropriate quantitative information is available. Furthermore, we validate some of the predictions using experimental data from additional synthetic maize lines for which no models were developed. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Enhancing power density of biophotovoltaics by decoupling storage and power delivery

NASA Astrophysics Data System (ADS)

Saar, Kadi L.; Bombelli, Paolo; Lea-Smith, David J.; Call, Toby; Aro, Eva-Mari; Müller, Thomas; Howe, Christopher J.; Knowles, Tuomas P. J.

2018-01-01

Biophotovoltaic devices (BPVs), which use photosynthetic organisms as active materials to harvest light, have a range of attractive features relative to synthetic and non-biological photovoltaics, including their environmentally friendly nature and ability to self-repair. However, efficiencies of BPVs are currently lower than those of synthetic analogues. Here, we demonstrate BPVs delivering anodic power densities of over 0.5 W m-2, a value five times that for previously described BPVs. We achieved this through the use of cyanobacterial mutants with increased electron export characteristics together with a microscale flow-based design that allowed independent optimization of the charging and power delivery processes, as well as membrane-free operation by exploiting laminar flow to separate the catholyte and anolyte streams. These results suggest that miniaturization of active elements and flow control for decoupled operation and independent optimization of the core processes involved in BPV design are effective strategies for enhancing power output and thus the potential of BPVs as viable systems for sustainable energy generation.

Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides

PubMed Central

Roberts, Andrew G.; Johnston, Eric V.; Shieh, Jae-Hung; Sondey, Joseph P.; Hendrickson, Ronald C.; Moore, Malcolm A. S.; Danishefsky, Samuel J.

2015-01-01

Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation–desulfurization strategies. Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. PMID:26401918

Cyanobacterial chassis engineering for enhancing production of biofuels and chemicals.

PubMed

Gao, Xinyan; Sun, Tao; Pei, Guangsheng; Chen, Lei; Zhang, Weiwen

2016-04-01

To reduce dependence on fossil fuels and curb greenhouse effect, cyanobacteria have emerged as an important chassis candidate for producing biofuels and chemicals due to their capability to directly utilize sunlight and CO2 as the sole energy and carbon sources, respectively. Recent progresses in developing and applying various synthetic biology tools have led to the successful constructions of novel pathways of several dozen green fuels and chemicals utilizing cyanobacterial chassis. Meanwhile, it is increasingly recognized that in order to enhance productivity of the synthetic cyanobacterial systems, optimizing and engineering more robust and high-efficient cyanobacterial chassis should not be omitted. In recent years, numerous research studies have been conducted to enhance production of green fuels and chemicals through cyanobacterial chassis modifications involving photosynthesis, CO2 uptake and fixation, products exporting, tolerance, and cellular regulation. In this article, we critically reviewed recent progresses and universal strategies in cyanobacterial chassis engineering to make it more robust and effective for bio-chemicals production.

Rhamnolipids know-how: Looking for strategies for its industrial dissemination.

PubMed

Lovaglio, R B; Silva, V L; Ferreira, H; Hausmann, R; Contiero, J

2015-12-01

Despite the numerous advantages of biosurfactants, such as low toxicity, biodegradability and high stability, these compounds are not widely used because of the high cost of production. Details about genetics, regulation and biosynthesis of rhamnolipids by Pseudomonas aeruginosa, are extremely important to the development of bioprocesses involving the synthesis of these compounds. The holding of such knowledge associated with the use of metabolic engineering tools allow modification of producing strains and the development of synthetic routes, with the purpose of increasing the production of rhamnolipids. Considering the need to obtain this know-how, this review provides information on the rhamnolipids, covering genetics, biosynthesis of hydrophobic and hydrophilic portions, and regulation, plus some future strategies that would contribute to the expansion of the production of this green surfactant. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost-effectiveness of TNF inhibitors vs synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a Markov model study based on two longitudinal observational studies.

PubMed

Kvamme, Maria K; Lie, Elisabeth; Uhlig, Till; Moger, Tron A; Kvien, Tore K; Kristiansen, Ivar S

2015-07-01

The objective of this study was to estimate the additional costs and health benefits of adding a TNF inhibitor (TNFi) (adalimumab, certolizumab, etanercept, golimumab, infliximab) to a synthetic DMARD (sDMARD), e.g. MTX, in patients with RA. We developed the Norwegian RA model as a Markov model simulating 10 years of treatment with either TNFi plus sDMARDs (TNFi strategy) or sDMARDs alone (synthetic strategy). Patients in both strategies started in one of seven health states, based on the Short Form-6 Dimensions (SF-6D). The patients could move to better or worse health states according to transition probabilities. In the TNFi strategy, patients could stay on TNFi (including switch of TNFi), or switch to non-TNFi-biologics (abatacept, rituximab, tocilizumab), sDMARDs or no DMARD. In the synthetic strategy, patients remained on sDMARDs. Data from two observational studies were used for the assessment of resource use and utilities in the health states. Health benefits were evaluated using the EuroQol-5 Dimensions (EQ-5D) and SF-6D. The Norwegian RA model predicted that 10-year discounted health care costs totalled €124,942 (€475,266 including production losses) for the TNFi strategy and €65,584 (€436,517) for the synthetic strategy. The cost per additionally gained quality-adjusted life-year of adding a TNFi was €92,557 (€60,227 including production losses) using SF-6D and €61,285 (€39,841) using EQ-5D. Including health care costs only, the probability that TNFi treatment was cost-effective was 90% when using EQ-5D, assuming a Norwegian willingness-to-pay level of €67,300. TNFi treatment for RA is cost-effective when accounting for production losses. Excluding production losses, TNFi treatment is cost-effective using EQ-5D, but not SF-6D. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adherence to synthetic disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Results of the OBSERVAR Study.

PubMed

Juan Mas, Antonio; Castañeda, Santos; Cantero Santamaría, José I; Baquero, José L; Del Toro Santos, Francisco J

2017-12-27

Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy.

PubMed

Abbotts, Rachel; Jewell, Rosalyn; Nsengimana, Jérémie; Maloney, David J; Simeonov, Anton; Seedhouse, Claire; Elliott, Faye; Laye, Jon; Walker, Christy; Jadhav, Ajit; Grabowska, Anna; Ball, Graham; Patel, Poulam M; Newton-Bishop, Julia; Wilson, David M; Madhusudan, Srinivasan

2014-05-30

Phosphatase and tensin homolog (PTEN) loss is associated with genomic instability. APE1 is a key player in DNA base excision repair (BER) and an emerging drug target in cancer. We have developed small molecule inhibitors against APE1 repair nuclease activity. In the current study we explored a synthetic lethal relationship between PTEN and APE1 in melanoma. Clinicopathological significance of PTEN mRNA and APE1 mRNA expression was investigated in 191 human melanomas. Preclinically, PTEN-deficient BRAF-mutated (UACC62, HT144, and SKMel28), PTEN-proficient BRAF-wildtype (MeWo), and doxycycline-inducible PTEN-knockout BRAF-wildtype MeWo melanoma cells were DNA repair expression profiled and investigated for synthetic lethality using a panel of four prototypical APE1 inhibitors. In human tumours, low PTEN mRNA and high APE1 mRNA was significantly associated with reduced relapse free and overall survival. Pre-clinically, compared to PTEN-proficient cells, PTEN-deficient cells displayed impaired expression of genes involved in DNA double strand break (DSB) repair. Synthetic lethality in PTEN-deficient cells was evidenced by increased sensitivity, accumulation of DSBs and induction of apoptosis following treatment with APE1 inhibitors. We conclude that PTEN deficiency is not only a promising biomarker in melanoma, but can also be targeted by a synthetic lethality strategy using inhibitors of BER, such as those targeting APE1.

Dental materials for cleft palate repair.

PubMed

Sharif, Faiza; Ur Rehman, Ihtesham; Muhammad, Nawshad; MacNeil, Sheila

2016-04-01

Numerous bone and soft tissue grafting techniques are followed to repair cleft of lip and palate (CLP) defects. In addition to the gold standard surgical interventions involving the use of autogenous grafts, various allogenic and xenogenic graft materials are available for bone regeneration. In an attempt to discover minimally invasive and cost effective treatments for cleft repair, an exceptional growth in synthetic biomedical graft materials have occurred. This study gives an overview of the use of dental materials to repair cleft of lip and palate (CLP). The eligibility criteria for this review were case studies, clinical trials and retrospective studies on the use of various types of dental materials in surgical repair of cleft palate defects. Any data available on the surgical interventions to repair alveolar or palatal cleft, with natural or synthetic graft materials was included in this review. Those datasets with long term clinical follow-up results were referred to as particularly relevant. The results provide encouraging evidence in favor of dental and other related biomedical materials to fill the gaps in clefts of lip and palate. The review presents the various bones and soft tissue replacement strategies currently used, tested or explored for the repair of cleft defects. There was little available data on the use of synthetic materials in cleft repair which was a limitation of this study. In conclusion although clinical trials on the use of synthetic materials are currently underway the uses of autologous implants are the preferred treatment methods to date. Copyright © 2015 Elsevier B.V. All rights reserved.

Harbouring public good mutants within a pathogen population can increase both fitness and virulence.

PubMed

Lindsay, Richard J; Kershaw, Michael J; Pawlowska, Bogna J; Talbot, Nicholas J; Gudelj, Ivana

2016-12-28

Existing theory, empirical, clinical and field research all predict that reducing the virulence of individuals within a pathogen population will reduce the overall virulence, rendering disease less severe. Here, we show that this seemingly successful disease management strategy can fail with devastating consequences for infected hosts. We deploy cooperation theory and a novel synthetic system involving the rice blast fungus Magnaporthe oryzae . In vivo infections of rice demonstrate that M. oryzae virulence is enhanced, quite paradoxically, when a public good mutant is present in a population of high-virulence pathogens. We reason that during infection, the fungus engages in multiple cooperative acts to exploit host resources. We establish a multi-trait cooperation model which suggests that the observed failure of the virulence reduction strategy is caused by the interference between different social traits. Multi-trait cooperative interactions are widespread, so we caution against the indiscriminant application of anti-virulence therapy as a disease-management strategy.

Recent Developments in Organophosphorus Flame Retardants Containing P-C Bond and Their Applications

PubMed Central

Wendels, Sophie; Chavez, Thiebault; Bonnet, Martin; Gaan, Sabyasachi

2017-01-01

Organophosphorus compounds containing P-C bonds are increasingly developed as flame retardant additives due to their excellent thermal and hydrolytic stability and ease of synthesis. The latest development (since 2010) in organophosphorus flame retardants containing P-C bonds summarized in this review. In this review, we have broadly classified such phosphorus compounds based on the carbon unit linked to the phosphorus atom i.e., could be a part of either an aliphatic or an aromatic unit. We have only considered those published literature where a P-C bond was created as a part of synthetic strategy to make either an intermediate or a final organophosphorus compound with an aim to use it as a flame retardant. General synthetic strategies to create P-C bonds are briefly discussed. Most popular synthetic strategies used for developing P-C containing phosphorus based flame retardants include Michael addition, Michaelis–Arbuzov, Friedels–Crafts and Grignard reactions. In general, most flame retardant derivatives discussed in this review have been prepared via a one- to two-step synthetic strategy with relatively high yields greater than 80%. Specific examples of P-C containing flame retardants synthesized via suitable synthetic strategy and their applications on various polymer systems are described in detail. Aliphatic phosphorus compounds being liquids or low melting solids are generally applied in polymers via coatings (cellulose) or are incorporated in the bulk of the polymers (epoxy, polyurethanes) during their polymerization as reactive or non-reactive additives. Substituents on the P atoms and the chemistry of the polymer matrix greatly influence the flame retardant behavior of these compounds (condensed phase vs. the gas phase). Recently, aromatic DOPO based phosphinate flame retardants have been developed with relatively higher thermal stabilities (>250 °C). Such compounds have potential as flame retardants for high temperature processable polymers such as polyesters and polyamides. A vast variety of P-C bond containing efficient flame retardants are being developed; however, further work in terms of their economical synthetic methods, detailed impact on mechanical properties and processability, long term durability and their toxicity and environmental impact is much needed for their potential commercial exploitations. PMID:28773147

Investigation of the origin of ephedrine and methamphetamine by stable isotope ratio mass spectrometry: a Japanese experience.

PubMed

Makino, Y; Urano, Y; Nagano, T

2005-01-01

Illicit drug abuse is a serious global problem that can only be solved through international cooperation. In Asian countries, the abuse of methamphetamine is one of the most pressing problems. To assist in the control of methamphetamine, the authors investigated in detail the character of ephedrine, which is a key precursor for the illicit manufacture of methamphetamine. Commercial ephedrine is produced by one of three methods: (a) extraction from Ephedra plants, (b) full chemical synthesis or (c) via a semi-synthetic process involving the fermentation of sugar, followed by amination. Although chemically there is no difference between ephedrine samples from different origins (natural, synthetic or semi-synthetic), scientific and analytical tools such as drug-characterization and impurity-profiling programmes may provide valuable information for law enforcement and regulatory activities as part of precursor control strategies. During the research under discussion in the present article, in addition to classical impurity profiling of manufacturing by-products, the use of stable isotope ratio mass spectrometry was investigated for determining the origin of the ephedrine that had been used as a precursor in seized methamphetamine samples. The results of carbon and nitrogen stable isotope ratio (delta13C and delta15N) analysis of samples of crystalline methamphetamine seized in Japan suggested that the drug had been synthesized from either natural or semi-synthetic ephedrine and not from synthetic ephedrine. Stable isotope ratio analysis is expected to be a useful tool for tracing the origins of seized methamphetamine. It has attracted much interest from precursor control authorities in Japan and the East Asian region and may prove useful in the international control of precursors.

Simultaneous knockdown of six non-family genes using a single synthetic RNAi fragment in Arabidopsis thaliana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czarnecki, Olaf; Bryan, Anthony C.; Jawdy, Sara S.

Genetic engineering of plants that results in successful establishment of new biochemical or regulatory pathways requires stable introduction of one or more genes into the plant genome. It might also be necessary to down-regulate or turn off expression of endogenous genes in order to reduce activity of competing pathways. An established way to knockdown gene expression in plants is expressing a hairpin-RNAi construct, eventually leading to degradation of a specifically targeted mRNA. Knockdown of multiple genes that do not share homologous sequences is still challenging and involves either sophisticated cloning strategies to create vectors with different serial expression constructs ormore » multiple transformation events that is often restricted by a lack of available transformation markers. Synthetic RNAi fragments were assembled in yeast carrying homologous sequences to six or seven non-family genes and introduced into pAGRIKOLA. Transformation of Arabidopsis thaliana and subsequent expression analysis of targeted genes proved efficient knockdown of all target genes. In conclusion, we present a simple and cost-effective method to create constructs to simultaneously knockdown multiple non-family genes or genes that do not share sequence homology. The presented method can be applied in plant and animal synthetic biology as well as traditional plant and animal genetic engineering.« less

Simultaneous knockdown of six non-family genes using a single synthetic RNAi fragment in Arabidopsis thaliana

DOE PAGES

Czarnecki, Olaf; Bryan, Anthony C.; Jawdy, Sara S.; ...

2016-02-17

Genetic engineering of plants that results in successful establishment of new biochemical or regulatory pathways requires stable introduction of one or more genes into the plant genome. It might also be necessary to down-regulate or turn off expression of endogenous genes in order to reduce activity of competing pathways. An established way to knockdown gene expression in plants is expressing a hairpin-RNAi construct, eventually leading to degradation of a specifically targeted mRNA. Knockdown of multiple genes that do not share homologous sequences is still challenging and involves either sophisticated cloning strategies to create vectors with different serial expression constructs ormore » multiple transformation events that is often restricted by a lack of available transformation markers. Synthetic RNAi fragments were assembled in yeast carrying homologous sequences to six or seven non-family genes and introduced into pAGRIKOLA. Transformation of Arabidopsis thaliana and subsequent expression analysis of targeted genes proved efficient knockdown of all target genes. In conclusion, we present a simple and cost-effective method to create constructs to simultaneously knockdown multiple non-family genes or genes that do not share sequence homology. The presented method can be applied in plant and animal synthetic biology as well as traditional plant and animal genetic engineering.« less

Advances in Enterprise Control. AEC Proceedings, November 15-16, 1999/San Diego, California

DTIC Science & Technology

1999-11-16

structure of tropical termite mounds. 2.3. Mechanisms that each agent deposits one unit of pheromone per unit time and that a proportion 0 < E < 1 of the...Stubberud 137 Section 4: Distributed and Agent-Based Strategies 149 Synthetic Pheromones for Distributed Motion Control by H. Van Dyke Parunak and...Computer Engineering, June, 1994. 147 148 Section 4 Distributed and Agent-Based Strategies 149 150 Synthetic Pheromones for Distributed Motion

Simulation of Biomimetic Recognition between Polymers and Surfaces

NASA Astrophysics Data System (ADS)

Golumbfskie, Aaron J.; Pande, Vijay S.; Chakraborty, Arup K.

1999-10-01

Many biological processes, such as transmembrane signaling and pathogen-host interactions, are initiated by a protein recognizing a specific pattern of binding sites on part of a membrane or cell surface. By recognition, we imply that the polymer quickly finds and then adsorbs strongly on the pattern-matched region and not on others. The development of synthetic systems that can mimic such recognition between polymers and surfaces could have significant impact on advanced applications such as the development of sensors, molecular-scale separation processes, and synthetic viral inhibition agents. Attempting to affect recognition in synthetic systems by copying the detailed chemistries to which nature has been led over millenia of evolution does not seem practical for most applications. This leads us to the following question: Are there any universal strategies that can affect recognition between polymers and surfaces? Such generic strategies may be easier to implement in abiotic applications. We describe results that suggest that biomimetic recognition between synthetic polymers and surfaces is possible by exploiting certain generic strategies, and we elucidate the kinetic mechanisms by which this occurs. Our results suggest convenient model systems for experimental studies of dynamics in free energy landscapes characteristic of frustrated systems.

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.

Management of chronic unstable acromioclavicular joint injuries.

PubMed

Cisneros, Luis Natera; Reiriz, Juan Sarasquete

2017-12-01

The acromioclavicular joint represents the link between the clavicle and the scapula, which is responsible for the synchronized dynamic of the shoulder girdle. Chronic acromioclavicular joint instability involves changes in the orientation of the scapula, which provokes cinematic alterations that might result in chronic pain. Several surgical strategies for the management of patients with chronic and symptomatic acromioclavicular joint instability have been described. The range of possibilities includes anatomical and non-anatomical techniques, open and arthroscopy-assisted procedures, and biological and synthetic grafts. Surgical management of chronic acromioclavicular joint instability should involve the reconstruction of the torn ligaments because it is accepted that from three weeks after the injury, these structures may lack healing potential. Here, we provide a review of the literature regarding the management of chronic acromioclavicular joint instability. Expert opinion, Level V.

A biochemical network can control formation of a synthetic material by sensing numerous specific stimuli

NASA Astrophysics Data System (ADS)

Hun Yeon, Ju; Chan, Karen Y. T.; Wong, Ting-Chia; Chan, Kelvin; Sutherland, Michael R.; Ismagilov, Rustem F.; Pryzdial, Edward L. G.; Kastrup, Christian J.

2015-05-01

Developing bio-compatible smart materials that assemble in response to environmental cues requires strategies that can discriminate multiple specific stimuli in a complex milieu. Synthetic materials have yet to achieve this level of sensitivity, which would emulate the highly evolved and tailored reaction networks of complex biological systems. Here we show that the output of a naturally occurring network can be replaced with a synthetic material. Exploiting the blood coagulation system as an exquisite biological sensor, the fibrin clot end-product was replaced with a synthetic material under the biological control of a precisely regulated cross-linking enzyme. The functions of the coagulation network remained intact when the material was incorporated. Clot-like polymerization was induced in indirect response to distinct small molecules, phospholipids, enzymes, cells, viruses, an inorganic solid, a polyphenol, a polysaccharide, and a membrane protein. This strategy demonstrates for the first time that an existing stimulus-responsive biological network can be used to control the formation of a synthetic material by diverse classes of physiological triggers.

Microfluidic-Based Generation of Size-Controlled, Biofunctionalized Synthetic Polymer Microgels for Cell Encapsulation

PubMed Central

Headen, Devon M.; Aubry, Guillaume; Lu, Hang

2014-01-01

Cell and islet microencapsulation in synthetic hydrogels provide an immunoprotective and cell-supportive microenvironment. A microfluidic strategy for the genaration of biofunctionalized, synthetic microgel particles with precise control over particle size and molecular permeability for cell and protein delivery is presented. These engineered capsules support high cell viability and function of encapsulated human stem cells and islets. PMID:24615922

Application of the Organic Synthetic Designs to Astrobiology

NASA Astrophysics Data System (ADS)

Kolb, V. M.

2009-12-01

In this paper we propose a synthesis of the heterocyclic compounds and the insoluble materials on the meteorites. Our synthetic scheme involves the reaction of sugars and amino acids, the so-called Maillard reaction. We have developed this scheme based on the combined analysis of the regular and retrosynthetic organic synthetic principles. The merits of these synthetic methods for the prebiotic design are addressed.

Synthetic Strategies in the Preparation of Polymer/Inorganic Hybrid Nanoparticles

PubMed Central

Hood, Matthew A.; Mari, Margherita; Muñoz-Espí, Rafael

2014-01-01

This article reviews the recent advances and challenges in the preparation of polymer/inorganic hybrid nanoparticles. We mainly focus on synthetic strategies, basing our classification on whether the inorganic and the polymer components have been formed in situ or ex situ, of the hybrid material. Accordingly, four types of strategies are identified and described, referring to recent examples: (i) ex situ formation of the components and subsequent attachment or integration, either by covalent or noncovalent bonding; (ii) in situ polymerization in the presence of ex situ formed inorganic nanoparticles; (iii) in situ precipitation of the inorganic components on or in polymer structures; and (iv) strategies in which both polymer and inorganic component are simultaneously formed in situ. PMID:28788665

40 CFR 52.777 - Control strategy: photochemical oxidants (hydrocarbons).

Code of Federal Regulations, 2013 CFR

2013-07-01

... lithography operations, business plastics, automotive plastics, and synthetic organic chemical manufacturing..., automotive plastics, and synthetic organic chemical manufacturing industries (SOCMI) batch processes... Michigan area, and an agreed order between U.S. Steel (currently USX Corporation) and the IDEM signed by...

40 CFR 52.777 - Control strategy: photochemical oxidants (hydrocarbons).

Code of Federal Regulations, 2014 CFR

2014-07-01

... plastics, automotive plastics, and synthetic organic chemical manufacturing industries (SOCMI) batch... wastewater processes, offset lithography operations, business plastics, automotive plastics, and synthetic... order between U.S. Steel (currently USX Corporation) and the IDEM signed by IDEM on March 22, 1996...

40 CFR 52.777 - Control strategy: photochemical oxidants (hydrocarbons).

Code of Federal Regulations, 2010 CFR

2010-07-01

... plastics, automotive plastics, and synthetic organic chemical manufacturing industries (SOCMI) batch... wastewater processes, offset lithography operations, business plastics, automotive plastics, and synthetic... order between U.S. Steel (currently USX Corporation) and the IDEM signed by IDEM on March 22, 1996...

40 CFR 52.777 - Control strategy: photochemical oxidants (hydrocarbons).

Code of Federal Regulations, 2011 CFR

2011-07-01

... plastics, automotive plastics, and synthetic organic chemical manufacturing industries (SOCMI) batch... wastewater processes, offset lithography operations, business plastics, automotive plastics, and synthetic... order between U.S. Steel (currently USX Corporation) and the IDEM signed by IDEM on March 22, 1996...

40 CFR 52.777 - Control strategy: photochemical oxidants (hydrocarbons).

Code of Federal Regulations, 2012 CFR

2012-07-01

... lithography operations, business plastics, automotive plastics, and synthetic organic chemical manufacturing..., automotive plastics, and synthetic organic chemical manufacturing industries (SOCMI) batch processes... Michigan area, and an agreed order between U.S. Steel (currently USX Corporation) and the IDEM signed by...

Synthesis of Methyl Diantilis, a Commercially Important Fragrance

ERIC Educational Resources Information Center

Miles, William H.; Connell, Katelyn B.

2006-01-01

Synthetic sequences in the undergraduate organic chemistry laboratory illustrate important synthetic strategies, reagents, or experimental techniques, oftentimes resulting in the synthesis of commercially important compounds. A fragrance with a 'spicy, carnation, sweet, vanilla', named after carnations (Dianthus caryophllus), Methyl Diantillis is…

A robust gene-stacking method utilizing yeast assembly for plant synthetic biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shih, Patrick M.; Vuu, Khanh; Mansoori, Nasim

The advent and growth of synthetic biology has demonstrated its potential as a promising avenue of research to address many societal needs. But, plant synthetic biology efforts have been hampered by a dearth of DNA part libraries, versatile transformation vectors and efficient assembly strategies. We describe a versatile system (named jStack) utilizing yeast homologous recombination to efficiently assemble DNA into plant transformation vectors. We also demonstrate how this method can facilitate pathway engineering of molecules of pharmaceutical interest, production of potential biofuels and shuffling of disease-resistance traits between crop species. Our approach provides a powerful alternative to conventional strategies formore » stacking genes and traits to address many impending environmental and agricultural challenges.« less

A robust gene-stacking method utilizing yeast assembly for plant synthetic biology

DOE PAGES

Shih, Patrick M.; Vuu, Khanh; Mansoori, Nasim; ...

2016-10-26

The advent and growth of synthetic biology has demonstrated its potential as a promising avenue of research to address many societal needs. But, plant synthetic biology efforts have been hampered by a dearth of DNA part libraries, versatile transformation vectors and efficient assembly strategies. We describe a versatile system (named jStack) utilizing yeast homologous recombination to efficiently assemble DNA into plant transformation vectors. We also demonstrate how this method can facilitate pathway engineering of molecules of pharmaceutical interest, production of potential biofuels and shuffling of disease-resistance traits between crop species. Our approach provides a powerful alternative to conventional strategies formore » stacking genes and traits to address many impending environmental and agricultural challenges.« less

A versatile synthetic route for the preparation of titanium metal-organic frameworks

DOE PAGES

Zou, Lanfang; Feng, Dawei; Liu, Tian-Fu; ...

2016-02-01

Exploitation of new titanium metal–organic frameworks (Ti-MOFs) with high crystallinity has been attracting great attention due to their vast application potential in photocatalysis. Herein a versatile synthetic strategy, namely, High Valence Metathesis and Oxidation (HVMO), is developed to synthesize a series of Ti-MOFs with predesigned topologies and structures. The crystallinity of these Ti-MOFs was well maintained throughout, as confirmed by powder X-ray diffraction and gas adsorption measurements. Significantly, there were only a few examples of Ti-MOFs, not to mention a general synthetic strategy for various kinds of Ti-MOFs in the literature. This contribution also illustrates the intriguing potential of Ti-MOFmore » platforms in photocatalysis.« less

Biogenetically inspired synthesis and skeletal diversification of indole alkaloids.

PubMed

Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

2014-01-01

To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

Dearomative dihydroxylation with arenophiles

NASA Astrophysics Data System (ADS)

Southgate, Emma H.; Pospech, Jola; Fu, Junkai; Holycross, Daniel R.; Sarlah, David

2016-10-01

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N-N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

PubMed

Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

2018-05-01

NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

Chemical modulation of M13 bacteriophage and its functional opportunities for nanomedicine

PubMed Central

Chung, Woo-Jae; Lee, Doe-Young; Yoo, So Young

2014-01-01

M13 bacteriophage (phage) has emerged as an attractive bionanomaterial owing to its genetically tunable surface chemistry and its potential to self-assemble into hierarchical structures. Furthermore, because of its unique nanoscopic structure, phage has been proposed as a model system in soft condensed physics and as a biomimetic building block for structured functional materials. Genetic engineering of phage provides great opportunities to develop novel nanomaterials with functional surface peptide motifs; however, this biological approach is generally limited to peptides containing the 20 natural amino acids. To extend the scope of phage applications, strategies involving chemical modification have been employed to incorporate a wider range of functional groups, including synthetic chemical compounds. In this review, we introduce the design of chemoselective phage functionalization and discuss how such a strategy is combined with genetic engineering for a variety of medical applications, as reported in recent literature. PMID:25540583

Chemical modulation of M13 bacteriophage and its functional opportunities for nanomedicine.

PubMed

Chung, Woo-Jae; Lee, Doe-Young; Yoo, So Young

2014-01-01

M13 bacteriophage (phage) has emerged as an attractive bionanomaterial owing to its genetically tunable surface chemistry and its potential to self-assemble into hierarchical structures. Furthermore, because of its unique nanoscopic structure, phage has been proposed as a model system in soft condensed physics and as a biomimetic building block for structured functional materials. Genetic engineering of phage provides great opportunities to develop novel nanomaterials with functional surface peptide motifs; however, this biological approach is generally limited to peptides containing the 20 natural amino acids. To extend the scope of phage applications, strategies involving chemical modification have been employed to incorporate a wider range of functional groups, including synthetic chemical compounds. In this review, we introduce the design of chemoselective phage functionalization and discuss how such a strategy is combined with genetic engineering for a variety of medical applications, as reported in recent literature.

One-pot synthesis of hierarchical FeZSM-5 zeolites from natural aluminosilicates for selective catalytic reduction of NO by NH3

PubMed Central

Yue, Yuanyuan; Liu, Haiyan; Yuan, Pei; Yu, Chengzhong; Bao, Xiaojun

2015-01-01

Iron-modified ZSM-5 zeolites (FeZSM-5s) have been considered to be a promising catalyst system to reduce nitrogen oxide emissions, one of the most important global environmental issues, but their synthesis faces enormous economic and environmental challenges. Herein we report a cheap and green strategy to fabricate hierarchical FeZSM-5 zeolites from natural aluminosilicate minerals via a nanoscale depolymerization-reorganization method. Our strategy is featured by neither using any aluminum-, silicon-, or iron-containing inorganic chemical nor involving any mesoscale template and any post-synthetic modification. Compared with the conventional FeZSM-5 synthesized from inorganic chemicals with the similar Fe content, the resulting hierarchical FeZSM-5 with highly-dispersed iron species showed superior catalytic activity in the selective catalytic reduction of NO by NH3. PMID:25791958

A general strategy to synthesize chemically and topologically anisotropic Janus particles

PubMed Central

Fan, Jun-Bing; Song, Yongyang; Liu, Hong; Lu, Zhongyuan; Zhang, Feilong; Liu, Hongliang; Meng, Jingxin; Gu, Lin; Wang, Shutao; Jiang, Lei

2017-01-01

Emulsion polymerization is the most widely used synthetic technique for fabricating polymeric particles. The interfacial tension generated with this technique limits the ability to tune the topology and chemistry of the resultant particles. We demonstrate a general emulsion interfacial polymerization approach that involves introduction of additional anchoring molecules surrounding the microdroplets to synthesize a large variety of Janus particles with controllable topological and chemical anisotropy. This strategy is based on interfacial polymerization mediated by an anchoring effect at the interface of microdroplets. Along the interface of the microdroplets, the diverse topology and surface chemistry features of the Janus particles can be precisely tuned by regulating the monomer type and concentration as well as polymerization time. This method is applicable to a wide variety of monomers, including positively charged, neutrally charged, and negatively charged monomers, thereby enriching the community of Janus particles. PMID:28691089

Performance Guaranteed Inertia Emulation forDiesel-Wind System Feed Microgrid via ModelReference Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melin, Alexander M.; Zhang, Yichen; Djouadi, Seddik

In this paper, a model reference control based inertia emulation strategy is proposed. Desired inertia can be precisely emulated through this control strategy so that guaranteed performance is ensured. A typical frequency response model with parametrical inertia is set to be the reference model. A measurement at a specific location delivers the information of disturbance acting on the diesel-wind system to the referencemodel. The objective is for the speed of the diesel-wind system to track the reference model. Since active power variation is dominantly governed by mechanical dynamics and modes, only mechanical dynamics and states, i.e., a swing-engine-governor system plusmore » a reduced-order wind turbine generator, are involved in the feedback control design. The controller is implemented in a three-phase diesel-wind system feed microgrid. The results show exact synthetic inertia is emulated, leading to guaranteed performance and safety bounds.« less

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016.

PubMed

Seth, Puja; Scholl, Lawrence; Rudd, Rose A; Bacon, Sarah

2018-03-30

During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3), † CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids), § cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid. ¶ From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.

An implementation of differential evolution algorithm for inversion of geoelectrical data

NASA Astrophysics Data System (ADS)

Balkaya, Çağlayan

2013-11-01

Differential evolution (DE), a population-based evolutionary algorithm (EA) has been implemented to invert self-potential (SP) and vertical electrical sounding (VES) data sets. The algorithm uses three operators including mutation, crossover and selection similar to genetic algorithm (GA). Mutation is the most important operator for the success of DE. Three commonly used mutation strategies including DE/best/1 (strategy 1), DE/rand/1 (strategy 2) and DE/rand-to-best/1 (strategy 3) were applied together with a binomial type crossover. Evolution cycle of DE was realized without boundary constraints. For the test studies performed with SP data, in addition to both noise-free and noisy synthetic data sets two field data sets observed over the sulfide ore body in the Malachite mine (Colorado) and over the ore bodies in the Neem-Ka Thana cooper belt (India) were considered. VES test studies were carried out using synthetically produced resistivity data representing a three-layered earth model and a field data set example from Gökçeada (Turkey), which displays a seawater infiltration problem. Mutation strategies mentioned above were also extensively tested on both synthetic and field data sets in consideration. Of these, strategy 1 was found to be the most effective strategy for the parameter estimation by providing less computational cost together with a good accuracy. The solutions obtained by DE for the synthetic cases of SP were quite consistent with particle swarm optimization (PSO) which is a more widely used population-based optimization algorithm than DE in geophysics. Estimated parameters of SP and VES data were also compared with those obtained from Metropolis-Hastings (M-H) sampling algorithm based on simulated annealing (SA) without cooling to clarify uncertainties in the solutions. Comparison to the M-H algorithm shows that DE performs a fast approximate posterior sampling for the case of low-dimensional inverse geophysical problems.

Photoreactive synthetic regulator of protein function and methods of use thereof

DOEpatents

Trauner, Dirk; Isacoff, Ehud Y; Kramer, Richard H; Banghart, Matthew R; Fortin, Doris L; Mourot, Alexandre

2015-03-31

The present disclosure provides a photoreactive synthetic regulator of protein function. The present disclosure further provides a light-regulated polypeptide that includes a subject synthetic regulator. Also provided are cells and membranes comprising a subject light-regulated polypeptide. The present disclosure further provides methods of modulating protein function, involving use of light.

One-pot DNA construction for synthetic biology: the Modular Overlap-Directed Assembly with Linkers (MODAL) strategy

PubMed Central

Casini, Arturo; MacDonald, James T.; Jonghe, Joachim De; Christodoulou, Georgia; Freemont, Paul S.; Baldwin, Geoff S.; Ellis, Tom

2014-01-01

Overlap-directed DNA assembly methods allow multiple DNA parts to be assembled together in one reaction. These methods, which rely on sequence homology between the ends of DNA parts, have become widely adopted in synthetic biology, despite being incompatible with a key principle of engineering: modularity. To answer this, we present MODAL: a Modular Overlap-Directed Assembly with Linkers strategy that brings modularity to overlap-directed methods, allowing assembly of an initial set of DNA parts into a variety of arrangements in one-pot reactions. MODAL is accompanied by a custom software tool that designs overlap linkers to guide assembly, allowing parts to be assembled in any specified order and orientation. The in silico design of synthetic orthogonal overlapping junctions allows for much greater efficiency in DNA assembly for a variety of different methods compared with using non-designed sequence. In tests with three different assembly technologies, the MODAL strategy gives assembly of both yeast and bacterial plasmids, composed of up to five DNA parts in the kilobase range with efficiencies of between 75 and 100%. It also seamlessly allows mutagenesis to be performed on any specified DNA parts during the process, allowing the one-step creation of construct libraries valuable for synthetic biology applications. PMID:24153110

Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

PubMed

Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R; Galli, M

1976-04-20

Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

Evaluation of generic types of drilling fluid using a risk-based analytic hierarchy process.

PubMed

Sadiq, Rehan; Husain, Tahir; Veitch, Brian; Bose, Neil

2003-12-01

The composition of drilling muds is based on a mixture of clays and additives in a base fluid. There are three generic categories of base fluid--water, oil, and synthetic. Water-based fluids (WBFs) are relatively environmentally benign, but drilling performance is better with oil-based fluids (OBFs). The oil and gas industry developed synthetic-based fluids (SBFs), such as vegetable esters, olefins, ethers, and others, which provide drilling performance comparable to OBFs, but with lower environmental and occupational health effects. The primary objective of this paper is to present a methodology to guide decision-making in the selection and evaluation of three generic types of drilling fluids using a risk-based analytic hierarchy process (AHP). In this paper a comparison of drilling fluids is made considering various activities involved in the life cycle of drilling fluids. This paper evaluates OBFs, WBFs, and SBFs based on four major impacts--operations, resources, economics, and liabilities. Four major activities--drilling, discharging offshore, loading and transporting, and disposing onshore--cause the operational impacts. Each activity involves risks related to occupational injuries (safety), general public health, environmental impact, and energy use. A multicriteria analysis strategy was used for the selection and evaluation of drilling fluids using a risk-based AHP. A four-level hierarchical structure is developed to determine the final relative scores, and the SBFs are found to be the best option.

Engineering of synthetic, stress-responsive yeast promoters

PubMed Central

Rajkumar, Arun S.; Liu, Guodong; Bergenholm, David; Arsovska, Dushica; Kristensen, Mette; Nielsen, Jens; Jensen, Michael K.; Keasling, Jay D.

2016-01-01

Advances in synthetic biology and our understanding of the rules of promoter architecture have led to the development of diverse synthetic constitutive and inducible promoters in eukaryotes and prokaryotes. However, the design of promoters inducible by specific endogenous or environmental conditions is still rarely undertaken. In this study, we engineered and characterized a set of strong, synthetic promoters for budding yeast Saccharomyces cerevisiae that are inducible under acidic conditions (pH ≤ 3). Using available expression and transcription factor binding data, literature on transcriptional regulation, and known rules of promoter architecture we improved the low-pH performance of the YGP1 promoter by modifying transcription factor binding sites in its upstream activation sequence. The engineering strategy outlined for the YGP1 promoter was subsequently applied to create a response to low pH in the unrelated CCW14 promoter. We applied our best promoter variants to low-pH fermentations, enabling ten-fold increased production of lactic acid compared to titres obtained with the commonly used, native TEF1 promoter. Our findings outline and validate a general strategy to iteratively design and engineer synthetic yeast promoters inducible to environmental conditions or stresses of interest. PMID:27325743

Microbial colonization of biopolymeric thin films containing natural compounds and antibiotics fabricated by MAPLE

NASA Astrophysics Data System (ADS)

Cristescu, R.; Surdu, A. V.; Grumezescu, A. M.; Oprea, A. E.; Trusca, R.; Vasile, O.; Dorcioman, G.; Visan, A.; Socol, G.; Mihailescu, I. N.; Mihaiescu, D.; Enculescu, M.; Chifiriuc, M. C.; Boehm, R. D.; Narayan, R. J.; Chrisey, D. B.

2015-05-01

Although a great number of antibiotics are currently available, they are often rendered ineffective by the ability of microbial strains to develop genetic resistance and to grow in biofilms. Since many antimicrobial agents poorly penetrate biofilms, biofilm-associated infections often require high concentrations of antimicrobial agents for effective treatment. Among the various strategies that may be used to inhibit microbial biofilms, one strategy that has generated significant interest involves the use of bioactive surfaces that are resistant to microbial colonization. In this respect, we used matrix assisted pulsed laser evaporation (MAPLE) involving a pulsed KrF* excimer laser source (λ = 248 nm, τ = 25 ns, ν = 10 Hz) to obtain thin composite biopolymeric films containing natural (flavonoid) or synthetic (antibiotic) compounds as bioactive substances. Chemical composition and film structures were investigated by Fourier transform infrared spectroscopy and X-ray diffraction. Films morphology was studied by scanning electron microscopy and transmission electron microscopy. The antimicrobial assay of the microbial biofilms formed on these films was assessed by the viable cell counts method. The flavonoid-containing thin films showed increased resistance to microbial colonization, highlighting their potential to be used for the design of anti-biofilm surfaces.

Enzymatic Synthesis of Amino Acids Endcapped Polycaprolactone: A Green Route Towards Functional Polyesters.

PubMed

Duchiron, Stéphane W; Pollet, Eric; Givry, Sébastien; Avérous, Luc

2018-01-30

ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies were tested, a first one with direct polymerization of CL with the native amino acids and a second one involving the use of an amino acid with protected functional groups. The first route showed that mainly polycaprolactone (PCL) homopolymer could be obtained and highlighted the lack of reactivity of the unmodified amino acids due to poor solubility and affinity with the lipase active site. The second strategy based on protected cysteine showed higher monomer conversion, with the amino acids acting as (co-)initiators, but their insertion along the PCL chains remained limited to chain endcapping. These results thus showed the possibility to synthesize enzymatically polycaprolactone-based chains bearing amino acids units. Such cysteine endcapped PCL materials could then find application in the biomedical field. Indeed, subsequent functionalization of these polyesters with drugs or bioactive molecules can be obtained, by derivatization of the amino acids, after removal of the protecting group.

Hemostatic strategies for traumatic and surgical bleeding

PubMed Central

Behrens, Adam M.; Sikorski, Michael J.; Kofinas, Peter

2017-01-01

Wide interest in new hemostatic approaches has stemmed from unmet needs in the hospital and on the battlefield. Many current commercial hemostatic agents fail to fulfill the design requirements of safety, efficacy, cost, and storage. Academic focus has led to the improvement of existing strategies as well as new developments. This review will identify and discuss the three major classes of hemostatic approaches: biologically derived materials, synthetically derived materials, and intravenously administered hemostatic agents. The general class is first discussed, then specific approaches discussed in detail, including the hemostatic mechanisms and the advancement of the method. As hemostatic strategies evolve and synthetic-biologic interactions are more fully understood, current clinical methodologies will be replaced. PMID:24307256

Characterizing Chain Processes in Visible Light Photoredox Catalysis

PubMed Central

Cismesia, Megan A.

2015-01-01

The recognition that Ru(bpy)32+ andsimilar visible light absorbing transition metal complexes can be photocatalysts for a variety of synthetically useful organic reactions has resulted in a recent resurgence of interest in photoredox catalysis. However, many of the critical mechanistic aspects of this class of reactions remain poorly understood. In particular, the degree to which visible light photoredox reactions involve radical chain processes has been a point of some disagreement that has not been subjected to systematic analysis. We have now performed quantum yield measurements to demonstrate that threerepresentative, mechanistically distinct photoredox processes involve product-forming chain reactions. Moreover, we show that the combination of quantum yield and luminescence quenching experiments provides a rapid method to estimate the length of these chains. Together, these measurements constitute a robust, operationally facile strategy for characterizing chain processes in a wide range of visible light photoredox reactions. PMID:26668708

Utilizing Brassicaceae seed meal as a soil amendment to suppress weed and soil borne pathogens

USDA-ARS?s Scientific Manuscript database

Increased demand for organic and sustainable agricultural production systems and restrictions on registration and use of toxic synthetic pesticides have generated demand for effective non-synthetic and environmentally friendly alternative weed and pathogen management strategies. Lack of effective a...

Perspectives on social media in and as research: A synthetic review.

PubMed

Lafferty, Natalie T; Manca, Annalisa

2015-04-01

With the growth of social media use in both the private and public spheres, researchers are currently exploring the new opportunities and practices offered by these tools in the research lifecycle. This area is still in its infancy: As methodological approaches and methods are being tested - mainly through pragmatic and exploratory approaches - practices are being shaped and negotiated by the actors involved in research. A further element of complexity is added by the ambivalent status of social media within research activities. They can be both a tool - for recruitment, data collection, analysis - and data - as what constitutes the corpus to be analysed - both in an observational and interactive domain. This synthetic analysis of the literature is aimed at identifying how social media are currently being used in research and how they fit into the research lifecycle. We identify and discuss emerging evidence and trends in the adoption of social media in research, which can be used and applied by psychiatry research practitioners as a framework to inform the development of a personalized research network and social media strategy in research.

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

PubMed

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.

Diastereoselective addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones

NASA Astrophysics Data System (ADS)

Uteuliyev, Maulen M.; Nguyen, Thien T.; Coltart, Don M.

2015-12-01

The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones—directed by the alkoxide of the 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide—leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centres. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary and tertiary alkyl, as well as alkenyl, aryl, allenyl and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo numerous different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures.

Enchancement of Gamma-Aminobutyric Acid Production by Co-Localization of Neurospora crassa OR74A Glutamate Decarboxylase with Escherichia coli GABA Transporter Via Synthetic Scaffold Complex.

PubMed

Somasundaram, Sivachandiran; Maruthamuthu, Murali Kannan; Ganesh, Irisappan; Eom, Gyeong Tae; Hong, Soon Ho

2017-09-28

Gamma-aminobutyric acid is a precursor of nylon-4, which is a promising heat-resistant biopolymer. GABA can be produced from the decarboxylation of glutamate by glutamate decarboxylase. In this study, a synthetic scaffold complex strategy was employed involving the Neurospora crassa glutamate decarboxylase (GadB) and Escherichia coli GABA antiporter (GadC) to improve GABA production. To construct the complex, the SH3 domain was attached to the N. crassa GadB, and the SH3 ligand was attached to the N-terminus, middle, and C-terminus of E. coli GadC. In the C-terminus model, 5.8 g/l of GABA concentration was obtained from 10 g/l glutamate. When a competing pathway engineered strain was used, the final GABA concentration was further increased to 5.94 g/l, which corresponds to 97.5% of GABA yield. With the introduction of the scaffold complex, the GABA productivity increased by 2.9 folds during the initial culture period.

Synthetic circuit designs for earth terraformation.

PubMed

Solé, Ricard V; Montañez, Raúl; Duran-Nebreda, Salva

2015-07-18

Mounting evidence indicates that our planet might experience runaway effects associated to rising temperatures and ecosystem overexploitation, leading to catastrophic shifts on short time scales. Remediation scenarios capable of counterbalancing these effects involve geoengineering, sustainable practices and carbon sequestration, among others. None of these scenarios seems powerful enough to achieve the desired restoration of safe boundaries. We hypothesize that synthetic organisms with the appropriate engineering design could be used to safely prevent declines in some stressed ecosystems and help improving carbon sequestration. Such schemes would include engineering mutualistic dependencies preventing undesired evolutionary processes. We hypothesize that some particular design principles introduce unescapable constraints to the engineered organisms that act as effective firewalls. Testing this designed organisms can be achieved by using controlled bioreactor models, with single and heterogeneous populations, and accurate computational models including different scales (from genetic constructs and metabolic pathways to population dynamics). Our hypothesis heads towards a future anthropogenic action that should effectively act as Terraforming processes. It also implies a major challenge in the existing biosafety policies, since we suggest release of modified organisms as potentially necessary strategy for success.

Dual Catalysis Strategies in Photochemical Synthesis

PubMed Central

2016-01-01

The interaction between an electronically excited photocatalyst and an organic molecule can result in the genertion of a diverse array of reactive intermediates that can be manipulated in a variety of ways to result in synthetically useful bond constructions. This Review summarizes dual-catalyst strategies that have been applied to synthetic photochemistry. Mechanistically distinct modes of photocatalysis are discussed, including photoinduced electron transfer, hydrogen atom transfer, and energy transfer. We focus upon the cooperative interactions of photocatalysts with redox mediators, Lewis and Brønsted acids, organocatalysts, enzymes, and transition metal complexes. PMID:27109441

Dual Catalysis Strategies in Photochemical Synthesis.

PubMed

Skubi, Kazimer L; Blum, Travis R; Yoon, Tehshik P

2016-09-14

The interaction between an electronically excited photocatalyst and an organic molecule can result in the genertion of a diverse array of reactive intermediates that can be manipulated in a variety of ways to result in synthetically useful bond constructions. This Review summarizes dual-catalyst strategies that have been applied to synthetic photochemistry. Mechanistically distinct modes of photocatalysis are discussed, including photoinduced electron transfer, hydrogen atom transfer, and energy transfer. We focus upon the cooperative interactions of photocatalysts with redox mediators, Lewis and Brønsted acids, organocatalysts, enzymes, and transition metal complexes.

Sense codon emancipation for proteome-wide incorporation of noncanonical amino acids: rare isoleucine codon AUA as a target for genetic code expansion

PubMed Central

Bohlke, Nina; Budisa, Nediljko

2014-01-01

One of the major challenges in contemporary synthetic biology is to find a route to engineer synthetic organisms with altered chemical constitution. In terms of core reaction types, nature uses an astonishingly limited repertoire of chemistries when compared with the exceptionally rich and diverse methods of organic chemistry. In this context, the most promising route to change and expand the fundamental chemistry of life is the inclusion of amino acid building blocks beyond the canonical 20 (i.e. expanding the genetic code). This strategy would allow the transfer of numerous chemical functionalities and reactions from the synthetic laboratory into the cellular environment. Due to limitations in terms of both efficiency and practical applicability, state-of-the-art nonsense suppression- or frameshift suppression-based methods are less suitable for such engineering. Consequently, we set out to achieve this goal by sense codon emancipation, that is, liberation from its natural decoding function – a prerequisite for the reassignment of degenerate sense codons to a new 21st amino acid. We have achieved this by redesigning of several features of the post-transcriptional modification machinery which are directly involved in the decoding process. In particular, we report first steps towards the reassignment of 5797 AUA isoleucine codons in Escherichia coli using efficient tools for tRNA nucleotide modification pathway engineering. PMID:24433543

Synthesis of natural urolithin M6, a galloflavin mimetic, as a potential inhibitor of lactate dehydrogenase A.

PubMed

Rupiani, Sebastiano; Guidotti, Laura; Manerba, Marcella; Di Ianni, Lorenza; Giacomini, Elisa; Falchi, Federico; Di Stefano, Giuseppina; Roberti, Marinella; Recanatini, Maurizio

2016-11-22

Glycolysis is the main route for energy production in tumors. LDH-A is a key enzyme of this process and its inhibition represents an attractive strategy to hamper cancer cell metabolism. Galloflavin is a reliable LDH-A inhibitor as previously identified by us; however, its poor physicochemical properties and chemical tractability render it unsuitable for further development. Therefore, a rational design was undertaken with the aim to reproduce the pharmacophore of galloflavin on simpler, potentially more soluble and synthetic accessible scaffolds. Following a process of structural simplification, natural urolithin M6 (UM6), which is an ellagitannin metabolite produced by gut microbiota, was identified as a putative galloflavin mimetic. In the present study, the synthesis of UM6 is described for the first time. An efficient synthetic pathway has been developed, which involved five steps from readily accessible starting materials. The key reaction steps, a Suzuki coupling and an intramolecular C-H oxygenation, have been optimized to improve the synthetic feasibility and provide the best conditions in terms of reaction time and yield. Moreover, this route would be suitable to obtain other analogs for SAR studies. Preliminary biological tests revealed that UM6 was able to smoothly reproduce the behavior of galloflavin, confirming that our approach was successful in providing a new and accessible structure in the search for new LDH-A inhibitors.

Methods for preparing metal ion photocages: application to the synthesis of crowncast.

PubMed

Kennedy, Daniel P; Gwizdala, Celina; Burdette, Shawn C

2009-06-18

Three different synthetic strategies were utilized in the construction of a novel class of macrocyclic containing o-nitrobenzhydrol group II cation cages. The synthetic methodology presented herein is unparalleled in scope toward the preparation of caged complexes for various main group and transition block cations.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

USDA-ARS?s Scientific Manuscript database

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

Evaluation of organic alternatives for weed management in pulasan (Nephelium ramboutan-ake)

USDA-ARS?s Scientific Manuscript database

In Puerto Rico, most fruit crop growers use post-emergence synthetic herbicides as a major component of their weed management programs. Organic growers are not allowed to use synthetic herbicides; hence there is a need to develop alternative weed management strategies for current and prospective org...

Yeast synthetic biology for high-value metabolites.

PubMed

Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

2015-02-01

Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Pharmacological Activation of Protein Phosphatase 2 A (PP2A): A Novel Strategy to Fight Against Human Malignancies?

PubMed

Carratù, Maria Rosaria; Signorile, Anna; De Rasmo, Domenico; Reale, Antonia; Vacca, Angelo

2016-01-01

The serine-threonine protein phosphatase 2A (PP2A) regulates multiple cell signaling cascades and its inactivation by viral oncoproteins, mutation of specific structural subunits or upregulation of the cellular endogenous inhibitors may contribute to malignant transformation by regulating specific phosphorylation events. Pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. Some compounds targeting PP2A are able to induce PP2A reactivation and subsequent cell death in several types of cancer. We undertook a search of bibliographic databases for peer-reviewed articles focusing on the main item of the review. We selected articles published in indexed journals. The quality of retrieved papers was appraised using the standard bibliometric indicators. One hundred and fourteen papers were included in the review. Twenty-seven papers gave an overview of structure and physiological role of PP2A. Twenty-five papers outlined the role of PP2A in tumor suppression. Forty papers analyzed the mechanism involved in PP2A reactivation by synthetic compounds, and twenty-two papers outlined the capability of natural compounds of restoring PP2A activity and how this could be beneficial. Findings analyzed in this review underline the central role of PP2A as a regulator of cell growth and survival, hence its function as tumor suppressor. The discovery that some compounds, either synthetic or natural, are capable of reactivating PP2A opens up new perspectives for future strategies to fully exploit therapeutic potential in human cancer. Thus, this review could also be of particular interest to pharmaceutical or biotechnology companies for drug design and targeted delivery.

Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria

PubMed Central

Hui, Sheng; Silverman, Josh M; Chen, Stephen S; Erickson, David W; Basan, Markus; Wang, Jilong; Hwa, Terence; Williamson, James R

2015-01-01

A central aim of cell biology was to understand the strategy of gene expression in response to the environment. Here, we study gene expression response to metabolic challenges in exponentially growing Escherichia coli using mass spectrometry. Despite enormous complexity in the details of the underlying regulatory network, we find that the proteome partitions into several coarse-grained sectors, with each sector's total mass abundance exhibiting positive or negative linear relations with the growth rate. The growth rate-dependent components of the proteome fractions comprise about half of the proteome by mass, and their mutual dependencies can be characterized by a simple flux model involving only two effective parameters. The success and apparent generality of this model arises from tight coordination between proteome partition and metabolism, suggesting a principle for resource allocation in proteome economy of the cell. This strategy of global gene regulation should serve as a basis for future studies on gene expression and constructing synthetic biological circuits. Coarse graining may be an effective approach to derive predictive phenomenological models for other ‘omics’ studies. PMID:25678603

Evaluation of a Traffic Sign Detector by Synthetic Image Data for Advanced Driver Assistance Systems

NASA Astrophysics Data System (ADS)

Hanel, A.; Kreuzpaintner, D.; Stilla, U.

2018-05-01

Recently, several synthetic image datasets of street scenes have been published. These datasets contain various traffic signs and can therefore be used to train and test machine learning-based traffic sign detectors. In this contribution, selected datasets are compared regarding ther applicability for traffic sign detection. The comparison covers the process to produce the synthetic images and addresses the virtual worlds, needed to produce the synthetic images, and their environmental conditions. The comparison covers variations in the appearance of traffic signs and the labeling strategies used for the datasets, as well. A deep learning traffic sign detector is trained with multiple training datasets with different ratios between synthetic and real training samples to evaluate the synthetic SYNTHIA dataset. A test of the detector on real samples only has shown that an overall accuracy and ROC AUC of more than 95 % can be achieved for both a small rate of synthetic samples and a large rate of synthetic samples in the training dataset.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB{sub 1} receptors and apoptotic cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomiyama, Ken-ichi; Funada, Masahiko, E-mail: mfunada@ncnp.go.jp

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB{sub 1} receptor antagonist AM251, but not with the selective CB{sub 2} receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrainmore » cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB{sub 1} receptors.« less

Tracking the emergence of synthetic biology.

PubMed

Shapira, Philip; Kwon, Seokbeom; Youtie, Jan

2017-01-01

Synthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research, innovation, and policy interest in recent years. This paper contributes to efforts to delineate this emerging domain by presenting a newly constructed bibliometric definition of synthetic biology. Our approach is dimensioned from a core set of papers in synthetic biology, using procedures to obtain benchmark synthetic biology publication records, extract keywords from these benchmark records, and refine the keywords, supplemented with articles published in dedicated synthetic biology journals. We compare our search strategy with other recent bibliometric approaches to define synthetic biology, using a common source of publication data for the period from 2000 to 2015. The paper details the rapid growth and international spread of research in synthetic biology in recent years, demonstrates that diverse research disciplines are contributing to the multidisciplinary development of synthetic biology research, and visualizes this by profiling synthetic biology research on the map of science. We further show the roles of a relatively concentrated set of research sponsors in funding the growth and trajectories of synthetic biology. In addition to discussing these analyses, the paper notes limitations and suggests lines for further work.

Synthetic biology strategies toward heterologous phytochemical production.

PubMed

Kotopka, Benjamin J; Li, Yanran; Smolke, Christina D

2018-06-13

Covering: 2006 to 2018Phytochemicals are important sources for the discovery and development of agricultural and pharmaceutical compounds, such as pesticides and medicines. However, these compounds are typically present in low abundance in nature, and the biosynthetic pathways for most phytochemicals are not fully elucidated. Heterologous production of phytochemicals in plant, bacterial, and yeast hosts has been pursued as a potential approach to address sourcing issues associated with many valuable phytochemicals, and more recently has been utilized as a tool to aid in the elucidation of plant biosynthetic pathways. Due to the structural complexity of certain phytochemicals and the associated biosynthetic pathways, reconstitution of plant pathways in heterologous hosts can encounter numerous challenges. Synthetic biology approaches have been developed to address these challenges in areas such as precise control over heterologous gene expression, improving functional expression of heterologous enzymes, and modifying central metabolism to increase the supply of precursor compounds into the pathway. These strategies have been applied to advance plant pathway reconstitution and phytochemical production in a wide variety of heterologous hosts. Here, we review synthetic biology strategies that have been recently applied to advance complex phytochemical production in heterologous hosts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Synthetic Biology Research Program, National University of Singapore, Singapore

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fattymore » acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.« less

Graphitic Nitrogen Triggers Red Fluorescence in Carbon Dots.

PubMed

Holá, Kateřina; Sudolská, Mária; Kalytchuk, Sergii; Nachtigallová, Dana; Rogach, Andrey L; Otyepka, Michal; Zbořil, Radek

2017-12-26

Carbon dots (CDs) are a stable and highly biocompatible fluorescent material offering great application potential in cell labeling, optical imaging, LED diodes, and optoelectronic technologies. Because their emission wavelengths provide the best tissue penetration, red-emitting CDs are of particular interest for applications in biomedical technologies. Current synthetic strategies enabling red-shifted emission include increasing the CD particle size (sp 2 domain) by a proper synthetic strategy and tuning the surface chemistry of CDs with suitable functional groups (e.g., carboxyl). Here we present an elegant route for preparing full-color CDs with well-controllable fluorescence at blue, green, yellow, or red wavelengths. The two-step procedure involves the synthesis of a full-color-emitting mixture of CDs from citric acid and urea in formamide followed by separation of the individual fluorescent fractions by column chromatography based on differences in CD charge. Red-emitting CDs, which had the most negative charge, were separated as the last fraction. The trend in the separation, surface charge, and red-shift of photoluminescence was caused by increasing amount of graphitic nitrogen in the CD structure, as was clearly proved by XPS, FT-IR, Raman spectroscopy, and DFT calculations. Importantly, graphitic nitrogen generates midgap states within the HOMO-LUMO gap of the undoped systems, resulting in significantly red-shifted light absorption that in turn gives rise to fluorescence at the low-energy end of the visible spectrum. The presented findings identify graphitic nitrogen as another crucial factor that can red-shift the CD photoluminescence.

Strychnine as Target, Samarium Diiodide as Tool: A Personal Story.

PubMed

Beemelmanns, Christine; Reissig, Hans-Ulrich

2015-10-01

Strychnine stands out from the group of classical natural products as one of the first complex compounds to be isolated in pure form and an extreme challenge to be structurally characterized. It has played a central role in natural product total syntheses and the surge in the development of innovative synthetic methods for many decades. Recently, we have accomplished one of the shortest formal total syntheses of strychnine (in ten steps and 14% overall yield or even shorter in eight steps and 10% overall yield). The evolution of a productive synthetic strategy, as well as the synthetic challenges tackled, are described here in detail, including examples of related transformations. The successful synthetic strategy was inspired by the premise that the core structure could be derived from simple aromatic indole precursors by a reductive SmI2 -induced ketyl-aryl coupling. Other key reactions included a diastereoselective reduction and a regioselective elimination protocol. Altogether one of the shortest syntheses of iso-strychnine and hence of strychnine was established. Copyright © 2015 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

PubMed

Kang, Seounghun; Shin, Woojun; Choi, Myung-Ho; Ahn, Minchul; Kim, Young-Kwan; Kim, Seongchan; Min, Dal-Hee; Jang, Hongje

2018-06-22

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.

ENVIRONMENTALLY FRIENDLIER SYNTHETIC ALTERNATIVES USING NON-TRADITIONAL APPROACHES

EPA Science Inventory

Synthetic organic transformations performed under non-traditional conditions are becoming popular primarily to circumvent the growing environmental concerns. A solvent-free approach that involves microwave (MW) exposure of neat reactants (undiluted) either in presence of a cataly...

Palladium-Catalyzed Dehydrogenative Coupling: An Efficient Synthetic Strategy for the Construction of the Quinoline Core

PubMed Central

Carral-Menoyo, Asier; Ortiz-de-Elguea, Verónica; Martinez-Nunes, Mikel; Sotomayor, Nuria; Lete, Esther

2017-01-01

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners. PMID:28867803

The relevance of polymeric synthetic membranes in topical formulation assessment and drug diffusion study.

PubMed

Ng, Shiow-Fern; Rouse, Jennifer J; Sanderson, Francis D; Eccleston, Gillian M

2012-03-01

Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil, are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.

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. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Negotiating the dynamics of uncomfortable knowledge: The case of dual use and synthetic biology

PubMed Central

Marris, Claire; Jefferson, Catherine; Lentzos, Filippa

2014-01-01

Institutions need to ignore some knowledge in order to function. This is “uncomfortable knowledge” because it undermines the ability of those institutions to pursue their goals (Rayner, 2012). We identify three bodies of knowledge that are relevant to understandings of the dual use threat posed by synthetic biology but are excluded from related policy discussions. We demonstrate how these “unknown knowns” constitute uncomfortable knowledge because they disrupt the simplified worldview that underpins contemporary discourse on the potential misuse of synthetic biology by malign actors. We describe how these inconvenient truths have been systematically ignored and argue that this is because they are perceived as a threat by organisations involved in the promotion of synthetic biology as well as by those involved in managing biosecurity risks. This has led to a situation where concerns about the biosecurity threat posed by synthetic biology are not only exaggerated, but are, more importantly, misplaced. This, in turn, means that related policies are misdirected and unlikely to have much impact. We focus on the dynamics of discussions about synthetic biology and dual use to demonstrate how the same “knowns” that are denied or dismissed as “unknown knowns” in certain circumstances are sometimes mobilised as “known knowns” by the same category of actors in a different context, when this serves to sustain the goals of the individuals and institutions involved. Based on our own experience, we argue that negotiating the dynamics of uncomfortable knowledge is a difficult, but necessary, component of meaningful transdisciplinary collaborations. PMID:25484910

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

7 CFR 3201.41 - Metalworking fluids.

Code of Federal Regulations, 2013 CFR

2013-01-01

... feedstock during grinding and machining operations involving unusually high temperatures or corrosion... prevention when applied to metal feedstock during normal grinding and machining operations. (iii) High... percent. (3) High performance soluble, semi-synthetic, and synthetic oils—40 percent. (c) Preference...

7 CFR 3201.41 - Metalworking fluids.

Code of Federal Regulations, 2012 CFR

2012-01-01

... feedstock during grinding and machining operations involving unusually high temperatures or corrosion... prevention when applied to metal feedstock during normal grinding and machining operations. (iii) High... percent. (3) High performance soluble, semi-synthetic, and synthetic oils—40 percent. (c) Preference...

7 CFR 3201.41 - Metalworking fluids.

Code of Federal Regulations, 2014 CFR

2014-01-01

... feedstock during grinding and machining operations involving unusually high temperatures or corrosion... prevention when applied to metal feedstock during normal grinding and machining operations. (iii) High... percent. (3) High performance soluble, semi-synthetic, and synthetic oils—40 percent. (c) Preference...

NON-TRADITIONAL 'GREENER' ALTERNATIVES TO SYNTHETIC ORGANIC TRANSFORMATIONS USING MICROWAVES

EPA Science Inventory

Non-traditional 'Greener' Alternatives to synthetic Organic Transformations Using Microwaves

A rapid and environmentally friendlier approach for organic synthesis and transformations is described which involves microwave (MW) exposure of neat reactants (undiluted) often i...

Access to site-specific Fc-cRGD peptide conjugates through streamlined expressed protein ligation.

PubMed

Frutos, S; Jordan, J B; Bio, M M; Muir, T W; Thiel, O R; Vila-Perelló, M

2016-10-12

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners.

Protein recognition using synthetic small-molecular binders toward optical protein sensing in vitro and in live cells.

PubMed

Kubota, Ryou; Hamachi, Itaru

2015-07-07

Chemical sensing of amino acids, peptides, and proteins provides fruitful information to understand their biological functions, as well as to develop the medical and technological applications. To detect amino acids, peptides, and proteins in vitro and in vivo, vast kinds of chemical sensors including small synthetic binders/sensors, genetically-encoded fluorescent proteins and protein-based semisynthetic biosensors have been intensely investigated. This review deals with concepts, strategies, and applications of protein recognition and sensing using small synthetic binders/sensors, which are now actively studied but still in the early stage of investigation. The recognition strategies for peptides and proteins can be divided into three categories: (i) recognition of protein substructures, (ii) protein surface recognition, and (iii) protein sensing through protein-ligand interaction. Here, we overview representative examples of protein recognition and sensing, and discuss biological or diagnostic applications such as potent inhibitors/modulators of protein-protein interactions.

[Progress in synthetic biology of pinocembrin].

PubMed

Guo, Lei; Kong, Jianqiang

2015-04-01

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.

Total chemical synthesis of modified histones

NASA Astrophysics Data System (ADS)

Qi, Yun-Kun; Ai, Hua-Song; Li, Yi-Ming; Yan, Baihui

2018-02-01

In the post-genome era, epigenetics has received increasing attentions in recent years. The post-translational modifications (PTMs) of four core histones play central roles in epigenetic regulation of eukaryotic genome by either directly altering the biophysical properties of nucleosomes or by recruiting other effector proteins. In order to study the biological functions and structural mechanisms of these histone PTMs, an obligatory step is to prepare a sufficient amount of homogeneously modified histones. This task cannot be fully accomplished either by recombinant technology or enzymatic modification. In this context, synthetic chemists have developed novel protein synthetic tools and state-of-the-art chemical ligation strategies for the preparation of homologous modified histones. In this review, we summarize the recent advances in the preparation of modified histones, focusing on the total chemical synthesis strategies. The importance and potential of synthetic chemistry for the study of histone code will be also discussed.

Synthetic biology: Emerging bioengineering in Indonesia

NASA Astrophysics Data System (ADS)

Suhandono, Sony

2017-05-01

The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

General chemoselective and redox-responsive ligation and release strategy.

PubMed

Park, Sungjin; Westcott, Nathan P; Luo, Wei; Dutta, Debjit; Yousaf, Muhammad N

2014-03-19

We report a switchable redox click and cleave reaction strategy for conjugating and releasing a range of molecules on demand. This chemoselective redox-responsive ligation (CRRL) and release strategy is based on a redox switchable oxime linkage that is controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions without the use of a catalyst. Both conjugation and release reactions are kinetically well behaved and quantitative. The CRRL strategy is synthetically modular and easily monitored and characterized by routine analytical techniques. We demonstrate how the CRRL strategy can be used for the dynamic generation of cyclic peptides and the ligation of two different peptides that are stable but can be selectively cleaved upon changes in the redox environment. We also demonstrate a new redox based delivery of cargoes to live cells strategy via the CRRL methodology by synthesizing a FRET redox-responsive probe that is selectively activated within a cellular environment. We believe the ease of the CRRL strategy should find wide use in a range of applications in biology, tissue engineering, nanoscience, synthetic chemistry, and material science and will expand the suite of current conjugation and release strategies.

Biomedically relevant circuit-design strategies in mammalian synthetic biology

PubMed Central

Bacchus, William; Aubel, Dominique; Fussenegger, Martin

2013-01-01

The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design. PMID:24061539

Synthetic Biology and Personalized Medicine

PubMed Central

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. PMID:22907209

Genomic Aspects of Research Involving Polyploid Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaohan; Ye, Chuyu; Tschaplinski, Timothy J

2011-01-01

Almost all extant plant species have spontaneously doubled their genomes at least once in their evolutionary histories, resulting in polyploidy which provided a rich genomic resource for evolutionary processes. Moreover, superior polyploid clones have been created during the process of crop domestication. Polyploid plants generated by evolutionary processes and/or crop domestication have been the intentional or serendipitous focus of research dealing with the dynamics and consequences of genome evolution. One of the new trends in genomics research is to create synthetic polyploid plants which provide materials for studying the initial genomic changes/responses immediately after polyploid formation. Polyploid plants are alsomore » used in functional genomics research to study gene expression in a complex genomic background. In this review, we summarize the recent progress in genomics research involving ancient, young, and synthetic polyploid plants, with a focus on genome size evolution, genomics diversity, genomic rearrangement, genetic and epigenetic changes in duplicated genes, gene discovery, and comparative genomics. Implications on plant sciences including evolution, functional genomics, and plant breeding are presented. It is anticipated that polyploids will be a regular subject of genomics research in the foreseeable future as the rapid advances in DNA sequencing technology create unprecedented opportunities for discovering and monitoring genomic and transcriptomic changes in polyploid plants. The fast accumulation of knowledge on polyploid formation, maintenance, and divergence at whole-genome and subgenome levels will not only help plant biologists understand how plants have evolved and diversified, but also assist plant breeders in designing new strategies for crop improvement.« less

Vitamin E and mast cells.

PubMed

Zingg, Jean-Marc

2007-01-01

Mast cells play an important role in the immune system by interacting with B and T cells and by releasing several mediators involved in activating other cells. Hyperreactivity of mast cells and their uncontrolled accumulation in tissues lead to increased release of inflammatory mediators contributing to the pathogenesis of several diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and allergic disorders such as asthma and allergic rhinitis. Interference with mast cell proliferation, survival, degranulation, and migration by synthetic or natural compounds may represent a preventive strategy for the management of these diseases. Natural vitamin E covers a group of eight analogues-the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols, but only alpha-tocopherol is efficiently retained by the liver and distributed to peripheral tissues. Mast cells preferentially locate in the proximity of tissues that interface with the external environment (the epithelial surface of the skin, the gastrointestinal mucosa, and the respiratory system), what may render them accessible to treatments with inefficiently retained natural vitamin E analogues and synthetic derivatives. In addition to scavenging free radicals, the natural vitamin E analogues differently modulate signal transduction and gene expression in several cell lines; in mast cells, protein kinase C, protein phosphatase 2A, and protein kinase B are affected by vitamin E, leading to the modulation of proliferation, apoptosis, secretion, and migration. In this chapter, the possibility that vitamin E can prevent diseases with mast cells involvement by modulating signal transduction and gene expression is evaluated.

Precursor engineering and controlled conversion for the synthesis of monodisperse thiolate-protected metal nanoclusters

NASA Astrophysics Data System (ADS)

Yu, Yong; Yao, Qiaofeng; Luo, Zhentao; Yuan, Xun; Lee, Jim Yang; Xie, Jianping

2013-05-01

In very recent years, thiolate-protected metal nanoclusters (or thiolated MNCs) with core sizes smaller than 2 nm have emerged as a new direction in nanoparticle research due to their discrete and size dependent electronic structures and molecular-like properties, such as HOMO-LUMO transitions in optical absorptions, quantized charging, and strong luminescence. Synthesis of monodisperse thiolated MNCs in sufficiently large quantities (up to several hundred micrograms) is necessary for establishing reliable size-property relationships and exploring potential applications. This Feature Article reviews recent progress in the development of synthetic strategies for the production of monodisperse thiolated MNCs. The preparation of monodisperse thiolated MNCs is viewed as an engineerable process where both the precursors (input) and their conversion chemistry (processing) may be rationally designed to achieve the desired outcome - monodisperse thiolated MNCs (output). Several strategies for tailoring the precursor and the conversion process are analyzed to arrive at a unifying understanding of the processes involved.

USING ISOTHERMS TO PREDICT GAC'S CAPACITY FOR SYNTHETIC ORGANICS

EPA Science Inventory

This investigation involved operating a pilot granular activated carbon (GAC) plant to obtain capacity data under typical field conditions, determining isotherms for selected synthetic organic chemicals, and comparing the capacity predicted by the isotherm data with the pilot-pla...

Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

PubMed

O'Donnell, Julie K; Gladden, R Matthew; Seth, Puja

2017-09-01

Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015. † In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

System and method for forming synthetic protein crystals to determine the conformational structure by crystallography

DOEpatents

Craig, George D.; Glass, Robert; Rupp, Bernhard

1997-01-01

A method for forming synthetic crystals of proteins in a carrier fluid by use of the dipole moments of protein macromolecules that self-align in the Helmholtz layer adjacent to an electrode. The voltage gradients of such layers easily exceed 10.sup.6 V/m. The synthetic protein crystals are subjected to x-ray crystallography to determine the conformational structure of the protein involved.

Enhancement of astaxanthin production in Xanthophyllomyces dendrorhous by efficient method for the complete deletion of genes.

PubMed

Yamamoto, Keisuke; Hara, Kiyotaka Y; Morita, Toshihiko; Nishimura, Akira; Sasaki, Daisuke; Ishii, Jun; Ogino, Chiaki; Kizaki, Noriyuki; Kondo, Akihiko

2016-09-13

Red yeast, Xanthophyllomyces dendrorhous is the only yeast known to produce astaxanthin, an anti-oxidant isoprenoid (carotenoid) widely used in the aquaculture, food, pharmaceutical and cosmetic industries. The potential of this microorganism as a platform cell factory for isoprenoid production has been recognized because of high flux through its native terpene pathway. Recently, we developed a multiple gene expression system in X. dendrorhous and enhanced the mevalonate synthetic pathway to increase astaxanthin production. In contrast, the mevalonate synthetic pathway is suppressed by ergosterol through feedback inhibition. Therefore, releasing the mevalonate synthetic pathway from this inhibition through the deletion of genes involved in ergosterol synthesis is a promising strategy to improve isoprenoid production. An efficient method for deleting diploid genes in X. dendrorhous, however, has not yet been developed. Xanthophyllomyces dendrorhous was cultivated under gradually increasing concentrations of antibiotics following the introduction of antibiotic resistant genes to be replaced with target genes. Using this method, double CYP61 genes encoding C-22 sterol desaturases relating to ergosterol biosynthesis were deleted sequentially. This double CYP61 deleted strain showed decreased ergosterol biosynthesis compared with the parental strain and single CYP61 disrupted strain. Additionally, this double deletion of CYP61 genes showed increased astaxanthin production compared with the parental strain and the single CYP61 knockout strain. Finally, astaxanthin production was enhanced by 1.4-fold compared with the parental strain, although astaxanthin production was not affected in the single CYP61 knockout strain. In this study, we developed a system to completely delete target diploid genes in X. dendrorhous. Using this method, we deleted diploid CYP61 genes involved in the synthesis of ergosterol that inhibits the pathway for mevalonate, which is a common substrate for isoprenoid biosynthesis. The resulting decrease in ergosterol biosynthesis increased astaxanthin production. The efficient method for deleting diploid genes developed in this study has the potential to improve industrial production of various isoprenoids in X. dendrorhous.

Evaluation of a bifurcation drug-eluting stent system versus provisional T-stenting in a perfused synthetic coronary artery model.

PubMed

Rizik, David G; Klag, Joseph M; Tenaglia, Alan; Hatten, Thomas R; Barnhart, Marianne; Warnack, Boris

2009-12-01

Provisional T-stenting is a widely used strategy for the treatment of coronary artery bifurcation lesions. However, the use of conventional stents in this setting is limited by multiple factors; this includes technical considerations such as wire wrap when accessing the involved vessel, and stent overlap at or near the carina of the lesion. In addition, current slotted tube stent technology tends to be associated with gaps in the coverage of the side branch ostium, which may result in restenosis in that segment of the lesion. The Pathfinder device, now more commonly referred to as the Xience Side Branch Access System (Xience SBA) is a drug-eluting stent (DES) designed specifically to assist in the treatment of bifurcation lesions by allowing wire access into the side branch, irrespective of the treatment strategy to be employed. The Xience SBA drug-eluting stent was compared with the standard Vision coronary stent system using a provisional T-stenting strategy in a perfused synthetic model of the coronary vasculature with side branch angulations of 30 degrees , 50 degrees , 70 degrees , and 90 degrees . Stent delivery was performed under fluoroscopic guidance. Following the procedure, high-resolution 2D Faxitron imaging was used to evaluate deployment accuracy of the side branch stent relative to the main branch stent. Deployment of the Xience SBA was accomplished in the same total time as the standard stents in a provisional T-stenting approach (14.9 vs. 14.6 minutes). However, the time required to achieve stent deployment in the main branch was less with the Xience SBA (4.0 vs. 6.6 minutes), and as a result, total contrast usage (49.4 vs. 69.4 cm(3)) and fluoroscopy time (5.1 vs. 6.2 minutes) was lower. Additionally, the Xience SBA had a lower incidence of wire wrap (22% vs. 89%) and less distal protrusion of the side branch stent into the main branch (0.54 vs. 1.21 mm). Significant gaps in ostial side branch coverage were not seen in either group. The Xience Side Branch Access DES is a viable device for consistently accessing coronary bifurcation lesions; it allows for easy wire access into the side branch. This may assist the operator in overcoming those well-recognized limitations associated with use of standard one- or two-stent strategies. In this perfused synthetic coronary model, Xience SBA deployment required less contrast usage and shorter fluoroscopy times. Further testing of this device is warranted.

A Facile One-Pot Construction of Succinimide-Fused Spiro[Pyrrolidine-2,3'-Oxindoles] via 1,3-Dipolar Cycloaddition Involving 3-Amino Oxindoles and Maleimides.

PubMed

Jin, Lunqiang; Liang, Feng

2018-03-05

Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3'-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with maleimides has been described. The protocol provides a facile and efficient access to structurally diverse succinimide-fused spiro[pyrrolidine-2,3'-oxindole] compounds in good to high yields (up to 93%) with moderate to excellent diastereoselectivities (up to >95:5). The relative stereochemistry of cycloaddition products has been assigned by X-ray diffraction analysis.

Molecularly Imprinted Microrods via Mesophase Polymerization.

PubMed

Parisi, Ortensia Ilaria; Scrivano, Luca; Candamano, Sebastiano; Ruffo, Mariarosa; Vattimo, Anna Francesca; Spanedda, Maria Vittoria; Puoci, Francesco

2017-12-28

The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via "mesophase polymerization". The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology.

A new synthetic approach to functionalize pyrimido[4,5-b]quinoline-2,4(1H,3H)-diones via a three-component one-pot reaction.

PubMed

Aknin, Karen; Desbène-Finck, Stéphanie; Helissey, Philippe; Giorgi-Renault, Sylviane

2010-02-01

Functionalized pyrimido[4,5-b]quinoline-2,4 (1H,3H)-diones were synthesized by a three-component one-pot reaction involving barbituric acid, aldehydes, and anilines. The use of commercially available anilines allowed the facile syntheses of pyrimido[4,5-b]quinolinediones substituted in all the positions on the benzene ring with electron donor or electron withdrawing groups. This straightforward method circumvents the preparation of unstable substituted 2-aminobenzaldehydes that limits the scope of previously described syntheses. Furthermore, access to the 5-substituted derivatives is now also possible starting from aliphatic or aromatic aldehydes. Our strategy and methodology offer significant and practical improvements over other methodologies.

Carotenoids from microalgae: A review of recent developments.

PubMed

Gong, Mengyue; Bassi, Amarjeet

2016-12-01

Carotenoids have been receiving increasing attention due to their potential health benefits. Microalgae are recognized as a natural source of carotenoids and other beneficial byproducts. However, the production of micro-algal carotenoids is not yet sufficiently cost-effective to compete with traditional chemical synthetic methods and other technologies such as extraction from plant based sources. This review presents the recent biotechnological developments in microalgal carotenoid production. The current technologies involved in their bioprocessing including cultivation, harvesting, extraction, and purification are discussed with a specific focus on downstream processing. The recent advances in chemical and biochemical synthesis of carotenoids are also reviewed for a better understanding of suitable and economically feasible biotechnological strategies. Some possible future directions are also proposed. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of 2-Amino-3-hydroxy-3H-indoles via Palladium-Catalyzed One-Pot Reaction of Isonitriles, Oxygen, and N-Tosylhydrazones Derived from 2-Acylanilines.

PubMed

Chu, Haoke; Dai, Qiang; Jiang, Yan; Cheng, Jiang

2017-08-04

A cyanide-free one-pot procedure was developed to access 2-amino-3-hydroxy-3H-indoles, which involved: (1) in situ formation of ketenimines by the reaction of N'-(1-(2-aminophenyl)ethylidene)-p-tosylhydrazones with isonitriles; (2) the intramolecular nucleophilic attack of ketenimines by the amino in phenyl furnishing the ring closure leading to 2-aminoindoles; (3) the oxidation of 2-aminoindoles by O 2 leading to 2-amino-3-hydroxy-3H-indoles. This strategy represents not only a key compliment to the sporadic synthetic methods toward 2-amino-3-hydroxy-3H-indoles but also progress in N-tosylhydrazone, isonitrile, and ketenimine chemistry.

Stibathiolanes: Synthesis, solid state structure, and solution behavior

NASA Astrophysics Data System (ADS)

Fisher, Richard A.; Nielsen, Ralph B.; Davis, William M.; Buchwald, Stephen L.

1990-06-01

Interest in organometallic compounds of the main group metals has recently grown tremendously, due in part to the wide variety of applications of these compounds in the materials sciences. Despite this new activity, the synthetic strategies for main group organometallics have remained relatively undeveloped. The majority of syntheses of these compounds involve classical metathesis reactions between a main group halide and an organometallic compound such as an organolithium or Grignard reagent and are limited by a lack of selectivity and by the availability of suitable organometallic precursors. The latter limitation is severe for main group metallacycles because of the paucity of suitable 1, n(n=3,4,5)-dianionic reagents or their equivalents, which are most often used for the synthesis of this class of molecules.

Recent Advances in Microbial Production of Aromatic Chemicals and Derivatives.

PubMed

Noda, Shuhei; Kondo, Akihiko

2017-08-01

Along with the development of metabolic engineering and synthetic biology tools, various microbes are being used to produce aromatic chemicals. In microbes, aromatics are mainly produced via a common important precursor, chorismate, in the shikimate pathway. Natural or non-natural aromatics have been produced by engineering metabolic pathways involving chorismate. In the past decade, novel approaches have appeared to produce various aromatics or to increase their productivity, whereas previously, the targets were mainly aromatic amino acids and the strategy was deregulating feedback inhibition. In this review, we summarize recent studies of microbial production of aromatics based on metabolic engineering approaches. In addition, future perspectives and challenges in this research area are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Road to the future of systems biotechnology: CRISPR-Cas-mediated metabolic engineering for recombinant protein production.

PubMed

Roointan, Amir; Morowvat, Mohammad Hossein

The rising potential for CRISPR-Cas-mediated genome editing has revolutionized our strategies in basic and practical bioengineering research. It provides a predictable and precise method for genome modification in a robust and reproducible fashion. Emergence of systems biotechnology and synthetic biology approaches coupled with CRISPR-Cas technology could change the future of cell factories to possess some new features which have not been found naturally. We have discussed the possibility and versatile potentials of CRISPR-Cas technology for metabolic engineering of a recombinant host for heterologous protein production. We describe the mechanisms involved in this metabolic engineering approach and present the diverse features of its application in biotechnology and protein production.

2014 update of the Consensus Statement of the Spanish Society of Rheumatology on the use of biological therapies in rheumatoid arthritis.

PubMed

Sanmartí, Raimon; García-Rodríguez, Susana; Álvaro-Gracia, José María; Andreu, José Luis; Balsa, Alejandro; Cáliz, Rafael; Fernández-Nebro, Antonio; Ferraz-Amaro, Iván; Gómez-Reino, Juan Jesús; González-Álvaro, Isidoro; Martín-Mola, Emilio; Martínez-Taboada, Víctor Manuel; Ortiz, Ana M; Tornero, Jesús; Marsal, Sara; Moreno-Muelas, José Vicente

2015-01-01

To establish recommendations for the management of patients with rheumatoid arthritis (RA) to serve as a reference for all health professionals involved in the care of these patients, and focusing on the role of available synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). Consensual recommendations were agreed on by a panel of 14 experts selected by the Spanish Society of Rheumatology (SER). The available scientific evidence was collected by updating three systematic reviews (SR) used for the EULAR 2013 recommendations. A new SR was added to answer an additional question. The literature review of the scientific evidence was made by the SER reviewer's group. The level of evidence and the degree of recommendation was classified according to the Oxford Centre for Evidence-Based Medicine system. A Delphi panel was used to evaluate the level of agreement between panellists (strength of recommendation). Thirteen recommendations for the management of adult RA were emitted. The therapeutic objective should be to treat patients in the early phases of the disease with the aim of achieving clinical remission, with methotrexate playing a central role in the therapeutic strategy of RA as the reference synthetic DMARD. Indications for biologic DMARDs were updated and the concept of the optimization of biologicals was introduced. We present the fifth update of the SER recommendations for the management of RA with synthetic and biologic DMARDs. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Detecting representative data and generating synthetic samples to improve learning accuracy with imbalanced data sets.

PubMed

Li, Der-Chiang; Hu, Susan C; Lin, Liang-Sian; Yeh, Chun-Wu

2017-01-01

It is difficult for learning models to achieve high classification performances with imbalanced data sets, because with imbalanced data sets, when one of the classes is much larger than the others, most machine learning and data mining classifiers are overly influenced by the larger classes and ignore the smaller ones. As a result, the classification algorithms often have poor learning performances due to slow convergence in the smaller classes. To balance such data sets, this paper presents a strategy that involves reducing the sizes of the majority data and generating synthetic samples for the minority data. In the reducing operation, we use the box-and-whisker plot approach to exclude outliers and the Mega-Trend-Diffusion method to find representative data from the majority data. To generate the synthetic samples, we propose a counterintuitive hypothesis to find the distributed shape of the minority data, and then produce samples according to this distribution. Four real datasets were used to examine the performance of the proposed approach. We used paired t-tests to compare the Accuracy, G-mean, and F-measure scores of the proposed data pre-processing (PPDP) method merging in the D3C method (PPDP+D3C) with those of the one-sided selection (OSS), the well-known SMOTEBoost (SB) study, and the normal distribution-based oversampling (NDO) approach, and the proposed data pre-processing (PPDP) method. The results indicate that the classification performance of the proposed approach is better than that of above-mentioned methods.

Sense codon emancipation for proteome-wide incorporation of noncanonical amino acids: rare isoleucine codon AUA as a target for genetic code expansion.

PubMed

Bohlke, Nina; Budisa, Nediljko

2014-02-01

One of the major challenges in contemporary synthetic biology is to find a route to engineer synthetic organisms with altered chemical constitution. In terms of core reaction types, nature uses an astonishingly limited repertoire of chemistries when compared with the exceptionally rich and diverse methods of organic chemistry. In this context, the most promising route to change and expand the fundamental chemistry of life is the inclusion of amino acid building blocks beyond the canonical 20 (i.e. expanding the genetic code). This strategy would allow the transfer of numerous chemical functionalities and reactions from the synthetic laboratory into the cellular environment. Due to limitations in terms of both efficiency and practical applicability, state-of-the-art nonsense suppression- or frameshift suppression-based methods are less suitable for such engineering. Consequently, we set out to achieve this goal by sense codon emancipation, that is, liberation from its natural decoding function - a prerequisite for the reassignment of degenerate sense codons to a new 21st amino acid. We have achieved this by redesigning of several features of the post-transcriptional modification machinery which are directly involved in the decoding process. In particular, we report first steps towards the reassignment of 5797 AUA isoleucine codons in Escherichia coli using efficient tools for tRNA nucleotide modification pathway engineering. © 2014 The Authors. FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of the Federation of European Microbiological Societies.

Process Extension from Embryonic Stem Cell-Derived Motor Neurons through Synthetic Extracellular Matrix Mimics

NASA Astrophysics Data System (ADS)

McKinnon, Daniel Devaud

This thesis focuses on studying the extension of motor axons through synthetic poly(ethylene glycol) PEG hydrogels that have been modified with biochemical functionalities to render them more biologically relevant. Specifically, the research strategy is to encapsulate embryonic stem cell-derived motor neurons (ESMNs) in synthetic PEG hydrogels crosslinked through three different chemistries providing three mechanisms for dynamically tuning material properties. First, a covalently crosslinked, enzymatically degradable hydrogel is developed and exploited to study the biophysical dynamics of axon extension and matrix remodeling. It is demonstrated that dispersed motor neurons require a battery of adhesive peptides and growth factors to maintain viability and extend axons while those in contact with supportive neuroglial cells do not. Additionally, cell-degradable crosslinker peptides and a soft modulus mimicking that of the spinal cord are requirements for axon extension. However, because local degradation of the hydrogel results in a cellular environment significantly different than that of the bulk, enzymatically degradable peptide crosslinkers were replaced with reversible covalent hydrazone bonds to study the effect of hydrogel modulus on axon extension. This material is characterized in detail and used to measure forces involved in axon extension. Finally, a hydrogel with photocleavable linkers incorporated into the network structure is exploited to explore motor axon response to physical channels. This system is used to direct the growth of motor axons towards co-cultured myotubes, resulting in the formation of an in vitro neural circuit.

A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation

PubMed Central

2015-01-01

For the past dozen years, homogeneous gold catalysis has evolved from a little known topic in organic synthesis to a fully blown research field of significant importance to synthetic practitioners, due to its novel reactivities and reaction modes. Cationic gold(I) complexes are powerful soft Lewis acids that can activate alkynes and allenes toward efficient attack by nucleophiles, leading to the generation of alkenyl gold intermediates. Some of the most versatile aspects of gold catalysis involve the generation of gold carbene intermediates, which occurs through the approach of an electrophile to the distal end of the alkenyl gold moiety, and their diverse transformations thereafter. On the other hand, α-oxo metal carbene/carbenoids are highly versatile intermediates in organic synthesis and can undergo various synthetically challenging yet highly valuable transformations such as C–H insertion, ylide formation, and cyclopropanation reactions. Metal-catalyzed dediazotizations of diazo carbonyl compounds are the principle and most reliable strategy to access them. Unfortunately, the substrates contain a highly energetic diazo moiety and are potentially explosive. Moreover, chemists need to use energetic reagents to prepare them, putting further constrains on operational safety. In this Account, we show that the unique access to the gold carbene species in homogeneous gold catalysis offers an opportunity to generate α-oxo gold carbenes if both nucleophile and electrophile are oxygen. Hence, this approach would enable readily available and safer alkynes to replace hazardous α-diazo carbonyl compounds as precursors in the realm of gold carbene chemistry. For the past several years, we have demonstrated that alkynes can indeed effectively serve as precursors to versatile α-oxo gold carbenes. In our initial study, we showed that a tethered sulfoxide can be a suitable oxidant, which in some cases leads to the formation of α-oxo gold carbene intermediates. The intermolecular approach offers excellent synthetic flexibility because no tethering of the oxidant is required, and its reduced form is not tangled with the product. We were the first research group to develop this strategy, through the use of pyridine/quinolone N-oxides as the external oxidants. In this manner, we can effectively make a C–C triple bond a surrogate of an α-diazo carbonyl moiety in various gold catalyses. With terminal alkynes, we demonstrated that we can efficiently trap exclusively formed terminal carbene centers by internal nucleophiles en route to the formation of cyclic products, including strained oxetan-3-ones and azetidin-3-ones, and by external nucleophiles when a P,N-bidentate ligand is coordinated to gold. With internal alkynes, we generated synthetically useful regioselectivities in the generation of the α-oxo gold carbene moiety, which enables expedient formation of versatile enone products. Other research groups have also applied this strategy en route to versatile synthetic methods. The α-oxo gold carbenes appear to be more electrophilic than their Rh counterpart, which many chemists have focused on in a large array of excellent work on metal carbene chemistry. The ease of accessing the reactive gold carbenes opens up a vast area for developing new synthetic methods that would be distinctively different from the known Rh chemistry and promises to generate a new round of “gold rush”. PMID:24428596

A non-diazo approach to α-oxo gold carbenes via gold-catalyzed alkyne oxidation.

PubMed

Zhang, Liming

2014-03-18

For the past dozen years, homogeneous gold catalysis has evolved from a little known topic in organic synthesis to a fully blown research field of significant importance to synthetic practitioners, due to its novel reactivities and reaction modes. Cationic gold(I) complexes are powerful soft Lewis acids that can activate alkynes and allenes toward efficient attack by nucleophiles, leading to the generation of alkenyl gold intermediates. Some of the most versatile aspects of gold catalysis involve the generation of gold carbene intermediates, which occurs through the approach of an electrophile to the distal end of the alkenyl gold moiety, and their diverse transformations thereafter. On the other hand, α-oxo metal carbene/carbenoids are highly versatile intermediates in organic synthesis and can undergo various synthetically challenging yet highly valuable transformations such as C-H insertion, ylide formation, and cyclopropanation reactions. Metal-catalyzed dediazotizations of diazo carbonyl compounds are the principle and most reliable strategy to access them. Unfortunately, the substrates contain a highly energetic diazo moiety and are potentially explosive. Moreover, chemists need to use energetic reagents to prepare them, putting further constrains on operational safety. In this Account, we show that the unique access to the gold carbene species in homogeneous gold catalysis offers an opportunity to generate α-oxo gold carbenes if both nucleophile and electrophile are oxygen. Hence, this approach would enable readily available and safer alkynes to replace hazardous α-diazo carbonyl compounds as precursors in the realm of gold carbene chemistry. For the past several years, we have demonstrated that alkynes can indeed effectively serve as precursors to versatile α-oxo gold carbenes. In our initial study, we showed that a tethered sulfoxide can be a suitable oxidant, which in some cases leads to the formation of α-oxo gold carbene intermediates. The intermolecular approach offers excellent synthetic flexibility because no tethering of the oxidant is required, and its reduced form is not tangled with the product. We were the first research group to develop this strategy, through the use of pyridine/quinolone N-oxides as the external oxidants. In this manner, we can effectively make a C-C triple bond a surrogate of an α-diazo carbonyl moiety in various gold catalyses. With terminal alkynes, we demonstrated that we can efficiently trap exclusively formed terminal carbene centers by internal nucleophiles en route to the formation of cyclic products, including strained oxetan-3-ones and azetidin-3-ones, and by external nucleophiles when a P,N-bidentate ligand is coordinated to gold. With internal alkynes, we generated synthetically useful regioselectivities in the generation of the α-oxo gold carbene moiety, which enables expedient formation of versatile enone products. Other research groups have also applied this strategy en route to versatile synthetic methods. The α-oxo gold carbenes appear to be more electrophilic than their Rh counterpart, which many chemists have focused on in a large array of excellent work on metal carbene chemistry. The ease of accessing the reactive gold carbenes opens up a vast area for developing new synthetic methods that would be distinctively different from the known Rh chemistry and promises to generate a new round of "gold rush".

Transition-Metal Substitution Doping in Synthetic Atomically Thin Semiconductors

DOE PAGES

Gao, Jian; Kim, Young Duck; Liang, Liangbo; ...

2016-09-20

Semiconductor impurity doping has enabled an entire generation of technology. The emergence of alternative semiconductor material systems, such as transition metal dichalcogenides (TMDCs), requires the development of scalable doping strategies. We report an unprecedented one-pot synthesis for transition-metal substitution in large-area, synthetic monolayer TMDCs. Electron microscopy, optical and electronic transport characterization and ab initio calculations indicate that our doping strategy preserves the attractive qualities of TMDC monolayers, including semiconducting transport and strong direct-gap luminescence. These results are expected to encourage exploration of transition-metal substitution in two-dimensional systems, potentially enabling next-generation optoelectronic technology in the atomically-thin regime.

Square sugars: challenges and synthetic strategies.

PubMed

Hazelard, Damien; Compain, Philippe

2017-05-10

Square sugars (4-membered ring carbohydrate mimetics) are at the intersection of several important topics concerning the recent emergence, in medicinal chemistry, of glycomimetic drugs and small ring systems. Monosaccharide mimetics containing oxetane, azetidine, thiethane or cyclobutane rings present a number of synthetic challenges that are a powerful driving force for innovation in organic synthesis. In addition to the inherent issues associated with 4-membered rings, the high density of functional groups and asymmetric centres found in glycomimetics further complicates the matter and requires efficient stereoselective methodologies. The purpose of this review is to present an overview of the elegant strategies that have been developed to synthesize the different types of square sugars.

Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria.

PubMed

Lozano, José Manuel; Lesmes, Liliana P; Carreño, Luisa F; Gallego, Gina M; Patarroyo, Manuel Elkin

2010-12-06

Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.

Precursor Mediated Synthesis of Nanostructured Silicas: From Precursor-Surfactant Ion Pairs to Structured Materials.

PubMed

Hesemann, Peter; Nguyen, Thy Phung; Hankari, Samir El

2014-04-11

The synthesis of nanostructured anionic-surfactant-templated mesoporous silica (AMS) recently appeared as a new strategy for the formation of nanostructured silica based materials. This method is based on the use of anionic surfactants together with a co-structure-directing agent (CSDA), mostly a silylated ammonium precursor. The presence of this CSDA is necessary in order to create ionic interactions between template and silica forming phases and to ensure sufficient affinity between the two phases. This synthetic strategy was for the first time applied in view of the synthesis of surface functionalized silica bearing ammonium groups and was then extended on the formation of materials functionalized with anionic carboxylate and bifunctional amine-carboxylate groups. In the field of silica hybrid materials, the "anionic templating" strategy has recently been applied for the synthesis of silica hybrid materials from cationic precursors. Starting from di- or oligosilylated imidazolium and ammonium precursors, only template directed hydrolysis-polycondensation reactions involving complementary anionic surfactants allowed accessing structured ionosilica hybrid materials. The mechanistic particularity of this approach resides in the formation of precursor-surfactant ion pairs in the hydrolysis-polycondensation mixture. This review gives a systematic overview over the various types of materials accessed from this cooperative ionic templating approach and highlights the high potential of this original strategy for the formation of nanostructured silica based materials which appears as a complementary strategy to conventional soft templating approaches.

Selective sp3 C-H alkylation via polarity-match-based cross-coupling.

PubMed

Le, Chip; Liang, Yufan; Evans, Ryan W; Li, Ximing; MacMillan, David W C

2017-07-06

The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp 3 )-C(sp 2 ) coupling, there is a growing demand for C-H alkylation reactions, wherein sp 3 C-H bonds are replaced with sp 3 C-alkyl groups. Here we describe a polarity-match-based selective sp 3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp 3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

Monitoring of In-Situ Remediation By Time Lapse 3D Geo-Electric Measurements

NASA Astrophysics Data System (ADS)

Kanli, A. I.; Tildy, P.; Neducza, B.; Nagy, P.; Hegymegi, C.

2017-12-01

Injection of chemical oxidant solution to degrade the subsurface contaminants can be used for hydrocarbon contamination remediation. In this study, we developed a non-destructive measurement strategy to monitor oxidative in-situ remediation processes. The difficulties of the presented study originate from the small volume of conductive solution that can be used due to environmental considerations. Due to the effect of conductive groundwater and the high clay content of the targeted layer and the small volume of conductive solution that can be used due to environmental considerations, a site specific synthetic modelling is necessary for measurement design involving the results of preliminary 2D ERT measurements, electrical conductivity measurements of different active agents and expected resistivity changes calculated by soil resistivity modelling. Because of chemical biodegradation, the results of soil resistivity modelling have suggested that the reagent have complex effects on contaminated soils. As a result the plume of resistivity changes caused by the injected agent was determined showing strong fracturing effect because of the high pressure of injection. 3D time-lapse geo-electric measurements were proven to provide a usable monitoring tool for in-situ remediation as a result of our sophisticated tests and synthetic modelling.

Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1

PubMed Central

Barbie, David A.; Tamayo, Pablo; Boehm, Jesse S.; Kim, So Young; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Sandy, Peter; Meylan, Etienne; Scholl, Claudia; Fröhling, Stefan; Chan, Edmond M.; Sos, Martin L.; Michel, Kathrin; Mermel, Craig; Silver, Serena J.; Weir, Barbara A.; Reiling, Jan H.; Sheng, Qing; Gupta, Piyush B.; Wadlow, Raymond C.; Le, Hanh; Hoersch, Sebastian; Wittner, Ben S.; Ramaswamy, Sridhar; Livingston, David M.; Sabatini, David M.; Meyerson, Matthew; Thomas, Roman K.; Lander, Eric S.; Mesirov, Jill P.; Root, David E.; Gilliland, D. Gary; Jacks, Tyler; Hahn, William C.

2009-01-01

The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. A complementary strategy for targeting KRAS is to identify gene products that, when inhibited, result in cell death only in the presence of an oncogenic allele1,2. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IκB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF-κB anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 and NF-κB signaling as essential in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer. PMID:19847166

Synthetic Arabinomannan Heptasaccharide Glycolipids Inhibit Biofilm Growth and Augment Isoniazid Effects in Mycobacterium smegmatis.

PubMed

Maiti, Krishnagopal; Syal, Kirtimaan; Chatterji, Dipankar; Jayaraman, Narayanaswamy

2017-10-05

Biofilm formation, involving attachment to an adherent surface, is a critical survival strategy of mycobacterial colonies in hostile environmental conditions. Here we report the synthesis of heptasaccharide glycolipids based on mannopyranoside units anchored on to a branched arabinofuranoside core. Two types of glycolipids-2,3-branched and 2,5-branched-were synthesized and evaluated for their efficacies in inhibiting biofilm growth by the non-pathogenic mycobacterium variant Mycobacterium smegmatis. Biofilm formation was inhibited at a minimum biofilm growth inhibition concentration (MBIC) of 100 μg mL -1 in the case of the 2,5-branched heptasaccharide glycolipid. Further, we were able to ascertain that a combination of the drug isoniazid with the branched heptasaccharide glycolipid (50 μg mL -1 ) potentiates the drug, making it three times more effective, with an improved MBIC of 30 μg mL -1 . These studies establish that synthetic glycolipids not only act as inhibitors of biofilm growth, but also provide a synergistic effect when combined with significantly lowered concentrations of isoniazid to disrupt the biofilm structures of the mycobacteria. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective sp3 C–H alkylation via polarity-match-based cross-coupling

PubMed Central

Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

2017-01-01

The functionalization of carbon–hydrogen (C–H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence1. Although many C–H functionalization reactions involve C(sp3)–C(sp2) coupling, there is a growing demand for C–H alkylation reactions, wherein sp3 C–H bonds are replaced with sp3 C–alkyl groups. Here we describe a polarity-match-based selective sp3 C–H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C–H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl–alkyl fragment coupling. The sp3 C–H alkylation is highly selective for the α-C–H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry. PMID:28636596

Selective sp3 C-H alkylation via polarity-match-based cross-coupling

NASA Astrophysics Data System (ADS)

Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

2017-07-01

The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp3)-C(sp2) coupling, there is a growing demand for C-H alkylation reactions, wherein sp3 C-H bonds are replaced with sp3 C-alkyl groups. Here we describe a polarity-match-based selective sp3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against MRSA.

PubMed

Yu, Guanping; Kuo, David; Shoham, Menachem; Viswanathan, Rajesh

2014-02-10

Antibiotic resistance coupled with decreased development of new antibiotics necessitates the search for novel antibacterial agents. Antivirulence agents offer an alternative to conventional antibiotics. In this work, we report on a family of small-molecule antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA), the most widespread bacterial pathogen. Structure-activity relationship studies led to the development of a concise synthesis of a 148-member biarylhydroxyketone library. An acylation bond-forming process afforded resorcinols (1) and aryloxy acetonitriles (2) as synthons. A Lewis-acid-activated Friedel-Crafts' acylation step involving a nitrile functionality of 2 by ZnCl2, followed by nucleophilic attack by 1 was executed to obtain biaryl hydroxyketones in excellent yields. A large number of products crystallized. This strategy affords a range of biarylhydroxyketones in a single step. This is the first collective synthetic study documenting access to this class of compounds through a single synthetic operation. In vitro efficacy of compounds in this library was evaluated by a rabbit erythrocyte hemolysis assay. The most efficacious compound, 4f-12, inhibits hemolysis by 98.1 ± 0.1% compared to control in the absence of the compound.

Synthetic Approaches to the Lamellarins—A Comprehensive Review

PubMed Central

Imbri, Dennis; Tauber, Johannes; Opatz, Till

2014-01-01

The present review discusses the known synthetic routes to the lamellarin alkaloids published until 2014. It begins with syntheses of the structurally simpler type-II lamellarins and then focuses on the larger class of the 5,6-saturated and -unsaturated type-I lamellarins. The syntheses are grouped by the strategy employed for the assembly of the central pyrrole ring. PMID:25528958

Phage Therapy in the Era of Synthetic Biology.

PubMed

Barbu, E Magda; Cady, Kyle C; Hubby, Bolyn

2016-10-03

For more than a century, bacteriophage (or phage) research has enabled some of the most important discoveries in biological sciences and has equipped scientists with many of the molecular biology tools that have advanced our understanding of replication, maintenance, and expression of genetic material. Phages have also been recognized and exploited as natural antimicrobial agents and nanovectors for gene therapy, but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as narrow host range, bacterial resistance, and unique pharmacokinetics. However, increasing concern related to the emergence of bacteria resistant to multiple antibiotics has heightened interest in phage therapy and the development of strategies to overcome hurdles associated with bacteriophage therapeutics. Recent progress in sequencing technologies, DNA manipulation, and synthetic biology allowed scientists to refactor the entire bacterial genome of Mycoplasma mycoides, thereby creating the first synthetic cell. These new strategies for engineering genomes may have the potential to accelerate the construction of designer phage genomes with superior therapeutic potential. Here, we discuss the use of phage as therapeutics, as well as how synthetic biology can create bacteriophage with desirable attributes. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Feasibility of nitrification/denitrification in a sequencing batch biofilm reactor with liquid circulation applied to post-treatment.

PubMed

Andrade do Canto, Catarina Simone; Rodrigues, José Alberto Domingues; Ratusznei, Suzana Maria; Zaiat, Marcelo; Foresti, Eugênio

2008-02-01

An investigation was performed on the biological removal of ammonium nitrogen from synthetic wastewater by the simultaneous nitrification/denitrification (SND) process, using a sequencing batch biofilm reactor (SBBR). System behavior was analyzed as to the effects of sludge type used as inoculum (autotrophic/heterotrophic), wastewater feed strategy (batch/fed-batch) and aeration strategy (continuous/intermittent). The presence of an autotrophic aerobic sludge showed to be essential for nitrification startup, despite publications stating the existence of heterotrophic organisms capable of nitrifying organic and inorganic nitrogen compounds at low dissolved oxygen concentrations. As to feed strategy, batch operation (synthetic wastewater containing 100 mg COD/L and 50 mg N-NH(4)(+)/L) followed by fed-batch (synthetic wastewater with 100 mg COD/L) during a whole cycle seemed to be the most adequate, mainly during the denitrification phase. Regarding aeration strategy, an intermittent mode, with dissolved oxygen concentration of 2.0mg/L in the aeration phase, showed the best results. Under these optimal conditions, 97% of influent ammonium nitrogen (80% of total nitrogen) was removed at a rate of 86.5 mg N-NH(4)(+)/Ld. In the treated effluent only 0.2 mg N-NO(2)(-)/L,4.6 mg N-NO(3)(-)/L and 1.0 mg N-NH(4)(+)/L remained, demonstrating the potential viability of this process in post-treatment of wastewaters containing ammonium nitrogen.

Aligator: A computational tool for optimizing total chemical synthesis of large proteins.

PubMed

Jacobsen, Michael T; Erickson, Patrick W; Kay, Michael S

2017-09-15

The scope of chemical protein synthesis (CPS) continues to expand, driven primarily by advances in chemical ligation tools (e.g., reversible solubilizing groups and novel ligation chemistries). However, the design of an optimal synthesis route can be an arduous and fickle task due to the large number of theoretically possible, and in many cases problematic, synthetic strategies. In this perspective, we highlight recent CPS tool advances and then introduce a new and easy-to-use program, Aligator (Automated Ligator), for analyzing and designing the most efficient strategies for constructing large targets using CPS. As a model set, we selected the E. coli ribosomal proteins and associated factors for computational analysis. Aligator systematically scores and ranks all feasible synthetic strategies for a particular CPS target. The Aligator script methodically evaluates potential peptide segments for a target using a scoring function that includes solubility, ligation site quality, segment lengths, and number of ligations to provide a ranked list of potential synthetic strategies. We demonstrate the utility of Aligator by analyzing three recent CPS projects from our lab: TNFα (157 aa), GroES (97 aa), and DapA (312 aa). As the limits of CPS are extended, we expect that computational tools will play an increasingly important role in the efficient execution of ambitious CPS projects such as production of a mirror-image ribosome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer

DTIC Science & Technology

2013-02-01

looking at the interaction of the synthetic cannabinoid WIN55,212-2 and ionizing radiation has led to preliminary results implicating a novel site of...we found that the various cannabinoids do not interfere with the anti-proliferative effects of either treatment; furthermore, the synthetic ...aminoalkylindole series, is one of the most highly studied synthetic cannabinoids. It has been shown to produce the full spectrum of psychoactive effects

System and method for forming synthetic protein crystals to determine the conformational structure by crystallography

DOEpatents

Craig, G.D.; Glass, R.; Rupp, B.

1997-01-28

A method is disclosed for forming synthetic crystals of proteins in a carrier fluid by use of the dipole moments of protein macromolecules that self-align in the Helmholtz layer adjacent to an electrode. The voltage gradients of such layers easily exceed 10{sup 6}V/m. The synthetic protein crystals are subjected to x-ray crystallography to determine the conformational structure of the protein involved. 2 figs.

Evaluation of the effect of synthetic fibers and nonwoven geotextile reinforcement on the stability of heavy clay embankments.

DOT National Transportation Integrated Search

2003-04-01

This study evaluates two methods for repairing slope surface failures of clayey soil embankments. One method involves reinforcing the cohesive soils with randomly oriented synthetic fibers; the other method incorporates non-woven geotextiles. The per...

Metal-directed design of supramolecular protein assemblies

PubMed Central

Bailey, Jake B.; Subramanian, Rohit H.; Churchfield, Lewis A.

2016-01-01

Owing to their central roles in cellular signaling, construction, and biochemistry, protein-protein interactions (PPIs) and protein self-assembly have become a major focus of molecular design and synthetic biology. In order to circumvent the complexity of constructing extensive non-covalent interfaces, which are typically involved in natural PPIs and protein self-assembly, we have developed two design strategies, Metal-Directed Protein Self-Assembly (MDPSA) and Metal-Templated Interface Redesign (MeTIR). These strategies, inspired by both the proposed evolutionary roles of metals and their prevalence in natural PPIs, take advantage of the favorable properties of metal coordination (bonding strength, directionality, and reversibility) to guide protein self-assembly with minimal design and engineering. Using a small, monomeric protein (cytochrome cb562) as a model building block, we employed MDPSA and MeTIR to create a diverse array of functional supramolecular architectures which range from structurally tunable oligomers to metalloprotein complexes that can properly self-assemble in living cells into novel metalloenzymes. The design principles and strategies outlined herein should be readily applicable to other protein systems with the goal of creating new PPIs and protein assemblies with structures and functions not yet produced by natural evolution. PMID:27586336

Radical covalent organic frameworks: a general strategy to immobilize open-accessible polyradicals for high-performance capacitive energy storage.

PubMed

Xu, Fei; Xu, Hong; Chen, Xiong; Wu, Dingcai; Wu, Yang; Liu, Hao; Gu, Cheng; Fu, Ruowen; Jiang, Donglin

2015-06-01

Ordered π-columns and open nanochannels found in covalent organic frameworks (COFs) could render them able to store electric energy. However, the synthetic difficulty in achieving redox-active skeletons has thus far restricted their potential for energy storage. A general strategy is presented for converting a conventional COF into an outstanding platform for energy storage through post-synthetic functionalization with organic radicals. The radical frameworks with openly accessible polyradicals immobilized on the pore walls undergo rapid and reversible redox reactions, leading to capacitive energy storage with high capacitance, high-rate kinetics, and robust cycle stability. The results suggest that channel-wall functional engineering with redox-active species will be a facile and versatile strategy to explore COFs for energy storage. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Guiding bioprocess design by microbial ecology.

PubMed

Volmer, Jan; Schmid, Andreas; Bühler, Bruno

2015-06-01

Industrial bioprocess development is driven by profitability and eco-efficiency. It profits from an early stage definition of process and biocatalyst design objectives. Microbial bioprocess environments can be considered as synthetic technical microbial ecosystems. Natural systems follow Darwinian evolution principles aiming at survival and reproduction. Technical systems objectives are eco-efficiency, productivity, and profitable production. Deciphering technical microbial ecology reveals differences and similarities of natural and technical systems objectives, which are discussed in this review in view of biocatalyst and process design and engineering strategies. Strategies for handling opposing objectives of natural and technical systems and for exploiting and engineering natural properties of microorganisms for technical systems are reviewed based on examples. This illustrates the relevance of considering microbial ecology for bioprocess design and the potential for exploitation by synthetic biology strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design properties of hydrogel tissue-engineering scaffolds

PubMed Central

Zhu, Junmin; Marchant, Roger E

2011-01-01

This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding. PMID:22026626

Synthetic and semi-synthetic strategies to study ubiquitin signaling.

PubMed

van Tilburg, Gabriëlle Ba; Elhebieshy, Angela F; Ovaa, Huib

2016-06-01

The post-translational modification ubiquitin can be attached to the ɛ-amino group of lysine residues or to a protein's N-terminus as a mono ubiquitin moiety. Via its seven intrinsic lysine residues and its N-terminus, it can also form ubiquitin chains on substrates in many possible ways. To study ubiquitin signals, many synthetic and semi-synthetic routes have been developed for generation of ubiquitin-derived tools and conjugates. The strength of these methods lies in their ability to introduce chemo-selective ligation handles at sites that currently cannot be enzymatically modified. Here, we review the different synthetic and semi-synthetic methods available for ubiquitin conjugate synthesis and their contribution to how they have helped investigating conformational diversity of diubiquitin signals. Next, we discuss how these methods help understanding the ubiquitin conjugation-deconjugation system by recent advances in ubiquitin ligase probes and diubiquitin-based DUB probes. Lastly, we discuss how these methods help studying post-translational modification of ubiquitin itself. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Synthetic Model of Mass Persuasion.

ERIC Educational Resources Information Center

Kneupper, Charles W.; Underwood, Willard A.

Mass persuasion involves a message production process which significantly alters or reinforces an attitude, belief, or action of the members of a large, heterogeneous audience. A synthetic communication model for mass persuasion has been constructed which incorporates aspects of several models created to describe the process of effective…

A Series of Synthetic Organic Experiments Demonstrating Physical Organic Principles.

ERIC Educational Resources Information Center

Sayed, Yousry; And Others

1989-01-01

Describes several common synthetic organic transformations involving alkenes, alcohols, alkyl halides, and ketones. Includes concepts on kinetic versus thermodynamic control of reaction, rearrangement of a secondary carbocation to a tertiary cation, and the effect of the size of the base on orientation during elimination. (MVL)

Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel.

PubMed

Saeed, Aamer; Shahzad, Danish; Faisal, Muhammad; Larik, Fayaz Ali; El-Seedi, Hesham R; Channar, Pervaiz Ali

2017-11-01

S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments. Worldwide sales of Plavix amounted to $6.4 billion yearly, which ranks second. Attributed to the increased demand of (S)-clopidogrel drug, it provoked the synthetic community to devise facile synthetic approaches. This review aims to summarize the synthetic methods of (S)-clopidogrel drug reported in the literature. The present review discusses the pros and cons of each synthetic methodology, which would be beneficial to the scientific community for further developments in the synthetic methodologies for (S)-clopidogrel. In addition, the compilation approach of literature-reported synthetic strategies of (S)-clopidogrel in one platform is advantageous, supportive, and crucial for the synthetic community to elect the best synthetic methodology of (S)-clopidogrel and to create new synthesis ideas. © 2017 Wiley Periodicals, Inc.

The population genetics of X-autosome synthetic lethals and steriles.

PubMed

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Emerging biomedical applications of synthetic biology.

PubMed

Weber, Wilfried; Fussenegger, Martin

2011-11-29

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

An Ontology of Power: Perception and Reality in Conflict

DTIC Science & Technology

2016-12-01

synthetic model was developed as the constant comparative analysis was resumed through the application of selected theory toward the original source...The synthetic model represents a series of maxims for the analysis of a complex social system, developed through a study of contemporary national...and categories. A model of strategic agency is proposed as an alternative framework for developing security strategy. The strategic agency model draws

A perspective on slow-relaxing molecular magnets built from rare-earths and nitronyl-nitroxide building blocks (invited)

NASA Astrophysics Data System (ADS)

Bogani, Lapo

2011-04-01

We offer a perspective, accessible to both chemists and physicists, of recent developments in the synthesis and characterization of molecular magnetic materials based on rare-earths and nitronyl-nitroxide radicals. We show both the rationale of the synthetic strategies and the observed behaviors. We highlight the relevance of these findings for synthetic chemists, material scientists, and physicists.

Hoechst tagging: a modular strategy to design synthetic fluorescent probes for live-cell nucleus imaging.

PubMed

Nakamura, Akinobu; Takigawa, Kazumasa; Kurishita, Yasutaka; Kuwata, Keiko; Ishida, Manabu; Shimoda, Yasushi; Hamachi, Itaru; Tsukiji, Shinya

2014-06-11

We report a general strategy to create small-molecule fluorescent probes for the nucleus in living cells. Our strategy is based on the attachment of the DNA-binding Hoechst compound to a fluorophore of interest. Using this approach, simple fluorescein, BODIPY, and rhodamine dyes were readily converted to novel turn-on fluorescent nucleus-imaging probes.

Access to site-specific Fc–cRGD peptide conjugates through streamlined expressed protein ligation†

PubMed Central

Frutos, S.; Jordan, J. B.; Bio, M. M.; Muir, T. W.; Thiel, O. R.; Vila-Perelló, M.

2018-01-01

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners. PMID:27722696

Rational design of inducible CRISPR guide RNAs for de novo assembly of transcriptional programs

PubMed Central

Ferry, Quentin R. V.; Lyutova, Radostina; Fulga, Tudor A.

2017-01-01

CRISPR-based transcription regulators (CRISPR-TRs) have transformed the current synthetic biology landscape by allowing specific activation or repression of any target gene. Here we report a modular and versatile framework enabling rapid implementation of inducible CRISPR-TRs in mammalian cells. This strategy relies on the design of a spacer-blocking hairpin (SBH) structure at the 5′ end of the single guide RNA (sgRNA), which abrogates the function of CRISPR-transcriptional activators. By replacing the SBH loop with ligand-controlled RNA-cleaving units, we demonstrate conditional activation of quiescent sgRNAs programmed to respond to genetically encoded or externally delivered triggers. We use this system to couple multiple synthetic and endogenous target genes with specific inducers, and assemble gene regulatory modules demonstrating parallel and orthogonal transcriptional programs. We anticipate that this ‘plug and play' approach will be a valuable addition to the synthetic biology toolkit, facilitating the understanding of natural gene circuits and the design of cell-based therapeutic strategies. PMID:28256578

Synthetic biology: new engineering rules for an emerging discipline

PubMed Central

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development. PMID:16738572

Synthetic biology: new engineering rules for an emerging discipline.

PubMed

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

Programmed coherent coupling in a synthetic DNA-based excitonic circuit

NASA Astrophysics Data System (ADS)

Boulais, Étienne; Sawaya, Nicolas P. D.; Veneziano, Rémi; Andreoni, Alessio; Banal, James L.; Kondo, Toru; Mandal, Sarthak; Lin, Su; Schlau-Cohen, Gabriela S.; Woodbury, Neal W.; Yan, Hao; Aspuru-Guzik, Alán; Bathe, Mark

2018-02-01

Natural light-harvesting systems spatially organize densely packed chromophore aggregates using rigid protein scaffolds to achieve highly efficient, directed energy transfer. Here, we report a synthetic strategy using rigid DNA scaffolds to similarly program the spatial organization of densely packed, discrete clusters of cyanine dye aggregates with tunable absorption spectra and strongly coupled exciton dynamics present in natural light-harvesting systems. We first characterize the range of dye-aggregate sizes that can be templated spatially by A-tracts of B-form DNA while retaining coherent energy transfer. We then use structure-based modelling and quantum dynamics to guide the rational design of higher-order synthetic circuits consisting of multiple discrete dye aggregates within a DX-tile. These programmed circuits exhibit excitonic transport properties with prominent circular dichroism, superradiance, and fast delocalized exciton transfer, consistent with our quantum dynamics predictions. This bottom-up strategy offers a versatile approach to the rational design of strongly coupled excitonic circuits using spatially organized dye aggregates for use in coherent nanoscale energy transport, artificial light-harvesting, and nanophotonics.

Hydrogen from coal

NASA Technical Reports Server (NTRS)

1975-01-01

Hydrogen production from coal by hydrogasification is described. The process involves the solubilization of coal to form coal liquids, which are hydrogasified to produce synthetic pipeline gas; steam reforming this synthetic gas by a nuclear heat source produces hydrogen. A description is given of the hydrogen plant, its performance, and its effect on the environment.

Strategies for the preparation of bifunctional gadolinium(III) chelators

PubMed Central

Frullano, Luca; Caravan, Peter

2012-01-01

The development of gadolinium chelators that can be easily and readily linked to various substrates is of primary importance for the development high relaxation efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over the last 25 years a large number of bifunctional chelators have been prepared. For the most part, these compounds are based on ligands that are already used in clinically approved contrast agents. More recently, new bifunctional chelators have been reported based on complexes that show a more potent relaxation effect, faster complexation kinetics and in some cases simpler synthetic procedures. This review provides an overview of the synthetic strategies used for the preparation of bifunctional chelators for MRI applications. PMID:22375102

Mapping and proteomic analysis of albumin and globulin proteins in hexaploid wheat kernels (Triticum aestivum L.).

PubMed

Merlino, Marielle; Leroy, Philippe; Chambon, Christophe; Branlard, Gérard

2009-05-01

Albumins and globulins of wheat endosperm represent 20% of total kernel protein. They are soluble proteins, mainly enzymes and proteins involved in cell functions. Two-dimensional gel immobiline electrophoresis (2DE) (pH 4-7) x SDS-Page revealed around 2,250 spots. Ninety percent of the spots were common between the very distantly related cultivars 'Opata 85' and 'Synthetic W7984', the two parents of the International Triticeae Mapping Initiative (ITMI) progeny. 'Opata' had 130 specific spots while 'Synthetic' had 96. 2DE and image analysis of the soluble proteins present in 112 recombinant inbred lines of the F9-mapped ITMI progeny enabled 120 unbiased segregating spots to be mapped on 21 wheat (Triticum aestivum L. em. Thell) chromosomes. After trypsic digestion, mapped spots were subjected to MALDI-Tof or tandem mass spectrometry for protein identification by database mining. Among the 'Opata' and 'Synthetic' spots identified, many enzymes have already been mapped in the barley and rice genomes. Multigene families of Heat Shock Proteins, beta-amylases, UDP-glucose pyrophosphorylases, peroxydases and thioredoxins were successfully identified. Although other proteins remain to be identified, some differences were found in the number of segregating proteins involved in response to stress: 11 proteins found in the modern selected cultivar 'Opata 85' as compared to 4 in the new hexaploid ;Synthetic W7984'. In addition, 'Opata' and 'Synthetic' differed in the number of proteins involved in protein folding (2 and 10, respectively). The usefulness of the mapped enzymes for future research on seed composition and characteristics is discussed.

Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics and autopsy findings.

PubMed

Ezaki, Jiro; Ro, Ayako; Hasegawa, Masayuki; Kibayashi, Kazuhiko

2016-09-01

Sixty-one autopsy cases involving cathinones and/or cannabinoids (synthetic cathinones/cannabinoids) use have been reported. However, little is known about the demographics and autopsy findings in fatal synthetic cathinones/cannabinoids users. To elucidate demographic and autopsy findings (i.e. major organ pathology and causes of death) in synthetic cathinones/cannabinoids cases. We reviewed forensic autopsy reports in Department of Legal Medicine of Tokyo Women's Medical University (Tokyo, Japan) between 2011 and 2015 (a total of 359). We compared demographic and autopsy findings between synthetic cathinones/cannabinoids and methamphetamine cases (as control subjects). There were 12 synthetic cathinones/cannabinoids cases and 10 methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly younger than methamphetamine users (p < 0.01), and there were no cases that used both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication and cardiac ischemia were the two most prominent causes of death in both synthetic cathinones/cannabinoids users and methamphetamine users. Excited delirium syndrome and pulmonary aspiration were found only in synthetic cathinones/cannabinoids cases. The populations of synthetic cathinones/cannabinoids and methamphetamine users who died of an overdose are different in Japan. Acute intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration, and drowning are the major autopsy findings in synthetic cathinones/cannabinoids-related death. Clinicians shuld be aware of these potentially fatal complications in the medical management of synthetic cathinones/cannabinoids users.

Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

PubMed

Gauthier, Marc A; Klok, Harm-Anton

2008-06-21

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

Masters of defence: biomechanics of stinging nettles

NASA Astrophysics Data System (ADS)

Jensen, Kaare H.; Knoblauch, Jan

2017-11-01

The techniques employed by plants and animals to defend themselves are very varied. Some involve extremely refined armaments. Stinging nettles employ hollow needle-like stinging hairs constructed from silica, the mineral from which we make glass, and they are filled with poison. The hairs are remarkably rigid and rarely break. Yet the tip is so sharp that the slightest touch cuts human skin, and so fragile that it breaks at that touch and releases poison into the wound. How the seemingly antagonist mechanical functions of rigidity and fragility are achieved, however, is unknown. We combine experiments on real and synthetic stingers to elucidate the poison injection mechanism. The design of plant stingers is compared to other natural systems and optimal stinging strategies are discussed. This work was supported by a research Grant (13166) from VILLUM FONDEN.

Tissue engineering and peripheral nerve reconstruction: an overview.

PubMed

Geuna, Stefano; Gnavi, Sara; Perroteau, Isabelle; Tos, Pierluigi; Battiston, Bruno

2013-01-01

Nerve repair is no more regarded as merely a matter of microsurgical reconstruction. To define this evolving reconstructive/regenerative approach, the term tissue engineering is being increasingly used since it reflects the search for interdisciplinary and integrated treatment strategies. However, the drawback of this new approach is its intrinsic complexity, which is the result of the variety of scientific disciplines involved. This chapter presents a synthetic overview of the state of the art in peripheral nerve tissue engineering with a look forward at the most promising innovations emerging from basic science investigation. This review is intended to set the stage for the collection of papers in the thematic issue of the International Review of Neurobiology that is focused on the various interdisciplinary approaches in peripheral nerve tissue engineering. © 2013 Elsevier Inc. All rights reserved.

Computational genomic identification and functional reconstitution of plant natural product biosynthetic pathways

PubMed Central

2016-01-01

Covering: 2003 to 2016 The last decade has seen the first major discoveries regarding the genomic basis of plant natural product biosynthetic pathways. Four key computationally driven strategies have been developed to identify such pathways, which make use of physical clustering, co-expression, evolutionary co-occurrence and epigenomic co-regulation of the genes involved in producing a plant natural product. Here, we discuss how these approaches can be used for the discovery of plant biosynthetic pathways encoded by both chromosomally clustered and non-clustered genes. Additionally, we will discuss opportunities to prioritize plant gene clusters for experimental characterization, and end with a forward-looking perspective on how synthetic biology technologies will allow effective functional reconstitution of candidate pathways using a variety of genetic systems. PMID:27321668

3D hierarchical Ag nanostructures formed on poly(acrylic acid) brushes grafted graphene oxide as promising SERS substrates

NASA Astrophysics Data System (ADS)

Xing, Guoke; Wang, Ke; Li, Ping; Wang, Wenqin; Chen, Tao

2018-03-01

In this study, in situ generation of Ag nanostructures with various morphology on poly(acrylic acid) (PAA) brushes grafted onto graphene oxide (GO), for use as substrates for surface-enhanced Raman scattering (SERS), is demonstrated. The overall synthetic strategy involves the loading of Ag precursor ions ((Ag+ and [Ag(NH3)2]+) onto PAA brush-grafted GO, followed by their in situ reduction to Ag nanostructures of various morphology using a reducing agent (NaBH4 or ascorbic acid). Novel 3D hierarchical flowerlike Ag nanostructures were obtained by using AgNO3 as precursor and ascorbic acid as reducing agent. Using 4-aminothiophenol as probe molecules, the as-prepared hierarchical Ag nanostructures exhibited excellent SERS performance, providing enhancement factors of ˜107.

Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance

PubMed Central

Eckelbarger, Joseph D.; Wilmot, Jeremy T.; Epperson, Matthew T.; Thakur, Chandar S.; Shum, David; Antczak, Christophe; Tarassishin, Leonid; Djaballah, Hakim; Gin, David Y.

2008-01-01

Deoxyharringtonine (2), homoharringtonine (3), homodeoxyharringtonine (4), and anhydroharringtonine (5) are reported to be among the most potent members of the antileukemia alkaloids isolated from the Cephalotaxus genus. Convergent syntheses of these four natural products are described, each involving novel synthetic methods and strategies. These syntheses enabled evaluation of several advanced natural and non-natural compounds against an array of human hematopoietic and solid tumor cells. Potent cytotoxicity was observed in several cell lines previously not challenged with these alkaloids. Variations in the structure of the ester chain within this family of alkaloids confer differing activity profiles against vincristine-resistant HL-60/RV+, signalling new avenues for molecular design of these natural products to combat multi-drug resistance. PMID:18366032

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis.

PubMed

Kärkäs, Markus D; Porco, John A; Stephenson, Corey R J

2016-09-14

The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.

Synthesis of Sequence-Specific DNA-Protein Conjugates via a Reductive Amination Strategy

PubMed Central

Wickramaratne, Susith; Mukherjee, Shivam; Villalta, Peter W.; Schärer, Orlando D.; Tretyakova, Natalia

2013-01-01

DNA-protein cross-links (DPCs) are ubiquitous, structurally diverse DNA lesions formed upon exposure to bis-electrophiles, transition metals, UV light, and reactive oxygen species. Because of their super-bulky, helix distorting nature, DPCs interfere with DNA replication, transcription, and repair, potentially contributing to mutagenesis and carcinogenesis. However, the biological implications of DPC lesions have not been fully elucidated due to the difficulty of generating site-specific DNA substrates representative of DPC lesions formed in vivo. In the present study, a novel approach involving post-synthetic reductive amination has been developed to prepare a range of hydrolytically stable lesions structurally mimicking the DPCs produced between the N7 position of guanine in DNA and basic lysine or arginine side chains of proteins and peptides. PMID:23885807

Membrane transporter engineering in industrial biotechnology and whole cell biocatalysis.

PubMed

Kell, Douglas B; Swainston, Neil; Pir, Pınar; Oliver, Stephen G

2015-04-01

Because they mainly do not involve chemical changes, membrane transporters have been a Cinderella subject in the biotechnology of small molecule production, but this is a serious oversight. Influx transporters contribute significantly to the flux towards product, and efflux transporters ensure the accumulation of product in the much greater extracellular space of fermentors. Programmes for improving biotechnological processes might therefore give greater consideration to transporters than may have been commonplace. Strategies for identifying important transporters include expression profiling, genome-wide knockout studies, stress-based selection, and the use of inhibitors. In addition, modern methods of directed evolution and synthetic biology, especially those effecting changes in energy coupling, offer huge opportunities for increasing the flux towards extracellular product formation by transporter engineering. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel perspectives for the engineering of abiotic stress tolerance in plants.

PubMed

Cabello, Julieta V; Lodeyro, Anabella F; Zurbriggen, Matias D

2014-04-01

Adverse environmental conditions pose serious limitations to agricultural production. Classical biotechnological approaches towards increasing abiotic stress tolerance focus on boosting plant endogenous defence mechanisms. However, overexpression of regulatory elements or effectors is usually accompanied by growth handicap and yield penalties due to crosstalk between developmental and stress-response networks. Herein we offer an overview on novel strategies with the potential to overcome these limitations based on the engineering of regulatory systems involved in the fine-tuning of the plant response to environmental hardships, including post-translational modifications, small RNAs, epigenetic control of gene expression and hormonal networks. The development and application of plant synthetic biology tools and approaches will add new functionalities and perspectives to genetic engineering programs for enhancing abiotic stress tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

An In Situ One-Pot Synthetic Approach towards Multivariate Zirconium MOFs.

PubMed

Sun, Yujia; Sun, Lixian; Feng, Dawei; Zhou, Hong-Cai

2016-05-23

Chemically highly stable MOFs incorporating multiple functionalities are of great interest for applications under harsh environments. Herein, we presented a facile one-pot synthetic strategy to incorporate multiple functionalities into stable Zr-MOFs from mixed ligands of different geometry and connectivity. Via our strategy, tetratopic tetrakis(4-carboxyphenyl)porphyrin (TCPP) ligands were successfully integrated into UiO-66 while maintaining the crystal structure, morphology, and ultrahigh chemical stability of UiO-66. The amount of incorporated TCPP is controllable. Through various combinations of BDC derivatives and TCPP, 49 MOFs with multiple functionalities were obtained. Among them, MOFs modified with FeTCPPCl were demonstrated to be catalytically active for the oxidation of ABTS. We anticipate our strategy to provide a facile route to introduce multiple functionalities into stable Zr-MOFs for a wide variety of potential applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination.

PubMed

Bailey, Lucas J; Sheehy, Kimberly M; Dominik, Pawel K; Liang, Wenguang G; Rui, Huan; Clark, Michael; Jaskolowski, Mateusz; Kim, Yejoon; Deneka, Dawid; Tang, Wei-Jen; Kossiakoff, Anthony A

2018-02-02

Antibody Fab fragments have been exploited with significant success to facilitate the structure determination of challenging macromolecules as crystallization chaperones and as molecular fiducial marks for single particle cryo-electron microscopy approaches. However, the inherent flexibility of the "elbow" regions, which link the constant and variable domains of the Fab, can introduce disorder and thus diminish their effectiveness. We have developed a phage display engineering strategy to generate synthetic Fab variants that significantly reduces elbow flexibility, while maintaining their high affinity and stability. This strategy was validated using previously recalcitrant Fab-antigen complexes where introduction of an engineered elbow region enhanced crystallization and diffraction resolution. Furthermore, incorporation of the mutations appears to be generally portable to other synthetic antibodies and may serve as a universal strategy to enhance the success rates of Fabs as structure determination chaperones. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developing a synthetic national population to investigate the impact of different cardiovascular disease risk management strategies: A derivation and validation study.

PubMed

Knight, Josh; Wells, Susan; Marshall, Roger; Exeter, Daniel; Jackson, Rod

2017-01-01

Many national cardiovascular disease (CVD) risk factor management guidelines now recommend that drug treatment decisions should be informed primarily by patients' multi-variable predicted risk of CVD, rather than on the basis of single risk factor thresholds. To investigate the potential impact of treatment guidelines based on CVD risk thresholds at a national level requires individual level data representing the multi-variable CVD risk factor profiles for a country's total adult population. As these data are seldom, if ever, available, we aimed to create a synthetic population, representing the joint CVD risk factor distributions of the adult New Zealand population. A synthetic population of 2,451,278 individuals, representing the actual age, gender, ethnicity and social deprivation composition of people aged 30-84 years who completed the 2013 New Zealand census was generated using Monte Carlo sampling. Each 'synthetic' person was then probabilistically assigned values of the remaining cardiovascular disease (CVD) risk factors required for predicting their CVD risk, based on data from the national census national hospitalisation and drug dispensing databases and a large regional cohort study, using Monte Carlo sampling and multiple imputation. Where possible, the synthetic population CVD risk distributions for each non-demographic risk factor were validated against independent New Zealand data sources. We were able to develop a synthetic national population with realistic multi-variable CVD risk characteristics. The construction of this population is the first step in the development of a micro-simulation model intended to investigate the likely impact of a range of national CVD risk management strategies that will inform CVD risk management guideline updates in New Zealand and elsewhere.

Synthetic miR-34a mimics as a novel therapeutic agent for Multiple Myeloma: in vitro and in vivo evidence

PubMed Central

Di Martino, Maria T.; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Lionetti, Marta; Pitari, Maria R.; Gallo Cantafio, Maria E.; Gullà, Annamaria; Conforti, Francesco; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Negrini, Massimo; Ferrarini, Manlio; Caraglia, Michele; Shammas, Masood A.; Munshi, Nikhil C.; Anderson, Kenneth C.; Neri, Antonino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2015-01-01

Purpose Deregulated expression of microRNAs (miRNAs) has been demonstrated in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Experimental Design Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Results Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6 and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in SCID mice. The anti-MM activity of lipidic-formulated miR-34a was further demonstrated in vivo in two different experimental settings: i) SCID mice bearing non-transduced MM xenografts; and ii) SCID-synth-hu mice implanted with synthetic 3D scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Conclusions Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. PMID:23035210

Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence.

PubMed

Di Martino, Maria T; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Lionetti, Marta; Pitari, Maria R; Cantafio, Maria E Gallo; Gullà, Annamaria; Conforti, Francesco; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Negrini, Massimo; Ferrarini, Manlio; Caraglia, Michele; Shammas, Masood A; Munshi, Nikhil C; Anderson, Kenneth C; Neri, Antonino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2012-11-15

Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. ©2012 AACR.

Direct Partial Oxidations Using Molecular Oxygen - Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kemp, Richard

In 2006, Richard A. Kemp (University of New Mexico) and Karen I. Goldberg (University of Washington) formed a team and began to investigate new strategies to accomplish direct selective aerobic oxidations, with a particular emphasis on the epoxidation of propylene and higher olefins. This DOE-BES funded project was renewed twice and concluded after a no-cost extension earlier this year. Multiple novel strategies involving homogeneous catalyst systems were initiated and investigated during the award. Important fundamental understanding and insight concerning requirements for promotion of aerobic olefin epoxidation was generated. During the tenure of this project, new knowledge was generated concerning themore » synthesis, characterization and aerobic reactivity of metal hydrides and hydroxides. Key results describing synthetic strategies and optimization of the preparation of mononuclear late metal hydrides were published. The team reported the first example of O2 insertion into a Pd-H bond, a reaction which had been proposed in the literature but never previously observed. Our experimental investigation of the mechanism was later followed by computational work, and a description of what is now referred to as the Hydrogen Atom Abstraction (HAA) pathway for this reaction has been widely accepted in the community. After investigation of many other late metal hydrides, both experimentally and computationally, the team put together a chapter that included a description of key contributing factors that allow reaction by the HAA mechanism. A brief sampling of other classic papers from our project include hydrogenolysis reactions of late metal hydroxide and alkoxide complexes, the synthesis of nickel-hydrides, and the involvement of hemilabile ligands in promoting new reaction pathways.« less

Development of a codon optimization strategy using the efor RED reporter gene as a test case

NASA Astrophysics Data System (ADS)

Yip, Chee-Hoo; Yarkoni, Orr; Ajioka, James; Wan, Kiew-Lian; Nathan, Sheila

2018-04-01

Synthetic biology is a platform that enables high-level synthesis of useful products such as pharmaceutically related drugs, bioplastics and green fuels from synthetic DNA constructs. Large-scale expression of these products can be achieved in an industrial compliant host such as Escherichia coli. To maximise the production of recombinant proteins in a heterologous host, the genes of interest are usually codon optimized based on the codon usage of the host. However, the bioinformatics freeware available for standard codon optimization might not be ideal in determining the best sequence for the synthesis of synthetic DNA. Synthesis of incorrect sequences can prove to be a costly error and to avoid this, a codon optimization strategy was developed based on the E. coli codon usage using the efor RED reporter gene as a test case. This strategy replaces codons encoding for serine, leucine, proline and threonine with the most frequently used codons in E. coli. Furthermore, codons encoding for valine and glycine are substituted with the second highly used codons in E. coli. Both the optimized and original efor RED genes were ligated to the pJS209 plasmid backbone using Gibson Assembly and the recombinant DNAs were transformed into E. coli E. cloni 10G strain. The fluorescence intensity per cell density of the optimized sequence was improved by 20% compared to the original sequence. Hence, the developed codon optimization strategy is proposed when designing an optimal sequence for heterologous protein production in E. coli.

The path to next generation biofuels: successes and challenges in the era of synthetic biology

PubMed Central

2010-01-01

Volatility of oil prices along with major concerns about climate change, oil supply security and depleting reserves have sparked renewed interest in the production of fuels from renewable resources. Recent advances in synthetic biology provide new tools for metabolic engineers to direct their strategies and construct optimal biocatalysts for the sustainable production of biofuels. Metabolic engineering and synthetic biology efforts entailing the engineering of native and de novo pathways for conversion of biomass constituents to short-chain alcohols and advanced biofuels are herewith reviewed. In the foreseeable future, formal integration of functional genomics and systems biology with synthetic biology and metabolic engineering will undoubtedly support the discovery, characterization, and engineering of new metabolic routes and more efficient microbial systems for the production of biofuels. PMID:20089184

Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization.

PubMed

Whitaker, William B; Sandoval, Nicholas R; Bennett, Robert K; Fast, Alan G; Papoutsakis, Eleftherios T

2015-06-01

Synthetic methylotrophy is the development of non-native methylotrophs that can utilize methane and methanol as sole carbon and energy sources or as co-substrates with carbohydrates to produce metabolites as biofuels and chemicals. The availability of methane (from natural gas) and its oxidation product, methanol, has been increasing, while prices have been decreasing, thus rendering them as attractive fermentation substrates. As they are more reduced than most carbohydrates, methane and methanol, as co-substrates, can enhance the yields of biologically produced metabolites. Here we discuss synthetic biology and metabolic engineering strategies based on the native biology of aerobic methylotrophs for developing synthetic strains grown on methanol, with Escherichia coli as the prototype. Copyright © 2015. Published by Elsevier Ltd.

Towards seismic waveform inversion of long-offset Ocean-Bottom Seismic data for deep crustal imaging offshore Western Australia

NASA Astrophysics Data System (ADS)

Monnier, S.; Lumley, D. E.; Kamei, R.; Goncharov, A.; Shragge, J. C.

2016-12-01

Ocean Bottom Seismic datasets have become increasingly used in recent years to develop high-resolution, wavelength-scale P-wave velocity models of the lithosphere from waveform inversion, due to their recording of long-offset transmitted phases. New OBS surveys evolve towards novel acquisition geometries involving longer offsets (several hundreds of km), broader frequency content (1-100 Hz), while receiver sampling often remains sparse (several km). Therefore, it is critical to assess the effects of such geometries on the eventual success and resolution of waveform inversion velocity models. In this study, we investigate the feasibility of waveform inversion on the Bart 2D OBS profile acquired offshore Western Australia, to investigate regional crustal and Moho structures. The dataset features 14 broadband seismometers (0.01-100 Hz) from AuScope's national OBS fleet, offsets in excess of 280 km, and a sparse receiver sampling (18 km). We perform our analysis in four stages: (1) field data analysis, (2) 2D P-wave velocity model building, synthetic data (3) modelling, and (4) waveform inversion. Data exploration shows high-quality active-source signal down to 2Hz, and usable first arrivals to offsets greater than 100 km. The background velocity model is constructed by combining crustal and Moho information in continental reference models (e.g., AuSREM, AusMoho). These low-resolution studies suggest a crustal thickness of 20-25 km along our seismic line and constitute a starting point for synthetic modelling and inversion. We perform synthetic 2D time-domain modelling to: (1) evaluate the misfit between synthetic and field data within the usable frequency band (2-10 Hz); (2) validate our velocity model; and (3) observe the effects of sparse OBS interval on data quality. Finally, we apply 2D acoustic frequency-domain waveform inversion to the synthetic data to generate velocity model updates. The inverted model is compared to the reference model to investigate the improved crustal resolution and Moho boundary delineation that could be realized using waveform inversion, and to evaluate the effects of the acquisition parameters. The inversion strategies developed through the synthetic tests will help the subsequent inversion of sparse, long-offset OBS field data.

A top-down strategy to synthesize wurtzite Cu2ZnSnS4 nanocrystals by green chemistry.

PubMed

Sun, Yiwen; Hu, Zhengqiao; Zhang, Junjun; Wang, Li; Wu, Chunyan; Xu, Jun

2016-07-28

Green synthesis of metastable wurtzite Cu2ZnSnS4 nanocrystals through a top-down synthetic strategy is presented. Formation mechanisms associated with Kirkendall and etching effects are illustrated in detail. The nanocrystals exhibit remarkable photoluminescence properties at room temperature.

A colloidal water-stable MOF as a broad-range fluorescent pH sensor via post-synthetic modification.

PubMed

Aguilera-Sigalat, Jordi; Bradshaw, Darren

2014-05-11

We report for the first time the pH-dependent fluorescence of UiO-66-NH2 across the wide range from 1 to 9. By application of a post-synthetic modification (PSM) diazotisation strategy, we synthesized a new material, UiO-66-N=N-ind, which shows increased chemical stability and enhanced sensing up to pH 12.

Synthetic biology: Novel approaches for microbiology.

PubMed

Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo

2015-06-01

In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

KEAP1-dependent synthetic lethality induced by AKT and TXNRD1 inhibitors in lung cancer

PubMed Central

Dai, Bingbing; Yoo, Suk-Yuong; Bartholomeusz, Geoffrey; Graham, Ryan A.; Majidi, Mourad; Yan, Shaoyu; Meng, Jieru; Ji, Lin; Coombes, Kevin; Minna, John D.; Fang, Bingliang; Roth, Jack A.

2013-01-01

Intrinsic resistance to agents targeting phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the major challenges in cancer treatment with such agents. The objective of this study is to identify the genes or pathways that can be targeted to overcome the resistance of non-small cell lung cancer to the AKT inhibitor, MK2206, which is currently being evaluated in phase I and II clinical trials. Using a genome-wide small interfering RNA (siRNA) library screening and biological characterization we identified that inhibition of Thioredoxin Reductase-1 (TXNRD1), one of the key anti-oxidant enzymes, with siRNAs or its inhibitor, Auranofin, sensitized non-small cell lung cancer cells to MK2206 treatment in vitro and in vivo. We found that simultaneous inhibition of TXNRD1 and AKT pathways induced robust reactive oxygen species (ROS) production, which was involved in c-Jun N-terminal Kinase (JNK, MAPK8) activation and cell apoptosis. Furthermore we found that the synthetic lethality interaction between the TXNRD1 and AKT pathways occurred through the KEAP1/NRF2 cellular antioxidant pathway. Lastly, we found that synthetic lethality induced by TXNRD1 and AKT inhibitors relied on wild type KEAP1 function. Our study indicates that targeting the interaction between AKT and TXNRD1 antioxidant pathways with MK2206 and Auranofin, a FDA approved drug, is a rational strategy to treat lung cancer and that KEAP1 mutation status may offer a predicative biomarker for such combination approaches. PMID:23824739

Neuroethology of Olfactory-Guided Behavior and Its Potential Application in the Control of Harmful Insects.

PubMed

Reisenman, Carolina E; Lei, Hong; Guerenstein, Pablo G

2016-01-01

Harmful insects include pests of crops and storage goods, and vectors of human and animal diseases. Throughout their history, humans have been fighting them using diverse methods. The fairly recent development of synthetic chemical insecticides promised efficient crop and health protection at a relatively low cost. However, the negative effects of those insecticides on human health and the environment, as well as the development of insect resistance, have been fueling the search for alternative control tools. New and promising alternative methods to fight harmful insects include the manipulation of their behavior using synthetic versions of "semiochemicals", which are natural volatile and non-volatile substances involved in the intra- and/or inter-specific communication between organisms. Synthetic semiochemicals can be used as trap baits to monitor the presence of insects, so that insecticide spraying can be planned rationally (i.e., only when and where insects are actually present). Other methods that use semiochemicals include insect annihilation by mass trapping, attract-and- kill techniques, behavioral disruption, and the use of repellents. In the last decades many investigations focused on the neural bases of insect's responses to semiochemicals. Those studies help understand how the olfactory system detects and processes information about odors, which could lead to the design of efficient control tools, including odor baits, repellents or ways to confound insects. Here we review our current knowledge about the neural mechanisms controlling olfactory responses to semiochemicals in harmful insects. We also discuss how this neuroethology approach can be used to design or improve pest/vector management strategies.

Neuroethology of Olfactory-Guided Behavior and Its Potential Application in the Control of Harmful Insects

PubMed Central

Reisenman, Carolina E.; Lei, Hong; Guerenstein, Pablo G.

2016-01-01

Harmful insects include pests of crops and storage goods, and vectors of human and animal diseases. Throughout their history, humans have been fighting them using diverse methods. The fairly recent development of synthetic chemical insecticides promised efficient crop and health protection at a relatively low cost. However, the negative effects of those insecticides on human health and the environment, as well as the development of insect resistance, have been fueling the search for alternative control tools. New and promising alternative methods to fight harmful insects include the manipulation of their behavior using synthetic versions of “semiochemicals”, which are natural volatile and non-volatile substances involved in the intra- and/or inter-specific communication between organisms. Synthetic semiochemicals can be used as trap baits to monitor the presence of insects, so that insecticide spraying can be planned rationally (i.e., only when and where insects are actually present). Other methods that use semiochemicals include insect annihilation by mass trapping, attract-and- kill techniques, behavioral disruption, and the use of repellents. In the last decades many investigations focused on the neural bases of insect's responses to semiochemicals. Those studies help understand how the olfactory system detects and processes information about odors, which could lead to the design of efficient control tools, including odor baits, repellents or ways to confound insects. Here we review our current knowledge about the neural mechanisms controlling olfactory responses to semiochemicals in harmful insects. We also discuss how this neuroethology approach can be used to design or improve pest/vector management strategies. PMID:27445858

Rate and onset cues can improve cochlear implant synthetic vowel recognition in noise

PubMed Central

Mc Laughlin, Myles; Reilly, Richard B.; Zeng, Fan-Gang

2013-01-01

Understanding speech-in-noise is difficult for most cochlear implant (CI) users. Speech-in-noise segregation cues are well understood for acoustic hearing but not for electric hearing. This study investigated the effects of stimulation rate and onset delay on synthetic vowel-in-noise recognition in CI subjects. In experiment I, synthetic vowels were presented at 50, 145, or 795 pulse/s and noise at the same three rates, yielding nine combinations. Recognition improved significantly if the noise had a lower rate than the vowel, suggesting that listeners can use temporal gaps in the noise to detect a synthetic vowel. This hypothesis is supported by accurate prediction of synthetic vowel recognition using a temporal integration window model. Using lower rates a similar trend was observed in normal hearing subjects. Experiment II found that for CI subjects, a vowel onset delay improved performance if the noise had a lower or higher rate than the synthetic vowel. These results show that differing rates or onset times can improve synthetic vowel-in-noise recognition, indicating a need to develop speech processing strategies that encode or emphasize these cues. PMID:23464025

Photoinduced release of Zn2+ with ZinCleav-1: a nitrobenzyl-based caged complex.

PubMed

Bandara, H M Dhammika; Kennedy, Daniel P; Akin, Elif; Incarvito, Christopher D; Burdette, Shawn C

2009-09-07

Caged complexes are metal ion chelators that release analytes when exposed to light of a specific wavelength. The synthesis and properties of ZinCleav-1, a cage for Zn(2+) that fragments upon photolysis, is reported. The general uncaging strategy involves integrating a nitrobenzyl group on the backbone of the ligand so that a carbon-heteroatom bond is cleaved by the photoreaction. The caged complex was obtained using a new synthetic strategy involving a Strecker synthesis to prepare a key aldehyde intermediate. ZinCleav-1 has a K(d) of 0.23 pM for Zn(2+) as measured by competitive titration with [Zn(PAR)(2)] (PAR = 4-(2-pyridyl-2-azo) resorcinol). The quantum yield for ZinCleav-1 is 2.4% and 0.55% for the apo and Zn(2+) complex, respectively. The ability of ZinCleav-1 to increase free [Zn(2+)] is calculated theoretically using the binding constants for the uncaged photoproducts, and demonstrated practically by using a fluorescent sensor to image the liberated Zn(2+). Free Zn(2+) may function as a neurotransmitter and have a role in the pathology of several neurological diseases. Studying these physiological functions remains challenging because Zn(2+) is silent to most common spectroscopic techniques. We expect ZinCleav-1 to be the first in a class of caged complexes that will facilitate biological investigations.

Synthetic biology for microbial production of lipid-based biofuels.

PubMed

d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

2015-12-01

The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

Design Space Toolbox V2: Automated Software Enabling a Novel Phenotype-Centric Modeling Strategy for Natural and Synthetic Biological Systems

PubMed Central

Lomnitz, Jason G.; Savageau, Michael A.

2016-01-01

Mathematical models of biochemical systems provide a means to elucidate the link between the genotype, environment, and phenotype. A subclass of mathematical models, known as mechanistic models, quantitatively describe the complex non-linear mechanisms that capture the intricate interactions between biochemical components. However, the study of mechanistic models is challenging because most are analytically intractable and involve large numbers of system parameters. Conventional methods to analyze them rely on local analyses about a nominal parameter set and they do not reveal the vast majority of potential phenotypes possible for a given system design. We have recently developed a new modeling approach that does not require estimated values for the parameters initially and inverts the typical steps of the conventional modeling strategy. Instead, this approach relies on architectural features of the model to identify the phenotypic repertoire and then predict values for the parameters that yield specific instances of the system that realize desired phenotypic characteristics. Here, we present a collection of software tools, the Design Space Toolbox V2 based on the System Design Space method, that automates (1) enumeration of the repertoire of model phenotypes, (2) prediction of values for the parameters for any model phenotype, and (3) analysis of model phenotypes through analytical and numerical methods. The result is an enabling technology that facilitates this radically new, phenotype-centric, modeling approach. We illustrate the power of these new tools by applying them to a synthetic gene circuit that can exhibit multi-stability. We then predict values for the system parameters such that the design exhibits 2, 3, and 4 stable steady states. In one example, inspection of the basins of attraction reveals that the circuit can count between three stable states by transient stimulation through one of two input channels: a positive channel that increases the count, and a negative channel that decreases the count. This example shows the power of these new automated methods to rapidly identify behaviors of interest and efficiently predict parameter values for their realization. These tools may be applied to understand complex natural circuitry and to aid in the rational design of synthetic circuits. PMID:27462346

Precursor Mediated Synthesis of Nanostructured Silicas: From Precursor-Surfactant Ion Pairs to Structured Materials

PubMed Central

Hesemann, Peter; Nguyen, Thy Phung; Hankari, Samir El

2014-01-01

The synthesis of nanostructured anionic-surfactant-templated mesoporous silica (AMS) recently appeared as a new strategy for the formation of nanostructured silica based materials. This method is based on the use of anionic surfactants together with a co-structure-directing agent (CSDA), mostly a silylated ammonium precursor. The presence of this CSDA is necessary in order to create ionic interactions between template and silica forming phases and to ensure sufficient affinity between the two phases. This synthetic strategy was for the first time applied in view of the synthesis of surface functionalized silica bearing ammonium groups and was then extended on the formation of materials functionalized with anionic carboxylate and bifunctional amine-carboxylate groups. In the field of silica hybrid materials, the “anionic templating” strategy has recently been applied for the synthesis of silica hybrid materials from cationic precursors. Starting from di- or oligosilylated imidazolium and ammonium precursors, only template directed hydrolysis-polycondensation reactions involving complementary anionic surfactants allowed accessing structured ionosilica hybrid materials. The mechanistic particularity of this approach resides in the formation of precursor-surfactant ion pairs in the hydrolysis-polycondensation mixture. This review gives a systematic overview over the various types of materials accessed from this cooperative ionic templating approach and highlights the high potential of this original strategy for the formation of nanostructured silica based materials which appears as a complementary strategy to conventional soft templating approaches. PMID:28788602

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

PubMed

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

Functional imaging studies of emotion regulation: A synthetic review and evolving model of the cognitive control of emotion

PubMed Central

Ochsner, Kevin N.; Silvers, Jennifer A.; Buhle, Jason T.

2014-01-01

This paper reviews and synthesizes functional imaging research that over the past decade has begun to offer new insights into the brain mechanisms underlying emotion regulation. Towards that end, the first section of the paper outlines a model of the processes and neural systems involved in emotion generation and regulation. The second section surveys recent research supporting and elaborating the model, focusing primarily on studies of the most commonly investigated strategy, which is known as reappraisal. At its core, the model specifies how prefrontal and cingulate control systems modulate activity in perceptual, semantic and affect systems as a function of one's regulatory goals, tactics, and the nature of the stimuli and emotions being regulated. This section also shows how the model can be generalized to understand the brain mechanisms underlying other emotion regulation strategies as well as a range of other allied phenomena. The third and last section considers directions for future research, including how basic models of emotion regulation can be translated to understand changes in emotion across the lifespan and in clinical disorders. PMID:23025352

In situ growth of capping-free magnetic iron oxide nanoparticles on liquid-phase exfoliated graphene

NASA Astrophysics Data System (ADS)

Tsoufis, T.; Syrgiannis, Z.; Akhtar, N.; Prato, M.; Katsaros, F.; Sideratou, Z.; Kouloumpis, A.; Gournis, D.; Rudolf, P.

2015-05-01

We report a facile approach for the in situ synthesis of very small iron oxide nanoparticles on the surface of high-quality graphene sheets. Our synthetic strategy involved the direct, liquid-phase exfoliation of highly crystalline graphite (avoiding any oxidation treatment) and the subsequent chemical functionalization of the graphene sheets via the well-established 1,3-dipolar cycloaddition reaction. The resulting graphene derivatives were employed for the immobilization of the nanoparticle precursor (Fe cations) at the introduced organic groups by a modified wet-impregnation method, followed by interaction with acetic acid vapours. The final graphene-iron oxide hybrid material was achieved by heating (calcination) in an inert atmosphere. Characterization by X-ray diffraction, transmission electron and atomic force microscopy, Raman and X-ray photoelectron spectroscopy gave evidence for the formation of rather small (<12 nm), spherical, magnetite-rich nanoparticles which were evenly distributed on the surface of few-layer (<1.2 nm thick) graphene. Due to the presence of the iron oxide nanoparticles, the hybrid material showed a superparamagnetic behaviour at room temperature.We report a facile approach for the in situ synthesis of very small iron oxide nanoparticles on the surface of high-quality graphene sheets. Our synthetic strategy involved the direct, liquid-phase exfoliation of highly crystalline graphite (avoiding any oxidation treatment) and the subsequent chemical functionalization of the graphene sheets via the well-established 1,3-dipolar cycloaddition reaction. The resulting graphene derivatives were employed for the immobilization of the nanoparticle precursor (Fe cations) at the introduced organic groups by a modified wet-impregnation method, followed by interaction with acetic acid vapours. The final graphene-iron oxide hybrid material was achieved by heating (calcination) in an inert atmosphere. Characterization by X-ray diffraction, transmission electron and atomic force microscopy, Raman and X-ray photoelectron spectroscopy gave evidence for the formation of rather small (<12 nm), spherical, magnetite-rich nanoparticles which were evenly distributed on the surface of few-layer (<1.2 nm thick) graphene. Due to the presence of the iron oxide nanoparticles, the hybrid material showed a superparamagnetic behaviour at room temperature. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00765h

Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives: Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural Product

PubMed Central

Fuwa, Haruhiko

2016-01-01

Tetrahydropyrans are structural motifs that are abundantly present in a range of biologically important marine natural products. As such, significant efforts have been paid to the development of efficient and versatile methods for the synthesis of tetrahydropyran derivatives. Neopeltolide, a potent antiproliferative marine natural product, has been an attractive target compound for synthetic chemists because of its complex structure comprised of a 14-membered macrolactone embedded with a tetrahydropyran ring, and twenty total and formal syntheses of this natural product have been reported so far. This review summarizes the total and formal syntheses of neopeltolide and its analogues, highlighting the synthetic strategies exploited for constructing the tetrahydropyran ring. PMID:27023567

Multimodal and synthetic aperture approach to full-field 3D shape and displacement measurements

NASA Astrophysics Data System (ADS)

Kujawińska, M.; Sitnik, R.

2017-08-01

Recently most of the measurement tasks in industry, civil engineering and culture heritage applications require archiving, characterization and monitoring of 3D objects and structures and their performance under changing conditions. These requirements can be met if multimodal measurement (MM) strategy is applied. It rely on effective combining structured light method and 3D digital image correlation with laser scanning/ToF, thermal imaging, multispectral imaging and BDRF measurements. In the case of big size and/or complicated objects MM have to be combined with hierarchical or synthetic aperture (SA) measurements. The new solutions in MM and SA strategies are presented and their applicability is shown at interesting cultural heritage and civil engineering applications.

Network-analysis-guided synthesis of weisaconitine D and liljestrandinine

NASA Astrophysics Data System (ADS)

Marth, C. J.; Gallego, G. M.; Lee, J. C.; Lebold, T. P.; Kulyk, S.; Kou, K. G. M.; Qin, J.; Lilien, R.; Sarpong, R.

2015-12-01

General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three subfamilies of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites.

Synthetic cannabinoids found in "spice" products alter body temperature and cardiovascular parameters in conscious male rats.

PubMed

Schindler, Charles W; Gramling, Benjamin R; Justinova, Zuzana; Thorndike, Eric B; Baumann, Michael H

2017-10-01

The misuse of synthetic cannabinoids is a persistent public health concern. Because these drugs target the same cannabinoid receptors as the active ingredient of marijuana, Δ 9 -tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters. Biotelemetry transmitters for the measurement of body temperature or blood pressure (BP) were surgically implanted into separate groups of male rats. THC and the synthetic cannabinoids CP55,940, JWH-018, AM2201 and XLR-11 were injected s.c., and rats were placed into isolation cubicles for 3h. THC and synthetic cannabinoids produced dose-related decreases in body temperature that were most prominent in the final 2h of the session. The rank order of potency was CP55,940>AM2201=JWH-018>THC=XLR-11. The cannabinoid inverse agonist rimonabant antagonized the hypothermic effect of all compounds. Synthetic cannabinoids elevated BP in comparison to vehicle treatment during the first h of the session, while heart rate was unaffected. The rank order of potency for BP increases was similar to that seen for hypothermia. Hypertensive effects of CP55,940 and JWH-018 were not antagonized by rimonabant or the neutral antagonist AM4113. However, the BP responses to both drugs were antagonized by pretreatment with either the ganglionic blocker hexamethonium or the α 1 adrenergic antagonist prazosin. Our results show that synthetic cannabinoids produce hypothermia in rats by a mechanism involving cannabinoid receptors, while they increase BP by a mechanism independent of these sites. The hypertensive effect appears to involve central sympathetic outflow. Published by Elsevier B.V.

Experiments in Natural and Synthetic Dental Materials: A Mouthful of Experiments

NASA Technical Reports Server (NTRS)

Masi, James V.

1996-01-01

The objectives of these experiments are to show that the area of biomaterials, especially dental materials (natural and synthetic), contain all of the elements of good and bad design, with the caveat that a person's health is directly involved. The students learn the process of designing materials for the complex interactions in the oral cavity, analyze those already used, and suggest possible solutions to the problems involved with present technology. The N.I.O.S.H. Handbook is used extensively by the students and judgement calls are made, even without extensive biology education.

Strategies for the Synthesis of Higher Acenes

PubMed Central

Dorel, Ruth

2016-01-01

The outstanding performance of pentacene‐based molecules in molecular electronics, as well as the predicted enhanced semiconducting properties of extended acenes, have stimulated the development of new synthetic methods and functionalization strategies for the preparation of stable and soluble acenes larger than tetracene with the aim of obtaining improved functional materials. PMID:28747846

FL3, a Synthetic Flavagline and Ligand of Prohibitins, Protects Cardiomyocytes via STAT3 from Doxorubicin Toxicity

PubMed Central

Gasser, Adeline; Basmadjian, Christine; Zhao, Qian; Wilmet, Jean-Philippe; Désaubry, Laurent; Nebigil, Canan G.

2015-01-01

Aims The clinical use of doxorubicin for the treatment of cancer is limited by its cardiotoxicity. Flavaglines are natural products that have both potent anticancer and cardioprotective properties. A synthetic analog of flavaglines, FL3, efficiently protects mice from the cardiotoxicity of doxorubicin. The mechanism underlying this cardioprotective effect has yet to be elucidated. Methods and Results Here, we show that FL3 binds to the scaffold proteins prohibitins (PHBs) and thus promotes their translocation to mitochondria in the H9c2 cardiomyocytes. FL3 induces heterodimerization of PHB1 with STAT3, thereby ensuring cardioprotection from doxorubicin toxicity. This interaction is associated with phosphorylation of STAT3. A JAK2 inhibitor, WP1066, suppresses both the phosphorylation of STAT3 and the protective effect of FL3 in cardiomyocytes. The involvement of PHBs in the FL3-mediated cardioprotection was confirmed by means of small interfering RNAs (siRNAs) targeting PHB1 and PHB2. The siRNA knockdown of PHBs inhibits both phosphorylation of STAT3 and the cardioprotective effect of FL3. Conclusion Activation of mitochondrial STAT3/PHB1 complex by PHB ligands may be a new strategy against doxorubicin-induced cardiotoxicity and possibly other cardiac problems. PMID:26536361

Innovative Poly(Ionic Liquid)s by the Polymerization of Deep Eutectic Monomers.

PubMed

Isik, Mehmet; Ruiperez, Fernando; Sardon, Haritz; Gonzalez, Alba; Zulfiqar, Sonia; Mecerreyes, David

2016-07-01

The incorporation of ionic liquid (IL) chemistry into functional polymers has extended the properties and applications of polyelectrolytes. However, ILs are expensive due to the presence of fluorinated anions or complicated synthetic steps which limit their technological viability. Here, we show a new family of poly(ionic liquid)s (PILs) which are based in cheap and renewable chemicals and involves facile synthetic approaches. Thus, deep eutectic monomers (DEMs) are prepared for the first time by using quaternary ammonium compounds and various hydrogen bond donors such as citric acid, terephthalic acid or an amidoxime. The deep eutectic formation is made through a simple mixing of the ingredients. Differential scanning calorimetry, nuclear magnetic resonance (NMR) and computational studies reveal the formation of the DEMs due to the ionic interactions. The resulting DEMs are liquid which facilitates their polymerization using mild photopolymerization or polycondensation strategies. Spectroscopic characterizations reveal the successful formation of the polymers. By this way, a new family of PILs can be synthesized which can be used for different applications. As an example, the polymers show promising performance as solid CO2 sorbents. Altogether the deep eutectic monomer route can lead to non-toxic, cheap and easy-to-prepare alternatives to current PILs for different applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of Chemical Reactivity and Transition State Modeling for Virtual Screening.

PubMed

Karthikeyan, Muthukumarasamy; Vyas, Renu; Tambe, Sanjeev S; Radhamohan, Deepthi; Kulkarni, Bhaskar D

2015-01-01

Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening.

The challenges of informatics in synthetic biology: from biomolecular networks to artificial organisms

PubMed Central

Ramoni, Marco F.

2010-01-01

The field of synthetic biology holds an inspiring vision for the future; it integrates computational analysis, biological data and the systems engineering paradigm in the design of new biological machines and systems. These biological machines are built from basic biomolecular components analogous to electrical devices, and the information flow among these components requires the augmentation of biological insight with the power of a formal approach to information management. Here we review the informatics challenges in synthetic biology along three dimensions: in silico, in vitro and in vivo. First, we describe state of the art of the in silico support of synthetic biology, from the specific data exchange formats, to the most popular software platforms and algorithms. Next, we cast in vitro synthetic biology in terms of information flow, and discuss genetic fidelity in DNA manipulation, development strategies of biological parts and the regulation of biomolecular networks. Finally, we explore how the engineering chassis can manipulate biological circuitries in vivo to give rise to future artificial organisms. PMID:19906839

TOMO3D: 3-D joint refraction and reflection traveltime tomography parallel code for active-source seismic data—synthetic test

NASA Astrophysics Data System (ADS)

Meléndez, A.; Korenaga, J.; Sallarès, V.; Miniussi, A.; Ranero, C. R.

2015-10-01

We present a new 3-D traveltime tomography code (TOMO3D) for the modelling of active-source seismic data that uses the arrival times of both refracted and reflected seismic phases to derive the velocity distribution and the geometry of reflecting boundaries in the subsurface. This code is based on its popular 2-D version TOMO2D from which it inherited the methods to solve the forward and inverse problems. The traveltime calculations are done using a hybrid ray-tracing technique combining the graph and bending methods. The LSQR algorithm is used to perform the iterative regularized inversion to improve the initial velocity and depth models. In order to cope with an increased computational demand due to the incorporation of the third dimension, the forward problem solver, which takes most of the run time (˜90 per cent in the test presented here), has been parallelized with a combination of multi-processing and message passing interface standards. This parallelization distributes the ray-tracing and traveltime calculations among available computational resources. The code's performance is illustrated with a realistic synthetic example, including a checkerboard anomaly and two reflectors, which simulates the geometry of a subduction zone. The code is designed to invert for a single reflector at a time. A data-driven layer-stripping strategy is proposed for cases involving multiple reflectors, and it is tested for the successive inversion of the two reflectors. Layers are bound by consecutive reflectors, and an initial velocity model for each inversion step incorporates the results from previous steps. This strategy poses simpler inversion problems at each step, allowing the recovery of strong velocity discontinuities that would otherwise be smoothened.

Synthetic Glycopolymers for Highly Efficient Differentiation of Embryonic Stem Cells into Neurons: Lipo- or Not?

PubMed

Liu, Qi; Lyu, Zhonglin; Yu, You; Zhao, Zhen-Ao; Hu, Shijun; Yuan, Lin; Chen, Gaojian; Chen, Hong

2017-04-05

To realize the potential application of embryonic stem cells (ESCs) for the treatment of neurodegenerative diseases, it is a prerequisite to develop an effective strategy for the neural differentiation of ESCs so as to obtain adequate amount of neurons. Considering the efficacy of glycosaminoglycans (GAG) and their disadvantages (e.g., structure heterogeneity and impurity), GAG-mimicking glycopolymers (designed polymers containing functional units similar to natural GAG) with or without phospholipid groups were synthesized in the present work and their ability to promote neural differentiation of mouse ESCs (mESCs) was investigated. It was found that the lipid-anchored GAG-mimicking glycopolymers (lipo-pSGF) retained on the membrane of mESCs rather than being internalized by cells after 1 h of incubation. Besides, lipo-pSGF showed better activity in promoting neural differentiation. The expression of the neural-specific maker β3-tubulin in lipo-pSGF-treated cells was ∼3.8- and ∼1.9-fold higher compared to natural heparin- and pSGF-treated cells at day 14. The likely mechanism involved in lipo-pSGF-mediated neural differentiation was further investigated by analyzing its effect on fibroblast growth factor 2 (FGF2)-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway which is important for neural differentiation of ESCs. Lipo-pSGF was found to efficiently bind FGF2 and enhance the phosphorylation of ERK1/2, thus promoting neural differentiation. These findings demonstrated that engineering of cell surface glycan using our synthetic lipo-glycopolymer is a highly efficient approach for neural differentiation of ESCs and this strategy can be applied for the regulation of other cellular activities mediated by cell membrane receptors.

Effort Optimization in Minimizing Food Related Greenhouse Gas Emissions, a look at "Organic" and "Local"

NASA Astrophysics Data System (ADS)

Bowen, E.; Martin, P. A.; Eshel, G.

2008-12-01

The adverse environmental effects, especially energy use and resultant GHG emissions, of food production and consumption are becoming more widely appreciated and increasingly well documented. Our insights into the thorny problem of how to mitigate some of those effects, however, are far less evolved. Two of the most commonly advocated strategies are "organic" and "local", referring, respectively, to growing food without major inputs of fossil fuel based synthetic fertilizers and pesticides and to food consumption near its agricultural origin. Indeed, both agrochemical manufacture and transportation of produce to market make up a significant percentage of energy use in agriculture. While there can be unique environmental benefits to each strategy, "organic" and "local" each may potentially result in energy and emissions savings relative to conventionally grown produce. Here, we quantify the potential energy and greenhouse gas emissions savings associated with "organic" and "local". We take note of energy use and actual GHG costs of the major synthetic fertilizers and transportation by various modes routinely employed in agricultural distribution chains, and compare them for ~35 frequently consumed nutritional mainstays. We present new, current, lower-bound energy and greenhouse gas efficiency estimates for these items and compare energy consumption and GHG emissions incurred during producing those food items to consumption and emissions resulting from transporting them, considering travel distances ranging from local to continental and transportation modes ranging from (most efficient) rail to (least efficient) air. In performing those calculations, we demonstrate the environmental superiority of either local or organic over conventional foods, and illuminate the complexities involved in entertaining the timely yet currently unanswered, and previously unanswerable, question of "Which is Environmentally Superior, Organic or Local?". More broadly, we put forth a database that amounts to a general blueprint for rigorous comparative evaluation of any competing diets.

A Selectivity based approach to Continuous Pattern Detection in Streaming Graphs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choudhury, Sutanay; Holder, Larry; Chin, George

2015-05-27

Cyber security is one of the most significant technical challenges in current times. Detecting adversarial activities, prevention of theft of intellectual properties and customer data is a high priority for corporations and government agencies around the world. Cyber defenders need to analyze massive-scale, high-resolution network flows to identify, categorize, and mitigate attacks involving networks spanning institutional and national boundaries. Many of the cyber attacks can be described as subgraph patterns, with prominent examples being insider infiltrations (path queries), denial of service (parallel paths) and malicious spreads (tree queries). This motivates us to explore subgraph matching on streaming graphs in amore » continuous setting. The novelty of our work lies in using the subgraph distributional statistics collected from the streaming graph to determine the query processing strategy. We introduce a ``Lazy Search" algorithm where the search strategy is decided on a vertex-to-vertex basis depending on the likelihood of a match in the vertex neighborhood. We also propose a metric named ``Relative Selectivity" that is used to select between different query processing strategies. Our experiments performed on real online news, network traffic stream and a synthetic social network benchmark demonstrate 10-100x speedups over non-incremental, selectivity agnostic approaches.« less

Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas.

PubMed

Caruso, Gerardo; Caffo, Mariella; Raudino, Giuseppe; Alafaci, Concetta; Salpietro, Francesco M; Tomasello, Francesco

2010-01-01

Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

[Strategies to prevent bacteriophage infection in industrial fermentation].

PubMed

Shen, Juntao; Xiu, Zhilong

2017-12-25

During the development of bacteria-based biotechnology, bacteriophage infection is one of the constant threats and troublesome problems in industrial fermentation. The core of puzzled bacteriophage infection is a complex arm race of coevolution between bacteriophages and their hosts where bacteriophage has evolved lots of escaped ways against bacterial resistance mechanisms. The strategies of rationally designing factories and rotation of starter strains could reduce the risk of bacteriophage infection, but often fail to avoid. Genetic engineering to increase bacterial resistance is one of the strategies to prevent bacteriophage infection and more knowledge about bacteriophage and its host is needed. Recently, there are some new findings on bacterial resistance mechanisms which provide new solutions for bacteriophage infection. For example, it is possible for a rational design of resistant strains to use CRISPR-Cas based technologies just based on the sequences of bacteriophages. Moreover, it is also possible to avoid the escape of bacteriophage by iteratively building up resistance levels to generate robust industrial starter cultures. Quorum-sensing signal molecules have recently been proved to be involved in the interactions between bacteria and bacteriophages, which provides a possible way to solve bacteriophage infection from a population level. Finally, the rapid development of bacteriophage genome editing and synthetic biology will bring some new cues for preventing bacteriophage infection in industrial fermentation.

Electron delocalization and charge mobility as a function of reduction in a metal-organic framework.

PubMed

Aubrey, Michael L; Wiers, Brian M; Andrews, Sean C; Sakurai, Tsuneaki; Reyes-Lillo, Sebastian E; Hamed, Samia M; Yu, Chung-Jui; Darago, Lucy E; Mason, Jarad A; Baeg, Jin-Ook; Grandjean, Fernande; Long, Gary J; Seki, Shu; Neaton, Jeffrey B; Yang, Peidong; Long, Jeffrey R

2018-06-04

Conductive metal-organic frameworks are an emerging class of three-dimensional architectures with degrees of modularity, synthetic flexibility and structural predictability that are unprecedented in other porous materials. However, engendering long-range charge delocalization and establishing synthetic strategies that are broadly applicable to the diverse range of structures encountered for this class of materials remain challenging. Here, we report the synthesis of K x Fe 2 (BDP) 3 (0 ≤ x ≤ 2; BDP 2-  = 1,4-benzenedipyrazolate), which exhibits full charge delocalization within the parent framework and charge mobilities comparable to technologically relevant polymers and ceramics. Through a battery of spectroscopic methods, computational techniques and single-microcrystal field-effect transistor measurements, we demonstrate that fractional reduction of Fe 2 (BDP) 3 results in a metal-organic framework that displays a nearly 10,000-fold enhancement in conductivity along a single crystallographic axis. The attainment of such properties in a K x Fe 2 (BDP) 3 field-effect transistor represents the realization of a general synthetic strategy for the creation of new porous conductor-based devices.

Design of Organic Transformations at Ambient Conditions: Our Sincere Efforts to the Cause of Green Chemistry Practice.

PubMed

Brahmachari, Goutam

2016-02-01

This account summarizes our recent efforts in designing a good number of important organic transformations leading to the synthesis of biologically relevant compounds at room temperature and pressure. Currently, the concept of green chemistry is globally acclaimed and has already advanced quite significantly to emerge as a distinct branch of chemical sciences. Among the principles of green chemistry, one principle is dedicated to the "design of energy efficiency" - that is, to develop synthetic strategies that require less or the minimum amount of energy to carry out a specific reaction with optimum productivity - and the most effective way to save energy is to develop strategies/protocols that are capable enough to carry out the transformations at ambient temperature! As part of on-going developments in green synthetic strategies, the design of reactions under ambient conditions coupled with other green aspects is, thus, an area of current interest. The concept of developing reaction strategies at room temperature and pressure is now an emerging field of research in organic chemistry and is progressing steadily. This account is aimed to offer an overview of our recent research works directly related to this particular field of interest, and highlights the green chemistry practice leading to carbon-carbon and carbon-heteroatom bond-forming reactions of topical significance. Green synthetic routes to a variety of biologically relevant organic molecules (heterocyclic, heteroaromatic, alicyclic, acyclic, etc.) at room temperature and pressure are discussed. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uranium(III)-carbon multiple bonding supported by arene δ-bonding in mixed-valence hexauranium nanometre-scale rings.

PubMed

Wooles, Ashley J; Mills, David P; Tuna, Floriana; McInnes, Eric J L; Law, Gareth T W; Fuller, Adam J; Kremer, Felipe; Ridgway, Mark; Lewis, William; Gagliardi, Laura; Vlaisavljevich, Bess; Liddle, Stephen T

2018-05-29

Despite the fact that non-aqueous uranium chemistry is over 60 years old, most polarised-covalent uranium-element multiple bonds involve formal uranium oxidation states IV, V, and VI. The paucity of uranium(III) congeners is because, in common with metal-ligand multiple bonding generally, such linkages involve strongly donating, charge-loaded ligands that bind best to electron-poor metals and inherently promote disproportionation of uranium(III). Here, we report the synthesis of hexauranium-methanediide nanometre-scale rings. Combined experimental and computational studies suggest overall the presence of formal uranium(III) and (IV) ions, though electron delocalisation in this Kramers system cannot be definitively ruled out, and the resulting polarised-covalent U = C bonds are supported by iodide and δ-bonded arene bridges. The arenes provide reservoirs that accommodate charge, thus avoiding inter-electronic repulsion that would destabilise these low oxidation state metal-ligand multiple bonds. Using arenes as electronic buffers could constitute a general synthetic strategy by which to stabilise otherwise inherently unstable metal-ligand linkages.

Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction

PubMed Central

Olière, Stéphanie; Jolette-Riopel, Antoine; Potvin, Stéphane; Jutras-Aswad, Didier

2013-01-01

Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants. PMID:24069004

Co-culture systems and technologies: taking synthetic biology to the next level

PubMed Central

Goers, Lisa; Freemont, Paul; Polizzi, Karen M.

2014-01-01

Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell–cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions. PMID:24829281

Light-responsive smart surface with controllable wettability and excellent stability.

PubMed

Zhou, Yin-Ning; Li, Jin-Jin; Zhang, Qing; Luo, Zheng-Hong

2014-10-21

Novel fluorinated gradient copolymer was designed for smart surface with light-responsive controllable wettability and excellent stability. The switchable mechanism and physicochemical characteristics of the as-prepared surface decorated by designed polymeric material were investigated by ultraviolet-visible (UV-vis) spectrum, scanning electron microscope (SEM), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Thanks to the functional film and surface roughening, etched silicon surface fabricated by copolymer involving spiropyran (Sp) moieties possesses a fairly large variation range of WCA (28.1°) and achieves the transformation between hydrophilicity (95.2° < 109.2°) and hydrophobicity (123.3° > 109.2°) relative to blank sample (109.2°). The synthetic strategy and developed smart surface offer a promising application in coating with controllable wettability, which bridge the gap between chemical structure and material properties.

Dekkera and Brettanomyces growth and utilisation of hydroxycinnamic acids in synthetic media.

PubMed

Harris, Victoria; Ford, Christopher M; Jiranek, Vladimir; Grbin, Paul R

2008-04-01

Dekkera and Brettanomyces yeast are important spoilage organisms in a number of food and beverage products. Isolates of both genera were cultured in a defined medium and supplemented with hydroxycinnamic acids and vinylphenols to investigate their influence on growth and the formation of ethyl phenol derivatives. The growth rate of Brettanomyces species in the presence of acids was reduced, and no significant conversion to vinyl or ethyl derivatives was observed. The growth rate and substrate utilisation rates of Dekkera anomala and Dekkera bruxellensis yeast differed depending on strain and the acid precursor present. Growth of D. bruxellensis was slowed by the presence of ferulic acid with the addition of 1 mM ferulic acid completely inhibiting growth. This study provides an insight into the spoilage potential of these organisms and possible control strategies involving hydroxycinnamic acids.

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

PubMed Central

2016-01-01

The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis. PMID:27120289

Crystallization Pathways in Biomineralization

NASA Astrophysics Data System (ADS)

Weiner, Steve; Addadi, Lia

2011-08-01

A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

Synthesis and characterizations of novel polymer electrolytes

NASA Astrophysics Data System (ADS)

Chanthad, Chalathorn

Polymer electrolytes are an important component of many electrochemical devices. The ability to control the structures, properties, and functions of polymer electrolytes remains a key subject for the development of next generation functional polymers. Taking advantage of synthetic strategies is a promising approach to achieve the desired chemical structures, morphologies, thermal, mechanical, and electrochemical properties. Therefore, the major goal of this thesis is to develop synthetic methods for of novel proton exchange membranes and ion conductive membranes. In Chapter 2, new classes of fluorinated polymer- polysilsesquioxane nanocomposites have been designed and synthesized. The synthetic method employed includes radical polymerization using the functional benzoyl peroxide initiator for the telechelic fluorinated polymers with perfluorosulfonic acids in the side chains and a subsequent in-situ sol-gel condensation of the prepared triethoxylsilane-terminated fluorinated polymers with alkoxide precursors. The properties of the composite membranes have been studied as a function of the content and structure of the fillers. The proton conductivity of the prepared membranes increases steadily with the addition of small amounts of the polysilsesquioxane fillers. In particular, the sulfopropylated polysilsesquioxane based nanocomposites display proton conductivities greater than Nafion. This is attributed to the presence of pendant sulfonic acids in the fillers, which increases ion-exchange capacity and offers continuous proton transport channels between the fillers and the polymer matrix. The methanol permeability of the prepared membranes has also been examined. Lower methanol permeability and higher electrochemical selectivity than those of Nafion have been demonstrated in the polysilsesquioxane based nanocomposites. In Chapter 3, the synthesis of a new class of ionic liquid-containing triblock copolymers with fluoropolymer mid-block and imidazolium methacrylate end-blocks is described for the first time. The synthetic strategy involves the preparation of the telechelic fluoropolymers using a functional benzoyl peroxide initiator as the macro-chain transfer agent for subsequent RAFT polymerization of the imidazolium methacrylate monomer. As revealed in DSC, SAXS and dielectric relaxation spectroscopy (DRS) measurements, there was no microphase separation in the triblock copolymers, likely due to solubility of ionic liquid moieties in the fluoropolymer matrix. The anionic counterion has direct impact on the thermal properties, ionic conductivity and segmental dynamics of the polymers. The temperature dependence of the ionic conductivity is well described by the Vogel-Tamman-Fulcher model, suggesting that ion motion is closely coupled to segmental motion. In Chapter 4 and 5, new solid electrolytes for lithium cations have been synthesized by catalyzed hydrosilylation reaction involving hydrogen atoms of polysiloxane and polyhedral oligomeric silsesquioxane (POSS) and double bonds of vinyl tris17-bromo-3,6,9,12,15- pentaoxaheptadecan-1-ol silane. The obtained structures are based on branched or dendritic with ionic liquid-ethylene oxide oligomer. High room temperature ionic conductivities have been obtained in the range of 10-4-10-5 can be regarded as solid electrolytes. This is attributed to the high concentration of ions from ionic liquid moieties in the tripodand molecule, high segmental mobility, and high ion dissociation from ethylene oxide spacers. The influence of anion structures and lithium salts and concentration has been investigated.

Synthetic biology for microbial production of lipid-based biofuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

d’Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel

The risks of maintaining current CO 2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO 2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential ofmore » synthetic biology for sustainable manufacturing.« less

Increased synthetic drug abuse and trends in HIV and syphilis prevalence among female drug users from 2010-2014 from Beijing, China.

PubMed

Sun, Yanming; Guo, Wei; Li, Guiying; He, Shufang; Lu, Hongyan

2018-01-01

The objective of this study was to monitor the trend of addiction drug use and its relationship with sexually transmitted infections (STIs) among female drug users (FDUs). Serial cross-sectional surveys were conducted during 2010-2014 among FDUs in Beijing to collect information on addiction drug usage, sexual behaviors, and STI prevalence. Characteristics were analyzed and compared between traditional and synthetic drug users among FDUs by logistic regression method. A total of 3859 FDUs were surveyed during 2010-2014, with the median age being 32.7 years old. The proportion of synthetic drug users among FDUs increased from 43.7% in 2010 to 70.7% in 2014. Compared with traditional drug users, synthetic drug users were younger (P < 0.001), lacked education (P < 0.001), were unmarried (P < 0.001), and were non-local residents (P < 0.001). No significant difference was found with condom usage during sexual activity between traditional and synthetic drug FDUs. However, the engagement of commercial sexual activities (P < 0.001) and syphilis prevalence (P < 0.001) among synthetic drug users were significantly higher than traditional drug users. Synthetic drug abuse appears to be correlated with commercial sex behavior and higher syphilis prevalence among FDUs. Tailored strategies on health education to curb the prevalence of synthetic drug abuse are urgently needed in Beijing.

Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients.

PubMed

Rakic, Milenko; Wienand, Isabelle; Shaw, David; Nast, Rebecca; Elger, Bernice S

2017-04-01

We analyzed stable patients' views regarding synthetic biology in general, the medical application of synthetic biology, and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients, who suffered from diabetes or gout. Interviews were transcribed verbatim, translated and fully anonymized. Thematic analysis was applied in order to examine stable patients' attitudes towards synthetic biology, its medical application, and their participation in trials. When patients were asked about synthetic biology in general, most of them were anxious that something uncontrollable could be created. After a concrete example of possible future treatment options, patients started to see synthetic biology in a more positive way. Our study constitutes an important first empirical insight into stable patients' views on synthetic biology and into the kind of fears triggered by the term "synthetic biology." Our results show that clear and concrete information can change patients' initial negative feelings towards synthetic biology. Information should thus be transmitted with great accuracy and transparency in order to reduce irrational fears of patients and to minimize the risk that researchers present facts too positively for the purposes of persuading patients to participate in clinical trials. Potential participants need to be adequately informed in order to be able to autonomously decide whether to participate in human subject research involving synthetic biology.

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

PubMed

Sharma, Sunil V; Tong, Xiaoxue; Pubill-Ulldemolins, Cristina; Cartmell, Christopher; Bogosyan, Emma J A; Rackham, Emma J; Marelli, Enrico; Hamed, Refaat B; Goss, Rebecca J M

2017-08-09

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset.

PubMed

Martinotti, Giovanni; Santacroce, Rita; Papanti, Duccio; Elgharably, Yasmine; Prilutskaya, Mariya; Corazza, Ornella

2017-01-01

Synthetic Cannabinoids (SC) are the widest and most diffused class of Novel Psychoactive Substances. The short- and long- term health risks associated with the consumption of SC are often unknown to both users and health professionals. This review aims to provide a synthesis of the most recent and relevant insights on the pharmacology, clinical and psychopathological aspects of SC. A structured search of two bibliographic databases (PubMed and Scopus) was undertaken according to inclusion/exclusion criteria. The following terms "synthetic cannabinoid*", "synthetic cannabimimetic*", "synthetic cannabis", "synthetic marijuana" and "Spice AND cannabinoid*" were used as search strings. 162 relevant results, mainly published in the past two years were revealed. Most results emerged for the keyword "synthetic cannabinoid*", followed by the combination "Spice* AND "cannabinoid*". Most papers were epidemiological, forensic, toxicologic, or analytical. The results of studies were systematized according their contribution to the comprehension of pharmacological, clinical and psychopathological effects of SC. Fifteen SC-related fatality cases were reviewed according to their histories, pathology and toxicology findings. The findings of this review confirm the importance of prompt and reliable information available for health professionals More specific analytic techniques and designed preventive strategies are required to face unprecedented SC challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Catalytic conversion wood syngas to synthetic aviation turbine fuels over a multifunctional catalyst

Treesearch

Qiangu Yan; Fei Yu; Jian Liu; Jason Street; Jinsen Gao; Zhiyong Cai; Jilei Zhang

2013-01-01

A continuous process involving gasification, syngas cleaning, and Fischer–Tropsch (FT) synthesis was developed to efficiently produce synthetic aviation turbine fuels (SATFs). Oak-tree wood chips were first gasified to syngas over a commercial pilot plant downdraft gasifier. The raw wood syngas contains about 47% N2, 21% CO, 18% H2...

Design and construction of a first-generation high-throughput integrated molecular biology platform for production of optimized synthetic genes and improved industrial strains

USDA-ARS?s Scientific Manuscript database

The molecular biological techniques for plasmid-based assembly and cloning of synthetic assembled gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. These techniques involve the production of full-length cDNA libraries as a source of plasmid-bas...

β-Lactam Ring Opening: A Useful Entry to Amino Acids and Relevant Nitrogen-Containing Compounds

NASA Astrophysics Data System (ADS)

Palomo, C.; Oiarbide, M.

The main strategies for the ring opening of β-lactams by chemical means are described. The discovery of each approach is put into context, sometimes in connection to processes occurring in biological systems, and the synthetic opportunities each approach offers are shown. Thus, this β-lactam route affords a number of synthetically relevant building-blocks, including α-amino acids, β-amino acids, their derived peptides, and other nitrogen containing heterocycles and open chain molecules. The content, which encompases references to initial work, further major development, and the most relevant recent literature contributions, is categorized according to the ring bond cleavaged (N 1-C 2, C 2-C 3, C 3 -C 4 , N 1-C 4), to finish with ring opening strategies leading to large heterocyclic compounds. Within each category, distinction has been made according to the type of nucleophilic agent employed, principally O-, N-, and C-nucleophiles. Also, a variety of applications of the strategy to the synthesis of interesting target compounds are shown.

Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization

NASA Astrophysics Data System (ADS)

Niu, Jia; Lunn, David J.; Pusuluri, Anusha; Yoo, Justin I.; O'Malley, Michelle A.; Mitragotri, Samir; Soh, H. Tom; Hawker, Craig J.

2017-06-01

The capability to graft synthetic polymers onto the surfaces of live cells offers the potential to manipulate and control their phenotype and underlying cellular processes. Conventional grafting-to strategies for conjugating preformed polymers to cell surfaces are limited by low polymer grafting efficiency. Here we report an alternative grafting-from strategy for directly engineering the surfaces of live yeast and mammalian cells through cell surface-initiated controlled radical polymerization. By developing cytocompatible PET-RAFT (photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization), synthetic polymers with narrow polydispersity (Mw/Mn < 1.3) could be obtained at room temperature in 5 minutes. This polymerization strategy enables chain growth to be initiated directly from chain-transfer agents anchored on the surface of live cells using either covalent attachment or non-covalent insertion, while maintaining high cell viability. Compared with conventional grafting-to approaches, these methods significantly improve the efficiency of grafting polymer chains and enable the active manipulation of cellular phenotypes.

NTS-polyplex: A potential nanocarrier for neurotrophic therapy of Parkinson’s disease

PubMed Central

Martinez-Fong, Daniel; Bannon, Michael J.; Trudeau, Louis-Eric; Gonzalez-Barrios, Juan A.; Arango-Rodriguez, Martha L.; Hernandez-Chan, Nancy G.; Reyes-Corona, David; Armendáriz-Borunda, Juan; Navarro-Quiroga, Ivan

2012-01-01

Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a strategy to stop and reverse neurodegeneration in Parkinson’s disease. Because of improved transfection ability, synthetic nanocarriers have become candidates for neurotrophic therapy. Neurotensin (NTS)-polyplex is a “Trojan horse” synthetic nanocarrier system that enters dopaminergic neurons through NTS receptor internalization to deliver a genetic cargo. The success of preclinical studies with different neurotrophic genes supports the possibility of using NTS-polyplex in nanomedicine. In this review, we describe the mechanism of NTS-polyplex transfection. We discuss the concept that an effective neurotrophic therapy requires a simultaneous effect on the axon terminals and soma of the remaining dopaminergic neurons. We also discuss the future of this strategy for the treatment of Parkinson’s disease. PMID:22406187

A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.

PubMed

Das, Samir; Nag, Arundhati; Liang, JingXin; Bunck, David N; Umeda, Aiko; Farrow, Blake; Coppock, Matthew B; Sarkes, Deborah A; Finch, Amethist S; Agnew, Heather D; Pitram, Suresh; Lai, Bert; Yu, Mary Beth; Museth, A Katrine; Deyle, Kaycie M; Lepe, Bianca; Rodriguez-Rivera, Frances P; McCarthy, Amy; Alvarez-Villalonga, Belen; Chen, Ann; Heath, John; Stratis-Cullum, Dimitra N; Heath, James R

2015-11-02

We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light Activated Cell Migration in Synthetic Extracellular Matrices

PubMed Central

Guo, Qiongyu; Wang, Xiaobo; Tibbitt, Mark W.; Anseth, Kristi S.; Montell, Denise J.; Elisseeff, Jennifer H.

2012-01-01

Synthetic extracellular matrices provide a framework in which cells can be exposed to defined physical and biological cues. However no method exists to manipulate single cells within these matrices. It is desirable to develop such methods in order to understand fundamental principles of cell migration and define conditions that support or inhibit cell movement within these matrices. Here, we present a strategy for manipulating individual mammalian stem cells in defined synthetic hydrogels through selective optical activation of Rac, which is an intracellular signaling protein that plays a key role in cell migration. Photoactivated cell migration in synthetic hydrogels depended on mechanical and biological cues in the biomaterial. Real-time hydrogel photodegradation was employed to create geometrically defined channels and spaces in which cells could be photoactivated to migrate. Cell migration speed was significantly higher in the photo-etched channels and cells could easily change direction of movement compared to the bulk hydrogels. PMID:22889487

Library Design-Facilitated High-Throughput Sequencing of Synthetic Peptide Libraries.

PubMed

Vinogradov, Alexander A; Gates, Zachary P; Zhang, Chi; Quartararo, Anthony J; Halloran, Kathryn H; Pentelute, Bradley L

2017-11-13

A methodology to achieve high-throughput de novo sequencing of synthetic peptide mixtures is reported. The approach leverages shotgun nanoliquid chromatography coupled with tandem mass spectrometry-based de novo sequencing of library mixtures (up to 2000 peptides) as well as automated data analysis protocols to filter away incorrect assignments, noise, and synthetic side-products. For increasing the confidence in the sequencing results, mass spectrometry-friendly library designs were developed that enabled unambiguous decoding of up to 600 peptide sequences per hour while maintaining greater than 85% sequence identification rates in most cases. The reliability of the reported decoding strategy was additionally confirmed by matching fragmentation spectra for select authentic peptides identified from library sequencing samples. The methods reported here are directly applicable to screening techniques that yield mixtures of active compounds, including particle sorting of one-bead one-compound libraries and affinity enrichment of synthetic library mixtures performed in solution.

Engineering Cell-Cell Signaling

PubMed Central

Milano, Daniel F.; Natividad, Robert J.; Asthagiri, Anand R.

2014-01-01

Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining mammalian cells is arguably the mode of cell communication that is most recalcitrant to engineering. Overcoming this challenge is crucial for progress in biomedical applications, such as tissue engineering, regenerative medicine, immune system engineering and therapeutic design. Here, we describe the significant advances that have been made in developing synthetic platforms (materials and devices) and synthetic cells (cell surface engineering and synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition, significant progress has been made in elucidating design rules and strategies to modulate juxtacrine signaling based on quantitative, engineering analysis of the mechanical and regulatory role of juxtacrine signals in the context of other cues and physical constraints in the microenvironment. These advances in engineering juxtacrine signaling lay a strong foundation for an integrative approach to utilizing synthetic cells, advanced ‘chassis’ and predictive modeling to engineer the form and function of living tissues. PMID:23856592

[Applications of synthetic biology in materials science].

PubMed

Zhao, Tianxin; Zhong, Chao

2017-03-25

Materials are the basis for human being survival and social development. To keep abreast with the increasing needs from all aspects of human society, there are huge needs in the development of advanced materials as well as high-efficiency but low-cost manufacturing strategies that are both sustainable and tunable. Synthetic biology, a new engineering principle taking gene regulation and engineering design as the core, greatly promotes the development of life sciences. This discipline has also contributed to the development of material sciences and will continuously bring new ideas to future new material design. In this paper, we review recent advances in applications of synthetic biology in material sciences, with the focus on how synthetic biology could enable synthesis of new polymeric biomaterials and inorganic materials, phage display and directed evolution of proteins relevant to materials development, living functional materials, engineered bacteria-regulated artificial photosynthesis system as well as applications of gene circuits for material sciences.

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria.

PubMed

Tan, Gao-Yi; Liu, Tiangang

2017-01-01

Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Iron-Catalyzed C-O Bond Activation: Opportunity for Sustainable Catalysis.

PubMed

Bisz, Elwira; Szostak, Michal

2017-10-23

Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to several major strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. In this context, iron-catalyzed C-O activation/cross-coupling holds particular promise to achieve sustainable catalytic protocols due to its natural abundance, inherent low toxicity, and excellent economic and ecological profile. Recently, tremendous progress has been achieved in the development of new methods for functional-group-tolerant iron-catalyzed cross-coupling reactions by selective C-O cleavage. These methods establish highly attractive alternatives to traditional cross-coupling reactions by using halides as electrophilic partners. In particular, new easily accessible oxygen-based electrophiles have emerged as substrates in iron-catalyzed cross-coupling reactions, which significantly broaden the scope of this catalysis platform. New mechanistic manifolds involving iron catalysis have been established; thus opening up vistas for the development of a wide range of unprecedented reactions. The synthetic potential of this sustainable mode of reactivity has been highlighted by the development of new strategies in the construction of complex motifs, including in target synthesis. The most recent advances in sustainable iron-catalyzed cross-coupling of C-O-based electrophiles are reviewed, with a focus on both mechanistic aspects and synthetic utility. It should be noted that this catalytic manifold provides access to motifs that are often not easily available by other methods, such as the assembly of stereodefined dienes or C(sp 2 )-C(sp 3 ) cross-couplings, thus emphasizing the synthetic importance of this mode of reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bacterium Escherichia coli- and phage P22-templated synthesis of semiconductor nanostructures

NASA Astrophysics Data System (ADS)

Shen, Liming

The properties of inorganic materials in the nanoscale are found to be size- and shape-dependent due to quantum confinement effects, and thereby nanomaterials possess properties very different from those of single molecules as well as those of bulk materials. Assembling monodispersed nanoparticles into highly ordered hierarchical architectures is expected to generate novel collective properties for potential applications in catalysis, energy, biomedicine, etc. The major challenge in the assembly of nanoparticles lies in the development of controllable synthetic strategies that enable the growth and assembly of nanoparticles with high selectivity and good controllability. Biological matter possesses robust and precisely ordered structures that exist in a large variety of shapes and sizes, providing an ideal platform for synthesizing high-performance nanostructures. The primary goal of this thesis work has been to develop rational synthetic strategies for high-performance nanostructured materials using biological templates, which are difficult to achieve through traditional chemical synthetic methods. These approaches can serve as general bio-inspired approaches for synthesizing nanoparticle assemblies with desired components and architectures. CdS- and TiO2-binding peptides have been identified using phage display biopanning technique and the mechanism behind the specific affinity between the selected peptides and inorganic substrates are analyzed. The ZnS- and CdS-binding peptides, identified by the phage display biopanning, are utilized for the selective nucleation and growth of sulfides over self-assembled genetically engineered P22 coat proteins, resulting in ordered nanostructures of sulfide nanocrystal assemblies. The synthetic strategy can be extended to the fabrication of a variety of other nanostructures. A simple sonochemical route for the synthesis and assembly of CdS nanostructures with high yield under ambient conditions has been developed by exploiting the chemical characteristics and structure of permeabilized E. coli bacteria. The crystal phase, morphology, micro/nanostructure, optical absorption, and photocatalytic properties of the CdS nanostructures are tailored over a wide range by merely changing the synthetic conditions. Photoanodes fabricated using the nanoporous hollow CdS microrods exhibit excellent performance for the photocatalytic hydrogen production. This facile approach has been extended to the synthesis and assembly of other semiconducting sulfides, including PbS, ZnS, and HgS.

TU-AB-BRA-03: Atlas-Based Algorithms with Local Registration-Goodness Weighting for MRI-Driven Electron Density Mapping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farjam, R; Tyagi, N; Veeraraghavan, H

Purpose: To develop image-analysis algorithms to synthesize CT with accurate electron densities for MR-only radiotherapy of head & neck (H&N) and pelvis anatomies. Methods: CT and 3T-MRI (Philips, mDixon sequence) scans were randomly selected from a pool of H&N (n=11) and pelvis (n=12) anatomies to form an atlas. All MRIs were pre-processed to eliminate scanner and patient-induced intensity inhomogeneities and standardize their intensity histograms. CT and MRI for each patient were then co-registered to construct CT-MRI atlases. For more accurate CT-MR fusion, bone intensities in CT were suppressed to improve the similarity between CT and MRI. For a new patient,more » all CT-MRI atlases are deformed onto the new patients’ MRI initially. A newly-developed generalized registration error (GRE) metric was then calculated as a measure of local registration accuracy. The synthetic CT value at each point is a 1/GRE-weighted average of CTs from all CT-MR atlases. For evaluation, the mean absolute error (MAE) between the original and synthetic CT (generated in a leave-one-out scheme) was computed. The planning dose from the original and synthetic CT was also compared. Results: For H&N patients, MAE was 67±9, 114±22, and 116±9 HU over the entire-CT, air and bone regions, respectively. For pelvis anatomy, MAE was 47±5 and 146±14 for the entire and bone regions. In comparison with MIRADA medical, an FDA-approved registration tool, we found that our proposed registration strategy reduces MAE by ∼30% and ∼50% over the entire and bone regions, respectively. GRE-weighted strategy further lowers MAE by ∼15% to ∼40%. Our primary dose calculation also showed highly consistent results between the original and synthetic CT. Conclusion: We’ve developed a novel image-analysis technique to synthesize CT for H&N and pelvis anatomies. Our proposed image fusion strategy and GRE metric help generate more accurate synthetic CT using locally more similar atlases (Support: Philips Healthcare). The research is supported by Philips HealthCare.« less

Strategy to Combat Transnational Organized Crime: Addressing Converging Threats to National Security

DTIC Science & Technology

2011-07-01

routes and Western European markets. The Balkans region has become a new entry point for Latin American cocaine, a source of synthetic drugs, and a...of heroin, 69 tons of marijuana , 501 weapons, and 527 vehicles during the entire course of the operation. S T R AT E G Y TO CO M BAT T R A N S...Coordinate with international partners to prevent synthetic drug production, trafficking, and pre- cursor chemical diversion. Countering Illicit Finance for

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark

A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

Developing a synthetic national population to investigate the impact of different cardiovascular disease risk management strategies: A derivation and validation study

PubMed Central

Jackson, Rod

2017-01-01

Background Many national cardiovascular disease (CVD) risk factor management guidelines now recommend that drug treatment decisions should be informed primarily by patients’ multi-variable predicted risk of CVD, rather than on the basis of single risk factor thresholds. To investigate the potential impact of treatment guidelines based on CVD risk thresholds at a national level requires individual level data representing the multi-variable CVD risk factor profiles for a country’s total adult population. As these data are seldom, if ever, available, we aimed to create a synthetic population, representing the joint CVD risk factor distributions of the adult New Zealand population. Methods and results A synthetic population of 2,451,278 individuals, representing the actual age, gender, ethnicity and social deprivation composition of people aged 30–84 years who completed the 2013 New Zealand census was generated using Monte Carlo sampling. Each ‘synthetic’ person was then probabilistically assigned values of the remaining cardiovascular disease (CVD) risk factors required for predicting their CVD risk, based on data from the national census national hospitalisation and drug dispensing databases and a large regional cohort study, using Monte Carlo sampling and multiple imputation. Where possible, the synthetic population CVD risk distributions for each non-demographic risk factor were validated against independent New Zealand data sources. Conclusions We were able to develop a synthetic national population with realistic multi-variable CVD risk characteristics. The construction of this population is the first step in the development of a micro-simulation model intended to investigate the likely impact of a range of national CVD risk management strategies that will inform CVD risk management guideline updates in New Zealand and elsewhere. PMID:28384217

Crystal methamphetamine and initiation of injection drug use among street-involved youth in a Canadian setting.

PubMed

Werb, Dan; Kerr, Thomas; Buxton, Jane; Shoveller, Jeannie; Richardson, Chris; Montaner, Julio; Wood, Evan

2013-12-10

Although injection drug use is known to result in a range of health-related harms, including transmission of HIV and fatal overdose, little is known about the possible role of synthetic drugs in injection initiation. We sought to determine the effect of crystal methamphetamine use on risk of injection initiation among street-involved youth in a Canadian setting. We used Cox regression analyses to identify predictors of injection initiation among injection-naive street-involved youth enrolled in the At-Risk Youth Study, a prospective cohort study of street-involved youth in Vancouver, British Columbia. Data on circumstances of first injection were also obtained. Between October 2005 and November 2010, a total of 395 drug injection-naive, street-involved youth provided 1434 observations, with 64 (16.2%) participants initiating injection drug use during the follow-up period, for a cumulative incidence of 21.7 (95% confidence interval [CI] 1.7-41.7) per 100 person-years. In multivariable analysis, recent noninjection use of crystal methamphetamine was positively associated with subsequent injection initiation (adjusted hazard ratio 1.93, 95% CI 1.31-2.85). The drug of first injection was most commonly reported as crystal methamphetamine (14/31 [45%]). Noninjection use of crystal methamphetamine predicted subsequent injection initiation, and crystal methamphetamine was the most commonly used drug at the time of first injection. Evidence-based strategies to prevent transition to injection drug use among crystal methamphetamine users are urgently needed.

Patterns of NPS Use and Risk Reduction in Slovenia.

PubMed

Sande, Matej; Paš, Mina; Nahtigal, Klara; Šabić, Simona

2018-01-15

The following study presents factors influencing the decision to use/not to use new psychoactive substances (NPS), various patterns of NPS use, the problems experienced by users, and the methods for reducing the risks associated with NPS use. The study seeks to provide an in-depth look into the characteristics of NPS use and support the planning of targeted interventions in the field of NPS. The study involved 19 in-depth interviews carried out with 25 individuals divided into three subsamples in order to gain insight into the various experiences of NPS users. The interviews were conducted in Slovenia between December 2013 and October 2014. The sample was obtained by using the convenience sampling and snowball sampling methods. The main pattern of NPS use determined by the study concerned synthetic cathinones, specifically 3-MMC, with binge use spanning several days being a prominent feature. The main risks involving NPS use were: mixing various drugs, inappropriate dosing, lack of information prior to use, and the use of unknown substances. Several users spoke about effective strategies for reducing risks, such as obtaining information beforehand, using one's own implements and using only small quantities of unknown substances. Conclusions/Importance: The study revealed various factors based on which users decide to use NPS. Furthermore, users reported a number of problems resulting from NPS use, while risk reduction strategies are employed to a much lesser extent. Based on the results obtained, specific intervention efforts concerning NPS use and targeting specific groups of younger users were designed.

Promoter and Terminator Discovery and Engineering.

PubMed

Deaner, Matthew; Alper, Hal S

Control of gene expression is crucial to optimize metabolic pathways and synthetic gene networks. Promoters and terminators are stretches of DNA upstream and downstream (respectively) of genes that control both the rate at which the gene is transcribed and the rate at which mRNA is degraded. As a result, both of these elements control net protein expression from a synthetic construct. Thus, it is highly important to discover and engineer promoters and terminators with desired characteristics. This chapter highlights various approaches taken to catalogue these important synthetic elements. Specifically, early strategies have focused largely on semi-rational techniques such as saturation mutagenesis to diversify native promoters and terminators. Next, in an effort to reduce the length of the synthetic biology design cycle, efforts in the field have turned towards the rational design of synthetic promoters and terminators. In this vein, we cover recently developed methods such as hybrid engineering, high throughput characterization, and thermodynamic modeling which allow finer control in the rational design of novel promoters and terminators. Emphasis is placed on the methodologies used and this chapter showcases the utility of these methods across multiple host organisms.

Simultaneous non-contiguous deletions using large synthetic DNA and site-specific recombinases

PubMed Central

Krishnakumar, Radha; Grose, Carissa; Haft, Daniel H.; Zaveri, Jayshree; Alperovich, Nina; Gibson, Daniel G.; Merryman, Chuck; Glass, John I.

2014-01-01

Toward achieving rapid and large scale genome modification directly in a target organism, we have developed a new genome engineering strategy that uses a combination of bioinformatics aided design, large synthetic DNA and site-specific recombinases. Using Cre recombinase we swapped a target 126-kb segment of the Escherichia coli genome with a 72-kb synthetic DNA cassette, thereby effectively eliminating over 54 kb of genomic DNA from three non-contiguous regions in a single recombination event. We observed complete replacement of the native sequence with the modified synthetic sequence through the action of the Cre recombinase and no competition from homologous recombination. Because of the versatility and high-efficiency of the Cre-lox system, this method can be used in any organism where this system is functional as well as adapted to use with other highly precise genome engineering systems. Compared to present-day iterative approaches in genome engineering, we anticipate this method will greatly speed up the creation of reduced, modularized and optimized genomes through the integration of deletion analyses data, transcriptomics, synthetic biology and site-specific recombination. PMID:24914053

Will Kentucky lead the way in synthetic fuels production? A history lesson

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musulin, M.

2008-07-01

At four times in the history of the United States, synthetic fuels have been used as the energy savior of the country, from the period immediately following the second World War to the mid 1980s when the Synthetic Fuels Corporation was unceremoniously demolished by the Reagan administration. The Center for Applied Energy Research at the University of Kentucky has been a major player in the game and the state of Kentucky has received much funding for synthetic fuels development since the 1970s. The article traces the history of developments in the field. The fate of the development has in themore » author's opinion been influenced by the misalignment of three 'spheres of influence' - in essence the political economy, environmental/regulatory issues, and the technological innovation process. Synthetic fuels can now become an integral part of what is called a 'multiplex energy strategy' and Kentucky again has the opportunity to build on its prior experience and embrace a new paradigm regarding how clean energy solutions based on gasification technologies can aid the USA. 4 photos.« less

The new pattern of drug abuse in China.

PubMed

Sun, Hong-qiang; Bao, Yan-ping; Zhou, Shuang-jiang; Meng, Shi-qiu; Lu, Lin

2014-07-01

Drug abuse has resulted in a huge burden on public health and the economy in China. Since the reemergence of drug abuse in China in the 1980s, the number of drug addicts has increased dramatically, especially the proportion of users of synthetic drugs, such as amphetamine-type stimulant (ATS). Further, the proportion of opiate addicts has decreased among the new initiates. This review describes the new pattern of drug abuse and the resultant intervention strategy in China. The demographics regarding drug abuse in China point to a trend of younger users, and indicate that Internet and telephone are facilitating drug trafficking. Furthermore, polydrug use is common. Many heroin addicts have used ATS and other synthetic drugs, and some synthetic drug abusers have used opiate drugs too. HIV infection and psychosis comorbidity are primarily associated with drug abuse in China. Although opiate drug use and its associated harm have been controlled effectively in some areas, the synthetic drugs and new designer drugs have complicated the drug abuse scene. A national system of management and intervention for synthetic drugs and associated diseases urgently needs to be established in China.

[Advances in microbial genome reduction and modification].

PubMed

Wang, Jianli; Wang, Xiaoyuan

2013-08-01

Microbial genome reduction and modification are important strategies for constructing cellular chassis used for synthetic biology. This article summarized the essential genes and the methods to identify them in microorganisms, compared various strategies for microbial genome reduction, and analyzed the characteristics of some microorganisms with the minimized genome. This review shows the important role of genome reduction in constructing cellular chassis.

Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

PubMed

Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

2017-01-01

Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Heterobimetallic Pd–K carbene complexes via one-electron reductions of palladium radical carbenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Peng; Hoffbauer, Melissa R.; Vyushkova, Mariya

2016-03-24

Unprecedented sequential substitution/reduction synthetic strategy on the Pd radical carbenes afforded heterobimetallic Pd–K carbene complexes, which features novel Pd–C carbene–K structural moieties.

Heterobimetallic Pd–K carbene complexes via one-electron reductions of palladium radical carbenes

DOE PAGES

Cui, Peng; Hoffbauer, Melissa R.; Vyushkova, Mariya; ...

2016-01-01

Unprecedented sequential substitution/reduction synthetic strategy on the Pd radical carbenes afforded heterobimetallic Pd–K carbene complexes, which features novel Pd–C carbene–K structural moieties.

The use of synthetic bedding in children. Do strategies of change influence associations with asthma?

PubMed

Behrens, Thomas; Maziak, Wasim; Weiland, Stephan K; Siebert, Edith; Rzehak, Peter; Keil, Ulrich

2005-04-01

Epidemiological data suggest in contrast to clinical recommendations a negative effect of synthetic bedding on asthma and respiratory symptoms. To assess the effects of bedding filled with synthetic material on the risk of asthma and respiratory symptoms in 6- to 7-year-old children, taking into account allergy-related change of bedding material. We analyzed data from the ISAAC Phase III cross-sectional survey (1999/2000) in Münster, Germany. Data were collected by parental report from representative school-based samples of 6- to 7-year old children (n = 3,529). We calculated prevalence ratios with 95% confidence intervals for the association between respiratory symptoms suggestive of asthma and synthetic pillows and blankets and adjusting for potential confounders. In the preliminary analyses, synthetic pillows and synthetic blankets were positively associated with the studied respiratory outcomes. For example, a high number of wheezing attacks was positively associated with synthetic pillows (PR = 4.44; 95% CI 2.84-6.94) and synthetic blankets (PR = 3.80; 95% CI 2.48-5.82). However, in the restricted analysis, excluding participants reporting allergy-related change of bedding (pillows n = 440; blankets n = 437), the positive associations disappeared for all studied outcomes. Our findings suggest that allergy-related choice of bedding is an important factor in the assessment of the relation between synthetic bedding and asthma symptoms. Ignoring those changes can lead to false-positive risk estimates. Prospective studies that allow to disentangle the temporal sequence of disease, exposure, and change of bedding should help to further clarify this issue.

Health Risk Behaviors With Synthetic Cannabinoids Versus Marijuana.

PubMed

Clayton, Heather B; Lowry, Richard; Ashley, Carmen; Wolkin, Amy; Grant, Althea M

2017-04-01

Data are limited on the behavioral risk correlates of synthetic cannabinoid use. The purpose of this study was to compare the behavioral risk correlates of synthetic cannabinoid use with those among marijuana users. Data from the 2015 Youth Risk Behavior Survey, a cross-sectional survey conducted in a nationally representative sample of students in grades 9 through 12 ( N = 15 624), were used to examine the association between self-reported type of marijuana use (ie, never use of marijuana and synthetic cannabinoids, ever use of marijuana only, and ever use of synthetic cannabinoids) and self-report of 36 risk behaviors across 4 domains: substance use, injury/violence, mental health, and sexual health. Multivariable models were used to calculate adjusted prevalence ratios. Students who ever used synthetic cannabinoids had a significantly greater likelihood of engaging in each of the behaviors in the substance use and sexual risk domains compared with students who ever used marijuana only. Students who ever used synthetic cannabinoids were more likely than students who ever used marijuana only to have used marijuana before age 13 years, to have used marijuana ≥1 times during the past 30 days, and to have used marijuana ≥20 times during the past 30 days. Several injury/violence behaviors were more prevalent among students who ever used synthetic cannabinoids compared with students who ever used marijuana only. Health professionals and school-based substance use prevention programs should include strategies focused on the prevention of both synthetic cannabinoids and marijuana. Copyright © 2017 by the American Academy of Pediatrics.

Synthetic Adhesive Attachment Discs based on Spider Pyriform Silk Architecture

NASA Astrophysics Data System (ADS)

Jain, Dharamdeep; Sahni, Vasav; Dhinojwala, Ali

2014-03-01

Among the variety of silks produced by spiders, pyriform silk is used in conjunction with the dragline silk to attach webs to different surfaces. Cob weaver spiders employ different architectural patterns to utilize the pyriform silk and form attachment joints with each pattern having a characteristic adhesive performance. The staple pin architecture is a one of the strongest attachment designs employed by spiders to attach their webs. Here we use a synthetic approach to create the a similar patterned architecture attachment discs on aluminum substrate using thermoplastic polyurethane. Measurable pull off forces are generated when the synthetic discs are peeled off a surface. This innovative adhesive strategy can be a source of design in various biomedical applications. Financial Support from National Science Foundation.

Ensuring the security of synthetic biology-towards a 5P governance strategy.

PubMed

Kelle, Alexander

2009-12-01

Over recent years the label "synthetic biology" has been attached to a number of diverse research and commercial activities, ranging from the search for a minimal cell to the quick delivery of customized genes by DNA synthesis companies. Based on the analysis of biosecurity issues surrounding synthetic biology during the SYNBIOSAFE project, this paper will first provide a rationale for taking security, in addition to safety aspects of this new field, seriously. It will then take stock of the initiatives and measures that have already been taken in this area and will lastly try to map out future areas of activities in order to minimise the security risks emanating from this promising new field of scientific inquiry and technological progress.

Annotating novel genes by integrating synthetic lethals and genomic information

PubMed Central

Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

2008-01-01

Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains.

PubMed

Fernández-Cruz, E; Álvarez-Fernández, M A; Valero, E; Troncoso, A M; García-Parrilla, M C

2017-02-15

Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway. This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC-HRMS system (Qexactive). Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Research Translation and Emerging Health Technologies: Synthetic Biology and Beyond.

PubMed

Chan, Sarah

2016-12-09

New health technologies are rapidly emerging from various areas of bioscience research, such as gene editing, regenerative medicine and synthetic biology. These technologies raise promising medical possibilities but also a range of ethical considerations. Apart from the issues involved in considering whether novel health technologies can or should become part of mainstream medical treatment once established, the process of research translation to develop such therapies itself entails particular ethical concerns. In this paper I use synthetic biology as an example of a new and largely unexplored area of health technology to consider the ways in which novel health technologies are likely to emerge and the ethical challenges these will present. I argue that such developments require us to rethink conventional attitudes towards clinical research, the roles of doctors/researchers and patients/participants with respect to research, and the relationship between science and society; and that a broader framework is required to address the plurality of stakeholder roles and interests involved in the development of treatments based on novel technologies.

Can Universities Develop Advanced Technology and Solve Social Problems?

NASA Astrophysics Data System (ADS)

Pérez Ones, Isarelis; Núñez Jover, Jorge

This paper presents case studies on how Cuban universities have increasingly become directly involved with the economic and social development of the country. The paper shows how Cuban universities, from the early 1980s and early 1990s, started reorientation and organization of their scientific research, becoming more directly and intensely involved in the economic and social development of the country. In this way, special reference is made to the case of a research group at the University of Havana: the Laboratory of Synthetic Antigens. This group developed the first synthetic vaccine for human use approved in the world. In the article, public policies involved in this success as well as different obstacles are discussed. These obstacles demonstrate the difficulties and challenges that universities face when carrying out research and innovation activities related to economic and social development.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

PubMed

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

2015-07-06

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

PubMed Central

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R.

2015-01-01

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed. PMID:26109634

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. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Co-culture systems and technologies: taking synthetic biology to the next level.

PubMed

Goers, Lisa; Freemont, Paul; Polizzi, Karen M

2014-07-06

Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell-cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Total Synthesis of Purported Cephalosporolides H and I, Penisporolide B, and Their Stereoisomers.

PubMed

Wang, Jian; Tong, Rongbiao

2016-05-20

Development of a unified, bioinspired synthetic strategy to access four possible diastereomers of unique 2,2-dimethyl-[5,5]-spiroacetal-cis-fused-γ-lactone (Me2SAFL) is reported, featuring pyridinium chlorochromate (PCC)-promoted oxidative ring expansion of β-hydroxy cyclic ethers and dehydrative ring-contraction rearrangement of 10-membered lactones. Synthetic utility of this strategy was demonstrated by total syntheses of 12 Me2SAFLs, corresponding to the purported cephalosporolide H (CesH), cephalosporolide I (CesI), and penisporolide B (PenB) and their possible diastereomers. Comprehensive NMR data analysis suggested that the tricyclic Me2SAFL core of CesH, CesI, and PenB should be revised to the same relative (3R*, 4R*, 6S*, 9R*) configuration and that the side chains required an unknown constitutional structure revision.

Synthetic biology era: Improving antibiotic's world.

PubMed

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

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. Copyright © 2017. Published by Elsevier Inc.

Wing motion transformation to evaluate aerodynamic coupling in flapping wing flight.

PubMed

Faruque, Imraan A; Humbert, J Sean

2014-12-21

Whether the remarkable flight performance of insects is because the animals leverage inherent physics at this scale or because they employ specialized neural feedback mechanisms is an active research question. In this study, an empirically derived aerodynamics model is used with a transformation involving a delay and a rotation to identify a class of kinematics that provide favorable roll-yaw coupling. The transformation is also used to transform both synthetic and experimentally measured wing motions onto the manifold representing proverse yaw and to quantify the degree to which freely flying insects make use of passive aerodynamic mechanisms to provide proverse roll-yaw turn coordination. The transformation indicates that recorded insect kinematics do act to provide proverse yaw for a variety of maneuvers. This finding suggests that passive aerodynamic mechanisms can act to reduce the neural feedback demands of an insect׳s flight control strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology.

PubMed

Ojima, Iwao

2013-07-05

Over the last three decades, my engagement in "fluorine chemistry" has evolved substantially because of the multidisciplinary nature of the research programs. I began my research career as a synthetic chemist in organometallic chemistry and homogeneous catalysis directed toward organic synthesis. Then, I was brought into a very unique world of "fluorine chemistry" in the end of 1970s. I started exploring the interface of fluorine chemistry and transition metal homogeneous catalysis first, which was followed by amino acids, peptides, and peptidomimetics for medicinal chemistry. Since then, I have been exploring the interfaces of fluorine chemistry and multidisciplinary fields of research involving medicinal chemistry, chemical biology, cancer biology, and molecular imaging. This perspective intends to cover my fruitful endeavor in the exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology in a chronological order to show the evolution of my research interest and strategy.

Exploration of Fluorine Chemistry at the Multidisciplinary Interface of Chemistry and Biology

PubMed Central

Ojima, Iwao

2013-01-01

Over the last three decades, my engagement in “fluorine chemistry” has evolved substantially, because of the multidisciplinary nature of the research programs. I began my research career as a synthetic chemist in organometallic chemistry and homogeneous catalysis directed toward organic synthesis. Then, I was brought into a very unique world of “fluorine chemistry” in the end of 1970s. I started exploring the interface of fluorine chemistry and transition metal homogeneous catalysis first, which was followed by amino acids, peptides, and peptidomimetics for medicinal chemistry. Since then, I have been exploring the interfaces of fluorine chemistry and multidisciplinary fields of research involving medicinal chemistry, chemical biology, cancer biology and molecular imaging. This perspective intends to cover my fruitful endeavor in the exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology in a chronological order to show the evolution of my research interest and strategy. PMID:23614876

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease.

PubMed

Kokona, Despina; Georgiou, Panagiota-Christina; Kounenidakis, Mihalis; Kiagiadaki, Foteini; Thermos, Kyriaki

2016-01-01

The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.

Synthetic Studies of Complex Immunostimulants from Quillaja saponaria: Synthesis of the Potent Clinical Immunoadjuvant QS-21Aapi

PubMed Central

Kim, Yong-Jae; Wang, Pengfei; Navarro-Villalobos, Mauricio; Rohde, Bridget D.; Derryberry, JohnMark; Gin, David Y.

2008-01-01

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21Aapi in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues. PMID:16953631

True and masked three-coordinate T-shaped platinum(II) intermediates.

PubMed

Ortuño, Manuel A; Conejero, Salvador; Lledós, Agustí

2013-01-01

Although four-coordinate square-planar geometries, with a formally 16-electron counting, are absolutely dominant in isolated Pt(II) complexes, three-coordinate, 14-electron Pt(II) complexes are believed to be key intermediates in a number of platinum-mediated organometallic transformations. Although very few authenticated three-coordinate Pt(II) complexes have been characterized, a much larger number of complexes can be described as operationally three-coordinate in a kinetic sense. In these compounds, which we have called masked T-shaped complexes, the fourth position is occupied by a very weak ligand (agostic bond, solvent molecule or counteranion), which can be easily displaced. This review summarizes the structural features of the true and masked T-shaped Pt(II) complexes reported so far and describes synthetic strategies employed for their formation. Moreover, recent experimental and theoretical reports are analyzed, which suggest the involvement of such intermediates in reaction mechanisms, particularly C-H bond-activation processes.

Palladium-mediated strategies for functionalizing the dihydroazulene photoswitch: paving the way for its exploitation in molecular electronics.

PubMed

Jevric, Martyn; Broman, Søren Lindbæk; Nielsen, Mogens Brøndsted

2013-05-03

The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has attracted interest as a molecular switch for advanced materials and molecular electronics. We report here two synthetic approaches using palladium catalysis for synthesizing dihydroazulene (DHA) photoswitches with thioacetate anchoring groups intended for molecular electronics applications. The first methodology involves a Suzuki coupling using tert-butyl thioether protecting groups. Conversion to the thioacetate using boron tribromide/acetyl chloride results in the formation of the product as a mixture of regioisomers mediated by a ring-opening reaction. The second approach circumvents isomerization by the synthesis of stannanes as intermediates and their use in a Stille coupling. Although fully unsaturated azulenes are formed as byproducts during the synthesis of the DHA stannanes, this approach allowed the regioselective incorporation of the thioacetate anchoring group in either one of the two ends (positions 2 or 7) or at both.

Functionalizing the γ-Position of α-Diazo-β-ketoesters.

PubMed

Nguyen, Thu Q; Alqurafi, Maha; Edwards, Cash; Nguyen, Pauline; Kim, Jean; Casco, Samuel; Bennet, Maricka; Chiang, Christopher; Lohry, Maureen; Cox, Melina; Meshram, Byron; Le, Duyen; Kim, Eugene; Smriti, Snigdha; Oelschlaeger, Peter; Buynak, John D

2016-06-27

Although α-diazo-β-ketoesters are synthetically versatile intermediates, methodology for introducing this functionality into complex molecules is still limited, most frequently involving a carboxylic acid precursor, which is then activated and transformed into a β-ketoester, with the diazo group being subsequently added with a diazo transfer reagent. While introducing this highly functional moiety in a convergent one step process would be ideal, such an objective is limited by the relatively few studies which address functionalization of the α-diazo-β-ketoester at the γ-position. In the present investigation, we evaluate strategies, both new and established, for functionalizing α-diazo-β-ketoesters, particularly with regard to generating compounds prospectively useful in the synthesis of C1-substituted carbapenems. We report the first δ-aldehydo-α-diazo-β-ketoester as well as a method for its oxidation to the corresponding methyl ester, and the formation of a new substituted pyrazole under basic conditions.

Synthesis with Ultrasonic Waves.

ERIC Educational Resources Information Center

Boudjouk, Phillip

1986-01-01

Reviews recent developments in synthetic organic sonochemistry, focusing on reactions involving metals. Cites important historical findings, discusses cavitation effects, and describes important reactions. (JM)

RNA Interference: A Novel Source of Resistance to Combat Plant Parasitic Nematodes.

PubMed

Banerjee, Sagar; Banerjee, Anamika; Gill, Sarvajeet S; Gupta, Om P; Dahuja, Anil; Jain, Pradeep K; Sirohi, Anil

2017-01-01

Plant parasitic nematodes cause severe damage and yield loss in major crops all over the world. Available control strategies include use of insecticides/nematicides but these have proved detrimental to the environment, while other strategies like crop rotation and resistant cultivars have serious limitations. This scenario provides an opportunity for the utilization of technological advances like RNA interference (RNAi) to engineer resistance against these devastating parasites. First demonstrated in the model free living nematode, Caenorhabtidis elegans ; the phenomenon of RNAi has been successfully used to suppress essential genes of plant parasitic nematodes involved in parasitism, nematode development and mRNA metabolism. Synthetic neurotransmitants mixed with dsRNA solutions are used for in vitro RNAi in plant parasitic nematodes with significant success. However, host delivered in planta RNAi has proved to be a pioneering phenomenon to deliver dsRNAs to feeding nematodes and silence the target genes to achieve resistance. Highly enriched genomic databases are exploited to limit off target effects and ensure sequence specific silencing. Technological advances like gene stacking and use of nematode inducible and tissue specific promoters can further enhance the utility of RNAi based transgenics against plant parasitic nematodes.

Rational Combinations of Targeted Agents in AML

PubMed Central

Bose, Prithviraj; Grant, Steven

2015-01-01

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. PMID:26113989

Gene and process level modulation to overcome the bottlenecks of recombinant proteins expression in Pichia pastoris.

PubMed

Prabhu, Ashish A; Boro, Bibari; Bharali, Biju; Chakraborty, Shuchishloka; Dasu, Veeranki V

2017-01-01

Process development involving system metabolic engineering and bioprocess engineering has become one of the major thrust for the development of therapeutic proteins or enzymes. Pichia pastoris has emerged as a prominent host for the production of therapeutic protein or enzymes. Regardless of producing high protein titers, various cellular and process level bottlenecks restrict the expression of recombinant proteins in P. pastoris. In the present review, we have summarized the recent developments in the expression of foreign proteins in P. pastoris. Further, we have discussed various cellular engineering strategies which include codon optimization, pathway engineering, signal peptide processing, development of protease deficient strain and glyco-engineered strains for the high yield protein secretion of recombinant protein. Bioprocess development of recombinant proteins in large-scale bioreactor including medium optimization, optimum feeding strategy and co-substrate feeding in fed-batch as well as continuous cultivation have been described. The recent advances in system and synthetic biology studies including metabolic flux analysis in understanding the phenotypic characteristics of recombinant Pichia and genome editing with CRISPR-CAS system have also been summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nanowell-Trapped Charged Ligand-Bearing Nanoparticle Surfaces – A Novel Method of Enhancing Flow-Resistant Cell Adhesion

PubMed Central

Tran, Phat L.; Gamboa, Jessica R.; McCracken, Katherine E.; Riley, Mark R.

2014-01-01

Assuring cell adhesion to an underlying biomaterial surface is vital in implant device design and tissue engineering, particularly under circumstances where cells are subjected to potential detachment from overriding fluid flow. Cell-substrate adhesion is a highly regulated process involving the interplay of mechanical properties, surface topographic features, electrostatic charge, and biochemical mechanisms. At the nanoscale level the physical properties of the underlying substrate are of particular importance in cell adhesion. Conventionally, natural, pro-adhesive, and often thrombogenic, protein biomaterials are frequently utilized to facilitate adhesion. In the present study nanofabrication techniques are utilized to enhance the biological functionality of a synthetic polymer surface, polymethymethacrylate, with respect to cell adhesion. Specifically we examine the effect on cell adhesion of combining: 1. optimized surface texturing, 2. electrostatic charge and 3. cell adhesive ligands, uniquely assembled on the substrata surface, as an ensemble of nanoparticles trapped in nanowells. Our results reveal that the ensemble strategy leads to enhanced, more than simply additive, endothelial cell adhesion under both static and flow conditions. This strategy may be of particular utility for enhancing flow-resistant endothelialization of blood-contacting surfaces of cardiovascular devices subjected to flow-mediated shear. PMID:23225491

New and Emerging Treatment Options for Irritable Bowel Syndrome

PubMed Central

Lacy, Brian E.; Chey, William D.; Lembo, Anthony J.

2015-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS. PMID:26491416

Polybenzoxazole via aromatic nucleophilic displacement

NASA Technical Reports Server (NTRS)

Hergenrother, Paul M. (Inventor); Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor)

1993-01-01

Polybenzoxazoles (PBO) are heterocyclic macromolecules which were first synthesized in a two-step process by the initial formation of aromatic diacid chlorides with bis(o-aminophenol)s through solution condensation of aromatic diacid chlorides with bis(o-aminophenol)s followed by thermal cyclodehydration. Since then several methods were utilized in their synthesis. The most common synthetic method for PBO involves a polycondensation of bis(o-aminophenol)s with aromatic diacid diphenyl esters. Another preparative route involves the solution polycondensation of the hydrochloride salts of bis(o-amino phenol)s with aromatic diacids in polyphosphoric acid. Another synthetic method involves the initial formation of poly(o-hydroxy amide)s from silylated bis(o-aminophenol)s with aromatic diacid chlorides followed by thermal cyclodehydration to PBO. A recent preparative route involves the reaction of aromatic bisphenols with bis(fluorophenyl) benzoxazoles by the displacement reaction to form PBO. The novelty of the present invention is that high molecular weight PBO of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

Comparative assessment of synthetic strategies toward active platinum-rhodium-tin electrocatalysts for efficient ethanol electro-oxidation

NASA Astrophysics Data System (ADS)

Erini, Nina; Krause, Paul; Gliech, Manuel; Yang, Ruizhi; Huang, Yunhui; Strasser, Peter

2015-10-01

The present work explores the effect of autoclave-based autogenous-pressure vs. ambient pressure conditions on the synthesis and properties of carbon-supported Pt-Rh-Sn nanoparticle electrocatalysts. The Pt-Rh-Sn nanoparticles were characterized by X-ray spectroscopy, electron microscopy and mass spectroscopy and deployed as catalysts for the electrocatalytic ethanol oxidation reaction. Pt-Rh-Sn catalysts precipitated with carbon already present showed narrow particle size distribution around 7 nm, while catalysts supported on carbon after particle formation showed broader size distribution ranging from 8 to 16 nm, similar metal loadings between 40 and 48 wt.% and similar atomic ratios of Pt:Rh:Sn of 30:10:60. The highest ethanol oxidation activity at low overpotentials associated with exceptionally early ethanol oxidation onset potential was observed for ambient-pressure catalysts with the active ternary alloy phase formed in presence of the carbon supports. In contrast, catalysts prepared under ambient pressure in a two-step approach, involving alloy particle formation followed by particle separation and subsequent deposition on the carbon support, yielded the highest overall mass activities. Based on the observed synthesis-activity correlations, a comparative assessment is provided of the synthetic techniques at high vs. low pressures, and in presence and absence of carbon support. Plausible hypotheses in terms of particle dispersion and interparticle distance accounting for these observed differences are discussed.

From self-organization to self-assembly: a new materialism?

PubMed

Vincent, Bernadette Bensaude

2016-09-01

While self-organization has been an integral part of academic discussions about the distinctive features of living organisms, at least since Immanuel Kant's Critique of Judgement, the term 'self-assembly' has only been used for a few decades as it became a hot research topic with the emergence of nanotechnology. Could it be considered as an attempt at reducing vital organization to a sort of assembly line of molecules? Considering the context of research on self-assembly I argue that the shift of attention from self-organization to self-assembly does not really challenge the boundary between chemistry and biology. Self-assembly was first and foremost investigated in an engineering context as a strategy for manufacturing without human intervention and did not raise new perspectives on the emergence of vital organization itself. However self-assembly implies metaphysical assumptions that this paper tries to disentangle. It first describes the emergence of self-assembly as a research field in the context of materials science and nanotechnology. The second section outlines the metaphysical implications and will emphasize a sharp contrast between the ontology underlying two practices of self-assembly developed under the umbrella of synthetic biology. And unexpectedly, we shall see that chemists are less on the reductionist side than most synthetic biologists. Finally, the third section ventures some reflections on the kind of design involved in self-assembly practices.

Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation.

PubMed

Ohyoshi, Takayuki; Tamura, Yuki; Hayakawa, Ichiro; Hirai, Go; Miyazawa, Yamato; Funakubo, Shota; Sodeoka, Mikiko; Kigoshi, Hideo

2016-12-28

We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the "direct" construction of a highly strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation. The PKCα- or PKCδ-activating 13-oxyingenol and ingenol analogs induced both distinct morphological changes and increases of CD11b expression in HL-60 cells, which would be typical signs of HL-60 cell differentiation to macrophage-like cells, as expected by previous reports. Intriguingly, however, similar differentiation phenotypes were observed with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13-dodecanoate showing a remarkably less potent PKCα or PKCδ activation ability, which the PKC inhibitor Gö6983 diminished. This indicated the involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death, similar to the action of a phorbol ester, a strong PKC activator.

Decarboxylative Fluorination Strategies for Accessing Medicinally-relevant Products

PubMed Central

Qiao, Yupu; Zhu, Lingui; Ambler, Brett R.

2014-01-01

Fluorinated organic compounds have a long history in medicinal chemistry, and synthetic methods to access target fluorinated compounds are undergoing a revolution. One powerful strategy for the installation of fluorine-containing functional groups includes decarboxylative reactions. Benefits of decarboxylative approaches potentially include: 1) readily available substrates or reagents 2) mild reaction conditions; 3) simplified purification. This focus review highlights the applications of decarboxylation strategies for fluorination reactions to access compounds with biomedical potential. The manuscript highlights on two general strategies, fluorination by decarboxylative reagents and by decarboxylation of substrates. Where relevant, examples of medicinally useful compounds that can be accessed using these strategies are highlighted. PMID:24484421

A little adjustment of synthetic strategy led to a new highly repeated heteropolyblue: Structure, characterizations and photocatalytic properties

NASA Astrophysics Data System (ADS)

Chen, Wu-Hua; Zhang, Zhu-Sen; Zhao, Jin-Hua; Qiu, Ze-Hai; Yuan, Qiu-Lan; Huang, Tian-Fu; Lin, Xue-Yu; Hu, Zhi-Biao

2017-06-01

Hydrothermal synthesis is known as the most efficient method to prepare novel structural polyoxometalate (POM)-based materials, but controlled synthesis of a structure-directing POM is always challenging task. The experimental repeatability is usually one of the key topics. To explore a reliable hydrothermal synthesis approach for new POMs will be a meaningful work. Our previous work, which we have hydrothermally synthesized the first Cr-complexes-capped Keggin-type POM, [Hdma]3[H2phen]{[Cr(phen)]2[MoV8MoVI4O36(PO4)]}·nH2O (n ≈ 2) (Chen et al., polyhedron, 2015, 85, 117), afford us some commendable synthetic experiences, arouse us some introspections as well for its tricky preparation conditions and low experimental repeatability. Based on the aforementioned work, a new high-repetition-rate and more steady heteropolyblue, [H3O]0.5(Hdma)2.5(dma)0.25{[Cr(phen)]2[MoV6MoVI6O8(PO4)]}·2H2O (1) (dma = dimethylamine (C2H7N), phen = 1,10-phenanthroline (C12H8N2)), has been successfully obtained by virtue of reasonably adjusting synthetic strategy. The adjustment of synthetic strategy includes controlling ratio of reactants and aging time, reasonably using redoxes and stepwise self-assembly plans. Compound 1 is the second POM with Keggin-type polyanion capped by Cr-complexes. Experiments demonstrate that compound 1 has good catalytic activity in the both degradation reactions of rhodamine B (RHB) and methyl orange (MO) under ultraviolet (UV)-light and oxidant H2O2 conditions. Detailed structural characterizations include single-crystal X-ray diffraction (XRD) analyses, energy-dispersive X-ray spectrometry (EDS) analyses, elemental analyses, cerate oxidimetry, powder XRD, fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible-near-infrared (UV-Vis-NIR) solid diffuse reflection spectrum and X-ray photoelectron spectroscopy (XPS) analyses. The electrochemical property (cyclic voltammetry (CV)) of compound 1 has also been studied.

Complete Biosynthesis of Anthocyanins Using E. coli Polycultures.

PubMed

Jones, J Andrew; Vernacchio, Victoria R; Collins, Shannon M; Shirke, Abhijit N; Xiu, Yu; Englaender, Jacob A; Cress, Brady F; McCutcheon, Catherine C; Linhardt, Robert J; Gross, Richard A; Koffas, Mattheos A G

2017-06-06

Fermentation-based chemical production strategies provide a feasible route for the rapid, safe, and sustainable production of a wide variety of important chemical products, ranging from fuels to pharmaceuticals. These strategies have yet to find wide industrial utilization due to their inability to economically compete with traditional extraction and chemical production methods. Here, we engineer for the first time the complex microbial biosynthesis of an anthocyanin plant natural product, starting from sugar. This was accomplished through the development of a synthetic, 4-strain Escherichia coli polyculture collectively expressing 15 exogenous or modified pathway enzymes from diverse plants and other microbes. This synthetic consortium-based approach enables the functional expression and connection of lengthy pathways while effectively managing the accompanying metabolic burden. The de novo production of specific anthocyanin molecules, such as calistephin, has been an elusive metabolic engineering target for over a decade. The utilization of our polyculture strategy affords milligram-per-liter production titers. This study also lays the groundwork for significant advances in strain and process design toward the development of cost-competitive biochemical production hosts through nontraditional methodologies. IMPORTANCE To efficiently express active extensive recombinant pathways with high flux in microbial hosts requires careful balance and allocation of metabolic resources such as ATP, reducing equivalents, and malonyl coenzyme A (malonyl-CoA), as well as various other pathway-dependent cofactors and precursors. To address this issue, we report the design, characterization, and implementation of the first synthetic 4-strain polyculture. Division of the overexpression of 15 enzymes and transcription factors over 4 independent strain modules allowed for the division of metabolic burden and for independent strain optimization for module-specific metabolite needs. This study represents the most complex synthetic consortia constructed to date for metabolic engineering applications and provides a new paradigm in metabolic engineering for the reconstitution of extensive metabolic pathways in nonnative hosts. Copyright © 2017 Jones et al.

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids-A Systematic Review.

PubMed

Cohen, Koby; Weinstein, Aviv

2018-02-27

Background-Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method-A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., "synthetic cannabinoids AND cognition," "cannabis AND cognition" and "cannabinoids AND cognition"). Results-The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions-Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs.

Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

PubMed Central

Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

Precision control of recombinant gene transcription for CHO cell synthetic biology.

PubMed

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology.

PubMed

Blount, Benjamin A; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex "multi-wire" logic functions.

NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells.

PubMed

She, Zhi-Gang; Chang, Yunchao; Pang, Hong-Bo; Han, Wenlong; Chen, Hou-Zao; Smith, Jeffrey W; Stallcup, William B

2016-01-01

Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice. Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta. These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis. © 2015 American Heart Association, Inc.

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

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review

PubMed Central

Cohen, Koby; Weinstein, Aviv

2018-01-01

Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”). Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs. PMID:29495540

WISB: Warwick Integrative Synthetic Biology Centre.

PubMed

McCarthy, John

2016-06-15

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. © 2016 The Author(s).

Drug discovery: Fighting evolution with chemical synthesis

NASA Astrophysics Data System (ADS)

Yan, Ming; Baran, Phil S.

2016-05-01

A synthetic strategy has been developed that provides easy access to structurally diverse analogues of naturally occurring antibiotics, providing a fresh means of attack in the war against drug-resistant bacteria. See Article p.338

[Toxic phosphorous osteonecrosis of facial bones among drug addicts to desomorphine and pervitin. Part II].

PubMed

Basin, E M; Medvedev, Yu A

2015-01-01

Article describes literature review of "atypical" osteomyelitis--osteonecrosis of facial bones among addicts to synthetic narcotics desomorphine and pervitin, different comorbidities, treatment strategy and prognosis were outlined

Supramolecular analytical chemistry.

PubMed

Anslyn, Eric V

2007-02-02

A large fraction of the field of supramolecular chemistry has focused in previous decades upon the study and use of synthetic receptors as a means of mimicking natural receptors. Recently, the demand for synthetic receptors is rapidly increasing within the analytical sciences. These classes of receptors are finding uses in simple indicator chemistry, cellular imaging, and enantiomeric excess analysis, while also being involved in various truly practical assays of bodily fluids. Moreover, one of the most promising areas for the use of synthetic receptors is in the arena of differential sensing. Although many synthetic receptors have been shown to yield exquisite selectivities, in general, this class of receptor suffers from cross-reactivities. Yet, cross-reactivity is an attribute that is crucial to the success of differential sensing schemes. Therefore, both selective and nonselective synthetic receptors are finding uses in analytical applications. Hence, a field of chemistry that herein is entitled "Supramolecular Analytical Chemistry" is emerging, and is predicted to undergo increasingly rapid growth in the near future.

The major synthetic evolutionary transitions.

PubMed

Solé, Ricard

2016-08-19

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'. © 2016 The Author(s).

A Sacrificial Coating Strategy Toward Enhancement of Metal-Support Interaction for Ultrastable Au Nanocatalysts

DOE PAGES

Zhan, Wangcheng; He, Qian; Liu, Xiaofei; ...

2016-11-22

Supported gold (Au) nanocatalysts hold great promise for heterogeneous catalysis; however, their practical application is greatly hampered by poor thermodynamic stability. Herein, a general synthetic strategy is reported where discrete metal nanoparticles are made resistant to sintering, preserving their catalytic activities in high-temperature oxidation processes. Taking advantage of the unique coating chemistry of dopamine, sacrificial carbon layers are constructed on the material surface, stabilizing the supported catalyst. Upon annealing at high temperature under an inert atmosphere, the interactions between support and metal nanoparticle are dramatically enhanced, while the sacrificial carbon layers can be subsequently removed through oxidative calcination in air.more » Owing to the improved metal-support contact and strengthened electronic interactions, the resulting Au nanocatalysts are resistant to sintering and exhibit excellent durability for catalytic combustion of propylene at elevated temperatures. Moreover, the facile synthetic strategy can be extended to the stabilization of other supported catalysts on a broad range of supports, providing a general approach to enhancing the thermal stability and sintering resistance of supported nanocatalysts.« less

Regulation of p53 Stability and Apoptosis by a ROR Agonist

PubMed Central

Wang, Yongjun; Solt, Laura A.; Kojetin, Douglas J.; Burris, Thomas P.

2012-01-01

Activation of p53 function leading to cell-cycle arrest and/or apoptosis is a promising strategy for development of anti-cancer therapeutic agents. Here, we describe a novel mechanism for stabilization of p53 protein expression via activation of the orphan nuclear receptor, RORα. We demonstrate that treatment of cancer cells with a newly described synthetic ROR agonist, SR1078, leads to p53 stabilization and induction of apoptosis. These data suggest that synthetic ROR agonists may hold utility in the treatment of cancer. PMID:22509368

Regulation of p53 stability and apoptosis by a ROR agonist.

PubMed

Wang, Yongjun; Solt, Laura A; Kojetin, Douglas J; Burris, Thomas P

2012-01-01

Activation of p53 function leading to cell-cycle arrest and/or apoptosis is a promising strategy for development of anti-cancer therapeutic agents. Here, we describe a novel mechanism for stabilization of p53 protein expression via activation of the orphan nuclear receptor, RORα. We demonstrate that treatment of cancer cells with a newly described synthetic ROR agonist, SR1078, leads to p53 stabilization and induction of apoptosis. These data suggest that synthetic ROR agonists may hold utility in the treatment of cancer.

Hypercrosslinked phenolic polymers with well developed mesoporous frameworks

DOE PAGES

Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark; ...

2015-02-12

A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

Turning carbon dioxide into fuel.

PubMed

Jiang, Z; Xiao, T; Kuznetsov, V L; Edwards, P P

2010-07-28

Our present dependence on fossil fuels means that, as our demand for energy inevitably increases, so do emissions of greenhouse gases, most notably carbon dioxide (CO2). To avoid the obvious consequences on climate change, the concentration of such greenhouse gases in the atmosphere must be stabilized. But, as populations grow and economies develop, future demands now ensure that energy will be one of the defining issues of this century. This unique set of (coupled) challenges also means that science and engineering have a unique opportunity-and a burgeoning challenge-to apply their understanding to provide sustainable energy solutions. Integrated carbon capture and subsequent sequestration is generally advanced as the most promising option to tackle greenhouse gases in the short to medium term. Here, we provide a brief overview of an alternative mid- to long-term option, namely, the capture and conversion of CO2, to produce sustainable, synthetic hydrocarbon or carbonaceous fuels, most notably for transportation purposes. Basically, the approach centres on the concept of the large-scale re-use of CO2 released by human activity to produce synthetic fuels, and how this challenging approach could assume an important role in tackling the issue of global CO2 emissions. We highlight three possible strategies involving CO2 conversion by physico-chemical approaches: sustainable (or renewable) synthetic methanol, syngas production derived from flue gases from coal-, gas- or oil-fired electric power stations, and photochemical production of synthetic fuels. The use of CO2 to synthesize commodity chemicals is covered elsewhere (Arakawa et al. 2001 Chem. Rev. 101, 953-996); this review is focused on the possibilities for the conversion of CO2 to fuels. Although these three prototypical areas differ in their ultimate applications, the underpinning thermodynamic considerations centre on the conversion-and hence the utilization-of CO2. Here, we hope to illustrate that advances in the science and engineering of materials are critical for these new energy technologies, and specific examples are given for all three examples. With sufficient advances, and institutional and political support, such scientific and technological innovations could help to regulate/stabilize the CO2 levels in the atmosphere and thereby extend the use of fossil-fuel-derived feedstocks.

Programming mRNA decay to modulate synthetic circuit resource allocation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venturelli, Ophelia S.; Tei, Mika; Bauer, Stefan

Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstratesmore » that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.« less

Programming mRNA decay to modulate synthetic circuit resource allocation

DOE PAGES

Venturelli, Ophelia S.; Tei, Mika; Bauer, Stefan; ...

2017-04-26

Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstratesmore » that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.« less

Rapid identification of illegal synthetic adulterants in herbal anti-diabetic medicines using near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Feng, Yanchun; Lei, Deqing; Hu, Changqin

We created a rapid detection procedure for identifying herbal medicines illegally adulterated with synthetic drugs using near infrared spectroscopy. This procedure includes a reverse correlation coefficient method (RCCM) and comparison of characteristic peaks. Moreover, we made improvements to the RCCM based on new strategies for threshold settings. Any tested herbal medicine must meet two criteria to be identified with our procedure as adulterated. First, the correlation coefficient between the tested sample and the reference must be greater than the RCCM threshold. Next, the NIR spectrum of the tested sample must contain the same characteristic peaks as the reference. In this study, four pure synthetic anti-diabetic drugs (i.e., metformin, gliclazide, glibenclamide and glimepiride), 174 batches of laboratory samples and 127 batches of herbal anti-diabetic medicines were used to construct and validate the procedure. The accuracy of this procedure was greater than 80%. Our data suggest that this protocol is a rapid screening tool to identify synthetic drug adulterants in herbal medicines on the market.

Hybrid protein-synthetic polymer nanoparticles for drug delivery.

PubMed

Koseva, Neli S; Rydz, Joanna; Stoyanova, Ekaterina V; Mitova, Violeta A

2015-01-01

Among the most common nanoparticulate systems, the polymeric nanocarriers have a number of key benefits, which give a great choice of delivery platforms. Nevertheless, polymeric nanoparticles possess some limitations that include use of toxic solvents in the production process, polymer degradation, drug leakage outside the diseased tissue, and polymer cytotoxicity. The combination of polymers of biological and synthetic origin is an appealing modern strategy for the production of novel nanocarriers with unprecedented properties. Proteins' interface can play an important role in determining bioactivity and toxicity and gives perspective for future development of the polymer-based nanoparticles. The design of hybrid constructs composed of synthetic polymer and biological molecules such as proteins can be considered as a straightforward tool to integrate a broad spectrum of properties and biofunctions into a single device. This review discusses hybrid protein-synthetic polymer nanoparticles with different structures and levels in complexity and functionality, in view of their applications as drug delivery systems. © 2015 Elsevier Inc. All rights reserved.

Inorganic phosphate deprivation causes tRNA nuclear accumulation via retrograde transport in Saccharomyces cerevisiae.

PubMed

Hurto, Rebecca L; Tong, Amy Hin Yan; Boone, Charles; Hopper, Anita K

2007-06-01

Nuclear export of tRNA is an essential eukaryotic function, yet the one known yeast tRNA nuclear exporter, Los1, is nonessential. Moreover recent studies have shown that tRNAs can move retrograde from the cytosol to the nucleus by an undefined process. Therefore, additional gene products involved in tRNA nucleus-cytosol dynamics have yet to be identified. Synthetic genetic array (SGA) analysis was employed to identify proteins involved in Los1-independent tRNA transport and in regulating tRNA nucleus-cytosol distribution. These studies uncovered synthetic interactions between los1Delta and pho88Delta involved in inorganic phopsphate uptake. Further analysis revealed that inorganic phosphate deprivation causes transient, temperature-dependent nuclear accumulation of mature cytoplasmic tRNA within nuclei via a Mtr10- and retrograde-dependent pathway, providing a novel connection between tRNA subcellular dynamics and phosphate availability.

Inorganic Phosphate Deprivation Causes tRNA Nuclear Accumulation via Retrograde Transport in Saccharomyces cerevisiae

PubMed Central

Hurto, Rebecca L.; Tong, Amy Hin Yan; Boone, Charles; Hopper, Anita K.

2007-01-01

Nuclear export of tRNA is an essential eukaryotic function, yet the one known yeast tRNA nuclear exporter, Los1, is nonessential. Moreover recent studies have shown that tRNAs can move retrograde from the cytosol to the nucleus by an undefined process. Therefore, additional gene products involved in tRNA nucleus–cytosol dynamics have yet to be identified. Synthetic genetic array (SGA) analysis was employed to identify proteins involved in Los1-independent tRNA transport and in regulating tRNA nucleus–cytosol distribution. These studies uncovered synthetic interactions between los1Δ and pho88Δ involved in inorganic phopshate uptake. Further analysis revealed that inorganic phosphate deprivation causes transient, temperature-dependent nuclear accumulation of mature cytoplasmic tRNA within nuclei via a Mtr10- and retrograde-dependent pathway, providing a novel connection between tRNA subcellular dynamics and phosphate availability. PMID:17409072

A Statistical Approach For Modeling Tropical Cyclones. Synthetic Hurricanes Generator Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasqualini, Donatella

This manuscript brie y describes a statistical ap- proach to generate synthetic tropical cyclone tracks to be used in risk evaluations. The Synthetic Hur- ricane Generator (SynHurG) model allows model- ing hurricane risk in the United States supporting decision makers and implementations of adaptation strategies to extreme weather. In the literature there are mainly two approaches to model hurricane hazard for risk prediction: deterministic-statistical approaches, where the storm key physical parameters are calculated using physi- cal complex climate models and the tracks are usually determined statistically from historical data; and sta- tistical approaches, where both variables and tracks are estimatedmore » stochastically using historical records. SynHurG falls in the second category adopting a pure stochastic approach.« less

Programmable genetic circuits for pathway engineering.

PubMed

Hoynes-O'Connor, Allison; Moon, Tae Seok

2015-12-01

Synthetic biology has the potential to provide decisive advances in genetic control of metabolic pathways. However, there are several challenges that synthetic biologists must overcome before this vision becomes a reality. First, a library of diverse and well-characterized sensors, such as metabolite-sensing or condition-sensing promoters, must be constructed. Second, robust programmable circuits that link input conditions with a specific gene regulation response must be developed. Finally, multi-gene targeting strategies must be integrated with metabolically relevant sensors and complex, robust logic. Achievements in each of these areas, which employ the CRISPR/Cas system, in silico modeling, and dynamic sensor-regulators, among other tools, provide a strong basis for future research. Overall, the future for synthetic biology approaches in metabolic engineering holds immense promise. Copyright © 2015 Elsevier Ltd. All rights reserved.

Directed evolution and synthetic biology applications to microbial systems.

PubMed

Bassalo, Marcelo C; Liu, Rongming; Gill, Ryan T

2016-06-01

Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic approaches to construct viral capsid-like spherical nanomaterials.

PubMed

Matsuura, Kazunori

2018-06-06

This feature article describes recent progress in synthetic strategies to construct viral capsid-like spherical nanomaterials using the self-assembly of peptides and/or proteins. By mimicking the self-assembly of spherical viral capsids and clathrin, trigonal peptide conjugates bearing β-sheet-forming peptides, glutathiones, or coiled-coil-forming peptides were developed to construct viral capsid-like particles. β-Annulus peptides from tomato bushy stunt virus self-assembled into viral capsid-like nanocapsules with a size of 30-50 nm, which could encapsulate various guest molecules and be decorated with different molecules on their surface. Rationally designed fusion proteins bearing symmetric assembling units afforded precise viral capsid-like polyhedral assemblies. These synthetic approaches to construct artificial viruses could become useful guidelines to develop novel drug carriers, vaccine platforms, nanotemplates and nanoreactors.

Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014.

PubMed

Rudd, Rose A; Aleshire, Noah; Zibbell, Jon E; Gladden, R Matthew

2016-01-01

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25-44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as "prescription" opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid abuse, dependence, and death, improve treatment capacity for opioid use disorders, and reduce the supply of illicit opioids, particularly heroin and illicit fentanyl.

Assessment of types of synthetic cannabinoids in narcotic cases assessed by the Council of Forensic Medicine between 2011-2015, Ankara, Turkey.

PubMed

Göl, Ersin; Çok, İsmet

2017-11-01

Synthetic cannabinoids mimic the effects of cannabis and are the largest and fastest growing class of newly appearing designer drugs. Reports have revealed that various types of synthetic cannabinoids are mixed with herbal substances. The present study investigated the herbal substance cases involving synthetic cannabinoids in Ankara and nearby cities in Turkey. Data were collected from the reports of synthetic cannabinoids that were analyzed between January 01, 2011 and December 31, 2015 in the Ankara Narcotic Department of the Council of Forensic Medicine at the request of the judicial authorities. In all, 4610 narcotic reports were obtained and reviewed. Among these narcotic reports during the period, 370 reports (8%) were related to synthetic cannabinoids. 28 synthetic cannabinoid compounds could be identified in herbals: 5-F-AB-PINACA, 5-F-AKB-48, 5-F-NNEI, 5-F-PB-22, AB-CHMINACA, AB-FUBINACA, AB-PINACA, ADB-CHMINACA, ADB-FUBINACA, AKB-48, AM-2201, EAM-2201, JWH-018, JWH-022, JWH-031, JWH-122, JWH-201, JWH-210, JWH-250, JWH-251, JWH-307, MAM-2201, NM-2201, PB-22, RCS-4, THJ-2201, UR-144, XLR-11. The amount of herbals was 30.72g, 329.22g, 665.89g, 4844.7g, and 5684.3g in 2011, 2012, 2013, 2014, and 2015, respectively. Generally, herbals contained more than one synthetic cannabinoids. ADB-FUBINACA was the most common synthetic cannabinoid among the herbals determined in this study, which was 3132.43g, excepting multi-synthetic cannabinoid herbals. The amount and diversity of synthetic cannabinoid compounds have increased dramatically between 2011 and 2015. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer

DTIC Science & Technology

2012-02-01

maximally efficacious synthetic cannabinoid that would ensure full activation of the cannabinoid receptors (1,2). We also expanded the spectrum of...of the data failed to demonstrate significance (fig 2A, B and C). We then expanded these experiments to the synthetic cannabinoid CP55,940 (CP55...radiation treatment in various breast cancer cell lines has the capacity to enhance the inhibition of tumor growth. Marijuana and its related

Enzymatic catalysis of the Diels-Alder reaction in the biosynthesis of natural products.

PubMed

Oikawa, Hideaki; Tokiwano, Tetsuo

2004-06-01

Recent studies on enzymes catalyzing the Diels- Alder reaction. often named "Diels-Alderases", clearlydemonstrated the involvement of this synthetically useful reaction in the biosynthesis of natural products.This review covers natural Diels-Alder type cycloadducts. synthetic efforts on the chemical feasibility ofthe biosynthctic Diels - Alder reaction and a brief history of studies on Diels-Alderases. In addition,reaction mechanisms of artificial and natural Diels--Alderases are discussed.

Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for Liver Cancer Therapy

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0162 TITLE: Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for...in HCC cells to compensate energy loss. Compared to normal liver, HCC up-regulates expression of genes involved in FA biosynthesis and down-regulates... energy generation triangle” (glycolysis, oxidative phosphorylation, and FAO) as a translational, effective and safe therapy for HCC. 15. SUBJECT

Non-equilibrium behaviour in coacervate-based protocells under electric-field-induced excitation

NASA Astrophysics Data System (ADS)

Yin, Yudan; Niu, Lin; Zhu, Xiaocui; Zhao, Meiping; Zhang, Zexin; Mann, Stephen; Liang, Dehai

2016-02-01

Although numerous strategies are now available to generate rudimentary forms of synthetic cell-like entities, minimal progress has been made in the sustained excitation of artificial protocells under non-equilibrium conditions. Here we demonstrate that the electric field energization of coacervate microdroplets comprising polylysine and short single strands of DNA generates membrane-free protocells with complex, dynamical behaviours. By confining the droplets within a microfluidic channel and applying a range of electric field strengths, we produce protocells that exhibit repetitive cycles of vacuolarization, dynamical fluctuations in size and shape, chaotic growth and fusion, spontaneous ejection and sequestration of matter, directional capture of solute molecules, and pulsed enhancement of enzyme cascade reactions. Our results highlight new opportunities for the study of non-equilibrium phenomena in synthetic protocells, provide a strategy for inducing complex behaviour in electrostatically assembled soft matter microsystems and illustrate how dynamical properties can be activated and sustained in microcompartmentalized media.

How Well Has Global Ocean Heat Content Variability Been Measured?

NASA Astrophysics Data System (ADS)

Nelson, A.; Weiss, J.; Fox-Kemper, B.; Fabienne, G.

2016-12-01

We introduce a new strategy that uses synthetic observations of an ensemble of model simulations to test the fidelity of an observational strategy, quantifying how well it captures the statistics of variability. We apply this test to the 0-700m global ocean heat content anomaly (OHCA) as observed with in-situ measurements by the Coriolis Dataset for Reanalysis (CORA), using the Community Climate System Model (CCSM) version 3.5. One-year running mean OHCAs for the years 2005 onward are found to faithfully capture the variability. During these years, synthetic observations of the model are strongly correlated at 0.94±0.06 with the actual state of the model. Overall, sub-annual variability and data before 2005 are significantly affected by the variability of the observing system. In contrast, the sometimes-used weighted integral of observations is not a good indicator of OHCA as variability in the observing system contaminates dynamical variability.

Single-stranded DNA and RNA origami.

PubMed

Han, Dongran; Qi, Xiaodong; Myhrvold, Cameron; Wang, Bei; Dai, Mingjie; Jiang, Shuoxing; Bates, Maxwell; Liu, Yan; An, Byoungkwon; Zhang, Fei; Yan, Hao; Yin, Peng

2017-12-15

Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure and a ~6000-nt RNA structure. We demonstrate facile replication of the strand in vitro and in living cells. The work here thus establishes unimolecular folding as a general strategy for constructing complex and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Novel green synthetic strategy to prepare ZnO nanocrystals using rambutan (Nephelium lappaceum L.) peel extract and its antibacterial applications.

PubMed

Yuvakkumar, R; Suresh, J; Nathanael, A Joseph; Sundrarajan, M; Hong, S I

2014-08-01

In the present investigation, we report a sustainable novel green synthetic strategy to synthesis zinc oxide nanocrystals. This is the first report on sustainable biosynthesis of zinc oxide nanocrystals employing Nephelium lappaceum L., peel extract as a natural ligation agent. Green synthesis of zinc oxide nanocrystals was carried out via zinc-ellagate complex formation using rambutan peel wastes. The successful formation of zinc oxide nanocrystals was confirmed employing standard characterisation studies. A possible mechanism for the formation of ZnO nanocrystals with rambutan peel extract was also proposed. The prepared ZnO nanocrystals were coated on the cotton fabric and their antibacterial activity were analyzed. ZnO nanocrystals coated cotton showed good antibacterial activity towards Escherichia coli (E. coli), gram negative bacteria and Staphylococcus aureus (S. aureus), gram positive bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-equilibrium behaviour in coacervate-based protocells under electric-field-induced excitation

PubMed Central

Yin, Yudan; Niu, Lin; Zhu, Xiaocui; Zhao, Meiping; Zhang, Zexin; Mann, Stephen; Liang, Dehai

2016-01-01

Although numerous strategies are now available to generate rudimentary forms of synthetic cell-like entities, minimal progress has been made in the sustained excitation of artificial protocells under non-equilibrium conditions. Here we demonstrate that the electric field energization of coacervate microdroplets comprising polylysine and short single strands of DNA generates membrane-free protocells with complex, dynamical behaviours. By confining the droplets within a microfluidic channel and applying a range of electric field strengths, we produce protocells that exhibit repetitive cycles of vacuolarization, dynamical fluctuations in size and shape, chaotic growth and fusion, spontaneous ejection and sequestration of matter, directional capture of solute molecules, and pulsed enhancement of enzyme cascade reactions. Our results highlight new opportunities for the study of non-equilibrium phenomena in synthetic protocells, provide a strategy for inducing complex behaviour in electrostatically assembled soft matter microsystems and illustrate how dynamical properties can be activated and sustained in microcompartmentalized media. PMID:26876162

AJIPHASE®: A Highly Efficient Synthetic Method for One-Pot Peptide Elongation in the Solution Phase by an Fmoc Strategy.

PubMed

Takahashi, Daisuke; Inomata, Tatsuji; Fukui, Tatsuya

2017-06-26

We previously reported an efficient peptide synthesis method, AJIPHASE®, that comprises repeated reactions and isolations by precipitation. This method utilizes an anchor molecule with long-chain alkyl groups as a protecting group for the C-terminus. To further improve this method, we developed a one-pot synthesis of a peptide sequence wherein the synthetic intermediates were isolated by solvent extraction instead of precipitation. A branched-chain anchor molecule was used in the new process, significantly enhancing the solubility of long peptides and the operational efficiency compared with the previous method, which employed precipitation for isolation and a straight-chain aliphatic group. Another prerequisite for this solvent-extraction-based strategy was the use of thiomalic acid and DBU for Fmoc deprotection, which facilitates the removal of byproducts, such as the fulvene adduct. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances and prospects of Bacillus subtilis cellular factories: From rational design to industrial applications.

PubMed

Gu, Yang; Xu, Xianhao; Wu, Yaokang; Niu, Tengfei; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Liu, Long

2018-05-15

Bacillus subtilis is the most characterized gram-positive bacterium that has significant attributes, such as growing well on cheap carbon sources, possessing clear inherited backgrounds, having mature genetic manipulation methods, and exhibiting robustness in large-scale fermentations. Till date, B. subtilis has been identified as attractive hosts for the production of recombinant proteins and chemicals. By applying various systems and synthetic biology tools, the productivity features of B. subtilis can be thoroughly analyzed and further optimized via metabolic engineering. In the present review, we discussed why B. subtilis is the primary organisms used for metabolic engineering and industrial applications. Additionally, we summarized the recent advances in systems and synthetic biology, engineering strategies for improving cellular performances, and metabolic engineering applications of B. subtilis. In particular, we proposed emerging opportunities and essential strategies to enable the successful development of B. subtilis as microbial cell factories. Copyright © 2018. Published by Elsevier Inc.

Extended fault inversion with random slipmaps: A resolution test for the 2012 Mw 7.6 Nicoya, Costa Rica earthquake from a Popperian inversion strategy.

NASA Astrophysics Data System (ADS)

Ángel López Comino, José; Stich, Daniel; Ferreira, Ana M. G.; Morales Soto, José

2015-04-01

The inversion of seismic data for extended fault slip distributions provides us detailed models of earthquake sources. The validity of the solutions depends on the fit between observed and synthetic seismograms generated with the source model. However, there may exist more than one model that fit the data in a similar way, leading to a multiplicity of solutions. This underdetermined problem has been analyzed and studied by several authors, who agree that inverting for a single best model may become overly dependent on the details of the procedure. We have addressed this resolution problem by using a global search that scans the solutions domain using random slipmaps, applying a Popperian inversion strategy that involves the generation of a representative set of slip distributions. The proposed technique solves the forward problem for a large set of models calculating their corresponding synthetic seismograms. Then, we propose to perform extended fault inversion through falsification, that is, falsify inappropriate trial models that do not reproduce the data within a reasonable level of mismodelling. The remainder of surviving trial models forms our set of coequal solutions. Thereby the ambiguities that might exist can be detected by taking a look at the solutions, allowing for an efficient assessment of the resolution. The solution set may contain only members with similar slip distributions, or else uncover some fundamental ambiguity like, for example, different patterns of main slip patches or different patterns of rupture propagation. For a feasibility study, the proposed resolution test has been evaluated using teleseismic body wave recordings from the September 5th 2012 Nicoya, Costa Rica earthquake. Note that the inversion strategy can be applied to any type of seismic, geodetic or tsunami data for which we can handle the forward problem. A 2D von Karman distribution is used to describe the spectrum of heterogeneity in slipmaps, and we generate possible models by spectral synthesis for random phase, keeping the rake angle, rupture velocity and slip velocity function fixed. The 2012 Nicoya earthquake turns out to be relatively well constrained from 50 teleseismic waveforms. The solution set contains 252 out of 10.000 trial models with normalized L1-fit within 5 percent from the global minimum. The set includes only similar solutions -a single centred slip patch- with minor differences. Uncertainties are related to the details of the slip maximum, including the amount of peak slip (2m to 3.5m), as well as the characteristics of peripheral slip below 1 m. Synthetic tests suggest that slip patterns like Nicoya may be a fortunate case, while it may be more difficult to unambiguously reconstruct more distributed slip from teleseismic data.

Nonlinear dimensionality reduction methods for synthetic biology biobricks' visualization.

PubMed

Yang, Jiaoyun; Wang, Haipeng; Ding, Huitong; An, Ning; Alterovitz, Gil

2017-01-19

Visualizing data by dimensionality reduction is an important strategy in Bioinformatics, which could help to discover hidden data properties and detect data quality issues, e.g. data noise, inappropriately labeled data, etc. As crowdsourcing-based synthetic biology databases face similar data quality issues, we propose to visualize biobricks to tackle them. However, existing dimensionality reduction methods could not be directly applied on biobricks datasets. Hereby, we use normalized edit distance to enhance dimensionality reduction methods, including Isomap and Laplacian Eigenmaps. By extracting biobricks from synthetic biology database Registry of Standard Biological Parts, six combinations of various types of biobricks are tested. The visualization graphs illustrate discriminated biobricks and inappropriately labeled biobricks. Clustering algorithm K-means is adopted to quantify the reduction results. The average clustering accuracy for Isomap and Laplacian Eigenmaps are 0.857 and 0.844, respectively. Besides, Laplacian Eigenmaps is 5 times faster than Isomap, and its visualization graph is more concentrated to discriminate biobricks. By combining normalized edit distance with Isomap and Laplacian Eigenmaps, synthetic biology biobircks are successfully visualized in two dimensional space. Various types of biobricks could be discriminated and inappropriately labeled biobricks could be determined, which could help to assess crowdsourcing-based synthetic biology databases' quality, and make biobricks selection.

Development of a Synthetic Switch to Control Protein Stability in Eukaryotic Cells with Light.

PubMed

Taxis, Christof

2017-01-01

In eukaryotic cells, virtually all regulatory processes are influenced by proteolysis. Thus, synthetic control of protein stability is a powerful approach to influence cellular behavior. To achieve this, selected target proteins are modified with a conditional degradation sequence (degron) that responds to a distinct signal. For development of a synthetic degron, an appropriate sensor domain is fused with a degron such that activity of the degron is under control of the sensor. This chapter describes the development of a light-activated, synthetic degron in the model organism Saccharomyces cerevisiae. This photosensitive degron module is composed of the light-oxygen-voltage (LOV) 2 photoreceptor domain of Arabidopsis thaliana phototropin 1 and a degron derived from murine ornithine decarboxylase (ODC). Excitation of the photoreceptor with blue light induces a conformational change that leads to exposure and activation of the degron. Subsequently, the protein is targeted for degradation by the proteasome. Here, the strategy for degron module development and optimization is described in detail together with experimental aspects, which were pivotal for successful implementation of light-controlled proteolysis. The engineering of the photosensitive degron (psd) module may well serve as a blueprint for future development of sophisticated synthetic switches.

A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments

PubMed Central

Mohni, Kareem N.; Thompson, Petria S.; Luzwick, Jessica W.; Glick, Gloria G.; Pendleton, Christopher S.; Lehmann, Brian D.; Pietenpol, Jennifer A.; Cortez, David

2015-01-01

The DNA damage response kinase ATR may be a useful cancer therapeutic target. ATR inhibition synergizes with loss of ERCC1, ATM, XRCC1 and DNA damaging chemotherapy agents. Clinical trials have begun using ATR inhibitors in combination with cisplatin. Here we report the first synthetic lethality screen with a combination treatment of an ATR inhibitor (ATRi) and cisplatin. Combination treatment with ATRi/cisplatin is synthetically lethal with loss of the TLS polymerase ζ and 53BP1. Other DNA repair pathways including homologous recombination and mismatch repair do not exhibit synthetic lethal interactions with ATRi/cisplatin, even though loss of some of these repair pathways sensitizes cells to cisplatin as a single-agent. We also report that ATRi strongly synergizes with PARP inhibition, even in homologous recombination-proficient backgrounds. Lastly, ATR inhibitors were able to resensitize cisplatin-resistant cell lines to cisplatin. These data provide a comprehensive analysis of DNA repair pathways that exhibit synthetic lethality with ATR inhibitors when combined with cisplatin chemotherapy, and will help guide patient selection strategies as ATR inhibitors progress into the cancer clinic. PMID:25965342

How to Make a Synthetic Multicellular Computer

PubMed Central

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. PMID:24586222

Antimicrobial Peptides in Biomedical Device Manufacturing.

PubMed

Riool, Martijn; de Breij, Anna; Drijfhout, Jan W; Nibbering, Peter H; Zaat, Sebastian A J

2017-01-01

Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints, and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures, and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured/3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe antimicrobial medical devices, reducing complications and associated costs of device infection.

Antimicrobial Peptides in Biomedical Device Manufacturing

NASA Astrophysics Data System (ADS)

Riool, Martijn; de Breij, Anna; Drijfhout, Jan W.; Nibbering, Peter H.; Zaat, Sebastian A. J.

2017-08-01

Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured / 3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe antimicrobial medical devices, reducing complications and associated costs of device infection.

The Fragrant Chemist

ERIC Educational Resources Information Center

Ward, P.

1973-01-01

The chemist plays an important role in perfumery. There are scientific problems involved in relating odour to structure, including analysis of essential oils, quality control, and synthetic chemistry. (DF)

Synthetic biology expands chemical control of microorganisms.

PubMed

Ford, Tyler J; Silver, Pamela A

2015-10-01

The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabolic coordination among multiple cells or organisms. Herein, we discuss how synthetic biology alters microorganisms' responses to chemical stimuli resulting in the development of microbes as toxicity sensors, disease treatments, and chemical factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yongxin; University of the Chinese Academy of Science, Beijing 100049; Liu, Dan, E-mail: liudan2007@ciac.ac.cn

Trivalent metal-based MIL-53 (Al{sup 3+}, Cr{sup 3+}, Fe{sup 3+}, In{sup 3+}) compounds are interesting metal–organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ{sub 2}-OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}), typically, focusing on the synthetic strategies and potentialmore » applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted. - Graphical abstract: The recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}) on their synthetic strategies, properties and potential applications was reviewed. - Highlights: • Structure features of bivalent metal-based MIL-53 analogues are illustrated. • Important properties and application are presented. • Host–guest interactions are main impetus for liquid-phase separation. • Promising directions of bivalent metal-based MIL-53 analogues are highlighted.« less

Synthetic biology: applying biological circuits beyond novel therapies.

PubMed

Dobrin, Anton; Saxena, Pratik; Fussenegger, Martin

2016-04-18

Synthetic biology, an engineering, circuit-driven approach to biology, has developed whole new classes of therapeutics. Unfortunately, these advances have thus far been undercapitalized upon by basic researchers. As discussed herein, using synthetic circuits, one can undertake exhaustive investigations of the endogenous circuitry found in nature, develop novel detectors and better temporally and spatially controlled inducers. One could detect changes in DNA, RNA, protein or even transient signaling events, in cell-based systems, in live mice, and in humans. Synthetic biology has also developed inducible systems that can be induced chemically, optically or using radio waves. This induction has been re-wired to lead to changes in gene expression, RNA stability and splicing, protein stability and splicing, and signaling via endogenous pathways. Beyond simple detectors and inducible systems, one can combine these modalities and develop novel signal integration circuits that can react to a very precise pre-programmed set of conditions or even to multiple sets of precise conditions. In this review, we highlight some tools that were developed in which these circuits were combined such that the detection of a particular event automatically triggered a specific output. Furthermore, using novel circuit-design strategies, circuits have been developed that can integrate multiple inputs together in Boolean logic gates composed of up to 6 inputs. We highlight the tools available and what has been developed thus far, and highlight how some clinical tools can be very useful in basic science. Most of the systems that are presented can be integrated together; and the possibilities far exceed the number of currently developed strategies.

Rooting and acclimatization of micropropagated marubakaido apple rootstock using Adesmia latifolia rhizobia.

PubMed

Muniz, Aleksander Westphal; de Sá, Enilson Luiz; Dalagnol, Gilberto Luíz; Filho, João Américo

2013-01-01

In vitro rooting and the acclimatization of micropropagated rootstocks of apple trees is essential for plant development in the field. The aim of this work was to assess the use of rhizobia of Adesmia latifolia to promote rooting and acclimatization in micropropagated Marubakaido apple rootstock. An experiment involving in vitro rooting and acclimatization was performed with four strains of rhizobium and two controls, one with and the other without the addition of synthetic indoleacetic acid. The inoculated treatments involved the use of sterile inoculum and inoculum containing live rhizobia. The most significant effects on the rooting rate, primary-root length, number of roots, root length, fresh-shoot biomass, and fresh-root biomass were obtained by inoculation with strain EEL16010B and with synthetic indole acetic acid. However, there was no difference in the growth of apple explants in the acclimatization experiments. Strain EEL16010B can be used to induce in vitro rooting of the Marubakaido rootstock and can replace the use of synthetic indoleacetic acid in the rooting of this cultivar.

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus‐like particle

PubMed Central

Tekewe, Alemu; Connors, Natalie K.; Middelberg, Anton P. J.

2016-01-01

Abstract Virus‐like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co‐expression of unmodified VP1 and modular VP1‐RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. PMID:27222486

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus-like particle.

PubMed

Tekewe, Alemu; Connors, Natalie K; Middelberg, Anton P J; Lua, Linda H L

2016-08-01

Virus-like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co-expression of unmodified VP1 and modular VP1-RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. © 2016 The Protein Society.

Spirolactones: Recent Advances in Natural Products, Bioactive Compounds and Synthetic Strategies.

PubMed

Quintavalla, Arianna

2018-01-01

The spirocyclic compounds have always aroused a great interest because this motif is present as structural core in a number of natural products and bioactive compounds. In particular, the spirolactone moiety has been recognized in a wide array of natural and non-natural scaffolds showing a variety of useful pharmacological properties. Extensive literature search using SciFinder (Databases: CA Plus, CAS Registry, CAS React, Chemlist, Chemcat and Medline) and Web of Science (Database: Web of Science Core Collection) was conducted. Nowadays, many efforts are being devoted to the discovery of new natural products containing the promising spirolactone framework and to the disclosure of the potential bioactivities of these chemical entities. Moreover, the medicinal relevance of many spirolactones makes these scaffolds attractive targets for the design and development of innovative and efficient synthetic strategies, enabling the construction of complex and variably substituted products. This review gives an overview on the recent advances in the spirolactones field, in terms of new compounds isolated from natural sources, recently determined bioactivity profiles and innovative synthetic approaches. The collected data demonstrate the key role played by spirolactones in medicinal chemistry and the great attention still devoted by the scientific community to these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The synthesis of high yield Au nanoplate and optimized optical properties

NASA Astrophysics Data System (ADS)

Ni, Yuan; Kan, Caixia; Xu, Juan; Liu, Yang

2018-02-01

The applications of Au nanoplates based on the tunable plasmon properties and enhanced electromagnetic field at the sharp tip and straight edges, have generated a great deal of interest in recent years, especially in the fields of the bio-chemical sensing and imaging. In this review, we focus on the synthesis of nanoscale platelike structures by multiple synthetic strategies (such as thermal solution method, seed-mediated method, seedless method, and some greener methods), and explore corresponding growth mechanism in different synthetic approaches. Other than to review the fabrication of Au nanoplates, the purification strategies are also discussed in order to support the applications in various fields. Modifying synthetic method to obtain well-defined nanoplates can tuned optical absorption from visible to near-infrared region. Moreover, the Au nanoplate dimers (vertex-to-vertex and edge-by-edge assemblies) can induce more specific plasmon properties and stronger localized field due to coupling of interparticles. Compared with 0D quasi-spherical nanoparticles and 1D nanorods, the 2D nanoplates can be applied as a good surface-enhanced Raman scattering (SERS) substrate because of the sharp corners and straight edges. This review will provide background information for the controllable synthesis of anisotropic nanoparticles and advance the application of coupled nanostructures.

Assessing community pharmacist engagement in a policing partnership strategy to reduce the illicit diversion of pseudoephedrine products.

PubMed

Webster, Julianne L

2013-01-01

The incidence of illicit diversion of pharmaceutical products is a worldwide problem associated with negative health consequences and with other crimes. The illicit diversion of pharmaceuticals containing the active ingredient pseudoephedrine is of concern, primarily due to the role this substance plays in the manufacture of synthetic illicit drugs such as methylamphetamine. There are a range of strategies employed to curb the problem of precursor diversion. Not least is the development of strategies involving front-line health professionals such as community pharmacists to play an important role in reducing the incidence of diversion. This study aimed to examine levels of pharmacist engagement in an intervention expected to decrease diversion of pseudoephedrine products from community pharmacies. The primary objective was to explore levels of community pharmacist engagement with the intervention and to explore their perceptions of intervention effectiveness. A survey instrument was developed to examine six main areas relating to the implementation, operation and outcomes of the intervention, in addition to the roles performed by community pharmacists in two Australian State jurisdictions. The respondent pharmacists were recruited through a combination of email and facsimile communications from the Pharmacy Guild of Australia and through an electronic pharmacy newsletter. Thirty percent of eligible community pharmacies in the study jurisdictions responded to the survey. The results of the survey highlight that in the absence of an alternative strategy to assist community pharmacists to reduce pseudoephedrine diversion, the majority of respondents were satisfied with the effectiveness of the police-pharmacy intervention. It was found that a pharmacist's positive perception of the role police played in the intervention strongly influenced their engagement in the strategy. Identifying the factors that significantly influence pharmacist engagement in this strategy has broader implications for other law enforcement-public health strategies. It is important for policy models to incorporate these significant elements in their design to enhance the implementation, operation and outcomes of prevention-type interventions. Copyright © 2013 Elsevier Inc. All rights reserved.

Changing the facial features of patients with Treacher Collins syndrome: protocol for 3-stage treatment of hard and soft tissue hypoplasia in the upper half of the face.

PubMed

Mitsukawa, Nobuyuki; Saiga, Atsuomi; Satoh, Kaneshige

2014-07-01

Treacher Collins syndrome is a disorder characterized by various congenital soft tissue anomalies involving hypoplasia of the zygoma, maxilla, and mandible. A variety of treatments have been reported to date. These treatments can be classified into 2 major types. The first type involves osteotomy for hard tissue such as the zygoma and mandible. The second type involves plastic surgery using bone grafting in the malar region and soft tissue repair of eyelid deformities. We devised a new treatment to comprehensively correct hard and soft tissue deformities in the upper half of the face of Treacher Collins patients. The aim was to "change facial features and make it difficult to tell that the patients have this disorder." This innovative treatment strategy consists of 3 stages: (1) placement of dermal fat graft from the lower eyelid to the malar subcutaneous area, (2) custom-made synthetic zygomatic bone grafting, and (3) Z-plasty flap transposition from the upper to the lower eyelid and superior repositioning and fixation of the lateral canthal tendon using a Mitek anchor system. This method was used on 4 patients with Treacher Collins syndrome who had moderate to severe hypoplasia of the zygomas and the lower eyelids. Facial features of these patients were markedly improved and very good results were obtained. There were no major complications intraoperatively or postoperatively in any of the patients during the series of treatments. In synthetic bone grafting in the second stage, the implant in some patients was in the way of the infraorbital nerve. Thus, the nerve was detached and then sutured under the microscope. Postoperatively, patients had almost full restoration of sensory nerve torpor within 5 to 6 months. We devised a 3-stage treatment to "change facial features" of patients with hypoplasia of the upper half of the face due to Treacher Collins syndrome. The treatment protocol provided a very effective way to treat deformities of the upper half of the face in patients with Treacher Collins syndrome.

Synthetic octacalcium phosphate-enhanced reparative dentine formation via induction of odontoblast differentiation.

PubMed

Wang, Xiaogu; Suzawa, Tetsuo; Miyauchi, Tomohiko; Zhao, Baohong; Yasuhara, Rika; Anada, Takahisa; Nakamura, Masanori; Suzuki, Osamu; Kamijo, Ryutaro

2015-11-01

Synthetic octacalcium phosphate (OCP) has been suggested to be a useful biomaterial for the regeneration of hard tissues, including bone. However, it remains unknown whether OCP induces dentine formation by dental pulp. We investigated biomineralization of dental pulp exposed to synthetic OCP in vitro and in vivo. When dental pulp was exposed directly to OCP, rapid formation of reparative dentine (RD) was induced and expression of dentine sialoprotein synthesis was observed in dental pulp adjacent to newly synthesized RD. OCP inhibited the proliferation of rat pulp cells and also promoted their odontoblastic differentiation in vitro, as alkaline phosphatase activity, mineralization of pulp cells and the expression level of dentine sialophosphoprotein were enhanced. Direct contact between OCP and pulp cells is required for OCP to exhibit its effects in vitro. The expression level of Runx2, a transcription factor whose downregulation is closely related to odontoblast differentiation, was downregulated in pulp cells cultured with OCP. Structural changes of OCP during culture were determined by Fourier transform infrared spectroscopy. OCP tended to be converted to carbonate hydroxyapatite after incubation with or without pulp cells, which may be analogous to biological apatite crystals. Taken together, our data suggest that synthetic OCP supports RD formation by dental pulp and downregulation of Runx2 may be involved in that stimulatory activity. Furthermore, OCP-apatite conversion is involved in this stimulatory capacity of OCP. Copyright © 2013 John Wiley & Sons, Ltd.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

PubMed

Gossec, L; Smolen, J S; Ramiro, S; de Wit, M; Cutolo, M; Dougados, M; Emery, P; Landewé, R; Oliver, S; Aletaha, D; Betteridge, N; Braun, J; Burmester, G; Cañete, J D; Damjanov, N; FitzGerald, O; Haglund, E; Helliwell, P; Kvien, T K; Lories, R; Luger, T; Maccarone, M; Marzo-Ortega, H; McGonagle, D; McInnes, I B; Olivieri, I; Pavelka, K; Schett, G; Sieper, J; van den Bosch, F; Veale, D J; Wollenhaupt, J; Zink, A; van der Heijde, D

2016-03-01

Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Prion Concept and Synthetic Prions.

PubMed

Legname, Giuseppe; Moda, Fabio

2017-01-01

Transmissible spongiform encephalopathies or prion diseases are a group of fatal neurodegenerative diseases caused by unconventional infectious agents, known as prions (PrP Sc ). Prions derive from a conformational conversion of the normally folded prion protein (PrP C ), which acquires pathological and infectious features. Moreover, PrP Sc is able to transmit the pathological conformation to PrP C through a mechanism that is still not well understood. The generation of synthetic prions, which behave like natural prions, is of fundamental importance to study the process of PrP C conversion and to assess the efficacy of therapeutic strategies to interfere with this process. Moreover, the ability of synthetic prions to induce pathology in animals confirms that the pathological properties of the prion strains are all enciphered in abnormal conformations, characterizing these infectious agents. © 2017 Elsevier Inc. All rights reserved.

Protein-Polymer Conjugates: Synthetic Approaches by Controlled Radical Polymerizations & Interesting Applications

PubMed Central

Grover, Gregory N.; Maynard, Heather D.

2011-01-01

Protein-polymer conjugates are of interest to researchers in diverse fields. Attachment of polymers to proteins results in improved pharmacokinetics, which is important in medicine. From an engineering standpoint, conjugates are exciting because they exhibit properties of both the biomolecules and synthetic polymers. This allows the activity of the protein to be altered or tuned, a key aspect in therapeutic design, anchoring conjugates to surfaces, and utilizing these materials for supramolecular self-assembly. Thus, there is broad interest in straightforward synthetic methods to make protein-polymer conjugates. Controlled radical polymerization (CRP) techniques have emerged as excellent strategies to make conjugates because the resulting polymers have narrow molecular weight distributions, targeted molecular weights, and attach to specific sites on proteins. Herein, recent advances in the synthesis and application of protein-polymer conjugates by CRP are highlighted. PMID:21071260

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

Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

PubMed Central

Bayer, Travis S; Hoff, Kevin G; Beisel, Chase L; Lee, Jack J; Smolke, Christina D

2009-01-01

Background Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities. PMID:19118500

SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes

PubMed Central

Shen, Yue; Stracquadanio, Giovanni; Wang, Yun; Yang, Kun; Mitchell, Leslie A.; Xue, Yaxin; Cai, Yizhi; Chen, Tai; Dymond, Jessica S.; Kang, Kang; Gong, Jianhui; Zeng, Xiaofan; Zhang, Yongfen; Li, Yingrui; Feng, Qiang; Xu, Xun; Wang, Jun; Wang, Jian; Yang, Huanming; Boeke, Jef D.; Bader, Joel S.

2016-01-01

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes. PMID:26566658

Datalink in air traffic management: Human factors issues in communications.

PubMed

Stedmon, Alex W; Sharples, Sarah; Littlewood, Robert; Cox, Gemma; Patel, Harshada; Wilson, John R

2007-07-01

This paper examines issues underpinning the potential move in aviation away from real speech radiotelephony (R/T) communications towards datalink communications involving text and synthetic speech communications. Using a novel air traffic control (ATC) task, two experiments are reported. Experiment 1 compared the use of speech and text while Experiment 2 compared the use of real and synthetic speech communications. Results indicated that generally there were no significant differences between speech and text communications and that either type could be used without any main effects on performance. However, a number of specific differences were observed across the different phases of the scenarios indicating that workload levels may be more varied when speech communications are used. Experiment 2 illustrated that participants placed a greater level of trust in real speech than synthetic speech, and trusted true communications more than false communications (regardless of whether they were real or synthetic voices). The findings are considered in terms of datalink initiatives for future air traffic management, the importance placed on real speech R/T communications, and the need to develop more natural synthetic speech in this application area.

Antifungal and Antiaflatoxigenic Methylenedioxy-Containing Compounds and Piperine-Like Synthetic Compounds

PubMed Central

Moon, Young-Sun; Choi, Won-Sik; Park, Eun-Sil; Bae, In Kyung; Choi, Sung-Deuk; Paek, Ockjin; Kim, Sheen-Hee; Chun, Hyang Sook; Lee, Sung-Eun

2016-01-01

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure–activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 μg/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 μg/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes. PMID:27537912

Strategies for the synthesis of the novel antitumor agent peloruside A

PubMed Central

Williams, David R; Nag, Partha P; Zorn, Nicolas

2009-01-01

The microtubule-stabilizing agent (+)-peloruside A has emerged as a potential therapeutic agent for the treatment of cancer. Two total syntheses have been published and these reports have stimulated additional studies to advance the methodology and strategies for accessing this molecular architecture. This review details the biological data, modeling and conformation analyses, and synthetic studies toward the synthesis of (+)-peloruside A, that were reported prior to December 2007. PMID:18283613

Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid.

PubMed

Toh, Seok-Ming; Xiong, Liqun; Arias, Cesar A; Villegas, Maria V; Lolans, Karen; Quinn, John; Mankin, Alexander S

2007-06-01

Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram-positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resistance in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is determined by the presence of the cfr gene whose product, Cfr methyltransferase, modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit. The molecular model of the linezolid-ribosome complex reveals localization of A2503 within the drug binding site. The natural function of cfr likely involves protection against natural antibiotics whose site of action overlaps that of linezolid. In the chromosome of the clinical strain, cfr is linked to ermB, a gene responsible for dimethylation of A2058 in 23S rRNA. Coexpression of these two genes confers resistance to all the clinically relevant antibiotics that target the large ribosomal subunit. The association of the ermB/cfr operon with transposon and plasmid genetic elements indicates its possible mobile nature. This is the first example of clinical resistance to the synthetic drug linezolid which involves a natural resistance gene with the capability of disseminating among Gram-positive pathogenic strains.

Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications. Nuclear Science Series: Nuclear Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

1982-09-01

Carbon 11, Fluorine 18, and Nitrogen 13-labeled radiotracers are reviewed from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. The reactions used, the principles used to adapt these reactions to labeling with short-lived radionuclides, and the concepts of chemical reactivity form the framework upon which synthetic strategies for short-lived radiotracers are developed. Potentially new routes are suggested which may be applied to problems in labeling organic molecules. (ACR)

Late-stage divergent synthesis and antifouling activity of geraniol-butenolide hybrid molecules.

PubMed

Takamura, Hiroyoshi; Ohashi, Takumi; Kikuchi, Takahiro; Endo, Noriyuki; Fukuda, Yuji; Kadota, Isao

2017-07-05

Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC 50 values of 0.30-1.31 μg mL -1 . These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity.

The first nanocar race

NASA Astrophysics Data System (ADS)

Rapenne, Gwénaël; Joachim, Christian

2017-06-01

The first race involving molecular 'cars' stimulated technical advances in scanning tunnelling microscopy and provided insights in surface science and synthetic chemistry — it also attracted wide interest from the public.

Associations of Posttraumatic Stress Disorder Symptoms With Marijuana and Synthetic Cannabis Use Among Young Adult U.S. Veterans: A Pilot Investigation

PubMed Central

Grant, Sean; Pedersen, Eric R.; Neighbors, Clayton

2016-01-01

Objective: This study involves a pilot investigation of associations between marijuana and synthetic cannabis use with PTSD symptoms among a young adult sample of U.S. veterans. Method: In a cross-sectional survey of a community sample of 790 young adult U.S. veterans, we assessed demographics, combat severity, marijuana and synthetic cannabis use, expectancies of marijuana use, and PTSD symptoms. Results: Overall, 61.8% and 20.4% of our sample reported lifetime and past-month marijuana use, whereas 17.0% and 3.4% reported lifetime and past-month synthetic cannabis use. Veterans screening positive for PTSD were more likely to use marijuana and synthetic cannabis in their lifetime and in the past month. Positive PTSD screens, as well as greater expectancies that marijuana leads to relaxation and tension reduction, were associated with past-month marijuana use in logistic regression analyses. Expectancies moderated the relationship between PTSD and marijuana use, such that those with positive PTSD screens reporting higher levels of relaxation and tension-reduction expectancies were most likely to report past-month marijuana use. Conclusions: Our findings suggest an association of PTSD symptoms with marijuana and synthetic cannabis use among young adult U.S. veterans. Future research should further investigate the link between PTSD and marijuana use, as well as the rates and consequences of synthetic cannabis use among veterans. PMID:27172584

Synthetic cannabinoid and marijuana exposures reported to poison centers.

PubMed

Forrester, M B; Kleinschmidt, K; Schwarz, E; Young, A

2012-10-01

Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38-2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87-1.51), 40.2% and 56.6% age ≤ 19 years (RR 0.71, 95% CI 0.52-0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02-1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28-1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03-2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.

SynBioSS designer: a web-based tool for the automated generation of kinetic models for synthetic biological constructs

PubMed Central

Weeding, Emma; Houle, Jason

2010-01-01

Modeling tools can play an important role in synthetic biology the same way modeling helps in other engineering disciplines: simulations can quickly probe mechanisms and provide a clear picture of how different components influence the behavior of the whole. We present a brief review of available tools and present SynBioSS Designer. The Synthetic Biology Software Suite (SynBioSS) is used for the generation, storing, retrieval and quantitative simulation of synthetic biological networks. SynBioSS consists of three distinct components: the Desktop Simulator, the Wiki, and the Designer. SynBioSS Designer takes as input molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosome binding sites, etc.), and automatically generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. Effectively, Designer uses DNA sequences as input and generates networks of biomolecular reactions as output. In this paper we describe how Designer uses universal principles of molecular biology to generate models of any arbitrary synthetic biological system. These models are useful as they explain biological phenotypic complexity in mechanistic terms. In turn, such mechanistic explanations can assist in designing synthetic biological systems. We also discuss, giving practical guidance to users, how Designer interfaces with the Registry of Standard Biological Parts, the de facto compendium of parts used in synthetic biology applications. PMID:20639523

Associations of Posttraumatic Stress Disorder Symptoms With Marijuana and Synthetic Cannabis Use Among Young Adult U.S. Veterans: A Pilot Investigation.

PubMed

Grant, Sean; Pedersen, Eric R; Neighbors, Clayton

2016-05-01

This study involves a pilot investigation of associations between marijuana and synthetic cannabis use with PTSD symptoms among a young adult sample of U.S. veterans. In a cross-sectional survey of a community sample of 790 young adult U.S. veterans, we assessed demographics, combat severity, marijuana and synthetic cannabis use, expectancies of marijuana use, and PTSD symptoms. Overall, 61.8% and 20.4% of our sample reported lifetime and past-month marijuana use, whereas 17.0% and 3.4% reported lifetime and past-month synthetic cannabis use. Veterans screening positive for PTSD were more likely to use marijuana and synthetic cannabis in their lifetime and in the past month. Positive PTSD screens, as well as greater expectancies that marijuana leads to relaxation and tension reduction, were associated with past-month marijuana use in logistic regression analyses. Expectancies moderated the relationship between PTSD and marijuana use, such that those with positive PTSD screens reporting higher levels of relaxation and tension-reduction expectancies were most likely to report past-month marijuana use. Our findings suggest an association of PTSD symptoms with marijuana and synthetic cannabis use among young adult U.S. veterans. Future research should further investigate the link between PTSD and marijuana use, as well as the rates and consequences of synthetic cannabis use among veterans.

Tangential synthetic jets for separation control

NASA Astrophysics Data System (ADS)

Esmaeili Monir, H.; Tadjfar, M.; Bakhtian, A.

2014-02-01

A numerical study of separation control has been made to investigate aerodynamic characteristics of a NACA23012 airfoil with a tangential synthetic jet. Simulations are carried out at the chord Reynolds number of Re=2.19×106. The present approach relies on solving the Unsteady Reynolds-Averaged Navier-Stokes (URANS) equations. The turbulence model used in the present computation is the Spalart-Allmaras one-equation model. All computations are performed with a finite volume based code. Stall characteristics are significantly improved by controlling the formation of separation vortices in the flow. We placed the synthetic jet at the 12% chord, xj=0.12c, where we expected the separation to occur. Two distinct jet oscillating frequencies: Fj+=0.159 and Fj+=1 were considered. We studied the effect of blowing ratio, Vj/U∞, where it was varied from 0 to 5. The inclined angle of the synthetic jet was varied from αj=0° up to αj=83°. For the non-zero inclined angles, the local maximum in the aerodynamic performance, Cl/Cd, of 6.89 was found for the inclined angle of about 43°. In the present method, by means of creating a dent on the airfoil, linear momentum is transferred to the flow system in tangential direction to the airfoil surface. Thus the absolute maximum of 11.19 was found for the tangential synthetic jet at the inclined angle of the jet of 0°. The mechanisms involved for a tangential jet appear to behave linearly, as by multiplying the activation frequency of the jet by a factor produces the same multiplication factor in the resulting frequency in the flow. However, the mechanisms involved in the non-zero inclined angle cases behave nonlinearly when the activation frequency is multiplied.

Demonstrating Interactions of Transcription Factors with DNA by Electrophoretic Mobility Shift Assay.

PubMed

Yousaf, Nasim; Gould, David

2017-01-01

Confirming the binding of a transcription factor with a particular DNA sequence may be important in characterizing interactions with a synthetic promoter. Electrophoretic mobility shift assay is a powerful approach to demonstrate the specific DNA sequence that is bound by a transcription factor and also to confirm the specific transcription factor involved in the interaction. In this chapter we describe a method we have successfully used to demonstrate interactions of endogenous transcription factors with sequences derived from endogenous and synthetic promoters.

Discovery of a diazo-forming enzyme in cremeomycin biosynthesis.

PubMed

Waldman, Abraham J; Balskus, Emily P

2018-05-17

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology and enable genome-based discovery of new diazo-containing metabolites.

Post-synthetic transformation of a Zn(ii) polyhedral coordination network into a new supramolecular isomer of HKUST-1.

PubMed

Chen, Yao; Wojtas, Lukasz; Ma, Shengqian; Zaworotko, Michael J; Zhang, Zhenjie

2017-08-03

A Zn-based porphyrin containing metal-organic material (porphMOM-1) was transformed into a novel Cu-based porphyrin-encapsulating metal-organic material (porph@HKUST-1-β) via a one-pot post-synthetic modification (PSM) process involving both metal ion exchange and linker installation of trimesic acid. HKUST-1-β is the first example of yao topology and is to our knowledge the first supramolecular isomer of the archetypal coordination network HKUST-1.

Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

NASA Technical Reports Server (NTRS)

Li, X.; Eastman, E. M.; Schwartz, R. J.; Draghia-Akli, R.

1999-01-01

Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

Synthetic Development of Low Dimensional Materials

DOE PAGES

Men, Long; White, Miles A.; Andaraarachchi, Himashi; ...

2016-11-02

Here, in this invited paper, we highlight some of our most recent work on the synthesis of low dimensional nanomaterials. Current graduate students and members of our group present four specific case systems: Nowotny-Juza phases, nickel phosphides, germanium-based core/shells, and organolead mixed-halide perovskites. Each system is accompanied by commentary from the student involved, which explains our motivation behind our work, as well as by a protocol detailing the key experimental considerations involved in their synthesis. We trust these and similar efforts by others and us will help further advance our understanding of the broader field of synthetic nanomaterials chemistry, while,more » at the same time, highlighting how important this area is to the development of new materials for technologically relevant applications.« less

Adhesion of Blood Clots Can Be Enhanced When Copolymerized with a Macromer That Is Crosslinked by Coagulation Factor XIIIa.

PubMed

Chan, Karen Y T; Zhao, Chunyi; Siren, Erika M J; Chan, Jeanne C Y; Boschman, Jeffrey; Kastrup, Christian J

2016-06-13

The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.

Hierarchy concepts: classification and preparation strategies for zeolite containing materials with hierarchical porosity.

PubMed

Schwieger, Wilhelm; Machoke, Albert Gonche; Weissenberger, Tobias; Inayat, Amer; Selvam, Thangaraj; Klumpp, Michael; Inayat, Alexandra

2016-06-13

'Hierarchy' is a property which can be attributed to a manifold of different immaterial systems, such as ideas, items and organisations or material ones like biological systems within living organisms or artificial, man-made constructions. The property 'hierarchy' is mainly characterised by a certain ordering of individual elements relative to each other, often in combination with a certain degree of branching. Especially mass-flow related systems in the natural environment feature special hierarchically branched patterns. This review is a survey into the world of hierarchical systems with special focus on hierarchically porous zeolite materials. A classification of hierarchical porosity is proposed based on the flow distribution pattern within the respective pore systems. In addition, this review might serve as a toolbox providing several synthetic and post-synthetic strategies to prepare zeolitic or zeolite containing material with tailored hierarchical porosity. Very often, such strategies with their underlying principles were developed for improving the performance of the final materials in different technical applications like adsorptive or catalytic processes. In the present review, besides on the hierarchically porous all-zeolite material, special focus is laid on the preparation of zeolitic composite materials with hierarchical porosity capable to face the demands of industrial application.

Strategies for cloning and manipulating natural and synthetic chromosomes.

PubMed

Karas, Bogumil J; Suzuki, Yo; Weyman, Philip D

2015-02-01

Advances in synthetic biology methods to assemble and edit DNA are enabling genome engineering at a previously impracticable scale and scope. The synthesis of the Mycoplasma mycoides genome followed by its transplantation to convert a related cell into M. mycoides has transformed strain engineering. This approach exemplifies the combination of newly emerging chromosome-scale genome editing strategies that can be defined in three main steps: (1) chromosome acquisition into a microbial engineering platform, (2) alteration and improvement of the acquired chromosome, and (3) installation of the modified chromosome into the original or alternative organism. In this review, we outline recent progress in methods for acquiring chromosomes and chromosome-scale DNA molecules in the workhorse organisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. We present overviews of important genetic strategies and tools for each of the three organisms, point out their respective strengths and weaknesses, and highlight how the host systems can be used in combination to facilitate chromosome assembly or engineering. Finally, we highlight efforts for the installation of the cloned/altered chromosomes or fragments into the target organism and present remaining challenges in expanding this powerful experimental approach to a wider range of target organisms.

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.

From Never Born Proteins to Minimal Living Cells: two projects in synthetic biology.

PubMed

Luisi, Pier Luigi; Chiarabelli, Cristiano; Stano, Pasquale

2006-12-01

The Never Born Proteins (NBPs) and the Minimal Cell projects are two currently developed research lines belonging to the field of synthetic biology. The first deals with the investigation of structural and functional properties of de novo proteins with random sequences, selected and isolated using phage display methods. The minimal cell is the simplest cellular construct which displays living properties, such as self-maintenance, self-reproduction and evolvability. The semi-synthetic approach to minimal cells involves the use of extant genes and proteins in order to build a supramolecular construct based on lipid vesicles. Results and outlooks on these two research lines are shortly discussed, mainly focusing on their relevance to the origin of life studies.

Combining living anionic polymerization with branching reactions in an iterative fashion to design branched polymers.

PubMed

Higashihara, Tomoya; Sugiyama, Kenji; Yoo, Hee-Soo; Hayashi, Mayumi; Hirao, Akira

2010-06-16

This paper reviews the precise synthesis of many-armed and multi-compositional star-branched polymers, exact graft (co)polymers, and structurally well-defined dendrimer-like star-branched polymers, which are synthetically difficult, by a commonly-featured iterative methodology combining living anionic polymerization with branched reactions to design branched polymers. The methodology basically involves only two synthetic steps; (a) preparation of a polymeric building block corresponding to each branched polymer and (b) connection of the resulting building unit to another unit. The synthetic steps were repeated in a stepwise fashion several times to successively synthesize a series of well-defined target branched polymers. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination.

PubMed

Vashee, Sanjay; Stockwell, Timothy B; Alperovich, Nina; Denisova, Evgeniya A; Gibson, Daniel G; Cady, Kyle C; Miller, Kristofer; Kannan, Krishna; Malouli, Daniel; Crawford, Lindsey B; Voorhies, Alexander A; Bruening, Eric; Caposio, Patrizia; Früh, Klaus

2017-01-01

Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae . Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae . Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.

Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination

PubMed Central

Vashee, Sanjay; Stockwell, Timothy B.; Alperovich, Nina; Denisova, Evgeniya A.; Gibson, Daniel G.; Cady, Kyle C.; Miller, Kristofer; Kannan, Krishna; Malouli, Daniel; Crawford, Lindsey B.; Voorhies, Alexander A.; Bruening, Eric; Caposio, Patrizia

2017-01-01

ABSTRACT Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes. PMID:28989973

Synthetic nat- or ent-steroids in as few as five chemical steps from epichlorohydrin

NASA Astrophysics Data System (ADS)

Kim, Wan Shin; Du, Kang; Eastman, Alan; Hughes, Russell P.; Micalizio, Glenn C.

2018-01-01

Today, more than 100 Food and Drug Administration-approved steroidal agents are prescribed daily for indications including heart failure, inflammation, pain and cancer. While triumphs in organic chemistry have enabled the establishment and sustained growth of the steroid pharmaceutical industry, the production of highly functionalized synthetic steroids of varying substitution and stereochemistry remains challenging, despite the numerous reports of elegant strategies for their de novo synthesis. Here, we describe an advance in chemical synthesis that has established an enantiospecific means to access novel steroids with unprecedented facility and flexibility through the sequential use of two powerful ring-forming reactions: a modern metallacycle-mediated annulative cross-coupling and a new acid-catalysed vinylcyclopropane rearrangement cascade. In addition to accessing synthetic steroids of either enantiomeric series, these steroidal products have been selectively functionalized within each of the four carbocyclic rings, a synthetic ent-steroid has been prepared on a multigram scale, the enantiomer of a selective oestrogen has been synthesized, and a novel ent-steroid with growth inhibitory properties in three cancer cell lines has been discovered.

Children's weighting strategies for word-final stop voicing are not explained by auditory sensitivities.

PubMed

Nittrouer, Susan; Lowenstein, Joanna H

2007-02-01

It has been reported that children and adults weight differently the various acoustic properties of the speech signal that support phonetic decisions. This finding is generally attributed to the fact that the amount of weight assigned to various acoustic properties by adults varies across languages, and that children have not yet discovered the mature weighting strategies of their own native languages. But an alternative explanation exists: Perhaps children's auditory sensitivities for some acoustic properties of speech are poorer than those of adults, and children cannot categorize stimuli based on properties to which they are not keenly sensitive. The purpose of the current study was to test that hypothesis. Edited-natural, synthetic-formant, and sine wave stimuli were all used, and all were modeled after words with voiced and voiceless final stops. Adults and children (5 and 7 years of age) listened to pairs of stimuli in 5 conditions: 2 involving a temporal property (1 with speech and 1 with nonspeech stimuli) and 3 involving a spectral property (1 with speech and 2 with nonspeech stimuli). An AX discrimination task was used in which a standard stimulus (A) was compared with all other stimuli (X) equal numbers of times (method of constant stimuli). Adults and children had similar difference thresholds (i.e., 50% point on the discrimination function) for 2 of the 3 sets of nonspeech stimuli (1 temporal and 1 spectral), but children's thresholds were greater for both sets of speech stimuli. Results are interpreted as evidence that children's auditory sensitivities are adequate to support weighting strategies similar to those of adults, and so observed differences between children and adults in speech perception cannot be explained by differences in auditory perception. Furthermore, it is concluded that listeners bring expectations to the listening task about the nature of the signals they are hearing based on their experiences with those signals.

Substance use is a risk factor for violent behavior in male patients with bipolar disorder.

PubMed

Alnıak, İzgi; Erkıran, Murat; Mutlu, Elif

2016-03-15

To determine the factors involved in violent behavior in patients with bipolar disorder (BD) and to investigate the relationship between violence and substance use disorder (SUD). A sample of 100 male inpatients diagnosed with BD type I who were experiencing a current mood episode participated in the study. Violent behavior was defined as physical aggression against others. All patients were evaluated using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Positive and Negative Syndrome Scale-positive subscale (PANSS-p), Barratt Impulsivity Scale-11 (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ) and Overt Aggression Scale (OAS). Lifetime SUD and current use of substances were evaluated. Logistic regression analysis was conducted to predict violent behavior. Current substance use (CSU) rather than lifetime SUD was found to be related to violent behavior in patients with BD, and CSU was associated with a threefold increase in the risk of violence. The rate of lifetime SUD in our sample was 59%, and the rate of CSU was 39%. The most commonly abused substances were cannabis and alcohol, followed by synthetic cannabinoids, in both groups of patients with lifetime SUD and CSU. Individuals abusing any substance were more likely to have a criminal record and history of incarceration than other patients. One of the most significant risk factors for violence was a previous history of violent behavior. The sample was limited to male patients. Data on some participants' recent substance use from standard urine analysis was not obtained. The data on the use of synthetic cannabinoids was obtained from patients and their families owing to the lack of equipment for detecting synthetic cannabinoids using laboratory analysis. CSU appears to be a significant predictive factor in violent behavior in male patients. Further investigation of co-occurrence of violence with CSU and improvement in treatment strategies might reduce or prevent violence in patients with BD. Copyright © 2015 Elsevier B.V. All rights reserved.

A Generic Self-Assembly Process in Microcompartments and Synthetic Protein Nanotubes.

PubMed

Uddin, Ismail; Frank, Stefanie; Warren, Martin J; Pickersgill, Richard W

2018-05-01

Bacterial microcompartments enclose a biochemical pathway and reactive intermediate within a protein envelope formed by the shell proteins. Herein, the orientation of the propanediol-utilization (Pdu) microcompartment shell protein PduA in bacterial microcompartments and in synthetic nanotubes, and the orientation of PduB in synthetic nanotubes are revealed. When produced individually, PduA hexamers and PduB trimers, tessellate to form flat sheets in the crystal, or they can self-assemble to form synthetic protein nanotubes in solution. Modelling the orientation of PduA in the 20 nm nanotube so as to preserve the shape complementarity and key interactions seen in the crystal structure suggests that the concave surface of the PduA hexamer faces out. This orientation is confirmed experimentally in synthetic nanotubes and in the bacterial microcompartment produced in vivo. The PduB nanotubes described here have a larger diameter, 63 nm, with the concave surface of the trimer again facing out. The conserved concave surface out characteristic of these nano-structures reveals a generic assembly process that causes the interface between adjacent subunits to bend in a common direction that optimizes shape complementarity and minimizes steric clashes. This understanding underpins engineering strategies for the biotechnological application of protein nanotubes. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A rapid and low noise switch from RANS to WMLES on curvilinear grids with compressible flow solvers

NASA Astrophysics Data System (ADS)

Deck, Sébastien; Weiss, Pierre-Elie; Renard, Nicolas

2018-06-01

A turbulent inflow for a rapid and low noise switch from RANS to Wall-Modelled LES on curvilinear grids with compressible flow solvers is presented. It can be embedded within the computational domain in practical applications with WMLES grids around three-dimensional geometries in a flexible zonal hybrid RANS/LES modelling context. It relies on a physics-motivated combination of Zonal Detached Eddy Simulation (ZDES) as the WMLES technique together with a Dynamic Forcing method processing the fluctuations caused by a Zonal Immersed Boundary Condition describing roughness elements. The performance in generating a physically-sound turbulent flow field with the proper mean skin friction and turbulent profiles after a short relaxation length is equivalent to more common inflow methods thanks to the generation of large-scale streamwise vorticity by the roughness elements. Comparisons in a low Mach-number zero-pressure-gradient flat-plate turbulent boundary layer up to Reθ = 6 100 reveal that the pressure field is dominated by the spurious noise caused by the synthetic turbulence methods (Synthetic Eddy Method and White Noise injection), contrary to the new low-noise approach which may be used to obtain the low-frequency component of wall pressure and reproduce its intermittent nature. The robustness of the method is tested in the flow around a three-element airfoil with WMLES in the upper boundary layer near the trailing edge of the main element. In spite of the very short relaxation distance allowed, self-sustainable resolved turbulence is generated in the outer layer with significantly less spurious noise than with the approach involving White Noise. The ZDES grid count for this latter test case is more than two orders of magnitude lower than the Wall-Resolved LES requirement and a unique mesh is involved, which is much simpler than some multiple-mesh strategies devised for WMLES or turbulent inflow.

Triptycene: A Nucleic Acid Three-Way Junction Binder Scaffold

NASA Astrophysics Data System (ADS)

Yoon, Ina

Nucleic acids play a critical role in many biological processes such as gene regulation and replication. The development of small molecules that modulate nucleic acids with sequence or structure specificity would provide new strategies for regulating disease states at the nucleic acid level. However, this remains challenging mainly because of the nonspecific interactions between nucleic acids and small molecules. Three-way junctions are critical structural elements of nucleic acids. They are present in many important targets such as trinucleotide repeat junctions related to Huntington's disease, a temperature sensor sigma32 in E. coli, Dengue virus, and HIV. Triptycene-derived small molecules have been shown to bind to nucleic acid three-way junctions, resulting from their shape complementary. To develop a better understanding of designing molecules for targeting different junctions, a rapid screening of triptycene-based small molecules is needed. We envisioned that the installation of a linker at C9 position of the bicyclic core would allow for a rapid solid phase diversification. To achieve this aim, we synthesized 9-substituted triptycene scaffolds by using two different synthetic routes. The first synthetic route installed the linker from the amidation reaction between carboxylic acid at C9 position of the triptycene and an amine linker, beta-alanine ethyl ester. This new 9-substituted triptycene scaffold was then attached to a 2-chlorotrityl chloride resin for solid-phase diversification. This enabled a rapid diversification and an easy purification of mono-, di-, and tri-peptide triptycene derivatives. The binding affinities of these compounds were investigated towards a (CAG)˙(CTG) trinucleotide repeat junction. In the modified second synthetic route, we utilized a combined Heck coupling/benzyne Diels-Alder strategy. This improved synthetic strategy reduced the number of steps and total reaction times, increased the overall yield, improved solubilities of intermediates, and provided a new regioisomer that was not observed in the previous synthesis. Through this investigation, we discovered new high-affinity lead compounds towards a d(CAG)·(CTG) trinucleotide repeat junction. In addition, we turned our attention to sigma 32 mRNA, which contains a RNA three-way junction in E. coli. We demonstrated that triptycene-based small molecules can modulate the heat shock response in E. coli..

Improving the performance of solventogenic clostridia by reinforcing the biotin synthetic pathway.

PubMed

Yang, Yunpeng; Lang, Nannan; Yang, Gaohua; Yang, Sheng; Jiang, Weihong; Gu, Yang

2016-05-01

An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of solventogenic clostridia, we revealed that the insufficient biosynthesis of biotin, a pivotal coenzyme for many important biological processes, is a major limiting bottleneck in this anaerobe's performance. To address this problem, we strengthened the biotin synthesis of C. acetobutylicum by overexpressing four relevant genes involved in biotin transport and biosynthesis. This strategy led to faster growth and improved the titer and productivity of acetone, butanol and ethanol (ABE solvents) of C. acetobutylicum in both biotin-containing and biotin-free media. Expressionally modulating these four genes by modifying the ribosome binding site further promoted cellular performance, achieving ABE solvent titer and productivity as high as 21.9g/L and 0.30g/L/h, respectively, in biotin-free medium; these values exceeded those of the wild-type strain by over 30%. More importantly, biotin synthesis reinforcement also conferred improved ability of C. acetobutylicum to use hexose and pentose sugars, further demonstrating the potential of this metabolic-engineering strategy in solventogenic clostridia. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

A Machine-Learning and Filtering Based Data Assimilation Framework for Geologic Carbon Sequestration Monitoring Optimization

NASA Astrophysics Data System (ADS)

Chen, B.; Harp, D. R.; Lin, Y.; Keating, E. H.; Pawar, R.

2017-12-01

Monitoring is a crucial aspect of geologic carbon sequestration (GCS) risk management. It has gained importance as a means to ensure CO2 is safely and permanently stored underground throughout the lifecycle of a GCS project. Three issues are often involved in a monitoring project: (i) where is the optimal location to place the monitoring well(s), (ii) what type of data (pressure, rate and/or CO2 concentration) should be measured, and (iii) What is the optimal frequency to collect the data. In order to address these important issues, a filtering-based data assimilation procedure is developed to perform the monitoring optimization. The optimal monitoring strategy is selected based on the uncertainty reduction of the objective of interest (e.g., cumulative CO2 leak) for all potential monitoring strategies. To reduce the computational cost of the filtering-based data assimilation process, two machine-learning algorithms: Support Vector Regression (SVR) and Multivariate Adaptive Regression Splines (MARS) are used to develop the computationally efficient reduced-order-models (ROMs) from full numerical simulations of CO2 and brine flow. The proposed framework for GCS monitoring optimization is demonstrated with two examples: a simple 3D synthetic case and a real field case named Rock Spring Uplift carbon storage site in Southwestern Wyoming.

Offset-electrode profile acquisition strategy for electrical resistivity tomography

NASA Astrophysics Data System (ADS)

Robbins, Austin R.; Plattner, Alain

2018-04-01

We present an electrode layout strategy that allows electrical resistivity profiles to image the third dimension close to the profile plane. This "offset-electrode profile" approach involves laterally displacing electrodes away from the profile line in an alternating fashion and then inverting the resulting data using three-dimensional electrical resistivity tomography software. In our synthetic and field surveys, the offset-electrode method succeeds in revealing three-dimensional structures in the vicinity of the profile plane, which we could not achieve using three-dimensional inversions of linear profiles. We confirm and explain the limits of linear electrode profiles through a discussion of the three-dimensional sensitivity patterns: For a homogeneous starting model together with a linear electrode layout, all sensitivities remain symmetric with respect to the profile plane through each inversion step. This limitation can be overcome with offset-electrode layouts by breaking the symmetry pattern among the sensitivities. Thanks to freely available powerful three-dimensional resistivity tomography software and cheap modern computing power, the requirement for full three-dimensional calculations does not create a significant burden and renders the offset-electrode approach a cost-effective method. By offsetting the electrodes in an alternating pattern, as opposed to laying the profile out in a U-shape, we minimize shortening the profile length.

Engineering bacterial translation initiation - Do we have all the tools we need?

PubMed

Vigar, Justin R J; Wieden, Hans-Joachim

2017-11-01

Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Solid-phase organic synthesis of difluoroalkyl entities using a novel fluorinating cleavage strategy: part 2. Synthesis of three small gem-difluorinated compound libraries using a dithiane linker.

PubMed

Wiehn, Matthias S; Fürniss, Daniel; Bräse, Stefan

2009-01-01

Three small compound biaryl libraries featuring a novel fluorinating cleavage strategy for preparation of a difluoromethyl group were assembled on solid supports. The average reaction yield per step was up to 96% in a synthetic sequence over five to six steps. Key features were Suzuki coupling reactions, transesterification with potassium cyanide and amidation reaction with trimethyl aluminum on solid supports.

Systems metabolic engineering strategies for the production of amino acids.

PubMed

Ma, Qian; Zhang, Quanwei; Xu, Qingyang; Zhang, Chenglin; Li, Yanjun; Fan, Xiaoguang; Xie, Xixian; Chen, Ning

2017-06-01

Systems metabolic engineering is a multidisciplinary area that integrates systems biology, synthetic biology and evolutionary engineering. It is an efficient approach for strain improvement and process optimization, and has been successfully applied in the microbial production of various chemicals including amino acids. In this review, systems metabolic engineering strategies including pathway-focused approaches, systems biology-based approaches, evolutionary approaches and their applications in two major amino acid producing microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

Are synthetic scaffolds suitable for the development of clinical tissue-engineered tubular organs?

PubMed

Del Gaudio, Costantino; Baiguera, Silvia; Ajalloueian, Fatemeh; Bianco, Alessandra; Macchiarini, Paolo

2014-07-01

Transplantation of tissues and organs is currently the only available treatment for patients with end-stage diseases. However, its feasibility is limited by the chronic shortage of suitable donors, the need for life-long immunosuppression, and by socioeconomical and religious concerns. Recently, tissue engineering has garnered interest as a means to generate cell-seeded three-dimensional scaffolds that could replace diseased organs without requiring immunosuppression. Using a regenerative approach, scaffolds made by synthetic, nonimmunogenic, and biocompatible materials have been developed and successfully clinically implanted. This strategy, based on a viable and ready-to-use bioengineered scaffold, able to promote novel tissue formation, favoring cell adhesion and proliferation, could become a reliable alternative to allotransplatation in the next future. In this article, tissue-engineered synthetic substitutes for tubular organs (such as trachea, esophagus, bile ducts, and bowel) are reviewed, including a discussion on their morphological and functional properties. © 2013 Wiley Periodicals, Inc.

Synthetic polymers enable non-vitreous cellular cryopreservation by reducing ice crystal growth during thawing.

PubMed

Deller, Robert C; Vatish, Manu; Mitchell, Daniel A; Gibson, Matthew I

2014-01-01

The cryopreservation of cells, tissue and organs is fundamental to modern biotechnology, transplantation medicine and chemical biology. The current state-of-the-art method of cryopreservation is the addition of large amounts of organic solvents such as glycerol or dimethyl sulfoxide, to promote vitrification and prevent ice formation. Here we employ a synthetic, biomimetic, polymer, which is capable of slowing the growth of ice crystals in a manner similar to antifreeze (glyco)proteins to enhance the cryopreservation of sheep and human red blood cells. We find that only 0.1 wt% of the polymer is required to attain significant cell recovery post freezing, compared with over 20 wt% required for solvent-based strategies. These results demonstrate that synthetic antifreeze (glyco)protein mimics could have a crucial role in modern regenerative medicine to improve the storage and distribution of biological material for transplantation.

Electrospinning polymer blends for biomimetic scaffolds for ACL tissue engineering

NASA Astrophysics Data System (ADS)

Garcia, Vanessa Lizeth

The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to create tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength of the synthetic polymers when blended. Scanning electron microscopy display bead-free and enzyme biodegradability of the fibers. Raman spectroscopy confirms the presence of the natural and synthetic polymers in the scaffolds while, amino acid analysis present the types of amino acids and their concentrations found in the natural polymers.

A synthetic pathway for the fixation of carbon dioxide in vitro.

PubMed

Schwander, Thomas; Schada von Borzyskowski, Lennart; Burgener, Simon; Cortina, Niña Socorro; Erb, Tobias J

2016-11-18

Carbon dioxide (CO 2 ) is an important carbon feedstock for a future green economy. This requires the development of efficient strategies for its conversion into multicarbon compounds. We describe a synthetic cycle for the continuous fixation of CO 2 in vitro. The crotonyl-coenzyme A (CoA)/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle is a reaction network of 17 enzymes that converts CO 2 into organic molecules at a rate of 5 nanomoles of CO 2 per minute per milligram of protein. The CETCH cycle was drafted by metabolic retrosynthesis, established with enzymes originating from nine different organisms of all three domains of life, and optimized in several rounds by enzyme engineering and metabolic proofreading. The CETCH cycle adds a seventh, synthetic alternative to the six naturally evolved CO 2 fixation pathways, thereby opening the way for in vitro and in vivo applications. Copyright © 2016, American Association for the Advancement of Science.

Failure of Synthetic Implants: Strategies and Management.

PubMed

Jang, Yong Ju; Kim, Shin Ae; Alharethy, Sami

2018-06-01

Dorsal augmentation with synthetic implants is the most commonly performed rhinoplasty procedure, especially in the East-Asian region. However, as in all other surgical procedures, complications are inevitable. Complications that need to be managed surgically include displacement, deviation, suboptimal aesthetic outcome, extrusion, inflammation, infection, and changes in skin quality. Most complications can be easily managed with revision surgery. After the removal of the synthetic implant from the nasal dorsum, different dorsal implant materials such as dermofat, alloderm, or fascia-wrapped diced cartilage, conchal cartilage with perichondrial attachment, and costal cartilage are preferred. An irreversible change in the skin/soft tissue envelope poses a challenge that usually requires reconstructive surgery with a local flap. Therefore, early detection and prompt management of the complication are essential for minimizing the severity of the deformity and the complexity of the surgical procedures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Rule-Based Design of Plant Expression Vectors Using GenoCAD.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2015-01-01

Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer-Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein-protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects.

Recent progress in the synthesis of metal–organic frameworks

DOE PAGES

Sun, Yujia; Zhou, Hong -Cai

2015-09-25

Metal–organic frameworks (MOFs) have attracted considerable attention for various applications due to their tunable structure, porosity and functionality. In general, MOFs have been synthesized from isolated metal ions and organic linkers under hydrothermal or solvothermal conditions via one-spot reactions. The emerging precursor approach and kinetically tuned dimensional augmentation strategy add more diversity to this field. In addition, to speed up the crystallization process and create uniform crystals with reduced size, many alternative synthesis routes have been explored. Recent advances in microwave-assisted synthesis and electrochemical synthesis are presented in this review. In recent years, post-synthetic approaches have been shown to bemore » powerful tools to synthesize MOFs with modified functionality, which cannot be attained via de novo synthesis. In this study, some current accomplishments of post-synthetic modification (PSM) based on covalent transformations and coordinative interactions as well as post-synthetic exchange (PSE) in robust MOFs are provided.« less

Engineering the vibrational coherence of vision into a synthetic molecular device.

PubMed

Gueye, Moussa; Manathunga, Madushanka; Agathangelou, Damianos; Orozco, Yoelvis; Paolino, Marco; Fusi, Stefania; Haacke, Stefan; Olivucci, Massimo; Léonard, Jérémie

2018-01-22

The light-induced double-bond isomerization of the visual pigment rhodopsin operates a molecular-level optomechanical energy transduction, which triggers a crucial protein structure change. In fact, rhodopsin isomerization occurs according to a unique, ultrafast mechanism that preserves mode-specific vibrational coherence all the way from the reactant excited state to the primary photoproduct ground state. The engineering of such an energy-funnelling function in synthetic compounds would pave the way towards biomimetic molecular machines capable of achieving optimum light-to-mechanical energy conversion. Here we use resonance and off-resonance vibrational coherence spectroscopy to demonstrate that a rhodopsin-like isomerization operates in a biomimetic molecular switch in solution. Furthermore, by using quantum chemical simulations, we show why the observed coherent nuclear motion critically depends on minor chemical modifications capable to induce specific geometric and electronic effects. This finding provides a strategy for engineering vibrationally coherent motions in other synthetic systems.

Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions

NASA Astrophysics Data System (ADS)

Nakamura, Hideki; Lee, Albert A.; Afshar, Ali Sobhi; Watanabe, Shigeki; Rho, Elmer; Razavi, Shiva; Suarez, Allister; Lin, Yu-Chun; Tanigawa, Makoto; Huang, Brian; Derose, Robert; Bobb, Diana; Hong, William; Gabelli, Sandra B.; Goutsias, John; Inoue, Takanari

2018-01-01

Some protein components of intracellular non-membrane-bound entities, such as RNA granules, are known to form hydrogels in vitro. The physico-chemical properties and functional role of these intracellular hydrogels are difficult to study, primarily due to technical challenges in probing these materials in situ. Here, we present iPOLYMER, a strategy for a rapid induction of protein-based hydrogels inside living cells that explores the chemically inducible dimerization paradigm. Biochemical and biophysical characterizations aided by computational modelling show that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that acts as a size-dependent molecular sieve. We functionalize these polymers with RNA-binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. These results show that iPOLYMER can be used to synthetically reconstitute the nucleation of biologically functional entities, including RNA granules in intact cells.

Novel and Recent Synthesis and Applications of β-Lactams

NASA Astrophysics Data System (ADS)

Troisi, Luigino; Granito, Catia; Pindinelli, Emanuela

In this chapter, a comprehensive overview of the most significant and interesting contributions published from 2000 until now, concerning the preparation of novel β-lactam structures is presented. Among the different synthetic strategies available, either novel or already known but efficient and versatile methodologies are covered. The simple modifications of one or more substituents linked to the nitrogen N-1, the C-3, and the C-4 carbon atoms of the β-lactam nucleus were considered as an alternative synthetic protocol of more complex and polyfunctionalized molecules. Indeed, it is well known and extensively reviewed that the biological activity of this strained four-membered heterocycle is strictly dependent on the nature of the substituent groups that affect the reactivity towards the molecular active sites, increasing or lowering the possibility of interaction with the substrates. Finally, a synthetic survey of the most significant biological and pharmacological applications of the 2-azetidinones is reported.

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory.

PubMed

Nicolaou, K C

2014-03-08

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author's laboratories, and their impact on chemistry, biology and medicine.

Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine

PubMed Central

Poh, Chit Laa; Kirk, Kristin; McBride, William John Hannan; Aaskov, John; Grollo, Lara

2016-01-01

Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine. PMID:27223692

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

PubMed Central

Salvador, Aiala; Igartua, Manoli; Hernández, Rosa Maria; Pedraz, José Luis

2011-01-01

The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity. PMID:21773041

Co-design in synthetic biology: a system-level analysis of the development of an environmental sensing device.

PubMed

Ball, David A; Lux, Matthew W; Graef, Russell R; Peterson, Matthew W; Valenti, Jane D; Dileo, John; Peccoud, Jean

2010-01-01

The concept of co-design is common in engineering, where it is necessary, for example, to determine the optimal partitioning between hardware and software of the implementation of a system features. Here we propose to adapt co-design methodologies for synthetic biology. As a test case, we have designed an environmental sensing device that detects the presence of three chemicals, and returns an output only if at least two of the three chemicals are present. We show that the logical operations can be implemented in three different design domains: (1) the transcriptional domain using synthetically designed hybrid promoters, (2) the protein domain using bi-molecular fluorescence complementation, and (3) the fluorescence domain using spectral unmixing and relying on electronic processing. We discuss how these heterogeneous design strategies could be formalized to develop co-design algorithms capable of identifying optimal designs meeting user specifications.

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

PubMed Central

Nicolaou, K. C.

2014-01-01

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author’s laboratories, and their impact on chemistry, biology and medicine. PMID:24611027

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

PubMed Central

Kostyuchenko, Anastasia S; L.Yurpalov, Vyacheslav; Kurowska, Aleksandra; Domagala, Wojciech; Pron, Adam

2014-01-01

Summary A new synthetic approach towards the preparation of functionalised, soluble, donor–acceptor (DA) alkylbithiophene derivatives of oxadiazole, thiadiazole and triazole is reported. Taking advantage of the Fiesselmann reaction, reactive bithiophene synthons having alkyl or alkoxy substituents at designated positions are prepared. Following a synthetic strategy, featuring the bottom-up approach, sequential structural elements are built, starting from a simple thiophene compound, until the target molecule is obtained, all in good yield. Supplementing the well established methods of oxadiazole and thiadiazole synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically functionalised oligothiophenes, coupled to other heteroaromatic cores. PMID:25161716

Synthesis of new, highly luminescent bis(2,2'-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole.

PubMed

Kostyuchenko, Anastasia S; L Yurpalov, Vyacheslav; Kurowska, Aleksandra; Domagala, Wojciech; Pron, Adam; Fisyuk, Alexander S

2014-01-01

A new synthetic approach towards the preparation of functionalised, soluble, donor-acceptor (DA) alkylbithiophene derivatives of oxadiazole, thiadiazole and triazole is reported. Taking advantage of the Fiesselmann reaction, reactive bithiophene synthons having alkyl or alkoxy substituents at designated positions are prepared. Following a synthetic strategy, featuring the bottom-up approach, sequential structural elements are built, starting from a simple thiophene compound, until the target molecule is obtained, all in good yield. Supplementing the well established methods of oxadiazole and thiadiazole synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically functionalised oligothiophenes, coupled to other heteroaromatic cores.

A life scientist, an engineer and a social scientist walk into a lab: challenges of dual-use engagement and education in synthetic biology.

PubMed

Edwards, Brett; Kelle, Alexander

2012-01-01

The discussion of dual-use education is often predicated on a discrete population of practicing life scientists exhibiting certain deficiencies in awareness or expertise. This has lead to the claim that there is a greater requirement for awareness raising and education amongst this population. However, there is yet to be an inquiry into the impact of the 'convergent' nature of emerging techno-sciences upon the prospects of dual-use education. The field of synthetic biology, although often portrayed as homogeneous, is in fact composed of various sub-fields and communities. Its practitioners have diverse academic backgrounds. The research institutions that have fostered its development in the UK often have their own sets of norms and practices in engagement with ethical, legal and social issues associated with scientific knowledge and technologies. The area is also complicated by the emergence of synthetic biologists outside traditional research environments, the so called 'do-it-yourself' or 'garage biologists'. This paper untangles some of the complexities in the current state of synthetic biology and addresses the prospects for dual-use education for practitioners. It provides a short overview of the field and discusses identified dual-use issues. There follows a discussion of UK networks in synthetic biology, including their engagement with ethical, legal, social and dual-use issues and limited educational efforts in relation to these. It concludes by outlining options for developing a more systematic dual-use education strategy for synthetic biology.

Hacking DNA copy number for circuit engineering.

PubMed

Wu, Feilun; You, Lingchong

2017-07-27

DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust oscillations in gene expression circuits.

Sustainable Strategies For The Production Of Nanomaterials And Their Greener Applications

EPA Science Inventory

Vitamins B2, B1, C, tea polyphenols, and natural surfactants, which function both as reducing and capping agents, provide simple, one-pot, green synthetic methods to bulk quantities of nanomaterials. Synthesis of noble nanostructures via microwave (MW)-assisted spontaneous reduct...