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Sample records for synthetic mammalian electro-genetic

  1. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  3. Mammalian Synthetic Biology: Time for Big MACs.

    Science.gov (United States)

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-10-21

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

  4. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  5. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  6. [Research progress of mammalian synthetic biology in biomedical field].

    Science.gov (United States)

    Yang, Linfeng; Yin, Jianli; Wang, Meiyan; Ye, Haifeng

    2017-03-25

    Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

  7. A mammalianized synthetic nitroreductase gene for high-level expression

    International Nuclear Information System (INIS)

    Grohmann, Maik; Paulmann, Nils; Fleischhauer, Sebastian; Vowinckel, Jakob; Priller, Josef; Walther, Diego J

    2009-01-01

    The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy. We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays. In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect. Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans

  8. Generation of a synthetic mammalian promoter library by modification of sequences spacing transcription factor binding sites

    DEFF Research Database (Denmark)

    Tornøe, Jens; Kusk, P.; Johansen, T.E.

    2002-01-01

    The development of a set of synthetic mammalian promoters with different specific activities is described. The library is based on a synthetic promoter, JeT, constructed as a 200 bp chimeric promoter built from fragments of the viral SV40 early promoter and the human beta-actin and ubiquitin C...

  9. Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.

    Science.gov (United States)

    Angelici, Bartolomeo; Mailand, Erik; Haefliger, Benjamin; Benenson, Yaakov

    2016-08-30

    One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Generation of a synthetic mammalian promoter library by modification of sequences spacing transcription factor binding sites

    DEFF Research Database (Denmark)

    Tornøe, Jens; Kusk, P.; Johansen, T.E.

    2002-01-01

    The development of a set of synthetic mammalian promoters with different specific activities is described. The library is based on a synthetic promoter, JeT, constructed as a 200 bp chimeric promoter built from fragments of the viral SV40 early promoter and the human beta-actin and ubiquitin C......, was obtained. The measured activity of each promoter in the library was highly specific and reproducible when tested in HiB5 and ARPE-19 cell culture....

  11. Synthetic biology in mammalian cells: Next generation research tools and therapeutics

    Science.gov (United States)

    Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

    2014-01-01

    Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

  12. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems

    OpenAIRE

    Chen, Yvonne Y.; Jensen, Michael C.; Smolke, Christina D.

    2010-01-01

    RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional res...

  13. A platform for rapid prototyping of synthetic gene networks in mammalian cells

    Science.gov (United States)

    Duportet, Xavier; Wroblewska, Liliana; Guye, Patrick; Li, Yinqing; Eyquem, Justin; Rieders, Julianne; Rimchala, Tharathorn; Batt, Gregory; Weiss, Ron

    2014-01-01

    Mammalian synthetic biology may provide novel therapeutic strategies, help decipher new paths for drug discovery and facilitate synthesis of valuable molecules. Yet, our capacity to genetically program cells is currently hampered by the lack of efficient approaches to streamline the design, construction and screening of synthetic gene networks. To address this problem, here we present a framework for modular and combinatorial assembly of functional (multi)gene expression vectors and their efficient and specific targeted integration into a well-defined chromosomal context in mammalian cells. We demonstrate the potential of this framework by assembling and integrating different functional mammalian regulatory networks including the largest gene circuit built and chromosomally integrated to date (6 transcription units, 27kb) encoding an inducible memory device. Using a library of 18 different circuits as a proof of concept, we also demonstrate that our method enables one-pot/single-flask chromosomal integration and screening of circuit libraries. This rapid and powerful prototyping platform is well suited for comparative studies of genetic regulatory elements, genes and multi-gene circuits as well as facile development of libraries of isogenic engineered cell lines. PMID:25378321

  14. Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

    Science.gov (United States)

    Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

    2017-07-07

    Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion.

    Directory of Open Access Journals (Sweden)

    Xinhe Wang

    2015-07-01

    Full Text Available The prion hypothesis postulates that the infectious agent in transmissible spongiform encephalopathies (TSEs is an unorthodox protein conformation based agent. Recent successes in generating mammalian prions in vitro with bacterially expressed recombinant prion protein provide strong support for the hypothesis. However, whether the pathogenic properties of synthetically generated prion (rec-Prion recapitulate those of naturally occurring prions remains unresolved. Using end-point titration assay, we showed that the in vitro prepared rec-Prions have infectious titers of around 104 LD50/μg. In addition, intraperitoneal (i.p. inoculation of wild-type mice with rec-Prion caused prion disease with an average survival time of 210-220 days post inoculation. Detailed pathological analyses revealed that the nature of rec-Prion induced lesions, including spongiform change, disease specific prion protein accumulation (PrP-d and the PrP-d dissemination amongst lymphoid and peripheral nervous system tissues, the route and mechanisms of neuroinvasion were all typical of classical rodent prions. Our results revealed that, similar to naturally occurring prions, the rec-Prion has a titratable infectivity and is capable of causing prion disease via routes other than direct intra-cerebral challenge. More importantly, our results established that the rec-Prion caused disease is pathogenically and pathologically identical to naturally occurring contagious TSEs, supporting the concept that a conformationally altered protein agent is responsible for the infectivity in TSEs.

  16. Inhibition of Dengue Virus 3 in Mammalian Cell Culture by Synthetic ...

    African Journals Online (AJOL)

    HP

    Purpose: To evaluate the inhibition of Dengue virus 3 by synthetic siRNAs targeting the untranslated regions UTR and structural regions of DENV3 genome in Vero-81 cell line. Methods: Vero-81 cells transfected with synthetic siRNAs were challenged by DENV3. The effectiveness of siRNAs was confirmed by four ...

  17. Study of the immunological relatedness of goldfish MSH in an RIA for synthetic mammalian α MSH

    International Nuclear Information System (INIS)

    Follenius, Ernest; Schmitt, Gabrielle; Meunier, Annie

    1980-01-01

    α MSH from the neuro-intermediate lobe of the pituitary gland of the goldfish displays a competitive behaviour in an RIA for synthetic α MSH. The inhibition curves from neuro-intermediate homogenates parallel the standard curve (P [fr

  18. A synthetic multifunctional mammalian pH sensor and CO2 transgene-control device.

    Science.gov (United States)

    Ausländer, David; Ausländer, Simon; Charpin-El Hamri, Ghislaine; Sedlmayer, Ferdinand; Müller, Marius; Frey, Olivier; Hierlemann, Andreas; Stelling, Jörg; Fussenegger, Martin

    2014-08-07

    All metabolic activities operate within a narrow pH range that is controlled by the CO2-bicarbonate buffering system. We hypothesized that pH could serve as surrogate signal to monitor and respond to the physiological state. By functionally rewiring the human proton-activated cell-surface receptor TDAG8 to chimeric promoters, we created a synthetic signaling cascade that precisely monitors extracellular pH within the physiological range. The synthetic pH sensor could be adjusted by organic acids as well as gaseous CO2 that shifts the CO2-bicarbonate balance toward hydrogen ions. This enabled the design of gas-programmable logic gates, provided remote control of cellular behavior inside microfluidic devices, and allowed for CO2-triggered production of biopharmaceuticals in standard bioreactors. When implanting cells containing the synthetic pH sensor linked to production of insulin into type 1 diabetic mice developing diabetic ketoacidosis, the prosthetic network automatically scored acidic pH and coordinated an insulin expression response that corrected ketoacidosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Sensitive detection of proteasomal activation using the Deg-On mammalian synthetic gene circuit.

    Science.gov (United States)

    Zhao, Wenting; Bonem, Matthew; McWhite, Claire; Silberg, Jonathan J; Segatori, Laura

    2014-04-08

    The ubiquitin proteasome system (UPS) has emerged as a drug target for diverse diseases characterized by altered proteostasis, but pharmacological agents that enhance UPS activity have been challenging to establish. Here we report the Deg-On system, a genetic inverter that translates proteasomal degradation of the transcriptional regulator TetR into a fluorescent signal, thereby linking UPS activity to an easily detectable output, which can be tuned using tetracycline. We demonstrate that this circuit responds to modulation of UPS activity in cell culture arising from the inhibitor MG-132 and activator PA28γ. Guided by predictive modelling, we enhanced the circuit's signal sensitivity and dynamic range by introducing a feedback loop that enables self-amplification of TetR. By linking UPS activity to a simple and tunable fluorescence output, these genetic inverters will enable a variety of applications, including screening for UPS activating molecules and selecting for mammalian cells with different levels of proteasome activity.

  20. Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Wendy C Carcamo

    Full Text Available Cytoplasmic filamentous rods and rings (RR structures were identified using human autoantibodies as probes. In the present study, the formation of these conserved structures in mammalian cells and functions linked to these structures were examined.Distinct cytoplasmic rods (∼3-10 µm in length and rings (∼2-5 µm in diameter in HEp-2 cells were initially observed in immunofluorescence using human autoantibodies. Co-localization studies revealed that, although RR had filament-like features, they were not enriched in actin, tubulin, or vimentin, and not associated with centrosomes or other known cytoplasmic structures. Further independent studies revealed that two key enzymes in the nucleotide synthetic pathway cytidine triphosphate synthase 1 (CTPS1 and inosine monophosphate dehydrogenase 2 (IMPDH2 were highly enriched in RR. CTPS1 enzyme inhibitors 6-diazo-5-oxo-L-norleucine and Acivicin as well as the IMPDH2 inhibitor Ribavirin exhibited dose-dependent induction of RR in >95% of cells in all cancer cell lines tested as well as mouse primary cells. RR formation by lower concentration of Ribavirin was enhanced in IMPDH2-knockdown HeLa cells whereas it was inhibited in GFP-IMPDH2 overexpressed HeLa cells. Interestingly, RR were detected readily in untreated mouse embryonic stem cells (>95%; upon retinoic acid differentiation, RR disassembled in these cells but reformed when treated with Acivicin.RR formation represented response to disturbances in the CTP or GTP synthetic pathways in cancer cell lines and mouse primary cells and RR are the convergence physical structures in these pathways. The availability of specific markers for these conserved structures and the ability to induce formation in vitro will allow further investigations in structure and function of RR in many biological systems in health and diseases.

  1. Interference of a synthetic C18 juvenile hormone with mammalian cells in vitro, I. Effects on growth and morphology.

    Science.gov (United States)

    Zielińska, Z M; Laskowska-Bozek, H; Jastreboff, P

    1978-01-01

    Some of structural and functional analogs of juvenile hormones are now under field examinations as growth inhibitors of some pest-insect populations. So far however very little is known about the possible interference of these compounds with mammalian cells or organisms. In this research the interference of a synthetic preparation of the insect C18 juvenile hormone with mouse embryo fibroblasts (ME-cells) and mouse cells of an established line (L-cells) was studied. Aliquots of juvenile hormone solution or those of the solvent (DMSO plus ethanol, 9:1) were included into the culture medium and after defined times of contact the cells were tested for their morphology, pattern of growth, proliferation rate and viability. The data for the parameters under examination were evaluated by means of the analysis of variance and checked by the Tuckey test. The sensitivity of ME-cells and L-cells to the agent tested was compared by means of the analysis of variance of the data for mitotic indices of these cells and by evaluation of the number of dead cells in cultures under the particular conditions of the experiments. The main findings can be summarized as follows: 1. Cells of both types are evidently more sensitive to juvenile hormone than to the solvent. 2. ME-cells are more sensitive to both agents than are L-cells. 3. The concentrations of the hormone in the medium required to evoked the cytocidal effect on the mouse cells similarly as those affecting some insect non-target cells were far above concentrations found in insect blood, but they were of the same order of magnitude as those used in physiological experiments with insect organs in vitro.

  2. Synthetic

    Directory of Open Access Journals (Sweden)

    Anna Maria Manferdini

    2010-06-01

    Full Text Available Traditionally materials have been associated with a series of physical properties that can be used as inputs to production and manufacturing. Recently we witnessed an interest in materials considered not only as ‘true matter’, but also as new breeds where geometry, texture, tooling and finish are able to provoke new sensations when they are applied to a substance. These artificial materials can be described as synthetic because they are the outcome of various qualities that are not necessarily true to the original matter, but they are the combination of two or more parts, whether by design or by natural processes. The aim of this paper is to investigate the potential of architectural surfaces to produce effects through the invention of new breeds of artificial matter, using micro-scale details derived from Nature as an inspiration.

  3. Benchmarking of TALE- and CRISPR/dCas9-Based Transcriptional Regulators in Mammalian Cells for the Construction of Synthetic Genetic Circuits.

    Science.gov (United States)

    Lebar, Tina; Jerala, Roman

    2016-10-21

    Transcriptional activator-like effector (TALE)- and CRISPR/Cas9-based designable recognition domains represent a technological breakthrough not only for genome editing but also for building designed genetic circuits. Both platforms are able to target rarely occurring DNA segments, even within complex genomes. TALE and dCas9 domains, genetically fused to transcriptional regulatory domains, can be used for the construction of engineered logic circuits. Here we benchmarked the performance of the two platforms, targeting the same DNA sequences, to compare their advantages for the construction of designed circuits in mammalian cells. Optimal targeting strands for repression and activation of dCas9-based designed transcription factors were identified; both platforms exhibited good orthogonality and were used to construct functionally complete NOR gates. Although the CRISPR/dCas9 system is clearly easier to construct, TALE-based activators were significantly stronger, and the TALE-based platform performed better, especially for the construction of layered circuits.

  4. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  5. Towards a synthetic chloroplast.

    Directory of Open Access Journals (Sweden)

    Christina M Agapakis

    2011-04-01

    Full Text Available The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner.We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages.Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices.

  6. [Progress in synthetic biology of "973 Funding Program" in China].

    Science.gov (United States)

    Chen, Guoqiang; Wang, Ying

    2015-06-01

    This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems.

  7. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  8. Synthetic Cannabinoids

    Directory of Open Access Journals (Sweden)

    Aslihan Okan Ibiloglu

    2017-09-01

    Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

  9. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Progress is reported on the following research projects: the effects of N-ethyl-maleimide and hydroxyurea on hamster cells in culture; sensitization of synchronized human cells to x rays by N-ethylmaleimide; sensitization of hypoxic mammalian cells with a sulfhydryl inhibitor; damage interaction due to ionizing and nonionizing radiation in mammalian cells; DNA damage relative to radioinduced cell killing; spurious photolability of DNA labeled with methyl- 14 C-thymidine; radioinduced malignant transformation of cultured mouse cells; a comparison of properties of uv and near uv light relative to cell function and DNA damage; Monte Carlo simulation of DNA damage and repair mechanisms; and radiobiology of fast neutrons

  10. Building the mammalian testis

    DEFF Research Database (Denmark)

    Svingen, Terje; Koopman, Peter

    2013-01-01

    Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial...

  11. Synthetic environments

    Science.gov (United States)

    Lukes, George E.; Cain, Joel M.

    1996-02-01

    The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

  12. [Smart therapeutics based on synthetic gene circuits].

    Science.gov (United States)

    Peng, Shuguang; Xie, Zhen

    2017-03-25

    Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

  13. Mammalian development in space

    Science.gov (United States)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  14. Synthetic Rutile

    International Nuclear Information System (INIS)

    Burastero, J.

    1975-01-01

    This work is about the laboratory scale investigation of the conditions in the rutile synthetic production from one me nita in Aguas Dulces reservoir. The iron mineral is chlorinated and volatilized selectively leaving a residue enriched in titanium dioxide which can be used as a substitute of rutile mineral

  15. Homogenization of Mammalian Cells.

    Science.gov (United States)

    de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

    2015-11-02

    Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

  16. Rheotaxis guides mammalian sperm

    Science.gov (United States)

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  17. Natural - synthetic - artificial!

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life.......The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life....

  18. Synthetic Cannabinoids.

    Science.gov (United States)

    Mills, Brooke; Yepes, Andres; Nugent, Kenneth

    2015-07-01

    Synthetic cannabinoids (SCBs), also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

  19. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

  20. Synthetic Brainbows

    KAUST Repository

    Wan, Y.

    2013-06-01

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

  1. Synthetic Botany.

    Science.gov (United States)

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

    2017-07-05

    Plants are attractive platforms for synthetic biology and metabolic engineering. Plants' modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. However, efforts in this area have been constrained by slow growth, long life cycles, the requirement for specialized facilities, a paucity of efficient tools for genetic manipulation, and the complexity of multicellularity. There is a need for better experimental and theoretical frameworks to understand the way genetic networks, cellular populations, and tissue-wide physical processes interact at different scales. We highlight new approaches to the DNA-based manipulation of plants and the use of advanced quantitative imaging techniques in simple plant models such as Marchantia polymorpha. These offer the prospects of improved understanding of plant dynamics and new approaches to rational engineering of plant traits. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  2. An evaluation of multiple annealing and looping based genome amplification using a synthetic bacterial community

    KAUST Repository

    Wang, Yong; Gao, Zhaoming; Xu, Ying; Li, Guangyu; He, Lisheng; Qian, Peiyuan

    2016-01-01

    -generation-sequencing technology. Using a synthetic bacterial community, the amplification efficiency of the Multiple Annealing and Looping Based Amplification Cycles (MALBAC) kit that is originally developed to amplify the single-cell genomic DNA of mammalian organisms

  3. Synthetic Astrobiology

    Science.gov (United States)

    Rothschild, Lynn J.

    2017-01-01

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

  4. Localization of two mammalian cyclin dependent kinases during mammalian meiosis

    NARCIS (Netherlands)

    Ashley, T.; Walpita, D.; de rooij, D. G.

    2001-01-01

    Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

  5. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  6. Mammalian cell biology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

  7. Cryopreservation of mammalian semen.

    Science.gov (United States)

    Curry, Mark R

    2007-01-01

    Mammalian spermatozoa were among the very first cells to be successfully cryopreserved and over the last five decades the use of frozen-thawed semen for artificial insemination has come to play an important role in domestic livestock production. More recently, semen freezing has increasingly been utilized in the establishment of genetic resource banks for endangered species. Semen is collected, most commonly either by use of an artificial vagina or by electroejaculation of an anaesthetized animal, and basic sperm parameters assessed. Semen is extended using a TEST-egg yolk-glycerol diluent, packaged in 0.25-mL plastic straws and slowly cooled to 5 degrees C over a period of 1-2 h. Cooled straws are frozen by suspending within liquid nitrogen vapor above the liquid nitrogen surface before plunging into the liquid phase. Straws are thawed briefly in air before immersing in a 35 degrees C water bath for 15 s, and often are used directly for insemination without any further processing.

  8. mammalian brain system

    Directory of Open Access Journals (Sweden)

    Alan Kania

    2014-06-01

    Full Text Available Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin – a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3 was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.

  9. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  10. From noise to synthetic nucleoli: can synthetic biology achieve new insights?

    Science.gov (United States)

    Ciechonska, Marta; Grob, Alice; Isalan, Mark

    2016-04-18

    Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks. This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks. Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

  11. Synthetic mimics of antimicrobial peptides.

    Science.gov (United States)

    Som, Abhigyan; Vemparala, Satyavani; Ivanov, Ivaylo; Tew, Gregory N

    2008-01-01

    Infectious diseases and antibiotic resistance are now considered the most imperative global healthcare problem. In the search for new treatments, host defense, or antimicrobial, peptides have attracted considerable attention due to their various unique properties; however, attempts to develop in vivo therapies have been severely limited. Efforts to develop synthetic mimics of antimicrobial peptides (SMAMPs) have increased significantly in the last decade, and this review will focus primarily on the structural evolution of SMAMPs and their membrane activity. This review will attempt to make a bridge between the design of SMAMPs and the fundamentals of SMAMP-membrane interactions. In discussions regarding the membrane interaction of SMAMPs, close attention will be paid to the lipid composition of the bilayer. Despite many years of study, the exact conformational aspects responsible for the high selectivity of these AMPs and SMAMPs toward bacterial cells over mammalian cells are still not fully understood. The ability to design SMAMPs that are potently antimicrobial, yet nontoxic to mammalian cells has been demonstrated with a variety of molecular scaffolds. Initial animal studies show very good tissue distribution along with more than a 4-log reduction in bacterial counts. The results on SMAMPs are not only extremely promising for novel antibiotics, but also provide an optimistic picture for the greater challenge of general proteomimetics.

  12. Hydrolysis of synthetic mixed-acid phosphatides by phospholipase A from human pancreas

    NARCIS (Netherlands)

    Deenen, L.L.M. van; Haas, Gerard H. de; Heemskerk, C.H.Th.

    1963-01-01

    An investigation was made into the action of a human pancreatic phospholipase A on various synthetic phosphatides. L-α-Phosphatidyl ethanolamines were readily hydrolysed in an aqueous system by this enzyme. Synthetic lecithins, however, were not attacked in an appreciable rate by the mammalian

  13. Chromatin regulation at the frontier of synthetic biology

    Science.gov (United States)

    Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

    2016-01-01

    As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

  14. Synthetic biology, inspired by synthetic chemistry.

    Science.gov (United States)

    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.

  15. DEOXYRIBONUCLEASE IV: A NEW EXONUCLEASE FROM MAMMALIAN TISSUES*

    Science.gov (United States)

    Lindahl, Tomas; Gally, Joseph A.; Edelman, Gerald M.

    1969-01-01

    An exonuclease which specifically degrades double-standard DNA has been isolated from rabbit tissues. The enzyme has an approximate molecular weight of 42,000, requires a divalent metal ion as cofactor, and attacks DNA at the 5′-terminal ends, thereby liberating 5′-mononucleotides. It degrades several synthetic polydeoxynucleotides of single repeating base sequences more rapidly than DNA from natural sources. The specificity of this mammalian enzyme resembles that of several microbial enzymes (phage λ exonuclease and DNA polymerase) which appear to be required for repair and recombination of DNA. PMID:5256235

  16. The shape of mammalian phylogeny

    DEFF Research Database (Denmark)

    Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

    2011-01-01

    an assemblage, ecoregion or larger area always tends to be more unbalanced than expected from the phylogeny of species at the next more inclusive spatial scale. We conclude with a verbal model of mammalian macroevolution, which emphasizes the importance to diversification of accessing new regions...

  17. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  18. Technology of mammalian cell encapsulation

    NARCIS (Netherlands)

    Uludag, H; De Vos, P; Tresco, PA

    2000-01-01

    Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

  19. Plant synthetic biology.

    Science.gov (United States)

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Synthetic Cathinones ("Bath Salts")

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  1. Programming Morphogenesis through Systems and Synthetic Biology.

    Science.gov (United States)

    Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

    2018-04-01

    Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Bioenergetics of mammalian sperm capacitation.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  3. Mammalian designer cells: Engineering principles and biomedical applications.

    Science.gov (United States)

    Xie, Mingqi; Fussenegger, Martin

    2015-07-01

    Biotechnology is a widely interdisciplinary field focusing on the use of living cells or organisms to solve established problems in medicine, food production and agriculture. Synthetic biology, the science of engineering complex biological systems that do not exist in nature, continues to provide the biotechnology industry with tools, technologies and intellectual property leading to improved cellular performance. One key aspect of synthetic biology is the engineering of deliberately reprogrammed designer cells whose behavior can be controlled over time and space. This review discusses the most commonly used techniques to engineer mammalian designer cells; while control elements acting on the transcriptional and translational levels of target gene expression determine the kinetic and dynamic profiles, coupling them to a variety of extracellular stimuli permits their remote control with user-defined trigger signals. Designer mammalian cells with novel or improved biological functions not only directly improve the production efficiency during biopharmaceutical manufacturing but also open the door for cell-based treatment strategies in molecular and translational medicine. In the future, the rational combination of multiple sets of designer cells could permit the construction and regulation of higher-order systems with increased complexity, thereby enabling the molecular reprogramming of tissues, organisms or even populations with highest precision. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Apple derived cellulose scaffolds for 3D mammalian cell culture.

    Directory of Open Access Journals (Sweden)

    Daniel J Modulevsky

    Full Text Available There are numerous approaches for producing natural and synthetic 3D scaffolds that support the proliferation of mammalian cells. 3D scaffolds better represent the natural cellular microenvironment and have many potential applications in vitro and in vivo. Here, we demonstrate that 3D cellulose scaffolds produced by decellularizing apple hypanthium tissue can be employed for in vitro 3D culture of NIH3T3 fibroblasts, mouse C2C12 muscle myoblasts and human HeLa epithelial cells. We show that these cells can adhere, invade and proliferate in the cellulose scaffolds. In addition, biochemical functionalization or chemical cross-linking can be employed to control the surface biochemistry and/or mechanical properties of the scaffold. The cells retain high viability even after 12 continuous weeks of culture and can achieve cell densities comparable with other natural and synthetic scaffold materials. Apple derived cellulose scaffolds are easily produced, inexpensive and originate from a renewable source. Taken together, these results demonstrate that naturally derived cellulose scaffolds offer a complementary approach to existing techniques for the in vitro culture of mammalian cells in a 3D environment.

  5. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

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

  6. [From synthetic biology to synthetic humankind].

    Science.gov (United States)

    Nouvel, Pascal

    2015-01-01

    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  7. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, Christopher [Massachusetts Institute of Technology

    2014-07-01

    SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

  8. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

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

  9. Enhancer evolution across 20 mammalian species

    DEFF Research Database (Denmark)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah

    2015-01-01

    The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

  10. Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells

    Science.gov (United States)

    Ede, Christopher; Chen, Ximin; Lin, Meng-Yin; Chen, Yvonne Y.

    2016-01-01

    Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning two orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality. PMID:26883397

  11. Synthetic smooth muscle in the outer blood plexus of the rhinarium skin of Lemur catta L.

    Science.gov (United States)

    Elofsson, Rolf; Kröger, Ronald H H

    2017-01-01

    The skin of the lemur nose tip (rhinarium) has arterioles in the outer vascular plexus that are endowed with an unusual coat of smooth muscle cells. Comparison with the arterioles of the same area in a number of unrelated mammalians shows that the lemur pattern is unique. The vascular smooth muscle cells belong to the synthetic type. The function of synthetic smooth muscles around the terminal vessels in the lemur rhinarium is unclear but may have additional functions beyond regulation of vessel diameter.

  12. Mutation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Okada, S.

    1982-01-01

    Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

  13. Interaction theory of mammalian mitochondria.

    Science.gov (United States)

    Nakada, K; Inoue, K; Hayashi, J

    2001-11-09

    We generated mice with deletion mutant mtDNA by its introduction from somatic cells into mouse zygotes. Expressions of disease phenotypes are limited to tissues expressing mitochondrial dysfunction. Considering that all these mice share the same nuclear background, these observations suggest that accumulation of the mutant mtDNA and resultant expressions of mitochondrial dysfunction are responsible for expression of disease phenotypes. On the other hand, mitochondrial dysfunction and expression of clinical abnormalities were not observed until the mutant mtDNA accumulated predominantly. This protection is due to the presence of extensive and continuous interaction between exogenous mitochondria from cybrids and recipient mitochondria from embryos. Thus, we would like to propose a new hypothesis on mitochondrial biogenesis, interaction theory of mitochondria: mammalian mitochondria exchange genetic contents, and thus lost the individuality and function as a single dynamic cellular unit. Copyright 2001 Academic Press.

  14. Producing Newborn Synchronous Mammalian Cells

    Science.gov (United States)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  15. Synthetic Defects for Vibrothermography

    Science.gov (United States)

    Renshaw, Jeremy; Holland, Stephen D.; Thompson, R. Bruce; Eisenmann, David J.

    2010-02-01

    Synthetic defects are an important tool used for characterizing the performance of nondestructive evaluation techniques. Viscous material-filled synthetic defects were developed for use in vibrothermography (also known as sonic IR) as a tool to improve inspection accuracy and reliability. This paper describes how the heat-generation response of these VMF synthetic defects is similar to the response of real defects. It also shows how VMF defects can be applied to improve inspection accuracy for complex industrial parts and presents a study of their application in an aircraft engine stator vane.

  16. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M

    2013-01-01

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

  17. Mammalian gastrointestinal parasites in rainforest remnants

    Indian Academy of Sciences (India)

    Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

  18. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  19. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

  20. Technical Assessment: Synthetic Biology

    Science.gov (United States)

    2015-01-01

    Pfizer, Bausch & Lomb, Coca - Cola , and other Fortune 500 companies 8 Data estimated by the... financial prize for ideas to drive forward the production of a sensor relying on synthetic organisms that can detect exposure to 500 specific chemicals

  1. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.; Gadê lha, H.; Smith, D.J.; Blake, J.R.; Kirkman-Brown, J.C.

    2011-01-01

    the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian

  2. Enhancer Evolution across 20 Mammalian Species

    Science.gov (United States)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  3. Mammalian Genetics and Teratology Section

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The work of the Mammalian Genetics and Teratology Section includes research in mutagenesis, basic genetics, reproductive biology, and teratogenesis involving basic studies, method development, including exploration of the biological material, and testing. The basic studies make good use of the genetic material accumulated in mutagenesis experiments of various kinds, or of the findings of mutagenesis experiments themselves. In the latter category is the finding of a repair system in the fertilized egg. The genetics of repair competency or deficiency are now under study. A linear relationship between gene dosage and level of expression of an enzyme has been demonstrated. Opportunities for the study of gene action are provided by a number of X-autosome translocations which continue to be discovered in the course of mutagenesis experiments. In these rearrangements, X-chromosome inactivation extends to neighboring autosomal loci. Considerable progress has been made in developing the skeletal mutation system, which provides information on dominants that is highly useful for risk assessment. A sensitive-indicator test is now under development which will make the screening for skeletal mutations much faster and easier. Method development has also progressed on the in vivo somatic-mutation test now being widely used as an in vivo screen for mutagens. Another method developed here is the numerical sex-chromosome anomaly (NSA) test for nondisjunction. The NSA method is being used to explore the effects of female age on chromosome loss and nondisjunction. A model for estimating the misclassification error was experimentally established for the heritable translocation test. A rapid, easy, and sensitive in vivo screening test for teratogenesis was developed. An in vitro teratogenic prescreen being developed makes use of teratocarcinoma-derived cell lines

  4. What Are Synthetic Cannabinoids?

    Science.gov (United States)

    ... years, synthetic cannabinoid mixtures have been easy to buy in drug paraphernalia shops, novelty stores, gas stations, and over ... abuse, authorities have made it illegal to sell, buy, or possess some of ... use is that standard drug tests cannot easily detect many of the chemicals ...

  5. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

    2008-01-01

    A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective is to im......A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is to improve and obtain a more range independent lateral resolution compared to conventional dynamic receive focusing (DRF) without compromising frame rate. SASB is a two-stage procedure using two separate beamformers. First a set of Bmode image lines using a single focal point in both transmit and receive...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

  6. Building synthetic cellular organization

    OpenAIRE

    Polka, Jessica K.; Silver, Pamela A.

    2013-01-01

    The elaborate spatial organization of cells enhances, restricts, and regulates protein–protein interactions. However, the biological significance of this organization has been difficult to study without ways of directly perturbing it. We highlight synthetic biology tools for engineering novel cellular organization, describing how they have been, and can be, used to advance cell biology.

  7. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  8. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  9. Mosaic evolution of the mammalian auditory periphery.

    Science.gov (United States)

    Manley, Geoffrey A

    2013-01-01

    The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

  10. Synthetic Electric Microbial Biosensors

    Science.gov (United States)

    2017-06-10

    domains and DNA-binding domains into a single protein for deregulation of down stream genes of have been favored [10]. Initially experiments with... Germany DISTRIBUTION A. Approved for public release: distribution unlimited.   Talk title: “Synthetic biology based microbial biosensors for the...toolbox” in Heidelberg, Germany Poster title: “Anaerobic whole cell microbial biosensors” Link: http://phdsymposium.embl.org/#home   September, 2014

  11. Surgical manipulation of mammalian embryos in vitro.

    Science.gov (United States)

    Naruse, I; Keino, H; Taniguchi, M

    1997-04-01

    Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

  12. Mammalian diversity: gametes, embryos and reproduction.

    Science.gov (United States)

    Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

    2006-01-01

    The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

  13. Acoustophoretic Synchronization of Mammalian Cells in Microchannels

    DEFF Research Database (Denmark)

    Thévoz, P.; Adams, J.D.; Shea, H.

    2010-01-01

    We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel to selec......We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel...

  14. DNA repair in non-mammalian animals

    International Nuclear Information System (INIS)

    Mitani, Hiroshi

    1984-01-01

    Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

  15. Opportunities in plant synthetic biology.

    Science.gov (United States)

    Cook, Charis; Martin, Lisa; Bastow, Ruth

    2014-05-01

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

  16. Tunable signal processing in synthetic MAP kinase cascades.

    Science.gov (United States)

    O'Shaughnessy, Ellen C; Palani, Santhosh; Collins, James J; Sarkar, Casim A

    2011-01-07

    The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Engineering Synthetic Proteins to Generate Ca2+ Signals in Mammalian Cells.

    Science.gov (United States)

    Qudrat, Anam; Truong, Kevin

    2017-03-17

    The versatility of Ca 2+ signals allows it to regulate diverse cellular processes such as migration, apoptosis, motility and exocytosis. In some receptors (e.g., VEGFR2), Ca 2+ signals are generated upon binding their ligand(s) (e.g., VEGF-A). Here, we employed a design strategy to engineer proteins that generate a Ca 2+ signal upon binding various extracellular stimuli by creating fusions of protein domains that oligomerize to the transmembrane domain and the cytoplasmic tail of the VEGFR2. To test the strategy, we created chimeric proteins that generate Ca 2+ signals upon stimulation with various extracellular stimuli (e.g., rapamycin, EDTA or extracellular free Ca 2+ ). By coupling these chimeric proteins that generate Ca 2+ signals with proteins that respond to Ca 2+ signals, we rewired, for example, dynamic cellular blebbing to increases in extracellular free Ca 2+ . Thus, using this design strategy, it is possible to engineer proteins to generate a Ca 2+ signal to rewire a wide range of extracellular stimuli to a wide range of Ca 2+ -activated processes.

  18. Synthetic staggered architecture composites

    International Nuclear Information System (INIS)

    Dutta, Abhishek; Tekalur, Srinivasan Arjun

    2013-01-01

    Highlights: ► Composite design inspired by nature. ► Tuning microstructure via changing ceramic content and aspect ratio. ► Experimental display of structure–property correlationship in synthetic composites. - Abstract: Structural biocomposites (for example, nacre in seashells, bone, etc.) are designed according to the functional role they are delegated for. For instance, bone is primarily designed for withstanding time-dependent loading (for example, withstanding stresses while running, jumping, accidental fall) and hence the microstructure is designed primarily from enhanced toughness and moderate stiffness point of view. On the contrary, seashells (which lie in the abyss of oceans) apart from providing defense to the organism (it is hosting) against predatory attacks, are subjected to static loading (for example, enormous hydrostatic pressure). Hence, emphasis on the shell structure evolution is directed primarily towards providing enhanced stiffness. In order to conform between stiffness and toughness, nature precisely employs a staggered arrangement of inorganic bricks in a biopolymer matrix (at its most elementary level of architecture). Aspect ratio and content of ceramic bricks are meticulously used by nature to synthesize composites having varying degrees of stiffness, strength and toughness. Such an amazing capability of structure–property correlationship has rarely been demonstrated in synthetic composites. Therefore, in order to better understand the mechanical behavior of synthetic staggered composites, the problem becomes two-pronged: (a) synthesize composites with varying brick size and contents and (b) experimental investigation of the material response. In this article, an attempt has been made to synthesize and characterize staggered ceramic–polymer composites having varying aspect ratio and ceramic content using freeze-casting technique. This will in-turn help us in custom-design manufacture of hybrid bio-inspired composite materials

  19. Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Nikolov, Svetoslav; Gammelmark, Kim Løkke

    2006-01-01

    The paper describes the use of synthetic aperture (SA) imaging in medical ultrasound. SA imaging is a radical break with today's commercial systems, where the image is acquired sequentially one image line at a time. This puts a strict limit on the frame rate and the possibility of acquiring...... a sufficient amount of data for high precision flow estimation. These constrictions can be lifted by employing SA imaging. Here data is acquired simultaneously from all directions over a number of emissions, and the full image can be reconstructed from this data. The talk will demonstrate the many benefits...

  20. Transition in synthetic jets

    Czech Academy of Sciences Publication Activity Database

    Tesař, Václav; Kordík, Jozef

    2012-01-01

    Roč. 187, NOV 2012 (2012), s. 105-117 ISSN 0924-4247 R&D Projects: GA TA ČR(CZ) TA02020795; GA ČR(CZ) GPP101/12/P556; GA ČR(CZ) GCP101/11/J019 Institutional research plan: CEZ:AV0Z20760514 Keywords : turbulence * synthetic jet * transition * velocity spectra Subject RIV: BK - Fluid Dynamics Impact factor: 1.841, year: 2012 http://www. science direct.com/ science /article/pii/S0924424712005031

  1. Automatic Control of Gene Expression in Mammalian Cells.

    Science.gov (United States)

    Fracassi, Chiara; Postiglione, Lorena; Fiore, Gianfranco; di Bernardo, Diego

    2016-04-15

    Automatic control of gene expression in living cells is paramount importance to characterize both endogenous gene regulatory networks and synthetic circuits. In addition, such a technology can be used to maintain the expression of synthetic circuit components in an optimal range in order to ensure reliable performance. Here we present a microfluidics-based method to automatically control gene expression from the tetracycline-inducible promoter in mammalian cells in real time. Our approach is based on the negative-feedback control engineering paradigm. We validated our method in a monoclonal population of cells constitutively expressing a fluorescent reporter protein (d2EYFP) downstream of a minimal CMV promoter with seven tet-responsive operator motifs (CMV-TET). These cells also constitutively express the tetracycline transactivator protein (tTA). In cells grown in standard growth medium, tTA is able to bind the CMV-TET promoter, causing d2EYFP to be maximally expressed. Upon addition of tetracycline to the culture medium, tTA detaches from the CMV-TET promoter, thus preventing d2EYFP expression. We tested two different model-independent control algorithms (relay and proportional-integral (PI)) to force a monoclonal population of cells to express an intermediate level of d2EYFP equal to 50% of its maximum expression level for up to 3500 min. The control input is either tetracycline-rich or standard growth medium. We demonstrated that both the relay and PI controllers can regulate gene expression at the desired level, despite oscillations (dampened in the case of the PI controller) around the chosen set point.

  2. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  3. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  4. Locomotor circuits in the mammalian spinal cord

    DEFF Research Database (Denmark)

    Kiehn, Ole

    2006-01-01

    Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network struct...

  5. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

    2014-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  6. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...

  7. Archetype, adaptation and the mammalian heart

    NARCIS (Netherlands)

    Meijler, F.L.; Meijler, T.D.

    2011-01-01

    Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural

  8. EMMA: An Extensible Mammalian Modular Assembly Toolkit for the Rapid Design and Production of Diverse Expression Vectors.

    Science.gov (United States)

    Martella, Andrea; Matjusaitis, Mantas; Auxillos, Jamie; Pollard, Steven M; Cai, Yizhi

    2017-07-21

    Mammalian plasmid expression vectors are critical reagents underpinning many facets of research across biology, biomedical research, and the biotechnology industry. Traditional cloning methods often require laborious manual design and assembly of plasmids using tailored sequential cloning steps. This process can be protracted, complicated, expensive, and error-prone. New tools and strategies that facilitate the efficient design and production of bespoke vectors would help relieve a current bottleneck for researchers. To address this, we have developed an extensible mammalian modular assembly kit (EMMA). This enables rapid and efficient modular assembly of mammalian expression vectors in a one-tube, one-step golden-gate cloning reaction, using a standardized library of compatible genetic parts. The high modularity, flexibility, and extensibility of EMMA provide a simple method for the production of functionally diverse mammalian expression vectors. We demonstrate the value of this toolkit by constructing and validating a range of representative vectors, such as transient and stable expression vectors (transposon based vectors), targeting vectors, inducible systems, polycistronic expression cassettes, fusion proteins, and fluorescent reporters. The method also supports simple assembly combinatorial libraries and hierarchical assembly for production of larger multigenetic cargos. In summary, EMMA is compatible with automated production, and novel genetic parts can be easily incorporated, providing new opportunities for mammalian synthetic biology.

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

    OpenAIRE

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

    2015-01-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with...

  10. Analog synthetic biology.

    Science.gov (United States)

    Sarpeshkar, R

    2014-03-28

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

  11. Synthetic lubricating oils

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Jurado, J

    1953-01-01

    A yellow solid petroleum paraffin d/sup 60/ 0.808, I number 3.5, average molecular weight 350, chlorinated and condensed with benzene, xylene, or naphthalene by the Friedel and Crafts reaction, in the presence of anhydrous AlCl/sub 3/ or activated Al, gave synthetic lubricating oils. Xylene was the preferred aromatic compound, naphthalene required the use of less completely chlorinated paraffin, benzene produced resins difficult to remove and gave darker oils with excessive green fluorescence. Activated Al rather than anhydrous AlCl/sub 3/ gave darker oils with higher viscosity and Conradson C values. Tar from the low-temperature distillation of lignite, used as a source of a paraffin fraction melting 40/sup 0/ to 48/sup 0/ (chlorinated to 26.5 percent Cl) and an aromatic fraction, 45 percent aromatic compounds by volume (mainly polysubstituted benzenes), I number 10, was converted to a similar synthetic lubricant with the following properties: Kinematic viscosity at 210/sup 0/ F., 50.4 centistokes; viscosity index, 92; Conradson C, 1.5 percent; solidification point, 9/sup 0/; S, 0.41 percent.

  12. Coloring of synthetic fluorite

    International Nuclear Information System (INIS)

    Birsoy, R.

    1980-01-01

    A synthetic fluorite of the Harshaw Chemical Company is analyzed for rare earth elements, yttrium, and sodium. Samples of this fluorite are irradiated with X-rays, γ-rays, neutrons, electrons, protons, and α-particles at different energies, and their absorption spectra are analyzed. Analyzing the thermal bleaching of these radiation-coloured fluorites shows that both, impurities and radiation play a part in the coloration of synthetic fluorite. However, the main contribution comes from the radiation induced lattice defects. In the visible region spectra, the colour centre of the 5800 to 5900 A absorption band is probably mainly related with large aggregates of F-centres. The 5450 and the 5300 A absorption bands are mainly related to monovalent and divalent ion impurities and their association with lattice defects. The 3800 A absorption band seems to be related with F-centre aggregates. However, the contribution from the rare earth elements related complex color centres also plays some part for the production of this absorption band. These results indicate that the color centres of different origin can absorb light at the same wavelength. (author)

  13. Antioxidation activities of pteridines in mammalian cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Shen, R. (Univ. of Texas, Galveston (United States))

    1991-03-11

    L-erythro-5,6,7,8-Tetrahydrobiopterin (BH{sub 4}), the cofactor for aromatic amino acid hydroxylases (AAA-H), is a predominant form of pteridines which occur ubiquitously in nature. When BH{sub 4} is oxidized to quinonoid dihydrobiopterin by AAA-H, it is regenerated by dihydropteridine reductase (DHPR) at the expense of NADH. The role of BH{sub 4} other than serving as the hydroxylase cofactor is not clear. The existence of BH{sub 4} and DHPR in tissues which are devoid of AAA-H suggests that BH{sub 4} may play an as yet undiscovered physiological function. This study demonstrates a BH{sub 4}-mediated antioxidation system, which consists of BH{sub 4}, DHPR, peroxidase and NADH in rat pheochromocytoma PC 12 cells and mouse macrophages J774A.1. This system was as effective as catalase and ascorbic acid in protecting cells against H{sub 2}O{sub 2} and xanthine/xanthine oxidase-induced toxicity and was more effective than catalase in defense against nitrofurantoin-induced toxicity. The antioxidation effect of this system was not due to peroxidase and was improved when synthetic pteridines were substituted for BH{sub 4}. Since BH{sub 4}, DHPR, peroxidases and NADH are widely distributed in major organs and blood cells, they may constitute an as yet little known antioxidation system in mammalian cells.

  14. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    Science.gov (United States)

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

  15. Space Synthetic Biology Project

    Science.gov (United States)

    Howard, David; Roman, Monsi; Mansell, James (Matt)

    2015-01-01

    Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the

  16. Current status of synthetic epikeratoplasty.

    Science.gov (United States)

    Thompson, K P; Hanna, K; Waring, G O; Gipson, I; Liu, Y; Gailitis, R P; Johnson-Wint, B; Green, K

    1991-01-01

    Many of the deficiencies with human tissue epikeratoplasty might be improved by the use of a suitable synthetic lenticule. Potential biomaterials for epikeratoplasty include collagen (types I, III, or IV), collagen-hydrogel copolymers, bioactive synthetics, and coated hydrogels. The biomaterial must be engineered to achieve strict specifications of optical clarity, support of epithelial migration and adhesion, permeability to solutes, and stability to corneal proteases. Attaching synthetic lenticules to the cornea without cutting Bowman's layer by adhesives, laser welding, or direct adhesion may also improve the efficacy of synthetic epikeratoplasty.

  17. Synthetic biology and occupational risk.

    Science.gov (United States)

    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.

  18. Finding Hope in Synthetic Biology.

    Science.gov (United States)

    Takala, Tuija

    2017-04-01

    For some, synthetic biology represents great hope in offering possible solutions to many of the world's biggest problems, from hunger to sustainable development. Others remain fearful of the harmful uses, such as bioweapons, that synthetic biology can lend itself to, and most hold that issues of biosafety are of utmost importance. In this article, I will evaluate these points of view and conclude that although the biggest promises of synthetic biology are unlikely to become reality, and the probability of accidents is fairly substantial, synthetic biology could still be seen to benefit humanity by enhancing our ethical understanding and by offering a boost to world economy.

  19. Tissue Harmonic Synthetic Aperture Imaging

    DEFF Research Database (Denmark)

    Rasmussen, Joachim

    The main purpose of this PhD project is to develop an ultrasonic method for tissue harmonic synthetic aperture imaging. The motivation is to advance the field of synthetic aperture imaging in ultrasound, which has shown great potentials in the clinic. Suggestions for synthetic aperture tissue...... system complexity compared to conventional synthetic aperture techniques. In this project, SASB is sought combined with a pulse inversion technique for 2nd harmonic tissue harmonic imaging. The advantages in tissue harmonic imaging (THI) are expected to further improve the image quality of SASB...

  20. Life after the synthetic cell

    DEFF Research Database (Denmark)

    Rasmussen, Steen

    2010-01-01

    Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self-replicating ......Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self...

  1. Computational synthetic geometry

    CERN Document Server

    Bokowski, Jürgen

    1989-01-01

    Computational synthetic geometry deals with methods for realizing abstract geometric objects in concrete vector spaces. This research monograph considers a large class of problems from convexity and discrete geometry including constructing convex polytopes from simplicial complexes, vector geometries from incidence structures and hyperplane arrangements from oriented matroids. It turns out that algorithms for these constructions exist if and only if arbitrary polynomial equations are decidable with respect to the underlying field. Besides such complexity theorems a variety of symbolic algorithms are discussed, and the methods are applied to obtain new mathematical results on convex polytopes, projective configurations and the combinatorics of Grassmann varieties. Finally algebraic varieties characterizing matroids and oriented matroids are introduced providing a new basis for applying computer algebra methods in this field. The necessary background knowledge is reviewed briefly. The text is accessible to stud...

  2. Synthetic Aperture Compound Imaging

    DEFF Research Database (Denmark)

    Hansen, Jens Munk

    and the limiting factor is the amount of memory IO resources available. An equally high demand for memory throughput is found in the computer gaming industry, where a large part of the processing takes place on the graphics processing unit (GPU). Using the GPU, a framework for synthetic aperture imaging......Medical ultrasound imaging is used for many purposes, e.g. for localizing and classifying cysts, lesions, and other processes. Almost any mass is first observed using B-mode imaging and later classified using e.g. color flow, strain, or attenuation imaging. It is therefore important that the B......-mode images have high contrast. Like all imaging modalities, ultrasound is subject to a number of inherent artifacts that compromise image quality. The most prominent artifact is the degradation by coherent wave interference, known as “speckle”, which gives a granular appearance to an otherwise homogeneous...

  3. Transionospheric synthetic aperture imaging

    CERN Document Server

    Gilman, Mikhail; Tsynkov, Semyon

    2017-01-01

    This landmark monograph presents the most recent mathematical developments in the analysis of ionospheric distortions of SAR images and offers innovative new strategies for their mitigation. As a prerequisite to addressing these topics, the book also discusses the radar ambiguity theory as it applies to synthetic aperture imaging and the propagation of radio waves through the ionospheric plasma, including the anisotropic and turbulent cases. In addition, it covers a host of related subjects, such as the mathematical modeling of extended radar targets (as opposed to point-wise targets) and the scattering of radio waves off those targets, as well as the theoretical analysis of the start-stop approximation, which is used routinely in SAR signal processing but often without proper justification. The mathematics in this volume is clean and rigorous – no assumptions are hidden or ambiguously stated. The resulting work is truly interdisciplinary, providing both a comprehensive and thorough exposition of the field,...

  4. Radioimmunoassay of synthetic steroids

    Energy Technology Data Exchange (ETDEWEB)

    Raynaud, J -P; Bucourt, R; Salmon, J

    1975-12-01

    The sensitivity of a radioimmunoassay depends on the intrinsic association constant of the interaction between ligand and antibody. Its specificity depends on the position of the chain which forms the link with the antigen. Thus, an antibody specific of estradiol has been obtained by coupling estradiol to albumin via a chain at position 7. For synthetic steroids the structure of which is sufficiency different from that of natural hormones, the requirements for a sensitive assay method not involving chromatography are simply maximum affinity and positioning of the couple at a site which does not undergo metabolic attack. These criteria were used to develop assays for R 2858 and R 2453 which obviate the need to administer radioactive product in clinical pharmacology. Cross-reaction with structural analogs may be used to assay competitors. Thus, R 2323 antibody, highly specific for endogenous steroids, may be used to assay other trienes such as R 1697 (trenbolone) and R 2010 (norgestrienone).

  5. Synthetic fuels and fusion

    Energy Technology Data Exchange (ETDEWEB)

    Fillo, J A; Powell, J; Steinberg, M [Brookhaven National Lab., Upton, NY (USA)

    1981-03-01

    The decreasing availability of fossil fuels emphasizes the need to develop systems which will produce synthetic fuel to substitute for and supplement the natural supply. An important first step in the synthesis of liquid and gaseous fuels is the production of hydrogen. Thermonuclear fusion offers an inexhaustible source of energy for the production of hydrogen from water. Depending on design, electric generation efficiencies of approx. equal to 40-60% and hydrogen production efficiencies by high temperature electrolysis of approx. equal to 50-70% are projected for fusion reactors using high temperature blankets. Fusion/coal symbiotic systems appear economically promising for the first generation of commercial fusion synfuels plants. Coal production requirements and the environmental effects of large-scale coal usage would be greatly reduced by a fusion/coal system. In the long-term, there could be a gradual transition to an inexhaustible energy system based solely on fusion.

  6. Integrating biological redesign: where synthetic biology came from and where it needs to go.

    Science.gov (United States)

    Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

    2014-03-27

    Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.

    2011-01-21

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.

  8. Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters

    OpenAIRE

    Ferreira, Joshua P.; Peacock, Ryan W. S.; Lawhorn, Ingrid E. B.; Wang, Clifford L.

    2011-01-01

    The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evalua...

  9. Antagonistic control of a dual-input mammalian gene switch by food additives.

    Science.gov (United States)

    Xie, Mingqi; Ye, Haifeng; Hamri, Ghislaine Charpin-El; Fussenegger, Martin

    2014-08-01

    Synthetic biology has significantly advanced the design of mammalian trigger-inducible transgene-control devices that are able to programme complex cellular behaviour. Fruit-based benzoate derivatives licensed as food additives, such as flavours (e.g. vanillate) and preservatives (e.g. benzoate), are a particularly attractive class of trigger compounds for orthogonal mammalian transgene control devices because of their innocuousness, physiological compatibility and simple oral administration. Capitalizing on the genetic componentry of the soil bacterium Comamonas testosteroni, which has evolved to catabolize a variety of aromatic compounds, we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate. When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme. Additionally, the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch. Designer gene switches using licensed food additives as trigger compounds to achieve antagonistic dual-input expression profiles and provide novel control topologies and regulation dynamics may advance future gene- and cell-based therapies. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. The food additive vanillic acid controls transgene expression in mammalian cells and mice.

    Science.gov (United States)

    Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

    2012-03-01

    Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

  11. Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.

    Science.gov (United States)

    Li, Kui; Sun, Xiaohui; Chen, Meixiu; Sun, Yingying; Tian, Ran; Wang, Zhengfei; Xu, Shixia; Yang, Guang

    2018-01-01

    The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body. © 2017 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  12. Radiation effects in mammalian cells in vitro

    International Nuclear Information System (INIS)

    Hill, C.K.; Han, A.; Elkind, M.M.; Wells, R.L.; Buess, E.M.; Lin, C.M.

    1985-01-01

    The purpose of this research effort is to elucidate the mechanisms for the radiation-induced changes in mammalian cells that lead to cell death, mutation, neoplastic transformation, DNA damage, and chromosomal alterations. Of particular interest are the effects of low-dose-rate and fractionated irradiation on these end points with respect to the mechanisms whereby these effects are influenced by cellular repair processes, inhibitors, and promoters that act at the genetic or biochemical level. 17 refs

  13. Cellular and Chemical Neuroscience of Mammalian Sleep

    OpenAIRE

    Datta, Subimal

    2010-01-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

  14. Comparison of amphibian and mammalian thyroperoxidase ...

    Science.gov (United States)

    Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

  15. Imaging with Synthetic Aperture Radar

    CERN Document Server

    Massonnet, Didier

    2008-01-01

    Describing a field that has been transformed by the recent availability of data from a new generation of space and airborne systems, the authors offer a synthetic geometrical approach to the description of synthetic aperture radar, one that addresses physicists, radar specialists, as well as experts in image processing.  

  16. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

  17. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)

    1995-01-01

    textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

  18. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

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

  19. The Ethics of Synthetic Biology

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    The dissertation analyses and discusses a number of ethical issues that have been raised in connection with the development of synthetic biology. Synthetic biology is a set of new techniques for DNA-level design and construction of living beings with useful properties. The dissertation especially...

  20. Synthetic biology of polyketide synthases

    DEFF Research Database (Denmark)

    Yuzawa, Satoshi; Backman, Tyler W.H.; Keasling, Jay D.

    2018-01-01

    ). The modules are composed of enzymatic domains that share sequence and functional similarity across all known PKSs. We have used the nomenclature of synthetic biology to classify the enzymatic domains and modules as parts and devices, respectively, and have generated detailed lists of both. In addition, we...... realize the potential that synthetic biology approaches bring to this class of molecules....

  1. Computing with synthetic protocells.

    Science.gov (United States)

    Courbet, Alexis; Molina, Franck; Amar, Patrick

    2015-09-01

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

  2. Synthetic Biology and Personalized Medicine

    Science.gov (United States)

    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

  3. Synthetic Biology: Advancing Biological Frontiers by Building Synthetic Systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E; Smolke, Christina D

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  4. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  5. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  6. Mammalian developmental genetics in the twentieth century.

    Science.gov (United States)

    Artzt, Karen

    2012-12-01

    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.

  7. Nutrient acquisition strategies of mammalian cells.

    Science.gov (United States)

    Palm, Wilhelm; Thompson, Craig B

    2017-06-07

    Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

  8. Preservation of mammalian germ plasm by freezing

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, P.

    1978-01-01

    Embryos of several mammalian species can be frozen to -196/sup 0/C (or below) by procedures that result in the thawed embryos being indistinguishable from their unfrozen counterparts. The survival often exceeds 90%, and in liquid nitrogen it should remain at that high level for centuries. Sublethal biochemical changes are also precluded at -196/sup 0/C. No developmental abnormalities have been detected in mouse offspring derived from frozen-thawed embryos, and, since all the manipulations are carried out on the preimplantation stages, none would be expected.

  9. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    Science.gov (United States)

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years.

  10. Mammalian Gravity Receptors: Structure and Metabolism

    Science.gov (United States)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  11. Approaches to chemical synthetic biology.

    Science.gov (United States)

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

    2012-07-16

    Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Synthetic Biology for Specialty Chemicals.

    Science.gov (United States)

    Markham, Kelly A; Alper, Hal S

    2015-01-01

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

  13. Is synthetic biology mechanical biology?

    Science.gov (United States)

    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.

  14. Adaptive Synthetic Forces: Situation Awareness

    National Research Council Canada - National Science Library

    Hill, Randall

    2001-01-01

    ...: perception, comprehension, and prediction. Building on these ideas, we developed techniques for improving the situation awareness in synthetic helicopter pilots for the ModSAF military simulation by giving them more human-like perception...

  15. Programming languages for synthetic biology.

    Science.gov (United States)

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

    2010-12-01

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

  16. Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

    Science.gov (United States)

    Jenkins, F A; Crompton, A W; Downs, W R

    1983-12-16

    Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

  17. Ecology and evolution of mammalian biodiversity.

    Science.gov (United States)

    Jones, Kate E; Safi, Kamran

    2011-09-12

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future.

  18. The mammalian ovary from genesis to revelation.

    Science.gov (United States)

    Edson, Mark A; Nagaraja, Ankur K; Matzuk, Martin M

    2009-10-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

  19. Ecology and evolution of mammalian biodiversity

    Science.gov (United States)

    Jones, Kate E.; Safi, Kamran

    2011-01-01

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

  20. Focusing on RISC assembly in mammalian cells.

    Science.gov (United States)

    Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  1. Focusing on RISC assembly in mammalian cells

    International Nuclear Information System (INIS)

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

    2008-01-01

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

  2. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

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

    Science.gov (United States)

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

    2015-08-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

  4. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    Science.gov (United States)

    Campbell, A. Malcolm

    2005-01-01

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

  5. Synthetic biology, metaphors and responsibility.

    Science.gov (United States)

    McLeod, Carmen; Nerlich, Brigitte

    2017-08-29

    Metaphors are not just decorative rhetorical devices that make speech pretty. They are fundamental tools for thinking about the world and acting on the world. The language we use to make a better world matters; words matter; metaphors matter. Words have consequences - ethical, social and legal ones, as well as political and economic ones. They need to be used 'responsibly'. They also need to be studied carefully - this is what we want to do through this editorial and the related thematic collection. In the context of synthetic biology, natural and social scientists have become increasingly interested in metaphors, a wave of interest that we want to exploit and amplify. We want to build on emerging articles and books on synthetic biology, metaphors of life and the ethical and moral implications of such metaphors. This editorial provides a brief introduction to synthetic biology and responsible innovation, as well as a comprehensive review of literature on the social, cultural and ethical impacts of metaphor use in genomics and synthetic biology. Our aim is to stimulate an interdisciplinary and international discussion on the impact that metaphors can have on science, policy and publics in the context of synthetic biology.

  6. Content metamorphosis in synthetic holography

    International Nuclear Information System (INIS)

    Desbiens, Jacques

    2013-01-01

    A synthetic hologram is an optical system made of hundreds of images amalgamated in a structure of holographic cells. Each of these images represents a point of view on a three-dimensional space which makes us consider synthetic holography as a multiple points of view perspective system. In the composition of a computer graphics scene for a synthetic hologram, the field of view of the holographic image can be divided into several viewing zones. We can attribute these divisions to any object or image feature independently and operate different transformations on image content. In computer generated holography, we tend to consider content variations as a continuous animation much like a short movie. However, by composing sequential variations of image features in relation with spatial divisions, we can build new narrative forms distinct from linear cinematographic narration. When observers move freely and change their viewing positions, they travel from one field of view division to another. In synthetic holography, metamorphoses of image content are within the observer's path. In all imaging Medias, the transformation of image features in synchronisation with the observer's position is a rare occurrence. However, this is a predominant characteristic of synthetic holography. This paper describes some of my experimental works in the development of metamorphic holographic images.

  7. Control theory meets synthetic biology.

    Science.gov (United States)

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

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. © 2016 The Author(s).

  8. A universal mammalian vaccine cell line substrate.

    Directory of Open Access Journals (Sweden)

    Jackelyn Murray

    Full Text Available Using genome-wide small interfering RNA (siRNA screens for poliovirus, influenza A virus and rotavirus, we validated the top 6 gene hits PV, RV or IAV to search for host genes that when knocked-down (KD enhanced virus permissiveness and replication over wild type Vero cells or HEp-2 cells. The enhanced virus replication was tested for 12 viruses and ranged from 2-fold to >1000-fold. There were variations in virus-specific replication (strain differences across the cell lines examined. Some host genes (CNTD2, COQ9, GCGR, NDUFA9, NEU2, PYCR1, SEC16G, SVOPL, ZFYVE9, and ZNF205 showed that KD resulted in enhanced virus replication. These findings advance platform-enabling vaccine technology, the creation of diagnostic cells substrates, and are informative about the host mechanisms that affect virus replication in mammalian cells.

  9. Modeling Exposure of Mammalian Predatorsto Anticoagulant Rodenticides

    DEFF Research Database (Denmark)

    Topping, Christopher John; Elmeros, Morten

    2016-01-01

    as vectors of AR, and was used to evaluate likely impacts of restrictions imposed on AR use in Denmark banning the use of rodenticides for plant protection in woodlands and tree-crops. The model uses input based on frequencies and timings of baiting for rodent control for urban, rural and woodland locations......Anticoagulant rodenticides (AR) are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is very...... high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice...

  10. Physiological significance of polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; de Bruin, Alain

    2013-11-01

    Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. X-rays sensitive mammalian cell mutant

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1982-01-01

    A phenomenon that in x-ray-sensitive mammalian-cell mutants, cellular death due to x-ray radiation was not increased by caffeine, but on the contrary, the dead cells were resuscitated by it was discussed. The survival rate of mutant cells increased by caffein in a low concentration. This suggested that caffeine may have induced some mechanism to produce x-ray resistant mutant cells. Postirradiation treatment with caffeine increased considerably the survival rate of the mutant cells, and this suggested the existence of latent caffeine-sensitive potentially lethal damage repair system. This system, after a few hours, is thought to be substituted by caffeine-resistant repair system which is induced by caffeine, and this may be further substituted by x-ray-resistant repair system. The repair system was also induced by adenine. (Ueda, J.)

  12. Redox signaling during hypoxia in mammalian cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Smith

    2017-10-01

    Full Text Available Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS such as hydrogen peroxide (H2O2 occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(PH oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

  13. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  14. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  15. Cellular and chemical neuroscience of mammalian sleep.

    Science.gov (United States)

    Datta, Subimal

    2010-05-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Magnetism in plant and mammalian ferritin

    International Nuclear Information System (INIS)

    Bauminger, E.R.; Nowik, I.

    1989-01-01

    A rich variety of magnetic phenomena is observed in Moessbauer studies of ferritin. Depending on the amount of iron in the horse spleen ferritin core, a paramagnetic relaxation spectrum, or quadrupole split doublet or a magnetically split sextet showing superparamagnetism, are obtained at 4.1 K. Moessbauer studies of the recently prepared iron loaded concanavalin A yield hyperfine parameters identical to those found previously in mammalian ferritin, yet show the existence of larger iron aggregates. Due to the larger particle size it is possible to follow the magnetic hyperfine field and to obtain the magnetic ordering temperature as 240 K. This is exactly the Neel temperature of ferrihydrite, thus establishing that this is indeed the iron compound in the ferritin core. (orig.)

  17. Engineered Trehalose Permeable to Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Alireza Abazari

    Full Text Available Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre and trehalose tetraacetate (4-O-Ac-Tre. Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies.

  18. The DNA damage response in mammalian oocytes

    Directory of Open Access Journals (Sweden)

    John eCarroll

    2013-06-01

    Full Text Available DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumour formation. In the context of oocytes, the impact of DNA damage is not one of tumour formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.

  19. The architecture of mammalian ribosomal protein promoters

    Directory of Open Access Journals (Sweden)

    Perry Robert P

    2005-02-01

    Full Text Available Abstract Background Mammalian ribosomes contain 79 different proteins encoded by widely scattered single copy genes. Coordinate expression of these genes at transcriptional and post-transcriptional levels is required to ensure a roughly equimolar accumulation of ribosomal proteins. To date, detailed studies of only a very few ribosomal protein (rp promoters have been made. To elucidate the general features of rp promoter architecture, I made a detailed sequence comparison of the promoter regions of the entire set of orthologous human and mouse rp genes. Results A striking evolutionarily conserved feature of most rp genes is the separation by an intron of the sequences involved in transcriptional and translational regulation from the sequences with protein encoding function. Another conserved feature is the polypyrimidine initiator, which conforms to the consensus (Y2C+1TY(T2(Y3. At least 60 % of the rp promoters contain a largely conserved TATA box or A/T-rich motif, which should theoretically have TBP-binding capability. A remarkably high proportion of the promoters contain conserved binding sites for transcription factors that were previously implicated in rp gene expression, namely upstream GABP and Sp1 sites and downstream YY1 sites. Over 80 % of human and mouse rp genes contain a transposable element residue within 900 bp of 5' flanking sequence; very little sequence identity between human and mouse orthologues was evident more than 200 bp upstream of the transcriptional start point. Conclusions This analysis has provided some valuable insights into the general architecture of mammalian rp promoters and has identified parameters that might coordinately regulate the transcriptional activity of certain subsets of rp genes.

  20. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  1. Plasma treatment of mammalian vascular cells : A quantitative description

    NARCIS (Netherlands)

    Kieft, IE; Darios, D; Roks, AJM; Stoffels, E

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  2. Plasma treatment of mammalian vascular cells: a quantitative description

    NARCIS (Netherlands)

    Kieft, I.E.; Darios, D.; Roks, A.J.M.; Stoffels - Adamowicz, E.

    2005-01-01

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  3. Microfluidic Technologies for Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Sung Kuk Lee

    2011-06-01

    Full Text Available Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

  4. Synthetic neurosteroids on brain protection

    Directory of Open Access Journals (Sweden)

    Mariana Rey

    2015-01-01

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

  5. Synthetic biology as red herring.

    Science.gov (United States)

    Preston, Beth

    2013-12-01

    It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. US Competitiveness in Synthetic Biology.

    Science.gov (United States)

    Gronvall, Gigi Kwik

    2015-01-01

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

  7. On activation of cholesterologenesis under the effect of ionizing radiation on mammalian body

    International Nuclear Information System (INIS)

    Kolomijtseva, I.K.

    1986-01-01

    The assumption is made that ionizing radiation induces cholesterologenesis activation in different cells of mammalian organism as an early reaction to the harmful effect necessary for restoration of biomembranes. Liver cells activate adaptively the cholesterol synthesis in the animal body irradiated with lethal doses in response to the injury to radiosensitive cells in order to make them recover and compensate for their functions (with the gastrointestinal syndrome, for instance, to compensate for the cholesterol-producing function of the intestine and to make it recover). With lethal radiation doses, a change in the lipid content and metabolism of microsomal membrane lipids of the liver is associated with activation of synthetic functions of the liver due to compensation of the injury to radiosensitive tissues

  8. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  9. Synthetic biology and its promises

    Directory of Open Access Journals (Sweden)

    José Manuel De Cózar Escalante

    2016-12-01

    Full Text Available Synthetic biology is a new science and emerging technology, or rather a technoscience, which converges with others such as nanotechnology, information technology, robotics, artificial intelligence and neuroscience. All have common features that could have highly concerning social and environmental impacts. With its ambitious goals of controlling complexity, redesigning and creating new living entities, synthetic biology perfectly exemplifies the new bioeconomic reality. This requires expanding the focus of the discussion beyond the limited comparative analysis of risks and benefits, to address uncertainties, reassign responsibilities and initiate a thorough social assessment of what is at stake.

  10. Targeted mutations induced by a single acetylaminofluorene DNA adduct in mammalian cells and bacteria

    International Nuclear Information System (INIS)

    Moryia, M.; Takeshita, M.; Johnson, F.; Peden, K.; Will, S.; Grollman, A.P.

    1988-01-01

    Mutagenic specificity of 2-acetylaminofluorene (AAF) has been established in mammalian cells and several strains of bacteria by using a shuttle plasmid vector containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene (C8-dG-AAF) adduct. The nucleotide sequence of the gene conferring tetracycline resistance was modified by conservative codon replacement so as to accommodate the sequence d(CCTTCGCTAC) flanked by two restriction sites, Bsm I and Xho I. The corresponding synthetic oligodeoxynucleotide underwent reaction with 2-(N-acetoxy-N-acetylamino)-fluorene (AAAF), forming a single dG-AAF adduct. This modified oligodeoxynucleotide was hybridized to its complementary strand and ligated between the Bsm I and Xho I sites of the vector. Plasmids containing the C8-dG-AAF adduct were used to transfect simian virus 40-transformed simian kidney (COS-1) cells and to transform several AB strains of Escherichia coli. Colonies containing mutant plasmides were detected by hybridization to 32 P-labeled oligodeoxynucleotides. Presence of the single DNA adduct increased the mutation frequency by 8-fold in both COS cells and E. coli. Over 80% of mutations detected in both systems were targeted and represented G x C → C x G or G x C → T x A transversions or single nucleotide deletions. The authors conclude that modification of a deoxyguanosine residue with AAF preferentially induces mutations targeted at this site when a plasmid containing a single C8-dG-AAF adduct is introduced into mammalian cells or bacteria

  11. A multi-landing pad DNA integration platform for mammalian cell engineering

    Science.gov (United States)

    Gaidukov, Leonid; Wroblewska, Liliana; Teague, Brian; Nelson, Tom; Zhang, Xin; Liu, Yan; Jagtap, Kalpana; Mamo, Selamawit; Tseng, Wen Allen; Lowe, Alexis; Das, Jishnu; Bandara, Kalpanie; Baijuraj, Swetha; Summers, Nevin M; Zhang, Lin; Weiss, Ron

    2018-01-01

    Abstract Engineering mammalian cell lines that stably express many transgenes requires the precise insertion of large amounts of heterologous DNA into well-characterized genomic loci, but current methods are limited. To facilitate reliable large-scale engineering of CHO cells, we identified 21 novel genomic sites that supported stable long-term expression of transgenes, and then constructed cell lines containing one, two or three ‘landing pad’ recombination sites at selected loci. By using a highly efficient BxB1 recombinase along with different selection markers at each site, we directed recombinase-mediated insertion of heterologous DNA to selected sites, including targeting all three with a single transfection. We used this method to controllably integrate up to nine copies of a monoclonal antibody, representing about 100 kb of heterologous DNA in 21 transcriptional units. Because the integration was targeted to pre-validated loci, recombinant protein expression remained stable for weeks and additional copies of the antibody cassette in the integrated payload resulted in a linear increase in antibody expression. Overall, this multi-copy site-specific integration platform allows for controllable and reproducible insertion of large amounts of DNA into stable genomic sites, which has broad applications for mammalian synthetic biology, recombinant protein production and biomanufacturing. PMID:29617873

  12. Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Y.

    1989-01-01

    The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the {alpha}-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced {sup 22}Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the {gamma}, {delta}, and {epsilon} subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four ({alpha}, {beta}, {gamma}, and {delta}) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the {alpha}, {beta}, and {delta} subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the {gamma}- and {epsilon}- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the {gamma} is replaced by {epsilon}.

  13. Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

    International Nuclear Information System (INIS)

    Gu, Y.

    1989-01-01

    The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the α-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced 22 Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the γ, δ, and ε subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four (α, β, γ, and δ) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the α, β, and δ subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the γ- and ε- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the γ is replaced by ε

  14. Fluorescence and confocal imaging of mammalian cells using conjugated oligoelectrolytes with phenylenevinylene core

    Energy Technology Data Exchange (ETDEWEB)

    Milczarek, Justyna; Pawlowska, Roza; Zurawinski, Remigiusz; Lukasik, Beata; Garner, Logan E.; Chworos, Arkadiusz

    2017-05-01

    Over the last few years, considerable efforts are taken, in order to find a molecular fluorescent probe fulfilling their applicability requirements. Due to a good optical properties and affinity to biological structures conjugated oligoelectrolytes (COEs) can be considered as a promising dyes for application in fluorescence-based bioimaging. In this work, we synthetized COEs with phenylenevinylene core (PV-COEs) and applied as fluorescent membranous-specific probes. Cytotoxicity effects of each COE were probed on cancerous and non-cancerous cell types and little to no toxicity effects were observed at the high range of concentrations. The intensity of cell fluorescence following the COE staining was determined by the photoluminescence analysis and fluorescence activated cell sorting method (FACS). Intercalation of tested COEs into mammalian cell membranes was revealed by fluorescent and confocal microscopy colocalization with commercial dyes specific for cellular structures including mitochondria, Golgi apparatus and endoplasmic reticulum. The phenylenevinylene conjugated oligoelectrolytes have been found to be suitable for fluorescent bioimaging of mammalian cells and membrane-rich organelles. Due to their water solubility coupled with spontaneous intercalation into cells, favorable photophysical features, ease of cell staining, low cytotoxicity and selectivity for membranous structures, PV-COEs can be applied as markers for fluorescence imaging of a variety of cell types.

  15. Where Synthetic Biology Meets ET

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

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

  16. Stereoscopy in cinematographic synthetic imagery

    Science.gov (United States)

    Eisenmann, Jonathan; Parent, Rick

    2009-02-01

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

  17. Synthetic biology meets tissue engineering.

    Science.gov (United States)

    Davies, Jamie A; Cachat, Elise

    2016-06-15

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

  18. Shock compression of synthetic opal

    International Nuclear Information System (INIS)

    Inoue, A; Okuno, M; Okudera, H; Mashimo, T; Omurzak, E; Katayama, S; Koyano, M

    2010-01-01

    Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO 4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO 2 glass. However, internal silanole groups still remain even at 38.1 GPa.

  19. Assessment of synthetic image fidelity

    Science.gov (United States)

    Mitchell, Kevin D.; Moorhead, Ian R.; Gilmore, Marilyn A.; Watson, Graham H.; Thomson, Mitch; Yates, T.; Troscianko, Tomasz; Tolhurst, David J.

    2000-07-01

    Computer generated imagery is increasingly used for a wide variety of purposes ranging from computer games to flight simulators to camouflage and sensor assessment. The fidelity required for this imagery is dependent on the anticipated use - for example when used for camouflage design it must be physically correct spectrally and spatially. The rendering techniques used will also depend upon the waveband being simulated, spatial resolution of the sensor and the required frame rate. Rendering of natural outdoor scenes is particularly demanding, because of the statistical variation in materials and illumination, atmospheric effects and the complex geometric structures of objects such as trees. The accuracy of the simulated imagery has tended to be assessed subjectively in the past. First and second order statistics do not capture many of the essential characteristics of natural scenes. Direct pixel comparison would impose an unachievable demand on the synthetic imagery. For many applications, such as camouflage design, it is important that nay metrics used will work in both visible and infrared wavebands. We are investigating a variety of different methods of comparing real and synthetic imagery and comparing synthetic imagery rendered to different levels of fidelity. These techniques will include neural networks (ICA), higher order statistics and models of human contrast perception. This paper will present an overview of the analyses we have carried out and some initial results along with some preliminary conclusions regarding the fidelity of synthetic imagery.

  20. Shock compression of synthetic opal

    Science.gov (United States)

    Inoue, A.; Okuno, M.; Okudera, H.; Mashimo, T.; Omurzak, E.; Katayama, S.; Koyano, M.

    2010-03-01

    Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO2 glass. However, internal silanole groups still remain even at 38.1 GPa.

  1. Shock compression of synthetic opal

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, A; Okuno, M; Okudera, H [Department of Earth Sciences, Kanazawa University Kanazawa, Ishikawa, 920-1192 (Japan); Mashimo, T; Omurzak, E [Shock Wave and Condensed Matter Research Center, Kumamoto University, Kumamoto, 860-8555 (Japan); Katayama, S; Koyano, M, E-mail: okuno@kenroku.kanazawa-u.ac.j [JAIST, Nomi, Ishikawa, 923-1297 (Japan)

    2010-03-01

    Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO{sub 4} tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO{sub 2} glass. However, internal silanole groups still remain even at 38.1 GPa.

  2. Methods for preparing synthetic freshwaters.

    Science.gov (United States)

    Smith, E J; Davison, W; Hamilton-Taylor, J

    2002-03-01

    Synthetic solutions that emulate the major ion compositions of natural waters are useful in experiments aimed at understanding biogeochemical processes. Standard recipes exist for preparing synthetic analogues of seawater, with its relatively constant composition, but, due to the diversity of freshwaters, a range of compositions and recipes is required. Generic protocols are developed for preparing synthetic freshwaters of any desired composition. The major problems encountered in preparing hard and soft waters include dissolving sparingly soluble calcium carbonate, ensuring that the ionic components of each concentrated stock solution cannot form an insoluble salt and dealing with the supersaturation of calcium carbonate in many hard waters. For acidic waters the poor solubility of aluminium salts requires attention. These problems are overcome by preparing concentrated stock solutions according to carefully designed reaction paths that were tested using a combination of experiment and equilibrium modeling. These stock solutions must then be added in a prescribed order to prepare a final solution that is brought into equilibrium with the atmosphere. The example calculations for preparing hard, soft and acidic freshwater surrogates with major ion compositions the same as published analyses, are presented in a generalized fashion that should allow preparation of any synthetic freshwater according to its known analysis.

  3. Annotation of mammalian primary microRNAs

    Directory of Open Access Journals (Sweden)

    Enright Anton J

    2008-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are important regulators of gene expression and have been implicated in development, differentiation and pathogenesis. Hundreds of miRNAs have been discovered in mammalian genomes. Approximately 50% of mammalian miRNAs are expressed from introns of protein-coding genes; the primary transcript (pri-miRNA is therefore assumed to be the host transcript. However, very little is known about the structure of pri-miRNAs expressed from intergenic regions. Here we annotate transcript boundaries of miRNAs in human, mouse and rat genomes using various transcription features. The 5' end of the pri-miRNA is predicted from transcription start sites, CpG islands and 5' CAGE tags mapped in the upstream flanking region surrounding the precursor miRNA (pre-miRNA. The 3' end of the pri-miRNA is predicted based on the mapping of polyA signals, and supported by cDNA/EST and ditags data. The predicted pri-miRNAs are also analyzed for promoter and insulator-associated regulatory regions. Results We define sets of conserved and non-conserved human, mouse and rat pre-miRNAs using bidirectional BLAST and synteny analysis. Transcription features in their flanking regions are used to demarcate the 5' and 3' boundaries of the pri-miRNAs. The lengths and boundaries of primary transcripts are highly conserved between orthologous miRNAs. A significant fraction of pri-miRNAs have lengths between 1 and 10 kb, with very few introns. We annotate a total of 59 pri-miRNA structures, which include 82 pre-miRNAs. 36 pri-miRNAs are conserved in all 3 species. In total, 18 of the confidently annotated transcripts express more than one pre-miRNA. The upstream regions of 54% of the predicted pri-miRNAs are found to be associated with promoter and insulator regulatory sequences. Conclusion Little is known about the primary transcripts of intergenic miRNAs. Using comparative data, we are able to identify the boundaries of a significant proportion of

  4. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby

    2010-01-01

    Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

  5. A versatile cis-acting inverter module for synthetic translational switches.

    Science.gov (United States)

    Endo, Kei; Hayashi, Karin; Inoue, Tan; Saito, Hirohide

    2013-01-01

    Artificial genetic switches have been designed and tuned individually in living cells. A method to directly invert an existing OFF switch to an ON switch should be highly convenient to construct complex circuits from well-characterized modules, but developing such a technique has remained a challenge. Here we present a cis-acting RNA module to invert the function of a synthetic translational OFF switch to an ON switch in mammalian cells. This inversion maintains the property of the parental switch in response to a particular input signal. In addition, we demonstrate simultaneous and specific expression control of both the OFF and ON switches. The module fits the criteria of universality and expands the versatility of mRNA-based information processing systems developed for artificially controlling mammalian cellular behaviour.

  6. Precision control of recombinant gene transcription for CHO cell synthetic biology.

    Science.gov (United States)

    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.

  7. Origins and Impacts of New Mammalian Exons

    Directory of Open Access Journals (Sweden)

    Jason J. Merkin

    2015-03-01

    Full Text Available Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5′ UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5′ ends of genes enhances expression and that changes in 5′ end splicing alter gene expression between tissues and between species.

  8. Imaging intraflagellar transport in mammalian primary cilia.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Roy, Barnali; Shah, Jagesh V

    2009-01-01

    The primary cilium is a specialized organelle that projects from the surface of many cell types. Unlike its motile counterpart it cannot beat but does transduce extracellular stimuli into intracellular signals and acts as a specialized subcellular compartment. The cilium is built and maintained by the transport of proteins and other biomolecules into and out of this compartment. The trafficking machinery for the cilium is referred to as IFT or intraflagellar transport. It was originally identified in the green algae Chlamydomonas and has been discovered throughout the evolutionary tree. The IFT machinery is widely conserved and acts to establish, maintain, and disassemble cilia and flagella. Understanding the role of IFT in cilium signaling and regulation requires a methodology for observing it directly. Here we describe current methods for observing the IFT process in mammalian primary cilia through the generation of fluorescent protein fusions and their expression in ciliated cell lines. The observation protocol uses high-resolution time-lapse microscopy to provide detailed quantitative measurements of IFT particle velocities in wild-type cells or in the context of genetic or other perturbations. Direct observation of IFT trafficking will provide a unique tool to dissect the processes that govern cilium regulation and signaling. 2009 Elsevier Inc. All rights reserved.

  9. DNA synthesis in irradiated mammalian cells

    International Nuclear Information System (INIS)

    Painter, R.B.; California Univ., San Francisco; Young, B.R.

    1987-01-01

    One of the first responses observed in S phase mammalian cells that have suffered DNA damage is the inhibition of initiation of DNA replicons. In cells exposed to ionizing radiation, a single-strand break appears to be the stimulus for this effect, whereby the initiation of many adjacent replicons (a replicon cluster) is blocked by a single-strand break in any one of them. In cells exposed to ultraviolet light (u.v.), replicon initiation is blocked at fluences that induce about one pyrimidine dimer per replicon. The inhibition of replicon initiation by u.v. in Chinese hamster cells that are incapable of excising pyrimidine dimers from their DNA is virtually the same as in cells that are proficient in dimer excision. Therefore, a single-strand break formed during excision repair of pyrimidine dimers is not the stimulus for inhibition of replicon initiation in u.v.-irradiated cells. Considering this fact, as well as the comparative insensitivity of human ataxia telangiectasia cells to u.v.-induced inhibition of replicon initiation, we propose that a relatively rare lesion is the stimulus for u.v. -induced inhibition of replicon initiation. (author

  10. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  11. Apoptosis in mammalian oocytes: a review.

    Science.gov (United States)

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

  12. Protection of cultured mammalian cells by rebamipide

    Energy Technology Data Exchange (ETDEWEB)

    Antoku, Shigetoshi; Aramaki, Ryoji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine; Tanaka, Hisashi; Kusumoto, Naotoshi

    1997-06-01

    Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle`s minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO{sub 2} incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with {sup 14}C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleus rather than cytoplasm. (author)

  13. Mammalian oocyte growth and development in vitro.

    Science.gov (United States)

    Eppig, J J; O'Brien, M; Wigglesworth, K

    1996-06-01

    This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk.

  14. A rule of thumb in mammalian herbivores?

    Science.gov (United States)

    Augner; Provenza; Villalba

    1998-08-01

    In two experiments on appetitive learning we conditioned lambs, Ovis aries, to particular concentrations of a flavour by mixing the flavour with an energy-rich food that complemented their energy-poor diet. The lambs were subsequently offered energy-rich food with five different concentrations of the flavour (the concentration to which they were conditioned, two higher concentrations, and two lower concentrations). At these tests, the lambs consistently preferred the weaker flavours. This finding stands in contrast to earlier results on generalization gradients. In a third experiment, similarly designed to the other two, we tested for effects of a strong flavour on the behaviour of lambs when they were offered a novel nutritious food. Half of the lambs were offered unadulterated wheat, and the others strongly flavoured wheat. We found that the flavour in itself was initially aversive. We propose that the lambs' avoidance of foods with strong flavours may be an expression of a rule of thumb of the type 'given a choice, avoid food with strong flavours'. Such a rule could be part of a risk-averse foraging strategy displayed by mammalian herbivores, and which could be of particular importance when they encounter unfamiliar foods. Copyright 1998 The Association for the Study of Animal Behaviour

  15. Functional Amyloid Formation within Mammalian Tissue.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

  16. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  17. Protection of cultured mammalian cells by rebamipide

    International Nuclear Information System (INIS)

    Antoku, Shigetoshi; Aramaki, Ryoji; Tanaka, Hisashi; Kusumoto, Naotoshi.

    1997-01-01

    Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO 2 incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with 14 C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleus rather than cytoplasm. (author)

  18. Angiogenesis is inhibitory for mammalian digit regeneration

    Science.gov (United States)

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration. PMID:27499862

  19. Functional amyloid formation within mammalian tissue.

    Directory of Open Access Journals (Sweden)

    Douglas M Fowler

    2006-01-01

    Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

  20. Mitochondrial dynamics in mammalian health and disease.

    Science.gov (United States)

    Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

    2009-07-01

    The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

  1. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  2. A hybrid mammalian cell cycle model

    Directory of Open Access Journals (Sweden)

    Vincent Noël

    2013-08-01

    Full Text Available Hybrid modeling provides an effective solution to cope with multiple time scales dynamics in systems biology. Among the applications of this method, one of the most important is the cell cycle regulation. The machinery of the cell cycle, leading to cell division and proliferation, combines slow growth, spatio-temporal re-organisation of the cell, and rapid changes of regulatory proteins concentrations induced by post-translational modifications. The advancement through the cell cycle comprises a well defined sequence of stages, separated by checkpoint transitions. The combination of continuous and discrete changes justifies hybrid modelling approaches to cell cycle dynamics. We present a piecewise-smooth version of a mammalian cell cycle model, obtained by hybridization from a smooth biochemical model. The approximate hybridization scheme, leading to simplified reaction rates and binary event location functions, is based on learning from a training set of trajectories of the smooth model. We discuss several learning strategies for the parameters of the hybrid model.

  3. Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

    Directory of Open Access Journals (Sweden)

    Jung Dongju

    2012-06-01

    Full Text Available Abstract Background Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. Results Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. Conclusions PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations.

  4. Catalysts for synthetic liquid fuels

    Energy Technology Data Exchange (ETDEWEB)

    Bruce, L.A.; Turney, T.W.

    1987-12-01

    Fischer-Tropsch catalysts have been designed, characterized and tested for the selective production of hydrocarbons suitable as synthetic liquid transport fuels from synthesis gas (i.e., by the reduction of carbon monoxide with hydrogen). It was found that hydrocarbons in the middle distillate range, or suitable for conversion to that range, could be produced over several of the new catalyst systems. The various catalysts examined included: (1) synthetic cobalt clays, mainly cobalt chlorites; (2) cobalt hydrotalcites; (3) ruthenium metal supported on rare earth oxides of high surface area; and (4) a novel promoted cobalt catalyst. Active and selective catalysts have been obtained, in each category. With the exception of the clays, reproducibility of catalyst performance has been good. Catalysts in groups 2 and 4 have exhibited very high activity, with long lifetimes and easy regeneration.

  5. Design Automation in Synthetic Biology.

    Science.gov (United States)

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

    2017-04-03

    Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. Synthetic biology character and impact

    CERN Document Server

    Pade, Christian; Wigger, Henning; Gleich, Arnim

    2015-01-01

    Synthetic Biology is already an object of intensive debate. However, to a great extent the discussion to date has been concerned with fundamental ethical, religious and philosophical questions. By contrast, based on an investigation of the field’s scientific and technological character, this book focuses on new functionalities provided by synthetic biology and explores the associated opportunities and risks. Following an introduction to the subject and a discussion of the most central paradigms and methodologies, the book provides an overview of the structure of this field of science and technology. It informs the reader about the current stage of development, as well as topical problems and potential opportunities in important fields of application. But not only the science itself is in focus. In order to investigate its broader impact, ecological as well as ethical implications will be considered, paving the way for a discussion of responsibilities in the context of a field at a transitional crossroads be...

  7. Synthetic greenhouse gases under control

    International Nuclear Information System (INIS)

    Horisberger, B.; Karlaganis, G.

    2003-01-01

    This article discusses new Swiss regulations on the use of synthetic materials that posses a considerable greenhouse-warming potential. Synthetic materials such as hydro-chlorofluorocarbons HCFCs, perfluoride-hydrocarbons and sulphur hexafluoride have, in recent years, replaced chlorofluorocarbons CFCs, which were banned on account of their ozone depletion characteristics. The use of these persistent substances is now being limited to applications where more environment-friendly alternatives are not available. The measures decreed in the legislation, which include a general ban on HCFCs as of 2004 and a ban on the export of installations and equipment that use ozone-depleting refrigerants are described. Details on the legislation's effects on the Swiss refrigeration industry are listed and discussed

  8. Synthetic LDL as targeted drug delivery vehicle

    Science.gov (United States)

    Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA

    2012-08-28

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

  9. Vibrational spectrum of synthetic carnotite

    Energy Technology Data Exchange (ETDEWEB)

    Baran, E J; Botto, I L [La Plata Univ. Nacional (Argentina). Facultad de Ciencias Exactas

    1976-05-01

    The infrared and laser-Raman spectra of synthetic carnotite, K/sub 2/((UO/sub 2/)/sub 2/V/sub 2/O/sub 8/), are reported and discussed. Force constants for the terminal V-O bonds as well as for the UO/sub 2//sup 2 +/ ions are evaluated. From the spectroscopic data, a U-O bond length of 1.81 A is estimated for the uranyl ion in this compound.

  10. Designer Drugs: A Synthetic Catastrophe

    OpenAIRE

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    2015-01-01

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are "Not for Human Consumption", therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance...

  11. Does autophagy have a license to kill mammalian cells?

    NARCIS (Netherlands)

    Scarlatti, F.; Granata, R.; Meijer, A. J.; Codogno, P.

    2009-01-01

    Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the

  12. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2001-01-01

    The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

  13. Hydrogen speciation in synthetic quartz

    Science.gov (United States)

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

    1984-01-01

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

  14. Repair of furocoumarin adducts in mammalian cells

    International Nuclear Information System (INIS)

    Zolan, M.E.; Smith, C.A.; Hanawalt, P.C.

    1984-01-01

    DNA repair was studied in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. A comparison was also made of repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly

  15. Acidic mammalian chitinase in dry eye conditions.

    Science.gov (United States)

    Musumeci, Maria; Aragona, Pasquale; Bellin, Milena; Maugeri, Francesco; Rania, Laura; Bucolo, Claudio; Musumeci, Salvatore

    2009-07-01

    An acidic mammalian chitinase (AMCase) seems to be implicated in allergic asthma and allergic ocular pathologies. The aim of this work was to investigate the role of AMCase during Sjögren's Syndrome (SS) and Meibomian Gland Dysfunction (MGD) dry eye diseases. Six patients with MGD dry eye (20-58 years, median 40) and six patients with dry eye associated to SS (32-60 years, median 47) were enrolled in this study. AMCase activity was measured in tears and AMCase mRNA expression was evaluated by real-time polymerase chain reaction from RNA extracted from epithelial cells of the conjunctiva. Six healthy adult subjects of the same age (34-44 years, median 39) were also studied as the control group. AMCase activity was significantly increased in patients affected by MGD dry eye (18.54 +/- 1.5 nmol/ml/h) and SS dry eye (8.94 +/- 1.0 nmol/ml/h) respectively, compared to healthy controls (1.6 +/- 0.2 nmol/ml/h). AMCase activity was higher in the tears of subjects with MGD dry eye (P < 0.001). AMCase mRNA was detected in conjunctival epithelial cells and the expression was significantly higher in MGD dry eye than SS dry eye. A significant correlation between AMCase activity in the tears and mRNA in conjunctival epithelial cells was found. AMCase may be an important marker in the pathogenesis of dry eye, suggesting the potential role of AMCase as a therapeutic target in these frequent pathologies.

  16. Assays for mammalian tyrosinase: a comparative study

    International Nuclear Information System (INIS)

    Jara, J.R.; Solano, F.; Lozano, J.A.

    1988-01-01

    This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed

  17. Mammalian play: training for the unexpected.

    Science.gov (United States)

    Spinka, M; Newberry, R C; Bekoff, M

    2001-06-01

    In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling

  18. Characterization of synthetic peptides by mass spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala Krishna; Mirza, Osman Asghar; Højrup, Peter

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI......-TOF-MS and LC-MS of synthetic peptides....

  19. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  20. Role of cyclins in controlling progression of mammalian spermatogenesis

    OpenAIRE

    WOLGEMUTH, DEBRA J.; MANTEROLA, MARCIA; VASILEVA, ANA

    2013-01-01

    Cyclins are key regulators of the mammalian cell cycle, functioning primarily in concert with their catalytic partners, the cyclin-dependent kinases (Cdks). While their function during mitosis in somatic cells has been extensively documented, their function during both mitosis and meiosis in the germ line is poorly understood. From the perspective of cell cycle regulation there are several aspects of mammalian spermatogenesis that suggest unique modes of regulation and hence, possible unique ...

  1. Evaluation of Mammalian Interspersed Repeats to investigate the goat genome

    Directory of Open Access Journals (Sweden)

    P. Mariani

    2010-01-01

    Full Text Available Among the repeated sequences present in most eukaryotic genomes, SINEs (Short Interspersed Nuclear Elements are widely used to investigate evolution in the mammalian order (Buchanan et al., 1999. One family of these repetitive sequences, the MIR (Mammalian Interspersed Repeats; Jurka et al., 1995, is ubiquitous in all mammals.MIR elements are tRNA-derived SINEs and are identifiable by a conserved core region of about 70 nucleotides.

  2. An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

    Directory of Open Access Journals (Sweden)

    Young-Geun Lee

    2013-11-01

    Full Text Available BackgroundMammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds.MethodsWe performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course.ResultsAmong the 68 cases of mammalian bite injury, 58 (85% were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap.ConclusionsBased on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds.

  3. Incorporation of mammalian actin into microfilaments in plant cell nucleus

    Directory of Open Access Journals (Sweden)

    Paves Heiti

    2004-04-01

    Full Text Available Abstract Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area.

  4. A Canadian refiner's perspective of synthetic crudes

    International Nuclear Information System (INIS)

    Halford, T.L.; McIntosh, A.P.; Rasmussen

    1997-01-01

    Some of the factors affecting a refiner's choice of crude oil include refinery hardware, particularly gas oil crackers, products slate and product specifications, crude availability, relative crude price and crude quality. An overview of synthetic crude, the use of synthetic crude combined with other crudes and a comparison of synthetic crude with conventional crude oil was given. The two main users of synthetic crude are basically two groups of refiners, those large groups who use synthetic crude combined with other crudes, and a smaller group who run synthetic crude on specially designed units as a sole feed. The effects of changes in fuel legislation were reviewed. It was predicted that the changes will have a mixed impact on the value of synthetic crude, but low sulphur diesel regulations and gasoline sulphur regulations will make current synthetic crudes attractive. The big future change with a negative impact will be diesel cetane increases to reduce engine emissions. This will reduce synthetic crude attractiveness due to distillate yields and quality and high gas oil yields. Similarly, any legislation limiting aromatics in diesel fuel will also make synthetic crudes less attractive. Problems experienced by refiners with hardware dedicated to synthetic crude (salt, naphthenic acid, fouling, quality variations) were also reviewed. 3 tabs

  5. Synthetic biology: Emerging bioengineering in Indonesia

    Science.gov (United States)

    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.

  6. Printability of Synthetic Papers by Electrophotography

    Directory of Open Access Journals (Sweden)

    Rozália Szentgyörgyvölgyi

    2010-04-01

    Full Text Available This paper deals with the printability of synthetic papers by the electrophotography technique. Prints of cmyk colour fields from 20% to 100% raster tone values were printed on three types of synthetic papers (one film synthetic paper and two fiber synthetic papers. The investigation of the appearance included densitometric measurement of the cmyk prints. The results have shown differences in the optical density and optical tone value between cmyk prints made on various synthetic papers. The highest optical density and the increase of the optical tone value were observed on the film synthetic paper, where cmyk prints were more saturated. The highest abrasion resistance of cmyk prints was obtained from the fibre synthetic paper.

  7. Mammalian hibernation: lessons for organ preparation?

    Science.gov (United States)

    Green, C

    2000-01-01

    The adaptations to low environmental temperatures exhibited in mammalian hibernation are many and varied, and involve molecular and cellular mechanisms as well as the systematic physiology of the whole organism. Natural torpidity is characterised by a profound reduction in body temperature and other functions lasting from a few hours to several weeks. Controlled reduction of heart rate, respiration and oxygen consumption is followed by the fall in body temperature. However, thermoregulation persists such that a decrease in ambient temperature below dangerous levels typically triggers arousal, and shivering and non-shivering thermogenesis from brown fat provide the heat to restore body temperature to normal levels. Many of the cellular mechanisms for survival are similar to those brought into play during medium-term storage of organs destined for transplantation. For example maintenance of ionic regulation and membrane fluxes is fundamental to cell survival and function at low body temperatures. Differences between hibernating and non-hibernating species are marked by differences in Na+/K+ transport and Ca++pumps. These in turn are probably associated with alterations in the lipoproteins of the plasma membrane and inner mitochondrial membrane. We have accordingly conducted a series of pilot studies in captured Richardson's ground squirrels kept in laboratory conditions as a model for hypothermic organ preservation. Tissue function was compared during the summer (non-hibernating season) with that in the winter when the animals could be: (i) in deep hibernation in a cold chamber at 4 degree C; (ii) maintained in an ambient temperature of 4 degree C but active and awake; or (iii) active at an ambient temperature of 22 degree C. The studies involved: whole animal monitoring of standard physiological parameters; whole organ (kidney) storage and transplantation for viability assessment; storage and functional assessment on an ex vivo test circuit with capacity for

  8. Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

    Science.gov (United States)

    Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2016-09-11

    A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Villagómez Hoyos, Carlos Armando

    The main objective of this project was to continue the development of a synthetic aperture vector flow estimator. This type of estimator is capable of overcoming two of the major limitations in conventional ultrasound systems: 1) the inability to scan large region of interest with high temporal......, this thesis showed that novel information can be obtained with vector velocity methods providing quantitative estimates of blood flow and insight into the complexity of the hemodynamics dynamics. This could give the clinician a new tool in assessment and treatment of a broad range of diseases....

  10. Synthetic Biology Guides Biofuel Production

    Directory of Open Access Journals (Sweden)

    Michael R. Connor

    2010-01-01

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

  11. Tracking the emergence of synthetic biology.

    Science.gov (United States)

    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.

  12. Synthetic mimetics of the endogenous gastrointestinal nanomineral: Silent constructs that trap macromolecules for intracellular delivery.

    Science.gov (United States)

    Pele, Laetitia C; Haas, Carolin T; Hewitt, Rachel E; Robertson, Jack; Skepper, Jeremy; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Faria, Nuno; Chappell, Helen; Powell, Jonathan J

    2017-02-01

    Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles (75-150nm) form constitutively in large numbers in the mammalian gut. Collective evidence indicates that they trap and deliver luminal macromolecules to mucosal antigen presenting cells (APCs) and facilitate gut immune homeostasis. Here, we report on a synthetic mimetic of the endogenous AMCP and show that it has marked capacity to trap macromolecules during formation. Macromolecular capture into AMCP involved incorporation as shown by STEM tomography of the synthetic AMCP particle with 5nm ultra-fine iron (III) oxohydroxide. In vitro, organic cargo-loaded synthetic AMCP was taken up by APCs and tracked to lysosomal compartments. The AMCP itself did not regulate any gene, or modify any gene regulation by its cargo, based upon whole genome transcriptomic analyses. We conclude that synthetic AMCP can efficiently trap macromolecules and deliver them to APCs in a silent fashion, and may thus represent a new platform for antigen delivery. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Reward-based hypertension control by a synthetic brain-dopamine interface.

    Science.gov (United States)

    Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2013-11-05

    Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

  14. Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters.

    Science.gov (United States)

    Ferreira, Joshua P; Peacock, Ryan W S; Lawhorn, Ingrid E B; Wang, Clifford L

    2011-12-01

    The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evaluation using plasmid vectors integrated at a single site in the genome revealed that these various synthetic promoters were capable of expression levels spanning a 40-fold range. Retroviral vectors were equipped with the synthetic promoters and evaluated for their ability to reproduce the graded expression demonstrated by plasmid integration. A vector with a self-inactivating long terminal repeat could neither reproduce the full range of expression levels nor produce stable expression. Using a second vector design, the different synthetic promoters enabled stable expression over a broad range of expression levels in different cell lines. The online version of this article (doi:10.1007/s11693-011-9089-0) contains supplementary material, which is available to authorized users.

  15. DNA recognition by synthetic constructs.

    Science.gov (United States)

    Pazos, Elena; Mosquera, Jesús; Vázquez, M Eugenio; Mascareñas, José L

    2011-09-05

    The interaction of transcription factors with specific DNA sites is key for the regulation of gene expression. Despite the availability of a large body of structural data on protein-DNA complexes, we are still far from fully understanding the molecular and biophysical bases underlying such interactions. Therefore, the development of non-natural agents that can reproduce the DNA-recognition properties of natural transcription factors remains a major and challenging goal in chemical biology. In this review we summarize the basics of double-stranded DNA recognition by transcription factors, and describe recent developments in the design and preparation of synthetic DNA binders. We mainly focus on synthetic peptides that have been designed by following the DNA interaction of natural proteins, and we discuss how the tools of organic synthesis can be used to make artificial constructs equipped with functionalities that introduce additional properties to the recognition process, such as sensing and controllability. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Synthetic Biology of Polyhydroxyalkanoates (PHA).

    Science.gov (United States)

    Meng, De-Chuan; Chen, Guo-Qiang

    Microbial polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible polyesters which have been extensively studied using synthetic biology and metabolic engineering methods for improving production and for widening its diversity. Synthetic biology has allowed PHA to become composition controllable random copolymers, homopolymers, and block copolymers. Recent developments showed that it is possible to establish a microbial platform for producing not only random copolymers with controllable monomers and their ratios but also structurally defined homopolymers and block copolymers. This was achieved by engineering the genome of Pseudomonas putida or Pseudomonas entomophiles to weaken the β-oxidation and in situ fatty acid synthesis pathways, so that a fatty acid fed to the bacteria maintains its original chain length and structures when incorporated into the PHA chains. The engineered bacterium allows functional groups in a fatty acid to be introduced into PHA, forming functional PHA, which, upon grafting, generates endless PHA variety. Recombinant Escherichia coli also succeeded in producing efficiently poly(3-hydroxypropionate) or P3HP, the strongest member of PHA. Synthesis pathways of P3HP and its copolymer P3HB3HP of 3-hydroxybutyrate and 3-hydroxypropionate were assembled respectively to allow their synthesis from glucose. CRISPRi was also successfully used to manipulate simultaneously multiple genes and control metabolic flux in E. coli to obtain a series of copolymer P3HB4HB of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB). The bacterial shapes were successfully engineered for enhanced PHA accumulation.

  17. Vectoring of parallel synthetic jets

    Science.gov (United States)

    Berk, Tim; Ganapathisubramani, Bharathram; Gomit, Guillaume

    2015-11-01

    A pair of parallel synthetic jets can be vectored by applying a phase difference between the two driving signals. The resulting jet can be merged or bifurcated and either vectored towards the actuator leading in phase or the actuator lagging in phase. In the present study, the influence of phase difference and Strouhal number on the vectoring behaviour is examined experimentally. Phase-locked vorticity fields, measured using Particle Image Velocimetry (PIV), are used to track vortex pairs. The physical mechanisms that explain the diversity in vectoring behaviour are observed based on the vortex trajectories. For a fixed phase difference, the vectoring behaviour is shown to be primarily influenced by pinch-off time of vortex rings generated by the synthetic jets. Beyond a certain formation number, the pinch-off timescale becomes invariant. In this region, the vectoring behaviour is determined by the distance between subsequent vortex rings. We acknowledge the financial support from the European Research Council (ERC grant agreement no. 277472).

  18. Synthetic membrane-targeted antibiotics.

    Science.gov (United States)

    Vooturi, S K; Firestine, S M

    2010-01-01

    Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

  19. Synthetic vision display evaluation studies

    Science.gov (United States)

    Regal, David M.; Whittington, David H.

    1994-01-01

    The goal of this research was to help us understand the display requirements for a synthetic vision system for the High Speed Civil Transport (HSCT). Four experiments were conducted to examine the effects of different levels of perceptual cue complexity in displays used by pilots in a flare and landing task. Increased levels of texture mapping of terrain and runway produced mixed results, including harder but shorter landings and a lower flare initiation altitude. Under higher workload conditions, increased texture resulted in an improvement in performance. An increase in familiar size cues did not result in improved performance. Only a small difference was found between displays using two patterns of high resolution texture mapping. The effects of increased perceptual cue complexity on performance was not as strong as would be predicted from the pilot's subjective reports or from related literature. A description of the role of a synthetic vision system in the High Speed Civil Transport is provide along with a literature review covering applied research related to perceptual cue usage in aircraft displays.

  20. TRANSPLANTATION AND POTENTIAL IMMORTALITY OF MAMMALIAN TISSUES.

    Science.gov (United States)

    Loeb, L

    1926-06-20

    1. Serial transplantation of tumors made it possible in 1901 and following years to draw the conclusion that various mammalian tissues have potential immortality. Serial transplantations of normal tissues did not succeed at first, because the homoioreaction on the part of the lymphocytes and connective tissue of the host injures the transplant. 2. In continuation of these experiments we found that cartilage of the rat can be transplanted serially to other rats at least for a period of 3 years. At the end of that time great parts of the transplanted cartilage and perichondrium are alive. 3. Not only the cartilage of young rats can be homoiotransplanted, but also the cartilage of very old rats which are nearing the end of life. By using such animals we have been able to obtain cartilage and perichondrium approaching an age of 6 years which is almost double the average age of a rat. 4. We found that cartilage can be homoiotransplanted more readily than other tissues for the following reasons: (a) While in principle the homoioreaction towards cartilage is the same as against other tissues, cartilage elicits this reaction with less intensity; (b) cartilage is better able to resist the invasion of lymphocytes and connective tissue than the majority of other tissues; (c) a gradual adaptation between transplant and host seems to take place in the case of cartilage transplantation, as a result of which the lymphocytic reaction on the part of the host tissue decreases progressively the longer the cartilage is kept in the strange host. 5. At time of examination we not only found living transplanted cartilage tissue, but also perichondrial tissue, which in response to a stimulus apparently originating in the necrotic central cartilage, had been proliferating and replacing it. These results suggest that it may perhaps be possible under favorable conditions to keep cartilage alive indefinitely through serial transplantations. 6. At the same time these experiments permit the

  1. Amino acids in the cultivation of mammalian cells.

    Science.gov (United States)

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

  2. Possible involvement of SINEs in mammalian-specific brain formation.

    Science.gov (United States)

    Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

    2008-03-18

    Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

  3. A synthetic prestin reveals protein domains and molecular operation of outer hair cell piezoelectricity.

    Science.gov (United States)

    Schaechinger, Thorsten J; Gorbunov, Dmitry; Halaszovich, Christian R; Moser, Tobias; Kügler, Sebastian; Fakler, Bernd; Oliver, Dominik

    2011-06-24

    Prestin, a transporter-like protein of the SLC26A family, acts as a piezoelectric transducer that mediates the fast electromotility of outer hair cells required for cochlear amplification and auditory acuity in mammals. Non-mammalian prestin orthologues are anion transporters without piezoelectric activity. Here, we generated synthetic prestin (SynPres), a chimera of mammalian and non-mammalian prestin exhibiting both, piezoelectric properties and anion transport. SynPres delineates two distinct domains in the protein's transmembrane core that are necessary and sufficient for generating electromotility and associated non-linear charge movement (NLC). Functional analysis of SynPres showed that the amplitude of NLC and hence electromotility are determined by the transport of monovalent anions. Thus, prestin-mediated electromotility is a dual-step process: transport of anions by an alternate access cycle, followed by an anion-dependent transition generating electromotility. The findings define structural and functional determinants of prestin's piezoelectric activity and indicate that the electromechanical process evolved from the ancestral transport mechanism.

  4. Word selection affects perceptions of synthetic biology

    Directory of Open Access Journals (Sweden)

    Tonidandel Scott

    2011-07-01

    Full Text Available Abstract Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008. Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  5. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    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. (review)

  6. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    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.

  7. Synthetic approaches to uniform polymers.

    Science.gov (United States)

    Ali, Monzur; Brocchini, Steve

    2006-12-30

    Uniform polymers are characterised by a narrow molecular weight distribution (MWD). Uniformity is also defined by chemical structure in respect of (1) monomer orientation, sequence and stereo-regularity, (2) polymer shape and morphology and (3) chemical functionality. The function of natural polymers such as polypeptides and polynucleotides is related to their conformational structure (e.g. folded tertiary structure). This is only possible because of their high degree of uniformity. While completely uniform synthetic polymers are rare, polymers with broad structure and MWD are widely used in medicine and the biomedical sciences. They are integral components in final dosage forms, drug delivery systems (DDS) and in implantable devices. Increasingly uniform polymers are being used to develop more complex medicines (e.g. delivery of biopharmaceuticals, enhanced formulations or DDS's for existing actives). In addition to the function imparted by any new polymer it will be required to meet stringent specifications in terms of cost containment, scalability, biocompatibility and performance. Synthetic polymers with therapeutic activity are also being developed to exploit their polyvalent properties, which is not possible with low molecular weight molecules. There is need to utilise uniform polymers for applications where the polymer may interact with the systemic circulation, tissues or cellular environment. There are also potential applications (e.g. stimuli responsive coatings) where uniform polymers may be used for their more defined property profile. While it is not yet practical to prepare synthetic polymers to the same high degree of uniformity as proteins, nature also effectively utilises many polymers with lower degrees of uniformity (e.g. polysaccharides, poly(amino acids), polyhydroxyalkanoates). In recent years it has become possible to prepare with practical experimental protocols sufficient quantities of polymers that display many aspects of uniformity. This

  8. Synthetic Lipoproteins as Carriers for Drug Delivery.

    Science.gov (United States)

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  9. Geo synthetic-reinforced Pavement systems

    International Nuclear Information System (INIS)

    Zornberg, J. G.

    2014-01-01

    Geo synthetics have been used as reinforcement inclusions to improve pavement performance. while there are clear field evidence of the benefit of using geo synthetic reinforcements, the specific conditions or mechanisms that govern the reinforcement of pavements are, at best, unclear and have remained largely unmeasured. Significant research has been recently conducted with the objectives of: (i) determining the relevant properties of geo synthetics that contribute to the enhanced performance of pavement systems, (ii) developing appropriate analytical, laboratory and field methods capable of quantifying the pavement performance, and (iii) enabling the prediction of pavement performance as a function of the properties of the various types of geo synthetics. (Author)

  10. Veterans Affairs Suicide Prevention Synthetic Dataset

    Data.gov (United States)

    Department of Veterans Affairs — The VA's Veteran Health Administration, in support of the Open Data Initiative, is providing the Veterans Affairs Suicide Prevention Synthetic Dataset (VASPSD). The...

  11. Synthetic biology assemblies for sustainable space exploration

    Data.gov (United States)

    National Aeronautics and Space Administration — The work utilized synthetic biology to create sustainable food production processes by developing technology to efficiently convert inedible crop waste to...

  12. Synthetic biology of antimicrobial discovery

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  13. Preparation of synthetic standard minerals

    International Nuclear Information System (INIS)

    Herrick, C.C.; Bustamante, S.J.; Charls, R.W.; Cowan, R.E.; Hakkila, E.A.; Hull, D.E.; Olinger, B.W.; Roof, R.B.; Sheinberg, H.; Herrick, G.C.

    1978-01-01

    A number of techniques for synthetic mineral preparations have been examined. These techniques include hot-pressing in graphite dies at moderate pressures, high-pressure, high-temperature synthesis in a piston and cylinder apparatus, isostatic pressing under helium gas pressures, hydrous mineral preparations using water as the pressure medium, explosion-generated shock waves, and radiofrequency heating. Minerals suitable for equation-of-state studies (three-inch, high-density discs), for thermodynamic property determinations (low-density powders) and for microprobe standards (fusion-cast microbeads) have been prepared. Mechanical stress-strain calculations in the piston-cylinder apparatus have been initiated and their integration with thermal stress calculations is currently under investigation

  14. Synthetic biology of antimicrobial discovery.

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  15. Synthetic biology: a utilitarian perspective.

    Science.gov (United States)

    Smith, Kevin

    2013-10-01

    I examine the positive and negative features of synthetic biology ('SynBio') from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a 'precautionary' approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio. © 2013 John Wiley & Sons Ltd.

  16. Synthetic biology: engineering molecular computers

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

  17. Retention of the Native Epigenome in Purified Mammalian Chromatin.

    Directory of Open Access Journals (Sweden)

    Andreas H Ehrensberger

    Full Text Available A protocol is presented for the isolation of native mammalian chromatin as fibers of 25-250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed.

  18. Role of Notch signaling in the mammalian heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

    2013-12-12

    Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

  19. Microorganism Utilization for Synthetic Milk

    Science.gov (United States)

    Morford, Megan A.; Khodadad, Christina L.; Caro, Janicce I.; Spencer, LaShelle E.; Richards, Jeffery T.; Strayer, Richard F.; Birmele, Michele N.; Wheeler, Raymond M.

    2014-01-01

    A desired architecture for long duration spaceflight, like aboard the International Space Station or for future missions to Mars, is to provide a supply of fresh food crops for the astronauts. However, some crops can create a high proportion of inedible plant waste. The main goal of the Synthetic Biology project, Cow in a Column, was to produce the components of milk (sugar, lipid, protein) from inedible plant waste by utilizing microorganisms (fungi, yeast, bacteria). Of particular interest was utilizing the valuable polysaccharide, cellulose, found in plant waste, to naturally fuel-through microorganism cellular metabolism- the creation of sugar (glucose), lipid (milk fat), and protein (casein) in order to produce a synthetic edible food product. Environmental conditions such as pH, temperature, carbon source, aeration, and choice microorganisms were optimized in the laboratory and the desired end-products, sugars and lipids, were analyzed. Trichoderma reesei, a known cellulolytic fungus, was utilized to drive the production of glucose, with the intent that the produced glucose would serve as the carbon source for milk fat production and be a substitute for the milk sugar lactose. Lipid production would be carried out by Rhodosporidium toruloides, yeast known to accumulate those lipids that are typically found in milk fat. Results showed that glucose and total lipid content were below what was expected during this phase of experimentation. In addition, individual analysis of six fatty acids revealed that the percentage of each fatty acid was lower than naturally produced bovine milk. Overall, this research indicates that microorganisms could be utilized to breakdown inedible solid waste to produce useable products. For future work, the production of the casein protein for milk would require the development of a genetically modified organism, which was beyond the scope of the original project. Additional trials would be needed to further refine the required

  20. Synthetic prions with novel strain-specified properties.

    Science.gov (United States)

    Moda, Fabio; Le, Thanh-Nhat T; Aulić, Suzana; Bistaffa, Edoardo; Campagnani, Ilaria; Virgilio, Tommaso; Indaco, Antonio; Palamara, Luisa; Andréoletti, Olivier; Tagliavini, Fabrizio; Legname, Giuseppe

    2015-12-01

    Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrP(Sc). Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrP(Sc) were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.

  1. Synergistic Synthetic Biology: Units in Concert

    International Nuclear Information System (INIS)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  2. Study of seed for synthetical quartz

    International Nuclear Information System (INIS)

    Suzuki, C.K.; Torikai, D.

    1988-01-01

    Natural quartz blocks for seed (synthetic quartz technology) were studied by using various characterization techniques, such as X-ray topography, optical micrography, inspectoscopy, polariscopy and conoscopy, and etching. One of the most commonly found defect is the electrical or Dauphine twin. In The present research, we have developed a methodology to obtain a highly perfect seed for the synthetic quartz industries. (author) [pt

  3. Synthetic biology: programming cells for biomedical applications.

    Science.gov (United States)

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

    2012-01-01

    The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

  4. Synergistic Synthetic Biology: Units in Concert

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

  5. Metal immobilization in soils using synthetic zeolites

    NARCIS (Netherlands)

    Osté, L.A.; Lexmond, T.M.; Riemsdijk, van W.H.

    2002-01-01

    In situ immobilization of heavy metals in contaminated soils is a technique to improve soil quality. Synthetic zeolites are potentially useful additives to bind heavy metals. This study selected the most effective zeolite in cadmium and zinc binding out of six synthetic zeolites (mordenite-type,

  6. Synthetic and Empirical Capsicum Annuum Image Dataset

    NARCIS (Netherlands)

    Barth, R.

    2016-01-01

    This dataset consists of per-pixel annotated synthetic (10500) and empirical images (50) of Capsicum annuum, also known as sweet or bell pepper, situated in a commercial greenhouse. Furthermore, the source models to generate the synthetic images are included. The aim of the datasets are to

  7. Synthetic aperture radar: principles and applications

    International Nuclear Information System (INIS)

    Khan, N.A.; Yahya, K.M.

    2003-01-01

    In this paper an introduction to synthetic aperture radar is presented. Synthetic aperture radar is a relatively new remote sensing platform and the technology has matured a lot in the last two decades. This paper introduces the concepts behind SAR principles as well as the major areas where this new technology has shown additional information. (author)

  8. Opportunities for microfluidic technologies in synthetic biology

    OpenAIRE

    Gulati, Shelly; Rouilly, Vincent; Niu, Xize; Chappell, James; Kitney, Richard I.; Edel, Joshua B.; Freemont, Paul S.; deMello, Andrew J.

    2009-01-01

    We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed.

  9. Paired Chicken and Mammalian Erythrocyte Indicator Systems for ...

    African Journals Online (AJOL)

    Three levels of erythrocytes suspensions, 1.5%, 1% and 0.5% respectively from goat and guinea pig, were compared to conventional 0.5% chicken erythrocytes, in an attempt to investigate the suitability for the two sources of mammalian erythrocytes as indicators for Newcastle disease virus haemagglutination (HA) tests.

  10. Is ultraviolet enhanced reactivation of mammalian virus mutagenic

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

    1981-01-01

    Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

  11. Engineered mammalian cells for production of recombinant proteins

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to mammalian cells modified to provide for improved expression of a recombinant protein of interest. In particular, the invention relates to CHO cells and other host cells in which the expression of one or more endogenous secreted proteins has been disrupted, as well...... as to the preparation, identification and use of such cells in the production of recombinant proteins....

  12. Mammalian motor neurons corelease glutamate and acetylcholine at central synapses

    DEFF Research Database (Denmark)

    Nishimaru, Hiroshi; Restrepo, Carlos Ernesto; Ryge, Jesper

    2005-01-01

    Motor neurons (MNs) are the principal neurons in the mammalian spinal cord whose activities cause muscles to contract. In addition to their peripheral axons, MNs have central collaterals that contact inhibitory Renshaw cells and other MNs. Since its original discovery > 60 years ago, it has been...

  13. Incorporation of nanoparticles within mammalian spermatozoa using in vitro capacitation

    Science.gov (United States)

    There is still much unknown about the journey of spermatozoa within the female genital tract. Recent studies have investigated mammalian spermatozoa labeling with fluorescent quantum dot nanoparticles (QD) for non-invasive imaging. Furthermore, the incorporation of these QD within the spermatozoa ma...

  14. Musculoskeletal networks reveal topological disparity in mammalian neck evolution.

    Science.gov (United States)

    Arnold, Patrick; Esteve-Altava, Borja; Fischer, Martin S

    2017-12-13

    The increase in locomotor and metabolic performance during mammalian evolution was accompanied by the limitation of the number of cervical vertebrae to only seven. In turn, nuchal muscles underwent a reorganization while forelimb muscles expanded into the neck region. As variation in the cervical spine is low, the variation in the arrangement of the neck muscles and their attachment sites (i.e., the variability of the neck's musculoskeletal organization) is thus proposed to be an important source of neck disparity across mammals. Anatomical network analysis provides a novel framework to study the organization of the anatomical arrangement, or connectivity pattern, of the bones and muscles that constitute the mammalian neck in an evolutionary context. Neck organization in mammals is characterized by a combination of conserved and highly variable network properties. We uncovered a conserved regionalization of the musculoskeletal organization of the neck into upper, mid and lower cervical modules. In contrast, there is a varying degree of complexity or specialization and of the integration of the pectoral elements. The musculoskeletal organization of the monotreme neck is distinctively different from that of therian mammals. Our findings reveal that the limited number of vertebrae in the mammalian neck does not result in a low musculoskeletal disparity when examined in an evolutionary context. However, this disparity evolved late in mammalian history in parallel with the radiation of certain lineages (e.g., cetartiodactyls, xenarthrans). Disparity is further facilitated by the enhanced incorporation of forelimb muscles into the neck and their variability in attachment sites.

  15. Optical sorting and photo-transfection of mammalian cells

    CSIR Research Space (South Africa)

    Mthunzi, P

    2010-02-01

    Full Text Available and that the scattering force can enable sorting through axial guiding onto laminin coated glass coverslips upon which the selected cells adhere. Following this, I report on transient photo-transfection of mammalian cells including neuroblastomas (rat/mouse and human...

  16. Intracellular dielectric tagging for improved optical manipulation of mammalian cells

    CSIR Research Space (South Africa)

    Mthunzi, P

    2010-05-01

    Full Text Available review the application of optical forces for cellmanipulation and sorting, highlighting some of the key experiments over the last twenty years.We then introduce a new technique for enhancing the dielectric contrast of mammalian cells, which is a result...

  17. Mammalian gamete plasma membranes re-assessments and reproductive implications

    Science.gov (United States)

    Establishment of the diploid status occurs with the fusion of female and male gametes. Both the mammalian oocyte and spermatozoa are haploid cells surrounded with plasma membranes that are rich in various proteins playing a crucial role during fertilization. Fertilization is a complex and ordered st...

  18. Mammalian Prolactin – An Ancient But Still A Mysterious Hormone

    Indian Academy of Sciences (India)

    Table of contents. Mammalian Prolactin – An Ancient But Still A Mysterious Hormone · Prolactin inhibits LHRH action during lactational ammenorrhoea · Slide 3 · Slide 4 · REDUCTIONIST VIEW OF HORMONES · CONCERN · PURIFICATION PROTOCOLS · CHARACTERIZATION OF HORMONES · Slide 9 · Slide 10.

  19. Steel desulphurization with synthetic slag

    Directory of Open Access Journals (Sweden)

    Heput, T.

    2007-02-01

    Full Text Available Generally speaking, sulphur is considered a harmful element for steel quality, reason why all the technological steps are being taken in order to eliminate it from the metal bath. This paper deals with the influence of the chemical composition, on the slag quantity and of the bath stirring condition upon the desulphurization process in the casting ladle by treatment with synthetic slag. The experiments were made at an open-hearth plant with the steel tapping in two ladles (the desulphurization was made with synthetic slag at one ladle while the other one was considered standard and at the electric steel plant and for the synthetic slag formation a mix was used, made, according to several receipts, of: lime (50-75%, fluorine (0-17%, bauxite (0-32% and aluminous slag (8-22%. The data were processed in the calculation programs EXCEL and MATLAB, which resulted in a series of correlations between the desulphurization degree and the chemical composition of the slag, respectively the slag quantity both for the charges bubbled with Argon and the unbubbled ones.

    En general, el azufre es considerado un elemento nocivo para la calidad del acero y, por eso, en la práctica, se toman todas las medidas de orden tecnológico para su eliminación del baño metálico. En este trabajo se analiza la influencia de la composición química, de la cantidad de escoria y del estado de agitación del baño sobre el proceso de desulfuración en la cuchara para fundir por tratamiento con escoria sintética. Los experimentos se han realizado en una acería evacuando el acero en dos ollas (en una cuchara se efectuó la desulfuración con escoria sintética y a la otra se consideró como patrón y en un acería eléctrica y para la formación de la escoria sintética se utilizó una mezcla producida según muchas recetas, formada por: cal (50-75%, fluorina (0-17%, bauxita (0-32% y escoria aluminosa (8-22%. Los datos han sido procesados en los programas de c

  20. Synthetic biology: an emerging engineering discipline.

    Science.gov (United States)

    Cheng, Allen A; Lu, Timothy K

    2012-01-01

    Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

  1. Mass Spectrometric Analysis of Synthetic Organic Pigments.

    Science.gov (United States)

    Sugaya, Naeko; Takahashi, Mitsuko; Sakurai, Katsumi; Tanaka, Nobuko; Okubo, Ichiro; Kawakami, Tsuyoshi

    2018-04-18

    Though synthetic organic colorants are used in various applications nowadays, there is the concern that impurities by-produced during the manufacturing and degradation products in some of these colorants are persistent organic pollutants and carcinogens. Thus, it is important to identify the synthetic organic colorants in various products, such as commercial paints, ink, cosmetics, food, textile, and plastics. Dyes, which are soluble in water and other solvents, could be analyzed by chromatographic methods. In contrast, it is difficult to analyze synthetic organic pigments by these methods because of their insolubility. This review is an overview of mass spectrometric analysis of synthetic organic pigments by various ionization methods. We highlight a recent study of textile samples by atmospheric pressure solid analysis probe MS. Furthermore, the mass spectral features of synthetic organic pigments and their separation from other components such as paint media and plasticizers are discussed.

  2. Science with Synthetic Stellar Surveys

    Science.gov (United States)

    Sanderson, Robyn Ellyn

    2018-04-01

    A new generation of observational projects is poised to revolutionize our understanding of the resolved stellar populations of Milky-Way-like galaxies at an unprecedented level of detail, ushering in an era of precision studies of galaxy formation. In the Milky Way itself, astrometric, spectroscopic and photometric surveys will measure three-dimensional positions and velocities and numerous chemical abundances for stars from the disk to the halo, as well as for many satellite dwarf galaxies. In the Local Group and beyond, HST, JWST and eventually WFIRST will deliver pristine views of resolved stars. The groundbreaking scale and dimensionality of this new view of resolved stellar populations in galaxies challenge us to develop new theoretical tools to robustly compare these surveys to simulated galaxies, in order to take full advantage of our new ability to make detailed predictions for stellar populations within a cosmological context. I will describe a framework for generating realistic synthetic star catalogs and mock surveys from state-of-the-art cosmological-hydrodynamical simulations, and present several early scientific results from, and predictions for, resolved stellar surveys of our Galaxy and its neighbors.

  3. Synthetic sustained gene delivery systems.

    Science.gov (United States)

    Agarwal, Ankit; Mallapragada, Surya K

    2008-01-01

    Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

  4. Online professionalism: A synthetic review.

    Science.gov (United States)

    Chretien, Katherine C; Tuck, Matthew G

    2015-04-01

    The rise of social media has increased connectivity and blurred personal and professional boundaries, bringing new challenges for medical professionalism. Whether traditional professionalism principles apply to the online social media space remains unknown. The purpose of this synthetic literature review was to characterize the original peer-reviewed research studies published between 1 January 2000-1 November 2014 on online professionalism, to assess methodologies and approaches used, and to provide insights to guide future studies in this area. The investigators searched three databases and performed manual searches of bibliographies to identify the 32 studies included. Most studies originated in the USA. Cross-sectional surveys and analyses of publicly available online content were the most common methodologies employed. Studies covered the general areas of use and privacy, assessment of unprofessional online behaviours, consensus-gathering of what constitutes unprofessional or inappropriate online behaviours, and education and policies. Studies were of variable quality; only around half of survey studies had response rates of 50% or greater. Medical trainees were the most common population studied. Future directions for research include public perspectives of online professionalism, impact on patient trust, and how to use social media productively as medical professionals.

  5. Influence of Polyplex Formation on the Performance of Star-Shaped Polycationic Transfection Agents for Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Alexander Raup

    2016-06-01

    Full Text Available Genetic modification (“transfection” of mammalian cells using non-viral, synthetic agents such as polycations, is still a challenge. Polyplex formation between the DNA and the polycation is a decisive step in such experiments. Star-shaped polycations have been proposed as superior transfection agents, yet have never before been compared side-by-side, e.g., in view of structural effects. Herein four star-shaped polycationic structures, all based on (2-dimethylamino ethyl methacrylate (DMAEMA building blocks, were investigated for their potential to deliver DNA to adherent (CHO, L929, HEK-293 and non-adherent (Jurkat, primary human T lymphocytes mammalian cells. The investigated vectors included three structures where the PDMAEMA arms (different arm length and grafting densities had been grown from a center silsesquioxane or silica-coated γ-Fe2O3-core and one micellar structure self-assembled from poly(1,2-butadiene-block PDMAEMA polymers. All nano-stars combined high transfection potential with excellent biocompatibility. The micelles slightly outperformed the covalently linked agents. For method development and optimization, the absolute amount of polycation added to the cells was more important than the N/P-ratio (ratio between polycation nitrogen and DNA phosphate, provided a lower limit was passed and enough polycation was present to overcompensate the negative charge of the plasmid DNA. Finally, the matrix (NaCl vs. HEPES-buffered glucose solution, but also the concentrations adjusted during polyplex formation, affected the results.

  6. Bisphenol A Effects on Mammalian Oogenesis and Epigenetic Integrity of Oocytes: A Case Study Exploring Risks of Endocrine Disrupting Chemicals

    Directory of Open Access Journals (Sweden)

    Ursula Eichenlaub-Ritter

    2015-01-01

    Full Text Available Bisphenol A (BPA, originally developed as a synthetic oestrogen, is nowadays extensively used in the production of polymeric plastics. Under harsh conditions, these plastics may release BPA, which then can leach into the environment. Detectable concentrations of BPA have been measured in most analysed samples of human serum, plasma, or urine, as well as in follicular fluid, foetal serum, and amniotic fluid. Here we summarize the evidence about adverse BPA effects on the genetic and epigenetic integrity of mammalian oocytes. We conclude that increasing evidence supports the notion that low BPA concentrations adversely affect the epigenome of mammalian female germ cells, with functional consequences on gene expression, chromosome dynamics in meiosis, and oocyte development. Specific time windows, during which profound chromatin remodelling occurs and maternal imprints are established or protected, appear particularly vulnerable to epigenetic deregulation by BPA. Transgenerational effects have been also observed in the offspring of BPA-treated rodents, although the epigenetic mechanisms of inheritance still need to be clarified. The relevance of these findings for human health protection still needs to be fully assessed, but they warrant further investigation in both experimental models and humans.

  7. Mammalian target of rapamycin activity is required for expansion of CD34(+) hematopoietic progenitor cells

    NARCIS (Netherlands)

    Geest, Christian R.; Zwartkruis, Fried J.; Vellenga, Edo; Coffer, Paul J.; Buitenhuis, Miranda

    Background The mammalian target of rapamycin is a conserved protein kinase known to regulate protein synthesis, cell size and proliferation. Aberrant regulation of mammalian target of rapamycin activity has been observed in hematopoietic malignancies, including acute leukemias and myelodysplastic

  8. Inorganic nanoparticles for transfection of mammalian cells and removal of viruses from aqueous solutions.

    Science.gov (United States)

    Link, Nils; Brunner, Tobias J; Dreesen, Imke A J; Stark, Wendelin J; Fussenegger, Martin

    2007-12-01

    Owing to their small size, synthetic nanoparticles show unprecedented biophysical and biochemical properties which may foster novel advances in life-science research. Using flame-spray synthesis technology we have produced non-coated aluminum-, calcium-, cerium-, and zirconium-derived inorganic metal oxide nanoparticles which not only exhibit high affinity for nucleic acids, but can sequester such compounds from aqueous solution. This non-covalent DNA-binding capacity was successfully used to transiently transfect a variety of mammalian cells including human, reaching transfection efficiencies which compared favorably with classic calcium phosphate precipitation (CaP) procedures and lipofection. In this straightforward protocol, transfection was enabled by simply mixing nanoparticles with DNA in solution prior to addition to the target cell population. Transiently transfected cells showed higher production levels of the human secreted glycoprotein SEAP compared to isogenic populations transfected with established technologies. Inorganic metal oxide nanoparticles also showed a high binding capacity to human-pathogenic viruses including adenovirus, adeno-associated virus and human immunodeficiency virus type 1 and were able to clear these pathogens from aqueous solutions. The DNA transfection and viral clearance capacities of inorganic metal oxide nanoparticles may provide cost-effective biopharmaceutical manufacturing and water treatment in developing countries.

  9. Spider Silk Fibers Spun from Soluble Recombinant Silk Produced in Mammalian Cells

    Science.gov (United States)

    Lazaris, Anthoula; Arcidiacono, Steven; Huang, Yue; Zhou, Jiang-Feng; Duguay, François; Chretien, Nathalie; Welsh, Elizabeth A.; Soares, Jason W.; Karatzas, Costas N.

    2002-01-01

    Spider silks are protein-based ``biopolymer'' filaments or threads secreted by specialized epithelial cells as concentrated soluble precursors of highly repetitive primary sequences. Spider dragline silk is a flexible, lightweight fiber of extraordinary strength and toughness comparable to that of synthetic high-performance fibers. We sought to ``biomimic'' the process of spider silk production by expressing in mammalian cells the dragline silk genes (ADF-3/MaSpII and MaSpI) of two spider species. We produced soluble recombinant (rc)-dragline silk proteins with molecular masses of 60 to 140 kilodaltons. We demonstrated the wet spinning of silk monofilaments spun from a concentrated aqueous solution of soluble rc-spider silk protein (ADF-3; 60 kilodaltons) under modest shear and coagulation conditions. The spun fibers were water insoluble with a fine diameter (10 to 40 micrometers) and exhibited toughness and modulus values comparable to those of native dragline silks but with lower tenacity. Dope solutions with rc-silk protein concentrations >20% and postspinning draw were necessary to achieve improved mechanical properties of the spun fibers. Fiber properties correlated with finer fiber diameter and increased birefringence.

  10. Ex vivo mammalian prions are formed of paired double helical prion protein fibrils.

    Science.gov (United States)

    Terry, Cassandra; Wenborn, Adam; Gros, Nathalie; Sells, Jessica; Joiner, Susan; Hosszu, Laszlo L P; Tattum, M Howard; Panico, Silvia; Clare, Daniel K; Collinge, John; Saibil, Helen R; Wadsworth, Jonathan D F

    2016-05-01

    Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity and the three-dimensional structure of infectious prions has remained obscure. Recently, we developed novel methods to obtain exceptionally pure preparations of prions from mouse brain and showed that pathogenic PrP in these high-titre preparations is assembled into rod-like assemblies. Here, we have used precise cell culture-based prion infectivity assays to define the physical relationship between the PrP rods and prion infectivity and have used electron tomography to define their architecture. We show that infectious PrP rods isolated from multiple prion strains have a common hierarchical assembly comprising twisted pairs of short fibres with repeating substructure. The architecture of the PrP rods provides a new structural basis for understanding prion infectivity and can explain the inability to systematically generate high-titre synthetic prions from recombinant PrP. © 2016 The Authors.

  11. Synthetic Biology: Mapping the Scientific Landscape

    Science.gov (United States)

    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

  12. Advances in Synthetic Peptides Reagent Discovery

    Science.gov (United States)

    2013-07-01

    phage [4], bacteria [5-7], yeast [8, 9], insect cell/baculovirus [10], as well as mammalian cell culture [11]. Although each system has its unique...dependent characteristics,” The Journal of Immunology , 147(10), 3545-3552 (1991). [32] S. Becker, H. Höbenreich, A. Vogel et al., “Single‐Cell High

  13. Synthetic Biology: game changer in intelectual property

    Directory of Open Access Journals (Sweden)

    Laurens Landeweerd

    2016-12-01

    Full Text Available Synthetic biology can be considered a game changer that plays an important role in the current NBIC, or BINC convergence of nano-, bio-, info and cognitive sciences. Although most synthetic biology experts are unaware of it, the field appeals to the imagination in its adherence to targets that were usually associated with premodern alchemist science. This paper elaborates several aspects of synthetic biology as well as its consequences for long held notions of intellectual property and the ontological categories of scientific discovery on the one hand and engineering on the other, the distinction between natural and artificial, the grown and the made.

  14. Defining the Synthetic Biology Supply Chain

    Energy Technology Data Exchange (ETDEWEB)

    Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.; Diggans, James; Bartholomew, Rachel A.; Gehrig, Lindsey; Greaves, Mark

    2017-08-01

    In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and means to interdict, detect, or deter suspicious activity.

  15. A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials

    Directory of Open Access Journals (Sweden)

    Rosalind A. Le Feuvre

    2018-06-01

    Full Text Available Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials, where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal. Keywords: Synthetic biology, Materials, Biological materials, Biomaterials, Advanced materials

  16. The evolution of gene expression levels in mammalian organs

    DEFF Research Database (Denmark)

    Brawand, David; Soumillon, Magali; Necsulea, Anamaria

    2011-01-01

    and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped......Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across...... ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages...

  17. Unconventional Trafficking of Mammalian Phospholipase D3 to Lysosomes

    Directory of Open Access Journals (Sweden)

    Adriana Carolina Gonzalez

    2018-01-01

    Full Text Available Variants in the phospholipase D3 (PLD3 gene have genetically been linked to late-onset Alzheimer's disease. We present a detailed biochemical analysis of PLD3 and reveal its endogenous localization in endosomes and lysosomes. PLD3 reaches lysosomes as a type II transmembrane protein via a (for mammalian cells uncommon intracellular biosynthetic route that depends on the ESCRT (endosomal sorting complex required for transport machinery. PLD3 is sorted into intraluminal vesicles of multivesicular endosomes, and ESCRT-dependent sorting correlates with ubiquitination. In multivesicular endosomes, PLD3 is subjected to proteolytic cleavage, yielding a stable glycosylated luminal polypeptide and a rapidly degraded N-terminal membrane-bound fragment. This pathway closely resembles the delivery route of carboxypeptidase S to the yeast vacuole. Our experiments reveal a biosynthetic route of PLD3 involving proteolytic processing and ESCRT-dependent sorting for its delivery to lysosomes in mammalian cells.

  18. Leadership in Mammalian Societies: Emergence, Distribution, Power, and Payoff.

    Science.gov (United States)

    Smith, Jennifer E; Gavrilets, Sergey; Mulder, Monique Borgerhoff; Hooper, Paul L; Mouden, Claire El; Nettle, Daniel; Hauert, Christoph; Hill, Kim; Perry, Susan; Pusey, Anne E; van Vugt, Mark; Smith, Eric Alden

    2016-01-01

    Leadership is an active area of research in both the biological and social sciences. This review provides a transdisciplinary synthesis of biological and social-science views of leadership from an evolutionary perspective, and examines patterns of leadership in a set of small-scale human and non-human mammalian societies. We review empirical and theoretical work on leadership in four domains: movement, food acquisition, within-group conflict mediation, and between-group interactions. We categorize patterns of variation in leadership in five dimensions: distribution (across individuals), emergence (achieved versus inherited), power, relative payoff to leadership, and generality (across domains). We find that human leadership exhibits commonalities with and differences from the broader mammalian pattern, raising interesting theoretical and empirical issues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Prdm9 controls activation of mammalian recombination hotspots.

    Science.gov (United States)

    Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

    2010-02-12

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

  20. Measurement of Heme Synthesis Levels in Mammalian Cells.

    Science.gov (United States)

    Hooda, Jagmohan; Alam, Maksudul; Zhang, Li

    2015-07-09

    Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5-aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines.

  1. Mammalian cycles: internally defined periods and interaction-driven amplitudes

    Directory of Open Access Journals (Sweden)

    LR Ginzburg

    2015-08-01

    Full Text Available The cause of mammalian cycles—the rise and fall of populations over a predictable period of time—has remained controversial since these patterns were first observed over a century ago. In spite of extensive work on observable mammalian cycles, the field has remained divided upon what the true cause is, with a majority of opinions attributing it to either predation or to intra-species mechanisms. Here we unite the eigenperiod hypothesis, which describes an internal, maternal effect-based mechanism to explain the cycles’ periods with a recent generalization explaining the amplitude of snowshoe hare cycles in northwestern North America based on initial predator abundance. By explaining the period and the amplitude of the cycle with separate mechanisms, a unified and consistent view of the causation of cycles is reached. Based on our suggested theory, we forecast the next snowshoe hare cycle (predicted peak in 2016 to be of extraordinarily low amplitude.

  2. Stability of resazurin in buffers and mammalian cell culture media

    DEFF Research Database (Denmark)

    Rasmussen, Eva; Nicolaisen, G.M.

    1999-01-01

    The utility of a ferricyanide/ferrocyanide system used in the AlamarBlue(TM) (Serotec, Oxford, UK) vital. dye to inhibit the reduction of resazurin by mammalian cell culture media is questioned. Resazurin was found to be relatively stable when dissolved in phosphate-buffered saline (PBS). The use...... of HEPES resulted in a huge immediate dye reduction, which was significantly enhanced by exposure to diffuse light from fluorescent tubes in the laboratory 8 h per day. The reduction of resazurin by various cell culture media was time and temperature dependent, and it was significantly enhanced......'s nutrient mixture F-10 and F-12. Fetal calf serum (5-20%) slightly decreased resazurin reduction during the first 2 days of incubation. The reduction of resazurin by mammalian cell culture media do not appear to be problematic under normal culture conditions, and it is primarily dependent upon the presence...

  3. The Degradome database: mammalian proteases and diseases of proteolysis.

    Science.gov (United States)

    Quesada, Víctor; Ordóñez, Gonzalo R; Sánchez, Luis M; Puente, Xose S; López-Otín, Carlos

    2009-01-01

    The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

  4. Regeneration of hair cells in the mammalian vestibular system.

    Science.gov (United States)

    Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

    2016-06-01

    Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

  5. Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

    2016-10-27

    Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

  6. CRISPR and the Rebirth of Synthetic Biology

    NARCIS (Netherlands)

    Heidari, Raheleh; Shaw, David Martin; Elger, Bernice Simone

    Emergence of novel genome engineering technologies such as clustered regularly interspaced short palindromic repeat (CRISPR) has refocused attention on unresolved ethical complications of synthetic biology. Biosecurity concerns, deontological issues and human right aspects of genome editing have

  7. Thermodynamic Analysis of Ionic Compounds: Synthetic Applications.

    Science.gov (United States)

    Yoder, Claude H.

    1986-01-01

    Shows how thermodynamic cycles can be used to understand trends in heats of formation and aqueous solubilities and, most importantly, how they may be used to choose synthetic routes to new ionic compounds. (JN)

  8. Synthetic biology platform technologies for antimicrobial applications.

    Science.gov (United States)

    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.

  9. Synthetic Sediments and Stochastic Groundwater Hydrology

    Science.gov (United States)

    Wilson, J. L.

    2002-12-01

    For over twenty years the groundwater community has pursued the somewhat elusive goal of describing the effects of aquifer heterogeneity on subsurface flow and chemical transport. While small perturbation stochastic moment methods have significantly advanced theoretical understanding, why is it that stochastic applications use instead simulations of flow and transport through multiple realizations of synthetic geology? Allan Gutjahr was a principle proponent of the Fast Fourier Transform method for the synthetic generation of aquifer properties and recently explored new, more geologically sound, synthetic methods based on multi-scale Markov random fields. Focusing on sedimentary aquifers, how has the state-of-the-art of synthetic generation changed and what new developments can be expected, for example, to deal with issues like conceptual model uncertainty, the differences between measurement and modeling scales, and subgrid scale variability? What will it take to get stochastic methods, whether based on moments, multiple realizations, or some other approach, into widespread application?

  10. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

    This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

  11. Defining the Synthetic Biology Supply Chain.

    Science.gov (United States)

    Frazar, Sarah L; Hund, Gretchen E; Bonheyo, George T; Diggans, James; Bartholomew, Rachel A; Gehrig, Lindsey; Greaves, Mark

    Several recent articles have described risks posed by synthetic biology and spurred vigorous discussion in the scientific, commercial, and government communities about how to best detect, prevent, regulate, and respond to these risks. The Pacific Northwest National Laboratory's (PNNL) deep experience working with dual-use technologies for the nuclear industry has shown that analysis of supply chains can reveal security vulnerabilities and ways to mitigate security risk without hindering beneficial research and commerce. In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology to illustrate new insights about the effectiveness of current regulations, the possible need for different screening approaches, and new technical solutions that could help identify or mitigate risks in the synthetic biology supply chain.

  12. Presence of abscisic acid, a phytohormone, in the mammalian brain.

    OpenAIRE

    Le Page-Degivry, M T; Bidard, J N; Rouvier, E; Bulard, C; Lazdunski, M

    1986-01-01

    This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention pr...

  13. Applications of stable isotope analysis in mammalian ecology.

    Science.gov (United States)

    Walter, W David; Kurle, Carolyn M; Hopkins, John B

    2014-01-01

    In this editorial, we provide a brief introduction and summarize the 10 research articles included in this Special Issue on Applications of stable isotope analysis in mammalian ecology. The first three articles report correction and discrimination factors that can be used to more accurately estimate the diets of extinct and extant mammals using stable isotope analysis. The remaining seven applied research articles use stable isotope analysis to address a variety of wildlife conservation and management questions from the oceans to the mountains.

  14. Global patterns of fragmentation and connectivity of mammalian carnivore habitat

    OpenAIRE

    Crooks, Kevin R.; Burdett, Christopher L.; Theobald, David M.; Rondinini, Carlo; Boitani, Luigi

    2011-01-01

    Although mammalian carnivores are vulnerable to habitat fragmentation and require landscape connectivity, their global patterns of fragmentation and connectivity have not been examined. We use recently developed high-resolution habitat suitability models to conduct comparative analyses and to identify global hotspots of fragmentation and connectivity for the world's terrestrial carnivores. Species with less fragmentation (i.e. more interior high-quality habitat) had larger geographical ranges...

  15. Regulation of Autophagy by Glucose in Mammalian Cells

    OpenAIRE

    Moruno, Félix; Pérez-Jiménez, Eva; Knecht, Erwin

    2012-01-01

    Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focu...

  16. Host-virus interactions of mammalian endogenous retroviruses

    OpenAIRE

    Farkašová, Helena

    2017-01-01

    Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

  17. Clotting of mammalian fibrinogens by papain: A re-examination

    OpenAIRE

    Doolittle, RF

    2014-01-01

    © 2014 American Chemical Society. Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be du...

  18. Report of the NASA Mammalian Developmental Biology Working Group

    Science.gov (United States)

    Keefe, J. R.

    1985-01-01

    Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

  19. Mottled Mice and Non-Mammalian Models of Menkes Disease

    DEFF Research Database (Denmark)

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critica......-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals....

  20. Prdm9 Controls Activation of Mammalian Recombination Hotspots

    OpenAIRE

    Parvanov, Emil D.; Petkov, Petko M.; Paigen, Kenneth

    2009-01-01

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, assures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse Chr 17, that controls activation of recombination at multiple distant hotspots, has been mapped within a 181 Kb interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is uniquel...

  1. Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons

    DEFF Research Database (Denmark)

    Hounsgaard, J; Yarom, Y

    1985-01-01

    The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete...... their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation....

  2. Photooxidative damage to mammalian cells and proteins by visible light

    International Nuclear Information System (INIS)

    Packer, L.; Kellogg, E.W. III

    1980-01-01

    In the present article, studies carried out in our laboratory on the effects of visible irradiation and O 2 in a variety of target systems ranging from cultured mammalian cells to purified catalase are reviewed. We will relate these studies of photooxidative damage to a scheme for the propagation of intracellular damage which traces a number of the possible pro-oxidant and anti-oxidant pathways found in the cell

  3. Digital microfluidic processing of mammalian embryos for vitrification.

    Directory of Open Access Journals (Sweden)

    Derek G Pyne

    Full Text Available Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

  4. Endogenous peripheral neuromodulators of the mammalian taste bud.

    Science.gov (United States)

    Dando, Robin

    2010-10-01

    The sensitivity of the mammalian taste system displays a degree of plasticity based on short-term nutritional requirements. Deficiency in a particular substance may lead to a perceived increase in palatability of this substance, providing an additional drive to redress this nutritional imbalance through modification of intake. This alteration occurs not only in the brain but also, before any higher level processing has occurred, in the taste buds themselves. A brief review of recent advances is offered.

  5. Generation of Induced Pluripotent Stem Cells from Mammalian Endangered Species.

    Science.gov (United States)

    Ben-Nun, Inbar Friedrich; Montague, Susanne C; Houck, Marlys L; Ryder, Oliver; Loring, Jeanne F

    2015-01-01

    For some highly endangered species there are too few reproductively capable animals to maintain adequate genetic diversity, and extraordinary measures are necessary to prevent their extinction. Cellular reprogramming is a means to capture the genomes of individual animals as induced pluripotent stem cells (iPSCs), which may eventually facilitate reintroduction of genetic material into breeding populations. Here, we describe a method for generating iPSCs from fibroblasts of mammalian endangered species.

  6. Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    2010-01-01

    Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex. TF Emx2 plays a crucial role in patterning...... later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex...

  7. Synthetic Sling Failure - Evaluations and Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, C. S. [Washington River Protection Solutions, Richland, WA (United States); Mackey, Thomas C. [Washington River Protection Solutions, Richland, WA (United States)

    2009-10-26

    The information and evaluations provided in this report were compiled to address the recurring problem of synthetic sling failure. As safety is the number one priority in all work aspects, a solution must be devised to prevent accidents from occurring. A total of thirteen cases regarding synthetic sling failure were evaluated in order to determine their causes, effects, and preventative measures. From the collected data, it was found that all cases in which the synthetic sling contacted the edge of its load resulted in sling failure. It is required that adequate synthetic sling protection devices be used to protect slings in any lift where the sling comes in direct contact with the edge or corner of its load. However, there are no consensus codes or standards stating the type, material, or purpose of the type of protective device used to protect the sling from being cut. Numerous industry standards and codes provide vague descriptions on how to protect synthetic slings. Without a clear, concise statement of how to protect synthetic slings, it is common for inadequate materials and sling protection devices to be used in an attempt to meet the intent of these requirements. The use of an inadequate sling protection device is the main cause of synthetic sling failure in all researched cases. Commercial sling protection devices come in many shapes and sizes, and have a variety of names, as well as advertised uses. 'Abrasion pads' and 'wear protectors' are two different names for products with the same intended purpose. There is no distinguishable way to determine the extent of sling protection which these devices will provide, or what specific scenarios they are made for. This creates room for error in a field where error is unacceptable. This report provides a recommended action for hoisting and rigging activities which require synthetic slings to contact a load, as well as recommended changes to industry standards which will benefit overall

  8. Base Composition Characteristics of Mammalian miRNAs

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

  9. Functional noncoding sequences derived from SINEs in the mammalian genome.

    Science.gov (United States)

    Nishihara, Hidenori; Smit, Arian F A; Okada, Norihiro

    2006-07-01

    Recent comparative analyses of mammalian sequences have revealed that a large number of nonprotein-coding genomic regions are under strong selective constraint. Here, we report that some of these loci have been derived from a newly defined family of ancient SINEs (short interspersed repetitive elements). This is a surprising result, as SINEs and other transposable elements are commonly thought to be genomic parasites. We named the ancient SINE family AmnSINE1, for Amniota SINE1, because we found it to be present in mammals as well as in birds, and some copies predate the mammalian-bird split 310 million years ago (Mya). AmnSINE1 has a chimeric structure of a 5S rRNA and a tRNA-derived SINE, and is related to five tRNA-derived SINE families that we characterized here in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. All of the newly described SINE families have a common central domain that is also shared by zebrafish SINE3, and we collectively name them the DeuSINE (Deuterostomia SINE) superfamily. Notably, of the approximately 1000 still identifiable copies of AmnSINE1 in the human genome, 105 correspond to loci phylogenetically highly conserved among mammalian orthologs. The conservation is strongest over the central domain. Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of the copies have acquired genomic functionality.

  10. DNA repair and radiation sensitivity in mammalian cells

    International Nuclear Information System (INIS)

    Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population

  11. Non-linear leak currents affect mammalian neuron physiology

    Directory of Open Access Journals (Sweden)

    Shiwei eHuang

    2015-11-01

    Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

  12. Current perspectives of CASA applications in diverse mammalian spermatozoa.

    Science.gov (United States)

    van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

    2018-03-26

    Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

  13. Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

    Science.gov (United States)

    Cassone, V M; Speh, J C; Card, J P; Moore, R Y

    1988-01-01

    A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

  14. Enamel formation and growth in non-mammalian cynodonts

    Science.gov (United States)

    Dirks, Wendy; Martinelli, Agustín G.

    2018-01-01

    The early evolution of mammals is associated with the linked evolutionary origin of diphyodont tooth replacement, rapid juvenile growth and determinate adult growth. However, specific relationships among these characters during non-mammalian cynodont evolution require further exploration. Here, polarized light microscopy revealed incremental lines, resembling daily laminations of extant mammals, in histological sections of enamel in eight non-mammalian cynodont species. In the more basal non-probainognathian group, enamel extends extremely rapidly from cusp to cervix. By contrast, the enamel of mammaliamorphs is gradually accreted, with slow rates of crown extension, more typical of the majority of non-hypsodont crown mammals. These results are consistent with the reduction in dental replacement rate across the non-mammalian cynodont lineage, with greater rates of crown extension required in most non-probainognathians, and slower crown extension rates permitted in mammaliamorphs, which have reduced patterns of dental replacement in comparison with many non-probainognathians. The evolution of mammal-like growth patterns, with faster juvenile growth and more abruptly terminating adult growth, is linked with this reduction in dental replacement rates and may provide an additional explanation for the observed pattern in enamel growth rates. It is possible that the reduction in enamel extension rates in mammaliamorphs reflects an underlying reduction in skeletal growth rates at the time of postcanine formation, due to a more abruptly terminating pattern of adult growth in these more mammal-like, crownward species. PMID:29892415

  15. A vaccine grade of yeast Saccharomyces cerevisiae expressing mammalian myostatin

    Directory of Open Access Journals (Sweden)

    Zhang Tingting

    2012-12-01

    Full Text Available Abstract Background Yeast Saccharomyces cerevisiae is a widely-used system for protein expression. We previously showed that heat-killed whole recombinant yeast vaccine expressing mammalian myostatin can modulate myostatin function in mice, resulting in increase of body weight and muscle composition in these animals. Foreign DNA introduced into yeast cells can be lost soon unless cells are continuously cultured in selection media, which usually contain antibiotics. For cost and safety concerns, it is essential to optimize conditions to produce quality food and pharmaceutical products. Results We developed a simple but effective method to engineer a yeast strain stably expressing mammalian myostatin. This method utilized high-copy-number integration of myostatin gene into the ribosomal DNA of Saccharomyces cerevisiae. In the final step, antibiotic selection marker was removed using the Cre-LoxP system to minimize any possible side-effects for animals. The resulting yeast strain can be maintained in rich culture media and stably express mammalian myostatin for two years. Oral administration of the recombinant yeast was able to induce immune response to myostatin and modulated the body weight of mice. Conclusions Establishment of such yeast strain is a step further toward transformation of yeast cells into edible vaccine to improve meat production in farm animals and treat human muscle-wasting diseases in the future.

  16. Fossilized Mammalian Erythrocytes Associated With a Tick Reveal Ancient Piroplasms.

    Science.gov (United States)

    Poinar, George

    2017-07-01

    Ticks transmit a variety of pathogenic organisms to vertebrates, especially mammals. The fossil record of such associations is extremely rare. An engorged nymphal tick of the genus Ambylomma in Dominican amber was surrounded by erythrocytes from its mammalian host. Some of the exposed erythrocytes contained developmental stages of a hemoprotozoan resembling members of the Order Piroplasmida. The fossil piroplasm is described, its stages compared with those of extant piroplasms, and reasons provided why the mammalian host could have been a primate. The parasites were also found in the gut epithelial cells and body cavity of the fossil tick. Aside from providing the first fossil mammalian red blood cells and the first fossil intraerythrocytic hemoparasites, the present discovery shows that tick-piroplasm associations were already well established in the Tertiary. This discovery provides a timescale that can be used in future studies on the evolution of the Piroplasmida. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com Version of Record, first published online March 20, 2017 with fixed content and layout in compliance with Art. 8.1.3.2 ICZN.

  17. Secondary osteons scale allometrically in mammalian humerus and femur.

    Science.gov (United States)

    Felder, A A; Phillips, C; Cornish, H; Cooke, M; Hutchinson, J R; Doube, M

    2017-11-01

    Intra-cortical bone remodelling is a cell-driven process that replaces existing bone tissue with new bone tissue in the bone cortex, leaving behind histological features called secondary osteons. While the scaling of bone dimensions on a macroscopic scale is well known, less is known about how the spatial dimensions of secondary osteons vary in relation to the adult body size of the species. We measured the cross-sectional area of individual intact secondary osteons and their central Haversian canals in transverse sections from 40 stylopodal bones of 39 mammalian species (body mass 0.3-21 000 kg). Scaling analysis of our data shows that mean osteonal resorption area (negative allometry, exponent 0.23, R 2  0.54, p <0.005) and Haversian canal area (negative allometry, exponent 0.31, R 2  0.45, p <0.005) are significantly related to body mass, independent of phylogeny. This study is the most comprehensive of its kind to date, and allows us to describe overall trends in the scaling behaviour of secondary osteon dimensions, supporting the inference that the osteonal resorption area may be limited by the need to avoid fracture in smaller mammalian species, but the need to maintain osteocyte viability in larger mammalian species.

  18. The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

    Science.gov (United States)

    Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

    2014-06-01

    The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

  19. Synthetic Biology and the Translational Imperative.

    Science.gov (United States)

    Heidari Feidt, Raheleh; Ienca, Marcello; Elger, Bernice Simone; Folcher, Marc

    2017-12-18

    Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may-together with financial and organizational problems-be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the "translational imperative."

  20. Synthetic biology era: Improving antibiotic's world.

    Science.gov (United States)

    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.

  1. Synthetic cannabis and acute ischemic stroke.

    Science.gov (United States)

    Bernson-Leung, Miya E; Leung, Lester Y; Kumar, Sandeep

    2014-01-01

    An association between marijuana use and stroke has been previously reported. However, the health risks of newer synthetic cannabinoid compounds are less well known. We describe 2 cases that introduce a previously unreported association between synthetic cannabis use and ischemic stroke in young adults. A 22-year-old woman presented with dysarthria, left hemiplegia, and left hemianesthesia within hours of first use of synthetic cannabis. She was healthy and without identified stroke risk factors other than oral contraceptive use and a patent foramen ovale without venous thromboses. A 26-year-old woman presented with nonfluent aphasia, left facial droop, and left hemianesthesia approximately 12 hours after first use of synthetic cannabis. Her other stroke risk factors included migraine with aura, oral contraceptive use, smoking, and a family history of superficial thrombophlebitis. Both women were found to have acute, large-territory infarctions of the right middle cerebral artery. Our 2 cases had risk factors for ischemic stroke but were otherwise young and healthy and the onset of their deficits occurred within hours after first-time exposure to synthetic cannabis. Synthetic cannabis use is an important consideration in the investigation of stroke in young adults. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials.

    Science.gov (United States)

    Le Feuvre, Rosalind A; Scrutton, Nigel S

    2018-06-01

    Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials , where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal.

  3. Synthetic bedding and wheeze in childhood.

    Science.gov (United States)

    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.

  4. 21 CFR 73.1200 - Synthetic iron oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

  5. 21 CFR 73.200 - Synthetic iron oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.200 Section 73.200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

  6. 21 CFR 172.888 - Synthetic petroleum wax.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is a...

  7. Synthetic biology and the technicity of biofuels.

    Science.gov (United States)

    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.

  8. WISB: Warwick Integrative Synthetic Biology Centre.

    Science.gov (United States)

    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).

  9. Cfd modeling of a synthetic jet actuator

    International Nuclear Information System (INIS)

    Dghim, Marouane; Ben Chiekh, Maher; Ben Nasrallah, Sassi

    2009-01-01

    Synthetic jet actuators show good promise as an enabling technology for innovative boundary layer flow control applied to external surfaces, like airplane wings, and to internal flows, like those occurring in a curved engine inlet. The appealing characteristics of a synthetic jet are zero-net-mass flux operation and an efficient control effect that takes advantages of unsteady fluid phenomena. The formation of a synthetic jet in a quiescent external air flow is only beginning to be understood and a rational understanding of these devices is necessary before they can be applied to the control of flows outside of the laboratory. The synthetic jet flow generated by a planar orifice is investigated here using computational approach. Computations of the 2D synthetic jet are performed with unsteady RANS modeled with the Realizable κ - ε turbulence model available in FLUENT environment. In this present work, the ability of the first order turbulence model, employed in our computations, to model the formation of the counter-rotating-vortex pair (CVP) that appears in the flow-field was investigated. Computational results were in good agreement with experimental measurements. The effectiveness of such control actuator was tested on separated boundary layer. Preliminary investigation were presented and discussed

  10. Synthetic cathinones: a new public health problem.

    Science.gov (United States)

    Karila, Laurent; Megarbane, Bruno; Cottencin, Olivier; Lejoyeux, Michel

    2015-01-01

    New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "mephedrone", "methylone", "MDPV", "4-MEC", "addiction", and "substance use disorder".

  11. Rheological characteristics of synthetic road binders

    Energy Technology Data Exchange (ETDEWEB)

    Gordon D. Airey; Musarrat H. Mohammed; Caroline Fichter [University of Nottingham, Nottingham (United Kingdom)

    2008-08-15

    This paper deals with the synthesis of polymer binders from monomers that could in future be derived from renewable resources. These binders consist of polyethyl acrylate (PEA) of different molecular weight, polymethyl acrylate (PMA) and polybutyl acrylate (PBA), which were synthesised from ethyl acrylate, methyl acrylate and butyl acrylate, respectively, by atom transfer radical polymerization (ATRP). The fundamental rheological properties of these binders were determined by means of a dynamic shear rheometer (DSR) using a combination of temperature and frequency sweeps. The results indicate that PEA has rheological properties similar to that of 100/150 penetration grade bitumen, PMA similar rheological properties to that of 10/20 penetration grade bitumen, while PBA, due to its highly viscous nature and low complex modulus, cannot be used on its own as an asphalt binder. The synthetic binders were also combined with conventional penetration grade bitumen to produce a range of bitumen-synthetic polymer binder blends. These blends were batched by mass in the ratio of 1:1 or 3:1 and subjected to the same DSR rheological testing as the synthetic binders. The blends consisting of a softer bitumen (70/100 pen or 100/150 pen) with a hard synthetic binder (PMA) tended to be more compatible and therefore stable and produced rheological properties that combined the properties of the two components. The synthetic binders and particularly the extended bitumen samples (blends) produced rheological properties that showed similar characteristics to elastomeric SBS PMBs. 30 refs., 12 figs., 2 tabs.

  12. [Treatment approaches for synthetic drug addiction].

    Science.gov (United States)

    Kobayashi, Ohji

    2015-09-01

    In Japan, synthetic drugs have emerged since late 2000s, and cases of emergency visits and fatal traffic accidents due to acute intoxication have rapidly increased. The synthetic drugs gained popularity mainly because they were cheap and thought to be "legal". The Japanese government restricted not only production and distribution, but also its possession and use in April 2014. As the synthetic drug dependent patients have better social profiles compared to methamphetamine abusers, this legal sanction may have triggered the decrease in the number of synthetic drug dependent patient visits observed at Kanagawa Psychiatric Center since July 2014. Treatment of the synthetic drug dependent patients should begin with empathic inquiry into the motives and positive psychological effects of the drug use. In the maintenance phase, training patients to trust others and express their hidden negative emotions through verbal communications is essential. The recovery is a process of understanding the relationship between psychological isolation and drug abuse, and gaining trust in others to cope with negative emotions that the patients inevitably would face in their subsequent lives.

  13. Role of Synthetic and Dimensional Synthetic Organic Chemistry in Block Copolymer Micelle Nanosensor Engineering

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar

    This thesis investigated the role of amphiphilic triblock copolymer micelle nanomaterials in nanosensors, with emphasis on the synthesis of micelle particle sensors. The thesis is focused on the role of synthetic and dimensional synthetic organic chemistry in amphiphilic triblock core-shellcorona...

  14. Mammalian amyloidogenic proteins promote prion nucleation in yeast.

    Science.gov (United States)

    Chandramowlishwaran, Pavithra; Sun, Meng; Casey, Kristin L; Romanyuk, Andrey V; Grizel, Anastasiya V; Sopova, Julia V; Rubel, Aleksandr A; Nussbaum-Krammer, Carmen; Vorberg, Ina M; Chernoff, Yury O

    2018-03-02

    Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and the expression of a mammalian amyloidogenic protein that is not fused to the Sup35 prion domain failed to promote prion nucleation, further indicating that physical linkage of a mammalian amyloidogenic protein to the prion domain of a yeast protein is required for the nucleation of a yeast prion. Biochemical and cytological approaches confirmed the nucleation of protein aggregates in the yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of human amyloid-β (associated with Alzheimer's disease) and mouse prion protein (associated with prion diseases), respectively, antagonized or enhanced nucleation of a yeast prion by these proteins. The yeast-based prion nucleation assay, developed in our work, can be employed for mutational dissection of amyloidogenic proteins. We anticipate that it will aid in the identification of chemicals that influence initial amyloid nucleation and in searching for new amyloidogenic proteins in a variety of proteomes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Labeling proteins on live mammalian cells using click chemistry.

    Science.gov (United States)

    Nikić, Ivana; Kang, Jun Hee; Girona, Gemma Estrada; Aramburu, Iker Valle; Lemke, Edward A

    2015-05-01

    We describe a protocol for the rapid labeling of cell-surface proteins in living mammalian cells using click chemistry. The labeling method is based on strain-promoted alkyne-azide cycloaddition (SPAAC) and strain-promoted inverse-electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions, in which noncanonical amino acids (ncAAs) bearing ring-strained alkynes or alkenes react, respectively, with dyes containing azide or tetrazine groups. To introduce ncAAs site specifically into a protein of interest (POI), we use genetic code expansion technology. The protocol can be described as comprising two steps. In the first step, an Amber stop codon is introduced--by site-directed mutagenesis--at the desired site on the gene encoding the POI. This plasmid is then transfected into mammalian cells, along with another plasmid that encodes an aminoacyl-tRNA synthetase/tRNA (RS/tRNA) pair that is orthogonal to the host's translational machinery. In the presence of the ncAA, the orthogonal RS/tRNA pair specifically suppresses the Amber codon by incorporating the ncAA into the polypeptide chain of the POI. In the second step, the expressed POI is labeled with a suitably reactive dye derivative that is directly supplied to the growth medium. We provide a detailed protocol for using commercially available ncAAs and dyes for labeling the insulin receptor, and we discuss the optimal surface-labeling conditions and the limitations of labeling living mammalian cells. The protocol involves an initial cloning step that can take 4-7 d, followed by the described transfections and labeling reaction steps, which can take 3-4 d.

  16. Nanoscale X-Ray Microscopic Imaging of Mammalian Mineralized Tissue

    OpenAIRE

    Andrews, Joy C.; Almeida, Eduardo; van der Meulen, Marjolein C.H.; Alwood, Joshua S.; Lee, Chialing; Liu, Yijin; Chen, Jie; Meirer, Florian; Feser, Michael; Gelb, Jeff; Rudati, Juana; Tkachuk, Andrei; Yun, Wenbing; Pianetta, Piero

    2010-01-01

    A novel hard transmission X-ray microscope (TXM) at the Stanford Synchrotron Radiation Light-source operating from 5 to 15 keV X-ray energy with 14 to 30 µm2 field of view has been used for high-resolution (30–40 nm) imaging and density quantification of mineralized tissue. TXM is uniquely suited for imaging of internal cellular structures and networks in mammalian mineralized tissues using relatively thick (50 µm), untreated samples that preserve tissue micro- and nanostructure. To test this...

  17. The neuroanatomy of the kisspeptin system in the mammalian brain

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Simonneaux, Valerie

    2008-01-01

    , little data are available about the localization of kisspeptin neurons in the brain, and in particular the projection patterns of kisspeptin containing axons implicated in regulation of the hypothalamo-pituitary gonadal axis. This review covers the current information about the localization of kisspeptin...... neurons in the mammalian brain and discusses the facts and artifacts of the methods of their detection. The available data suggest that kisspeptins are synthesized in neurons in the anteroventral periventricular nucleus and the arcuate nucleus. Both populations are considered to be involved in control...

  18. Small GTPases and formins in mammalian oocyte maturation: cytoskeletal organizers.

    Science.gov (United States)

    Kwon, Sojung; Lim, Hyunjung J

    2011-03-01

    The maturation process of mammalian oocytes accompanies an extensive rearrangement of the cytoskeleton and associated proteins. As this process requires a delicate interplay between the cytoskeleton and its regulators, it is often targeted by various external and internal adversaries that affect the congression and/or segregation of chromosomes. Asymmetric cell division in oocytes also requires specific regulators of the cytoskeleton, including formin-2 and small GTPases. Recent literature providing clues regarding how actin filaments and microtubules interact during spindle migration in mouse oocytes are highlighted in this review.

  19. Prevalence of sexual dimorphism in mammalian phenotypic traits

    Science.gov (United States)

    Karp, Natasha A.; Mason, Jeremy; Beaudet, Arthur L.; Benjamini, Yoav; Bower, Lynette; Braun, Robert E.; Brown, Steve D.M.; Chesler, Elissa J.; Dickinson, Mary E.; Flenniken, Ann M.; Fuchs, Helmut; Angelis, Martin Hrabe de; Gao, Xiang; Guo, Shiying; Greenaway, Simon; Heller, Ruth; Herault, Yann; Justice, Monica J.; Kurbatova, Natalja; Lelliott, Christopher J.; Lloyd, K.C. Kent; Mallon, Ann-Marie; Mank, Judith E.; Masuya, Hiroshi; McKerlie, Colin; Meehan, Terrence F.; Mott, Richard F.; Murray, Stephen A.; Parkinson, Helen; Ramirez-Solis, Ramiro; Santos, Luis; Seavitt, John R.; Smedley, Damian; Sorg, Tania; Speak, Anneliese O.; Steel, Karen P.; Svenson, Karen L.; Obata, Yuichi; Suzuki, Tomohiro; Tamura, Masaru; Kaneda, Hideki; Furuse, Tamio; Kobayashi, Kimio; Miura, Ikuo; Yamada, Ikuko; Tanaka, Nobuhiko; Yoshiki, Atsushi; Ayabe, Shinya; Clary, David A.; Tolentino, Heather A.; Schuchbauer, Michael A.; Tolentino, Todd; Aprile, Joseph Anthony; Pedroia, Sheryl M.; Kelsey, Lois; Vukobradovic, Igor; Berberovic, Zorana; Owen, Celeste; Qu, Dawei; Guo, Ruolin; Newbigging, Susan; Morikawa, Lily; Law, Napoleon; Shang, Xueyuan; Feugas, Patricia; Wang, Yanchun; Eskandarian, Mohammad; Zhu, Yingchun; Nutter, Lauryl M. J.; Penton, Patricia; Laurin, Valerie; Clarke, Shannon; Lan, Qing; Sohel, Khondoker; Miller, David; Clark, Greg; Hunter, Jane; Cabezas, Jorge; Bubshait, Mohammed; Carroll, Tracy; Tondat, Sandra; MacMaster, Suzanne; Pereira, Monica; Gertsenstein, Marina; Danisment, Ozge; Jacob, Elsa; Creighton, Amie; Sleep, Gillian; Clark, James; Teboul, Lydia; Fray, Martin; Caulder, Adam; Loeffler, Jorik; Codner, Gemma; Cleak, James; Johnson, Sara; Szoke-Kovacs, Zsombor; Radage, Adam; Maritati, Marina; Mianne, Joffrey; Gardiner, Wendy; Allen, Susan; Cater, Heather; Stewart, Michelle; Keskivali-Bond, Piia; Sinclair, Caroline; Brown, Ellen; Doe, Brendan; Wardle-Jones, Hannah; Grau, Evelyn; Griggs, Nicola; Woods, Mike; Kundi, Helen; Griffiths, Mark N. D.; Kipp, Christian; Melvin, David G.; Raj, Navis P. S.; Holroyd, Simon A.; Gannon, David J.; Alcantara, Rafael; Galli, Antonella; Hooks, Yvette E.; Tudor, Catherine L.; Green, Angela L.; Kussy, Fiona L.; Tuck, Elizabeth J.; Siragher, Emma J.; Maguire, Simon A.; Lafont, David T.; Vancollie, Valerie E.; Pearson, Selina A.; Gates, Amy S.; Sanderson, Mark; Shannon, Carl; Anthony, Lauren F. E.; Sumowski, Maksymilian T.; McLaren, Robbie S. B.; Swiatkowska, Agnieszka; Isherwood, Christopher M.; Cambridge, Emma L; Wilson, Heather M.; Caetano, Susana S.; Mazzeo, Cecilia Icoresi; Dabrowska, Monika H.; Lillistone, Charlotte; Estabel, Jeanne; Maguire, Anna Karin B.; Roberson, Laura-Anne; Pavlovic, Guillaume; Birling, Marie-Christine; Marie, Wattenhofer-Donze; Jacquot, Sylvie; Ayadi, Abdel; Ali-Hadji, Dalila; Charles, Philippe; André, Philippe; Le Marchand, Elise; El Amri, Amal; Vasseur, Laurent; Aguilar-Pimentel, Antonio; Becker, Lore; Treise, Irina; Moreth, Kristin; Stoeger, Tobias; Amarie, Oana V.; Neff, Frauke; Wurst, Wolfgang; Bekeredjian, Raffi; Ollert, Markus; Klopstock, Thomas; Calzada-Wack, Julia; Marschall, Susan; Brommage, Robert; Steinkamp, Ralph; Lengger, Christoph; Östereicher, Manuela A.; Maier, Holger; Stoeger, Claudia; Leuchtenberger, Stefanie; Yildrim, AliÖ; Garrett, Lillian; Hölter, Sabine M; Zimprich, Annemarie; Seisenberger, Claudia; Bürger, Antje; Graw, Jochen; Eickelberg, Oliver; Zimmer, Andreas; Wolf, Eckhard; Busch, Dirk H; Klingenspor, Martin; Schmidt-Weber, Carsten; Gailus-Durner, Valérie; Beckers, Johannes; Rathkolb, Birgit; Rozman, Jan; Wakana, Shigeharu; West, David; Wells, Sara; Westerberg, Henrik; Yaacoby, Shay; White, Jacqueline K.

    2017-01-01

    The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans. PMID:28650954

  20. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    Science.gov (United States)

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  1. Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

    Science.gov (United States)

    Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

    2017-01-01

    First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

  2. Factors affecting the spontaneous mutational spectra in somatic mammalian cells

    Directory of Open Access Journals (Sweden)

    О.А. Ковальова

    2006-04-01

    Full Text Available  In our survey of references we are discussed the influence of factors biological origin on the spontaneous mutation specters in mammalian. Seasonal and age components influence on the frequence of cytogenetic anomalies. The immune and endocrinous systems are take part in control of the alteration of the spontaneous mutation specters. Genetical difference of sensibility in animal and human at the alteration of factors enviroment as and  genetical differences of repair systems activity are may influence on individual variation of spontaneous destabilization characters of chromosomal apparatus.

  3. Robust expression of a bioactive mammalian protein in chlamydomonas chloroplast

    Science.gov (United States)

    Mayfield, Stephen P.

    2010-03-16

    Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery or proteins/peptides, especially gut active proteins, without purification is disclosed.

  4. Regulation of gene expression in mammalian cells following ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, D.A.; Lee, S.W

    1991-01-01

    Mammalian cells use a variety of mechanisms to control the expression of new gene transcrips elicited in response to ionizing radiation. Damage-induced proteins have been found which contain DNA binding sites located within the promoter regions of SV40 and human thymidine kinase genes. DNA binding proteins as well as proteins which bind to specific DNA lesions (e.g., XIP bp 175 binds specifically to X-ray-damaged DNA) may play a role in the initial recognition of DNA damage and may initiate DNA repair processes, along with new transcription. Mammalian gene expression after DNA damage is also regulated via the stabilization of preexisting mRNA transcripts. Stabilized mRNA transcripts are translated into protein products not previously present in the cell due to undefined posttranscriptional modifications. Thus far, the only example of mRNA stabilization following X-irradiation is the immediate induction of tissue-type plasminogen activator. Mammalian cells synthesize new mRNA transcripts indirect response to DNA damage. Using cDNA cloning, Northern RNA blotting and nuclear run-on techniques, the levels of a variety of known and previously unknown genes dramatically increase following X-irradiation. These genes/proteins now include; a) DNA binding transcripts factors, such as the UV-responsive element binding factors, ionizing radiation-induced DNA-binding proteins, and XIP bP 175; b) proto-oncogenes, such as c-fos, c-jun, and c-myc; c) several growth-related genes, (e.g., the gadd genes, protein kinase C, IL-1, and thymidine kinase); and d) a variety of other genes, including proteases, tumor necrosis factor-alpha, and DT diaphorase. Mammalian cells respond to X-irradiation by eliciting a very complex series of events resulting in the appearance of new genes and proteins. These gene products may affect DNA repair, adaptive responses, apoptosis, SOS-type mutagenic response, and/or carcinogenesis. (J.P.N.)

  5. A game of thrones: neural plasticity in mammalian social hierarchies.

    Science.gov (United States)

    Mooney, Skyler J; Peragine, Diana E; Hathaway, Georgia A; Holmes, Melissa M

    2014-01-01

    Social status is a key regulator of health and reproduction in mammals, including humans. Despite this, relatively little is known about how social status influences the mammalian brain. Furthermore, the extent to which status is an independent construct, i.e., not simply acting as a psychosocial stressor, is yet to be determined. Research to date reveals several promising mechanisms and/or systems associated with social status, including monoamine systems, hypothalamic neuroendocrine axes, and the hippocampus, though whether these differences are the cause or effect of status is often unclear. We review these candidates and propose how best to approach this research question in the future.

  6. Flavonoids in Helichrysum pamphylicum inhibit mammalian type I DNA topoisomerase.

    Science.gov (United States)

    Topcu, Zeki; Ozturk, Bintug; Kucukoglu, Ozlem; Kilinc, Emrah

    2008-01-01

    DNA topoisomerases are important targets for cancer chemotherapy. We investigated the effects of a methanolic extract of Helichrysum pamphylicum on mammalian DNA topoisomerase I via in vitro plasmid supercoil relaxation assays. The extracts manifested a considerable inhibition of the enzyme's activity in a dose-dependent manner. We also performed a HPLC analysis to identify the flavonoid content of the H. pamphylicum extract and tested the identified flavonoids; luteolin, luteolin-4-glucoside, naringenin, helichrysinA and isoquercitrin, on DNA topoisomerase I activity. The measurement of the total antioxidant capacity of the flavonoid standards suggested that the topoisomerase inhibition might be correlated with the antioxidant capacity of the plant.

  7. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

    Directory of Open Access Journals (Sweden)

    Xiaoling Lu

    2016-01-01

    Full Text Available Hair cells (HCs are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear.

  8. Caffeine, cyclic AMP and postreplication repair of mammalian DNA

    International Nuclear Information System (INIS)

    Ehmann, U.K.

    1976-01-01

    The methylxanthines, caffeine and theophylline, inhibit postreplication repair of DNA in mammalian cells. Because they also inhibit cyclic AMP phosphodiesterase, it was thought that there might be some connection between concentrations of cyclic AMP and postreplication repair. This possibility was tested by performing DNA sedimentation experiments with a cyclic AMP-resistant mouse lymphoma cell mutant and its wild-type counterpart. The results show that there is no connection between cellular cyclic AMP concentrations and the rate of postreplication repair. Therefore, it is more likely that caffeine and theophylline inhibit postreplication repair by some other means, such as by binding to DNA

  9. [Applications of synthetic biology in materials science].

    Science.gov (United States)

    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.

  10. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  11. CSBB: synthetic biology research at Newcastle University.

    Science.gov (United States)

    Goñi-Moreno, Angel; Wipat, Anil; Krasnogor, Natalio

    2017-06-15

    The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties - Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers. The CSBB trains the next generation of scientists through a 1-year MSc in Synthetic Biology. © 2017 The Author(s).

  12. Is It Time for Synthetic Biodiversity Conservation?

    Science.gov (United States)

    Piaggio, Antoinette J; Segelbacher, Gernot; Seddon, Philip J; Alphey, Luke; Bennett, Elizabeth L; Carlson, Robert H; Friedman, Robert M; Kanavy, Dona; Phelan, Ryan; Redford, Kent H; Rosales, Marina; Slobodian, Lydia; Wheeler, Keith

    2017-02-01

    Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology. Published by Elsevier Ltd.

  13. Bioinspired Chemical Communication between Synthetic Nanomotors.

    Science.gov (United States)

    Chen, Chuanrui; Chang, Xiaocong; Teymourian, Hazhir; Ramírez-Herrera, Doris E; Esteban-Fernández de Ávila, Berta; Lu, Xiaolong; Li, Jinxing; He, Sha; Fang, Chengcheng; Liang, Yuyan; Mou, Fangzhi; Guan, Jianguo; Wang, Joseph

    2018-01-02

    While chemical communication plays a key role in diverse natural processes, the intelligent chemical communication between synthetic nanomotors remains unexplored. The design and operation of bioinspired synthetic nanomotors is presented. Chemical communication between nanomotors is possible and has an influence on propulsion behavior. A chemical "message" is sent from a moving activator motor to a nearby activated (receiver) motor by release of Ag + ions from a Janus polystyrene/Ni/Au/Ag activator motor to the activated Janus SiO 2 /Pt nanomotor. The transmitted silver signal is translated rapidly into a dramatic speed change associated with the enhanced catalytic activity of activated motors. Selective and successive activation of multiple nanomotors is achieved by sequential localized chemical communications. The concept of establishing chemical communication between different synthetic nanomotors paves the way to intelligent nanoscale robotic systems that are capable of cooperating with each other. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Synthetic aperture tissue and flow ultrasound imaging

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav

    imaging applied to medical ultrasound. It is divided into two major parts: tissue and blood flow imaging. Tissue imaging using synthetic aperture algorithms has been investigated for about two decades, but has not been implemented in medical scanners yet. Among the other reasons, the conventional scanning...... and beamformation methods are adequate for the imaging modalities in clinical use - the B-mode imaging of tissue structures, and the color mapping of blood flow. The acquisition time, however, is too long, and these methods fail to perform real-time three-dimensional scans. The synthetic transmit aperture......, on the other hand, can create a Bmode image with as little as 2 emissions, thus significantly speeding-up the scan procedure. The first part of the dissertation describes the synthetic aperture tissue imaging. It starts with an overview of the efforts previously made by other research groups. A classification...

  15. Engineering emergent multicellular behavior through synthetic adhesion

    Science.gov (United States)

    Glass, David; Riedel-Kruse, Ingmar

    In over a decade, synthetic biology has developed increasingly robust gene networks within single cells, but constructed very few systems that demonstrate multicellular spatio-temporal dynamics. We are filling this gap in synthetic biology's toolbox by developing an E. coli self-assembly platform based on modular cell-cell adhesion. We developed a system in which adhesive selectivity is provided by a library of outer membrane-displayed peptides with intra-library specificities, while affinity is provided by consistent expression across the entire library. We further provide a biophysical model to help understand the parameter regimes in which this tool can be used to self-assemble into cellular clusters, filaments, or meshes. The combined platform will enable future development of synthetic multicellular systems for use in consortia-based metabolic engineering, in living materials, and in controlled study of minimal multicellular systems. Stanford Bio-X Bowes Fellowship.

  16. Anisotropic evaluation of synthetic surgical meshes.

    Science.gov (United States)

    Saberski, E R; Orenstein, S B; Novitsky, Y W

    2011-02-01

    The material properties of meshes used in hernia repair contribute to the overall mechanical behavior of the repair. The anisotropic potential of synthetic meshes, representing a difference in material properties (e.g., elasticity) in different material axes, is not well defined to date. Haphazard orientation of anisotropic mesh material can contribute to inconsistent surgical outcomes. We aimed to characterize and compare anisotropic properties of commonly used synthetic meshes. Six different polypropylene (Trelex(®), ProLite™, Ultrapro™), polyester (Parietex™), and PTFE-based (Dualmesh(®), Infinit) synthetic meshes were selected. Longitudinal and transverse axes were defined for each mesh, and samples were cut in each axis orientation. Samples underwent uniaxial tensile testing, from which the elastic modulus (E) in each axis was determined. The degree of anisotropy (λ) was calculated as a logarithmic expression of the ratio between the elastic modulus in each axis. Five of six meshes displayed significant anisotropic behavior. Ultrapro™ and Infinit exhibited approximately 12- and 20-fold differences between perpendicular axes, respectively. Trelex(®), ProLite™, and Parietex™ were 2.3-2.4 times. Dualmesh(®) was the least anisotropic mesh, without marked difference between the axes. Anisotropy of synthetic meshes has been underappreciated. In this study, we found striking differences between elastic properties of perpendicular axes for most commonly used synthetic meshes. Indiscriminate orientation of anisotropic mesh may adversely affect hernia repairs. Proper labeling of all implants by manufacturers should be mandatory. Understanding the specific anisotropic behavior of synthetic meshes should allow surgeons to employ rational implant orientation to maximize outcomes of hernia repair.

  17. Effect of surface organic coatings of cellulose nanocrystals on the viability of mammalian cell lines

    Directory of Open Access Journals (Sweden)

    Jimenez AS

    2017-09-01

    Full Text Available Ambar S Jimenez,1 Francesca Jaramillo,1 Usha D Hemraz,2 Yaman Boluk,3 Karina Ckless,1 Rajesh Sunasee1 1Department of Chemistry, State University of New York at Plattsburgh, Plattsburgh, NY, USA; 2National Research Council, Montreal, QC, Canada, 3Department of Civil & Environmental Engineering, University of Alberta and National Institute for Nanotechnology, National Research Council, Edmonton, AB, Canada Abstract: Cellulose nanocrystals (CNCs have emerged as promising candidates for a number of bio-applications. Surface modification of CNCs continues to gain significant research interest as it imparts new properties to the surface of the nanocrystals for the design of multifunctional CNCs-based materials. A small chemical surface modification can potentially lead to drastic behavioral changes of cell-material interactions thereby affecting the intended bio-application. In this work, unmodified CNCs were covalently decorated with four different organic moieties such as a diaminobutane fragment, a cyclic oligosaccharide (β-cyclodextrin, a thermoresponsive polymer (poly[N-isopropylacrylamide], and a cationic aminomethacrylamide-based polymer using different synthetic covalent methods. The effect of surface coatings of CNCs and the respective dose-response of the above organic moieties on the cell viability were evaluated on mammalian cell cultures (J774A.1 and MFC-7, using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Overall, the results indicated that cells exposed to surface-coated CNCs for 24 h did not display major changes in cell viability, membrane permeability as well as cell morphology. However, with longer exposure, all these parameters were somewhat affected, which appears not to be correlated with either anionic or cationic surface coatings of CNCs used in this study. Keywords: cellulose nanocrystals, surface coating, cell viability, MTT, LDH

  18. Synthetic biology approaches to engineer T cells.

    Science.gov (United States)

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

    2015-08-01

    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Synthetic mullite fabrication from smectite clays

    International Nuclear Information System (INIS)

    Lima, L.N. de; Kiminami, R.H.G.A.

    1988-01-01

    The technological importance of mullite is mostly due to its refractory properties. Mullite in native form is very rare, and therefore it may be necessary to produced it by synthetic means. Brazil has a large reserve of smectite clays. In this work the process to produce synthetic mullite from these clays by treatment with aluminum sulphate was studied. X-ray analyses has shown the presence of mullite crystals in treated smectite clays of several colours, sinterized at 1100 0 C. By sintering at 1300 0 C, pure mullite was obtained in some colours. (author) [pt

  20. Functional mining of transporters using synthetic selections

    DEFF Research Database (Denmark)

    Genee, Hans Jasper; Bali, Anne Pihl; Petersen, Søren Dalsgård

    2016-01-01

    transporters, PnuT, which is widely distributed across multiple bacterial phyla. We demonstrate that with modular replacement of the biosensor, we could expand our method to xanthine and identify xanthine permeases from gut and soil metagenomes. Our results demonstrate how synthetic-biology approaches can......-responsive biosensor systems that enable selective growth of cells only if they encode a ligand-specific importer. We developed such a synthetic selection system for thiamine pyrophosphate and mined soil and gut metagenomes for thiamine-uptake functions. We identified several members of a novel class of thiamine...

  1. New Synthetic Methods for Hypericum Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Insik [Iowa State Univ., Ames, IA (United States)

    2006-01-01

    Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

  2. Synthetic aperture radar capabilities in development

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The Imaging and Detection Program (IDP) within the Laser Program is currently developing an X-band Synthetic Aperture Radar (SAR) to support the Joint US/UK Radar Ocean Imaging Program. The radar system will be mounted in the program`s Airborne Experimental Test-Bed (AETB), where the initial mission is to image ocean surfaces and better understand the physics of low grazing angle backscatter. The Synthetic Aperture Radar presentation will discuss its overall functionality and a brief discussion on the AETB`s capabilities. Vital subsystems including radar, computer, navigation, antenna stabilization, and SAR focusing algorithms will be examined in more detail.

  3. Parity-Time Synthetic Phononic Media

    DEFF Research Database (Denmark)

    Christensen, Johan; Willatzen, Morten; Velasco, V. R.

    2016-01-01

    media, have been devised in many optical systems with the ground breaking potential to create nonreciprocal structures and one-way cloaks of invisibility. Here we demonstrate a feasible approach for the case of sound where the most important ingredients within synthetic materials, loss and gain......, are achieved through electrically biased piezoelectric semiconductors. We study first how wave attenuation and amplification can be tuned, and when combined, can give rise to a phononic PT synthetic media with unidirectional suppressed reflectance, a feature directly applicable to evading sonar detection....

  4. Synthetic biology of microbes synthesizing polyhydroxyalkanoates (PHA

    Directory of Open Access Journals (Sweden)

    Guo-Qiang Chen

    2016-12-01

    Full Text Available Microbial polyhydroxyalkanoates (PHA have been produced as bioplastics for various purposes. Under the support of China National Basic Research 973 Project, we developed synthetic biology methods to diversify the PHA structures into homo-, random, block polymers with improved properties to better meet various application requirements. At the same time, various pathways were assembled to produce various PHA from glucose as a simple carbon source. At the end, Halomonas bacteria were reconstructed to produce PHA in changing morphology for low cost production under unsterile and continuous conditions. The synthetic biology will advance the PHA into a bio- and material industry.

  5. Purifying synthetic or fermentation ethyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    1958-10-22

    Synthetic or fermentation grade ethanol is treated with an alkaki metal sulfite for about 10 hours then rectified to give a product free of odor and taste defects. For example, ethanol from molasses was treated with 10g Na/sub 2/SO/sub 3/.7H/sub 2/O per liter of alcohol, (70/sup 0/ Gay-Lussac) for 10 hours. Synthetic ethanol was treated with 3g Na/sub 2/SO/sub 3/.7H/sub 2/O for 10 hours.

  6. Purifying synthetic or fermentation ethyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    1958-10-22

    Synthetic or fermentation grade ethanol is treated with an alkali metal sulfite for about 10 hours then rectified to give a product free of odor and taste defects. For example, ethanol from molasses was treated with 10g, Na/sub 2/SO/sub 3/.7H/sub 2/0 per liter of alcohol, (70/sup 0/ Gay-Lussac) for 10 hours. Synthetic ethanol was treated with 3 g Na/sub 2/SO/sub 3/.7H/sub 2/O for 10 hours.

  7. Multi-antenna synthetic aperture radar

    CERN Document Server

    Wang, Wen-Qin

    2013-01-01

    Synthetic aperture radar (SAR) is a well-known remote sensing technique, but conventional single-antenna SAR is inherently limited by the minimum antenna area constraint. Although there are still technical issues to overcome, multi-antenna SAR offers many benefits, from improved system gain to increased degrees-of-freedom and system flexibility. Multi-Antenna Synthetic Aperture Radar explores the potential and challenges of using multi-antenna SAR in microwave remote sensing applications. These applications include high-resolution imaging, wide-swath remote sensing, ground moving target indica

  8. [Salem witches, flying brooms, and synthetic drugs].

    Science.gov (United States)

    Castellanos Tejero, Manuel; Castellanos Tejero, M de los Angeles

    2002-10-01

    As supplementary material to Health Education programs about synthetic drugs, the authors present a historical summary on LSD, stramonium and khat. "Tripis", Special K and other synthetic pills contain these substances and are being widely used by youths. The history of these main hallucinogenic active ingredients has a strong tie to the mythology of witchcraft and witches: a historically interesting time period bearing a large amount of religious intolerance. The objective of this review is to end the belief today's youth have that they are taking new substances which have no risks.

  9. Synthetic clay excels in 90Sr removal

    International Nuclear Information System (INIS)

    Komarneni, Sridhar; Kodama, Tatsuya; Paulus, William J.; Carlson, C.

    2000-01-01

    Tests with actual ground water from Hanford site, and fundamental studies of 2Na + →Sr 2+ exchange equilibria revealed that a synthetic clay is extremely selective for 90 Sr with a high capacity for uptake. Comparative studies with existing Sr selective ion exchangers clearly revealed that the present synthetic clay exhibited the best performance for 90 Sr removal from actual ground water collected from three different locations at Hanford. This novel Sr ion sieve is expected to be useful for the decontamination of the environment after accidental release and contamination with 90 Sr. (c) 2000 Materials Research Society

  10. Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

    OpenAIRE

    Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N.; Lee, Seung-Rock

    2014-01-01

    Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells ...

  11. Mammalian RNA polymerase II core promoters: insights from genome-wide studies

    DEFF Research Database (Denmark)

    Sandelin, Albin; Carninci, Piero; Lenhard, Boris

    2007-01-01

    The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing...... in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing...

  12. Regulation of Autophagy by Glucose in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Erwin Knecht

    2012-07-01

    Full Text Available Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role.

  13. Radiation enhanced reactivation of nuclear replicating mammalian viruses

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Lytle, C.D.

    1977-01-01

    When CV-1 monkey kidney cells were UV-irradiated (0 to 18 J/m 2 ) or X-irradiated (0 to 10 krads) before infection with UV-irradiated simian adenovirus 7 (SA7) or simian virus 40 (SV40), increases in the infectivity of these nuclear replicating viruses as measured by plaque formation were observed. These radiation enhanced reactivations, UV enhanced reactivation (UVER) and X-ray enhanced reactivation (X-ray ER), occurred both when virus infection immediately followed irradiation of the cells (except for X-ray ER with SA7) and when virus infection was delayed until 3 to 5 days after cell irradiation. While there was little difference in the levels of reactivation of UV-irradiated SV40 between immediate and delayed infection, delayed infection resulted in higher levels of reactivation of SA7. X-ray enhanced reactivation of UV-irradiated Herpes simplex virus persisted for several days but did not increase. Thus, X-ray enhanced and UV enhanced reactivations of these mammalian viruses were relatively long-lived effects. Essentially no UVER or X-ray ER was found in CV-1 cells for either immediate or delayed infection with UV-irradiated vaccinia virus or poliovirus, both of which replicate in the cell cytoplasm. These results suggest UVER and X-ray ER in mammalian cells may be restricted to viruses which are replicated in the cell nucleus. (author)

  14. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V.; Hazen, M.J.

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells

  15. Colour As a Signal for Entraining the Mammalian Circadian Clock

    Science.gov (United States)

    Walmsley, Lauren; Hanna, Lydia; Mouland, Josh; Martial, Franck; West, Alexander; Smedley, Andrew R.; Bechtold, David A.; Webb, Ann R.; Lucas, Robert J.; Brown, Timothy M.

    2015-01-01

    Twilight is characterised by changes in both quantity (“irradiance”) and quality (“colour”) of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue–yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision. PMID:25884537

  16. Colour as a signal for entraining the mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Lauren Walmsley

    2015-04-01

    Full Text Available Twilight is characterised by changes in both quantity ("irradiance" and quality ("colour" of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.

  17. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  18. Chemical test for mammalian feces in grain products: collaborative study.

    Science.gov (United States)

    Gerber, H R

    1989-01-01

    A collaborative study was conducted to validate the use of the AOAC alkaline phosphatase method for mammalian feces in corn meal, 44.B01-44.B06, for 7 additional products: brown rice cream, oat bran, grits, semolina, pasta flour, farina, and barley plus (a mixture of barley, oat bran, and brown rice). The proposed method determines the presence of alkaline phosphatase, an enzyme contained in mammalian feces, by using phenolphthalein diphosphate as the enzyme substrate in a test agar medium. Fecal matter is separated from the grain products by specific gravity differences in 1% test agar. As the product is distributed on liquid test agar, fecal fragments float while the grain products sink. The alkaline phosphatase cleaves phosphate radicals from phenolphthalein diphosphate, generating free phenolphthalein, which produces a pink to red-purple color around the fecal particles in the previously colorless medium. Collaborators' recovery averages ranged from 21.7 particles (72.3%) for oat bran to 25.3 particles (84.3%) for semolina at the 30 particle spike level. Overall average background was 0.4 positive reactions per food type. The collaborators reported that the method was quick, simple, and easy to use. The method has been approved interim official first action for all 7 grain products.

  19. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    Science.gov (United States)

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

    Directory of Open Access Journals (Sweden)

    Velia Siciliano

    2011-06-01

    Full Text Available Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL by generating a clonal population of mammalian cells (CHO carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA, whose expression is regulated by a tTA responsive promoter (CMV-TET, thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP, thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL, by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off, and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

  1. Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

    Science.gov (United States)

    Siciliano, Velia; Menolascina, Filippo; Marucci, Lucia; Fracassi, Chiara; Garzilli, Immacolata; Moretti, Maria Nicoletta; di Bernardo, Diego

    2011-06-01

    Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

  2. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain.

    Science.gov (United States)

    Edwards, Sarah R; Wandless, Thomas J

    2007-05-04

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C-16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to 10-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retained the ability to inhibit mTOR, although with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wild-type FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems.

  3. SYNTHETIC JET APPLIED TO DETECT POTENTIAL TERRORISTS

    Czech Academy of Sciences Publication Activity Database

    Tesař, Václav; Peszyński, K.

    2010-01-01

    Roč. 5, č. 3 (2010), s. 229-234 ISSN 1231-3998 R&D Projects: GA AV ČR IAA200760705; GA ČR GA101/07/1499 Institutional research plan: CEZ:AV0Z20760514 Keywords : synthetic jets * annular jets * terrorism Subject RIV: BK - Fluid Dynamics

  4. Synthetic biology advances for pharmaceutical production

    OpenAIRE

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.

  5. Homogeneous nucleation of water in synthetic air

    NARCIS (Netherlands)

    Fransen, M.A.L.J.; Sachteleben, E.; Hruby, J.; Smeulders, D.M.J.; DeMott, P.J.; O'Dowd, C.D.

    2013-01-01

    Homogeneous nucleation rates for water vapor in synthetic air are measured by means of a Pulse-Expansion Wave Tube (PEWT). A comparison of the experimental nucleation rates with the Classical Nucleation Theory (CNT) shows that a more elaborated model is necessary to describe supercooled water

  6. A combinatorial approach to synthetic receptors

    NARCIS (Netherlands)

    Timmerman, P.; Reinhoudt, David

    1999-01-01

    Antibodies, the workhorses of every living organisms immune system, are characterized by their extraordinarily high binding affinity and selectivity for a particular antigen. Despite numerous efforts to mimic these binding properties in synthetic molecules, chemists have so far not been able to

  7. Raman spectrum of natural and synthetic stishovite

    Science.gov (United States)

    Hemley, R.J.; Mao, Ho-kwang; Chao, E.C.T.

    1986-01-01

    Raman spectra of natural and synthetic samples of stishovite have been measured with a micro-optical spectrometer system. These spectra have a pattern that is characteristic of rutile-structured oxides. The spectrum of synthetic stishovite is characterized by well-resolved bands at 231, 589, 753, and 967 cm-1, which are assigned as the B1g, Eg, A1g, and B2g fundamentals, respectively, of the first-order Raman spectrum of the ideal, ordered structure. Natural stishovite obtained from Meteor Crater, Arizona has a first-order Raman spectrum that is fully consistent with that of the synthetic material. The observed spectrum of the natural sample, however, is weaker and has bands in addition to those identified as fundamentals in the spectrum of the synthetic material. A broad band at ???475 cm-1 may be indicative of glass or contaminants derived from the extraction procedure. Alternatively, this band may arise from multiphonon scattering that is enhanced by poor crystallinity or structural disorder in the natural shocked sample. ?? 1986 Springer-Verlag.

  8. Synthetic tsunamis along the Israeli coast.

    Science.gov (United States)

    Tobias, Joshua; Stiassnie, Michael

    2012-04-13

    The new mathematical model for tsunami evolution by Tobias & Stiassnie (Tobias & Stiassnie 2011 J. Geophys. Res. Oceans 116, C06026) is used to derive a synthetic tsunami database for the southern part of the Eastern Mediterranean coast. Information about coastal tsunami amplitudes, half-periods, currents and inundation levels is presented.

  9. DESCQA: Synthetic Sky Catalog Validation Framework

    Science.gov (United States)

    Mao, Yao-Yuan; Uram, Thomas D.; Zhou, Rongpu; Kovacs, Eve; Ricker, Paul M.; Kalmbach, J. Bryce; Padilla, Nelson; Lanusse, François; Zu, Ying; Tenneti, Ananth; Vikraman, Vinu; DeRose, Joseph

    2018-04-01

    The DESCQA framework provides rigorous validation protocols for assessing the quality of high-quality simulated sky catalogs in a straightforward and comprehensive way. DESCQA enables the inspection, validation, and comparison of an inhomogeneous set of synthetic catalogs via the provision of a common interface within an automated framework. An interactive web interface is also available at portal.nersc.gov/project/lsst/descqa.

  10. Synthetic Biology: Applications in the Food Sector.

    Science.gov (United States)

    Tyagi, Ashish; Kumar, Ashwani; Aparna, S V; Mallappa, Rashmi H; Grover, Sunita; Batish, Virender Kumar

    2016-08-17

    Synthetic biology also termed as "genomic alchemy" represents a powerful area of science that is based on the convergence of biological sciences with systems engineering. It has been fittingly described as "moving from reading the genetic code to writing it" as it focuses on building, modeling, designing and fabricating novel biological systems using customized gene components that result in artificially created genetic circuitry. The scientifically compelling idea of the technological manipulation of life has been advocated since long time. Realization of this idea has gained momentum with development of high speed automation and the falling cost of gene sequencing and synthesis following the completion of the human genome project. Synthetic biology will certainly be instrumental in shaping the development of varying areas ranging from biomedicine, biopharmaceuticals, chemical production, food and dairy quality monitoring, packaging, and storage of food and dairy products, bioremediation and bioenergy production, etc. However, potential dangers of using synthetic life forms have to be acknowledged and adoption of policies by the scientific community to ensure safe practice while making important advancements in the ever expanding field of synthetic biology is to be fully supported and implemented.

  11. Evaluation of synthetic promoters in Physcomitrella patens

    DEFF Research Database (Denmark)

    Peramuna, Anantha; Bae, Hansol; Rasmussen, Erling Koch

    2018-01-01

    Securing a molecular toolbox including diverse promoters is essential for genome engineering. However, native promoters have limitations such as the available number or the length of the promoter. In this work, three short synthetic promoters were characterized by using the yellow fluorescent...

  12. Synthetic biology advances for pharmaceutical production

    Science.gov (United States)

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  13. News: Synthetic biology leading to specialty chemicals

    Science.gov (United States)

    Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate productio...

  14. Synthetic biology for microbial heavy metal biosensors.

    Science.gov (United States)

    Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun

    2018-02-01

    Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

  15. Design and construction of "synthetic species".

    Directory of Open Access Journals (Sweden)

    Eduardo Moreno

    Full Text Available Synthetic biology is an area of biological research that combines science and engineering. Here, I merge the principles of synthetic biology and regulatory evolution to create a new species with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfils the criteria of a new species according to Mayr's Biological Species Concept. The population described here is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other identical transgenic animals. I therefore propose the term "synthetic species" to distinguish it from "natural species", not only because it has been created by genetic manipulation, but also because it may never be able to survive outside the laboratory environment. The use of genetic engineering to design artificial species barriers could help us understand natural speciation and may have practical applications. For instance, the transition from transgenic organisms towards synthetic species could constitute a safety mechanism to avoid the hybridization of genetically modified animals with wild type populations, preserving biodiversity.

  16. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  17. Synthetic analog computation in living cells.

    Science.gov (United States)

    Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

    2013-05-30

    A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

  18. Optimization of Synthetic Aperture Image Quality

    DEFF Research Database (Denmark)

    Moshavegh, Ramin; Jensen, Jonas; Villagómez Hoyos, Carlos Armando

    2016-01-01

    Synthetic Aperture (SA) imaging produces high-quality images and velocity estimates of both slow and fast flow at high frame rates. However, grating lobe artifacts can appear both in transmission and reception. These affect the image quality and the frame rate. Therefore optimization of parameter...

  19. Simultaneous adsorption and biodegradation of synthetic melanoidin

    African Journals Online (AJOL)

    Being an antioxidant, melanoidin removal through purely biodegradation has been inadequate. Consequently, in the current study, simultaneous adsorption and biodegradation (SAB) was employed in a stirred tank system to remove melanoidin from synthetic wastewater. Mixed microbial consortium was immobilized onto ...

  20. Super-Resolution for Synthetic Zooming

    Directory of Open Access Journals (Sweden)

    Li Xin

    2006-01-01

    Full Text Available Optical zooming is an important feature of imaging systems. In this paper, we investigate a low-cost signal processing alternative to optical zooming—synthetic zooming by super-resolution (SR techniques. Synthetic zooming is achieved by registering a sequence of low-resolution (LR images acquired at varying focal lengths and reconstructing the SR image at a larger focal length or increased spatial resolution. Under the assumptions of constant scene depth and zooming speed, we argue that the motion trajectories of all physical points are related to each other by a unique vanishing point and present a robust technique for estimating its D coordinate. Such a line-geometry-based registration is the foundation of SR for synthetic zooming. We address the issue of data inconsistency arising from the varying focal length of optical lens during the zooming process. To overcome the difficulty of data inconsistency, we propose a two-stage Delaunay-triangulation-based interpolation for fusing the LR image data. We also present a PDE-based nonlinear deblurring to accommodate the blindness and variation of sensor point spread functions. Simulation results with real-world images have verified the effectiveness of the proposed SR techniques for synthetic zooming.

  1. Preparation of Natural and Synthetic Porous Biodegradable ...

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Preparation of Natural and Synthetic Porous Biodegradable Scaffolds for Infected Wounds. Characterised for their physical properties, pore size and release kinetics. Release kinetics of bioactive molecules (antibiotics) in a controlled fashion. Release pattern of the ...

  2. 21 CFR 175.250 - Paraffin (synthetic).

    Science.gov (United States)

    2010-04-01

    ... hydrocarbons. Lower molecular-weight fractions are removed by distillation. The residue is hydrogenated and may... its components by a solvent separation method, using synthetic isoparaffinic petroleum hydrocarbons... method E131-81a, “Standard Definitions of Terms and Symbols Relating to Molecular-Spectroscopy,” which is...

  3. Immobilization of radioiodine in synthetic boracite

    Science.gov (United States)

    Babad, H.; Strachan, D.M.

    1982-09-23

    A nuclear waste storage product is disclosed in which radioiodine is incorporated in a synthetic boracite. The boracite may be prepared by reacting a transition metal iodide with an alkali horate under mild hydrothermal conditions, drying the reaction product, and then hot pressing.

  4. Sonar path correction in synthetic aperture processing

    NARCIS (Netherlands)

    Groen, J.; Hansen, R.E.; Sabel, J.C.

    2003-01-01

    In the next generation of mine hunting sonars, in particular on Autonomous Underwater Vehicles (AUVs), Synthetic Aperture Sonar (SAS) will play an important role. The benefit of SAS is to increase resolution and signal-tonoise ratio by coherent processing of successive pings. A challenge in SAS is

  5. Once more on Analytic vs. Synthetic

    Czech Academy of Sciences Publication Activity Database

    Materna, Pavel

    2007-01-01

    Roč. 16, č. 1 (2007), s. 3-43 ISSN 1425-3305 R&D Projects: GA ČR(CZ) GA401/07/0451 Institutional research plan: CEZ:AV0Z90090514 Keywords : analytic * synthetic * intensions * constructions * concepts * pragmatics Subject RIV: AA - Philosophy ; Religion

  6. SYNTHETIC AGB EVOLUTION .1. A NEW MODEL

    NARCIS (Netherlands)

    GROENEWEGEN, MAT; DEJONG, T

    We have constructed a model to calculate in a synthetic way the evolution of stars on the asymptotic giant branch (AGB). The evolution is started at the first thermal pulse (TP) and is terminated when the envelope mass has been lost due to mass loss or when the core mass reaches the Chandrasekhar

  7. Synthetic Aperture Beamformation using the GPU

    DEFF Research Database (Denmark)

    Hansen, Jens Munk; Schaa, Dana; Jensen, Jørgen Arendt

    2011-01-01

    A synthetic aperture ultrasound beamformer is implemented for a GPU using the OpenCL framework. The implementation supports beamformation of either RF signals or complex baseband signals. Transmit and receive apodization can be either parametric or dynamic using a fixed F-number, a reference...

  8. Wind energy applications of synthetic aperture radar

    DEFF Research Database (Denmark)

    Badger, Merete

    Synthetic aperture radars (SAR), mounted on satellites or aircraft, have proven useful for ocean wind mapping. Wind speeds at the height 10 m may be retrieved from measurements of radar backscatter using empirical model functions. The resulting windfields are valuable in offshore wind energy plan...

  9. Synthetic biology between technoscience and thing knowledge.

    Science.gov (United States)

    Gelfert, Axel

    2013-06-01

    Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Parts & Pools: A Framework for Modular Design of Synthetic Gene Circuits

    International Nuclear Information System (INIS)

    Marchisio, Mario Andrea

    2014-01-01

    Published in 2008, Parts & Pools represents one of the first attempts to conceptualize the modular design of bacterial synthetic gene circuits with Standard Biological Parts (DNA segments) and Pools of molecules referred to as common signal carriers (e.g., RNA polymerases and ribosomes). The original framework for modeling bacterial components and designing prokaryotic circuits evolved over the last years and brought, first, to the development of an algorithm for the automatic design of Boolean gene circuits. This is a remarkable achievement since gene digital circuits have a broad range of applications that goes from biosensors for health and environment care to computational devices. More recently, Parts & Pools was enabled to give a proper formal description of eukaryotic biological circuit components. This was possible by employing a rule-based modeling approach, a technique that permits a faithful calculation of all the species and reactions involved in complex systems such as eukaryotic cells and compartments. In this way, Parts & Pools is currently suitable for the visual and modular design of synthetic gene circuits in yeast and mammalian cells too.

  11. Parts & Pools: A Framework for Modular Design of Synthetic Gene Circuits

    Energy Technology Data Exchange (ETDEWEB)

    Marchisio, Mario Andrea, E-mail: marchisio@hit.edu.cn [School of Life Science and Technology, Harbin Institute of Technology, Harbin (China)

    2014-10-06

    Published in 2008, Parts & Pools represents one of the first attempts to conceptualize the modular design of bacterial synthetic gene circuits with Standard Biological Parts (DNA segments) and Pools of molecules referred to as common signal carriers (e.g., RNA polymerases and ribosomes). The original framework for modeling bacterial components and designing prokaryotic circuits evolved over the last years and brought, first, to the development of an algorithm for the automatic design of Boolean gene circuits. This is a remarkable achievement since gene digital circuits have a broad range of applications that goes from biosensors for health and environment care to computational devices. More recently, Parts & Pools was enabled to give a proper formal description of eukaryotic biological circuit components. This was possible by employing a rule-based modeling approach, a technique that permits a faithful calculation of all the species and reactions involved in complex systems such as eukaryotic cells and compartments. In this way, Parts & Pools is currently suitable for the visual and modular design of synthetic gene circuits in yeast and mammalian cells too.

  12. Reverse engineering validation using a benchmark synthetic gene circuit in human cells.

    Science.gov (United States)

    Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

    2013-05-17

    Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.

  13. Synthetic biology for pharmaceutical drug discovery

    Directory of Open Access Journals (Sweden)

    Trosset JY

    2015-12-01

    Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: Synthetic biology (SB is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance

  14. Synthetic biology and biosecurity: challenging the "myths".

    Science.gov (United States)

    Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

    2014-01-01

    Synthetic biology, a field that aims to "make biology easier to engineer," is routinely described as leading to an increase in the "dual-use" threat, i.e., the potential for the same scientific research to be "used" for peaceful purposes or "misused" for warfare or terrorism. Fears have been expressed that the "de-skilling" of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five "myths" that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these "myths" play an important role in defining synthetic biology as a "promissory" field of research and as an "emerging technology" in need of governance.

  15. Characterization of high speed synthetic jet actuators

    Science.gov (United States)

    Pikcilingis, Lucia

    Over the last 20 years, synthetic jets have been studied as a means for aerodynamic active flow control. Specifically, synthetic jets provide momentum transfer with zero-net mass flux, which has been proven to be effective for controlling flow fields. A synthetic jet is created by the periodic formation of vortex rings at its orifice due to the periodic motion of a piezoelectric disk(s). The present study seeks to optimize the performance of a synthetic jet actuator by utilizing different geometrical parameters such as disk thickness, orifice width and length, cavity height and cavity diameter, and different input parameters such as driving voltage and frequency. Two apparatuses were used with a cavity diameter of either 80 mm or 160 mm. Piezoelectric-based disks were provided by the Mide Corporation. Experiments were conducted using several synthetic jet apparatuses designed for various geometrical parameters utilizing a dual disk configuration. Velocity and temperature measurements were acquired at the center of the synthetic jet orifice using a temperature compensated hotwire and thermocouple probe. The disk(s) displacement was measured at the center of the disk with a laser displacement sensor. It was shown that the synthetic jets, having the 80 mm cavity diameter, are capable of exceeding peak velocities of 200 m/s with a relatively large orifice of dimensions AR = 12, hc* = 3, and hn* = 4. In addition, the conditions at which the disks were manufactured had minimal effect on the performance of the jet, except for the pair with overnight resting time as opposed to less than an hour resting time for the control units. Altering the tab style of the disks, where the tab allows the electrical circuit to be exposed for external power connection, showed that a thin fragile tab versus a tab of the same thickness as the disk has minimal effect on the performance but affects the durability of the disk due to the fragility or robustness of the tab. The synthetic jets

  16. A systematic investigation of production of synthetic prions from recombinant prion protein.

    Science.gov (United States)

    Schmidt, Christian; Fizet, Jeremie; Properzi, Francesca; Batchelor, Mark; Sandberg, Malin K; Edgeworth, Julie A; Afran, Louise; Ho, Sammy; Badhan, Anjna; Klier, Steffi; Linehan, Jacqueline M; Brandner, Sebastian; Hosszu, Laszlo L P; Tattum, M Howard; Jat, Parmjit; Clarke, Anthony R; Klöhn, Peter C; Wadsworth, Jonathan D F; Jackson, Graham S; Collinge, John

    2015-12-01

    According to the protein-only hypothesis, infectious mammalian prions, which exist as distinct strains with discrete biological properties, consist of multichain assemblies of misfolded cellular prion protein (PrP). A critical test would be to produce prion strains synthetically from defined components. Crucially, high-titre 'synthetic' prions could then be used to determine the structural basis of infectivity and strain diversity at the atomic level. While there have been multiple reports of production of prions from bacterially expressed recombinant PrP using various methods, systematic production of high-titre material in a form suitable for structural analysis remains a key goal. Here, we report a novel high-throughput strategy for exploring a matrix of conditions, additives and potential cofactors that might generate high-titre prions from recombinant mouse PrP, with screening for infectivity using a sensitive automated cell-based bioassay. Overall, approximately 20,000 unique conditions were examined. While some resulted in apparently infected cell cultures, this was transient and not reproducible. We also adapted published methods that reported production of synthetic prions from recombinant hamster PrP, but again did not find evidence of significant infectious titre when using recombinant mouse PrP as substrate. Collectively, our findings are consistent with the formation of prion infectivity from recombinant mouse PrP being a rare stochastic event and we conclude that systematic generation of prions from recombinant PrP may only become possible once the detailed structure of authentic ex vivo prions is solved. © 2015 The Authors.

  17. Genotoxic effects of synthetic amorphous silica nanoparticles in the mouse lymphoma assay

    Directory of Open Access Journals (Sweden)

    Eşref Demir

    Full Text Available Synthetic amorphous silica nanoparticles (SAS NPs have been used in various industries, such as plastics, glass, paints, electronics, synthetic rubber, in pharmaceutical drug tablets, and a as food additive in many processed foods. There are few studies in the literature on NPs using gene mutation approaches in mammalian cells, which represents an important gap for genotoxic risk estimations. To fill this gap, the mouse lymphoma L5178Y/Tk+/− assay (MLA was used to evaluate the mutagenic effect for five different concentrations (from 0.01 to 150 μg/mL of two different sizes of SAS NPs (7.172 and 7.652 nm and a fine collodial form of silicon dioxide (SiO2. This assay detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The results obtained indicate that the two selected SAS NPs are mutagenic in the MLA assay, showing a concentration-dependent effect. The relative mutagenic potencies according to the induced mutant frequency (IMF are as follows: SAS NPs (7.172 nm (IMF = 705.5 × 10−6, SAS NPs (7.652 nm (IMF = 575.5 × 10−6, and SiO2 (IMF = 57.5 × 10−6. These in vitro results, obtained from mouse lymphoma cells, support the genotoxic potential of NPs as well as focus the discussion of the benefits/risks associated with their use in different areas. Keywords: Synthetic amorphous silica nanoparticles, Mouse lymphoma assay, Mutagenic agents, Thymidine kinase (Tk gene, In vitro mutagenicity

  18. Characterization of Thermal Stability of Synthetic and Semi-Synthetic Engine Oils

    Directory of Open Access Journals (Sweden)

    Anand Kumar Tripathi

    2015-03-01

    Full Text Available Engine oils undergo oxidative degradation and wears out during service. Hence it is important to characterize ageing of engine oils at different simulated conditions to evaluate the performance of existing oils and also design new formulations. This work focuses on characterizing the thermo-oxidative degradation of synthetic and semi-synthetic engine oils aged at 120, 149 and 200 °C. Apparent activation energy of decomposition of aged oils evaluated using the isoconversional Kissinger-Akahira-Sunose technique was used as a thermal stability marker. The temporal variation of stability at different ageing temperatures was corroborated with kinematic viscosity, oxidation, sulfation and nitration indices, total base number, antiwear additive content and molecular structure of the organic species present in the oils. At the lowest temperature employed, synthetic oil underwent higher rate of oxidation, while semi-synthetic oil was stable for longer time periods. At higher temperatures, the initial rate of change of average apparent activation energy of synthetic oil correlated well with a similar variation in oxidation number. A mixture of long chain linear, branched, and cyclic hydrocarbons were observed when semi-synthetic oil was degraded at higher temperatures.

  19. Presence of abscisic acid, a phytohormone, in the mammalian brain

    International Nuclear Information System (INIS)

    Le Page-Degivry, M.T.; Bidard, J.N.; Rouvier, E.; Bulard, C.; Lazdunski, M.

    1986-01-01

    This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention properties and the same gas chromatography/mass spectrometry characteristics. Moreover, like (+)-cis-abscisic acid itself, the brain factor inhibits stomatal apertures of abaxial epidermis strips of Setcreasea purpurea Boom (Commelinaceae). The presence of abscisic acid conjugates that are present in plants has also been identified in brain

  20. Architecture of the large subunit of the mammalian mitochondrial ribosome.

    Science.gov (United States)

    Greber, Basil J; Boehringer, Daniel; Leitner, Alexander; Bieri, Philipp; Voigts-Hoffmann, Felix; Erzberger, Jan P; Leibundgut, Marc; Aebersold, Ruedi; Ban, Nenad

    2014-01-23

    Mitochondrial ribosomes synthesize a number of highly hydrophobic proteins encoded on the genome of mitochondria, the organelles in eukaryotic cells that are responsible for energy conversion by oxidative phosphorylation. The ribosomes in mammalian mitochondria have undergone massive structural changes throughout their evolution, including ribosomal RNA shortening and acquisition of mitochondria-specific ribosomal proteins. Here we present the three-dimensional structure of the 39S large subunit of the porcine mitochondrial ribosome determined by cryo-electron microscopy at 4.9 Å resolution. The structure, combined with data from chemical crosslinking and mass spectrometry experiments, reveals the unique features of the 39S subunit at near-atomic resolution and provides detailed insight into the architecture of the polypeptide exit site. This region of the mitochondrial ribosome has been considerably remodelled compared to its bacterial counterpart, providing a specialized platform for the synthesis and membrane insertion of the highly hydrophobic protein components of the respiratory chain.

  1. Membrane phospholipids and radiation-induced death of mammalian cells

    International Nuclear Information System (INIS)

    Wolters, H.

    1987-01-01

    Radiation-induced cell killing is generally believed to be a consequence of residual DNA damage or damage that is mis-repaired. However, besides this DNA damage, damage to other molecules or structures of the cell may be involved in the killing. Especially membranes have been suggested as a determinant in cellular radiosensitivity. In this thesis experiments are described, dealing with the possible involvement of membranes in radiation-induced killing of mammalian cells. A general treatise of membrane structure is followed by information concerning deleterious effects of radiation on membranes. Consequences of damage to structure and function of membranes are reviewed. Thereafter evidence relating to the possible involvement of membranes in radiation-induced cell killing is presented. (Auth.)

  2. Effects of exposure to electromagnetic fields (microwaves) on mammalian pregnancy

    International Nuclear Information System (INIS)

    Dugauquier, C.

    2006-01-01

    Women soldiers account now for nearly 10 % of the NATO forces. Some studies have alleged that exposure to microwaves may result in pregnancy mishaps. We have tried to assess what was the risk. A lot of studies were conducted on non mammalian species: birds, sea urchins, worms and insects. Extrapolation to the mammals is subject to caution due to the protective effect of intrauterine development. We reviewed the literature dealing only with mammals. Even if some discrepancy persists, it seems that the presence or the absence of thermic effect is essential in order to estimate the risk. Reduced birth weight and increased rate of miscarriage were the most common findings when the exposure reached a thermic effect. In the majority of the studies, non thermic exposure had no impact on pregnancy outcome. (authors)

  3. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.

    1981-01-01

    Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

  4. Liv. 52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    Saini, M.R.; Saini, N.

    1985-01-01

    Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

  5. Causes and significance of variation in mammalian basal metabolism.

    Science.gov (United States)

    Raichlen, David A; Gordon, Adam D; Muchlinski, Magdalena N; Snodgrass, J Josh

    2010-02-01

    Mammalian basal metabolic rates (BMR) increase with body mass, whichs explains approximately 95% of the variation in BMR. However, at a given mass, there remains a large amount of variation in BMR. While many researchers suggest that the overall scaling of BMR with body mass is due to physiological constraints, variation at a given body mass may provide clues as to how selection acts on BMR. Here, we examine this variation in BMR in a broad sample of mammals and we test the hypothesis that, across mammals, body composition explains differences in BMR at a given body mass. Variation in BMR is strongly correlated with variation in muscle mass, and both of these variables are correlated with latitude and ambient temperature. These results suggest that selection alters BMR in response to thermoregulatory pressures, and that selection uses muscle mass as a means to generate this variation.

  6. Sensitization of ultraviolet radiation damage in bacteria and mammalian cells

    International Nuclear Information System (INIS)

    Fisher, G.J.; Watts, M.E.; Patel, K.B.; Adams, G.E.

    1978-01-01

    Bacteria (Serratia marcescens) and mammalian cells (Chinese hamsters V79-379A) were irradiated in monolayers with ultraviolet light at 254 nm or 365 nm in the presence or absence of radiosensitizing drugs. At 254 nm, killing is very efficient (Dsub(37) approximately equal 1 J m -2 exposure, or approximately equal 6 x 10 4 photons absorbed by DNA per bacterium), and sensitizers have no effect. At 365 nm, cells are not killed in buffer, but are inactivated in the presence of nifurpipone or misonidazole. Lethal exposures (approximately equal 5 x 10 3 J m -2 at 10 nM misonidazole) correspond to about 10 7 photons absorbed by sensitizer molecules per bacterium. Toxicity of stable photoproducts of the drugs is not involved, nor is oxygen required. Hence the transient species formed by photo-excitation of radiosensitizer molecules are capable of killing cells in the absence of other types of radiation damage. (author)

  7. Mosaic serine proteases in the mammalian central nervous system.

    Science.gov (United States)

    Mitsui, Shinichi; Watanabe, Yoshihisa; Yamaguchi, Tatsuyuki; Yamaguchi, Nozomi

    2008-01-01

    We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

  8. Plasticity within stem cell hierarchies in mammalian epithelia.

    Science.gov (United States)

    Tetteh, Paul W; Farin, Henner F; Clevers, Hans

    2015-02-01

    Tissue homeostasis and regeneration are fueled by resident stem cells that have the capacity to self-renew, and to generate all the differentiated cell types that characterize a particular tissue. Classical models of such cellular hierarchies propose that commitment and differentiation occur unidirectionally, with the arrows 'pointing away' from the stem cell. Recent studies, all based on genetic lineage tracing, describe various strategies employed by epithelial stem cell hierarchies to replace damaged or lost cells. While transdifferentiation from one tissue type into another ('metaplasia') appears to be generally forbidden in nonpathological contexts, plasticity within an individual tissue stem cell hierarchy may be much more common than previously appreciated. In this review, we discuss recent examples of such plasticity in selected mammalian epithelia, highlighting the different modes of regeneration and their implications for our understanding of cellular hierarchy and tissue self-renewal. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Isolation of Lysosomes from Mammalian Tissues and Cultured Cells.

    Science.gov (United States)

    Aguado, Carmen; Pérez-Jiménez, Eva; Lahuerta, Marcos; Knecht, Erwin

    2016-01-01

    Lysosomes participate within the cells in the degradation of organelles, macromolecules, and a wide variety of substrates. In any study on specific roles of lysosomes, both under physiological and pathological conditions, it is advisable to include methods that allow their reproducible and reliable isolation. However, purification of lysosomes is a difficult task, particularly in the case of cultured cells. This is mainly because of the heterogeneity of these organelles, along with their low number and high fragility. Also, isolation methods, while disrupting plasma membranes, have to preserve the integrity of lysosomes, as the breakdown of their membranes releases enzymes that could damage all cell organelles, including themselves. The protocols described below have been routinely used in our laboratory for the specific isolation of lysosomes from rat liver, NIH/3T3, and other cultured cells, but can be adapted to other mammalian tissues or cell lines.

  10. Radiation activation of transcription factors in mammalian cells

    International Nuclear Information System (INIS)

    Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

    1990-01-01

    In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

  11. Recombinant protein production from stable mammalian cell lines and pools.

    Science.gov (United States)

    Hacker, David L; Balasubramanian, Sowmya

    2016-06-01

    We highlight recent developments for the production of recombinant proteins from suspension-adapted mammalian cell lines. We discuss the generation of stable cell lines using transposons and lentivirus vectors (non-targeted transgene integration) and site-specific recombinases (targeted transgene integration). Each of these methods results in the generation of cell lines with protein yields that are generally superior to those achievable through classical plasmid transfection that depends on the integration of the transfected DNA by non-homologous DNA end-joining. This is the main reason why these techniques can also be used for the generation of stable cell pools, heterogenous populations of recombinant cells generated by gene delivery and genetic selection without resorting to single cell cloning. This allows the time line from gene transfer to protein production to be reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Action spectra in mammalian cells exposed to ultraviolet radiation

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

  13. Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Saera Hihara

    2012-12-01

    Full Text Available Genome information, which is three-dimensionally organized within cells as chromatin, is searched and read by various proteins for diverse cell functions. Although how the protein factors find their targets remains unclear, the dynamic and flexible nature of chromatin is likely crucial. Using a combined approach of fluorescence correlation spectroscopy, single-nucleosome imaging, and Monte Carlo computer simulations, we demonstrate local chromatin dynamics in living mammalian cells. We show that similar to interphase chromatin, dense mitotic chromosomes also have considerable chromatin accessibility. For both interphase and mitotic chromatin, we observed local fluctuation of individual nucleosomes (∼50 nm movement/30 ms, which is caused by confined Brownian motion. Inhibition of these local dynamics by crosslinking impaired accessibility in the dense chromatin regions. Our findings show that local nucleosome dynamics drive chromatin accessibility. We propose that this local nucleosome fluctuation is the basis for scanning genome information.

  14. The completion of the Mammalian Gene Collection (MGC)

    Science.gov (United States)

    Temple, Gary; Gerhard, Daniela S.; Rasooly, Rebekah; Feingold, Elise A.; Good, Peter J.; Robinson, Cristen; Mandich, Allison; Derge, Jeffrey G.; Lewis, Jeanne; Shoaf, Debonny; Collins, Francis S.; Jang, Wonhee; Wagner, Lukas; Shenmen, Carolyn M.; Misquitta, Leonie; Schaefer, Carl F.; Buetow, Kenneth H.; Bonner, Tom I.; Yankie, Linda; Ward, Ming; Phan, Lon; Astashyn, Alex; Brown, Garth; Farrell, Catherine; Hart, Jennifer; Landrum, Melissa; Maidak, Bonnie L.; Murphy, Michael; Murphy, Terence; Rajput, Bhanu; Riddick, Lillian; Webb, David; Weber, Janet; Wu, Wendy; Pruitt, Kim D.; Maglott, Donna; Siepel, Adam; Brejova, Brona; Diekhans, Mark; Harte, Rachel; Baertsch, Robert; Kent, Jim; Haussler, David; Brent, Michael; Langton, Laura; Comstock, Charles L.G.; Stevens, Michael; Wei, Chaochun; van Baren, Marijke J.; Salehi-Ashtiani, Kourosh; Murray, Ryan R.; Ghamsari, Lila; Mello, Elizabeth; Lin, Chenwei; Pennacchio, Christa; Schreiber, Kirsten; Shapiro, Nicole; Marsh, Amber; Pardes, Elizabeth; Moore, Troy; Lebeau, Anita; Muratet, Mike; Simmons, Blake; Kloske, David; Sieja, Stephanie; Hudson, James; Sethupathy, Praveen; Brownstein, Michael; Bhat, Narayan; Lazar, Joseph; Jacob, Howard; Gruber, Chris E.; Smith, Mark R.; McPherson, John; Garcia, Angela M.; Gunaratne, Preethi H.; Wu, Jiaqian; Muzny, Donna; Gibbs, Richard A.; Young, Alice C.; Bouffard, Gerard G.; Blakesley, Robert W.; Mullikin, Jim; Green, Eric D.; Dickson, Mark C.; Rodriguez, Alex C.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.; Hirst, Martin; Zeng, Thomas; Tse, Kane; Moksa, Michelle; Deng, Merinda; Ma, Kevin; Mah, Diana; Pang, Johnson; Taylor, Greg; Chuah, Eric; Deng, Athena; Fichter, Keith; Go, Anne; Lee, Stephanie; Wang, Jing; Griffith, Malachi; Morin, Ryan; Moore, Richard A.; Mayo, Michael; Munro, Sarah; Wagner, Susan; Jones, Steven J.M.; Holt, Robert A.; Marra, Marco A.; Lu, Sun; Yang, Shuwei; Hartigan, James; Graf, Marcus; Wagner, Ralf; Letovksy, Stanley; Pulido, Jacqueline C.; Robison, Keith; Esposito, Dominic; Hartley, James; Wall, Vanessa E.; Hopkins, Ralph F.; Ohara, Osamu; Wiemann, Stefan

    2009-01-01

    Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide. PMID:19767417

  15. Application of recombinant fluorescent mammalian cells as a toxicity biosensor.

    Science.gov (United States)

    Kim, E J; Lee, Y; Lee, J E; Gu, M B

    2002-01-01

    With respect to developing a more sensitive biosensor, a recombinant fluorescent Chinese Hamster Ovary cell line was used for the monitoring of various toxicants. Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively. They were characterized with mitomycin C and gamma-ray as genotoxicants and bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs. When compared to each other, the response of KFC-A10 was generally more informative and sensitive. Compared to typical bacterial biosensor systems, these cell lines offered a sensitivity of 2- to 50-fold greater for the tested chemicals. Based on these results, the use of mammalian cells offers a sensitive biosensor system that is not only fast, cheap and reproducible but also capable of monitoring the endocrine-like characteristics of environmental toxicants.

  16. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  17. Romantic love: a mammalian brain system for mate choice.

    Science.gov (United States)

    Fisher, Helen E; Aron, Arthur; Brown, Lucy L

    2006-12-29

    Mammals and birds regularly express mate preferences and make mate choices. Data on mate choice among mammals suggest that this behavioural 'attraction system' is associated with dopaminergic reward pathways in the brain. It has been proposed that intense romantic love, a human cross-cultural universal, is a developed form of this attraction system. To begin to determine the neural mechanisms associated with romantic attraction in humans, we used functional magnetic resonance imaging (fMRI) to study 17 people who were intensely 'in love'. Activation specific to the beloved occurred in the brainstem right ventral tegmental area and right postero-dorsal body of the caudate nucleus. These and other results suggest that dopaminergic reward and motivation pathways contribute to aspects of romantic love. We also used fMRI to study 15 men and women who had just been rejected in love. Preliminary analysis showed activity specific to the beloved in related regions of the reward system associated with monetary gambling for uncertain large gains and losses, and in regions of the lateral orbitofrontal cortex associated with theory of mind, obsessive/compulsive behaviours and controlling anger. These data contribute to our view that romantic love is one of the three primary brain systems that evolved in avian and mammalian species to direct reproduction. The sex drive evolved to motivate individuals to seek a range of mating partners; attraction evolved to motivate individuals to prefer and pursue specific partners; and attachment evolved to motivate individuals to remain together long enough to complete species-specific parenting duties. These three behavioural repertoires appear to be based on brain systems that are largely distinct yet interrelated, and they interact in specific ways to orchestrate reproduction, using both hormones and monoamines. Romantic attraction in humans and its antecedent in other mammalian species play a primary role: this neural mechanism motivates

  18. Lateral diffusion of nutrients by mammalian herbivores in terrestrial ecosystems.

    Directory of Open Access Journals (Sweden)

    Adam Wolf

    Full Text Available Animals translocate nutrients by consuming nutrients at one point and excreting them or dying at another location. Such lateral fluxes may be an important mechanism of nutrient supply in many ecosystems, but lack quantification and a systematic theoretical framework for their evaluation. This paper presents a mathematical framework for quantifying such fluxes in the context of mammalian herbivores. We develop an expression for lateral diffusion of a nutrient, where the diffusivity is a biologically determined parameter depending on the characteristics of mammals occupying the domain, including size-dependent phenomena such as day range, metabolic demand, food passage time, and population size. Three findings stand out: (a Scaling law-derived estimates of diffusion parameters are comparable to estimates calculated from estimates of each coefficient gathered from primary literature. (b The diffusion term due to transport of nutrients in dung is orders of magnitude large than the coefficient representing nutrients in bodymass. (c The scaling coefficients show that large herbivores make a disproportionate contribution to lateral nutrient transfer. We apply the diffusion equation to a case study of Kruger National Park to estimate the conditions under which mammal-driven nutrient transport is comparable in magnitude to other (abiotic nutrient fluxes (inputs and losses. Finally, a global analysis of mammalian herbivore transport is presented, using a comprehensive database of contemporary animal distributions. We show that continents vary greatly in terms of the importance of animal-driven nutrient fluxes, and also that perturbations to nutrient cycles are potentially quite large if threatened large herbivores are driven to extinction.

  19. Human therapeutic cloning (NTSC): applying research from mammalian reproductive cloning.

    Science.gov (United States)

    French, Andrew J; Wood, Samuel H; Trounson, Alan O

    2006-01-01

    Human therapeutic cloning or nuclear transfer stem cells (NTSC) to produce patient-specific stem cells, holds considerable promise in the field of regenerative medicine. The recent withdrawal of the only scientific publications claiming the successful generation of NTSC lines afford an opportunity to review the available research in mammalian reproductive somatic cell nuclear transfer (SCNT) with the goal of progressing human NTSC. The process of SCNT is prone to epigenetic abnormalities that contribute to very low success rates. Although there are high mortality rates in some species of cloned animals, most surviving clones have been shown to have normal phenotypic and physiological characteristics and to produce healthy offspring. This technology has been applied to an increasing number of mammals for utility in research, agriculture, conservation, and biomedicine. In contrast, attempts at SCNT to produce human embryonic stem cells (hESCs) have been disappointing. Only one group has published reliable evidence of success in deriving a cloned human blastocyst, using an undifferentiated hESC donor cell, and it failed to develop into a hESC line. When optimal conditions are present, it appears that in vitro development of cloned and parthenogenetic embryos, both of which may be utilized to produce hESCs, may be similar to in vitro fertilized embryos. The derivation of ESC lines from cloned embryos is substantially more efficient than the production of viable offspring. This review summarizes developments in mammalian reproductive cloning, cell-to-cell fusion alternatives, and strategies for oocyte procurement that may provide important clues facilitating progress in human therapeutic cloning leading to the successful application of cell-based therapies utilizing autologous hESC lines.

  20. Problems of allometric scaling analysis: examples from mammalian reproductive biology.

    Science.gov (United States)

    Martin, Robert D; Genoud, Michel; Hemelrijk, Charlotte K

    2005-05-01

    Biological scaling analyses employing the widely used bivariate allometric model are beset by at least four interacting problems: (1) choice of an appropriate best-fit line with due attention to the influence of outliers; (2) objective recognition of divergent subsets in the data (allometric grades); (3) potential restrictions on statistical independence resulting from phylogenetic inertia; and (4) the need for extreme caution in inferring causation from correlation. A new non-parametric line-fitting technique has been developed that eliminates requirements for normality of distribution, greatly reduces the influence of outliers and permits objective recognition of grade shifts in substantial datasets. This technique is applied in scaling analyses of mammalian gestation periods and of neonatal body mass in primates. These analyses feed into a re-examination, conducted with partial correlation analysis, of the maternal energy hypothesis relating to mammalian brain evolution, which suggests links between body size and brain size in neonates and adults, gestation period and basal metabolic rate. Much has been made of the potential problem of phylogenetic inertia as a confounding factor in scaling analyses. However, this problem may be less severe than suspected earlier because nested analyses of variance conducted on residual variation (rather than on raw values) reveals that there is considerable variance at low taxonomic levels. In fact, limited divergence in body size between closely related species is one of the prime examples of phylogenetic inertia. One common approach to eliminating perceived problems of phylogenetic inertia in allometric analyses has been calculation of 'independent contrast values'. It is demonstrated that the reasoning behind this approach is flawed in several ways. Calculation of contrast values for closely related species of similar body size is, in fact, highly questionable, particularly when there are major deviations from the best

  1. Transcriptomic insights into the genetic basis of mammalian limb diversity.

    Science.gov (United States)

    Maier, Jennifer A; Rivas-Astroza, Marcelo; Deng, Jenny; Dowling, Anna; Oboikovitz, Paige; Cao, Xiaoyi; Behringer, Richard R; Cretekos, Chris J; Rasweiler, John J; Zhong, Sheng; Sears, Karen E

    2017-03-23

    From bat wings to whale flippers, limb diversification has been crucial to the evolutionary success of mammals. We performed the first transcriptome-wide study of limb development in multiple species to explore the hypothesis that mammalian limb diversification has proceeded through the differential expression of conserved shared genes, rather than by major changes to limb patterning. Specifically, we investigated the manner in which the expression of shared genes has evolved within and among mammalian species. We assembled and compared transcriptomes of bat, mouse, opossum, and pig fore- and hind limbs at the ridge, bud, and paddle stages of development. Results suggest that gene expression patterns exhibit larger variation among species during later than earlier stages of limb development, while within species results are more mixed. Consistent with the former, results also suggest that genes expressed at later developmental stages tend to have a younger evolutionary age than genes expressed at earlier stages. A suite of key limb-patterning genes was identified as being differentially expressed among the homologous limbs of all species. However, only a small subset of shared genes is differentially expressed in the fore- and hind limbs of all examined species. Similarly, a small subset of shared genes is differentially expressed within the fore- and hind limb of a single species and among the forelimbs of different species. Taken together, results of this study do not support the existence of a phylotypic period of limb development ending at chondrogenesis, but do support the hypothesis that the hierarchical nature of development translates into increasing variation among species as development progresses.

  2. The biology and dynamics of mammalian cortical granules

    Directory of Open Access Journals (Sweden)

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  3. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  4. Fentanyl and Other Synthetic Opioids Drug Overdose Deaths

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  5. GC X GCTOFMS OF SYNTHETIC PYRETHROIDS IN FOODS SAMPLES

    Science.gov (United States)

    Pyrethrins are natural insecticides in the extract of chrysanthemum flowers1. Pyrethroids are synthetic forms of pyrethrins, and many are halogenated (F, Cl, Br). Synthetic pyrethroids have become popular replacements for organophosphorus pesticides, which have become increasin...

  6. Ships as salient objects in synthetic aperture radar imaginary

    CSIR Research Space (South Africa)

    Schwegmann, Colin P

    2016-07-01

    Full Text Available The widespread access to Synthetic Aperture Radar data has created a need for more precise ship extraction, specifically in low-to-medium resolution imagery. While Synthetic Aperture Radar pixel resolution is improving for a large swaths...

  7. Engineering of synthetic, stress-responsive yeast promoters

    DEFF Research Database (Denmark)

    Rajkumar, Arun Stephen; Liu, Guodong; Bergenholm, David

    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 inducibleby specific endogenous or environmental conditions...

  8. Distributional congruence of mammalian herbivores in the Trans-Himalayan Mountains

    NARCIS (Netherlands)

    Namgail, T.; Wieren, van S.E.; Prins, H.H.T.

    2013-01-01

    Large-scale distribution and diversity patterns of mammalian herbivores, especially less charismatic species in alpine environments remain little understood. We studied distributional congruence of mammalian herbivores in the Trans-Himalayan region of Ladakh to see if the distributions of less

  9. Health safety issues of synthetic food colorants.

    Science.gov (United States)

    Amchova, Petra; Kotolova, Hana; Ruda-Kucerova, Jana

    2015-12-01

    Increasing attention has been recently paid to the toxicity of additives used in food. The European Parliament and the Council published the REGULATION (EC) No. 1333/2008 on food additives establishing that the toxicity of food additives evaluated before 20th January 2009 must be re-evaluated by European Food Safety Authority (EFSA). The aim of this review is to survey current knowledge specifically on the toxicity issues of synthetic food colorants using official reports published by the EFSA and other available studies published since the respective report. Synthetic colorants described are Tartrazine, Quinoline Yellow, Sunset Yellow, Azorubine, Ponceau 4R, Erythrosine, Allura Red, Patent Blue, Indigo Carmine, Brilliant Blue FCF, Green S, Brilliant Black and Brown HT. Moreover, a summary of evidence on possible detrimental effects of colorant mixes on children's behaviour is provided and future research directions are outlined. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. [Progress in synthetic biology of pinocembrin].

    Science.gov (United States)

    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.

  11. Fusion as a source of synthetic fuels

    International Nuclear Information System (INIS)

    Powell, J.R.; Fillo, J.A.; Steinberg, M.

    1981-01-01

    In the near-term, coal derived synthetic fuels will be used; but in the long-term, resource depletion and environmental effects will mandate synthetic fuels from inexhaustible sources - fission, fusion, and solar. Of the three sources, fusion appears uniquely suited for the efficient production of hydrogen-based fuels, due to its ability to directly generate very high process temperatures (up to approx. 2000 0 C) for water splitting reactions. Fusion-based water splitting reactions include high temperature electrolysis (HTE) of steam, thermochemical cycles, hybrid electrochemical/thermochemical, and direct thermal decomposition. HTE appears to be the simplest and most efficient process with efficiencies of 50 to 70% (fusion to hydrogen chemical energy), depending on process conditions

  12. Synthetic risks, risk potency, and carcinogen regulation.

    Science.gov (United States)

    Viscusi, W K; Hakes, J K

    1998-01-01

    This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

  13. The Prion Concept and Synthetic Prions.

    Science.gov (United States)

    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.

  14. Consequentialism and the Synthetic Biology Problem.

    Science.gov (United States)

    Heavey, Patrick

    2017-04-01

    This article analyzes the ethics of synthetic biology (synbio) from a consequentialist perspective, examining potential effects on food and agriculture, and on medicine, fuel, and the advancement of science. The issues of biosafety and biosecurity are also examined. A consequentialist analysis offers an essential road map to policymakers and regulators as to how to deal with synbio. Additionally, the article discusses the limitations of consequentialism as a tool for analysing synbioethics. Is it possible to predict, with any degree of plausibility, what the consequences of synthetic biology will be in 50 years, or in 100, or in 500? Synbio may take humanity to a place of radical departure from what is known or knowable.

  15. Designing synthetic RNA for delivery by nanoparticles

    International Nuclear Information System (INIS)

    Jedrzejczyk, Dominika; Pawlowska, Roza; Chworos, Arkadiusz; Gendaszewska-Darmach, Edyta

    2017-01-01

    The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid’s nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided. (topical review)

  16. High frame rate synthetic aperture duplex imaging

    DEFF Research Database (Denmark)

    Stuart, Matthias Bo; Tomov, Borislav Gueorguiev; Pihl, Michael Johannes

    2013-01-01

    aperture flow imaging as demonstrated in this paper. Synthetic aperture, directional beamforming, and cross-correlation are used to produce B-mode and vector velocity images at high frame rates. The frame rate equals the effective pulse repetition frequency of each imaging mode. Emissions for making the B...... estimation is −1.8% and the relative standard deviation 5.4%. The approach can thus estimate both high and low velocities with equal accuracy and thereby makes it possible to present vector flow images with a high dynamic range. Measurements are made using the SARUS research scanner, a linear array......Conventional color flow images are limited in velocity range and can either show the high velocities in systole or be optimized for the lower diastolic velocities. The full dynamics of the flow is, thus, hard to visualize. The dynamic range can be significantly increased by employing synthetic...

  17. Experience with synthetic fluorinated fluid lubricants

    Science.gov (United States)

    Conley, Peter L.; Bohner, John J.

    1990-01-01

    Since the late 1970's, the wet lubricant of choice for space mechanisms has been one of the family of synthetic perfluoro polyalkylether (PFPE) compounds, namely Fomblin Z-25 (Bray-815Z) or DuPont's Krytox 143xx series. While offering the advantages of extremely low vapor pressures and wide temperature ranges, these oils and derived greases have a complex chemistry compared to the more familiar natural and synthetic hydrocarbons. Many aerospace companies have conducted test programs to characterize the behavior of these compounds in a space environment, resulting in a large body of hard knowledge as well as considerable space lore concerning the suitability of the lubricants for particular applications and techniques for successful application. The facts are summarized and a few myths about the compounds are dispelled, and some performance guidelines for the mechanism design engineer are provided.

  18. The adjuvant potential of synthetic alkylglycerols.

    Science.gov (United States)

    Acevedo, Reinaldo; Gil, Danay; del Campo, Judith; Bracho, Gustavo; Valdés, Yolanda; Pérez, Oliver

    2006-04-12

    Alkylglycerols (AGs) have shown immune stimulant and adjuvant activity in many studies, but natural sources are not so accessible and their extraction from them is very complicated. Therefore, a group of chemists at IFAL have synthesized AG analogs. The aim of this work was to evaluate the adjuvant potential of different synthetic AGs. A mix of ovoalbumin (Ova) and AGs increase anti-Ova IgG antibodies production in sera of immunized mice. The predominant subclass was IgG1 although higher levels of IgG2a were observed as the carbon chain length of AGs increased. AGs also induced the production of IL-12 and nitric oxide (NO) in the U937 human histiocyte and J774 mouse macrophage cell lines, respectively. These results indicate that synthetic AGs are effective adjuvants for the standardized antigen, Ova.

  19. Prospects for applying synthetic biology to toxicology

    DEFF Research Database (Denmark)

    Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.

    2017-01-01

    The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

  20. Carbon monosulfide: a useful synthetic intermediate

    International Nuclear Information System (INIS)

    Kramer, M.P.

    1986-01-01

    The physical properties of carbon monosulfide, CS, are well documented. The molecule has been observed in interstellar space and is found to be a common intermediate in the thermal decomposition of carbon disulfide and other sulfur compounds. Interestingly enough, the chemistry of carbon monosulfide, a molecule that is isovalent with carbon monoxide, has received little attention. The explosive nature of the carbon monosulfide monomer, which hindered previous workers, was overcome by the development of special handling techniques. The ability to produce carbon monosulfide in gram quantities had lead to synthesis of novel compounds and to a more direct synthetic route for certain known compounds. Specifically, the following general reaction demonstrates the capabilities of carbon monosulfide on the synthetic scale. CS + RXY → RXC(S)Y;(X = N,S), (Y = H, Cl). Note: The initial product formed in the reaction can be an unstable intermediate