antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.

Science.gov (United States)

Weber, Tilmann; Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko; Medema, Marnix H

2015-07-01

Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters

NARCIS (Netherlands)

Cimermancic, P.; Medema, Marnix; Claesen, J.; Kurika, K.; Wieland Brown, L.C.; Mavrommatis, K.; Pati, A.; Godfrey, P.A.; Koehrsen, M.; Clardy, J.; Birren, B. W.; Takano, Eriko; Sali, A.; Linington, R.G.; Fischbach, M.A.

2014-01-01

Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the

Diversity of Culturable Thermophilic Actinobacteria in Hot Springs in Tengchong, China and Studies of their Biosynthetic Gene Profiles.

Science.gov (United States)

Liu, Lan; Salam, Nimaichand; Jiao, Jian-Yu; Jiang, Hong-Chen; Zhou, En-Min; Yin, Yi-Rui; Ming, Hong; Li, Wen-Jun

2016-07-01

The class Actinobacteria has been a goldmine for the discovery of antibiotics and has attracted interest from both academics and industries. However, an absence of novel approaches during the last few decades has limited the discovery of new microbial natural products useful for industries. Scientists are now focusing on the ecological aspects of diverse environments including unexplored or underexplored habitats and extreme environments in the search for new metabolites. This paper reports on the diversity of culturable actinobacteria associated with hot springs located in Tengchong County, Yunnan Province, southwestern China. A total of 58 thermophilic actinobacterial strains were isolated from the samples collected from ten hot springs distributed over three geothermal fields (e.g., Hehua, Rehai, and Ruidian). Phylogenetic positions and their biosynthetic profiles were analyzed by sequencing 16S rRNA gene and three biosynthetic gene clusters (KS domain of PKS-I, KSα domain of PKS-II and A domain of NRPS). On the basis of 16S rRNA gene phylogenetic analysis, the 58 strains were affiliated with 12 actinobacterial genera: Actinomadura Micromonospora, Microbispora, Micrococcus, Nocardiopsis, Nonomuraea, Promicromonospora, Pseudonocardia, Streptomyces, Thermoactinospora, Thermocatellispora, and Verrucosispora, of which the two novel genera Thermoactinospora and Thermocatellisopora were recently described from among these strains. Considering the biosynthetic potential of these actinobacterial strains, 22 were positive for PCR amplification of at least one of the three biosynthetic gene clusters (PKS-I, PKS-II, and NRPS). These actinobacteria were further subjected to antimicrobial assay against five opportunistic human pathogens (Acinetobacter baumannii, Escherichia coli, Micrococcus luteus, Staphylococcus aureus and Streptococcus faecalis). All of the 22 strains that were positive for PCR amplification of at least one of the biosynthetic gene domains exhibited

High GC Content Cas9-Mediated Genome-Editing and Biosynthetic Gene Cluster Activation in Saccharopolyspora erythraea.

Science.gov (United States)

Liu, Yong; Wei, Wen-Ping; Ye, Bang-Ce

2018-05-18

The overexpression of bacterial secondary metabolite biosynthetic enzymes is the basis for industrial overproducing strains. Genome editing tools can be used to further improve gene expression and yield. Saccharopolyspora erythraea produces erythromycin, which has extensive clinical applications. In this study, the CRISPR-Cas9 system was used to edit genes in the S. erythraea genome. A temperature-sensitive plasmid containing the PermE promoter, to drive Cas9 expression, and the Pj23119 and PkasO promoters, to drive sgRNAs, was designed. Erythromycin esterase, encoded by S. erythraea SACE_1765, inactivates erythromycin by hydrolyzing the macrolactone ring. Sequencing and qRT-PCR confirmed that reporter genes were successfully inserted into the SACE_1765 gene. Deletion of SACE_1765 in a high-producing strain resulted in a 12.7% increase in erythromycin levels. Subsequent PermE- egfp knock-in at the SACE_0712 locus resulted in an 80.3% increase in erythromycin production compared with that of wild type. Further investigation showed that PermE promoter knock-in activated the erythromycin biosynthetic gene clusters at the SACE_0712 locus. Additionally, deletion of indA (SACE_1229) using dual sgRNA targeting without markers increased the editing efficiency to 65%. In summary, we have successfully applied Cas9-based genome editing to a bacterial strain, S. erythraea, with a high GC content. This system has potential application for both genome-editing and biosynthetic gene cluster activation in Actinobacteria.

New insights into the organization and regulation of trichothecene biosynthetic genes in Trichoderma

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Collectively, species of the genus Trichoderma can produce numerous structurally diverse secondary metabolites (SM). This ability is conferred by the presence of SM biosynthetic gene clusters in their genomes. Species of Trichoderma in the Brevicompactum clade are able to produce trichothecenes, a f...

antiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters

DEFF Research Database (Denmark)

Weber, Tilmann; Blin, Kai; Duddela, Srikanth

2015-01-01

Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we...... introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration...... of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products...

Heterologous stable expression of terpenoid biosynthetic genes using the moss Physcomitrella patens

DEFF Research Database (Denmark)

Bach, Søren Spanner; King, Brian Christopher; Zhan, Xin

2014-01-01

Heterologous and stable expression of genes encoding terpenoid biosynthetic enzymes in planta is an important tool for functional characterization and is an attractive alternative to expression in microbial hosts for biotechnological production. Despite improvements to the procedure, such as stre...

Molecular characterization of tocopherol biosynthetic genes in sweetpotato that respond to stress and activate the tocopherol production in tobacco.

Science.gov (United States)

Ji, Chang Yoon; Kim, Yun-Hee; Kim, Ho Soo; Ke, Qingbo; Kim, Gun-Woo; Park, Sung-Chul; Lee, Haeng-Soon; Jeong, Jae Cheol; Kwak, Sang-Soo

2016-09-01

Tocopherol (vitamin E) is a chloroplast lipid that is presumed to be involved in the plant response to oxidative stress. In this study, we isolated and characterized five tocopherol biosynthetic genes from sweetpotato (Ipomoea batatas [L.] Lam) plants, including genes encoding 4-hydroxyphenylpyruvate dioxygenase (IbHPPD), homogentisate phytyltransferase (IbHPT), 2-methyl-6-phytylbenzoquinol methyltransferase (IbMPBQ MT), tocopherol cyclase (IbTC) and γ-tocopherol methyltransferase (IbTMT). Fluorescence microscope analysis indicated that four proteins localized into the chloroplast, whereas IbHPPD observed in the nuclear. Quantitative RT-PCR analysis revealed that the expression patterns of the five tocopherol biosynthetic genes varied in different plant tissues and under different stress conditions. All five genes were highly expressed in leaf tissues, whereas IbHPPD and IbHPT were highly expressed in the thick roots. The expression patterns of these five genes significantly differed in response to PEG, NaCl and H2O2-mediated oxidative stress. IbHPPD was strongly induced following PEG and H2O2 treatment and IbHPT was strongly induced following PEG treatment, whereas IbMPBQ MT and IbTC were highly expressed following NaCl treatment. Upon infection of the bacterial pathogen Pectobacterium chrysanthemi, the expression of IbHPPD increased sharply in sweetpotato leaves, whereas the expression of the other genes was reduced or unchanged. Additionally, transient expression of the five tocopherol biosynthetic genes in tobacco (Nicotiana bentamiana) leaves resulted in increased transcript levels of the transgenes expressions and tocopherol production. Therefore, our results suggested that the five tocopherol biosynthetic genes of sweetpotato play roles in the stress defense response as transcriptional regulators of the tocopherol production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters

KAUST Repository

Othoum, Ghofran K

2018-05-22

BackgroundThe increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions.ResultsWe report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species.ConclusionsB. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems.

Expression of Terpenoid Biosynthetic Genes and Accumulation of Chemical Constituents in Valeriana fauriei

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Yun Ji Park

2016-05-01

Full Text Available Valeriana fauriei (V. fauriei, which emits a characteristic and unpleasant odor, is important in traditional medicine. In this study, the expression of terpenoid biosynthetic genes was investigated in different organs that were also screened for volatile compounds including valerenic acid and its derivatives. Specific expression patterns from different parts of V. fauriei were observed using quantitative real-time PCR (qRT-PCR. The highest transcript levels of biosynthetic genes involved in mevalonic acid (MVA and methylerythritol phosphate (MEP production were found in the stem. Although the amounts of volatile compounds were varied by organ, most of the volatile terpenoids were accumulated in the root. Gas chromatography mass spectrometry (GC-MS analysis identified 128 volatile compounds, which represented 65.33% to 95.66% of total volatiles. Certain compounds were only found in specific organs. For example, isovalerenic acid and valerenic acid and its derivatives were restricted to the root. Organs with high transcript levels did not necessarily have high levels of the corresponding chemical constituents. According to these results, we hypothesize that translocation may occur between different organs in V. fauriei.

Multiplex PCR analysis of fumonisin biosynthetic genes in fumonisin-nonproducing Aspergillus niger and A. awamori strains

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In order to determine the genetic basis for loss of fumonisin B¬2 (FB2) biosynthesis in FB2 non-producing A. niger strains, we developed multiplex PCR primer sets to amplify fragments of eight fumonisin biosynthetic pathway (fum) genes. Fragments of all eight fum genes were amplified in FB2-produci...

Expression of phenazine biosynthetic genes during the arbuscular mycorrhizal symbiosis of Glomus intraradices

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Dionicia Gloria León-Martínez

2012-06-01

Full Text Available To explore the molecular mechanisms that prevail during the establishment of the arbuscular mycorrhiza symbiosis involving the genus Glomus, we transcriptionally analysed spores of Glomus intraradices BE3 during early hyphal growth. Among 458 transcripts initially identified as being expressed at presymbiotic stages, 20% of sequences had homology to previously characterized eukaryotic genes, 30% were homologous to fungal coding sequences, and 9% showed homology to previously characterized bacterial genes. Among them, GintPbr1a encodes a homolog to Phenazine Biosynthesis Regulator (Pbr of Burkholderia cenocepacia, an pleiotropic regulatory protein that activates phenazine production through transcriptional activation of the protein D isochorismatase biosynthetic enzyme phzD (Ramos et al., 2010. Whereas GintPbr1a is expressed during the presymbiotic phase, the G. intraradices BE3 homolog of phzD (BGintphzD is transcriptionally active at the time of the establishment of the arbuscular mycorrhizal symbiosis. DNA from isolated bacterial cultures found in spores of G. intraradices BE3 confirmed that both BGintPbr1a and BGintphzD are present in the genome of its potential endosymbionts. Taken together, our results indicate that spores of G. intraradices BE3 express bacterial phenazine biosynthetic genes at the onset of the fungal-plant symbiotic interaction.

The Cremeomycin Biosynthetic Gene Cluster Encodes a Pathway for Diazo Formation.

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Waldman, Abraham J; Pechersky, Yakov; Wang, Peng; Wang, Jennifer X; Balskus, Emily P

2015-10-12

Diazo groups are found in a range of natural products that possess potent biological activities. Despite longstanding interest in these metabolites, diazo group biosynthesis is not well understood, in part because of difficulties in identifying specific genes linked to diazo formation. Here we describe the discovery of the gene cluster that produces the o-diazoquinone natural product cremeomycin and its heterologous expression in Streptomyces lividans. We used stable isotope feeding experiments and in vitro characterization of biosynthetic enzymes to decipher the order of events in this pathway and establish that diazo construction involves late-stage N-N bond formation. This work represents the first successful production of a diazo-containing metabolite in a heterologous host, experimentally linking a set of genes with diazo formation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites.

Science.gov (United States)

Hadjithomas, Michalis; Chen, I-Min Amy; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Szeto, Ernest; Huang, Jinghua; Reddy, T B K; Cimermančič, Peter; Fischbach, Michael A; Ivanova, Natalia N; Markowitz, Victor M; Kyrpides, Nikos C; Pati, Amrita

2015-07-14

In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of "big" genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in Alphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to

Modular co-culture engineering, a new approach for metabolic engineering.

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Zhang, Haoran; Wang, Xiaonan

2016-09-01

With the development of metabolic engineering, employment of a selected microbial host for accommodation of a designed biosynthetic pathway to produce a target compound has achieved tremendous success in the past several decades. Yet, increasing requirements for sophisticated microbial biosynthesis call for establishment and application of more advanced metabolic engineering methodologies. Recently, important progress has been made towards employing more than one engineered microbial strains to constitute synthetic co-cultures and modularizing the biosynthetic labor between the co-culture members in order to improve bioproduction performance. This emerging approach, referred to as modular co-culture engineering in this review, presents a valuable opportunity for expanding the scope of the broad field of metabolic engineering. We highlight representative research accomplishments using this approach, especially those utilizing metabolic engineering tools for microbial co-culture manipulation. Key benefits and major challenges associated with modular co-culture engineering are also presented and discussed. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the Genomes of Marine Sponge Derived Streptomyces spp. Isolates

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Stephen A. Jackson

2018-02-01

Full Text Available The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs such as polyketide synthases (PKS and non-ribosomal peptide synthetases (NRPS which are modular and can be highly repetitive. Due to the repeats, these gene clusters can be difficult to resolve using short read next generation datasets and are often quite poorly predicted using standard approaches. We have sequenced the genomes of 13 Streptomyces spp. strains isolated from shallow water and deep-sea sponges that display antimicrobial activities against a number of clinically relevant bacterial and yeast species. Draft genomes have been assembled and smBGCs have been identified using the antiSMASH (antibiotics and Secondary Metabolite Analysis Shell web platform. We have compared the smBGCs amongst strains in the search for novel sequences conferring the potential to produce novel bioactive secondary metabolites. The strains in this study recruit to four distinct clades within the genus Streptomyces. The marine strains host abundant smBGCs which encode polyketides, NRPS, siderophores, bacteriocins and lantipeptides. The deep-sea strains appear to be enriched with gene clusters encoding NRPS. Marine adaptations are evident in the sponge-derived strains which are enriched for genes involved in the biosynthesis and transport of compatible solutes and for heat-shock proteins. Streptomyces spp. from marine environments are a promising source of novel bioactive secondary metabolites as the abundance and diversity of smBGCs show high degrees of novelty. Sponge derived Streptomyces spp. isolates appear to display genomic adaptations to marine living when compared to terrestrial strains.

The Arabidopsis histone chaperone FACT is required for stress-induced expression of anthocyanin biosynthetic genes.

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Pfab, Alexander; Breindl, Matthias; Grasser, Klaus D

2018-03-01

The histone chaperone FACT is involved in the expression of genes encoding anthocyanin biosynthetic enzymes also upon induction by moderate high-light and therefore contributes to the stress-induced plant pigmentation. The histone chaperone FACT consists of the SSRP1 and SPT16 proteins and associates with transcribing RNAPII (RNAPII) along the transcribed region of genes. FACT can promote transcriptional elongation by destabilising nucleosomes in the path of RNA polymerase II, thereby facilitating efficient transcription of chromatin templates. Transcript profiling of Arabidopsis plants depleted in SSRP1 or SPT16 demonstrates that only a small subset of genes is differentially expressed relative to wild type. The majority of these genes is either up- or down-regulated in both the ssrp1 and spt16 plants. Among the down-regulated genes, those encoding enzymes of the biosynthetic pathway of the plant secondary metabolites termed anthocyanins (but not regulators of the pathway) are overrepresented. Upon exposure to moderate high-light stress several of these genes are up-regulated to a lesser extent in ssrp1/spt16 compared to wild type plants, and accordingly the mutant plants accumulate lower amounts of anthocyanin pigments. Moreover, the expression of SSRP1 and SPT16 is induced under these conditions. Therefore, our findings indicate that FACT is a novel factor required for the accumulation of anthocyanins in response to light-induction.

Draft genome sequence of Streptomyces coelicoflavus ZG0656 reveals the putative biosynthetic gene cluster of acarviostatin family α-amylase inhibitors.

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Guo, X; Geng, P; Bai, F; Bai, G; Sun, T; Li, X; Shi, L; Zhong, Q

2012-08-01

The aims of this study are to obtain the draft genome sequence of Streptomyces coelicoflavus ZG0656, which produces novel acarviostatin family α-amylase inhibitors, and then to reveal the putative acarviostatin-related gene cluster and the biosynthetic pathway. The draft genome sequence of S. coelicoflavus ZG0656 was generated using a shotgun approach employing a combination of 454 and Solexa sequencing technologies. Genome analysis revealed a putative gene cluster for acarviostatin biosynthesis, termed sct-cluster. The cluster contains 13 acarviostatin synthetic genes, six transporter genes, four starch degrading or transglycosylation enzyme genes and two regulator genes. On the basis of bioinformatic analysis, we proposed a putative biosynthetic pathway of acarviostatins. The intracellular steps produce a structural core, acarviostatin I00-7-P, and the extracellular assemblies lead to diverse acarviostatin end products. The draft genome sequence of S. coelicoflavus ZG0656 revealed the putative biosynthetic gene cluster of acarviostatins and a putative pathway of acarviostatin production. To our knowledge, S. coelicoflavus ZG0656 is the first strain in this species for which a genome sequence has been reported. The analysis of sct-cluster provided important insights into the biosynthesis of acarviostatins. This work will be a platform for producing novel variants and yield improvement. © 2012 The Authors. Letters in Applied Microbiology © 2012 The Society for Applied Microbiology.

Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics.

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Lukežič, Tadeja; Lešnik, Urška; Podgoršek, Ajda; Horvat, Jaka; Polak, Tomaž; Šala, Martin; Jenko, Branko; Raspor, Peter; Herron, Paul R; Hunter, Iain S; Petković, Hrvoje

2013-12-01

Tetracyclines (TCs) are medically important antibiotics from the polyketide family of natural products. Chelocardin (CHD), produced by Amycolatopsis sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic activity against a number of Gram-positive and Gram-negative multi-resistant pathogens. CHD has an unknown mode of action that is different from TCs. It has some structural features that define it as 'atypical' and, notably, is active against tetracycline-resistant pathogens. Identification and characterization of the chelocardin biosynthetic gene cluster from A. sulphurea revealed 18 putative open reading frames including a type II polyketide synthase. Compared to typical TCs, the chd cluster contains a number of features that relate to its classification as 'atypical': an additional gene for a putative two-component cyclase/aromatase that may be responsible for the different aromatization pattern, a gene for a putative aminotransferase for C-4 with the opposite stereochemistry to TCs and a gene for a putative C-9 methylase that is a unique feature of this biosynthetic cluster within the TCs. Collectively, these enzymes deliver a molecule with different aromatization of ring C that results in an unusual planar structure of the TC backbone. This is a likely contributor to its different mode of action. In addition CHD biosynthesis is primed with acetate, unlike the TCs, which are primed with malonamate, and offers a biosynthetic engineering platform that represents a unique opportunity for efficient generation of novel tetracyclic backbones using combinatorial biosynthesis.

A modular positive feedback-based gene amplifier

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Bhalerao Kaustubh D

2010-02-01

Full Text Available Abstract Background Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors. Results We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity. Conclusions The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

Genetic interrelations in the actinomycin biosynthetic gene clusters of Streptomyces antibioticus IMRU 3720 and Streptomyces chrysomallus ATCC11523, producers of actinomycin X and actinomycin C

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Crnovčić I

2017-04-01

Full Text Available Ivana Crnovčić,1 Christian Rückert,2 Siamak Semsary,1 Manuel Lang,1 Jörn Kalinowski,2 Ullrich Keller1 1Institut für Chemie, Technische Universität Berlin, Berlin-Charlottenburg, 2Technology Platform Genomics, Center for Biotechnology, Bielefeld University, Bielefeld, Germany Abstract: Sequencing the actinomycin (acm biosynthetic gene cluster of Streptomyces antibioticus IMRU 3720, which produces actinomycin X (Acm X, revealed 20 genes organized into a highly similar framework as in the bi-armed acm C biosynthetic gene cluster of Streptomyces chrysomallus but without an attached additional extra arm of orthologues as in the latter. Curiously, the extra arm of the S. chrysomallus gene cluster turned out to perfectly match the single arm of the S. antibioticus gene cluster in the same order of orthologues including the the presence of two pseudogenes, scacmM and scacmN, encoding a cytochrome P450 and its ferredoxin, respectively. Orthologues of the latter genes were both missing in the principal arm of the S. chrysomallus acm C gene cluster. All orthologues of the extra arm showed a G +C-contents different from that of their counterparts in the principal arm. Moreover, the similarities of translation products from the extra arm were all higher to the corresponding translation products of orthologue genes from the S. antibioticus acm X gene cluster than to those encoded by the principal arm of their own gene cluster. This suggests that the duplicated structure of the S. chrysomallus acm C biosynthetic gene cluster evolved from previous fusion between two one-armed acm gene clusters each from a different genetic background. However, while scacmM and scacmN in the extra arm of the S. chrysomallus acm C gene cluster are mutated and therefore are non-functional, their orthologues saacmM and saacmN in the S. antibioticus acm C gene cluster show no defects seemingly encoding active enzymes with functions specific for Acm X biosynthesis. Both acm

Characterization of the fumonisin B2 biosynthetic gene cluster in Aspergillus niger and A. awamori.

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Aspergillus niger and A. awamori strains isolated from grapes cultivated in Mediterranean basin were examined for fumonisin B2 (FB2) production and presence/absence of sequences within the fumonisin biosynthetic gene (fum) cluster. Presence of 13 regions in the fum cluster was evaluated by PCR assay...

Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase.

Science.gov (United States)

Kudo, Fumitaka; Matsuura, Yasunori; Hayashi, Takaaki; Fukushima, Masayuki; Eguchi, Tadashi

2016-07-01

Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy-d-altrose to give 4'-O-demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed.

Expression of carotenoid biosynthetic pathway genes and changes in carotenoids during ripening in tomato (Lycopersicon esculentum).

Science.gov (United States)

Namitha, Kanakapura Krishnamurthy; Archana, Surya Narayana; Negi, Pradeep Singh

2011-04-01

To study the expression pattern of carotenoid biosynthetic pathway genes, changes in their expression at different stages of maturity in tomato fruit (cv. Arka Ahuti) were investigated. The genes regulating carotenoid production were quantified by a dot blot method using a DIG (dioxigenin) labelling and detection kit. The results revealed that there was an increase in the levels of upstream genes of the carotenoid biosynthetic pathway such as 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), 4-hydroxy-3-methyl-but-2-enyl diphosphate reductase (Lyt B), phytoene synthase (PSY), phytoene desaturase (PDS) and ζ-carotene desaturase (ZDS) by 2-4 fold at the breaker stage as compared to leaf. The lycopene and β-carotene content was analyzed by HPLC at different stages of maturity. The lycopene (15.33 ± 0.24 mg per 100 g) and β-carotene (10.37 ± 0.46 mg per 100 g) content were found to be highest at 5 days post-breaker and 10 days post-breaker stage, respectively. The lycopene accumulation pattern also coincided with the color values at different stages of maturity. These studies may provide insight into devising gene-based strategies for enhancing carotenoid accumulation in tomato fruits.

Bioengineering natural product biosynthetic pathways for therapeutic applications.

Science.gov (United States)

Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

2012-12-01

With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

SCS3 and YFT2 link transcription of phospholipid biosynthetic genes to ER stress and the UPR.

Directory of Open Access Journals (Sweden)

Robyn D Moir

2012-08-01

Full Text Available The ability to store nutrients in lipid droplets (LDs is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT proteins are conserved ER-resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2 and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER

Cloning of the staurosporine biosynthetic gene cluster from Streptomyces sp. TP-A0274 and its heterologous expression in Streptomyces lividans.

Science.gov (United States)

Onaka, Hiroyasu; Taniguchi, Shin-ichi; Igarashi, Yasuhiro; Furumai, Tamotsu

2002-12-01

Staurosporine is a representative member of indolocarbazole antibiotics. The entire staurosporine biosynthetic and regulatory gene cluster spanning 20-kb was cloned from Streptomyces sp. TP-A0274 and sequenced. The gene cluster consists of 14 ORFs and the amino acid sequence homology search revealed that it contains three genes, staO, staD, and staP, coding for the enzymes involved in the indolocarbazole aglycone biosynthesis, two genes, staG and staN, for the bond formation between the aglycone and deoxysugar, eight genes, staA, staB, staE, staJ, staI, staK, staMA, and staMB, for the deoxysugar biosynthesis and one gene, staR is a transcriptional regulator. Heterologous gene expression of a 38-kb fragment containing a complete set of the biosynthetic genes for staurosporine cloned into pTOYAMAcos confirmed its role in staurosporine biosynthesis. Moreover, the distribution of the gene for chromopyrrolic acid synthase, the key enzyme for the biosynthesis of indolocarbazole aglycone, in actinomycetes was investigated, and rebD homologs were shown to exist only in the strains producing indolocarbazole antibiotics.

IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes.

Science.gov (United States)

Hadjithomas, Michalis; Chen, I-Min A; Chu, Ken; Huang, Jinghua; Ratner, Anna; Palaniappan, Krishna; Andersen, Evan; Markowitz, Victor; Kyrpides, Nikos C; Ivanova, Natalia N

2017-01-04

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic gene clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Flg22-Triggered Immunity Negatively Regulates Key BR Biosynthetic Genes.

Science.gov (United States)

Jiménez-Góngora, Tamara; Kim, Seong-Ki; Lozano-Durán, Rosa; Zipfel, Cyril

2015-01-01

In plants, activation of growth and activation of immunity are opposing processes that define a trade-off. In the past few years, the growth-promoting hormones brassinosteroids (BR) have emerged as negative regulators of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), promoting growth at the expense of defense. The crosstalk between BR and PTI signaling was described as negative and unidirectional, since activation of PTI does not affect several analyzed steps in the BR signaling pathway. In this work, we describe that activation of PTI by the bacterial PAMP flg22 results in the reduced expression of BR biosynthetic genes. This effect does not require BR perception or signaling, and occurs within 15 min of flg22 treatment. Since the described PTI-induced repression of gene expression may result in a reduction in BR biosynthesis, the crosstalk between PTI and BR could actually be negative and bidirectional, a possibility that should be taken into account when considering the interaction between these two pathways.

IMG-ABC: An Atlas of Biosynthetic Gene Clusters to Fuel the Discovery of Novel Secondary Metabolites

Energy Technology Data Exchange (ETDEWEB)

Chen, I-Min; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Huang, Jinghua; Reddy, T. B.K.; Cimermancic, Peter; Fischbach, Michael; Ivanova, Natalia; Markowitz, Victor; Kyrpides, Nikos; Pati, Amrita

2014-10-28

In the discovery of secondary metabolites (SMs), large-scale analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of relevant computational resources. We present IMG-ABC (https://img.jgi.doe.gov/abc/) -- An Atlas of Biosynthetic gene Clusters within the Integrated Microbial Genomes (IMG) system1. IMG-ABC is a rich repository of both validated and predicted biosynthetic clusters (BCs) in cultured isolates, single-cells and metagenomes linked with the SM chemicals they produce and enhanced with focused analysis tools within IMG. The underlying scalable framework enables traversal of phylogenetic dark matter and chemical structure space -- serving as a doorway to a new era in the discovery of novel molecules.

Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

Science.gov (United States)

Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

2015-12-01

In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. Copyright © 2015 Elsevier Ltd. All rights reserved.

ATAF1 transcription factor directly regulates abscisic acid biosynthetic gene NCED3 in Arabidopsis thaliana

DEFF Research Database (Denmark)

Jensen, Michael Krogh; Lindemose, Søren; De Masi, Federico

2013-01-01

ATAF1, an Arabidopsis thaliana NAC transcription factor, plays important roles in plant adaptation to environmental stress and development. To search for ATAF1 target genes, we used protein binding microarrays and chromatin-immunoprecipitation (ChIP). This identified T[A,C,G]CGT[A,G] and TT[A,C,G...... abscisic acid (ABA) phytohormone biosynthetic gene NCED3. ChIP-qPCR and expression analysis showed that ATAF1 binding to the NCED3 promoter correlated with increased NCED3 expression and ABA hormone levels. These results indicate that ATAF1 regulates ABA biosynthesis....

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.

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.

Genetic interrelations in the actinomycin biosynthetic gene clusters of Streptomyces antibioticus IMRU 3720 and Streptomyces chrysomallus ATCC11523, producers of actinomycin X and actinomycin C

Science.gov (United States)

Crnovčić, Ivana; Rückert, Christian; Semsary, Siamak; Lang, Manuel; Kalinowski, Jörn; Keller, Ullrich

2017-01-01

Sequencing the actinomycin (acm) biosynthetic gene cluster of Streptomyces antibioticus IMRU 3720, which produces actinomycin X (Acm X), revealed 20 genes organized into a highly similar framework as in the bi-armed acm C biosynthetic gene cluster of Streptomyces chrysomallus but without an attached additional extra arm of orthologues as in the latter. Curiously, the extra arm of the S. chrysomallus gene cluster turned out to perfectly match the single arm of the S. antibioticus gene cluster in the same order of orthologues including the the presence of two pseudogenes, scacmM and scacmN, encoding a cytochrome P450 and its ferredoxin, respectively. Orthologues of the latter genes were both missing in the principal arm of the S. chrysomallus acm C gene cluster. All orthologues of the extra arm showed a G +C-contents different from that of their counterparts in the principal arm. Moreover, the similarities of translation products from the extra arm were all higher to the corresponding translation products of orthologue genes from the S. antibioticus acm X gene cluster than to those encoded by the principal arm of their own gene cluster. This suggests that the duplicated structure of the S. chrysomallus acm C biosynthetic gene cluster evolved from previous fusion between two one-armed acm gene clusters each from a different genetic background. However, while scacmM and scacmN in the extra arm of the S. chrysomallus acm C gene cluster are mutated and therefore are non-functional, their orthologues saacmM and saacmN in the S. antibioticus acm C gene cluster show no defects seemingly encoding active enzymes with functions specific for Acm X biosynthesis. Both acm biosynthetic gene clusters lack a kynurenine-3-monooxygenase gene necessary for biosynthesis of 3-hydroxy-4-methylanthranilic acid, the building block of the Acm chromophore, which suggests participation of a genome-encoded relevant monooxygenase during Acm biosynthesis in both S. chrysomallus and S

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters

KAUST Repository

Othoum, Ghofran K; Bougouffa, Salim; Razali, Rozaimi; Bokhari, Ameerah; Alamoudi, Soha; Antunes, André ; Gao, Xin; Hoehndorf, Robert; Arold, Stefan T.; Gojobori, Takashi; Hirt, Heribert; Mijakovic, Ivan; Bajic, Vladimir B.; Lafi, Feras Fawzi; Essack, Magbubah

2018-01-01

are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked

Specialization can drive the evolution of modularity.

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Carlos Espinosa-Soto

2010-03-01

Full Text Available Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations.

Vanillin biosynthetic pathways in plants.

Science.gov (United States)

Kundu, Anish

2017-06-01

The present review compiles the up-to-date knowledge on vanillin biosynthesis in plant systems to focus principally on the enzymatic reactions of in planta vanillin biosynthetic pathway and to find out its impact and prospect in future research in this field. Vanillin, a very popular flavouring compound, is widely used throughout the world. The principal natural resource of vanillin is the cured vanilla pods. Due to the high demand of vanillin as a flavouring agent, it is necessary to explore its biosynthetic enzymes and genes, so that improvement in its commercial production can be achieved through metabolic engineering. In spite of significant advancement in elucidating vanillin biosynthetic pathway in the last two decades, no conclusive demonstration had been reported yet for plant system. Several biosynthetic enzymes have been worked upon but divergences in published reports, particularly in characterizing the crucial biochemical steps of vanillin biosynthesis, such as side-chain shortening, methylation, and glucoside formation and have created a space for discussion. Recently, published reviews on vanillin biosynthesis have focused mainly on the biotechnological approaches and bioconversion in microbial systems. This review, however, aims to compile in brief the overall vanillin biosynthetic route and present a comparative as well as comprehensive description of enzymes involved in the pathway in Vanilla planifolia and other plants. Special emphasis has been given on the key enzymatic biochemical reactions that have been investigated extensively. Finally, the present standpoint and future prospects have been highlighted.

Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

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LJUBICA GAVRILOVIC

2013-09-01

Full Text Available ABSTRACT Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase and cyclic adenosine monophosphate response element-binding (CREB in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

Biosynthetic Pathways of Ergot Alkaloids

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Nina Gerhards

2014-12-01

Full Text Available Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines. All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine. Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.

Phenylpropanoids accumulation in eggplant fruit: characterization of biosynthetic genes and regulation by a MYB transcription factor

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Teresa eDocimo

2016-01-01

Full Text Available Phenylpropanoids are major secondary metabolites in eggplant (Solanum melongena fruits. Chlorogenic acid (CGA accounts for 70 to 90% of total phenolics in flesh tissues, while anthocyanins are mainly present in the fruit skin. As a contribution to the understanding of the peculiar accumulation of these health-promoting metabolites in eggplant, we report on metabolite abundance, regulation of CGA and anthocyanin biosynthesis, and characterization of candidate CGA biosynthetic genes in S. melongena.Higher contents of CGA, Delphinidin 3-rutinoside and rutin were found in eggplant fruits compared to other tissues, associated to an elevated transcript abundance of structural genes such as PAL, HQT, DFR and ANS, suggesting that active in situ biosynthesis contributes to anthocyanin and CGA accumulation in fruit tissues. Putative orthologs of the two CGA biosynthetic genes PAL and HQT, as well as a variant of a MYB1 transcription factor showing identity with group 6 MYBs, were isolated from an Occidental S. melongena traditional variety and demonstrated to differ from published sequences from Asiatic varieties.In silico analysis of the isolated SmPAL1, SmHQT1, SmANS, and SmMyb1 promoters revealed the presence of several Myb regulatory elements for the biosynthetic genes and unique elements for the TF, suggesting its involvement in other physiological roles beside phenylpropanoid biosynthesis regulation.Transient overexpression in Nicotiana benthamiana leaves of SmMyb1 and of a C-terminal SmMyb1 truncated form (SmMyb1Δ9 resulted in anthocyanin accumulation only of SmMyb1 agro-infiltrated leaves. A yeast two-hybrid assay confirmed the interaction of both SmMyb1 and SmMyb1Δ9 with an anthocyanin-related potato bHLH1 TF. Interestingly, a doubled amount of CGA was detected in both SmMyb1 and SmMyb1Δ9 agro-infiltrated leaves, thus suggesting that the N-terminal region of SmMyb1 is sufficient to activate its synthesis. These data suggest that a deletion of

Heterologous Expression of the Oxytetracycline Biosynthetic Pathway in Myxococcus xanthus▿

Science.gov (United States)

Stevens, D. Cole; Henry, Michael R.; Murphy, Kimberly A.; Boddy, Christopher N.

2010-01-01

New natural products for drug discovery may be accessed by heterologous expression of bacterial biosynthetic pathways in metagenomic DNA libraries. However, a “universal” host is needed for this experiment. Herein, we show that Myxococcus xanthus is a potential “universal” host for heterologous expression of polyketide biosynthetic gene clusters. PMID:20208031

Differential hexosamine biosynthetic pathway gene expression with type 2 diabetes

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Megan Coomer

2014-01-01

Full Text Available The hexosamine biosynthetic pathway (HBP culminates in the attachment of O-linked β-N-acetylglucosamine (O-GlcNAc onto serine/threonine residues of target proteins. The HBP is regulated by several modulators, i.e. O-linked β-N-acetylglucosaminyl transferase (OGT and β-N-acetylglucosaminidase (OGA catalyze the addition and removal of O-GlcNAc moieties, respectively; while flux is controlled by the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFPT, transcribed by two genes, GFPT1 and GFPT2. Since increased HBP flux is glucose-responsive and linked to insulin resistance/type 2 diabetes onset, we hypothesized that diabetic individuals exhibit differential expression of HBP regulatory genes. Volunteers (n = 60; n = 20 Mixed Ancestry, n = 40 Caucasian were recruited from Stellenbosch and Paarl (Western Cape, South Africa and classified as control, pre- or diabetic according to fasting plasma glucose and HbA1c levels, respectively. RNA was purified from leukocytes isolated from collected blood samples and OGT, OGA, GFPT1 and GFPT2 expressions determined by quantitative real-time PCR. The data reveal lower OGA expression in diabetic individuals (P < 0.01, while pre- and diabetic subjects displayed attenuated OGT expression vs. controls (P < 0.01 and P < 0.001, respectively. Moreover, GFPT2 expression decreased in pre- and diabetic Caucasians vs. controls (P < 0.05 and P < 0.01, respectively. We also found ethnic differences, i.e. Mixed Ancestry individuals exhibited a 2.4-fold increase in GFPT2 expression vs. Caucasians, despite diagnosis (P < 0.01. Gene expression of HBP regulators differs between diabetic and non-diabetic individuals, together with distinct ethnic-specific gene profiles. Thus differential HBP gene regulation may offer diagnostic utility and provide candidate susceptibility genes for different ethnic groupings.

Development of a gene cloning system in a fast-growing and moderately thermophilic Streptomyces species and heterologous expression of Streptomyces antibiotic biosynthetic gene clusters

Science.gov (United States)

2011-01-01

Background Streptomyces species are a major source of antibiotics. They usually grow slowly at their optimal temperature and fermentation of industrial strains in a large scale often takes a long time, consuming more energy and materials than some other bacterial industrial strains (e.g., E. coli and Bacillus). Most thermophilic Streptomyces species grow fast, but no gene cloning systems have been developed in such strains. Results We report here the isolation of 41 fast-growing (about twice the rate of S. coelicolor), moderately thermophilic (growing at both 30°C and 50°C) Streptomyces strains, detection of one linear and three circular plasmids in them, and sequencing of a 6996-bp plasmid, pTSC1, from one of them. pTSC1-derived pCWH1 could replicate in both thermophilic and mesophilic Streptomyces strains. On the other hand, several Streptomyces replicons function in thermophilic Streptomyces species. By examining ten well-sporulating strains, we found two promising cloning hosts, 2C and 4F. A gene cloning system was established by using the two strains. The actinorhodin and anthramycin biosynthetic gene clusters from mesophilic S. coelicolor A3(2) and thermophilic S. refuineus were heterologously expressed in one of the hosts. Conclusions We have developed a gene cloning and expression system in a fast-growing and moderately thermophilic Streptomyces species. Although just a few plasmids and one antibiotic biosynthetic gene cluster from mesophilic Streptomyces were successfully expressed in thermophilic Streptomyces species, we expect that by utilizing thermophilic Streptomyces-specific promoters, more genes and especially antibiotic genes clusters of mesophilic Streptomyces should be heterologously expressed. PMID:22032628

An indigoidine biosynthetic gene cluster from Streptomyces chromofuscus ATCC 49982 contains an unusual IndB homologue.

Science.gov (United States)

Yu, Dayu; Xu, Fuchao; Valiente, Jonathan; Wang, Siyuan; Zhan, Jixun

2013-01-01

A putative indigoidine biosynthetic gene cluster was located in the genome of Streptomyces chromofuscus ATCC 49982. The silent 9.4-kb gene cluster consists of five open reading frames, named orf1, Sc-indC, Sc-indA, Sc-indB, and orf2, respectively. Sc-IndC was functionally characterized as an indigoidine synthase through heterologous expression of the enzyme in both Streptomyces coelicolor CH999 and Escherichia coli BAP1. The yield of indigoidine in E. coli BAP1 reached 2.78 g/l under the optimized conditions. The predicted protein product of Sc-indB is unusual and much larger than any other reported IndB-like protein. The N-terminal portion of this enzyme resembles IdgB and the C-terminal portion is a hypothetical protein. Sc-IndA and/or Sc-IndB were co-expressed with Sc-IndC in E. coli BAP1, which demonstrated the involvement of Sc-IndB, but not Sc-IndA, in the biosynthetic pathway of indigoidine. The yield of indigoidine was dramatically increased by 41.4 % (3.93 g/l) when Sc-IndB was co-expressed with Sc-IndC in E. coli BAP1. Indigoidine is more stable at low temperatures.

Functional characterization of KanP, a methyltransferase from the kanamycin biosynthetic gene cluster of Streptomyces kanamyceticus.

Science.gov (United States)

Nepal, Keshav Kumar; Yoo, Jin Cheol; Sohng, Jae Kyung

2010-09-20

KanP, a putative methyltransferase, is located in the kanamycin biosynthetic gene cluster of Streptomyces kanamyceticus ATCC12853. Amino acid sequence analysis of KanP revealed the presence of S-adenosyl-L-methionine binding motifs, which are present in other O-methyltransferases. The kanP gene was expressed in Escherichia coli BL21 (DE3) to generate the E. coli KANP recombinant strain. The conversion of external quercetin to methylated quercetin in the culture extract of E. coli KANP proved the function of kanP as S-adenosyl-L-methionine-dependent methyltransferase. This is the first report concerning the identification of an O-methyltransferase gene from the kanamycin gene cluster. The resistant activity assay and RT-PCR analysis demonstrated the leeway for obtaining methylated kanamycin derivatives from the wild-type strain of kanamycin producer. 2009 Elsevier GmbH. All rights reserved.

Rational design of modular circuits for gene transcription: A test of the bottom-up approach

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Giordano Emanuele

2010-11-01

Full Text Available Abstract Background Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. Results We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. Conclusions This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.

In planta functions of cytochrome P450 monooxygenase genes in the phytocassane biosynthetic gene cluster on rice chromosome 2.

Science.gov (United States)

Ye, Zhongfeng; Yamazaki, Kohei; Minoda, Hiromi; Miyamoto, Koji; Miyazaki, Sho; Kawaide, Hiroshi; Yajima, Arata; Nojiri, Hideaki; Yamane, Hisakazu; Okada, Kazunori

2018-06-01

In response to environmental stressors such as blast fungal infections, rice produces phytoalexins, an antimicrobial diterpenoid compound. Together with momilactones, phytocassanes are among the major diterpenoid phytoalexins. The biosynthetic genes of diterpenoid phytoalexin are organized on the chromosome in functional gene clusters, comprising diterpene cyclase, dehydrogenase, and cytochrome P450 monooxygenase genes. Their functions have been studied extensively using in vitro enzyme assay systems. Specifically, P450 genes (CYP71Z6, Z7; CYP76M5, M6, M7, M8) on rice chromosome 2 have multifunctional activities associated with ent-copalyl diphosphate-related diterpene hydrocarbons, but the in planta contribution of these genes to diterpenoid phytoalexin production remains unknown. Here, we characterized cyp71z7 T-DNA mutant and CYP76M7/M8 RNAi lines to find that potential phytoalexin intermediates accumulated in these P450-suppressed rice plants. The results suggested that in planta, CYP71Z7 is responsible for C2-hydroxylation of phytocassanes and that CYP76M7/M8 is involved in C11α-hydroxylation of 3-hydroxy-cassadiene. Based on these results, we proposed potential routes of phytocassane biosynthesis in planta.

Expression of ethylene biosynthetic and receptor genes in rose floral tissues during ethylene-enhanced flower opening

OpenAIRE

Xue, Jingqi; Li, Yunhui; Tan, Hui; Yang, Feng; Ma, Nan; Gao, Junping

2008-01-01

Ethylene production, as well as the expression of ethylene biosynthetic (Rh-ACS1?4 and Rh-ACO1) and receptor (Rh-ETR1?5) genes, was determined in five different floral tissues (sepals, petals, stamens, gynoecia, and receptacles) of cut rose (Rosa hybrida cv. Samantha upon treatment with ethylene or the ethylene inhibitor 1-methylcyclopropene (1-MCP). Ethylene-enhanced ethylene production occurred only in gynoecia, petals, and receptacles, with gynoecia showing the greatest enhancement in the ...

Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria.

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Dittmann, Elke; Gugger, Muriel; Sivonen, Kaarina; Fewer, David P

2015-10-01

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms. Copyright © 2015. Published by Elsevier Ltd.

Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria.

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Cirillo, J D; Weisbrod, T R; Banerjee, A; Bloom, B R; Jacobs, W R

1994-07-01

The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.

Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

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Adam M Wentzell

2007-09-01

Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

Comparative modular analysis of gene expression in vertebrate organs

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Piasecka Barbara

2012-03-01

Full Text Available Abstract Background The degree of conservation of gene expression between homologous organs largely remains an open question. Several recent studies reported some evidence in favor of such conservation. Most studies compute organs' similarity across all orthologous genes, whereas the expression level of many genes are not informative about organ specificity. Results Here, we use a modularization algorithm to overcome this limitation through the identification of inter-species co-modules of organs and genes. We identify such co-modules using mouse and human microarray expression data. They are functionally coherent both in terms of genes and of organs from both organisms. We show that a large proportion of genes belonging to the same co-module are orthologous between mouse and human. Moreover, their zebrafish orthologs also tend to be expressed in the corresponding homologous organs. Notable exceptions to the general pattern of conservation are the testis and the olfactory bulb. Interestingly, some co-modules consist of single organs, while others combine several functionally related organs. For instance, amygdala, cerebral cortex, hypothalamus and spinal cord form a clearly discernible unit of expression, both in mouse and human. Conclusions Our study provides a new framework for comparative analysis which will be applicable also to other sets of large-scale phenotypic data collected across different species.

Comparative modular analysis of gene expression in vertebrate organs.

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Piasecka, Barbara; Kutalik, Zoltán; Roux, Julien; Bergmann, Sven; Robinson-Rechavi, Marc

2012-03-29

The degree of conservation of gene expression between homologous organs largely remains an open question. Several recent studies reported some evidence in favor of such conservation. Most studies compute organs' similarity across all orthologous genes, whereas the expression level of many genes are not informative about organ specificity. Here, we use a modularization algorithm to overcome this limitation through the identification of inter-species co-modules of organs and genes. We identify such co-modules using mouse and human microarray expression data. They are functionally coherent both in terms of genes and of organs from both organisms. We show that a large proportion of genes belonging to the same co-module are orthologous between mouse and human. Moreover, their zebrafish orthologs also tend to be expressed in the corresponding homologous organs. Notable exceptions to the general pattern of conservation are the testis and the olfactory bulb. Interestingly, some co-modules consist of single organs, while others combine several functionally related organs. For instance, amygdala, cerebral cortex, hypothalamus and spinal cord form a clearly discernible unit of expression, both in mouse and human. Our study provides a new framework for comparative analysis which will be applicable also to other sets of large-scale phenotypic data collected across different species.

Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis.

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Lin, Shan; Liu, Zhi-Qiang; Baker, Peter James; Yi, Ming; Wu, Hui; Xu, Feng; Teng, Yi; Zheng, Yu-Guo

2016-11-01

The addition of various sulfates for enhanced cordyceps polysaccharide (CP) production in submerged cultivation of H. sinensis was investigated, and manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day (d) was investigated as the optimal adding condition, and the CP production reached optimum with 5.33%, increasing by 93.3% compared with the control. Furthermore, the consumption of three main precursors of CP was studied over cultivation under two conditions. Intracellular mannose content decreased by 43.1% throughout 6days cultivation, which corresponded to CP accumulation rate sharply increased from 0 d to 6 d, and mannose was considered as the most preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway was constructed and verified for the first time in H. sinensis, which constituted the important part of CP biosynthesis, and transcriptional levels of the biosynthetic genes were studied. Transcriptional level of gene cpsA was significantly up-regulated 5.35-fold and it was a key gene involved both in mannose and CP biosynthesis. This study demonstrated that manganese sulfate addition is an efficient and simple way to improve CP production. Transcriptional analysis based on biosynthetic pathway was helpful to find key genes and better understand CP biosynthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Does habitat variability really promote metabolic network modularity?

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Takemoto, Kazuhiro

2013-01-01

The hypothesis that variability in natural habitats promotes modular organization is widely accepted for cellular networks. However, results of some data analyses and theoretical studies have begun to cast doubt on the impact of habitat variability on modularity in metabolic networks. Therefore, we re-evaluated this hypothesis using statistical data analysis and current metabolic information. We were unable to conclude that an increase in modularity was the result of habitat variability. Although horizontal gene transfer was also considered because it may contribute for survival in a variety of environments, closely related to habitat variability, and is known to be positively correlated with network modularity, such a positive correlation was not concluded in the latest version of metabolic networks. Furthermore, we demonstrated that the previously observed increase in network modularity due to habitat variability and horizontal gene transfer was probably due to a lack of available data on metabolic reactions. Instead, we determined that modularity in metabolic networks is dependent on species growth conditions. These results may not entirely discount the impact of habitat variability and horizontal gene transfer. Rather, they highlight the need for a more suitable definition of habitat variability and a more careful examination of relationships of the network modularity with horizontal gene transfer, habitats, and environments.

Cloning, reassembling and integration of the entire nikkomycin biosynthetic gene cluster into Streptomyces ansochromogenes lead to an improved nikkomycin production

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Yang Haihua

2010-01-01

Full Text Available Abstract Background Nikkomycins are a group of peptidyl nucleoside antibiotics produced by Streptomyces ansochromogenes. They are competitive inhibitors of chitin synthase and show potent fungicidal, insecticidal, and acaricidal activities. Nikkomycin X and Z are the main components produced by S. ansochromogenes. Generation of a high-producing strain is crucial to scale up nikkomycins production for further clinical trials. Results To increase the yields of nikkomycins, an additional copy of nikkomycin biosynthetic gene cluster (35 kb was introduced into nikkomycin producing strain, S. ansochromogenes 7100. The gene cluster was first reassembled into an integrative plasmid by Red/ET technology combining with classic cloning methods and then the resulting plasmid(pNIKwas introduced into S. ansochromogenes by conjugal transfer. Introduction of pNIK led to enhanced production of nikkomycins (880 mg L-1, 4 -fold nikkomycin X and 210 mg L-1, 1.8-fold nikkomycin Z in the resulting exconjugants comparing with the parent strain (220 mg L-1 nikkomycin X and 120 mg L-1 nikkomycin Z. The exconjugants are genetically stable in the absence of antibiotic resistance selection pressure. Conclusion A high nikkomycins producing strain (1100 mg L-1 nikkomycins was obtained by introduction of an extra nikkomycin biosynthetic gene cluster into the genome of S. ansochromogenes. The strategies presented here could be applicable to other bacteria to improve the yields of secondary metabolites.

Detection of biosynthetic gene and phytohormone production by endophytic actinobacteria associated with Solanum lycopersicum and their plant-growth-promoting effect.

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Passari, Ajit Kumar; Chandra, Preeti; Zothanpuia; Mishra, Vineet Kumar; Leo, Vincent Vineeth; Gupta, Vijai Kumar; Kumar, Brijesh; Singh, Bhim Pratap

2016-10-01

In the present study, fifteen endophytic actinobacterial isolates recovered from Solanum lycopersicum were studied for their antagonistic potential and plant-growth-promoting (PGP) traits. Among them, eight isolates showed significant antagonistic and PGP traits, identified by amplification of the 16S rRNA gene. Isolate number DBT204, identified as Streptomyces sp., showed multiple PGP traits tested in planta and improved a range of growth parameters in seedlings of chili (Capsicum annuum L.) and tomato (S. lycopersicum L.). Further, genes of indole acetic acid (iaaM) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase (acdS) were successively amplified from five strains. Six antibiotics (trimethoprim, fluconazole, chloramphenicol, nalidixic acid, rifampicin and streptomycin) and two phytohormones [indole acetic acid (IAA) and kinetin (KI)] were detected and quantified in Streptomyces sp. strain DBT204 using UPLC-ESI-MS/MS. The study indicates the potential of these PGP strains for production of phytohormones and shows the presence of biosynthetic genes responsible for production of secondary metabolites. It is the first report showing production of phytohormones (IAA and KI) by endophytic actinobacteria having PGP and biosynthetic potential. We propose Streptomyces sp. strain DBT204 for inoculums production and development of biofertilizers for enhancing growth of chili and tomato seedlings. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

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Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

2017-06-01

The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Identification of an unusual type II thioesterase in the dithiolopyrrolone antibiotics biosynthetic pathway

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Zhai, Ying; Bai, Silei; Liu, Jingjing; Yang, Liyuan [National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Han, Li; Huang, Xueshi [Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819 (China); He, Jing, E-mail: hejingjj@mail.hzau.edu.cn [National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China)

2016-04-22

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-frame gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. - Highlights: • Cloning of the aureothricin biosynthetic gene cluster from Streptomyces thioluteus DSM 40027. • Identification of the aureothricin gene cluster by heterologous expression and in-frame gene deletion. • The heterogenetic thioesterase HlmK significantly improved dithiolopyrrolones production of the aureothricin gene cluster. • Identification of HlmK as an unusual type II thioesterase.

Identification of an unusual type II thioesterase in the dithiolopyrrolone antibiotics biosynthetic pathway

International Nuclear Information System (INIS)

Zhai, Ying; Bai, Silei; Liu, Jingjing; Yang, Liyuan; Han, Li; Huang, Xueshi; He, Jing

2016-01-01

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-frame gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. - Highlights: • Cloning of the aureothricin biosynthetic gene cluster from Streptomyces thioluteus DSM 40027. • Identification of the aureothricin gene cluster by heterologous expression and in-frame gene deletion. • The heterogenetic thioesterase HlmK significantly improved dithiolopyrrolones production of the aureothricin gene cluster. • Identification of HlmK as an unusual type II thioesterase.

VIGS approach reveals the modulation of anthocyanin biosynthetic genes by CaMYB in Chili pepper leaves

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zhen ezhang

2015-07-01

Full Text Available The purple coloration of pepper leaves arises from the accumulation of anthocyanin. Three regulatory and 12 structural genes have been characterized for their involvement in the anthocyanin biosynthesis. Examination of the abundance of these genes in leaves showed that the majority of them differed between anthocyanin pigmented line Z1 and non-pigmented line A3. Silencing of the R2R3-MYB transcription factor CaMYB in pepper leaves of Z1 resulted in the loss of anthocyanin accumulation. Moreover, the expression of multiple genes was altered in the silenced leaves. The expression of MYC was significantly lower in CaMYB-silenced leaves, whereas WD40 showed the opposite pattern. Most structural genes including CHS, CHI, F3H, F3’5’H, DFR, ANS, UFGT, ANP and GST were repressed in CaMYB-silenced foliage with the exception of PAL, C4H and 4CL. These results indicated that MYB plays an important role in the regulation of anthocyanin biosynthetic related genes. Besides CaMYB silenced leaves rendered more sporulation of Phytophthora capsici Leonian indicating that CaMYB might be involved in the defense response to pathogens.

Evolutionary systems biology of amino acid biosynthetic cost in yeast.

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Michael D Barton

2010-08-01

Full Text Available Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental

Biosynthetic Pathway and Metabolic Engineering of Plant Dihydrochalcones.

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Ibdah, Mwafaq; Martens, Stefan; Gang, David R

2018-03-14

Dihydrochalcones are plant natural products containing the phenylpropanoid backbone and derived from the plant-specific phenylpropanoid pathway. Dihydrochalcone compounds are important in plant growth and response to stresses and, thus, can have large impacts on agricultural activity. In recent years, these compounds have also received increased attention from the biomedical community for their potential as anticancer treatments and other benefits for human health. However, they are typically produced at relatively low levels in plants. Therefore, an attractive alternative is to express the plant biosynthetic pathway genes in microbial hosts and to engineer the metabolic pathway/host to improve the production of these metabolites. In the present review, we discuss in detail the functions of genes and enzymes involved in the biosynthetic pathway of the dihydrochalcones and the recent strategies and achievements used in the reconstruction of multi-enzyme pathways in microorganisms in efforts to be able to attain higher amounts of desired dihydrochalcones.

Variation in the fumonisin biosynthetic gene cluster in fumonisin-producing and nonproducing black aspergilli.

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Susca, Antonia; Proctor, Robert H; Butchko, Robert A E; Haidukowski, Miriam; Stea, Gaetano; Logrieco, Antonio; Moretti, Antonio

2014-12-01

The ability to produce fumonisin mycotoxins varies among members of the black aspergilli. Previously, analyses of selected genes in the fumonisin biosynthetic gene (fum) cluster in black aspergilli from California grapes indicated that fumonisin-nonproducing isolates of Aspergillus welwitschiae lack six fum genes, but nonproducing isolates of Aspergillus niger do not. In the current study, analyses of black aspergilli from grapes from the Mediterranean Basin indicate that the genomic context of the fum cluster is the same in isolates of A. niger and A. welwitschiae regardless of fumonisin-production ability and that full-length clusters occur in producing isolates of both species and nonproducing isolates of A. niger. In contrast, the cluster has undergone an eight-gene deletion in fumonisin-nonproducing isolates of A. welwitschiae. Phylogenetic analyses suggest each species consists of a mixed population of fumonisin-producing and nonproducing individuals, and that existence of both production phenotypes may provide a selective advantage to these species. Differences in gene content of fum cluster homologues and phylogenetic relationships of fum genes suggest that the mutation(s) responsible for the nonproduction phenotype differs, and therefore arose independently, in the two species. Partial fum cluster homologues were also identified in genome sequences of four other black Aspergillus species. Gene content of these partial clusters and phylogenetic relationships of fum sequences indicate that non-random partial deletion of the cluster has occurred multiple times among the species. This in turn suggests that an intact cluster and fumonisin production were once more widespread among black aspergilli. Copyright © 2014 Elsevier Inc. All rights reserved.

Modular optimization of heterologous pathways for de novo synthesis of (2S-naringenin in Escherichia coli.

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Junjun Wu

Full Text Available Due to increasing concerns about food safety and environmental issues, bio-based production of flavonoids from safe, inexpensive, and renewable substrates is increasingly attracting attention. Here, the complete biosynthetic pathway, consisting of 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS, chorismate mutase/prephenate dehydrogenase (CM/PDH, tyrosine ammonia lyase (TAL, 4-coumarate:CoA ligase (4CL, chalcone synthase (CHS, chalcone isomerase (CHI, malonate synthetase, and malonate carrier protein, was constructed using pre-made modules to overproduce (2S-naringenin from D-glucose. Modular pathway engineering strategies were applied to the production of the flavonoid precursor (2S-naringenin from L-tyrosine to investigate the metabolic space for efficient conversion. Modular expression was combinatorially tuned by modifying plasmid gene copy numbers and promoter strengths to identify an optimally balanced pathway. Furthermore, a new modular pathway from D-glucose to L-tyrosine was assembled and re-optimized with the identified optimal modules to enable de novo synthesis of (2S-naringenin. Once this metabolic balance was achieved, the optimum strain was capable of producing 100.64 mg/L (2S-naringenin directly from D-glucose, which is the highest production titer from D-glucose in Escherichia coli. The fermentation system described here paves the way for the development of an economical process for microbial production of flavonoids.

Description of a Riboflavin Biosynthetic Gene Variant Prevalent in the Phylum Proteobacteria

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Brutinel, Evan D.; Dean, Antony M.

2013-01-01

Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide, which are cofactors essential for a host of intracellular redox reactions. Microorganisms synthesize flavins de novo to fulfill nutritional requirements, but it is becoming increasingly clear that flavins play a wider role in cellular physiology than was previously appreciated. Flavins mediate diverse processes beyond the cytoplasmic membrane, including iron acquisition, extracellular respiration, and interspecies interactions. While investigating the regulation of flavin electron shuttle biosynthesis in the Gram-negative gammaproteobacterium Shewanella oneidensis, we discovered that a riboflavin biosynthetic gene (ribBA) annotated as encoding a bifunctional 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase/GTP cyclohydrolase II does not possess both functions. The novel gene, renamed ribBX here, encodes an amino-terminal DHBP synthase domain. The carboxy-terminal end of RibBX not only lacks GTP cyclohydrolase II activity but also has evolved a different function altogether in S. oneidensis, regulating the activity of the DHBP synthase domain. Phylogenetic analysis revealed that the misannotation of ribBX as ribBA is rampant throughout the phylum Proteobacteria (40% of 2,173 annotated ribBA genes) and that ribBX emerged early in the evolution of this group of microorganisms. We examined the functionality of representative ribBX genes from Beta-, Gamma-, and Epsilonproteobacteria and found that, consistent with sequence-based predictions, the encoded GTP cyclohydrolase II domains lack catalytic activity. The persistence of ribBX in the genomes of so many phylogenetically divergent bacterial species lends weight to the argument that ribBX has evolved a function which lends a selective advantage to the host. PMID:24097946

Glutamic acid promotes monacolin K production and monacolin K biosynthetic gene cluster expression in Monascus.

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Zhang, Chan; Liang, Jian; Yang, Le; Chai, Shiyuan; Zhang, Chenxi; Sun, Baoguo; Wang, Chengtao

2017-12-01

This study investigated the effects of glutamic acid on production of monacolin K and expression of the monacolin K biosynthetic gene cluster. When Monascus M1 was grown in glutamic medium instead of in the original medium, monacolin K production increased from 48.4 to 215.4 mg l -1 , monacolin K production increased by 3.5 times. Glutamic acid enhanced monacolin K production by upregulating the expression of mokB-mokI; on day 8, the expression level of mokA tended to decrease by Reverse Transcription-polymerase Chain Reaction. Our findings demonstrated that mokA was not a key gene responsible for the quantity of monacolin K production in the presence of glutamic acid. Observation of Monascus mycelium morphology using Scanning Electron Microscope showed glutamic acid significantly increased the content of Monascus mycelium, altered the permeability of Monascus mycelium, enhanced secretion of monacolin K from the cell, and reduced the monacolin K content in Monascus mycelium, thereby enhancing monacolin K production.

Output ordering and prioritisation system (OOPS): ranking biosynthetic gene clusters to enhance bioactive metabolite discovery.

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Peña, Alejandro; Del Carratore, Francesco; Cummings, Matthew; Takano, Eriko; Breitling, Rainer

2017-12-18

The rapid increase of publicly available microbial genome sequences has highlighted the presence of hundreds of thousands of biosynthetic gene clusters (BGCs) encoding valuable secondary metabolites. The experimental characterization of new BGCs is extremely laborious and struggles to keep pace with the in silico identification of potential BGCs. Therefore, the prioritisation of promising candidates among computationally predicted BGCs represents a pressing need. Here, we propose an output ordering and prioritisation system (OOPS) which helps sorting identified BGCs by a wide variety of custom-weighted biological and biochemical criteria in a flexible and user-friendly interface. OOPS facilitates a judicious prioritisation of BGCs using G+C content, coding sequence length, gene number, cluster self-similarity and codon bias parameters, as well as enabling the user to rank BGCs based upon BGC type, novelty, and taxonomic distribution. Effective prioritisation of BGCs will help to reduce experimental attrition rates and improve the breadth of bioactive metabolites characterized.

An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome

NARCIS (Netherlands)

Fox, J.E.; Bridgham, J.T.; Bovee, T.F.H.; Thornton, J.W.

2007-01-01

To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a

Modulation of flavonoid biosynthetic pathway genes and anthocyanins due to virus infection in grapevine (Vitis vinifera L. leaves

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Gutha Linga R

2010-08-01

Full Text Available Abstract Background Symptoms of grapevine leafroll disease (GLRD in red-fruited wine grape (Vitis vinifera L. cultivars consist of green veins and red and reddish-purple discoloration of inter-veinal areas of leaves. The reddish-purple color of symptomatic leaves may be due to the accumulation of anthocyanins and could reflect an up-regulation of genes involved in their biosynthesis. Results We examined six putative constitutively expressed genes, Ubiquitin, Actin, GAPDH, EF1-a, SAND and NAD5, for their potential as references for normalization of gene expression in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR. Using the geNorm program, a combination of two genes (Actin and NAD5 was identified as the stable set of reference genes for normalization of gene expression data obtained from grapevine leaves. By using gene-specific RT-qPCR in combination with a reliable normalization factor, we compared relative expression of the flavonoid biosynthetic pathway genes between leaves infected with Grapevine leafroll-associated virus 3 (GLRaV-3 and exhibiting GLRD symptoms and virus-free green leaves obtained from a red-fruited wine grape cultivar (cv. Merlot. The expression levels of these different genes ranged from two- to fifty-fold increase in virus-infected leaves. Among them, CHS3, F3'5'H, F3H1, LDOX, LAR1 and MybA1 showed greater than 10-fold increase suggesting that they were expressed at significantly higher levels in virus-infected symptomatic leaves. HPLC profiling of anthocyanins extracted from leaves indicated the presence of cyanidin-3-glucoside and malvidin-3-glucoside only in virus-infected symptomatic leaves. The results also showed 24% higher levels of flavonols in virus-infected symptomatic leaves than in virus-free green leaves, with quercetin followed by myricetin being the predominant compounds. Proanthocyanidins, estimated as total tannins by protein precipitation method, were 36% higher in virus

Identification and characterization of lbpA, an indigoidine biosynthetic gene in the γ-butyrolactone signaling system of Streptomyces lavendulae FRI-5.

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Pait, Ivy Grace Umadhay; Kitani, Shigeru; Kurniawan, Yohanes Novi; Asa, Maeda; Iwai, Takashi; Ikeda, Haruo; Nihira, Takuya

2017-10-01

Streptomyces lavendulae FRI-5 produces the blue pigment indigoidine and other secondary metabolites (d-cycloserine and nucleoside antibiotics). The production of these useful compounds is controlled by a signaling cascade mediated by the γ-butyrolactone autoregulator IM-2. Previously we revealed that the far regulatory island includes the IM-2 receptor, the IM-2 biosynthetic enzyme, and several transcriptional regulators, and that it contributes to the regulation of indigoidine production in response to the signaling molecule. Here, we found that the vicinity of the far regulatory island includes the putative gene cluster for the biosynthesis of indigoidine and unidentified compounds, and demonstrated that the expression of the gene cluster is under the control of the IM-2 regulatory system. Heterologous expression of lbpA, encoding a plausible nonribosomal peptide synthetase, in the versatile model host Streptomyces avermitilis SUKA22 led to indigoidine production, which was enhanced dramatically by feeding of the indigoidine precursor l-glutamine. These results confirmed that LbpA is an indigoidine biosynthetic enzyme in the IM-2 signaling cascade. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

In silico analysis and expression profiling of miRNAs targeting genes of steviol glycosides biosynthetic pathway and their relationship with steviol glycosides content in different tissues of Stevia rebaudiana.

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Saifi, Monica; Nasrullah, Nazima; Ahmad, Malik Mobeen; Ali, Athar; Khan, Jawaid A; Abdin, M Z

2015-09-01

miRNAs are emerging as potential regulators of the gene expression. Their proven promising role in regulating biosynthetic pathways related gene networks may hold the key to understand the genetic regulation of these pathways which may assist in selection and manipulation to get high performing plant genotypes with better secondary metabolites yields and increased biomass. miRNAs associated with genes of steviol glycosides biosynthetic pathway, however, have not been identified so far. In this study miRNAs targeting genes of steviol glycosides biosynthetic pathway were identified for the first time whose precursors were potentially generated from ESTs and nucleotide sequences of Stevia rebaudiana. Thereafter, stem-loop coupled real time PCR based expressions of these miRNAs in different tissues of Stevia rebaudiana were investigated and their relationship pattern was analysed with the expression levels of their target mRNAs as well as steviol glycoside contents. All the miRNAs investigated showed differential expressions in all the three tissues studied, viz. leaves, flowers and stems. Out of the eleven miRNAs validated, the expression levels of nine miRNAs (miR319a, miR319b, miR319c, miR319d, miR319e, miR319f, miR319h, miRstv_7, miRstv_9) were found to be inversely related, while expression levels of the two, i.e. miR319g and miRstv_11 on the contrary, showed direct relation with the expression levels of their target mRNAs and steviol glycoside contents in the leaves, flowers and stems. This study provides a platform for better understanding of the steviol glycosides biosynthetic pathway and these miRNAs can further be employed to manipulate the biosynthesis of these metabolites to enhance their contents and yield in S. rebaudiana. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Distribution of secondary metabolite biosynthetic gene clusters in 343 Fusarium genomes

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Fusarium consists of over 200 phylogenetically distinct species, many of which cause important crop diseases and/or produce mycotoxins and other secondary metabolites (SMs). Some fusaria also cause opportunistic infections in humans and other animals. To investigate the distribution of biosynthetic ...

A gene expression analysis of cell wall biosynthetic genes in Malus × domestica infected by ‘Candidatus Phytoplasma mali’

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Guerriero, Gea; Giorno, Filomena; Ciccotti, Anna Maria; Schmidt, Silvia; Baric, Sanja

2016-01-01

Apple proliferation (AP) represents a serious threat to several fruit-growing areas and is responsible for great economic losses. Several studies have highlighted the key role played by the cell wall in response to pathogen attack. The existence of a cell wall integrity signaling pathway which senses perturbations in the cell wall architecture upon abiotic/biotic stresses and activates specific defence responses has been widely demonstrated in plants. More recently a role played by cell wall-related genes has also been reported in plants infected by phytoplasmas. With the aim of shedding light on the cell wall response to AP disease in the economically relevant fruit-tree Malus × domestica Borkh., we investigated the expression of the cellulose (CesA) and callose synthase (CalS) genes in different organs (i.e., leaves, roots and branch phloem) of healthy and infected symptomatic outdoor-grown trees, sampled over the course of two time points (i.e., spring and autumn 2011), as well as in in vitro micropropagated control and infected plantlets. A strong up-regulation in the expression of cell wall biosynthetic genes was recorded in roots from infected trees. Secondary cell wall CesAs showed up-regulation in the phloem tissue from branches of infected plants, while either a down-regulation of some genes or no major changes were observed in the leaves. Micropropagated plantlets also showed an increase in cell wall-related genes and constitute a useful system for a general assessment of gene expression analysis upon phytoplasma infection. Finally, we also report the presence of several ‘knot’-like structures along the roots of infected apple trees and discuss the occurrence of this interesting phenotype in relation to the gene expression results and the modalities of phytoplasma diffusion. PMID:23086810

Secondary metabolism in Fusarium fujikuroi: strategies to unravel the function of biosynthetic pathways.

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Janevska, Slavica; Tudzynski, Bettina

2018-01-01

The fungus Fusarium fujikuroi causes bakanae disease of rice due to its ability to produce the plant hormones, the gibberellins. The fungus is also known for producing harmful mycotoxins (e.g., fusaric acid and fusarins) and pigments (e.g., bikaverin and fusarubins). However, for a long time, most of these well-known products could not be linked to biosynthetic gene clusters. Recent genome sequencing has revealed altogether 47 putative gene clusters. Most of them were orphan clusters for which the encoded natural product(s) were unknown. In this review, we describe the current status of our research on identification and functional characterizations of novel secondary metabolite gene clusters. We present several examples where linking known metabolites to the respective biosynthetic genes has been achieved and describe recent strategies and methods to access new natural products, e.g., by genetic manipulation of pathway-specific or global transcritption factors. In addition, we demonstrate that deletion and over-expression of histone-modifying genes is a powerful tool to activate silent gene clusters and to discover their products.

Saponin determination, expression analysis and functional characterization of saponin biosynthetic genes in Chenopodium quinoa leaves.

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Fiallos-Jurado, Jennifer; Pollier, Jacob; Moses, Tessa; Arendt, Philipp; Barriga-Medina, Noelia; Morillo, Eduardo; Arahana, Venancio; de Lourdes Torres, Maria; Goossens, Alain; Leon-Reyes, Antonio

2016-09-01

Quinoa (Chenopodium quinoa Willd.) is a highly nutritious pseudocereal with an outstanding protein, vitamin, mineral and nutraceutical content. The leaves, flowers and seed coat of quinoa contain triterpenoid saponins, which impart bitterness to the grain and make them unpalatable without postharvest removal of the saponins. In this study, we quantified saponin content in quinoa leaves from Ecuadorian sweet and bitter genotypes and assessed the expression of saponin biosynthetic genes in leaf samples elicited with methyl jasmonate. We found saponin accumulation in leaves after MeJA treatment in both ecotypes tested. As no reference genes were available to perform qPCR in quinoa, we mined publicly available RNA-Seq data for orthologs of 22 genes known to be stably expressed in Arabidopsis thaliana using geNorm, NormFinder and BestKeeper algorithms. The quinoa ortholog of At2g28390 (Monensin Sensitivity 1, MON1) was stably expressed and chosen as a suitable reference gene for qPCR analysis. Candidate saponin biosynthesis genes were screened in the quinoa RNA-Seq data and subsequent functional characterization in yeast led to the identification of CqbAS1, CqCYP716A78 and CqCYP716A79. These genes were found to be induced by MeJA, suggesting this phytohormone might also modulate saponin biosynthesis in quinoa leaves. Knowledge of the saponin biosynthesis and its regulation in quinoa may aid the further development of sweet cultivars that do not require postharvest processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway

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Liu, Qing; Manzano, David; Tanić, Nikola

2014-01-01

Parthenolide, the main bioactive compound of the medicinal plant feverfew (Tanacetum parthenium), is a promising anti-cancer drug. However, the biosynthetic pathway of parthenolide has not been elucidated yet. Here we report on the isolation and characterization of all the genes from feverfew tha...

Sequencing, physical organization and kinetic expression of the patulin biosynthetic gene cluster from Penicillium expansum

International Nuclear Information System (INIS)

Tannous, J.; El Khoury, R.; El Khoury, A.; Lteif, R.; Snini, S.; Lippi, Y.; Oswald, I.; Olivier, P.; Atoui, A.

2014-01-01

Patulin is a polyketide-derived mycotoxin produced by numerous filamentous fungi. Among them, Penicillium expansum is by far the most problematic species. This fungus is a destructive phytopathogen capable of growing on fruit, provoking the blue mold decay of apples and producing significant amounts of patulin. The biosynthetic pathway of this mycotoxin is chemically well-characterized, but its genetic bases remain largely unknown with only few characterized genes in less economic relevant species. The present study consisted of the identification and positional organization of the patulin gene cluster in P. expansum strain NRRL 35695. Several amplification reactions were performed with degenerative primers that were designed based on sequences from the orthologous genes available in other species. An improved genome Walking approach was used in order to sequence the remaining adjacent genes of the cluster. RACE-PCR was also carried out from mRNAs to determine the start and stop codons of the coding sequences. The patulin gene cluster in P. expansum consists of 15 genes in the following order: patH, patG, patF, patE, patD, patC, patB, patA, patM, patN, patO, patL, patI, patJ, and patK. These genes share 60–70% of identity with orthologous genes grouped differently, within a putative patulin cluster described in a non-producing strain of Aspergillus clavatus. The kinetics of patulin cluster genes expression was studied under patulin-permissive conditions (natural apple-based medium) and patulin-restrictive conditions (Eagle's minimal essential medium), and demonstrated a significant association between gene expression and patulin production. In conclusion, the sequence of the patulin cluster in P. expansum constitutes a key step for a better understanding of themechanisms leading to patulin production in this fungus. It will allow the role of each gene to be elucidated, and help to define strategies to reduce patulin production in apple-based products

Defining Modules, Modularity and Modularization

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Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

Dynamic and modular gene regulatory networks drive the development of gametogenesis.

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Che, Dongxue; Wang, Yang; Bai, Weiyang; Li, Leijie; Liu, Guiyou; Zhang, Liangcai; Zuo, Yongchun; Tao, Shiheng; Hua, Jinlian; Liao, Mingzhi

2017-07-01

Gametogenesis is a complex process, which includes mitosis and meiosis and results in the production of ovum and sperm. The development of gametogenesis is dynamic and needs many different genes to work synergistically, but it is lack of global perspective research about this process. In this study, we detected the dynamic process of gametogenesis from the perspective of systems biology based on protein-protein interaction networks (PPINs) and functional analysis. Results showed that gametogenesis genes have strong synergistic effects in PPINs within and between different phases during the development. Addition to the synergistic effects on molecular networks, gametogenesis genes showed functional consistency within and between different phases, which provides the further evidence about the dynamic process during the development of gametogenesis. At last, we detected and provided the core molecular modules of different phases about gametogenesis. The gametogenesis genes and related modules can be obtained from our Web site Gametogenesis Molecule Online (GMO, http://gametsonline.nwsuaflmz.com/index.php), which is freely accessible. GMO may be helpful for the reference and application of these genes and modules in the future identification of key genes about gametogenesis. Summary, this work provided a computational perspective and frame to the analysis of the gametogenesis dynamics and modularity in both human and mouse. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enrichment of provitamin A content in wheat (Triticum aestivum L.) by introduction of the bacterial carotenoid biosynthetic genes CrtB and CrtI.

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Wang, Cheng; Zeng, Jian; Li, Yin; Hu, Wei; Chen, Ling; Miao, Yingjie; Deng, Pengyi; Yuan, Cuihong; Ma, Cheng; Chen, Xi; Zang, Mingli; Wang, Qiong; Li, Kexiu; Chang, Junli; Wang, Yuesheng; Yang, Guangxiao; He, Guangyuan

2014-06-01

Carotenoid content is a primary determinant of wheat nutritional value and affects its end-use quality. Wheat grains contain very low carotenoid levels and trace amounts of provitamin A content. In order to enrich the carotenoid content in wheat grains, the bacterial phytoene synthase gene (CrtB) and carotene desaturase gene (CrtI) were transformed into the common wheat cultivar Bobwhite. Expression of CrtB or CrtI alone slightly increased the carotenoid content in the grains of transgenic wheat, while co-expression of both genes resulted in a darker red/yellow grain phenotype, accompanied by a total carotenoid content increase of approximately 8-fold achieving 4.76 μg g(-1) of seed dry weight, a β-carotene increase of 65-fold to 3.21 μg g(-1) of seed dry weight, and a provitamin A content (sum of α-carotene, β-carotene, and β-cryptoxanthin) increase of 76-fold to 3.82 μg g(-1) of seed dry weight. The high provitamin A content in the transgenic wheat was stably inherited over four generations. Quantitative PCR analysis revealed that enhancement of provitamin A content in transgenic wheat was also a result of the highly coordinated regulation of endogenous carotenoid biosynthetic genes, suggesting a metabolic feedback regulation in the wheat carotenoid biosynthetic pathway. These transgenic wheat lines are not only valuable for breeding wheat varieties with nutritional benefits for human health but also for understanding the mechanism regulating carotenoid biosynthesis in wheat endosperm. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Accumulation of Kaempferitrin and Expression of Phenyl-Propanoid Biosynthetic Genes in Kenaf (Hibiscus cannabinus

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Shicheng Zhao

2014-10-01

Full Text Available Kenaf (Hibiscus cannabinus is cultivated worldwide for its fiber; however, the medicinal properties of this plant are currently attracting increasing attention. In this study, we investigated the expression levels of genes involved in the biosynthesis of kaempferitrin, a compound with many biological functions, in different kenaf organs. We found that phenylalanine ammonia lyase (HcPAL was more highly expressed in stems than in other organs. Expression levels of cinnamate 4-hydroxylase (HcC4H and 4-coumarate-CoA ligase (Hc4CL were highest in mature leaves, followed by stems and young leaves, and lowest in roots and mature flowers. The expression of chalcone synthase (HcCHS, chalcone isomerase (HcCHI, and flavone 3-hydroxylase (HcF3H was highest in young flowers, whereas that of flavone synthase (HcFLS was highest in leaves. An analysis of kaempferitrin accumulation in the different organs of kenaf revealed that the accumulation of this compound was considerably higher (>10-fold in leaves than in other organs. On the basis of a comparison of kaempferitrin contents with the expression levels of different genes in different organs, we speculate that HcFLS plays an important regulatory role in the kaempferitrin biosynthetic pathway in kenaf.

Accumulation of kaempferitrin and expression of phenyl-propanoid biosynthetic genes in kenaf (Hibiscus cannabinus).

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Zhao, Shicheng; Li, Xiaohua; Cho, Dong Ha; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Park, Sang Un

2014-10-23

Kenaf (Hibiscus cannabinus) is cultivated worldwide for its fiber; however, the medicinal properties of this plant are currently attracting increasing attention. In this study, we investigated the expression levels of genes involved in the biosynthesis of kaempferitrin, a compound with many biological functions, in different kenaf organs. We found that phenylalanine ammonia lyase (HcPAL) was more highly expressed in stems than in other organs. Expression levels of cinnamate 4-hydroxylase (HcC4H) and 4-coumarate-CoA ligase (Hc4CL) were highest in mature leaves, followed by stems and young leaves, and lowest in roots and mature flowers. The expression of chalcone synthase (HcCHS), chalcone isomerase (HcCHI), and flavone 3-hydroxylase (HcF3H) was highest in young flowers, whereas that of flavone synthase (HcFLS) was highest in leaves. An analysis of kaempferitrin accumulation in the different organs of kenaf revealed that the accumulation of this compound was considerably higher (>10-fold) in leaves than in other organs. On the basis of a comparison of kaempferitrin contents with the expression levels of different genes in different organs, we speculate that HcFLS plays an important regulatory role in the kaempferitrin biosynthetic pathway in kenaf.

Cell wall composition and lignin biosynthetic gene expression along a developmental gradient in an Australian sugarcane cultivar

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William P. Bewg

2017-12-01

Full Text Available Sugarcane bagasse is an abundant source of lignocellulosic material for bioethanol production. Utilisation of bagasse for biofuel production would be environmentally and economically beneficial, but the recalcitrance of lignin continues to provide a challenge. Further understanding of lignin production in specific cultivars will provide a basis for modification of genomes for the production of phenotypes with improved processing characteristics. Here we evaluated the expression profile of lignin biosynthetic genes and the cell wall composition along a developmental gradient in KQ228 sugarcane. The expression levels of nine lignin biosynthesis genes were quantified in five stem sections of increasing maturity and in root tissue. Two distinct expression patterns were seen. The first saw highest gene expression in the youngest tissue, with expression decreasing as tissue matured. The second pattern saw little to no change in transcription levels across the developmental gradient. Cell wall compositional analysis of the stem sections showed total lignin content to be significantly higher in more mature tissue than in the youngest section assessed. There were no changes in structural carbohydrates across developmental sections. These gene expression and cell wall compositional patterns can be used, along with other work in grasses, to inform biotechnological approaches to crop improvement for lignocellulosic biofuel production.

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

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Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Modular design of synthetic gene circuits with biological parts and pools.

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Marchisio, Mario Andrea

2015-01-01

Synthetic gene circuits can be designed in an electronic fashion by displaying their basic components-Standard Biological Parts and Pools of molecules-on the computer screen and connecting them with hypothetical wires. This procedure, achieved by our add-on for the software ProMoT, was successfully applied to bacterial circuits. Recently, we have extended this design-methodology to eukaryotic cells. Here, highly complex components such as promoters and Pools of mRNA contain hundreds of species and reactions whose calculation demands a rule-based modeling approach. We showed how to build such complex modules via the joint employment of the software BioNetGen (rule-based modeling) and ProMoT (modularization). In this chapter, we illustrate how to utilize our computational tool for synthetic biology with the in silico implementation of a simple eukaryotic gene circuit that performs the logic AND operation.

Engineering modular polyketide synthases for production of biofuels and industrial chemicals.

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Cai, Wenlong; Zhang, Wenjun

2018-04-01

Polyketide synthases (PKSs) are one of the most profound biosynthetic factories for producing polyketides with diverse structures and biological activities. These enzymes have been historically studied and engineered to make un-natural polyketides for drug discovery, and have also recently been explored for synthesizing biofuels and industrial chemicals due to their versatility and customizability. Here, we review recent advances in the mechanistic understanding and engineering of modular PKSs for producing polyketide-derived chemicals, and provide perspectives on this relatively new application of PKSs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

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Liu, Zhi-Qiang; Zhang, Bo; Lin, Shan; Baker, Peter James; Chen, Mao-Sheng; Xue, Ya-Ping; Wu, Hui; Xu, Feng; Yuan, Shui-Jin; Teng, Yi; Wu, Ling-Fang

2017-01-01

To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis. PMID:29333435

Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species

DEFF Research Database (Denmark)

Nielsen, Jens Christian; Grijseels, Sietske; Prigent, Sylvain

2017-01-01

Filamentous fungi produce a wide range of bioactive compounds with important pharmaceutical applications, such as antibiotic penicillins and cholesterol-lowering statins. However, less attention has been paid to fungal secondary metabolites compared to those from bacteria. In this study, we...... sequenced the genomes of 9 Penicillium species and, together with 15 published genomes, we investigated the secondary metabolism of Penicillium and identified an immense, unexploited potential for producing secondary metabolites by this genus. A total of 1,317 putative biosynthetic gene clusters (BGCs) were......-referenced the predicted pathways with published data on the production of secondary metabolites and experimentally validated the production of antibiotic yanuthones in Penicillia and identified a previously undescribed compound from the yanuthone pathway. This study is the first genus-wide analysis of the genomic...

Seasonal alteration in amounts of lignans and their glucosides and gene expression of the relevant biosynthetic enzymes in the Forsythia suspense leaf.

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Morimoto, Kinuyo; Satake, Honoo

2013-01-01

Lignans of Forsythia spp. are essential components of various Chinese medicines and health diets. However, the seasonal alteration in lignan amounts and the gene expression profile of lignan-biosynthetic enzymes has yet to be investigated. In this study, we have assessed seasonal alteration in amounts of major lignans, such as pinoresinol, matairesinol, and arctigenin, and examined the gene expression profile of pinoresinol/lariciresinol reductase (PLR), pinoresinol-glucosylating enzyme (UGT71A18), and secoisolariciresinol dehydrogenase (SIRD) in the leaf of Forsythia suspense from April to November. All of the lignans in the leaf continuously increased from April to June, reached the maximal level in June, and then decreased. Ninety percent of pinoresinol and matairesinol was converted into glucosides, while approximately 50% of arctigenin was aglycone. PLR was stably expressed from April to August, whereas the PLR expression was not detected from September to November. In contrast, the UGT71A18 expression was found from August to November, but not from April to July. The SIRD expression was prominent from April to May, not detected in June to July, and then increased again from September to November. These expression profiles of the lignan-synthetic enzymes are largely compatible with the alteration in lignan contents. Furthermore, such seasonal lignan profiles are in good agreement with the fact that the Forsythia leaves for Chinese medicinal tea are harvested in June. This is the first report on seasonal alteration in lignans and the relevant biosynthetic enzyme genes in the leaf of Forsythia species.

Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

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Jungsuwadee Paiboon

2011-02-01

Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

Perturbations in the Photosynthetic Pigment Status Result in Photooxidation-Induced Crosstalk between Carotenoid and Porphyrin Biosynthetic Pathways

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Joon-Heum Park

2017-11-01

Full Text Available Possible crosstalk between the carotenoid and porphyrin biosynthetic pathways under photooxidative conditions was investigated by using their biosynthetic inhibitors, norflurazon (NF and oxyfluorfen (OF. High levels of protoporphyrin IX (Proto IX accumulated in rice plants treated with OF, whereas Proto IX decreased in plants treated with NF. Both NF and OF treatments resulted in greater decreases in MgProto IX, MgProto IX methyl ester, and protochlorophyllide. Activities and transcript levels of most porphyrin biosynthetic enzymes, particularly in the Mg-porphyrin branch, were greatly down-regulated in NF and OF plants. In contrast, the transcript levels of GSA, PPO1, and CHLD as well as FC2 and HO2 were up-regulated in NF-treated plants, while only moderate increases in FC2 and HO2 were observed in the early stage of OF treatment. Phytoene, antheraxanthin, and zeaxanthin showed high accumulation in NF-treated plants, whereas other carotenoid intermediates greatly decreased. Transcript levels of carotenoid biosynthetic genes, PSY1 and PDS, decreased in response to NF and OF, whereas plants in the later stage of NF treatment exhibited up-regulation of BCH and VDE as well as recovery of PDS. However, perturbed porphyrin biosynthesis by OF did not noticeably influence levels of carotenoid metabolites, regardless of the strong down-regulation of carotenoid biosynthetic genes. Both NF and OF plants appeared to provide enhanced protection against photooxidative damage, not only by scavenging of Mg-porphyrins, but also by up-regulating FC2, HO2, and Fe-chelatase, particularly with increased levels of zeaxanthin via up-regulation of BCH and VDE in NF plants. On the other hand, the up-regulation of GSA, PPO1, and CHLD under inhibition of carotenogenic flux may be derived from the necessity to recover impaired chloroplast biogenesis during photooxidative stress. Our study demonstrates that perturbations in carotenoid and porphyrin biosynthesis coordinate

Perturbations in the Photosynthetic Pigment Status Result in Photooxidation-Induced Crosstalk between Carotenoid and Porphyrin Biosynthetic Pathways.

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Park, Joon-Heum; Tran, Lien H; Jung, Sunyo

2017-01-01

Possible crosstalk between the carotenoid and porphyrin biosynthetic pathways under photooxidative conditions was investigated by using their biosynthetic inhibitors, norflurazon (NF) and oxyfluorfen (OF). High levels of protoporphyrin IX (Proto IX) accumulated in rice plants treated with OF, whereas Proto IX decreased in plants treated with NF. Both NF and OF treatments resulted in greater decreases in MgProto IX, MgProto IX methyl ester, and protochlorophyllide. Activities and transcript levels of most porphyrin biosynthetic enzymes, particularly in the Mg-porphyrin branch, were greatly down-regulated in NF and OF plants. In contrast, the transcript levels of GSA, PPO1 , and CHLD as well as FC2 and HO2 were up-regulated in NF-treated plants, while only moderate increases in FC2 and HO2 were observed in the early stage of OF treatment. Phytoene, antheraxanthin, and zeaxanthin showed high accumulation in NF-treated plants, whereas other carotenoid intermediates greatly decreased. Transcript levels of carotenoid biosynthetic genes, PSY1 and PDS , decreased in response to NF and OF, whereas plants in the later stage of NF treatment exhibited up-regulation of BCH and VDE as well as recovery of PDS . However, perturbed porphyrin biosynthesis by OF did not noticeably influence levels of carotenoid metabolites, regardless of the strong down-regulation of carotenoid biosynthetic genes. Both NF and OF plants appeared to provide enhanced protection against photooxidative damage, not only by scavenging of Mg - porphyrins, but also by up-regulating FC2, HO2 , and Fe-chelatase, particularly with increased levels of zeaxanthin via up-regulation of BCH and VDE in NF plants. On the other hand, the up-regulation of GSA, PPO1 , and CHLD under inhibition of carotenogenic flux may be derived from the necessity to recover impaired chloroplast biogenesis during photooxidative stress. Our study demonstrates that perturbations in carotenoid and porphyrin biosynthesis coordinate the

Heterologous expression and transcript analysis of gibberellin biosynthetic genes of grasses reveals novel functionality in the GA3ox family.

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Pearce, Stephen; Huttly, Alison K; Prosser, Ian M; Li, Yi-dan; Vaughan, Simon P; Gallova, Barbora; Patil, Archana; Coghill, Jane A; Dubcovsky, Jorge; Hedden, Peter; Phillips, Andrew L

2015-06-05

The gibberellin (GA) pathway plays a central role in the regulation of plant development, with the 2-oxoglutarate-dependent dioxygenases (2-ODDs: GA20ox, GA3ox, GA2ox) that catalyse the later steps in the biosynthetic pathway of particularly importance in regulating bioactive GA levels. Although GA has important impacts on crop yield and quality, our understanding of the regulation of GA biosynthesis during wheat and barley development remains limited. In this study we identified or assembled genes encoding the GA 2-ODDs of wheat, barley and Brachypodium distachyon and characterised the wheat genes by heterologous expression and transcript analysis. The wheat, barley and Brachypodium genomes each contain orthologous copies of the GA20ox, GA3ox and GA2ox genes identified in rice, with the exception of OsGA3ox1 and OsGA2ox5 which are absent in these species. Some additional paralogs of 2-ODD genes were identified: notably, a novel gene in the wheat B genome related to GA3ox2 was shown to encode a GA 1-oxidase, named as TaGA1ox-B1. This enzyme is likely to be responsible for the abundant 1β-hydroxylated GAs present in developing wheat grains. We also identified a related gene in barley, located in a syntenic position to TaGA1ox-B1, that encodes a GA 3,18-dihydroxylase which similarly accounts for the accumulation of unusual GAs in barley grains. Transcript analysis showed that some paralogs of the different classes of 2-ODD were expressed mainly in a single tissue or at specific developmental stages. In particular, TaGA20ox3, TaGA1ox1, TaGA3ox3 and TaGA2ox7 were predominantly expressed in developing grain. More detailed analysis of grain-specific gene expression showed that while the transcripts of biosynthetic genes were most abundant in the endosperm, genes encoding inactivation and signalling components were more highly expressed in the seed coat and pericarp. The comprehensive expression and functional characterisation of the multigene families encoding the 2-ODD

Functional annotation of hierarchical modularity.

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Kanchana Padmanabhan

Full Text Available In biological networks of molecular interactions in a cell, network motifs that are biologically relevant are also functionally coherent, or form functional modules. These functionally coherent modules combine in a hierarchical manner into larger, less cohesive subsystems, thus revealing one of the essential design principles of system-level cellular organization and function-hierarchical modularity. Arguably, hierarchical modularity has not been explicitly taken into consideration by most, if not all, functional annotation systems. As a result, the existing methods would often fail to assign a statistically significant functional coherence score to biologically relevant molecular machines. We developed a methodology for hierarchical functional annotation. Given the hierarchical taxonomy of functional concepts (e.g., Gene Ontology and the association of individual genes or proteins with these concepts (e.g., GO terms, our method will assign a Hierarchical Modularity Score (HMS to each node in the hierarchy of functional modules; the HMS score and its p-value measure functional coherence of each module in the hierarchy. While existing methods annotate each module with a set of "enriched" functional terms in a bag of genes, our complementary method provides the hierarchical functional annotation of the modules and their hierarchically organized components. A hierarchical organization of functional modules often comes as a bi-product of cluster analysis of gene expression data or protein interaction data. Otherwise, our method will automatically build such a hierarchy by directly incorporating the functional taxonomy information into the hierarchy search process and by allowing multi-functional genes to be part of more than one component in the hierarchy. In addition, its underlying HMS scoring metric ensures that functional specificity of the terms across different levels of the hierarchical taxonomy is properly treated. We have evaluated our

Systems-level analysis of risk genes reveals the modular nature of schizophrenia.

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Liu, Jiewei; Li, Ming; Luo, Xiong-Jian; Su, Bing

2018-05-19

Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent genome-wide association studies) have identified many risk genes for schizophrenia. However, the physical interactions among the proteins encoded by schizophrenia risk genes remain elusive and it is not known whether the identified risk genes converge on common molecular networks or pathways. Here we systematically investigated the network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions (PPI) from the human interactome. We found that schizophrenia risk genes encode a densely interconnected PPI network (P = 4.15 × 10 -31 ). Compared with the background genes, the schizophrenia risk genes in the interactome have significantly higher degree (P = 5.39 × 10 -11 ), closeness centrality (P = 7.56 × 10 -11 ), betweeness centrality (P = 1.29 × 10 -11 ), clustering coefficient (P = 2.22 × 10 -2 ), and shorter average shortest path length (P = 7.56 × 10 -11 ). Based on the densely interconnected PPI network, we identified 48 hub genes and 4 modules formed by highly interconnected schizophrenia genes. We showed that the proteins encoded by schizophrenia hub genes have significantly more direct physical interactions. Gene ontology (GO) analysis revealed that cell adhesion, cell cycle, immune system response, and GABR-receptor complex categories were enriched in the modules formed by highly interconnected schizophrenia risk genes. Our study reveals that schizophrenia risk genes encode a densely interconnected molecular network and demonstrates the modular nature of schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeted Gene Disruption of the Cyclo (L-Phe, L-Pro Biosynthetic Pathway in Streptomyces sp. US24 Strain

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Samiha Sioud

2007-01-01

Full Text Available We have previously isolated a new actinomycete strain from Tunisian soil called Streptomyces sp. US24, and have shown that it produces two bioactive molecules including a Cyclo (L-Phe, L-Pro diketopiperazine (DKP. To identify the structural genes responsible for the synthesis of this DKP derivative, a PCR amplification (696 bp was carried out using the Streptomyces sp. US24 genomic DNA as template and two degenerate oligonucleotides designed by analogy with genes encoding peptide synthetases (NRPS. The detection of DKP derivative biosynthetic pathway of the Streptomyces sp. US24 strain was then achieved by gene disruption via homologous recombination using a suicide vector derived from the conjugative plasmid pSET152 and containing the PCR product. Chromatography analysis, biological tests and spectroscopic studies of supernatant cultures of the wild-type Streptomyces sp. US24 strain and three mutants obtained by this gene targeting disruption approach showed that the amplified DNA fragment is required for Cyclo (L-Phe, L-Pro biosynthesis in Streptomyces sp. US24 strain. This DKP derivative seems to be produced either directly via a nonribosomal pathway or as a side product in the course of nonribosomal synthesis of a longer peptide.

Modular Engineering of l-Tyrosine Production in Escherichia coli

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Juminaga, Darmawi; Baidoo, Edward E. K.; Redding-Johanson, Alyssa M.; Batth, Tanveer S.; Burd, Helcio; Mukhopadhyay, Aindrila; Petzold, Christopher J.

2012-01-01

Efficient biosynthesis of l-tyrosine from glucose is necessary to make biological production economically viable. To this end, we designed and constructed a modular biosynthetic pathway for l-tyrosine production in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to l-tyrosine on two plasmids. Rational engineering to improve l-tyrosine production and to identify pathway bottlenecks was directed by targeted proteomics and metabolite profiling. The bottlenecks in the pathway were relieved by modifications in plasmid copy numbers, promoter strength, gene codon usage, and the placement of genes in operons. One major bottleneck was due to the bifunctional activities of quinate/shikimate dehydrogenase (YdiB), which caused accumulation of the intermediates dehydroquinate (DHQ) and dehydroshikimate (DHS) and the side product quinate; this bottleneck was relieved by replacing YdiB with its paralog AroE, resulting in the production of over 700 mg/liter of shikimate. Another bottleneck in shikimate production, due to low expression of the dehydroquinate synthase (AroB), was alleviated by optimizing the first 15 codons of the gene. Shikimate conversion to l-tyrosine was improved by replacing the shikimate kinase AroK with its isozyme, AroL, which effectively consumed all intermediates formed in the first half of the pathway. Guided by the protein and metabolite measurements, the best producer, consisting of two medium-copy-number, dual-operon plasmids, was optimized to produce >2 g/liter l-tyrosine at 80% of the theoretical yield. This work demonstrates the utility of targeted proteomics and metabolite profiling in pathway construction and optimization, which should be applicable to other metabolic pathways. PMID:22020510

Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes.

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Stephen D Bentley

2006-03-01

Full Text Available Several major invasive bacterial pathogens are encapsulated. Expression of a polysaccharide capsule is essential for survival in the blood, and thus for virulence, but also is a target for host antibodies and the basis for effective vaccines. Encapsulated species typically exhibit antigenic variation and express one of a number of immunochemically distinct capsular polysaccharides that define serotypes. We provide the sequences of the capsular biosynthetic genes of all 90 serotypes of Streptococcus pneumoniae and relate these to the known polysaccharide structures and patterns of immunological reactivity of typing sera, thereby providing the most complete understanding of the genetics and origins of bacterial polysaccharide diversity, laying the foundations for molecular serotyping. This is the first time, to our knowledge, that a complete repertoire of capsular biosynthetic genes has been available, enabling a holistic analysis of a bacterial polysaccharide biosynthesis system. Remarkably, the total size of alternative coding DNA at this one locus exceeds 1.8 Mbp, almost equivalent to the entire S. pneumoniae chromosomal complement.

Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae.

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Wang, Yonglin; Hu, Xiaoping; Fang, Yulin; Anchieta, Amy; Goldman, Polly H; Hernandez, Gustavo; Klosterman, Steven J

2018-04-01

Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters.

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Kinashi, Haruyasu

2011-01-01

Many giant linear plasmids have been isolated from Streptomyces by using pulsed-field gel electrophoresis and some of them were found to carry an antibiotic biosynthetic cluster(s); SCP1 carries biosynthetic genes for methylenomycin, pSLA2-L for lankacidin and lankamycin, and pKSL for lasalocid and echinomycin. Accumulated data suggest that giant linear plasmids have played critical roles in genome evolution and horizontal transfer of secondary metabolism. In this review, I summarize typical examples of giant linear plasmids whose involvement in antibiotic production has been studied in some detail, emphasizing their finding processes and interaction with the host chromosomes. A hypothesis on horizontal transfer of secondary metabolism involving giant linear plasmids is proposed at the end.

Variation in fumonisin and ochratoxin production associated with differences in biosynthetic gene content in Aspergillus niger and A. welwitschiae isolates from multiple crop and geographic origins

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Antonia Susca

2016-09-01

Full Text Available The fungi Aspergillus niger and A. welwitschiae are morphologically indistinguishable species used for industrial fermentation and for food and beverage production. The fungi also occur widely on food crops. Concerns about their safety have arisen with the discovery that some isolates of both species produce fumonisin (FB and ochratoxin A (OTA mycotoxins. Here, we examined FB and OTA production as well as the presence of genes responsible for synthesis of the mycotoxins in a collection of 92 A. niger/A. welwitschiae isolates from multiple crop and geographic origins. The results indicate that i isolates of both species differed in ability to produce the mycotoxins; ii FB-nonproducing isolates of A. niger had an intact fumonisin biosynthetic gene (fum cluster; iii FB-nonproducing isolates of A. welwitschiae exhibited multiple patterns of fum gene deletion; and iv OTA-nonproducing isolates of both species lacked the ochratoxin A biosynthetic gene (ota cluster. Analysis of genome sequence data revealed a single pattern of ota gene deletion in the two species. Phylogenetic analysis suggest that the simplest explanation for this is that ota cluster deletion occurred in a common ancestor of A. niger and A. welwitschiae, and subsequently both the intact and deleted cluster were retained as alternate alleles during divergence of the ancestor into descendent species. Finally, comparison of results from this and previous studies indicate that a majority of A. niger isolates and a minority of A. welwitschiae isolates can produce FBs, whereas a minority of isolates of both species produce OTA. The comparison also suggested that the relative abundance of each species and frequency of FB/OTA-producing isolates can vary with crop and/or geographic origin.

Genomic characterization of a new endophytic Streptomyces kebangsaanensis identifies biosynthetic pathway gene clusters for novel phenazine antibiotic production

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Juwairiah Remali

2017-11-01

Full Text Available Background Streptomyces are well known for their capability to produce many bioactive secondary metabolites with medical and industrial importance. Here we report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy carbonyl phenazine-1-carboxylic acid (HCPCA extracted from Streptomyces kebangsaanensis, an endophyte isolated from the ethnomedicinal Portulaca oleracea. Methods The HCPCA chemical structure was determined using nuclear magnetic resonance spectroscopy. We conducted whole genome sequencing for the identification of the gene cluster(s believed to be responsible for phenazine biosynthesis in order to map its corresponding pathway, in addition to bioinformatics analysis to assess the potential of S. kebangsaanensis in producing other useful secondary metabolites. Results The S. kebangsaanensis genome comprises an 8,328,719 bp linear chromosome with high GC content (71.35% consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We identified 24 gene clusters involved in polyketide, nonribosomal peptide, terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster predicted to be responsible for phenazine biosynthesis. Discussion The HCPCA phenazine structure was hypothesized to derive from the combination of two biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2-diol, originated from the shikimic acid pathway. The identification of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics. Additionally, these findings confirm the potential of S. kebangsaanensis for producing various antibiotics and secondary metabolites.

Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

DEFF Research Database (Denmark)

Liu, Chengwei; Tagami, Koichi; Minami, Atsushi

2015-01-01

KULNJ). Importantly, without conventional gene disruption, reconstitution of the biosynthetic machinery provided sufficient data to determine the pathway. It was thus demonstrated that the Aspergillus oryzae reconstitution system is a powerful method for studying the biosynthesis of complex natural products....

Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis.

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Ohyama, Kiyoshi; Suzuki, Masashi; Kikuchi, Jun; Saito, Kazuki; Muranaka, Toshiya

2009-01-20

The differences between the biosynthesis of sterols in higher plants and yeast/mammals are believed to originate at the cyclization step of oxidosqualene, which is cyclized to cycloartenol in higher plants and lanosterol in yeast/mammals. Recently, lanosterol synthase genes were identified from dicotyledonous plant species including Arabidopsis, suggesting that higher plants possess dual biosynthetic pathways to phytosterols via lanosterol, and through cycloartenol. To identify the biosynthetic pathway to phytosterol via lanosterol, and to reveal the contributions to phytosterol biosynthesis via each cycloartenol and lanosterol, we performed feeding experiments by using [6-(13)C(2)H(3)]mevalonate with Arabidopsis seedlings. Applying (13)C-{(1)H}{(2)H} nuclear magnetic resonance (NMR) techniques, the elucidation of deuterium on C-19 behavior of phytosterol provided evidence that small amounts of phytosterol were biosynthesized via lanosterol. The levels of phytosterol increased on overexpression of LAS1, and phytosterols derived from lanosterol were not observed in a LAS1-knockout plant. This is direct evidence to indicate that the biosynthetic pathway for phytosterol via lanosterol exists in plant cells. We designate the biosynthetic pathway to phytosterols via lanosterol "the lanosterol pathway." LAS1 expression is reported to be induced by the application of jasmonate and is thought to have evolved from an ancestral cycloartenol synthase to a triterpenoid synthase, such as beta-amyrin synthase and lupeol synthase. Considering this background, the lanosterol pathway may contribute to the biosynthesis of not only phytosterols, but also steroids as secondary metabolites.

Sequence diversity and differential expression of major phenylpropanoid-flavonoid biosynthetic genes among three mango varieties.

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Hoang, Van L T; Innes, David J; Shaw, P Nicholas; Monteith, Gregory R; Gidley, Michael J; Dietzgen, Ralf G

2015-07-30

Mango fruits contain a broad spectrum of phenolic compounds which impart potential health benefits; their biosynthesis is catalysed by enzymes in the phenylpropanoid-flavonoid (PF) pathway. The aim of this study was to reveal the variability in genes involved in the PF pathway in three different mango varieties Mangifera indica L., a member of the family Anacardiaceae: Kensington Pride (KP), Irwin (IW) and Nam Doc Mai (NDM) and to determine associations with gene expression and mango flavonoid profiles. A close evolutionary relationship between mango genes and those from the woody species poplar of the Salicaceae family (Populus trichocarpa) and grape of the Vitaceae family (Vitis vinifera), was revealed through phylogenetic analysis of PF pathway genes. We discovered 145 SNPs in total within coding sequences with an average frequency of one SNP every 316 bp. Variety IW had the highest SNP frequency (one SNP every 258 bp) while KP and NDM had similar frequencies (one SNP every 369 bp and 360 bp, respectively). The position in the PF pathway appeared to influence the extent of genetic diversity of the encoded enzymes. The entry point enzymes phenylalanine lyase (PAL), cinnamate 4-mono-oxygenase (C4H) and chalcone synthase (CHS) had low levels of SNP diversity in their coding sequences, whereas anthocyanidin reductase (ANR) showed the highest SNP frequency followed by flavonoid 3'-hydroxylase (F3'H). Quantitative PCR revealed characteristic patterns of gene expression that differed between mango peel and flesh, and between varieties. The combination of mango expressed sequence tags and availability of well-established reference PF biosynthetic genes from other plant species allowed the identification of coding sequences of genes that may lead to the formation of important flavonoid compounds in mango fruits and facilitated characterisation of single nucleotide polymorphisms between varieties. We discovered an association between the extent of sequence variation and

Targeting fumonisin biosynthetic genes

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The fungus Fusarium is an agricultural problem because it can cause disease on most crop plants and can contaminate crops with mycotoxins. There is considerable variation in the presence/absence and genomic location of gene clusters responsible for synthesis of mycotoxins and other secondary metabol...

Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

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Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

2018-01-01

Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

Mutational studies of putative biosynthetic genes for the cyanobacterial sunscreen scytonemin in Nostoc punctiforme ATCC 29133

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Daniela eFerreira

2016-05-01

Full Text Available The heterocyclic indole-alkaloid scytonemin is a sunscreen found exclusively among cyanobacteria. An 18-gene cluster is responsible for scytonemin production in Nostoc punctiforme ATCC 29133. The upstream genes scyABCDEF in the cluster are proposed to be responsible for scytonemin biosynthesis from aromatic amino acid substrates. In vitro studies of ScyA, ScyB and ScyC proved that these enzymes indeed catalyze initial pathway reactions. Here we characterize the role of ScyD, ScyE and ScyF, which were logically predicted to be responsible for late biosynthetic steps, in the biological context of N. punctiforme. In-frame deletion mutants of each were constructed (∆scyD, ∆scyE and ∆scyF and their phenotypes studied. Expectedly, ∆scyE presents a scytoneminless phenotype, but no accumulation of the predicted intermediaries. Surprisingly, ∆scyD retains scytonemin production, implying that it is not required for biosynthesis. Indeed, scyD presents an interesting evolutionary paradox: it likely originated in a duplication event from scyE, and unlike other genes in the operon, it has not been subjected to purifying selection. This would suggest that it is a pseudogene, and yet scyD is highly conserved in the scytonemin operon of cyanobacteria. ∆scyF also retains scytonemin production, albeit exhibiting a reduction of the production yield compared with the wild-type. This indicates that ScyF is not essential but may play an adjuvant role for scytonemin synthesis. Altogether, our findings suggest that these downstream genes are not responsible, as expected, for the late steps of scytonemin synthesis and we must look for those functions elsewhere. These findings are particularly important for biotechnological production of this sunscreen through heterologous expression of its genes in more tractable organisms.

Targeting trichothecene biosynthetic genes

NARCIS (Netherlands)

Wei, Songhong; Lee, van der Theo; Verstappen, Els; Gent, van Marga; Waalwijk, Cees

2017-01-01

Biosynthesis of trichothecenes requires the involvement of at least 15 genes, most of which have been targeted for PCR. Qualitative PCRs are used to assign chemotypes to individual isolates, e.g., the capacity to produce type A and/or type B trichothecenes. Many regions in the core cluster

Perturbations of carotenoid and tetrapyrrole biosynthetic pathways result in differential alterations in chloroplast function and plastid signaling

International Nuclear Information System (INIS)

Park, Joon-Heum; Jung, Sunyo

2017-01-01

In this study, we used the biosynthetic inhibitors of carotenoid and tetrapyrrole biosynthetic pathways, norflurazon (NF) and oxyfluorfen (OF), as tools to gain insight into mechanisms of photooxidation in rice plants. NF resulted in bleaching symptom on leaves of the treated plants, whereas OF treatment developed a fast symptom of an apparent necrotic phenotype. Both plants exhibited decreases in photosynthetic efficiency, as indicated by F v /F m . NF caused severe disruption in thylakoid membranes, whereas OF-treated plants exhibited disruption of chloroplast envelope and plasma membrane. Levels of Lhca and Lhcb proteins in photosystem I (PSI) and PSII were reduced by photooxidative stress in NF- and OF-treated plants, with a greater decrease in NF plants. The down-regulation of nuclear-encoded photosynthesis genes Lhcb and rbcS was also found in both NF- and OF-treated plants, whereas plastid-encoded photosynthetic genes including RbcL, PsaC, and PsbD accumulated normally in NF plants but decreased drastically in OF plants. This proposes that the plastids in NF plants retain their potential to develop thylakoid membranes and that photobleaching is mainly controlled by nuclear genes. Distinct photooxidation patterns between NF- and OF-treated plants developed differential signaling, which might enable the plant to coordinate the expression of photosynthetic genes from the nuclear and plastidic genomes. - Highlights: • Two modes of photooxidation by carotenoid and tetrapyrrole biosynthetic inhibitors. • We examine differential alterations in chloroplast function and plastid signaling. • NF and OF cause differential alterations in chloroplast ultrastructure and function. • Photooxidation coordinates photosynthetic gene expression from nucleus and plastid.

Environmental cues induce changes of steviol glycosides contents and transcription of corresponding biosynthetic genes in Stevia rebaudiana.

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Yang, Yongheng; Huang, Suzhen; Han, Yulin; Yuan, Haiyan; Gu, Chunsun; Wang, Zhongwei

2015-01-01

Plant growth and secondary metabolism are commonly regulated by external cues such as light, temperature and water availability. In this study, the influences of low and high temperatures, dehydration, photoperiods, and different growing stages on the changes of steviol glycosides (SGs) contents and transcription levels of fifteen genes involved in SGs biosynthesis of Stevia rebaudiana Bertoni were examined using HPLC and RT-PCR. The observations showed that the transcript levels of all the fifteen genes were maximum under 25 °C treatment, and the transcription of SrDXS, SrDXR, SrMCT, SrCMK, SrMDS, SrHDS, SrHDR, SrIDI, SrGGDPS, SrCPPS1, SrUGT85C2 and SrUGT76G1 were restrained both in low temperature (15 °C) and high temperature (35 °C). Most genes in SGs biosynthesis pathway exhibited down-regulation in dehydration. To elucidate the effect of photoperiods, the plants were treated by different simulated photoperiods (8 L/16 D, 1 0L/14 D, 14 L/10 D and 16 L/8 D), but no significant transcription changes were observed. In the study of growing stages, there were evident changes of SGs contents, and the transcript levels of all the fifteen genes were minimal in fast growing period, and exhibited evident increase both in flower-bud appearing stage and flowering stage. The obtained results strongly suggest that the effect of environmental cues on steviol glycosides contents and transcription of corresponding biosynthetic genes in S. rebaudiana is significant. It is worth to study deeply. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Designing universal primers for the isolation of DNA sequences encoding Proanthocyanidins biosynthetic enzymes in Crataegus aronia

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Zuiter Afnan

2012-08-01

Full Text Available Abstract Background Hawthorn is the common name of all plant species in the genus Crataegus, which belongs to the Rosaceae family. Crataegus are considered useful medicinal plants because of their high content of proanthocyanidins (PAs and other related compounds. To improve PAs production in Crataegus tissues, the sequences of genes encoding PAs biosynthetic enzymes are required. Findings Different bioinformatics tools, including BLAST, multiple sequence alignment and alignment PCR analysis were used to design primers suitable for the amplification of DNA fragments from 10 candidate genes encoding enzymes involved in PAs biosynthesis in C. aronia. DNA sequencing results proved the utility of the designed primers. The primers were used successfully to amplify DNA fragments of different PAs biosynthesis genes in different Rosaceae plants. Conclusion To the best of our knowledge, this is the first use of the alignment PCR approach to isolate DNA sequences encoding PAs biosynthetic enzymes in Rosaceae plants.

Discovering potential Streptomyces hormone producers by using disruptants of essential biosynthetic genes as indicator strains.

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Thao, Nguyen B; Kitani, Shigeru; Nitta, Hiroko; Tomioka, Toshiya; Nihira, Takuya

2017-10-01

Autoregulators are low-molecular-weight signaling compounds that control the production of many secondary metabolites in actinomycetes and have been referred to as 'Streptomyces hormones'. Here, potential producers of Streptomyces hormones were investigated in 40 Streptomyces and 11 endophytic actinomycetes. Production of γ-butyrolactone-type (IM-2, VB) and butenolide-type (avenolide) Streptomyces hormones was screened using Streptomyces lavendulae FRI-5 (ΔfarX), Streptomyces virginiae (ΔbarX) and Streptomyces avermitilis (Δaco), respectively. In these strains, essential biosynthetic genes for Streptomyces hormones were disrupted, enabling them to respond solely to the externally added hormones. The results showed that 20% of each of the investigated strains produced IM-2 and VB, confirming that γ-butyrolactone-type Streptomyces hormones are the most common in actinomycetes. Unlike the γ-butyrolactone type, butenolide-type Streptomyces hormones have been discovered in recent years, but their distribution has been unclear. Our finding that 24% of actinomycetes (12 of 51 strains) showed avenolide activity revealed for the first time that the butenolide-type Streptomyces hormone is also common in actinomycetes.

De Novo Assembly and Genome Analyses of the Marine-Derived Scopulariopsis brevicaulis Strain LF580 Unravels Life-Style Traits and Anticancerous Scopularide Biosynthetic Gene Cluster.

Science.gov (United States)

Kumar, Abhishek; Henrissat, Bernard; Arvas, Mikko; Syed, Muhammad Fahad; Thieme, Nils; Benz, J Philipp; Sørensen, Jens Laurids; Record, Eric; Pöggeler, Stefanie; Kempken, Frank

2015-01-01

The marine-derived Scopulariopsis brevicaulis strain LF580 produces scopularides A and B, which have anticancerous properties. We carried out genome sequencing using three next-generation DNA sequencing methods. De novo hybrid assembly yielded 621 scaffolds with a total size of 32.2 Mb and 16298 putative gene models. We identified a large non-ribosomal peptide synthetase gene (nrps1) and supporting pks2 gene in the same biosynthetic gene cluster. This cluster and the genes within the cluster are functionally active as confirmed by RNA-Seq. Characterization of carbohydrate-active enzymes and major facilitator superfamily (MFS)-type transporters lead to postulate S. brevicaulis originated from a soil fungus, which came into contact with the marine sponge Tethya aurantium. This marine sponge seems to provide shelter to this fungus and micro-environment suitable for its survival in the ocean. This study also builds the platform for further investigations of the role of life-style and secondary metabolites from S. brevicaulis.

BGDMdocker: a Docker workflow for data mining and visualization of bacterial pan-genomes and biosynthetic gene clusters

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Gong Cheng

2017-11-01

Full Text Available Recently, Docker technology has received increasing attention throughout the bioinformatics community. However, its implementation has not yet been mastered by most biologists; accordingly, its application in biological research has been limited. In order to popularize this technology in the field of bioinformatics and to promote the use of publicly available bioinformatics tools, such as Dockerfiles and Images from communities, government sources, and private owners in the Docker Hub Registry and other Docker-based resources, we introduce here a complete and accurate bioinformatics workflow based on Docker. The present workflow enables analysis and visualization of pan-genomes and biosynthetic gene clusters of bacteria. This provides a new solution for bioinformatics mining of big data from various publicly available biological databases. The present step-by-step guide creates an integrative workflow through a Dockerfile to allow researchers to build their own Image and run Container easily.

BGDMdocker: a Docker workflow for data mining and visualization of bacterial pan-genomes and biosynthetic gene clusters.

Science.gov (United States)

Cheng, Gong; Lu, Quan; Ma, Ling; Zhang, Guocai; Xu, Liang; Zhou, Zongshan

2017-01-01

Recently, Docker technology has received increasing attention throughout the bioinformatics community. However, its implementation has not yet been mastered by most biologists; accordingly, its application in biological research has been limited. In order to popularize this technology in the field of bioinformatics and to promote the use of publicly available bioinformatics tools, such as Dockerfiles and Images from communities, government sources, and private owners in the Docker Hub Registry and other Docker-based resources, we introduce here a complete and accurate bioinformatics workflow based on Docker. The present workflow enables analysis and visualization of pan-genomes and biosynthetic gene clusters of bacteria. This provides a new solution for bioinformatics mining of big data from various publicly available biological databases. The present step-by-step guide creates an integrative workflow through a Dockerfile to allow researchers to build their own Image and run Container easily.

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

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Hiroki Oguri

2012-06-01

Full Text Available By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR studies were also undertaken.

Ultraviolet Radiation-Elicited Enhancement of Isoflavonoid Accumulation, Biosynthetic Gene Expression, and Antioxidant Activity in Astragalus membranaceus Hairy Root Cultures.

Science.gov (United States)

Jiao, Jiao; Gai, Qing-Yan; Wang, Wei; Luo, Meng; Gu, Cheng-Bo; Fu, Yu-Jie; Ma, Wei

2015-09-23

In this work, Astragalus membranaceus hairy root cultures (AMHRCs) were exposed to ultraviolet radiation (UV-A, UV-B, and UV-C) for promoting isoflavonoid accumulation. The optimum enhancement for isoflavonoid production was achieved in 34-day-old AMHRCs elicited by 86.4 kJ/m(2) of UV-B. The resulting isoflavonoid yield was 533.54 ± 13.61 μg/g dry weight (DW), which was 2.29-fold higher relative to control (232.93 ± 3.08 μg/g DW). UV-B up-regulated the transcriptional expressions of all investigated genes involved in isoflavonoid biosynthetic pathway. PAL and C4H were found to be two potential key genes that controlled isoflavonoid biosynthesis. Moreover, a significant increase was noted in antioxidant activity of extracts from UV-B-elicited AMHRCs (IC50 values = 0.85 and 1.08 mg/mL) in comparison with control (1.38 and 1.71 mg/mL). Overall, this study offered a feasible elicitation strategy to enhance isoflavonoid accumulation in AMHRCs and also provided a basis for metabolic engineering of isoflavonoid biosynthesis in the future.

Towards prediction of metabolic products of polyketide synthases: an in silico analysis.

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Gitanjali Yadav

2009-04-01

Full Text Available Sequence data arising from an increasing number of partial and complete genome projects is revealing the presence of the polyketide synthase (PKS family of genes not only in microbes and fungi but also in plants and other eukaryotes. PKSs are huge multifunctional megasynthases that use a variety of biosynthetic paradigms to generate enormously diverse arrays of polyketide products that posses several pharmaceutically important properties. The remarkable conservation of these gene clusters across organisms offers abundant scope for obtaining novel insights into PKS biosynthetic code by computational analysis. We have carried out a comprehensive in silico analysis of modular and iterative gene clusters to test whether chemical structures of the secondary metabolites can be predicted from PKS protein sequences. Here, we report the success of our method and demonstrate the feasibility of deciphering the putative metabolic products of uncharacterized PKS clusters found in newly sequenced genomes. Profile Hidden Markov Model analysis has revealed distinct sequence features that can distinguish modular PKS proteins from their iterative counterparts. For iterative PKS proteins, structural models of iterative ketosynthase (KS domains have revealed novel correlations between the size of the polyketide products and volume of the active site pocket. Furthermore, we have identified key residues in the substrate binding pocket that control the number of chain extensions in iterative PKSs. For modular PKS proteins, we describe for the first time an automated method based on crucial intermolecular contacts that can distinguish the correct biosynthetic order of substrate channeling from a large number of non-cognate combinatorial possibilities. Taken together, our in silico analysis provides valuable clues for formulating rules for predicting polyketide products of iterative as well as modular PKS clusters. These results have promising potential for discovery of

Identification and Functional Characterization of Genes Encoding Omega-3 Polyunsaturated Fatty Acid Biosynthetic Activities from Unicellular Microalgae

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Royah Vaezi

2013-12-01

Full Text Available In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative “front-end” desaturases (Δ6 and Δ4 from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15. These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in marine microalgae.

Rice ethylene-response AP2/ERF factor OsEATB restricts internode elongation by down-regulating a gibberellin biosynthetic gene.

Science.gov (United States)

Qi, Weiwei; Sun, Fan; Wang, Qianjie; Chen, Mingluan; Huang, Yunqing; Feng, Yu-Qi; Luo, Xiaojin; Yang, Jinshui

2011-09-01

Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops.

Elucidation of the biosynthetic pathway for the production of the pigment chrysogine by Penicillium chrysogenum

NARCIS (Netherlands)

Viggiano, Annarita; Salo, Oleksandr; Ali, Hazrat; Szymanski, Wiktor; Lankhorst, Peter P; Nygård, Yvonne; Bovenberg, Roel A L; Driessen, Arnold J M

Chrysogine is a yellow pigment produced by Penicillium chrysogenum and other filamentous fungi. Although it was first isolated in 1973, the biosynthetic pathway has so far not been resolved. Here, we show that the deletion of the highly expressed non-ribosomal peptide synthetase (NRPS) gene

Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process.

Science.gov (United States)

Yin, Shouliang; Li, Zilong; Wang, Xuefeng; Wang, Huizhuan; Jia, Xiaole; Ai, Guomin; Bai, Zishang; Shi, Mingxin; Yuan, Fang; Liu, Tiejun; Wang, Weishan; Yang, Keqian

2016-12-01

Heterologous expression is an important strategy to activate biosynthetic gene clusters of secondary metabolites. Here, it is employed to activate and manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation process. To achieve these goals, a fast-growing heterologous host Streptomyces venezuelae WVR2006 was rationally selected among several potential hosts. It shows rapid and dispersed growth and intrinsic high resistance to OTC. By manipulating the expression of two cluster-situated regulators (CSR) OtcR and OtrR and precursor supply, the OTC production level was significantly increased in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to the native producer Streptomyces rimosus M4018 in 8 days. This work shows that S. venezuelae WVR2006 is a promising chassis for the production of secondary metabolites, and the engineered heterologous OTC producer has the potential to completely alter the fermentation process of OTC production.

Modular protein switches derived from antibody mimetic proteins.

Science.gov (United States)

Nicholes, N; Date, A; Beaujean, P; Hauk, P; Kanwar, M; Ostermeier, M

2016-02-01

Protein switches have potential applications as biosensors and selective protein therapeutics. Protein switches built by fusion of proteins with the prerequisite input and output functions are currently developed using an ad hoc process. A modular switch platform in which existing switches could be readily adapted to respond to any ligand would be advantageous. We investigated the feasibility of a modular protein switch platform based on fusions of the enzyme TEM-1 β-lactamase (BLA) with two different antibody mimetic proteins: designed ankyrin repeat proteins (DARPins) and monobodies. We created libraries of random insertions of the gene encoding BLA into genes encoding a DARPin or a monobody designed to bind maltose-binding protein (MBP). From these libraries, we used a genetic selection system for β-lactamase activity to identify genes that conferred MBP-dependent ampicillin resistance to Escherichia coli. Some of these selected genes encoded switch proteins whose enzymatic activity increased up to 14-fold in the presence of MBP. We next introduced mutations into the antibody mimetic domain of these switches that were known to cause binding to different ligands. To different degrees, introduction of the mutations resulted in switches with the desired specificity, illustrating the potential modularity of these platforms. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Investigation on changes of modularity and robustness by edge-removal mutations in signaling networks.

Science.gov (United States)

Truong, Cong-Doan; Kwon, Yung-Keun

2017-12-21

Biological networks consisting of molecular components and interactions are represented by a graph model. There have been some studies based on that model to analyze a relationship between structural characteristics and dynamical behaviors in signaling network. However, little attention has been paid to changes of modularity and robustness in mutant networks. In this paper, we investigated the changes of modularity and robustness by edge-removal mutations in three signaling networks. We first observed that both the modularity and robustness increased on average in the mutant network by the edge-removal mutations. However, the modularity change was negatively correlated with the robustness change. This implies that it is unlikely that both the modularity and the robustness values simultaneously increase by the edge-removal mutations. Another interesting finding is that the modularity change was positively correlated with the degree, the number of feedback loops, and the edge betweenness of the removed edges whereas the robustness change was negatively correlated with them. We note that these results were consistently observed in randomly structure networks. Additionally, we identified two groups of genes which are incident to the highly-modularity-increasing and the highly-robustness-decreasing edges with respect to the edge-removal mutations, respectively, and observed that they are likely to be central by forming a connected component of a considerably large size. The gene-ontology enrichment of each of these gene groups was significantly different from the rest of genes. Finally, we showed that the highly-robustness-decreasing edges can be promising edgetic drug-targets, which validates the usefulness of our analysis. Taken together, the analysis of changes of robustness and modularity against edge-removal mutations can be useful to unravel novel dynamical characteristics underlying in signaling networks.

Modular co-evolution of metabolic networks

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Yu Zhong-Hao

2007-08-01

Full Text Available Abstract Background The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. Results In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. Conclusion The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.

Estimating P-coverage of biosynthetic pathways in DNA libraries and screening by genetic selection: biotin biosynthesis in the marine microorganism Chromohalobacter.

Science.gov (United States)

Kim, Eun Jin; Angell, Scott; Janes, Jeff; Watanabe, Coran M H

2008-06-01

Traditional approaches to natural product discovery involve cell-based screening of natural product extracts followed by compound isolation and characterization. Their importance notwithstanding, continued mining leads to depletion of natural resources and the reisolation of previously identified metabolites. Metagenomic strategies aimed at localizing the biosynthetic cluster genes and expressing them in surrogate hosts offers one possible alternative. A fundamental question that naturally arises when pursuing such a strategy is, how large must the genomic library be to effectively represent the genome of an organism(s) and the biosynthetic gene clusters they harbor? Such an issue is certainly augmented in the absence of expensive robotics to expedite colony picking and/or screening of clones. We have developed an algorism, named BPC (biosynthetic pathway coverage), supported by molecular simulations to deduce the number of BAC clones required to achieve proper coverage of the genome and their respective biosynthetic pathways. The strategy has been applied to the construction of a large-insert BAC library from a marine microorganism, Hon6 (isolated from Honokohau, Maui) thought to represent a new species. The genomic library is constructed with a BAC yeast shuttle vector pClasper lacZ paving the way for the culturing of libraries in both prokaryotic and eukaryotic hosts. Flow cytometric methods are utilized to estimate the genome size of the organism and BPC implemented to assess P-coverage or percent coverage. A genetic selection strategy is illustrated, applications of which could expedite screening efforts in the identification and localization of biosynthetic pathways from marine microbial consortia, offering a powerful complement to genome sequencing and degenerate probe strategies. Implementing this approach, we report on the biotin biosynthetic pathway from the marine microorganism Hon6.

Metric modular spaces

CERN Document Server

Chistyakov, Vyacheslav

2015-01-01

Aimed toward researchers and graduate students familiar with elements of functional analysis, linear algebra, and general topology; this book contains a general study of modulars, modular spaces, and metric modular spaces. Modulars may be thought of as generalized velocity fields and serve two important purposes: generate metric spaces in a unified manner and provide a weaker convergence, the modular convergence, whose topology is non-metrizable in general. Metric modular spaces are extensions of metric spaces, metric linear spaces, and classical modular linear spaces. The topics covered include the classification of modulars, metrizability of modular spaces, modular transforms and duality between modular spaces, metric  and modular topologies. Applications illustrated in this book include: the description of superposition operators acting in modular spaces, the existence of regular selections of set-valued mappings, new interpretations of spaces of Lipschitzian and absolutely continuous mappings, the existe...

Modular arrangement of regulatory RNA elements.

Science.gov (United States)

Roßmanith, Johanna; Narberhaus, Franz

2017-03-04

Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

Modular design of metabolic network for robust production of n-butanol from galactose-glucose mixtures.

Science.gov (United States)

Lim, Hyun Gyu; Lim, Jae Hyung; Jung, Gyoo Yeol

2015-01-01

Refactoring microorganisms for efficient production of advanced biofuel such as n-butanol from a mixture of sugars in the cheap feedstock is a prerequisite to achieve economic feasibility in biorefinery. However, production of biofuel from inedible and cheap feedstock is highly challenging due to the slower utilization of biomass-driven sugars, arising from complex assimilation pathway, difficulties in amplification of biosynthetic pathways for heterologous metabolite, and redox imbalance caused by consuming intracellular reducing power to produce quite reduced biofuel. Even with these problems, the microorganisms should show robust production of biofuel to obtain industrial feasibility. Thus, refactoring microorganisms for efficient conversion is highly desirable in biofuel production. In this study, we engineered robust Escherichia coli to accomplish high production of n-butanol from galactose-glucose mixtures via the design of modular pathway, an efficient and systematic way, to reconstruct the entire metabolic pathway with many target genes. Three modular pathways designed using the predictable genetic elements were assembled for efficient galactose utilization, n-butanol production, and redox re-balancing to robustly produce n-butanol from a sugar mixture of galactose and glucose. Specifically, the engineered strain showed dramatically increased n-butanol production (3.3-fold increased to 6.2 g/L after 48-h fermentation) compared to the parental strain (1.9 g/L) in galactose-supplemented medium. Moreover, fermentation with mixtures of galactose and glucose at various ratios from 2:1 to 1:2 confirmed that our engineered strain was able to robustly produce n-butanol regardless of sugar composition with simultaneous utilization of galactose and glucose. Collectively, modular pathway engineering of metabolic network can be an effective approach in strain development for optimal biofuel production with cost-effective fermentable sugars. To the best of our

Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

KAUST Repository

Ross, Avena C.

2013-01-23

Thalassospiramides A and B are immunosuppressant cyclic lipopeptides first reported from the marine α-proteobacterium Thalassospira sp. CNJ-328. We describe here the discovery and characterization of an extended family of 14 new analogues from four Tistrella and Thalassospira isolates. These potent calpain 1 protease inhibitors belong to six structure classes in which the length and composition of the acylpeptide side chain varies extensively. Genomic sequence analysis of the thalassospiramide-producing microbes revealed related, genus-specific biosynthetic loci encoding hybrid nonribosomal peptide synthetase/polyketide synthases consistent with thalassospiramide assembly. The bioinformatics analysis of the gene clusters suggests that structural diversity, which ranges from the 803.4 Da thalassospiramide C to the 1291.7 Da thalassospiramide F, results from a complex sequence of reactions involving amino acid substrate channeling and enzymatic multimodule skipping and iteration. Preliminary biochemical analysis of the N-terminal nonribosomal peptide synthetase module from the Thalassospira TtcA megasynthase supports a biosynthetic model in which in cis amino acid activation competes with in trans activation to increase the range of amino acid substrates incorporated at the N terminus. © 2012 American Chemical Society.

Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

KAUST Repository

Ross, Avena C.; Xü , Ying; Lu, Liang; Kersten, Roland D.; Shao, Zongze; Al-Suwailem, Abdulaziz M.; Dorrestein, Pieter C.; Qian, Peiyuan; Moore, Bradley S.

2013-01-01

Thalassospiramides A and B are immunosuppressant cyclic lipopeptides first reported from the marine α-proteobacterium Thalassospira sp. CNJ-328. We describe here the discovery and characterization of an extended family of 14 new analogues from four Tistrella and Thalassospira isolates. These potent calpain 1 protease inhibitors belong to six structure classes in which the length and composition of the acylpeptide side chain varies extensively. Genomic sequence analysis of the thalassospiramide-producing microbes revealed related, genus-specific biosynthetic loci encoding hybrid nonribosomal peptide synthetase/polyketide synthases consistent with thalassospiramide assembly. The bioinformatics analysis of the gene clusters suggests that structural diversity, which ranges from the 803.4 Da thalassospiramide C to the 1291.7 Da thalassospiramide F, results from a complex sequence of reactions involving amino acid substrate channeling and enzymatic multimodule skipping and iteration. Preliminary biochemical analysis of the N-terminal nonribosomal peptide synthetase module from the Thalassospira TtcA megasynthase supports a biosynthetic model in which in cis amino acid activation competes with in trans activation to increase the range of amino acid substrates incorporated at the N terminus. © 2012 American Chemical Society.

Overexpression of the riboflavin biosynthetic pathway in Pichia pastoris

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Mattanovich Diethard

2008-07-01

Full Text Available Abstract Background High cell density cultures of Pichia pastoris grown on methanol tend to develop yellow colored supernatants, attributed to the release of free flavins. The potential of P. pastoris for flavin overproduction is therefore given, but not pronounced when the yeast is grown on glucose. The aim of this study is to characterize the relative regulatory impact of each riboflavin synthesis gene. Deeper insight into pathway control and the potential of deregulation is established by overexpression of the single genes as well as a combined deregulation of up to all six riboflavin synthesis genes. Results Overexpression of the first gene of the riboflavin biosynthetic pathway (RIB1 is already sufficient to obtain yellow colonies and the accumulation of riboflavin in the supernatant of shake flask cultures growing on glucose. Sequential deregulation of all the genes, by exchange of their native promoter with the strong and constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP increases the riboflavin accumulation significantly. Conclusion The regulation of the pathway is distributed over more than one gene. High cell density cultivations of a P. pastoris strain overexpressing all six RIB genes allow the accumulation of 175 mg/L riboflavin in the supernatant. The basis for rational engineering of riboflavin production in P. pastoris has thus been established.

Habitat variability does not generally promote metabolic network modularity in flies and mammals.

Science.gov (United States)

Takemoto, Kazuhiro

2016-01-01

The evolution of species habitat range is an important topic over a wide range of research fields. In higher organisms, habitat range evolution is generally associated with genetic events such as gene duplication. However, the specific factors that determine habitat variability remain unclear at higher levels of biological organization (e.g., biochemical networks). One widely accepted hypothesis developed from both theoretical and empirical analyses is that habitat variability promotes network modularity; however, this relationship has not yet been directly tested in higher organisms. Therefore, I investigated the relationship between habitat variability and metabolic network modularity using compound and enzymatic networks in flies and mammals. Contrary to expectation, there was no clear positive correlation between habitat variability and network modularity. As an exception, the network modularity increased with habitat variability in the enzymatic networks of flies. However, the observed association was likely an artifact, and the frequency of gene duplication appears to be the main factor contributing to network modularity. These findings raise the question of whether or not there is a general mechanism for habitat range expansion at a higher level (i.e., above the gene scale). This study suggests that the currently widely accepted hypothesis for habitat variability should be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

NARCIS (Netherlands)

Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

2010-01-01

Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

Science.gov (United States)

Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

2006-01-01

Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA) administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene. PMID:16638118

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

Directory of Open Access Journals (Sweden)

Castellano Bernardo

2006-04-01

Full Text Available Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene.

ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster.

Science.gov (United States)

Mousa, Jarrod J; Newsome, Rachel C; Yang, Ye; Jobin, Christian; Bruner, Steven D

2017-01-22

Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export. We recently determined the X-ray structure of ClbM, and showed preliminary data suggesting its specific role in precolibactin transport. Here, we define a functional role of ClbM by examining transport capabilities under various biochemical conditions. Our data indicate ClbM responds to sodium, potassium, and rubidium ion gradients, while also having substantial transport activity in the absence of alkali cations. Copyright © 2016 Elsevier Inc. All rights reserved.

Biosynthetic origin of acetic acid using SNIF-NMR

International Nuclear Information System (INIS)

Boffo, Elisangela Fabiana; Ferreira, Antonio Gilberto

2006-01-01

The main purpose of this work is to describe the use of the technique Site-Specific Natural Isotopic Fractionation of hydrogen (SNIF-NMR), using 2 H and 1 H NMR spectroscopy, to investigate the biosynthetic origin of acetic acid in commercial samples of Brazilian vinegar. This method is based on the deuterium to hydrogen ratio at a specific position (methyl group) of acetic acid obtained by fermentation, through different biosynthetic mechanisms, which result in different isotopic ratios. We measured the isotopic ratio of vinegars obtained through C 3 , C 4 , and CAM biosynthetic mechanisms, blends of C 3 and C 4 (agrins) and synthetic acetic acid. (author)

On sub-modularization and morphological heterogeneity in modular robotics

DEFF Research Database (Denmark)

Lyder, A. H.; Stoy, K.; Garciá, R. F. M.

2012-01-01

Modular robots are a kind of robots built from mechatronic modules, which can be assembled in many different ways allowing the modular robot to assume a wide range of morphologies and functions. An important question in modular robotics is to which degree modules should be heterogeneous....... In this paper we introduce two contributing factors to heterogeneity namely morphological heterogeneity and sub-functional modularization. Respectively, the ideas are to create modules with significantly different morphologies and to spread sub-functionality across modules. Based on these principles we design...... and implement the Thor robot and evaluate it by participating in the ICRA Planetary Robotic Contingency Challenge. The Thor robot demonstrates that sub-functional modularity and morphological heterogeneity may increase the versatility of modular robots while reducing the complexity of individual modules, which...

Differential expression of anthocyanin biosynthetic genes in relation to anthocyanin accumulation in the pericarp of Litchi chinensis Sonn.

Directory of Open Access Journals (Sweden)

Yong-Zan Wei

Full Text Available Litchi has diverse fruit color phenotypes, yet no research reflects the biochemical background of this diversity. In this study, we evaluated 12 litchi cultivars for chromatic parameters and pigments, and investigated the effects of abscisic acid, forchlorofenron (CPPU, bagging and debagging treatments on fruit coloration in cv. Feizixiao, an unevenly red cultivar. Six genes encoding chalcone synthase (CHS, chalcone isomerase (CHI, flavanone 3-hydroxylase (F3H, dihydroflavonol 4-reductase (DFR, anthocyanidin synthase (ANS and UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT were isolated from the pericarp of the fully red litchi cv. Nuomici, and their expression was analyzed in different cultivars and under the above mentioned treatments. Pericarp anthocyanin concentration varied from none to 734 mg m(-2 among the 12 litchi cultivars, which were divided into three coloration types, i.e. non-red ('Kuixingqingpitian', 'Xingqiumili', 'Yamulong'and 'Yongxing No. 2', unevenly red ('Feizixiao' and 'Sanyuehong' and fully red ('Meiguili', 'Baila', Baitangying' 'Guiwei', 'Nuomici' and 'Guinuo'. The fully red type cultivars had different levels of anthocyanin but with the same composition. The expression of the six genes, especially LcF3H, LcDFR, LcANS and LcUFGT, in the pericarp of non-red cultivars was much weaker as compared to those red cultivars. Their expression, LcDFR and LcUFGT in particular, was positively correlated with anthocyanin concentrations in the pericarp. These results suggest the late genes in the anthocyanin biosynthetic pathway were coordinately expressed during red coloration of litchi fruits. Low expression of these genes resulted in absence or extremely low anthocyanin accumulation in non-red cultivars. Zero-red pericarp from either immature or CPPU treated fruits appeared to be lacking in anthocyanins due to the absence of UFGT expression. Among these six genes, only the expression of UFGT was found significantly correlated

An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

OpenAIRE

Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

2010-01-01

Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all th...

Molecular evolution of the lysine biosynthetic pathways.

Science.gov (United States)

Velasco, A M; Leguina, J I; Lazcano, A

2002-10-01

Among the different biosynthetic pathways found in extant organisms, lysine biosynthesis is peculiar because it has two different anabolic routes. One is the diaminopimelic acid pathway (DAP), and the other over the a-aminoadipic acid route (AAA). A variant of the AAA route that includes some enzymes involved in arginine and leucine biosyntheses has been recently reported in Thermus thermophilus (Nishida et al. 1999). Here we describe the results of a detailed genomic analysis of each of the sequences involved in the two lysine anabolic routes, as well as of genes from other routes related to them. No evidence was found of an evolutionary relationship between the DAP and AAA enzymes. Our results suggest that the DAP pathway is related to arginine metabolism, since the lysC, asd, dapC, dapE, and lysA genes from lysine biosynthesis are related to the argB, argC, argD, argE, and speAC genes, respectively, whose products catalyze different steps in arginine metabolism. This work supports previous reports on the relationship between AAA gene products and some enzymes involved in leucine biosynthesis and the tricarboxylic acid cycle (Irvin and Bhattacharjee 1998; Miyazaki et al. 2001). Here we discuss the significance of the recent finding that several genes involved in the arginine (Arg) and leucine (Leu) biosynthesis participate in a new alternative route of the AAA pathway (Miyazaki et al. 2001). Our results demonstrate a clear relationship between the DAP and Arg routes, and between the AAA and Leu pathways.

Rice Ethylene-Response AP2/ERF Factor OsEATB Restricts Internode Elongation by Down-Regulating a Gibberellin Biosynthetic Gene1[W][OA

Science.gov (United States)

Qi, Weiwei; Sun, Fan; Wang, Qianjie; Chen, Mingluan; Huang, Yunqing; Feng, Yu-Qi; Luo, Xiaojin; Yang, Jinshui

2011-01-01

Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops. PMID:21753115

Transcriptional repressor role of PocR on the 1,3-propanediol biosynthetic pathway by Lactobacillus panis PM1.

Science.gov (United States)

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2014-06-01

The regulatory role of a transcriptional regulator (PocR) in the 1,3-propanediol biosynthetic pathway of Lactobacillus panis PM1 contributes to the optimization of 1,3-propanediol production by this strain, which potentially will lead to 1,3-propanediol manufacturing efficiencies. Lactobacillus panis PM1 can utilize a 1,3-propanediol (1,3-PDO) biosynthetic pathway, consisting of diol dehydratase (PduCDE) and 1,3-PDO dehydrogenase, as a NADH recycling system, to survive under various environmental conditions. In this study, we identified a key transcriptional repressor (PocR) which was annotated as a transcriptional factor of AraC family as part of the 1,3-PDO biosynthetic pathway of L. panis PM1. The over-expression of the PocR gene resulted in the significant repression (81 %) of pduC (PduCDE large subunit) transcription, and subsequently, the decreased activity of PduCDE by 22 %. As a result of the regulation of PduCDE, production of both 3-hydroxypropionaldehyde and 1,3-PDO in the PocR over-expressing strain were significantly decreased by 40 % relative to the control strain. These results clearly demonstrate the transcriptional repressor role of PocR in the 1,3-PDO biosynthetic pathway.

Effect of immobilization stress on gene expression of catecholamine biosynthetic enzymes in heart auricles of socially isolated rats

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L. Gavrilovic

2009-12-01

Full Text Available Chronic stress is associated with the development of cardiovascular diseases. The sympathoneural system plays an important role in the regulation of cardiac function both in health and disease. In the present study, the changes in gene expression of the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH, dopamine-β-hydroxylase (DBH and phenylethanolamine N-methyltransferase (PNMT and protein levels in the right and left heart auricles of naive control and long-term (12 weeks socially isolated rats were investigated by Taqman RT-PCR and Western blot analysis. The response of these animals to additional immobilization stress (2 h was also examined. Long-term social isolation produced a decrease in TH mRNA level in left auricles (about 70% compared to the corresponding control. Expression of the DBH gene was markedly decreased both in the right (about 62% and left (about 81% auricles compared to the corresponding control, group-maintained rats, whereas PNMT mRNA levels remained unchanged. Exposure of group-housed rats to acute immobilization for 2 h led to a significant increase of mRNA levels of TH (about 267%, DBH (about 37% and PNMT (about 60% only in the right auricles. Additional 2-h immobilization of individually housed rats did not affect gene expression of these enzymes in either the right or left auricle. Protein levels of TH, DBH and PNMT in left and right heart auricles were unchanged either in both individually housed and immobilized rats. The unchanged mRNA levels of the enzymes examined after short-term immobilization suggest that the catecholaminergic system of the heart auricles of animals previously exposed to chronic psychosocial stress was adapted to maintain appropriate cardiovascular homeostasis.

Service Modularity

DEFF Research Database (Denmark)

Avlonitis, Viktor; Hsuan, Juliana

2015-01-01

The purpose of this research is to investigate the studies on service modularity with a goal of informing service science and advancing contemporary service systems research. Modularity, a general systems property, can add theoretical underpinnings to the conceptual development of service science...... in general and service systems in particular. Our research is guided by the following question: how can modularity theory inform service system design? We present a review of the modularity literature and associated concepts. We then introduce the contemporary service science and service system discourse...

Biosynthetic pathway for γ-cyclic sarcinaxanthin in Micrococcus luteus: heterologous expression and evidence for diverse and multiple catalytic functions of C(50) carotenoid cyclases.

Science.gov (United States)

Netzer, Roman; Stafsnes, Marit H; Andreassen, Trygve; Goksøyr, Audun; Bruheim, Per; Brautaset, Trygve

2010-11-01

We report the cloning and characterization of the biosynthetic gene cluster (crtE, crtB, crtI, crtE2, crtYg, crtYh, and crtX) of the γ-cyclic C(50) carotenoid sarcinaxanthin in Micrococcus luteus NCTC2665. Expression of the complete and partial gene cluster in Escherichia coli hosts revealed that sarcinaxanthin biosynthesis from the precursor molecule farnesyl pyrophosphate (FPP) proceeds via C(40) lycopene, C(45) nonaflavuxanthin, C(50) flavuxanthin, and C(50) sarcinaxanthin. Glucosylation of sarcinaxanthin was accomplished by the crtX gene product. This is the first report describing the biosynthetic pathway of a γ-cyclic C(50) carotenoid. Expression of the corresponding genes from the marine M. luteus isolate Otnes7 in a lycopene-producing E. coli host resulted in the production of up to 2.5 mg/g cell dry weight sarcinaxanthin in shake flasks. In an attempt to experimentally understand the specific difference between the biosynthetic pathways of sarcinaxanthin and the structurally related ε-cyclic decaprenoxanthin, we constructed a hybrid gene cluster with the γ-cyclic C(50) carotenoid cyclase genes crtYg and crtYh from M. luteus replaced with the analogous ε-cyclic C(50) carotenoid cyclase genes crtYe and crtYf from the natural decaprenoxanthin producer Corynebacterium glutamicum. Surprisingly, expression of this hybrid gene cluster in an E. coli host resulted in accumulation of not only decaprenoxanthin, but also sarcinaxanthin and the asymmetric ε- and γ-cyclic C(50) carotenoid sarprenoxanthin, described for the first time in this work. Together, these data contributed to new insight into the diverse and multiple functions of bacterial C(50) carotenoid cyclases as key catalysts for the synthesis of structurally different carotenoids.

Perturbations of carotenoid and tetrapyrrole biosynthetic pathways result in differential alterations in chloroplast function and plastid signaling.

Science.gov (United States)

Park, Joon-Heum; Jung, Sunyo

2017-01-22

In this study, we used the biosynthetic inhibitors of carotenoid and tetrapyrrole biosynthetic pathways, norflurazon (NF) and oxyfluorfen (OF), as tools to gain insight into mechanisms of photooxidation in rice plants. NF resulted in bleaching symptom on leaves of the treated plants, whereas OF treatment developed a fast symptom of an apparent necrotic phenotype. Both plants exhibited decreases in photosynthetic efficiency, as indicated by F v /F m . NF caused severe disruption in thylakoid membranes, whereas OF-treated plants exhibited disruption of chloroplast envelope and plasma membrane. Levels of Lhca and Lhcb proteins in photosystem I (PSI) and PSII were reduced by photooxidative stress in NF- and OF-treated plants, with a greater decrease in NF plants. The down-regulation of nuclear-encoded photosynthesis genes Lhcb and rbcS was also found in both NF- and OF-treated plants, whereas plastid-encoded photosynthetic genes including RbcL, PsaC, and PsbD accumulated normally in NF plants but decreased drastically in OF plants. This proposes that the plastids in NF plants retain their potential to develop thylakoid membranes and that photobleaching is mainly controlled by nuclear genes. Distinct photooxidation patterns between NF- and OF-treated plants developed differential signaling, which might enable the plant to coordinate the expression of photosynthetic genes from the nuclear and plastidic genomes. Copyright © 2016 Elsevier Inc. All rights reserved.

MIDAS: A Modular DNA Assembly System for Synthetic Biology.

Science.gov (United States)

van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

2018-04-20

A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

Modularity and Economic Organization

DEFF Research Database (Denmark)

Sanchez, Ron; Mahoney, Joseph T.

This paper addresses modularity as a basis for organizing economic activity. We first define the key concepts of architecture and of modularity as a special form of architecture. We then suggest how modular systems of all types may exhibit several properties of fundamental importance to the organ......This paper addresses modularity as a basis for organizing economic activity. We first define the key concepts of architecture and of modularity as a special form of architecture. We then suggest how modular systems of all types may exhibit several properties of fundamental importance...... to the organization of economic activities, including greater adaptability and evolvability than systems that lack modular properties. We draw extensively on our original 1996 paper on modularity and subsequent research to suggest broad theoretical implications of modularity for (i) firms' product strategies...... markets. We also discuss an evolutionary perspective on modularity as an emergent phenomenon in firms and industries. We explain how modularity as a relatively new field of strategy and economic research may provide a new theoretical perspective on economic organizing that has significant potential...

Functional Characterization of a Novel R2R3-MYB Transcription Factor Modulating the Flavonoid Biosynthetic Pathway from Epimedium sagittatum

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Wenjun Huang

2017-07-01

Full Text Available Epimedium species have been widely used both as traditional Chinese medicinal plants and ornamental perennials. Both flavonols, acting as the major bioactive components (BCs and anthocyanins, predominantly contributing to the color diversity of Epimedium flowers belong to different classes of flavonoids. It is well-acknowledged that flavonoid biosynthetic pathway is predominantly regulated by R2R3-MYB transcription factor (TF as well as bHLH TF and WD40 protein at the transcriptional level. MYB TFs specifically regulating anthocyanin or flavonol biosynthetic pathway have been already isolated and functionally characterized from Epimedium sagittatum, but a R2R3-MYB TF involved in regulating both these two pathways has not been functionally characterized to date in Epimedium plants. In this study, we report the functional characterization of EsMYB9, a R2R3-MYB TF previously isolated from E. sagittatum. The previous study indicated that EsMYB9 belongs to a small subfamily of R2R3-MYB TFs containing grape VvMYB5a and VvMYB5b TFs, which regulate flavonoid biosynthetic pathway. The present studies show that overexpression of EsMYB9 in tobacco leads to increased transcript levels of flavonoid pathway genes and increased contents of anthocyanins and flavonols. Yeast two-hybrid assay indicates that the C-terminal region of EsMYB9 contributes to the autoactivation activity, and EsMYB9 interacts with EsTT8 or AtTT8 bHLH regulator. Transient reporter assay shows that EsMYB9 slightly activates the expression of EsCHS (chalcone synthase promoter in transiently transformed leaves of Nicotiana benthamiana, but the addition of AtTT8 or EsTT8 bHLH regulator strongly enhances the transcriptional activation of EsMYB9 against five promoters of the flavonoid pathway genes except EsFLS (flavonol synthase. In addition, co-transformation of EsMYB9 and EsTT8 in transiently transfected tobacco leaves strongly induces the expressions of flavonoid biosynthetic genes. The

A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

Science.gov (United States)

Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

2016-06-01

Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs. Copyright © 2016 Elsevier Inc. All rights reserved.

ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster

International Nuclear Information System (INIS)

Mousa, Jarrod J.; Newsome, Rachel C.; Yang, Ye; Jobin, Christian; Bruner, Steven D.

2017-01-01

Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export. We recently determined the X-ray structure of ClbM, and showed preliminary data suggesting its specific role in precolibactin transport. Here, we define a functional role of ClbM by examining transport capabilities under various biochemical conditions. Our data indicate ClbM responds to sodium, potassium, and rubidium ion gradients, while also having substantial transport activity in the absence of alkali cations. - Highlights: • ClbM is a cation promiscuous MATE multidrug transporter. • The role of key residues were identified in both the cation and proton binding. • The biologically relevant substrate for ClbM is the natural product precolibactin.

Understanding Socio Technical Modularity

DEFF Research Database (Denmark)

Thuesen, Christian Langhoff; Kudsk, Anders; Hvam, Lars

2011-01-01

Modularity has gained an increasing popularity as a central concept for exploring product structure, process structure, organization structure and supply chain structure. With the offset in system theory the predominant understanding of modularity however faces difficulties in explaining the social...... dimension of modularity like irrational behaviors, cultural differences, learning processes, social organization and institutional influences on modularity. The paper addresses this gab offering a reinterpretation of the modularity concept from a socio-technical perspective in general and Actor Network...... Theory in particular. By formulating modularity from an ANT perspective covering social, material and process aspects, the modularity of a socio-technical system can be understood as an entanglement of product, process, organizational and institutional modularity. The theoretical framework is illustrated...

Lectures on Hilbert modular varieties and modular forms

CERN Document Server

Goren, Eyal Z

2001-01-01

This book is devoted to certain aspects of the theory of p-adic Hilbert modular forms and moduli spaces of abelian varieties with real multiplication. The theory of p-adic modular forms is presented first in the elliptic case, introducing the reader to key ideas of N. M. Katz and J.-P. Serre. It is re-interpreted from a geometric point of view, which is developed to present the rudiments of a similar theory for Hilbert modular forms. The theory of moduli spaces of abelian varieties with real multiplication is presented first very explicitly over the complex numbers. Aspects of the general theory are then exposed, in particular, local deformation theory of abelian varieties in positive characteristic. The arithmetic of p-adic Hilbert modular forms and the geometry of moduli spaces of abelian varieties are related. This relation is used to study q-expansions of Hilbert modular forms, on the one hand, and stratifications of moduli spaces on the other hand. The book is addressed to graduate students and non-exper...

Virulence factor rtx in Legionella pneumophila, evidence suggesting it is a modular multifunctional protein

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Pelaz Carmen

2008-01-01

Full Text Available Abstract Background The repeats in toxin (Rtx are an important pathogenicity factor involved in host cells invasion of Legionella pneumophila and other pathogenic bacteria. Its role in escaping the host immune system and cytotoxic activity is well known. Its repeated motives and modularity make Rtx a multifunctional factor in pathogenicity. Results The comparative analysis of rtx gene among 6 strains of L. pneumophila showed modularity in their structures. Among compared genomes, the N-terminal region of the protein presents highly dissimilar repeats with functionally similar domains. On the contrary, the C-terminal region is maintained with a fashionable modular configuration, which gives support to its proposed role in adhesion and pore formation. Despite the variability of rtx among the considered strains, the flanking genes are maintained in synteny and similarity. Conclusion In contrast to the extracellular bacteria Vibrio cholerae, in which the rtx gene is highly conserved and flanking genes have lost synteny and similarity, the gene region coding for the Rtx toxin in the intracellular pathogen L. pneumophila shows a rapid evolution. Changes in the rtx could play a role in pathogenicity. The interplay of the Rtx toxin with host membranes might lead to the evolution of new variants that are able to escape host cell defences.

Transcriptional regulation of genes involved in terpenoid índole alkaloid production in Catharanthus roseus seedlings

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Pedro J. Rocha

2002-07-01

Full Text Available Catharanthus roseus (L. G Don is a medicinal plant that produces a variety of terpenoid indole alkaloids (TIAs, some of which display pharmacological activity. C. roseus plants and cell cultures have been used to elucidate the TIAs biosynthetic pathway. A considerable number or enzymes have also been characterised, and their respective genes cloned. TIAs production in C. roseus plant and cell cultures is highly regulated at transcriptional-, develop-mental-, and environmental-level. Studies into TIAs biosynthetic gene regulation have been carried out using cell cultures. However, regulation in plants is almost unknown. Here, biosynthetic genes idc, strl, d4h and dat expres-sion levels are qualitatively examined in a developmental series of C. roseus seedlings. The effect of water- and light-stress and methyl jasmonate (MeJa and acetyl salicylic acid (ASA elicitation is also examined. Comparison between seedlings and cell cultures strongly suggests that TIAs biosynthetic gene transcriptional regulation is different in C.roseus plants and cell cultures.

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

Science.gov (United States)

2011-01-01

Background Panax notoginseng (Burk) F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. Results Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. Conclusion This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next-generation sequencing (NGS

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

Directory of Open Access Journals (Sweden)

Luo Hongmei

2011-12-01

Full Text Available Abstract Background Panax notoginseng (Burk F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. Results Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS, which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158 and UDP-glycosyltransferase (Pn00082 gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH, and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. Conclusion This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next

Modular implicits

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Leo White

2015-12-01

Full Text Available We present modular implicits, an extension to the OCaml language for ad-hoc polymorphism inspired by Scala implicits and modular type classes. Modular implicits are based on type-directed implicit module parameters, and elaborate straightforwardly into OCaml's first-class functors. Basing the design on OCaml's modules leads to a system that naturally supports many features from other languages with systematic ad-hoc overloading, including inheritance, instance constraints, constructor classes and associated types.

Product Architecture Modularity Strategies

DEFF Research Database (Denmark)

Mikkola, Juliana Hsuan

2003-01-01

The focus of this paper is to integrate various perspectives on product architecture modularity into a general framework, and also to propose a way to measure the degree of modularization embedded in product architectures. Various trade-offs between modular and integral product architectures...... and how components and interfaces influence the degree of modularization are considered. In order to gain a better understanding of product architecture modularity as a strategy, a theoretical framework and propositions are drawn from various academic literature sources. Based on the literature review......, the following key elements of product architecture are identified: components (standard and new-to-the-firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical function, termed modularization function, is introduced to measure the degree of modularization...

Modular entanglement.

Science.gov (United States)

Gualdi, Giulia; Giampaolo, Salvatore M; Illuminati, Fabrizio

2011-02-04

We introduce and discuss the concept of modular entanglement. This is the entanglement that is established between the end points of modular systems composed by sets of interacting moduli of arbitrarily fixed size. We show that end-to-end modular entanglement scales in the thermodynamic limit and rapidly saturates with the number of constituent moduli. We clarify the mechanisms underlying the onset of entanglement between distant and noninteracting quantum systems and its optimization for applications to quantum repeaters and entanglement distribution and sharing.

The expression of antibiotic resistance genes in antibiotic-producing bacteria.

Science.gov (United States)

Mak, Stefanie; Xu, Ye; Nodwell, Justin R

2014-08-01

Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

Overexpression of the Squalene Epoxidase Gene Alone and in Combination with the 3-Hydroxy-3-methylglutaryl Coenzyme A Gene Increases Ganoderic Acid Production in Ganoderma lingzhi.

Science.gov (United States)

Zhang, De-Huai; Jiang, Lu-Xi; Li, Na; Yu, Xuya; Zhao, Peng; Li, Tao; Xu, Jun-Wei

2017-06-14

The squalene epoxidase (SE) gene from the biosynthetic pathway of ganoderic acid (GA) was cloned and overexpressed in Ganoderma lingzhi. The strain that overexpressed the SE produced approximately 2 times more GA molecules than the wild-type (WT) strain. Moreover, SE overexpression upregulated lanosterol synthase gene expression in the biosynthetic pathway. These results indicated that SE stimulates GA accumulation. Then, the SE and 3-hydroxy-3-methylglutaryl coenzyme A (HMGR) genes were simultaneously overexpressed in G. lingzhi. Compared with the individual overexpression of SE or HMGR, the combined overexpression of the two genes further enhanced individual GA production. The overexpressing strain produced maximum GA-T, GA-S, GA-Mk, and GA-Me contents of 90.4 ± 7.5, 35.9 ± 5.4, 6.2 ± 0.5, and 61.8 ± 5.8 μg/100 mg dry weight, respectively. These values were 5.9, 4.5, 2.4, and 5.8 times higher than those produced by the WT strain. This is the first example of the successful manipulation of multiple biosynthetic genes to improve GA content in G. lingzhi.

Complexity in Managing Modularization

DEFF Research Database (Denmark)

Hansen, Poul H. Kyvsgård; Sun, Hongyi

2011-01-01

In general, the phenomenon of managing modularization is not well known. The cause-effect relationships between modularization and realized benefits are complex and comprehensive. Though a number of research works have contributed to the study of the phenomenon of efficient and effective...... modularization management it is far from clarified. Recognizing the need for further empirical research, we have studied 40 modularity cases in various companies. The studies have been designed as long-term studies leaving time for various types of modularization benefits to emerge. Based on these studies we...... have developed a framework to support the heuristic and iterative process of planning and realizing modularization benefits....

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

OpenAIRE

Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

2006-01-01

Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn S...

Modular organization of the white spruce (Picea glauca) transcriptome reveals functional organization and evolutionary signatures.

Science.gov (United States)

Raherison, Elie S M; Giguère, Isabelle; Caron, Sébastien; Lamara, Mebarek; MacKay, John J

2015-07-01

Transcript profiling has shown the molecular bases of several biological processes in plants but few studies have developed an understanding of overall transcriptome variation. We investigated transcriptome structure in white spruce (Picea glauca), aiming to delineate its modular organization and associated functional and evolutionary attributes. Microarray analyses were used to: identify and functionally characterize groups of co-expressed genes; investigate expressional and functional diversity of vascular tissue preferential genes which were conserved among Picea species, and identify expression networks underlying wood formation. We classified 22 857 genes as variable (79%; 22 coexpression groups) or invariant (21%) by profiling across several vegetative tissues. Modular organization and complex transcriptome restructuring among vascular tissue preferential genes was revealed by their assignment to coexpression groups with partially overlapping profiles and partially distinct functions. Integrated analyses of tissue-based and temporally variable profiles identified secondary xylem gene networks, showed their remodelling over a growing season and identified PgNAC-7 (no apical meristerm (NAM), Arabidopsis transcription activation factor (ATAF) and cup-shaped cotyledon (CUC) transcription factor 007 in Picea glauca) as a major hub gene specific to earlywood formation. Reference profiling identified comprehensive, statistically robust coexpressed groups, revealing that modular organization underpins the evolutionary conservation of the transcriptome structure. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Exploring Modularity in Services

DEFF Research Database (Denmark)

Avlonitis, Viktor; Hsuan, Juliana

2017-01-01

the effects of modularity and integrality on a range of different analytical levels in service architectures. Taking a holistic approach, the authors synthesize and empirically deploy a framework comprised of the three most prevalent themes in modularity and service design literature: Offering (service...... insights on the mirroring hypothesis of modularity theory to services. Originality/value The paper provides a conceptualization of service architectures drawing on service design, modularity, and market relationships. The study enriches service design literature with elements from modularity theory...

Network modularity reveals critical scales for connectivity in ecology and evolution

Science.gov (United States)

Fletcher, Robert J.; Revell, Andre; Reichert, Brian E.; Kitchens, Wiley M.; Dixon, J.; Austin, James D.

2013-01-01

For nearly a century, biologists have emphasized the profound importance of spatial scale for ecology, evolution and conservation. Nonetheless, objectively identifying critical scales has proven incredibly challenging. Here we extend new techniques from physics and social sciences that estimate modularity on networks to identify critical scales for movement and gene flow in animals. Using four species that vary widely in dispersal ability and include both mark-recapture and population genetic data, we identify significant modularity in three species, two of which cannot be explained by geographic distance alone. Importantly, the inclusion of modularity in connectivity and population viability assessments alters conclusions regarding patch importance to connectivity and suggests higher metapopulation viability than when ignoring this hidden spatial scale. We argue that network modularity reveals critical meso-scales that are probably common in populations, providing a powerful means of identifying fundamental scales for biology and for conservation strategies aimed at recovering imperilled species.

The preliminary research for biosynthetic engineering by radiation fusion technology

Energy Technology Data Exchange (ETDEWEB)

Roh, Chang Hyun; Jung, U Hee; Park, Hae Ran [KAERI, Daejeon (Korea, Republic of)

2012-01-15

The purpose of this project is to elucidate the solution to the production of bioactive substance using biotransformation process from core technology of biosynthetic engineering by radiation fusion technology. And, this strategy will provide core technology for development of drugs as new concept and category. Research scopes and contents of project include 1) The development of mutant for biosynthetic engineering by radiation fusion technology 2) The development of host for biosynthetic engineering by radiation fusion technology 3) The preliminary study for biosynthetic engineering of isoflavone by radiation fusion technology. The results are as follows. Isoflavone compounds(daidzein, hydroxylated isoflavone) were analyzed by GC-MS. The study of radiation doses and p-NCA high-throughput screening for mutant development were elucidated. And, it was carried out the study of radiation doses for host development. Furthermore, the study of redox partner and construction of recombinant strain for region-specific hydroxylation(P450, redox partner). In addition, the biological effect of 6,7,4'-trihydroxyisoflavone as an anti-obesity agent was elucidated in this study.

Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-l-galactose mutase.

Science.gov (United States)

Zhu, Qinghua; Chen, Qi; Song, Yongxiang; Huang, Hongbo; Li, Jun; Ma, Junying; Li, Qinglian; Ju, Jianhua

2017-05-09

Galactose, a monosaccharide capable of assuming two possible configurational isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Gal p ), or as a five-membered ring, galactofuranose (Gal f ). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for d-Gal f Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive l-Gal f production have not yet been characterized. Herein we report that efforts to decipher the sugar biosynthetic pathway and tailoring steps en route to nucleoside antibiotic A201A led to the discovery of a GDP-l-galactose mutase, MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A cluster and elucidation of 10 congeners, coupled with feeding and in vitro biochemical experiments, enabled us to: ( i ) decipher the unique enzyme, GDP-l-galactose mutase associated with production of two unique d-mannose-derived sugars, and ( ii ) assign two glycosyltransferases, four methyltransferases, and one desaturase that regiospecifically tailor the A201A scaffold and display relaxed substrate specificities. Taken together, these data provide important insight into the origin of l-Gal f -containing natural product biosynthetic pathways with likely ramifications in other organisms and possible antimicrobial drug targeting strategies.

The Mycoplasma hominis vaa gene displays a mosaic gene structure

DEFF Research Database (Denmark)

Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.

1998-01-01

Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

Mutation of a Rice Gene Encoding a Phenylalanine Biosynthetic Enzyme Results in Accumulation of Phenylalanine and Tryptophan[W

Science.gov (United States)

Yamada, Tetsuya; Matsuda, Fumio; Kasai, Koji; Fukuoka, Shuichi; Kitamura, Keisuke; Tozawa, Yuzuru; Miyagawa, Hisashi; Wakasa, Kyo

2008-01-01

Two distinct biosynthetic pathways for Phe in plants have been proposed: conversion of prephenate to Phe via phenylpyruvate or arogenate. The reactions catalyzed by prephenate dehydratase (PDT) and arogenate dehydratase (ADT) contribute to these respective pathways. The Mtr1 mutant of rice (Oryza sativa) manifests accumulation of Phe, Trp, and several phenylpropanoids, suggesting a link between the synthesis of Phe and Trp. Here, we show that the Mtr1 mutant gene (mtr1-D) encodes a form of rice PDT with a point mutation in the putative allosteric regulatory region of the protein. Transformed callus lines expressing mtr1-D exhibited all the characteristics of Mtr1 callus tissue. Biochemical analysis revealed that rice PDT possesses both PDT and ADT activities, with a preference for arogenate as substrate, suggesting that it functions primarily as an ADT. The wild-type enzyme is feedback regulated by Phe, whereas the mutant enzyme showed a reduced feedback sensitivity, resulting in Phe accumulation. In addition, these observations indicate that rice PDT is critical for regulating the size of the Phe pool in plant cells. Feeding external Phe to wild-type callus tissue and seedlings resulted in Trp accumulation, demonstrating a connection between Phe accumulation and Trp pool size. PMID:18487352

The hedgehog pathway gene shifted functions together with the hmgcr-dependent isoprenoid biosynthetic pathway to orchestrate germ cell migration.

Directory of Open Access Journals (Sweden)

Girish Deshpande

Full Text Available The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs and the Somatic Gonadal Precursor cells (SGPs. The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh pathway gene shifted (shf in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss- and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.

Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera

DEFF Research Database (Denmark)

Ono, Hajime; Rewitz, Kim; Shinoda, Tetsu

2006-01-01

is eliminated in larvae carrying mutations in molting defective (mld), a gene encoding a nuclear zinc finger protein that is required for production of ecdysone during Drosophila larval development. Intriguingly, mld is not present in the Bombyx mori genome, and we have identified only one spook homolog in both...... Bombyx and Manduca that is expressed in both embryos and larva. These studies suggest an evolutionary split between Diptera and Lepidoptera in how the ecdysone biosynthetic pathway is regulated during development....

Service Modularity and Architecture

DEFF Research Database (Denmark)

Brax, Saara A.; Bask, Anu; Hsuan, Juliana

2017-01-01

, platform-based and mass-customized service business models, comparative research designs, customer perspectives and service experience, performance in context of modular services, empirical evidence of benefits and challenges, architectural innovation in services, modularization in multi-provider contexts......Purpose: Services are highly important in a world economy which has increasingly become service driven. There is a growing need to better understand the possibilities for, and requirements of, designing modular service architectures. The purpose of this paper is to elaborate on the roots...... of the emerging research stream on service modularity, provide a concise overview of existing work on the subject, and outline an agenda for future research on service modularity and architecture. The articles in the special issue offer four diverse sets of research on service modularity and architecture. Design...

Modules Identification in Gene Positive Networks of Hepatocellular Carcinoma Using Pearson Agglomerative Method and Pearson Cohesion Coupling Modularity

Directory of Open Access Journals (Sweden)

Jinyu Hu

2012-01-01

Full Text Available In this study, a gene positive network is proposed based on a weighted undirected graph, where the weight represents the positive correlation of the genes. A Pearson agglomerative clustering algorithm is employed to build a clustering tree, where dotted lines cut the tree from bottom to top leading to a number of subsets of the modules. In order to achieve better module partitions, the Pearson correlation coefficient modularity is addressed to seek optimal module decomposition by selecting an optimal threshold value. For the liver cancer gene network under study, we obtain a strong threshold value at 0.67302, and a very strong correlation threshold at 0.80086. On the basis of these threshold values, fourteen strong modules and thirteen very strong modules are obtained respectively. A certain degree of correspondence between the two types of modules is addressed as well. Finally, the biological significance of the two types of modules is analyzed and explained, which shows that these modules are closely related to the proliferation and metastasis of liver cancer. This discovery of the new modules may provide new clues and ideas for liver cancer treatment.

Modular forms

NARCIS (Netherlands)

Edixhoven, B.; van der Geer, G.; Moonen, B.; Edixhoven, B.; van der Geer, G.; Moonen, B.

2008-01-01

Modular forms are functions with an enormous amount of symmetry that play a central role in number theory, connecting it with analysis and geometry. They have played a prominent role in mathematics since the 19th century and their study continues to flourish today. Modular forms formed the

Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery.

Science.gov (United States)

Rigali, Sébastien; Anderssen, Sinaeda; Naômé, Aymeric; van Wezel, Gilles P

2018-01-05

The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance in weeds threatens the crop industry. On the positive side, it is likely that the chemical space of natural products goes far beyond what has currently been discovered. This idea is fueled by genome sequencing of microorganisms which unveiled numerous so-called cryptic biosynthetic gene clusters (BGCs), many of which are transcriptionally silent under laboratory culture conditions, and by the fact that most bacteria cannot yet be cultivated in the laboratory. However, brute force antibiotic discovery does not yield the same results as it did in the past, and researchers have had to develop creative strategies in order to unravel the hidden potential of microorganisms such as Streptomyces and other antibiotic-producing microorganisms. Identifying the cis elements and their corresponding transcription factors(s) involved in the control of BGCs through bioinformatic approaches is a promising strategy. Theoretically, we are a few 'clicks' away from unveiling the culturing conditions or genetic changes needed to activate the production of cryptic metabolites or increase the production yield of known compounds to make them economically viable. In this opinion article, we describe and illustrate the idea beyond 'cracking' the regulatory code for natural product discovery, by presenting a series of proofs of concept, and discuss what still should be achieved to increase the rate of success of this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

Modular design in fahion industry

Directory of Open Access Journals (Sweden)

Ying Chen

2018-03-01

Full Text Available "Modular design" is a kind of design mode that not only can made clothing more interesting, makes the wearer can participate in choices, increase the possibility of clothing style .but also can extend the service cycle of clothing. In this "fast fashion" run market, the design idea of modular design can be a breakthrough point, help us find the way to balance the low-carbon and environmentally-friendly need and fashion. The article will combine the existing examples put the modular design summarized into three categories: component modular design and geometric modular design and compounded modular design.

[Modular enteral nutrition in pediatrics].

Science.gov (United States)

Murillo Sanchís, S; Prenafeta Ferré, M T; Sempere Luque, M D

1991-01-01

Modular Enteral Nutrition may be a substitute for Parenteral Nutrition in children with different pathologies. Study of 4 children with different pathologies selected from a group of 40 admitted to the Maternal-Childrens Hospital "Valle de Hebrón" in Barcelona, who received modular enteral nutrition. They were monitored on a daily basis by the Dietician Service. Modular enteral nutrition consists of modules of proteins, peptides, lipids, glucids and mineral salts-vitamins. 1.--Craneo-encephalic traumatisms with loss of consciousness, Feeding with a combination of parenteral nutrition and modular enteral nutrition for 7 days. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended and modular enteral nutrition alone used up to a total of 43 days. 2.--55% burns with 36 days of hyperproteic modular enteral nutrition together with normal feeding. A more rapid recovery was achieved with an increase in total proteins and albumin. 3.--Persistent diarrhoea with 31 days of modular enteral nutrition, 5 days on parenteral nutrition alone and 8 days on combined parenteral nutrition and modular enteral nutrition. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended. 4.--Mucoviscidosis with a total of 19 days on modular enteral nutrition, 12 of which were exclusively on modular enteral nutrition and 7 as a night supplement to normal feeding. We administered proteic intakes of up to 20% of the total calorific intake and in concentrations of up to 1.2 calories/ml of the final preparation, always with a good tolerance. Modular enteral nutrition can and should be used as a substitute for parenteral nutrition in children with different pathologies, thus preventing the complications inherent in parenteral nutrition.

Modular Robotic Wearable

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Pagliarini, Luigi

2009-01-01

In this concept paper we trace the contours and define a new approach to robotic systems, composed of interactive robotic modules which are somehow worn on the body. We label such a field as Modular Robotic Wearable (MRW). We describe how, by using modular robotics for creating wearable....... Finally, by focusing on the intersection of the combination modular robotic systems, wearability, and bodymind we attempt to explore the theoretical characteristics of such approach and exploit the possible playware application fields....

Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

Directory of Open Access Journals (Sweden)

Emily J. Parker

2013-08-01

Full Text Available The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse. This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.

A modular optical sensor

Science.gov (United States)

Conklin, John Albert

This dissertation presents the design of a modular, fiber-optic sensor and the results obtained from testing the modular sensor. The modular fiber-optic sensor is constructed in such manner that the sensor diaphragm can be replaced with different configurations to detect numerous physical phenomena. Additionally, different fiber-optic detection systems can be attached to the sensor. Initially, the modular sensor was developed to be used by university of students to investigate realistic optical sensors and detection systems to prepare for advance studies of micro-optical mechanical systems (MOMS). The design accomplishes this by doing two things. First, the design significantly lowers the costs associated with studying optical sensors by modularizing the sensor design. Second, the sensor broadens the number of physical phenomena that students can apply optical sensing techniques to in a fiber optics sensor course. The dissertation is divided into seven chapters covering the historical development of fiber-optic sensors, a theoretical overview of fiber-optic sensors, the design, fabrication, and the testing of the modular sensor developed in the course of this work. Chapter 1 discusses, in detail, how this dissertation is organized and states the purpose of the dissertation. Chapter 2 presents an historical overview of the development of optical fibers, optical pressure sensors, and fibers, optical pressure sensors, and optical microphones. Chapter 3 reviews the theory of multi-fiber optic detection systems, optical microphones, and pressure sensors. Chapter 4 presents the design details of the modular, optical sensor. Chapter 5 delves into how the modular sensor is fabricated and how the detection systems are constructed. Chapter 6 presents the data collected from the microphone and pressure sensor configurations of the modular sensor. Finally, Chapter 7 discusses the data collected and draws conclusions about the design based on the data collected. Chapter 7 also

From modular invariants to graphs: the modular splitting method

International Nuclear Information System (INIS)

Isasi, E; Schieber, G

2007-01-01

We start with a given modular invariant M of a two-dimensional su-hat(n) k conformal field theory (CFT) and present a general method for solving the Ocneanu modular splitting equation and then determine, in a step-by-step explicit construction (1) the generalized partition functions corresponding to the introduction of boundary conditions and defect lines; (2) the quantum symmetries of the higher ADE graph G associated with the initial modular invariant M. Note that one does not suppose here that the graph G is already known, since it appears as a by-product of the calculations. We analyse several su-hat(3) k exceptional cases at levels 5 and 9

Evolution of Modularity Literature

DEFF Research Database (Denmark)

Frandsen, Thomas

2017-01-01

Purpose The purpose of this paper is to review and analyze the modularity literature to identify the established and emerging perspectives. Design/methodology/approach A systematic literature search and review was conducted through the use of bibliometrics and network analysis. The analysis...... identified structure within the literature, which revealed how the research area evolved between 1990 and 2015. Based on this search, the paper establishes the basis for analyzing the structure of modularity literature. Findings Factors were identified within the literature, demonstrating how it has evolved...... from a primary focus on the modularity of products to a broader view of the applicability of modularity. Within the last decade, numerous research areas have emerged within the broader area of modularity. Through core-periphery analysis, eight emerging sub-research areas are identified, of which one...

Polycistronic gene expression in Aspergillus niger.

Science.gov (United States)

Schuetze, Tabea; Meyer, Vera

2017-09-25

Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

Modularization of Industrial Service Processes

DEFF Research Database (Denmark)

Frandsen, Thomas; Hsuan, Juliana

In this paper we examine how complex service processes can be dealt with through the lenses of modularization strategies. Through an illustrative case study of a manufacturer of industrial equipment for process industries we propose the use of the service modularity function to conceptualize...... and assess the service modularity of service offerings. The measured degree of modularity would allow us to sharpen our understanding of modularity in the context of industrial services, such as the role of standardization and component reuse on architecture flexibility. It would also provide a foundation...

Molecular characterization of a fungal gene paralogue of the penicillin penDE gene of Penicillium chrysogenum

Science.gov (United States)

2009-01-01

Background Penicillium chrysogenum converts isopenicillin N (IPN) into hydrophobic penicillins by means of the peroxisomal IPN acyltransferase (IAT), which is encoded by the penDE gene. In silico analysis of the P. chrysogenum genome revealed the presence of a gene, Pc13g09140, initially described as paralogue of the IAT-encoding penDE gene. We have termed this gene ial because it encodes a protein with high similarity to IAT (IAL for IAT-Like). We have conducted an investigation to characterize the ial gene and to determine the role of the IAL protein in the penicillin biosynthetic pathway. Results The IAL contains motifs characteristic of the IAT such as the processing site, but lacks the peroxisomal targeting sequence ARL. Null ial mutants and overexpressing strains indicated that IAL lacks acyltransferase (penicillin biosynthetic) and amidohydrolase (6-APA forming) activities in vivo. When the canonical ARL motif (leading to peroxisomal targeting) was added to the C-terminus of the IAL protein (IALARL) by site-directed mutagenesis, no penicillin biosynthetic activity was detected. Since the IAT is only active after an accurate self-processing of the preprotein into α and β subunits, self-processing of the IAL was tested in Escherichia coli. Overexpression experiments and SDS-PAGE analysis revealed that IAL is also self-processed in two subunits, but despite the correct processing, the enzyme remained inactive in vitro. Conclusion No activity related to the penicillin biosynthesis was detected for the IAL. Sequence comparison among the P. chrysogenum IAL, the A. nidulans IAL homologue and the IAT, revealed that the lack of enzyme activity seems to be due to an alteration of the essential Ser309 in the thioesterase active site. Homologues of the ial gene have been found in many other ascomycetes, including non-penicillin producers. Our data suggest that like in A. nidulans, the ial and penDE genes might have been formed from a single ancestral gene that became

Designing Modular Robotic Playware

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Marti, Patrizia

2009-01-01

In this paper, we explore the design of modular robotic objects that may enhance playful experiences. The approach builds upon the development of modular robotics to create a kind of playware, which is flexible in both set-up and activity building for the end-user to allow easy creation of games....... Key features of this design approach are modularity, flexibility, and construction, immediate feedback to stimulate engagement, activity design by end-users, and creative exploration of play activities. These features permit the use of such modular playware by a vast array of users, including disabled...... children who often could be prevented from using and taking benefits from modern technologies. The objective is to get any children moving, exchanging, experimenting and having fun, regardless of their cognitive or physical ability levels. The paper describes two prototype systems developed as modular...

RoboMusic with modular playware

DEFF Research Database (Denmark)

Falkenberg, Kasper; Bærendsen, Niels Kristian; Nielsen, Jacob

2011-01-01

Based on the concepts of RoboMusic and modular playware, we developed a system composed of modular playware devices which allow any user to perform music in a simple, interactive manner. The key features exploited in the modular playware approach are modularity, fl exibility, construction......, immediate feedback to stimulate engagement, creative exploration of play activities, and in some cases activity design by end-users (e.g., DJs). We exemplify the approach with the development of 11 rock genres and 6 pop music pieces for modular I-BLOCKS, which are exhibited and in daily use at the Rock Me...

RoboMusic with Modular Playware

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Bærendsen, Niels Kristian; Nielsen, Jacob

2010-01-01

Based on the concepts of RoboMusic and Modular Playware, we developed a system composed of modular playware devices, which allow any user to perform music in a simple, interactive manner. The key features exploited from the Modular Playware approach are modularity, flexibility, and construction......, immediate feedback to stimulate engagement, creative exploration of play activities, and in some cases activity design by end-users (e.g. DJ’s). We exemplify the approach with the development of 11 rock genres and 6 pop music pieces for modular I-BLOCKS, which are exhibited and in daily use at the Rock Me...

Portable modular detection system

Science.gov (United States)

Brennan, James S [Rodeo, CA; Singh, Anup [Danville, CA; Throckmorton, Daniel J [Tracy, CA; Stamps, James F [Livermore, CA

2009-10-13

Disclosed herein are portable and modular detection devices and systems for detecting electromagnetic radiation, such as fluorescence, from an analyte which comprises at least one optical element removably attached to at least one alignment rail. Also disclosed are modular detection devices and systems having an integrated lock-in amplifier and spatial filter and assay methods using the portable and modular detection devices.

Isolation and Biosynthetic Analysis of Haliamide, a New PKS-NRPS Hybrid Metabolite from the Marine Myxobacterium Haliangium ochraceum

Directory of Open Access Journals (Sweden)

Yuwei Sun

2016-01-01

Full Text Available Myxobacteria of marine origin are rare and hard-to-culture microorganisms, but they genetically harbor high potential to produce novel antibiotics. An extensive investigation on the secondary metabolome of the unique marine myxobacterium Haliangium ochraceum SMP-2 led to the isolation of a new polyketide-nonribosomal peptide hybrid product, haliamide (1. Its structure was elucidated by spectroscopic analyses including NMR and HR-MS. Haliamide (1 showed cytotoxicity against HeLa-S3 cells with IC50 of 12 μM. Feeding experiments were performed to identify the biosynthetic building blocks of 1, revealing one benzoate, one alanine, two propionates, one acetate and one acetate-derived terminal methylene. The biosynthetic gene cluster of haliamide (hla, 21.7 kbp was characterized through the genome mining of the producer, allowing us to establish a model for the haliamide biosynthesis. The sulfotransferase (ST-thioesterase (TE domains encoded in hlaB appears to be responsible for the terminal alkene formation via decarboxylation.

Proposal of 'modular heliotron'

International Nuclear Information System (INIS)

Yamazaki, Kozo.

1993-11-01

A new modular helical configuration named 'Modular Heliotron' with clean and efficient helical magnetic divertor is proposed as an extension of the present conventional design of the continuous helical coil system. The sectored helical coils on one plane of the torus and the sectored returning vertical field coils on the other plane are combined. This coil system produces magnetic surfaces nearly equivalent to those of the l=2 helical system with one-pair poloidal coils, and overcomes the defects of construction and maintenance difficulties of the continuous coil systems. This concept satisfies the compatibility between the coil modularity and the sufficient divertor-space utilization, different from previous modular coil designs. The allowable length of the gap between each modular coil is clarified to keep good magnetic surfaces. Typical examples of the reactor coil configuration are described as an extension of the LHD (Large Helical Device) configuration. (author)

Proposal of 'Modular Heliotron'

International Nuclear Information System (INIS)

Yamazaki, Kozo

1994-01-01

A new modular helical system named 'Modular Heliotron' with clean and efficient helical magnetic divertor is proposed as an extension of the present conventional design of the continuous helical coil system. The sectored helical coils on one plane of the torus and the sectored returning vertical field coils on the other plane are combined. This coil system produces magnetic surfaces nearly equivalent to those of the l=2 helical system with one-pair poloidal coils, and overcomes the defects of construction and maintenance difficulties of the continuous coil systems. This concept satisfies the compatibility between the coil modularity and the sufficient divertor-space utilization, different from previous modular coil designs. The allowable length of the gap between each modular coil is clarified to keep good magnetic surfaces. Typical examples of the reactor coil configuration are described as an extension of the LHD (Large Helical Device) configuration. (author)

Gene transcript profiles of the TIA biosynthetic pathway in response to ethylene and copper reveal their interactive role in modulating TIA biosynthesis in Catharanthus roseus.

Science.gov (United States)

Pan, Ya-Jie; Liu, Jia; Guo, Xiao-Rui; Zu, Yuan-Gang; Tang, Zhong-Hua

2015-05-01

Research on transcriptional regulation of terpenoid indole alkaloid (TIA) biosynthesis of the medicinal plant, Catharanthus roseus, has largely been focused on gene function and not clustering analysis of multiple genes at the transcript level. Here, more than ten key genes encoding key enzyme of alkaloid synthesis in TIA biosynthetic pathways were chosen to investigate the integrative responses to exogenous elicitor ethylene and copper (Cu) at both transcriptional and metabolic levels. The ethylene-induced gene transcripts in leaves and roots, respectively, were subjected to principal component analysis (PCA) and the results showed the overall expression of TIA pathway genes indicated as the Q value followed a standard normal distribution after ethylene treatments. Peak gene expression was at 15-30 μM of ethephon, and the pre-mature leaf had a higher Q value than the immature or mature leaf and root. Treatment with elicitor Cu found that Cu up-regulated overall TIA gene expression more in roots than in leaves. The combined effects of Cu and ethephon on TIA gene expression were stronger than their separate effects. It has been documented that TIA gene expression is tightly regulated by the transcriptional factor (TF) ethylene responsive factor (ERF) and mitogen-activated protein kinase (MAPK) cascade. The loading plot combination with correlation analysis for the genes of C. roseus showed that expression of the MPK gene correlated with strictosidine synthase (STR) and strictosidine b-D-glucosidase(SGD). In addition, ERF expression correlated with expression of secologanin synthase (SLS) and tryptophan decarboxylase (TDC), specifically in roots, whereas MPK and myelocytomatosis oncogene (MYC) correlated with STR and SGD genes. In conclusion, the ERF regulates the upstream pathway genes in response to heavy metal Cu mainly in C. roseus roots, while the MPK mainly participates in regulating the STR gene in response to ethylene in pre-mature leaf. Interestingly, the

Key roles of Arf small G proteins and biosynthetic trafficking for animal development.

Science.gov (United States)

Rodrigues, Francisco F; Harris, Tony J C

2017-04-14

Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis. Specific need for the biosynthetic trafficking system is also evident from conserved CrebA/Creb3-like transcription factors increasing the expression of secretory machinery during several of these developmental processes. Moreover, dysfunctional trafficking leads to a range of developmental syndromes.

Modular tree automata

DEFF Research Database (Denmark)

Bahr, Patrick

2012-01-01

Tree automata are traditionally used to study properties of tree languages and tree transformations. In this paper, we consider tree automata as the basis for modular and extensible recursion schemes. We show, using well-known techniques, how to derive from standard tree automata highly modular...

Construction of a controllable β-carotene biosynthetic pathway by decentralized assembly strategy in Saccharomyces cerevisiae.

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Xie, Wenping; Liu, Min; Lv, Xiaomei; Lu, Wenqiang; Gu, Jiali; Yu, Hongwei

2014-01-01

Saccharomyces cerevisiae is an important platform organism for the synthesis of a great number of natural products. However, the assembly of controllable and genetically stable heterogeneous biosynthetic pathways in S. cerevisiae still remains a significant challenge. Here, we present a strategy for reconstructing controllable multi-gene pathways by employing the GAL regulatory system. A set of marker recyclable integrative plasmids (pMRI) was designed for decentralized assembly of pathways. As proof-of-principle, a controllable β-carotene biosynthesis pathway (∼16 kb) was reconstructed and optimized by repeatedly using GAL10-GAL1 bidirectional promoters with high efficiency (80-100%). By controling the switch time of the pathway, production of 11 mg/g DCW of total carotenoids (72.57 mg/L) and 7.41 mg/g DCW of β-carotene was achieved in shake-flask culture. In addition, the engineered yeast strain exhibited high genetic stability after 20 generations of subculture. The results demonstrated a controllable and genetically stable biosynthetic pathway capable of increasing the yield of target products. Furthermore, the strategy presented in this study could be extended to construct other pathways in S. cerevisisae. © 2013 Wiley Periodicals, Inc.

Modular strategies for PET imaging agents

International Nuclear Information System (INIS)

Hooker, J.M.

2010-01-01

In recent years, modular and simplified chemical and biological strategies have been developed for the synthesis and implementation of positron emission tomography (PET) radiotracers. New developments in bioconjugation and synthetic methodologies, in combination with advances in macromolecular delivery systems and gene-expression imaging, reflect a need to reduce radiosynthesis burden in order to accelerate imaging agent development. These new approaches, which are often mindful of existing infrastructure and available resources, are anticipated to provide a more approachable entry point for researchers interested in using PET to translate in vitro research to in vivo imaging.

Expression of cocoa genes in Saccharomyces cerevisiae improves cocoa butter production

DEFF Research Database (Denmark)

Wei, Yongjun; Bergenholm, David; Gossing, Michael

2018-01-01

Background: Cocoa butter (CB) extracted from cocoa beans (Theobroma cacao) is the main raw material for chocolate production, but CB supply is insufficient due to the increased chocolate demand and limited CB production. CB is mainly composed of three different kinds of triacylglycerols (TAGs), 1......), and it is essential to modulate the yeast TAG biosynthetic pathway for higher CBL production.Results: We cloned seven GPAT genes and three LPAT genes from cocoa cDNA, in order to screen for CBL biosynthetic gene candidates. By expressing these cloned cocoa genes and two synthesized cocoa DGAT genes in S. cerevisiae......, we successfully increased total fatty acid production, TAG production and CBL production in some of the strains. In the best producer, the potential CBL content was eightfold higher than the control strain, suggesting the cocoa genes expressed in this strain were functional and might be responsible...

Modularization and Flexibilization.

Science.gov (United States)

Van Meel, R. M.

Publications in the fields of educational science, organization theory, and project management were analyzed to identify the possibilities that modularization offers to institutions of higher professional education and to obtain background information for use in developing a method for modularization in higher professional education. It was…

Self-organized modularization in evolutionary algorithms.

Science.gov (United States)

Dauscher, Peter; Uthmann, Thomas

2005-01-01

The principle of modularization has proven to be extremely successful in the field of technical applications and particularly for Software Engineering purposes. The question to be answered within the present article is whether mechanisms can also be identified within the framework of Evolutionary Computation that cause a modularization of solutions. We will concentrate on processes, where modularization results only from the typical evolutionary operators, i.e. selection and variation by recombination and mutation (and not, e.g., from special modularization operators). This is what we call Self-Organized Modularization. Based on a combination of two formalizations by Radcliffe and Altenberg, some quantitative measures of modularity are introduced. Particularly, we distinguish Built-in Modularity as an inherent property of a genotype and Effective Modularity, which depends on the rest of the population. These measures can easily be applied to a wide range of present Evolutionary Computation models. It will be shown, both theoretically and by simulation, that under certain conditions, Effective Modularity (as defined within this paper) can be a selection factor. This causes Self-Organized Modularization to take place. The experimental observations emphasize the importance of Effective Modularity in comparison with Built-in Modularity. Although the experimental results have been obtained using a minimalist toy model, they can lead to a number of consequences for existing models as well as for future approaches. Furthermore, the results suggest a complex self-amplification of highly modular equivalence classes in the case of respected relations. Since the well-known Holland schemata are just the equivalence classes of respected relations in most Simple Genetic Algorithms, this observation emphasizes the role of schemata as Building Blocks (in comparison with arbitrary subsets of the search space).

Expression profile of genes coding for carotenoid biosynthetic ...

Indian Academy of Sciences (India)

3Department of Biotechnology, School of Life Sciences, Assam University, Silchar 788 011, India. 4Reliance Industries ... mellitus, and helps to maintain prostate health (Stacewicz- ... mental stages to establish gene-to-metabolite links in high.

Biosynthesis of Akaeolide and Lorneic Acids and Annotation of Type I Polyketide Synthase Gene Clusters in the Genome of Streptomyces sp. NPS554

Directory of Open Access Journals (Sweden)

Tao Zhou

2015-01-01

Full Text Available The incorporation pattern of biosynthetic precursors into two structurally unique polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments with 13C-labeled precursors. In addition, the draft genome sequence of the producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene clusters for these polyketides were identified. The putative gene clusters contain all the polyketide synthase (PKS domains necessary for assembly of the carbon skeletons. Combined with the 13C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions. Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides.

The flavonoid biosynthetic pathway in plants: function and evolution

International Nuclear Information System (INIS)

Koes, R.E.; Quattrocchio, F.; Mol, J.N.M.

1994-01-01

Flavonoids are a class of low molecular weight phenolic compounds that is widely distributed in the plant kingdom. They exhibit a diverse spectrum of biological functions and play an important role in the interaction between plants and their environment. Flavonoids not only protect the plant from the harmful effects of UV irradiation but also play a crucial role in the sexual reproduction process. A special class of flavonoid polymers, the tannins, plays a structural role in the plant. Yet other classes of flavonoids, flavonols and anthocyanins, have been implicated in the attraction of pollinators. Certain flavonoids participate in the interaction between plants and other organisms such as symbiotic bacteria and parasites. This raises the intriguing question as to how these different compounds arose and evolved. Based on taxonomy and molecular analysis of gene expression patterns it is possible to deduce a putative sequence of acquisition of the different branches of the biosynthetic pathway and their regulators. (author)

The flavonoid biosynthetic pathway in plants: function and evolution

Energy Technology Data Exchange (ETDEWEB)

Koes, R. E.; Quattrocchio, F.; Mol, J. N.M. [Department of Genetics, Institute for Molecular Biological Sciences, Vrije Universiteit, BioCentrum Amsterdam, De Boelelaan 1087, 1081HV, Amsterdam (Netherlands)

1994-07-01

Flavonoids are a class of low molecular weight phenolic compounds that is widely distributed in the plant kingdom. They exhibit a diverse spectrum of biological functions and play an important role in the interaction between plants and their environment. Flavonoids not only protect the plant from the harmful effects of UV irradiation but also play a crucial role in the sexual reproduction process. A special class of flavonoid polymers, the tannins, plays a structural role in the plant. Yet other classes of flavonoids, flavonols and anthocyanins, have been implicated in the attraction of pollinators. Certain flavonoids participate in the interaction between plants and other organisms such as symbiotic bacteria and parasites. This raises the intriguing question as to how these different compounds arose and evolved. Based on taxonomy and molecular analysis of gene expression patterns it is possible to deduce a putative sequence of acquisition of the different branches of the biosynthetic pathway and their regulators. (author)

Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp.

Directory of Open Access Journals (Sweden)

Sandra Fresquet-Corrales

Full Text Available Proanthocyanidins (PAs, or condensed tannins, are powerful antioxidants that remove harmful free oxygen radicals from cells. To engineer the anthocyanin and proanthocyanidin biosynthetic pathways to de novo produce PAs in two Nicotiana species, we incorporated four transgenes to the plant chassis. We opted to perform a simultaneous transformation of the genes linked in a multigenic construct rather than classical breeding or retransformation approaches. We generated a GoldenBraid 2.0 multigenic construct containing two Antirrhinum majus transcription factors (AmRosea1 and AmDelila to upregulate the anthocyanin pathway in combination with two Medicago truncatula genes (MtLAR and MtANR to produce the enzymes that will derivate the biosynthetic pathway to PAs production. Transient and stable transformation of Nicotiana benthamiana and Nicotiana tabacum with the multigenic construct were respectively performed. Transient expression experiments in N. benthamiana showed the activation of the anthocyanin pathway producing a purple color in the agroinfiltrated leaves and also the effective production of 208.5 nmol (- catechin/g FW and 228.5 nmol (- epicatechin/g FW measured by the p-dimethylaminocinnamaldehyde (DMACA method. The integration capacity of the four transgenes, their respective expression levels and their heritability in the second generation were analyzed in stably transformed N. tabacum plants. DMACA and phoroglucinolysis/HPLC-MS analyses corroborated the activation of both pathways and the effective production of PAs in T0 and T1 transgenic tobacco plants up to a maximum of 3.48 mg/g DW. The possible biotechnological applications of the GB2.0 multigenic approach in forage legumes to produce "bloat-safe" plants and to improve the efficiency of conversion of plant protein into animal protein (ruminal protein bypass are discussed.

A R2R3-MYB transcription factor regulates the flavonol biosynthetic pathway in a traditional Chinese medicinal plant, Epimedium sagittatum

Directory of Open Access Journals (Sweden)

Wenjun Huang

2016-07-01

Full Text Available Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from E. sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase and EsFLS (flavonol synthase, but not the promoters of EsDFRs (dihydroflavonol 4-reductase and EsANS (anthocyanidin synthase in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase, NtCHI (chalcone isomerase, NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived bioactive components in E

Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.

Science.gov (United States)

Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong

2017-10-03

With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.

A nitrous acid biosynthetic pathway for diazo group formation in bacteria.

Science.gov (United States)

Sugai, Yoshinori; Katsuyama, Yohei; Ohnishi, Yasuo

2016-02-01

Although some diazo compounds have bioactivities of medicinal interest, little is known about diazo group formation in nature. Here we describe an unprecedented nitrous acid biosynthetic pathway responsible for the formation of a diazo group in the biosynthesis of the ortho-diazoquinone secondary metabolite cremeomycin in Streptomyces cremeus. This finding provides important insights into the biosynthetic pathways not only for diazo compounds but also for other naturally occurring compounds containing nitrogen-nitrogen bonds.

AES Modular Power Systems

Data.gov (United States)

National Aeronautics and Space Administration — The AES Modular Power Systems (AMPS) project will demonstrate and infuse modular power electronics, batteries, fuel cells, and autonomous control for exploration...

A Modularized Counselor-Education Program.

Science.gov (United States)

Miller, Thomas V.; Dimattia, Dominic J.

1978-01-01

Counselor-education programs may be enriched through the use of modularized learning experiences. This article notes several recent articles on competency-based counselor education, the concepts of simulation and modularization, and describes the process of developing a modularized master's program at the University of Bridgeport in Connecticut.…

Robotic hand with modular extensions

Science.gov (United States)

Salisbury, Curt Michael; Quigley, Morgan

2015-01-20

A robotic device is described herein. The robotic device includes a frame that comprises a plurality of receiving regions that are configured to receive a respective plurality of modular robotic extensions. The modular robotic extensions are removably attachable to the frame at the respective receiving regions by way of respective mechanical fuses. Each mechanical fuse is configured to trip when a respective modular robotic extension experiences a predefined load condition, such that the respective modular robotic extension detaches from the frame when the load condition is met.

Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network

Directory of Open Access Journals (Sweden)

Kim Hyun

2011-12-01

Full Text Available Abstract Background Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. Results We herein introduce a framework for network modularization and Bayesian network analysis (FMB to investigate organism’s metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. Conclusions After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network.

Science.gov (United States)

Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

2011-01-01

Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

Comparative analysis of chemical similarity methods for modular natural products with a hypothetical structure enumeration algorithm.

Science.gov (United States)

Skinnider, Michael A; Dejong, Chris A; Franczak, Brian C; McNicholas, Paul D; Magarvey, Nathan A

2017-08-16

Natural products represent a prominent source of pharmaceutically and industrially important agents. Calculating the chemical similarity of two molecules is a central task in cheminformatics, with applications at multiple stages of the drug discovery pipeline. Quantifying the similarity of natural products is a particularly important problem, as the biological activities of these molecules have been extensively optimized by natural selection. The large and structurally complex scaffolds of natural products distinguish their physical and chemical properties from those of synthetic compounds. However, no analysis of the performance of existing methods for molecular similarity calculation specific to natural products has been reported to date. Here, we present LEMONS, an algorithm for the enumeration of hypothetical modular natural product structures. We leverage this algorithm to conduct a comparative analysis of molecular similarity methods within the unique chemical space occupied by modular natural products using controlled synthetic data, and comprehensively investigate the impact of diverse biosynthetic parameters on similarity search. We additionally investigate a recently described algorithm for natural product retrobiosynthesis and alignment, and find that when rule-based retrobiosynthesis can be applied, this approach outperforms conventional two-dimensional fingerprints, suggesting it may represent a valuable approach for the targeted exploration of natural product chemical space and microbial genome mining. Our open-source algorithm is an extensible method of enumerating hypothetical natural product structures with diverse potential applications in bioinformatics.

[Advance in flavonoids biosynthetic pathway and synthetic biology].

Science.gov (United States)

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Modular organization and hospital performance.

Science.gov (United States)

Kuntz, Ludwig; Vera, Antonio

2007-02-01

The concept of modularization represents a modern form of organization, which contains the vertical disaggregation of the firm and the use of market mechanisms within hierarchies. The objective of this paper is to examine whether the use of modular structures has a positive effect on hospital performance. The empirical section makes use of multiple regression analyses and leads to the main result that modularization does not have a positive effect on hospital performance. However, the analysis also finds out positive efficiency effects of two central ideas of modularization, namely process orientation and internal market mechanisms.

Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS.

Science.gov (United States)

Ariyannur, Prasanth S; Moffett, John R; Manickam, Pachiappan; Pattabiraman, Nagarajan; Arun, Peethambaran; Nitta, Atsumi; Nabeshima, Toshitaka; Madhavarao, Chikkathur N; Namboodiri, Aryan M A

2010-06-04

N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism. However, studies have been hampered by an inability to identify the gene for the NAA biosynthetic enzyme aspartate N-acetyltransferase (Asp-NAT). A very recent report has identified Nat8l as the gene encoding Asp-NAT and confirmed that the only child diagnosed with a lack of NAA on brain magnetic resonance spectrograms has a 19-bp deletion in this gene. Based on in vitro Nat8l expression studies the researchers concluded that many previous biochemical investigations have been technically flawed and that NAA may not be associated with brain energy or lipid metabolism. In studies done concurrently in our laboratory we have demonstrated via cloning, expression, specificity for acetylation of aspartate, responsiveness to methamphetamine treatment, molecular modeling and comparative immunolocalization that NAT8L is the NAA biosynthetic enzyme Asp-NAT. We conclude that NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system, thus linking it to both lipid synthesis and energy metabolism. Published by Elsevier B.V.

Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.

Science.gov (United States)

Xu, Min; Wang, Yemin; Zhao, Zhilong; Gao, Guixi; Huang, Sheng-Xiong; Kang, Qianjin; He, Xinyi; Lin, Shuangjun; Pang, Xiuhua; Deng, Zixin

2016-01-01

ABSTRACT Genome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei. This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways. IMPORTANCE Microbial genomes encode numerous cryptic biosynthetic gene clusters for unknown small metabolites with potential biological activities. Several genome mining approaches have been developed to activate and bring these cryptic metabolites to biological tests for future drug discovery. Previous sequence-guided procedures relied on bioinformatic analysis to predict potentially interesting biosynthetic gene clusters. In this study, we describe an efficient approach based on heterologous expression and functional screening of a whole-genome library for the mining of bioactive metabolites from Streptomyces. The usefulness of this function-driven approach was demonstrated by the capture of four large biosynthetic gene clusters for metabolites of various chemical types, including

Modular Design in Treaty Verification Equipment

Energy Technology Data Exchange (ETDEWEB)

Macarthur, Duncan Whittemore [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Benz, Jacob [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tolk, Keith [Milagro Consulting, Albuquerque, NM (United States); Weber, Tom [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-01-27

It is widely believed that modular design is a good thing. However, there are often few explicit arguments, or even an agreed range of definitions, to back up this belief. In this paper, we examine the potential range of design modularity, the implications of various amounts of modularity, and the advantages and disadvantages of each level of modular construction. We conclude with a comparison of the advantages and disadvantages of each type, as well as discuss many caveats that should be observed to take advantage of the positive features of modularity and minimize the effects of the negative. The tradeoffs described in this paper will be evaluated during the conceptual design to determine what amount of modularity should be included.

Modular Robotics in an African Context

DEFF Research Database (Denmark)

Lund, Henrik Hautop

2011-01-01

In this paper, we review the concept, development and use of modular robotic devices for education, health improvements, and business in Africa. The modular robotics inspired technology has the advantage of allowing any user easy access to a physical construction of new and advanced technology. We...... conceptualized several educational tools inspired by modular robotics for contextualized IT education in Tanzania, leading to a novel IT degree program and the development of East Africa’s first science and business park in Iringa, Tanzania. The prototypes inspired by modular robotics were developed in the local......, rural context and tested by local users in hospitals and rehabilitation centres. In this paper, we review the development of both modular building blocks for education and modular robotic tiles for rehabilitation in Tanzania....

Anthocyanin accumulation and molecular analysis of anthocyanin biosynthesis-associated genes in eggplant (Solanum melongena L.).

Science.gov (United States)

Zhang, Yanjie; Hu, Zongli; Chu, Guihua; Huang, Cheng; Tian, Shibing; Zhao, Zhiping; Chen, Guoping

2014-04-02

Eggplant (Solanum melongena L.) is an edible fruit vegetable cultivated and consumed worldwide. The purple eggplant is more eye-catching and popular for the health-promoting anthocyanins contained in the fruit skin. Two kinds of anthocyanin were separated and identified from purple cultivar (Zi Chang) by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. To investigate the molecular mechanisms of anthocyanin accumulation in eggplant, the transcripts of anthocyanin biosynthetic and regulatory genes were analyzed in the fruit skin and the flesh of the purple cultivar and the white cultivar (Bai Xue). Compared with the other tissues, SmMYB1 and all anthocyanin biosynthetic genes except PAL were dramatically upregulated in the fruit skin of the purple cultivar. Overexpression of SmMYB1 activated abundant anthocyanin accumulation in the regenerating shoots of eggplant. These results prove that transcriptional activation of SmMYB1 accounts for constitutive upregulation of most anthocyanin biosynthetic genes and the onset of anthocyanin biosynthesis in the purple cultivar.

Modular interdependency in complex dynamical systems.

Science.gov (United States)

Watson, Richard A; Pollack, Jordan B

2005-01-01

Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an "aggregate" manner--but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability.

Modular evolution of glutathione peroxidase genes in association with different biochemical properties of their encoded proteins in invertebrate animals

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Zo Young-Gun

2009-04-01

Full Text Available Abstract Background Phospholipid hydroperoxide glutathione peroxidases (PHGPx, the most abundant isoforms of GPx families, interfere directly with hydroperoxidation of lipids. Biochemical properties of these proteins vary along with their donor organisms, which has complicated the phylogenetic classification of diverse PHGPx-like proteins. Despite efforts for comprehensive analyses, the evolutionary aspects of GPx genes in invertebrates remain largely unknown. Results We isolated GPx homologs via in silico screening of genomic and/or expressed sequence tag databases of eukaryotic organisms including protostomian species. Genes showing strong similarity to the mammalian PHGPx genes were commonly found in all genomes examined. GPx3- and GPx7-like genes were additionally detected from nematodes and platyhelminths, respectively. The overall distribution of the PHGPx-like proteins with different biochemical properties was biased across taxa; selenium- and glutathione (GSH-dependent proteins were exclusively detected in platyhelminth and deuterostomian species, whereas selenium-independent and thioredoxin (Trx-dependent enzymes were isolated in the other taxa. In comparison of genomic organization, the GSH-dependent PHGPx genes showed a conserved architectural pattern, while their Trx-dependent counterparts displayed complex exon-intron structures. A codon for the resolving Cys engaged in reductant binding was found to be substituted in a series of genes. Selection pressure to maintain the selenocysteine codon in GSH-dependent genes also appeared to be relaxed during their evolution. With the dichotomized fashion in genomic organizations, a highly polytomic topology of their phylogenetic trees implied that the GPx genes have multiple evolutionary intermediate forms. Conclusion Comparative analysis of invertebrate GPx genes provides informative evidence to support the modular pathways of GPx evolution, which have been accompanied with sporadic

Arabidopsis brassinosteroid biosynthetic mutant dwarf7-1 exhibits slower rates of cell division and shoot induction

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Schulz Burkhard

2010-12-01

Full Text Available Abstract Background Plant growth depends on both cell division and cell expansion. Plant hormones, including brassinosteroids (BRs, are central to the control of these two cellular processes. Despite clear evidence that BRs regulate cell elongation, their roles in cell division have remained elusive. Results Here, we report results emphasizing the importance of BRs in cell division. An Arabidopsis BR biosynthetic mutant, dwarf7-1, displayed various characteristics attributable to slower cell division rates. We found that the DWARF4 gene which encodes for an enzyme catalyzing a rate-determining step in the BR biosynthetic pathways, is highly expressed in the actively dividing callus, suggesting that BR biosynthesis is necessary for dividing cells. Furthermore, dwf7-1 showed noticeably slower rates of callus growth and shoot induction relative to wild-type control. Flow cytometric analyses of the nuclei derived from either calli or intact roots revealed that the cell division index, which was represented as the ratio of cells at the G2/M vs. G1 phases, was smaller in dwf7-1 plants. Finally, we found that the expression levels of the genes involved in cell division and shoot induction, such as PROLIFERATING CELL NUCLEAR ANTIGEN2 (PCNA2 and ENHANCER OF SHOOT REGENERATION2 (ESR2, were also lower in dwf7-1 as compared with wild type. Conclusions Taken together, results of callus induction, shoot regeneration, flow cytometry, and semi-quantitative RT-PCR analysis suggest that BRs play important roles in both cell division and cell differentiation in Arabidopsis.

Modular analysis of biological networks.

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Kaltenbach, Hans-Michael; Stelling, Jörg

2012-01-01

The analysis of complex biological networks has traditionally relied on decomposition into smaller, semi-autonomous units such as individual signaling pathways. With the increased scope of systems biology (models), rational approaches to modularization have become an important topic. With increasing acceptance of de facto modularity in biology, widely different definitions of what constitutes a module have sparked controversies. Here, we therefore review prominent classes of modular approaches based on formal network representations. Despite some promising research directions, several important theoretical challenges remain open on the way to formal, function-centered modular decompositions for dynamic biological networks.

Theoretical Analysis of the Relationships Between Modularity in Design and Modularity in Production

DEFF Research Database (Denmark)

Kubota, Flávio Issao; Hsuan, Juliana; Cauchick-Miguel, Paulo Augusto

2017-01-01

This paper investigates the relationships between modularity in design (MID) and modularity in production (MIP) in the automotive industry in terms of how automotive companies obtain benefits and/or drawbacks through MID/MIP relationships. A literature analysis was conducted in order to identify...... the possible relationships between MID and MIP as well as the concepts behind these connections. Sixty-one papers were identified to portray relationships between modular product architecture and modular production systems. Results show a representation of MID and MIP relationships by illustrating that many...... propositions are offered for future field research. Finally, relationships between MID and MIP might be connected with modularity’s maturity level in companies. This is a literature review paper; therefore, empirical evidence is needed to further support current findings. Future studies could analyze...

(Automated) software modularization using community detection

DEFF Research Database (Denmark)

Hansen, Klaus Marius; Manikas, Konstantinos

2015-01-01

The modularity of a software system is known to have an effect on, among other, development effort, change impact, and technical debt. Modularizing a specific system and evaluating this modularization is, however, challenging. In this paper, we apply community detection methods to the graph...... of class dependencies in software systems to find optimal modularizations through communities. We evaluate this approach through a study of 111 Java systems contained in the Qualitas Corpus. We found that using the modularity function of Newman with an Erdős-Rényi null-model and using the community...... detection algorithm of Reichardt and Bornholdt improved community quality for all systems, that coupling decreased for 99 of the systems, and that coherence increased for 102 of the systems. Furthermore, the modularity function correlates with existing metrics for coupling and coherence....

Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

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Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

2016-11-01

Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the

A modular platform for targeted RNAi therapeutics.

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Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-03-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

A modular platform for targeted RNAi therapeutics

Science.gov (United States)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-01-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Structural, evolutionary and genetic analysis of the histidine biosynthetic "core" in the genus Burkholderia.

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Papaleo, Maria Cristiana; Russo, Edda; Fondi, Marco; Emiliani, Giovanni; Frandi, Antonio; Brilli, Matteo; Pastorelli, Roberta; Fani, Renato

2009-12-01

In this work a detailed analysis of the structure, the expression and the organization of his genes belonging to the core of histidine biosynthesis (hisBHAF) in 40 newly determined and 13 available sequences of Burkholderia strains was carried out. Data obtained revealed a strong conservation of the structure and organization of these genes through the entire genus. The phylogenetic analysis showed the monophyletic origin of this gene cluster and indicated that it did not undergo horizontal gene transfer events. The analysis of the intergenic regions, based on the substitution rate, entropy plot and bendability suggested the existence of a putative transcription promoter upstream of hisB, that was supported by the genetic analysis that showed that this cluster was able to complement Escherichia colihisA, hisB, and hisF mutations. Moreover, a preliminary transcriptional analysis and the analysis of microarray data revealed that the expression of the his core was constitutive. These findings are in agreement with the fact that the entire Burkholderiahis operon is heterogeneous, in that it contains "alien" genes apparently not involved in histidine biosynthesis. Besides, they also support the idea that the proteobacterial his operon was piece-wisely assembled, i.e. through accretion of smaller units containing only some of the genes (eventually together with their own promoters) involved in this biosynthetic route. The correlation existing between the structure, organization and regulation of his "core" genes and the function(s) they perform in cellular metabolism is discussed.

Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

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Kimberley D Seed

2012-09-01

Full Text Available The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

Flavonoid Biosynthesis Genes Putatively Identified in the Aromatic Plant Polygonum minus via Expressed Sequences Tag (EST Analysis

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Zamri Zainal

2012-02-01

Full Text Available P. minus is an aromatic plant, the leaf of which is widely used as a food additive and in the perfume industry. The leaf also accumulates secondary metabolites that act as active ingredients such as flavonoid. Due to limited genomic and transcriptomic data, the biosynthetic pathway of flavonoids is currently unclear. Identification of candidate genes involved in the flavonoid biosynthetic pathway will significantly contribute to understanding the biosynthesis of active compounds. We have constructed a standard cDNA library from P. minus leaves, and two normalized full-length enriched cDNA libraries were constructed from stem and root organs in order to create a gene resource for the biosynthesis of secondary metabolites, especially flavonoid biosynthesis. Thus, large‑scale sequencing of P. minus cDNA libraries identified 4196 expressed sequences tags (ESTs which were deposited in dbEST in the National Center of Biotechnology Information (NCBI. From the three constructed cDNA libraries, 11 ESTs encoding seven genes were mapped to the flavonoid biosynthetic pathway. Finally, three flavonoid biosynthetic pathway-related ESTs chalcone synthase, CHS (JG745304, flavonol synthase, FLS (JG705819 and leucoanthocyanidin dioxygenase, LDOX (JG745247 were selected for further examination by quantitative RT-PCR (qRT-PCR in different P. minus organs. Expression was detected in leaf, stem and root. Gene expression studies have been initiated in order to better understand the underlying physiological processes.

Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes

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Horsman, Geoff P.; Chen, Yihua; Thorson, Jon S.; Shen, Ben

2010-01-01

Enediynes are potent antitumor antibiotics that are classified as 9- or 10-membered according to the size of the enediyne core structure. However, almost nothing is known about enediyne core biosynthesis, and the determinants of 9- versus 10-membered enediyne core biosynthetic divergence remain elusive. Previous work identified enediyne-specific polyketide synthases (PKSEs) that can be phylogenetically distinguished as being involved in 9- versus 10-membered enediyne biosynthesis, suggesting that biosynthetic divergence might originate from differing PKSE chemistries. Recent in vitro studies have identified several compounds produced by the PKSE and associated thioesterase (TE), but condition-dependent product profiles make it difficult to ascertain a true catalytic difference between 9- and 10-membered PKSE-TE systems. Here we report that PKSE chemistry does not direct 9- versus 10-membered enediyne core biosynthetic divergence as revealed by comparing the products from three 9-membered and two 10-membered PKSE-TE systems under identical conditions using robust in vivo assays. Three independent experiments support a common catalytic function for 9- and 10-membered PKSEs by the production of a heptaene metabolite from: (i) all five cognate PKSE-TE pairs in Escherichia coli; (ii) the C-1027 and calicheamicin cognate PKSE-TEs in Streptomyces lividans K4-114; and (iii) selected native producers of both 9- and 10-membered enediynes. Furthermore, PKSEs and TEs from different 9- and 10-membered enediyne biosynthetic machineries are freely interchangeable, revealing that 9- versus 10-membered enediyne core biosynthetic divergence occurs beyond the PKSE-TE level. These findings establish a starting point for determining the origins of this biosynthetic divergence. PMID:20534556

Reconstruction of cytosolic fumaric acid biosynthetic pathways in Saccharomyces cerevisiae

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Xu Guoqiang

2012-02-01

Full Text Available Abstract Background Fumaric acid is a commercially important component of foodstuffs, pharmaceuticals and industrial materials, yet the current methods of production are unsustainable and ecologically destructive. Results In this study, the fumarate biosynthetic pathway involving reductive reactions of the tricarboxylic acid cycle was exogenously introduced in S. cerevisiae by a series of simple genetic modifications. First, the Rhizopus oryzae genes for malate dehydrogenase (RoMDH and fumarase (RoFUM1 were heterologously expressed. Then, expression of the endogenous pyruvate carboxylase (PYC2 was up-regulated. The resultant yeast strain, FMME-001 ↑PYC2 + ↑RoMDH, was capable of producing significantly higher yields of fumarate in the glucose medium (3.18 ± 0.15 g liter-1 than the control strain FMME-001 empty vector. Conclusions The results presented here provide a novel strategy for fumarate biosynthesis, which represents an important advancement in producing high yields of fumarate in a sustainable and ecologically-friendly manner.

A gene encoding an abscisic acid biosynthetic enzyme (LsNCED4) collocates with the high temperature germination locus Htg6.1 in lettuce (Lactuca sp.).

Science.gov (United States)

Argyris, Jason; Truco, María José; Ochoa, Oswaldo; McHale, Leah; Dahal, Peetambar; Van Deynze, Allen; Michelmore, Richard W; Bradford, Kent J

2011-01-01

Thermoinhibition, or failure of seeds to germinate when imbibed at warm temperatures, can be a significant problem in lettuce (Lactuca sativa L.) production. The reliability of stand establishment would be improved by increasing the ability of lettuce seeds to germinate at high temperatures. Genes encoding germination- or dormancy-related proteins were mapped in a recombinant inbred line population derived from a cross between L. sativa cv. Salinas and L. serriola accession UC96US23. This revealed several candidate genes that are located in the genomic regions containing quantitative trait loci (QTLs) associated with temperature and light requirements for germination. In particular, LsNCED4, a temperature-regulated gene in the biosynthetic pathway for abscisic acid (ABA), a germination inhibitor, mapped to the center of a previously detected QTL for high temperature germination (Htg6.1) from UC96US23. Three sets of sister BC(3)S(2) near-isogenic lines (NILs) that were homozygous for the UC96US23 allele of LsNCED4 at Htg6.1 were developed by backcrossing to cv. Salinas and marker-assisted selection followed by selfing. The maximum temperature for germination of NIL seed lots with the UC96US23 allele at LsNCED4 was increased by 2-3°C when compared with sister NIL seed lots lacking the introgression. In addition, the expression of LsNCED4 was two- to threefold lower in the former NIL lines as compared to expression in the latter. Together, these data strongly implicate LsNCED4 as the candidate gene responsible for the Htg6.1 phenotype and indicate that decreased ABA biosynthesis at high imbibition temperatures is a major factor responsible for the increased germination thermotolerance of UC96US23 seeds.

Elucidating the biosynthetic and regulatory mechanisms of flavonoid-derived bioactive components in Epimedium sagittatum

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Wenjun eHuang

2015-09-01

Full Text Available Herba epimedii (Epimedium, a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. In Epimedium, flavonoids have been demonstrated to be the main bioactive components (BCs. However, the molecular biosynthetic and regulatory mechanisms of flavonoid-derived BCs remain obscure. In this study, we isolated twelve structural genes and two putative transcription factors (TFs in the flavonoid pathway. Phytochemical analysis showed that the total content of four representative BCs (epimedin A, B, C and icariin decreased slightly or dramatically in two lines of E. sagittatum during leaf development. Transcriptional analysis revealed that two R2R3-MYB TFs (EsMYBA1 and EsMYBF1, together with a bHLH TF (EsGL3 and WD40 protein (EsTTG1, were supposed to coordinately regulate the anthocyanin and flavonol-derived BCs biosynthesis in leaves. Overexpression of EsFLS (flavonol synthase in tobacco resulted in increased flavonols content and decreased anthocyanins content in flowers. Moreover, EsMYB12 negatively correlated with the accumulation of the four BCs, and might act as a transcriptional repressor in the flavonoid pathway. Therefore, the anthocyanin pathway may coordinate with the flavonol-derived BCs pathway in Epimedium leaves. A better understanding of the flavonoid biosynthetic and regulatory mechanisms in E. sagittatum will facilitate functional characterization, metabolic engineering and molecular breeding studies of Epimedium species.

Integrity and change in modular ontologies

NARCIS (Netherlands)

Stuckenschmidt, Heiner; Klein, Michel

2003-01-01

The benefits of modular representations arc well known from many areas of computer science. In this paper, we concentrate on the benefits of modular ontologies with respect to local containment of terminological reasoning. We define an architecture for modular ontologies that supports local

Analysis of flavonoids and the flavonoid structural genes in brown fiber of upland cotton.

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Hongjie Feng

Full Text Available BACKGROUND: As a result of changing consumer preferences, cotton (Gossypium Hirsutum L. from varieties with naturally colored fibers is becoming increasingly sought after in the textile industry. The molecular mechanisms leading to colored fiber development are still largely unknown, although it is expected that the color is derived from flavanoids. EXPERIMENTAL DESIGN: Firstly, four key genes of the flavonoid biosynthetic pathway in cotton (GhC4H, GhCHS, GhF3'H, and GhF3'5'H were cloned and studied their expression profiles during the development of brown- and white cotton fibers by QRT-PCR. And then, the concentrations of four components of the flavonoid biosynthetic pathway, naringenin, quercetin, kaempferol and myricetin in brown- and white fibers were analyzed at different developmental stages by HPLC. RESULT: The predicted proteins of the four flavonoid structural genes corresponding to these genes exhibit strong sequence similarity to their counterparts in various plant species. Transcript levels for all four genes were considerably higher in developing brown fibers than in white fibers from a near isogenic line (NIL. The contents of four flavonoids (naringenin, quercetin, kaempferol and myricetin were significantly higher in brown than in white fibers and corresponding to the biosynthetic gene expression levels. CONCLUSIONS: Flavonoid structural gene expression and flavonoid metabolism are important in the development of pigmentation in brown cotton fibers.

Emergent biosynthetic capacity in simple microbial communities.

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Hsuan-Chao Chiu

2014-07-01

Full Text Available Microbes have an astonishing capacity to transform their environments. Yet, the metabolic capacity of a single species is limited and the vast majority of microorganisms form complex communities and join forces to exhibit capabilities far exceeding those achieved by any single species. Such enhanced metabolic capacities represent a promising route to many medical, environmental, and industrial applications and call for the development of a predictive, systems-level understanding of synergistic microbial capacity. Here we present a comprehensive computational framework, integrating high-quality metabolic models of multiple species, temporal dynamics, and flux variability analysis, to study the metabolic capacity and dynamics of simple two-species microbial ecosystems. We specifically focus on detecting emergent biosynthetic capacity--instances in which a community growing on some medium produces and secretes metabolites that are not secreted by any member species when growing in isolation on that same medium. Using this framework to model a large collection of two-species communities on multiple media, we demonstrate that emergent biosynthetic capacity is highly prevalent. We identify commonly observed emergent metabolites and metabolic reprogramming patterns, characterizing typical mechanisms of emergent capacity. We further find that emergent secretion tends to occur in two waves, the first as soon as the two organisms are introduced, and the second when the medium is depleted and nutrients become limited. Finally, aiming to identify global community determinants of emergent capacity, we find a marked association between the level of emergent biosynthetic capacity and the functional/phylogenetic distance between community members. Specifically, we demonstrate a "Goldilocks" principle, where high levels of emergent capacity are observed when the species comprising the community are functionally neither too close, nor too distant. Taken together

Revisiting the variation of clustering coefficient of biological networks suggests new modular structure.

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Hao, Dapeng; Ren, Cong; Li, Chuanxing

2012-05-01

A central idea in biology is the hierarchical organization of cellular processes. A commonly used method to identify the hierarchical modular organization of network relies on detecting a global signature known as variation of clustering coefficient (so-called modularity scaling). Although several studies have suggested other possible origins of this signature, it is still widely used nowadays to identify hierarchical modularity, especially in the analysis of biological networks. Therefore, a further and systematical investigation of this signature for different types of biological networks is necessary. We analyzed a variety of biological networks and found that the commonly used signature of hierarchical modularity is actually the reflection of spoke-like topology, suggesting a different view of network architecture. We proved that the existence of super-hubs is the origin that the clustering coefficient of a node follows a particular scaling law with degree k in metabolic networks. To study the modularity of biological networks, we systematically investigated the relationship between repulsion of hubs and variation of clustering coefficient. We provided direct evidences for repulsion between hubs being the underlying origin of the variation of clustering coefficient, and found that for biological networks having no anti-correlation between hubs, such as gene co-expression network, the clustering coefficient doesn't show dependence of degree. Here we have shown that the variation of clustering coefficient is neither sufficient nor exclusive for a network to be hierarchical. Our results suggest the existence of spoke-like modules as opposed to "deterministic model" of hierarchical modularity, and suggest the need to reconsider the organizational principle of biological hierarchy.

Anthocyanin biosynthesis in fruit tree crops: Genes and their regulation

African Journals Online (AJOL)

The anthocyanin biosynthesis pathway is a little complex with branches responsible for the synthesis of a variety of metabolites. In fruit tree crops, during the past decade, many structural genes encoding enzymes in the anthocyanin biosynthetic pathway and various regulatory genes encoding transcription factors that ...

Synthesizing Modular Invariants for Synchronous Code

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Pierre-Loic Garoche

2014-12-01

Full Text Available In this paper, we explore different techniques to synthesize modular invariants for synchronous code encoded as Horn clauses. Modular invariants are a set of formulas that characterizes the validity of predicates. They are very useful for different aspects of analysis, synthesis, testing and program transformation. We describe two techniques to generate modular invariants for code written in the synchronous dataflow language Lustre. The first technique directly encodes the synchronous code in a modular fashion. While in the second technique, we synthesize modular invariants starting from a monolithic invariant. Both techniques, take advantage of analysis techniques based on property-directed reachability. We also describe a technique to minimize the synthesized invariants.

The 16-Year Evolution of Proximal Modular Stem Design – Eliminating Failure of Modular Junction

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Thomas Tkach

2017-10-01

Full Text Available Background: The complexity of hip reconstruction has been and continues to be a perplexing problem with restoring leg length, femoral offset, joint stability and overall hip implant fixation. These were contributing factors that lead to the development of a novel proximal femoral component design “Apex Modular Stem” (Omni, Raynham, MA. The basic stem geometry features a straight stem with a metaphyseal fit and fill cone, a medial triangle and a modular neck junction that allows for version and offset adjustment. In recent years, there has been great concern with the use of modularity in total hip arthroplasty. The goals of this study are (1 to identify complications with the use of a proximal modular design and (2 demonstrated factors that have eliminated those complications. Methods: This is a retrospective study of a single surgeon series (Design A and Design B of using the same cementless stem and proximal modular neck body (Apex Modular Stem and Omni Mod Hip Stem from 2000 to 2016 totaling 2,125 stems. 483 stems were the Design A and 1,642 stems, were of the Design B style. Results: Design A, 483 stems were implanted between 2000 and 2004. 31 alignment pins sheared resulting in a revision rate of 6.4%. Design B, 1,642 stems have been implanted between 2004 and 2016 all by the same surgeon, with no failures of the modular junction. Conclusion: All implant devices entail a multitude of risks and benefits. The Apex Modular Stem (Design A, provided excellent fixation, minimal risk of modular junction  corrosion, and simple control of anteversion and femoral offset. The limitation was found to be the risk of the alignment pin shearing (6.4%. The pin was enlarged to make it 225% stronger in torsional resistance, and in a subsequent series of over 1,600 femoral stems in a single surgeon series, there were no pin failures over a 12 year duration.

Modular Power Standard for Space Explorations Missions

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Oeftering, Richard C.; Gardner, Brent G.

2016-01-01

Future human space exploration will most likely be composed of assemblies of multiple modular spacecraft elements with interconnected electrical power systems. An electrical system composed of a standardized set modular building blocks provides significant development, integration, and operational cost advantages. The modular approach can also provide the flexibility to configure power systems to meet the mission needs. A primary goal of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project is to establish a Modular Power Standard that is needed to realize these benefits. This paper is intended to give the space exploration community a "first look" at the evolving Modular Power Standard and invite their comments and technical contributions.

The modularity of pollination networks

DEFF Research Database (Denmark)

Olesen, Jens Mogens; Bascompte, J.; Dupont, Yoko

2007-01-01

In natural communities, species and their interactions are often organized as nonrandom networks, showing distinct and repeated complex patterns. A prevalent, but poorly explored pattern is ecological modularity, with weakly interlinked subsets of species (modules), which, however, internally...... consist of strongly connected species. The importance of modularity has been discussed for a long time, but no consensus on its prevalence in ecological networks has yet been reached. Progress is hampered by inadequate methods and a lack of large datasets. We analyzed 51 pollination networks including...... almost 10,000 species and 20,000 links and tested for modularity by using a recently developed simulated annealing algorithm. All networks with >150 plant and pollinator species were modular, whereas networks with

Evolution of networks for body plan patterning; interplay of modularity, robustness and evolvability.

Directory of Open Access Journals (Sweden)

Kirsten H Ten Tusscher

2011-10-01

Full Text Available A major goal of evolutionary developmental biology (evo-devo is to understand how multicellular body plans of increasing complexity have evolved, and how the corresponding developmental programs are genetically encoded. It has been repeatedly argued that key to the evolution of increased body plan complexity is the modularity of the underlying developmental gene regulatory networks (GRNs. This modularity is considered essential for network robustness and evolvability. In our opinion, these ideas, appealing as they may sound, have not been sufficiently tested. Here we use computer simulations to study the evolution of GRNs' underlying body plan patterning. We select for body plan segmentation and differentiation, as these are considered to be major innovations in metazoan evolution. To allow modular networks to evolve, we independently select for segmentation and differentiation. We study both the occurrence and relation of robustness, evolvability and modularity of evolved networks. Interestingly, we observed two distinct evolutionary strategies to evolve a segmented, differentiated body plan. In the first strategy, first segments and then differentiation domains evolve (SF strategy. In the second scenario segments and domains evolve simultaneously (SS strategy. We demonstrate that under indirect selection for robustness the SF strategy becomes dominant. In addition, as a byproduct of this larger robustness, the SF strategy is also more evolvable. Finally, using a combined functional and architectural approach, we determine network modularity. We find that while SS networks generate segments and domains in an integrated manner, SF networks use largely independent modules to produce segments and domains. Surprisingly, we find that widely used, purely architectural methods for determining network modularity completely fail to establish this higher modularity of SF networks. Finally, we observe that, as a free side effect of evolving segmentation

Theory for the Emergence of Modularity in Complex Systems

Science.gov (United States)

Deem, Michael; Park, Jeong-Man

2013-03-01

Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a theory for the dynamics of modularity in these systems. We find a principle of least action for the evolved modularity at long times. In addition, we find a fluctuation dissipation relation for the rate of change of modularity at short times. We discuss a number of biological and social systems that can be understood with this framework. The modularity of the protein-protein interaction network increases when yeast are exposed to heat shock, and the modularity of the protein-protein networks in both yeast and E. coli appears to have increased over evolutionary time. Food webs in low-energy, stressful environments are more modular than those in plentiful environments, arid ecologies are more modular during droughts, and foraging of sea otters is more modular when food is limiting. The modularity of social networks changes over time: stock brokers instant messaging networks are more modular under stressful market conditions, criminal networks are more modular under increased police pressure, and world trade network modularity has decreased

Prospect of small modular reactor development

International Nuclear Information System (INIS)

Li Huailin; Zhu Qingyuan; Wang Suli; Xia Haihong

2014-01-01

Small modular reactor has the advantages of modular construction, enhanced safety/robustness from simplified designs, better ecomonic, clean and carbon free, compatible with the needs of smaller utilities and diversified application. In this paper, the prospect of small modular reactor is discussed from technology development status, constraints, economic. (authors)

Mapping Modular SOS to Rewriting Logic

DEFF Research Database (Denmark)

Braga, Christiano de Oliveira; Haeusler, Erik Hermann; Meseguer, José

Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution and verif......Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution...

Mapping Modular SOS to Rewriting Logic

DEFF Research Database (Denmark)

Braga, Christiano de Oliveira; Haeusler, Edward Hermann; Meseguer, José

2003-01-01

Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution and verif......Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution...

Bundling Products and Services Through Modularization Strategies

DEFF Research Database (Denmark)

Bask, Anu; Hsuan, Juliana; Rajahonka, Mervi

2012-01-01

Modularity has been recognized as a powerful tool in improving the efficiency and management of product design and manufacturing. However, the integrated view on covering both, product and service modularity for product-service systems (PSS), is under researched. Therefore, in this paper our...... objective is to contribute to the PSS modularity. Thus, we describe configurations of PSSs and the bundling of products and services through modularization strategies. So far there have not been tools to analyze and determine the correct combinations of degrees of product and service modularities....

Implementing Modular A Levels.

Science.gov (United States)

Holding, Gordon

This document, which is designed for curriculum managers at British further education (FE) colleges, presents basic information on the implementation and perceived benefits of the General Certificate of Education (GCE) modular A (Advanced) levels. The information was synthesized from a survey of 12 FE colleges that introduced the modular A levels…

A moth pheromone brewery: production of (Z)-11-hexadecenol by heterologous co-expression of two biosynthetic genes from a noctuid moth in a yeast cell factory.

Science.gov (United States)

Hagström, Åsa K; Wang, Hong-Lei; Liénard, Marjorie A; Lassance, Jean-Marc; Johansson, Tomas; Löfstedt, Christer

2013-12-13

Moths (Lepidoptera) are highly dependent on chemical communication to find a mate. Compared to conventional unselective insecticides, synthetic pheromones have successfully served to lure male moths as a specific and environmentally friendly way to control important pest species. However, the chemical synthesis and purification of the sex pheromone components in large amounts is a difficult and costly task. The repertoire of enzymes involved in moth pheromone biosynthesis in insecta can be seen as a library of specific catalysts that can be used to facilitate the synthesis of a particular chemical component. In this study, we present a novel approach to effectively aid in the preparation of semi-synthetic pheromone components using an engineered vector co-expressing two key biosynthetic enzymes in a simple yeast cell factory. We first identified and functionally characterized a ∆11 Fatty-Acyl Desaturase and a Fatty-Acyl Reductase from the Turnip moth, Agrotis segetum. The ∆11-desaturase produced predominantly Z11-16:acyl, a common pheromone component precursor, from the abundant yeast palmitic acid and the FAR transformed a series of saturated and unsaturated fatty acids into their corresponding alcohols which may serve as pheromone components in many moth species. Secondly, when we co-expressed the genes in the Brewer's yeast Saccharomyces cerevisiae, a set of long-chain fatty acids and alcohols that are not naturally occurring in yeast were produced from inherent yeast fatty acids, and the presence of (Z)-11-hexadecenol (Z11-16:OH), demonstrated that both heterologous enzymes were active in concert. A 100 ml batch yeast culture produced on average 19.5 μg Z11-16:OH. Finally, we demonstrated that oxidized extracts from the yeast cells containing (Z)-11-hexadecenal and other aldehyde pheromone compounds elicited specific electrophysiological activity from male antennae of the Tobacco budworm, Heliothis virescens, supporting the idea that genes from different

Size reduction of complex networks preserving modularity

Energy Technology Data Exchange (ETDEWEB)

Arenas, A.; Duch, J.; Fernandez, A.; Gomez, S.

2008-12-24

The ubiquity of modular structure in real-world complex networks is being the focus of attention in many trials to understand the interplay between network topology and functionality. The best approaches to the identification of modular structure are based on the optimization of a quality function known as modularity. However this optimization is a hard task provided that the computational complexity of the problem is in the NP-hard class. Here we propose an exact method for reducing the size of weighted (directed and undirected) complex networks while maintaining invariant its modularity. This size reduction allows the heuristic algorithms that optimize modularity for a better exploration of the modularity landscape. We compare the modularity obtained in several real complex-networks by using the Extremal Optimization algorithm, before and after the size reduction, showing the improvement obtained. We speculate that the proposed analytical size reduction could be extended to an exact coarse graining of the network in the scope of real-space renormalization.

Modular Product Families and Assembly Systems

DEFF Research Database (Denmark)

Thyssen, Jesper

2005-01-01

This research centres on assembly systems designed for utilizing product modularization. Altogether, the task for companies has become an issue of managing the overall trade-off between the external market’s desire for variety and the internal efficiency and effectiveness. Product modularization...... a number of theoretical and managerial implications are identified. From a management point of view, the most im-portant finding is that modularization needs to be configured for the two competitive situations, i.e. 1) the volume flexible configuration focusing on generational product variety and 2......) the mix flexible con-figuration focusing on the simultaneous product variety. These two views are in particular different in respect to the understanding of product modularization. All in all, modularization needs to be, and can be, configured in regard to the specific task, which is believed constituting...

On the biosynthetic origin of carminic acid

DEFF Research Database (Denmark)

Rasmussen, Silas A.; Kongstad, Kenneth T; Khorsand-Jamal, Paiman

2018-01-01

provides solid evidence of a polyketide, rather than a shikimate, origin of coccid pigments. Based on the newly identified compounds, we present a detailed biosynthetic scheme that accounts for the formation of carminic acid (CA) in D. coccus and all described coccid pigments which share a flavokermesic...... distribution suggests a common evolutionary origin for the trait in all coccid dye producing insect species....

Essential protein discovery based on a combination of modularity and conservatism.

Science.gov (United States)

Zhao, Bihai; Wang, Jianxin; Li, Xueyong; Wu, Fang-Xiang

2016-11-01

Essential proteins are indispensable for the survival of a living organism and play important roles in the emerging field of synthetic biology. Many computational methods have been proposed to identify essential proteins by using the topological features of interactome networks. However, most of these methods ignored intrinsic biological meaning of proteins. Researches show that essentiality is tied not only to the protein or gene itself, but also to the molecular modules to which that protein belongs. The results of this study reveal the modularity of essential proteins. On the other hand, essential proteins are more evolutionarily conserved than nonessential proteins and frequently bind each other. That is to say, conservatism is another important feature of essential proteins. Multiple networks are constructed by integrating protein-protein interaction (PPI) networks, time course gene expression data and protein domain information. Based on these networks, a new essential protein identification method is proposed based on a combination of modularity and conservatism of proteins. Experimental results show that the proposed method outperforms other essential protein identification methods in terms of a number essential protein out of top ranked candidates. Copyright © 2016. Published by Elsevier Inc.

In silico identification of miRNAs and their target genes and analysis of gene co-expression network in saffron (Crocus sativus L.) stigma

Science.gov (United States)

Zinati, Zahra; Shamloo-Dashtpagerdi, Roohollah; Behpouri, Ali

2016-01-01

As an aromatic and colorful plant of substantive taste, saffron (Crocus sativus L.) owes such properties of matter to growing class of the secondary metabolites derived from the carotenoids, apocarotenoids. Regarding the critical role of microRNAs in secondary metabolic synthesis and the limited number of identified miRNAs in C. sativus, on the other hand, one may see the point how the characterization of miRNAs along with the corresponding target genes in C. sativus might expand our perspectives on the roles of miRNAs in carotenoid/apocarotenoid biosynthetic pathway. A computational analysis was used to identify miRNAs and their targets using EST (Expressed Sequence Tag) library from mature saffron stigmas. Then, a gene co- expression network was constructed to identify genes which are potentially involved in carotenoid/apocarotenoid biosynthetic pathways. EST analysis led to the identification of two putative miRNAs (miR414 and miR837-5p) along with the corresponding stem- looped precursors. To our knowledge, this is the first report on miR414 and miR837-5p in C. sativus. Co-expression network analysis indicated that miR414 and miR837-5p may play roles in C. sativus metabolic pathways and led to identification of candidate genes including six transcription factors and one protein kinase probably involved in carotenoid/apocarotenoid biosynthetic pathway. Presence of transcription factors, miRNAs and protein kinase in the network indicated multiple layers of regulation in saffron stigma. The candidate genes from this study may help unraveling regulatory networks underlying the carotenoid/apocarotenoid biosynthesis in saffron and designing metabolic engineering for enhanced secondary metabolites. PMID:28261627

Symmetric modular torsatron

Science.gov (United States)

Rome, J.A.; Harris, J.H.

1984-01-01

A fusion reactor device is provided in which the magnetic fields for plasma confinement in a toroidal configuration is produced by a plurality of symmetrical modular coils arranged to form a symmetric modular torsatron referred to as a symmotron. Each of the identical modular coils is helically deformed and comprise one field period of the torsatron. Helical segments of each coil are connected by means of toroidally directed windbacks which may also provide part of the vertical field required for positioning the plasma. The stray fields of the windback segments may be compensated by toroidal coils. A variety of magnetic confinement flux surface configurations may be produced by proper modulation of the winding pitch of the helical segments of the coils, as in a conventional torsatron, winding the helix on a noncircular cross section and varying the poloidal and radial location of the windbacks and the compensating toroidal ring coils.

Revisiting the variation of clustering coefficient of biological networks suggests new modular structure

Directory of Open Access Journals (Sweden)

Hao Dapeng

2012-05-01

Full Text Available Abstract Background A central idea in biology is the hierarchical organization of cellular processes. A commonly used method to identify the hierarchical modular organization of network relies on detecting a global signature known as variation of clustering coefficient (so-called modularity scaling. Although several studies have suggested other possible origins of this signature, it is still widely used nowadays to identify hierarchical modularity, especially in the analysis of biological networks. Therefore, a further and systematical investigation of this signature for different types of biological networks is necessary. Results We analyzed a variety of biological networks and found that the commonly used signature of hierarchical modularity is actually the reflection of spoke-like topology, suggesting a different view of network architecture. We proved that the existence of super-hubs is the origin that the clustering coefficient of a node follows a particular scaling law with degree k in metabolic networks. To study the modularity of biological networks, we systematically investigated the relationship between repulsion of hubs and variation of clustering coefficient. We provided direct evidences for repulsion between hubs being the underlying origin of the variation of clustering coefficient, and found that for biological networks having no anti-correlation between hubs, such as gene co-expression network, the clustering coefficient doesn’t show dependence of degree. Conclusions Here we have shown that the variation of clustering coefficient is neither sufficient nor exclusive for a network to be hierarchical. Our results suggest the existence of spoke-like modules as opposed to “deterministic model” of hierarchical modularity, and suggest the need to reconsider the organizational principle of biological hierarchy.

Regulation of the Omega-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes.

Directory of Open Access Journals (Sweden)

Marte Avranden Kjær

Full Text Available Limited availability of the n-3 fatty acids EPA and DHA have led to an interest in better understanding of the n-3 biosynthetic pathway and its regulation. The biosynthesis of alpha-linolenic acid to EPA and DHA involves several complex reaction steps including desaturation-, elongation- and peroxisomal beta-oxidation enzymes. The aims of the present experiments were to gain more knowledge on how this biosynthesis is regulated over time by different doses and fatty acid combinations. Hepatocytes isolated from salmon were incubated with various levels and combinations of oleic acid, EPA and DHA. Oleic acid led to a higher expression of the Δ6 fatty acid desaturase (fad genes Δ6fad_a, Δ6fad_b, Δ6fad_c and the elongase genes elovl2 compared with cells cultured in medium enriched with DHA. Further, the study showed rhythmic variations in expression over time. Levels were reached where a further increase in specific fatty acids given to the cells not stimulated the conversion further. The gene expression of Δ6fad_a_and Δ6fad_b responded similar to fatty acid treatment, suggesting a co-regulation of these genes, whereas Δ5fad and Δ6fad_c showed a different regulation pattern. EPA and DHA induced different gene expression patterns, especially of Δ6fad_a. Addition of radiolabelled alpha-linolenic acid to the hepatocytes confirmed a higher degree of elongation and desaturation in cells treated with oleic acid compared to cells treated with DHA. This study suggests a complex regulation of the conversion process of n-3 fatty acids. Several factors, such as that the various gene copies are differently regulated, the gene expression show rhythmic variations and gene expression only affected to a certain level, determines when you get the maximum conversion of the beneficial n-3 fatty acids.

Decentralizing decision making in modularization strategies

DEFF Research Database (Denmark)

Israelsen, Poul; Jørgensen, Brian

2011-01-01

which distorts the economic effects of modularization at the level of the individual product. This has the implication that decisions on modularization can only be made by top management if decision authority and relevant information are to be aligned. To overcome this problem, we suggest a solution...... that aligns the descriptions of the economic consequences of modularization at the project and portfolio level which makes it possible to decentralize decision making while making sure that local goals are congruent with the global ones in order to avoid suboptimal behaviour. Keywords: Modularization......; Accounting; Cost allocation; Decision rule; Decentralization...

Identification of Secondary Metabolite Gene Clusters in the Pseudovibrio Genus Reveals Encouraging Biosynthetic Potential toward the Production of Novel Bioactive Compounds

Directory of Open Access Journals (Sweden)

Lynn M. Naughton

2017-08-01

Full Text Available Increased incidences of antimicrobial resistance and the emergence of pan-resistant ‘superbugs’ have provoked an extreme sense of urgency amongst researchers focusing on the discovery of potentially novel antimicrobial compounds. A strategic shift in focus from the terrestrial to the marine environment has resulted in the discovery of a wide variety of structurally and functionally diverse bioactive compounds from numerous marine sources, including sponges. Bacteria found in close association with sponges and other marine invertebrates have recently gained much attention as potential sources of many of these novel bioactive compounds. Members of the genus Pseudovibrio are one such group of organisms. In this study, we interrogate the genomes of 21 Pseudovibrio strains isolated from a variety of marine sources, for the presence, diversity and distribution of biosynthetic gene clusters (BGCs. We expand on results obtained from antiSMASH analysis to demonstrate the similarity between the Pseudovibrio-related BGCs and those characterized in other bacteria and corroborate our findings with phylogenetic analysis. We assess how domain organization of the most abundant type of BGCs present among the isolates (Non-ribosomal peptide synthetases and Polyketide synthases may influence the diversity of compounds produced by these organisms and highlight for the first time the potential for novel compound production from this genus of bacteria, using a genome guided approach.

Enablers & Barriers for Realizing Modularity Benefits

DEFF Research Database (Denmark)

Storbjerg, Simon Haahr; Brunø, Thomas Ditlev; Thyssen, Jesper

2012-01-01

far less attention compared to the theories and methods concerning modularization of technical systems. Harvesting the full potential of modularization, particularly in relation to product development agility, depends on more than an optimal architecture. Key enablers in this context......Although modularization is becoming both a well-described domain in academia and a broadly applied concept in business, many of today’s firm still struggle to realize the promised benefits of this approach. Managing modularization is a complex matter, and in spite of this, a topic that has received...... are the organizational and systems related aspects. Recognizing the need for guidance to realize the benefits of modularity, the purpose of this study is through a literature study and a case study to improve the insight into the organizational and systems related enablers and barriers with regard to obtaining the full...

Modular High Voltage Power Supply

Energy Technology Data Exchange (ETDEWEB)

Newell, Matthew R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-05-18

The goal of this project is to develop a modular high voltage power supply that will meet the needs of safeguards applications and provide a modular plug and play supply for use with standard electronic racks.

Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms.

Directory of Open Access Journals (Sweden)

Sacha Coesel

Full Text Available Carotenoids are produced by all photosynthetic organisms, where they play essential roles in light harvesting and photoprotection. The carotenoid biosynthetic pathway of diatoms is largely unstudied, but is of particular interest because these organisms have a very different evolutionary history with respect to the Plantae and are thought to be derived from an ancient secondary endosymbiosis between heterotrophic and autotrophic eukaryotes. Furthermore, diatoms have an additional xanthophyll-based cycle for dissipating excess light energy with respect to green algae and higher plants. To explore the origins and functions of the carotenoid pathway in diatoms we searched for genes encoding pathway components in the recently completed genome sequences of two marine diatoms. Consistent with the supplemental xanthophyll cycle in diatoms, we found more copies of the genes encoding violaxanthin de-epoxidase (VDE and zeaxanthin epoxidase (ZEP enzymes compared with other photosynthetic eukaryotes. However, the similarity of these enzymes with those of higher plants indicates that they had very probably diversified before the secondary endosymbiosis had occurred, implying that VDE and ZEP represent early eukaryotic innovations in the Plantae. Consequently, the diatom chromist lineage likely obtained all paralogues of ZEP and VDE genes during the process of secondary endosymbiosis by gene transfer from the nucleus of the algal endosymbiont to the host nucleus. Furthermore, the presence of a ZEP gene in Tetrahymena thermophila provides the first evidence for a secondary plastid gene encoded in a heterotrophic ciliate, providing support for the chromalveolate hypothesis. Protein domain structures and expression analyses in the pennate diatom Phaeodactylum tricornutum indicate diverse roles for the different ZEP and VDE isoforms and demonstrate that they are differentially regulated by light. These studies therefore reveal the ancient origins of several

Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms.

Science.gov (United States)

Coesel, Sacha; Oborník, Miroslav; Varela, Joao; Falciatore, Angela; Bowler, Chris

2008-08-06

Carotenoids are produced by all photosynthetic organisms, where they play essential roles in light harvesting and photoprotection. The carotenoid biosynthetic pathway of diatoms is largely unstudied, but is of particular interest because these organisms have a very different evolutionary history with respect to the Plantae and are thought to be derived from an ancient secondary endosymbiosis between heterotrophic and autotrophic eukaryotes. Furthermore, diatoms have an additional xanthophyll-based cycle for dissipating excess light energy with respect to green algae and higher plants. To explore the origins and functions of the carotenoid pathway in diatoms we searched for genes encoding pathway components in the recently completed genome sequences of two marine diatoms. Consistent with the supplemental xanthophyll cycle in diatoms, we found more copies of the genes encoding violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP) enzymes compared with other photosynthetic eukaryotes. However, the similarity of these enzymes with those of higher plants indicates that they had very probably diversified before the secondary endosymbiosis had occurred, implying that VDE and ZEP represent early eukaryotic innovations in the Plantae. Consequently, the diatom chromist lineage likely obtained all paralogues of ZEP and VDE genes during the process of secondary endosymbiosis by gene transfer from the nucleus of the algal endosymbiont to the host nucleus. Furthermore, the presence of a ZEP gene in Tetrahymena thermophila provides the first evidence for a secondary plastid gene encoded in a heterotrophic ciliate, providing support for the chromalveolate hypothesis. Protein domain structures and expression analyses in the pennate diatom Phaeodactylum tricornutum indicate diverse roles for the different ZEP and VDE isoforms and demonstrate that they are differentially regulated by light. These studies therefore reveal the ancient origins of several components of the

Modular representation and analysis of fault trees

Energy Technology Data Exchange (ETDEWEB)

Olmos, J; Wolf, L [Massachusetts Inst. of Tech., Cambridge (USA). Dept. of Nuclear Engineering

1978-08-01

An analytical method to describe fault tree diagrams in terms of their modular compositions is developed. Fault tree structures are characterized by recursively relating the top tree event to all its basic component inputs through a set of equations defining each of the modulus for the fault tree. It is shown that such a modular description is an extremely valuable tool for making a quantitative analysis of fault trees. The modularization methodology has been implemented into the PL-MOD computer code, written in PL/1 language, which is capable of modularizing fault trees containing replicated components and replicated modular gates. PL-MOD in addition can handle mutually exclusive inputs and explicit higher order symmetric (k-out-of-n) gates. The step-by-step modularization of fault trees performed by PL-MOD is demonstrated and it is shown how this procedure is only made possible through an extensive use of the list processing tools available in PL/1. A number of nuclear reactor safety system fault trees were analyzed. PL-MOD performed the modularization and evaluation of the modular occurrence probabilities and Vesely-Fussell importance measures for these systems very efficiently. In particular its execution time for the modularization of a PWR High Pressure Injection System reduced fault tree was 25 times faster than that necessary to generate its equivalent minimal cut-set description using MOCUS, a code considered to be fast by present standards.

Modularization and nuclear power. Report by the Technology Transfer Modularization Task Team

International Nuclear Information System (INIS)

1985-06-01

This report describes the results of the work performed by the Technology Transfer Task Team on Modularization. This work was performed as part of the Technology Transfer work being performed under Department of Energy Contract 54-7WM-335406, between December, 1984 and February, 1985. The purpose of this task team effort was to briefly survey the current use of modularization in the nuclear and non-nuclear industries and to assess and evaluate the techniques available for potential application to nuclear power. A key conclusion of the evaluation was that there was a need for a study to establish guidelines for the future development of Light Water Reactor, High Temperature Gas Reactor and Liquid Metal Reactor plants. The guidelines should identify how modularization can improve construction, maintenance, life extension and decommissioning

Fabrication of biosynthetic vascular prostheses by 193-nm excimer laser radiation

Science.gov (United States)

Husinsky, Wolfgang; Csek, Ch.; Bartel, A.; Grabenwoeger, M.; Fitzal, F.; Wolner, Ernst

1998-05-01

This study was undertaken to investigate the feasibility of transmural capillary ingrowth into the inner surface of biosynthetic vascular prostheses (OmniflowTM) through perforations created by an excimer-laser, thus inducing an endothelial cell coverage. The biosynthetic vascular prostheses (10 cm length, 6 mm (phi) ) were perforated with an excimer laser ((phi) of the holes 50 - 100 micrometer, distance 4 mm) and implanted into the carotid arteries of 8 sheep. The laser tissue interaction process of 193 nm radiation ensures minimal thermal damage to the prostheses. They were compared to untreated OmniflowTM prostheses implanted at the contralateral side. Three months after implantation the prostheses were explanted and evaluated by gross morphology, histological examination and scanning electron microscopy. Scanning electron microscopy showed endothelial cells in the midgraft portion of all perforated prostheses, whereas collagen fibers, fibrin meshwork and activated platelets formed the inner layer in 6 out of 8 untreated OmniflowTM prostheses. It can be concluded, that spontaneous endothelialization of biosynthetic vascular prostheses can be achieved by transmural capillary ingrowth through perforations in the wall of the prostheses in an experimental sheep model.

Modular robotics for playful physiotherapy

DEFF Research Database (Denmark)

Lund, Henrik Hautop

2009-01-01

We developed modular robotic tiles to be used for playful physiotherapy, which is supposed to motivate patients to engage in and perform physical rehabilitation exercises. We tested the modular robotic tiles for an extensive period of time (3 years) in daily use in a hospital rehabilitation unit e.......g. for cardiac patients. Also, the tiles were tested for performing physical rehabilitation of stroke patients in their private home. In all pilot test cases qualitative feedback indicate that the patients find the playful use of modular robotic tiles engaging and motivating for them to perform...

What is the evidence for the use of biologic or biosynthetic meshes in abdominal wall reconstruction?

Science.gov (United States)

Köckerling, F; Alam, N N; Antoniou, S A; Daniels, I R; Famiglietti, F; Fortelny, R H; Heiss, M M; Kallinowski, F; Kyle-Leinhase, I; Mayer, F; Miserez, M; Montgomery, A; Morales-Conde, S; Muysoms, F; Narang, S K; Petter-Puchner, A; Reinpold, W; Scheuerlein, H; Smietanski, M; Stechemesser, B; Strey, C; Woeste, G; Smart, N J

2018-04-01

Although many surgeons have adopted the use of biologic and biosynthetic meshes in complex abdominal wall hernia repair, others have questioned the use of these products. Criticism is addressed in several review articles on the poor standard of studies reporting on the use of biologic meshes for different abdominal wall repairs. The aim of this consensus review is to conduct an evidence-based analysis of the efficacy of biologic and biosynthetic meshes in predefined clinical situations. A European working group, "BioMesh Study Group", composed of invited surgeons with a special interest in surgical meshes, formulated key questions, and forwarded them for processing in subgroups. In January 2016, a workshop was held in Berlin where the findings were presented, discussed, and voted on for consensus. Findings were set out in writing by the subgroups followed by consensus being reached. For the review, 114 studies and background analyses were used. The cumulative data regarding biologic mesh under contaminated conditions do not support the claim that it is better than synthetic mesh. Biologic mesh use should be avoided when bridging is needed. In inguinal hernia repair biologic and biosynthetic meshes do not have a clear advantage over the synthetic meshes. For prevention of incisional or parastomal hernias, there is no evidence to support the use of biologic/biosynthetic meshes. In complex abdominal wall hernia repairs (incarcerated hernia, parastomal hernia, infected mesh, open abdomen, enterocutaneous fistula, and component separation technique), biologic and biosynthetic meshes do not provide a superior alternative to synthetic meshes. The routine use of biologic and biosynthetic meshes cannot be recommended.

Higher-order (non-)modularity

DEFF Research Database (Denmark)

Appel, Claus; van Oostrom, Vincent; Simonsen, Jakob Grue

2010-01-01

We show that, contrary to the situation in first-order term rewriting, almost none of the usual properties of rewriting are modular for higher-order rewriting, irrespective of the higher-order rewriting format. We show that for the particular format of simply typed applicative term rewriting...... systems modularity of confluence, normalization, and termination can be recovered by imposing suitable linearity constraints....

Reasoning and change management in modular ontologies

NARCIS (Netherlands)

Stuckenschmidt, Heiner; Klein, Michel

2007-01-01

The benefits of modular representations are well known from many areas of computer science. While in software engineering modularization is mainly a vehicle for supporting distributed development and re-use, in knowledge representation, the main goal of modularization is efficiency of reasoning. In

Modular properties of 6d (DELL) systems

Science.gov (United States)

Aminov, G.; Mironov, A.; Morozov, A.

2017-11-01

If super-Yang-Mills theory possesses the exact conformal invariance, there is an additional modular invariance under the change of the complex bare charge [InlineMediaObject not available: see fulltext.]. The low-energy Seiberg-Witten prepotential ℱ( a), however, is not explicitly invariant, because the flat moduli also change a - → a D = ∂ℱ/∂ a. In result, the prepotential is not a modular form and depends also on the anomalous Eisenstein series E 2. This dependence is usually described by the universal MNW modular anomaly equation. We demonstrate that, in the 6 d SU( N) theory with two independent modular parameters τ and \\widehat{τ} , the modular anomaly equation changes, because the modular transform of τ is accompanied by an ( N -dependent!) shift of \\widehat{τ} and vice versa. This is a new peculiarity of double-elliptic systems, which deserves further investigation.

Aflatoxin B1 inhibition in Aspergillus flavus by Aspergillus niger through down-regulating expression of major biosynthetic genes and AFB1 degradation by atoxigenic A. flavus.

Science.gov (United States)

Xing, Fuguo; Wang, Limin; Liu, Xiao; Selvaraj, Jonathan Nimal; Wang, Yan; Zhao, Yueju; Liu, Yang

2017-09-01

Twenty Aspergillus niger strains were isolated from peanuts and 14 strains were able to completely inhibit AFB 1 production with co-cultivation. By using a Spin-X centrifuge system, it was confirmed that there are some soluble signal molecules or antibiotics involved in the inhibition by A. niger, although they are absent during the initial 24h of A. flavus growth when it is sensitive to inhibition. In A. flavus, 19 of 20 aflatoxin biosynthetic genes were down-regulated by A. niger. Importantly, the expression of aflS was significantly down-regulated, resulting in a reduction of AflS/AflR ratio. The results suggest that A. niger could directly inhibit AFB 1 biosynthesis through reducing the abundance of aflS to aflR mRNAs. Interestingly, atoxigenic A. flavus JZ2 and GZ15 effectively degrade AFB 1 . Two new metabolites were identified and the key toxic lactone and furofuran rings both were destroyed and hydrogenated, meaning that lactonase and reductase might be involved in the degradation process. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive multi-resolution Modularity for detecting communities in networks

Science.gov (United States)

Chen, Shi; Wang, Zhi-Zhong; Bao, Mei-Hua; Tang, Liang; Zhou, Ji; Xiang, Ju; Li, Jian-Ming; Yi, Chen-He

2018-02-01

Community structure is a common topological property of complex networks, which attracted much attention from various fields. Optimizing quality functions for community structures is a kind of popular strategy for community detection, such as Modularity optimization. Here, we introduce a general definition of Modularity, by which several classical (multi-resolution) Modularity can be derived, and then propose a kind of adaptive (multi-resolution) Modularity that can combine the advantages of different Modularity. By applying the Modularity to various synthetic and real-world networks, we study the behaviors of the methods, showing the validity and advantages of the multi-resolution Modularity in community detection. The adaptive Modularity, as a kind of multi-resolution method, can naturally solve the first-type limit of Modularity and detect communities at different scales; it can quicken the disconnecting of communities and delay the breakup of communities in heterogeneous networks; and thus it is expected to generate the stable community structures in networks more effectively and have stronger tolerance against the second-type limit of Modularity.

Modular thought in the circuit analysis

Science.gov (United States)

Wang, Feng

2018-04-01

Applied to solve the problem of modular thought, provides a whole for simplification's method, the complex problems have become of, and the study of circuit is similar to the above problems: the complex connection between components, make the whole circuit topic solution seems to be more complex, and actually components the connection between the have rules to follow, this article mainly tells the story of study on the application of the circuit modular thought. First of all, this paper introduces the definition of two-terminal network and the concept of two-terminal network equivalent conversion, then summarizes the common source resistance hybrid network modular approach, containing controlled source network modular processing method, lists the common module, typical examples analysis.

Modular Engineering of Production Plants

DEFF Research Database (Denmark)

Miller, Thomas Dedenroth

1998-01-01

Based on a case-study on design of pharmaceutical production plants, this paper suggests that modularity may support business efficiency for companies with one-of-a-kind production and without in-house manufacturing. Modularity may support efficient management of design knowledge and may facilitate...

Comparative transcriptomic analyses of differentially expressed genes in transgenic melatonin biosynthesis ovine HIOMT gene in switchgrass

Directory of Open Access Journals (Sweden)

Shan Yuan

2016-11-01

Full Text Available Melatonin serves pleiotropic functions in prompting plant growth and resistance to various stresses. The accurate biosynthetic pathway of melatonin remains elusive in plant species, while the N-acetyltransferase and O-methyltransferase were considered to be the last two key enzymes during its biosynthesis. To investigate the biosynthesis and metabolic pathway of melatonin in plants, the RNA-seq profile of overexpression of the ovine HIOMT was analyzed and compared with the previous transcriptome of transgenic oAANAT gene in switchgrass, a model plant for cellulosic ethanol production. A total of 946, 405 and 807 differentially expressed unigenes were observed in AANAT vs. control, HIOMT vs. control, and AANAT vs. HIOMT, respectively. The significantly upregulated (F-box/kelch-repeat protein, zinc finger BED domain-containing protein-3 genes were consistent with enhanced phenotypes of shoot, stem and root growth in transgenic oHIOMT switchgrass. Early flowering in overexpression of oHIOMT switchgrass involved in the regulation of flowering-time genes (APETALA2. Several stress resistant related genes (SPX domain-containing membrane protein, copper transporter 1, late blight resistance protein homolog R1A-6 OS etc. were specifically and significantly upregulated in transgenic oHIOMT only, while metabolism-related genes (phenylalanine-4-hydroxylase, tyrosine decarboxylase 1, protein disulfide-isomerase and galactinol synthase 2 etc. were significantly upregulated in transgenic oAANAT only. These results provide new sights into the biosynthetic and physiological functional networks of melatonin in plants.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

KAUST Repository

Li, Yongxin

2015-03-24

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

Science.gov (United States)

Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

2015-03-01

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning ``plug-and-play'' approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Modular reconfigurable machines incorporating modular open architecture control

CSIR Research Space (South Africa)

Padayachee, J

2008-01-01

Full Text Available degrees of freedom on a single platform. A corresponding modular Open Architecture Control (OAC) system is presented. OAC overcomes the inflexibility of fixed proprietary automation, ensuring that MRMs provide the reconfigurability and extensibility...

KWU's modular approach to HTR commercialization

International Nuclear Information System (INIS)

Frewer, H.; Weisbrodt, I.

1983-01-01

As a way of avoiding the uncertainties, delays and unacceptable commercial risks which have plagued advanced reactor projects in Germany, KWU is advocating a modular approach to commercialization of the high-temperature reactor (HTR), using small size standard reactor units. KWU has received a contract for the study of a co-generation plant based on this modular system. Features of the KWU modular HTR, process heat, gasification, costs and future development are discussed. (UK)

Fable: Socially Interactive Modular Robot

DEFF Research Database (Denmark)

Magnússon, Arnþór; Pacheco, Moises; Moghadam, Mikael

2013-01-01

Modular robots have a significant potential as user-reconfigurable robotic playware, but often lack sufficient sensing for social interaction. We address this issue with the Fable modular robotic system by exploring the use of smart sensor modules that has a better ability to sense the behavior...

Modular forms a classical approach

CERN Document Server

Cohen, Henri

2017-01-01

The theory of modular forms is a fundamental tool used in many areas of mathematics and physics. It is also a very concrete and "fun" subject in itself and abounds with an amazing number of surprising identities. This comprehensive textbook, which includes numerous exercises, aims to give a complete picture of the classical aspects of the subject, with an emphasis on explicit formulas. After a number of motivating examples such as elliptic functions and theta functions, the modular group, its subgroups, and general aspects of holomorphic and nonholomorphic modular forms are explained, with an emphasis on explicit examples. The heart of the book is the classical theory developed by Hecke and continued up to the Atkin-Lehner-Li theory of newforms and including the theory of Eisenstein series, Rankin-Selberg theory, and a more general theory of theta series including the Weil representation. The final chapter explores in some detail more general types of modular forms such as half-integral weight, Hilbert, Jacob...

Modularity-like objective function in annotated networks

Science.gov (United States)

Xie, Jia-Rong; Wang, Bing-Hong

2017-12-01

We ascertain the modularity-like objective function whose optimization is equivalent to the maximum likelihood in annotated networks. We demonstrate that the modularity-like objective function is a linear combination of modularity and conditional entropy. In contrast with statistical inference methods, in our method, the influence of the metadata is adjustable; when its influence is strong enough, the metadata can be recovered. Conversely, when it is weak, the detection may correspond to another partition. Between the two, there is a transition. This paper provides a concept for expanding the scope of modularity methods.

Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.

Science.gov (United States)

Lemetre, Christophe; Maniko, Jeffrey; Charlop-Powers, Zachary; Sparrow, Ben; Lowe, Andrew J; Brady, Sean F

2017-10-31

Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts. Published under the PNAS license.

Modularization, inter-functional integration and operational performance

DEFF Research Database (Denmark)

Boer, Henrike Engele Elisabeth; Boer, Harry

2014-01-01

for firms to indeed use product modularity beneficially, in particular inter-functional integration between manufacturing and purchasing, design and sales, respectively. The purpose of the paper is to investigate the direct performance effects of modularization, as well as the mediating effects of the three...... forms of integration in the modularization-performance relationship....

Understanding Complex Construction Systems Through Modularity

DEFF Research Database (Denmark)

Jensen, Tor Clarke; Bekdik, Baris; Thuesen, Christian

2014-01-01

This paper develops a framework for understanding complexity in construction projects by combining theories of complexity management and modularization. The framework incorporates three dimensions of product, process, and organizational modularity with the case of gypsum wall elements. The analysis...... system, rather than a modular, although the industry forces modular organizational structures. This creates a high complexity degree caused by the non-alignment of building parts and organizations and the frequent swapping of modules....... finds that the main driver of complexity is the fragmentation of the design and production, which causes the production modules to construct and install new product types and variants for each project as the designers are swapped for every project. The many interfaces are characteristics of an integral...

A Formal Theory for Modular ERDF Ontologies

Science.gov (United States)

Analyti, Anastasia; Antoniou, Grigoris; Damásio, Carlos Viegas

The success of the Semantic Web is impossible without any form of modularity, encapsulation, and access control. In an earlier paper, we extended RDF graphs with weak and strong negation, as well as derivation rules. The ERDF #n-stable model semantics of the extended RDF framework (ERDF) is defined, extending RDF(S) semantics. In this paper, we propose a framework for modular ERDF ontologies, called modular ERDF framework, which enables collaborative reasoning over a set of ERDF ontologies, while support for hidden knowledge is also provided. In particular, the modular ERDF stable model semantics of modular ERDF ontologies is defined, extending the ERDF #n-stable model semantics. Our proposed framework supports local semantics and different points of view, local closed-world and open-world assumptions, and scoped negation-as-failure. Several complexity results are provided.

Analysis of enabling factors in realizing modularization benefits

DEFF Research Database (Denmark)

Storbjerg, Simon Haahr; Brunø, Thomas Ditlev

2012-01-01

Although modularization is becoming a welldescribed and broadly applied concept, many of today’s firms still struggle to realize the promised benefits of this approach. Managing modularization is a complex matter, and in spite of this, a topic that has received far less attention compared...... to theories and methods concerning modularization of technical systems.Recognizing the need for guidance to realize the benefits of modularity, the purpose of this study is through a literature study and a case study to improve the insight into the organizational and systems related enablers and barriers...... with regard to obtaining the full potential of modularization....

Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes

KAUST Repository

Zhang, Meiling; Chekan, Jonathan R.; Dodd, Dylan; Hong, Pei-Ying; Radlinsk, Lauren; Revindran, Vanessa; Nair, Satish K.; Mackie, Roderick Ian; Cann, Isaac Ko O

2014-01-01

highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT-04215 and BACOVA-04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture

A Comprehensive View On Benefits From Product Modularization

DEFF Research Database (Denmark)

Hansen, Poul H. Kyvsgård; Sun, Hongyi

2010-01-01

In many cases the phenomenon of product modularization is presented in an inherently positive way. Based on the frequency of these positive cases it might be expected that product modularization is a universal cure for any competitive weaknesses experienced by manufacturing or service companies....... Definitely, the many various aspects of product modularization have demonstrated substantial potentials regarding improved and enhanced competitiveness, but our empirical studies illustrate that the efforts in regards to realizing specific product modularization benefits need to be managed carefully. Our...... studies illustrates that the expected and the realized benefits from a product modularization effort rarely match. In most cases the companies have only weak estimations about both the type and the magnitude of the potential benefits when planning the modularization project. This indicates a serious need...

Genome sequence of Thermofilum pendens reveals an exceptional loss of biosynthetic pathways without genome reduction

Energy Technology Data Exchange (ETDEWEB)

Kyrpides, Nikos; Anderson, Iain; Rodriguez, Jason; Susanti, Dwi; Porat, Iris; Reich, Claudia; Ulrich, Luke E.; Elkins, James G.; Mavromatis, Kostas; Lykidis, Athanasios; Kim, Edwin; Thompson, Linda S.; Nolan, Matt; Land, Miriam; Copeland, Alex; Lapidus, Alla; Lucas, Susan; Detter, Chris; Zhulin, Igor B.; Olsen, Gary J.; Whitman, William; Mukhopadhyay, Biswarup; Bristow, James; Kyrpides, Nikos

2008-01-01

We report the complete genome of Thermofilum pendens, a deep-branching, hyperthermophilic member of the order Thermoproteales within the archaeal kingdom Crenarchaeota. T. pendens is a sulfur-dependent, anaerobic heterotroph isolated from a solfatara in Iceland. It is an extracellular commensal, requiring an extract of Thermoproteus tenax for growth, and the genome sequence reveals that biosynthetic pathways for purines, most amino acids, and most cofactors are absent. In fact T. pendens has fewer biosynthetic enzymes than obligate intracellular parasites, although it does not display other features common among obligate parasites and thus does not appear to be in the process of becoming a parasite. It appears that T. pendens has adapted to life in an environment rich in nutrients. T. pendens was known to utilize peptides as an energy source, but the genome reveals substantial ability to grow on carbohydrates. T. pendens is the first crenarchaeote and only the second archaeon found to have a transporter of the phosphotransferase system. In addition to fermentation, T. pendens may gain energy from sulfur reduction with hydrogen and formate as electron donors. It may also be capable of sulfur-independent growth on formate with formate hydrogenlyase. Additional novel features are the presence of a monomethylamine:corrinoid methyltransferase, the first time this enzyme has been found outside of Methanosarcinales, and a presenilin-related protein. Predicted highly expressed proteins do not include housekeeping genes, and instead include ABC transporters for carbohydrates and peptides, and CRISPR-associated proteins.

Modular low-voltage electron emitters

International Nuclear Information System (INIS)

Berejka, Anthony J.

2005-01-01

Modular, low-voltage electron emitters simplify electron beam (EB) technology for many industrial uses and for research and development. Modular electron emitters are produced in quantity as sealed systems that are evacuated at the factory, eliminating the need for vacuum pumps at the point of use. A plug-out-plug-in method of replacement facilitates servicing. By using an ultra-thin 6-7 μm titanium foil window, solid-state power supplies, an innovative design to extract and spread the beam (enabling systems to be placed adjacent to each other to extend beam width) and touch-screen computer controls, these modular units combine ease of use and electrical transfer efficiency at voltages that can be varied between 80 kV and 150 kV with beam currents up to 40 mA per 25 cm across the beam window. These new devices have been made in three widths: 5 cm, 25 cm, and 40 cm. Details of the beam construction and illustrations of industrial uses will be presented. Traditional uses in the graphic arts and coatings areas have welcomed this modular technology as well as uses for surface sterilization. Being compact and lightweight (∼15 kg/emitter), these modular beams have been configured around complex shapes to achieve three-dimensional surface curing at high production rates

Modular low-voltage electron emitters

Science.gov (United States)

Berejka, Anthony J.

2005-12-01

Modular, low-voltage electron emitters simplify electron beam (EB) technology for many industrial uses and for research and development. Modular electron emitters are produced in quantity as sealed systems that are evacuated at the factory, eliminating the need for vacuum pumps at the point of use. A plug-out-plug-in method of replacement facilitates servicing. By using an ultra-thin 6-7 μm titanium foil window, solid-state power supplies, an innovative design to extract and spread the beam (enabling systems to be placed adjacent to each other to extend beam width) and touch-screen computer controls, these modular units combine ease of use and electrical transfer efficiency at voltages that can be varied between 80 kV and 150 kV with beam currents up to 40 mA per 25 cm across the beam window. These new devices have been made in three widths: 5 cm, 25 cm, and 40 cm. Details of the beam construction and illustrations of industrial uses will be presented. Traditional uses in the graphic arts and coatings areas have welcomed this modular technology as well as uses for surface sterilization. Being compact and lightweight (∼15 kg/emitter), these modular beams have been configured around complex shapes to achieve three-dimensional surface curing at high production rates.

Markerless gene knockout and integration to express heterologous biosynthetic gene clusters in Pseudomonas putida

DEFF Research Database (Denmark)

Choi, Kyeong Rok; Cho, Jae Sung; Cho, In Jin

2018-01-01

Pseudomonas putida has gained much interest among metabolic engineers as a workhorse for producing valuable natural products. While a few gene knockout tools for P. putida have been reported, integration of heterologous genes into the chromosome of P. putida, an essential strategy to develop stable...... plasmid curing systems, generating final strains free of antibiotic markers and plasmids. This markerless recombineering system for efficient gene knockout and integration will expedite metabolic engineering of P. putida, a bacterial host strain of increasing academic and industrial interest....

Endomorphisms on half-sided modular inclusions

International Nuclear Information System (INIS)

Svegstrup, Rolf Dyre

2006-01-01

In algebraic quantum field theory we consider nets of von Neumann algebras indexed over regions of the space time. Wiesbrock [''Conformal quantum field theory and half-sided modular inclusions of von Neumann algebras,'' Commun. Math. Phys. 158, 537-543 (1993)] has shown that strongly additive nets of von Neumann algebras on the circle are in correspondence with standard half-sided modular inclusions. We show that a finite index endomorphism on a half-sided modular inclusion extends to a finite index endomorphism on the corresponding net of von Neumann algebras on the circle. Moreover, we present another approach to encoding endomorphisms on nets of von Neumann algebras on the circle into half-sided modular inclusions. There is a natural way to associate a weight to a Moebius covariant endomorphism. The properties of this weight have been studied by Bertozzini et al. [''Covariant sectors with infinite dimension and positivity of the energy,'' Commun. Math. Phys. 193, 471-492 (1998)]. In this paper we show the converse, namely, how to associate a Moebius covariant endomorphism to a given weight under certain assumptions, thus obtaining a correspondence between a class of weights on a half-sided modular inclusion and a subclass of the Moebius covariant endomorphisms on the associated net of von Neumann algebras. This allows us to treat Moebius covariant endomorphisms in terms of weights on half-sided modular inclusions. As our aim is to provide a framework for treating endomorphisms on nets of von Neumann algebras in terms of the apparently simpler objects of weights on half-sided modular inclusions, we lastly give some basic results for manipulations with such weights

Identification of drivers for modular production

DEFF Research Database (Denmark)

Brunoe, Thomas Ditlev; Bossen, Jacob; Nielsen, Kjeld

2015-01-01

Todays competitive environment in industry creates a need for companies to enhance their ability to introduce new products faster. To increase rampup speed reconfigurable manufacturing systems is a promising concept, however to implement this production platforms and modular manufacturing...... is required. This paper presents an analysis whether and which module drivers from general product development can be applied to the development process of a modular manufacturing system. The result is a compiled list of modular drivers for manufacturing and examples of their use....

Towards precise classification of cancers based on robust gene functional expression profiles

Directory of Open Access Journals (Sweden)

Zhu Jing

2005-03-01

Full Text Available Abstract Background Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. Results Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. Conclusion This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge

A Modular SOS for Action Notation - Revisited

DEFF Research Database (Denmark)

Mosses, Peter David

A draft modular SOS for the new version of AN, referred to as AN-2, has been available since 2000. It is written in CASL and has been checked for well-formedness using CATS (CASL Tool Set). It appears to be significantly more accessible than the original SOS of AN-1. However, it now appears......-notation for the modular SOS rules. After discussing the issues, we look at some illustrative examples taken from an improved modular SOS of AN-2 (in preparation). We also look at the possibility of empirical testing of the modular SOS by a straightforward translation to Prolog....

Contrasting platform thinking and product modularization

DEFF Research Database (Denmark)

Boer, Henrike Engele Elisabeth; Persson, Magnus

2015-01-01

Product modularization and platform thinking are both practices that seek to alleviate the negative impact of product customization and variety on internal operations by relying on economies of substitution. Through the use of a standardized pool of components and interfaces, these practices aim...... to create a broad spectrum of product choices. At first sight, product modularization and platform thinking are very similar. The difference between these practices can, however, be found in the manner in which they employ standardization. Where product modularization focuses on creating standardized...... variants. There is a general lack of research addressing the contingency factors that dictate the appropriateness of the use of product modularization and platform thinking in different contexts. To our knowledge, no large-scale empirical research has been reported in which the two concepts, contextual...

Modular robotic tiles: experiments for children with autism

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Dam Pedersen, Martin; Beck, Richard

2009-01-01

rehabilitation), and with the proper radio communication mechanism they may give unique possibilities for documentation of the physical activity (e.g., therapeutic treatment). A major point of concern in modular robotics is the connection mechanism, so we investigated different solutions for the connection......We developed a modular robotic tile and a system composed of a number of these modular robotic tiles. The system composed of the modular robotic tiles engages the user in physical activities, e.g., physiotherapy, sports, fitness, and entertainment. The modular robotic tiles motivate the user...... to perform physical activities by providing immediate feedback based upon their physical interaction with the system. With the modular robotic tiles, the user is able to make new physical set-ups within less than a minute. The tiles are applicable for different forms of physical activities (e.g., therapeutic...

De novo transcriptome sequencing and digital gene expression analysis predict biosynthetic pathway of rhynchophylline and isorhynchophylline from Uncaria rhynchophylla, a non-model plant with potent anti-alzheimer's properties.

Science.gov (United States)

Guo, Qianqian; Ma, Xiaojun; Wei, Shugen; Qiu, Deyou; Wilson, Iain W; Wu, Peng; Tang, Qi; Liu, Lijun; Dong, Shoukun; Zu, Wei

2014-08-12

The major medicinal alkaloids isolated from Uncaria rhynchophylla (gouteng in chinese) capsules are rhynchophylline (RIN) and isorhynchophylline (IRN). Extracts containing these terpene indole alkaloids (TIAs) can inhibit the formation and destabilize preformed fibrils of amyloid β protein (a pathological marker of Alzheimer's disease), and have been shown to improve the cognitive function of mice with Alzheimer-like symptoms. The biosynthetic pathways of RIN and IRN are largely unknown. In this study, RNA-sequencing of pooled Uncaria capsules RNA samples taken at three developmental stages that accumulate different amount of RIN and IRN was performed. More than 50 million high-quality reads from a cDNA library were generated and de novo assembled. Sequences for all of the known enzymes involved in TIAs synthesis were identified. Additionally, 193 cytochrome P450 (CYP450), 280 methyltransferase and 144 isomerase genes were identified, that are potential candidates for enzymes involved in RIN and IRN synthesis. Digital gene expression profile (DGE) analysis was performed on the three capsule developmental stages, and based on genes possessing expression profiles consistent with RIN and IRN levels; four CYP450s, three methyltransferases and three isomerases were identified as the candidates most likely to be involved in the later steps of RIN and IRN biosynthesis. A combination of de novo transcriptome assembly and DGE analysis was shown to be a powerful method for identifying genes encoding enzymes potentially involved in the biosynthesis of important secondary metabolites in a non-model plant. The transcriptome data from this study provides an important resource for understanding the formation of major bioactive constituents in the capsule extract from Uncaria, and provides information that may aid in metabolic engineering to increase yields of these important alkaloids.

Variation in sequence and location of the fumonisin mycotoxin niosynthetic gene cluster in Fusarium

NARCIS (Netherlands)

Proctor, R.H.; Hove, van F.; Susca, A.; Stea, A.; Busman, M.; Lee, van der T.A.J.; Waalwijk, C.; Moretti, A.

2010-01-01

In Fusarium, the ability to produce fumonisins is governed by a 17-gene fumonisin biosynthetic gene (FUM) cluster. Here, we examined the cluster in F. oxysporum strain O-1890 and nine other species selected to represent a wide range of the genetic diversity within the GFSC.

Modular invariance of N=2 minimal models

International Nuclear Information System (INIS)

Sidenius, J.

1991-01-01

We prove modular covariance of one-point functions at one loop in the diagonal N=2 minimal superconformal models. We use the recently derived general formalism for computing arbitrary conformal blocks in these models. Our result should be sufficient to guarantee modular covariance at arbitrary genus. It is thus an important check on the general formalism which is not manifestly modular covariant. (orig.)

Transcriptomic analysis of Siberian ginseng (Eleutherococcus senticosus) to discover genes involved in saponin biosynthesis.

Science.gov (United States)

Hwang, Hwan-Su; Lee, Hyoshin; Choi, Yong Eui

2015-03-14

Eleutherococcus senticosus, Siberian ginseng, is a highly valued woody medicinal plant belonging to the family Araliaceae. E. senticosus produces a rich variety of saponins such as oleanane-type, noroleanane-type, 29-hydroxyoleanan-type, and lupane-type saponins. Genomic or transcriptomic approaches have not been used to investigate the saponin biosynthetic pathway in this plant. In this study, de novo sequencing was performed to select candidate genes involved in the saponin biosynthetic pathway. A half-plate 454 pyrosequencing run produced 627,923 high-quality reads with an average sequence length of 422 bases. De novo assembly generated 72,811 unique sequences, including 15,217 contigs and 57,594 singletons. Approximately 48,300 (66.3%) unique sequences were annotated using BLAST similarity searches. All of the mevalonate pathway genes for saponin biosynthesis starting from acetyl-CoA were isolated. Moreover, 206 reads of cytochrome P450 (CYP) and 145 reads of uridine diphosphate glycosyltransferase (UGT) sequences were isolated. Based on methyl jasmonate (MeJA) treatment and real-time PCR (qPCR) analysis, 3 CYPs and 3 UGTs were finally selected as candidate genes involved in the saponin biosynthetic pathway. The identified sequences associated with saponin biosynthesis will facilitate the study of the functional genomics of saponin biosynthesis and genetic engineering of E. senticosus.

Discovering perturbation of modular structure in HIV progression by integrating multiple data sources through non-negative matrix factorization.

Science.gov (United States)

Ray, Sumanta; Maulik, Ujjwal

2016-12-20

Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified metamodules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

Duality ensures modular covariance

International Nuclear Information System (INIS)

Li Miao; Yu Ming

1989-11-01

We show that the modular transformations for one point functions on the torus, S(n), satisfy the polynomial equations derived by Moore and Seiberg, provided the duality property of the model is ensured. The formula for S(n) is derived by us previously and should be valid for any conformal field theory. As a consequence, the full consistency conditions for modular invariance at higher genus are completely guaranteed by duality of the theory on the sphere. (orig.)

Plasmid-encoded biosynthetic genes alleviate metabolic disadvantages while increasing glucose conversion to shikimate in an engineered Escherichia coli strain.

Science.gov (United States)

Rodriguez, Alberto; Martínez, Juan A; Millard, Pierre; Gosset, Guillermo; Portais, Jean-Charles; Létisse, Fabien; Bolivar, Francisco

2017-06-01

Metabolic engineering strategies applied over the last two decades to produce shikimate (SA) in Escherichia coli have resulted in a battery of strains bearing many expression systems. However, the effects that these systems have on the host physiology and how they impact the production of SA are still not well understood. In this work we utilized an engineered E. coli strain to determine the consequences of carrying a vector that promotes SA production from glucose with a high-yield but that is also expected to impose a significant cellular burden. Kinetic comparisons in fermentors showed that instead of exerting a negative effect, the sole presence of the plasmid increased glucose consumption without diminishing the growth rate. By constitutively expressing a biosynthetic operon from this vector, the more active glycolytic metabolism was exploited to redirect intermediates toward the production of SA, which further increased the glucose consumption rate and avoided excess acetate production. Fluxomics and metabolomics experiments revealed a global remodeling of the carbon and energy metabolism in the production strain, where the increased SA production reduced the carbon available for oxidative and fermentative pathways. Moreover, the results showed that the production of SA relies on a specific setup of the pentose phosphate pathway, where both its oxidative and non-oxidative branches are strongly activated to supply erythrose-4-phosphate and balance the NADPH requirements. This work improves our understanding of the metabolic reorganization observed in E. coli in response to the plasmid-based expression of the SA biosynthetic pathway. Biotechnol. Bioeng. 2017;114: 1319-1330. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Modular Software-Defined Radio

Directory of Open Access Journals (Sweden)

Rhiemeier Arnd-Ragnar

2005-01-01

Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster

Directory of Open Access Journals (Sweden)

Jakobek Judy L

2007-07-01

Full Text Available Abstract Background The biosynthesis of aflatoxin (AF involves over 20 enzymatic reactions in a complex polyketide pathway that converts acetate and malonate to the intermediates sterigmatocystin (ST and O-methylsterigmatocystin (OMST, the respective penultimate and ultimate precursors of AF. Although these precursors are chemically and structurally very similar, their accumulation differs at the species level for Aspergilli. Notable examples are A. nidulans that synthesizes only ST, A. flavus that makes predominantly AF, and A. parasiticus that generally produces either AF or OMST. Whether these differences are important in the evolutionary/ecological processes of species adaptation and diversification is unknown. Equally unknown are the specific genomic mechanisms responsible for ordering and clustering of genes in the AF pathway of Aspergillus. Results To elucidate the mechanisms that have driven formation of these clusters, we performed systematic searches of aflatoxin cluster homologs across five Aspergillus genomes. We found a high level of gene duplication and identified seven modules consisting of highly correlated gene pairs (aflA/aflB, aflR/aflS, aflX/aflY, aflF/aflE, aflT/aflQ, aflC/aflW, and aflG/aflL. With the exception of A. nomius, contrasts of mean Ka/Ks values across all cluster genes showed significant differences in selective pressure between section Flavi and non-section Flavi species. A. nomius mean Ka/Ks values were more similar to partial clusters in A. fumigatus and A. terreus. Overall, mean Ka/Ks values were significantly higher for section Flavi than for non-section Flavi species. Conclusion Our results implicate several genomic mechanisms in the evolution of ST, OMST and AF cluster genes. Gene modules may arise from duplications of a single gene, whereby the function of the pre-duplication gene is retained in the copy (aflF/aflE or the copies may partition the ancestral function (aflA/aflB. In some gene modules, the

Towards a Standard for Modular Petri Nets

DEFF Research Database (Denmark)

Kindler, Ekkart; Petrucci, Laure

2009-01-01

concepts could or should be subject to import and export in high-level Petri nets. In this paper, we formalise a minimal version of modular high-level Petri nets, which is based on the concepts of modular PNML. This shows that modular PNML can be formalised once a specific version of Petri net is fixed....... Moreover, we present and discuss some more advanced features of modular Petri nets that could be included in the standard. This way, we provide a formal foundation and a basis for a discussion of features to be included in the upcoming standard of a module concept for Petri nets in general and for high-level...

Problems in the theory of modular forms

CERN Document Server

Murty, M Ram; Graves, Hester

2016-01-01

This book introduces the reader to the fascinating world of modular forms through a problem-solving approach. As such, besides researchers, the book can be used by the undergraduate and graduate students for self-instruction. The topics covered include q-series, the modular group, the upper half-plane, modular forms of level one and higher level, the Ramanujan τ-function, the Petersson inner product, Hecke operators, Dirichlet series attached to modular forms and further special topics. It can be viewed as a gentle introduction for a deeper study of the subject. Thus, it is ideal for non-experts seeking an entry into the field. .

Summer School and Conference : Computations with Modular Forms

CERN Document Server

Wiese, Gabor

2014-01-01

This volume contains original research articles, survey articles and lecture notes related to the Computations with Modular Forms 2011 Summer School and Conference, held at the University of Heidelberg. A key theme of the Conference and Summer School was the interplay between theory, algorithms and experiment. The 14 papers offer readers both, instructional courses on the latest algorithms for computing modular and automorphic forms, as well as original research articles reporting on the latest developments in the field. The three Summer School lectures provide an introduction to modern algorithms together with some theoretical background for computations of and with modular forms, including computing cohomology of arithmetic groups, algebraic automorphic forms, and overconvergent modular symbols. The 11 Conference papers cover a wide range of themes related to computations with modular forms, including lattice methods for algebraic modular forms on classical groups, a generalization of the Maeda conjecture, ...

Towards a Formal Basis for Modular Safety Cases

Science.gov (United States)

Denney, Ewen; Pai, Ganesh

2015-01-01

Safety assurance using argument-based safety cases is an accepted best-practice in many safety-critical sectors. Goal Structuring Notation (GSN), which is widely used for presenting safety arguments graphically, provides a notion of modular arguments to support the goal of incremental certification. Despite the efforts at standardization, GSN remains an informal notation whereas the GSN standard contains appreciable ambiguity especially concerning modular extensions. This, in turn, presents challenges when developing tools and methods to intelligently manipulate modular GSN arguments. This paper develops the elements of a theory of modular safety cases, leveraging our previous work on formalizing GSN arguments. Using example argument structures we highlight some ambiguities arising through the existing guidance, present the intuition underlying the theory, clarify syntax, and address modular arguments, contracts, well-formedness and well-scopedness of modules. Based on this theory, we have a preliminary implementation of modular arguments in our toolset, AdvoCATE.

Modularity for Modulating Exercises and Levels

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Nielsen, Camilla Balslev

2011-01-01

The modular interactive tiles aim at engaging anybody (elderly, carer, hospital personnel, children) in performing playful and motivating physical activities. Inspired by modular robotics, each tile is a self-contained module with processing power and communication to neighbouring modules....... In this paper, we investigate the therapeutic use. We show how the tiles are tested extensively with cardiac patients, COLD patients and stroke patients in hospitals and in the private homes of patients and elderly. We find that therapists are using the modular aspect of the tiles for personalized training...

Equacions de corbes modulars biel.líptiques

OpenAIRE

Ribes González, Jordi

2013-01-01

This thesis deals primarily with the question of finding equations for bielliptic modular curves of the type $X_{0}(N)$. After introducing the reader to some of the fundamental aspects on the theory modular curves, we discuss four different techniques for finding such models and give examples of their implementation in Sage.. Es tracta d'estudiar les corbes modulars biel.líptiques, determinades per F. Bars en l'article Bielliptic Modular curves [1999], amb l'objectiu de trobar equacions i, en...

Functions of some capsular polysaccharide biosynthetic genes in Klebsiella pneumoniae NTUH K-2044.

Directory of Open Access Journals (Sweden)

Jin-Yuan Ho

Full Text Available The growing number of Klebsiella pneumoniae infections, commonly acquired in hospitals, has drawn great concern. It has been shown that the K1 and K2 capsular serotypes are the most detrimental strains, particularly to those with diabetes. The K1 cps (capsular polysaccharide locus in the NTUH-2044 strain of the pyogenic liver abscess (PLA K. pneumoniae has been identified recently, but little is known about the functions of the genes therein. Here we report characterization of a group of cps genes and their roles in the pathogenesis of K1 K. pneumoniae. By sequential gene deletion, the cps gene cluster was first re-delimited between genes galF and ugd, which serve as up- and down-stream ends, respectively. Eight gene products were characterized in vitro and in vivo to be involved in the syntheses of UDP-glucose, UDP-glucuronic acid and GDP-fucose building units. Twelve genes were identified as virulence factors based on the observation that their deletion mutants became avirulent or lost K1 antigenicity. Furthermore, deletion of kp3706, kp3709 or kp3712 (ΔwcaI, ΔwcaG or Δatf, respectively, which are all involved in fucose biosynthesis, led to a broad range of transcriptional suppression for 52 upstream genes. The genes suppressed include those coding for unknown regulatory membrane proteins and six multidrug efflux system proteins, as well as proteins required for the K1 CPS biosynthesis. In support of the suppression of multidrug efflux genes, we showed that these three mutants became more sensitive to antibiotics. Taken together, the results suggest that kp3706, kp3709 or kp3712 genes are strongly related to the pathogenesis of K. pneumoniae K1.

Model engineering in a modular PSA

International Nuclear Information System (INIS)

Friedlhuber, Thomas

2014-01-01

For the purpose of PSA (Probabilistic Safety Analysis) for complex industrial systems, often PSA models in the form of fault and event trees are developed to model the risk of unwanted situations (hazards). While the recent decades, PSA models have gained high acceptance and have been developed massively. This lead to an increase in model sizes and complexity. Today, PSA models are often difficult to understand and maintain. This manuscript presents the concept of a modular PSA. A modular PSA tries to cope with the increased complexity by the techniques of modularization and instantiation. Modularization targets to treat a model by smaller pieces (the 'modules') to regain control over models. Instantiation aims to configure a generic model to different contexts. Both try to reduce model complexity. A modular PSA proposes new functionality to manage PSA models. Current model management is rather limited and not efficient. This manuscript shows new methods to manage the evolutions (versions) and deviations (variants) of PSA models in a modular PSA. The concepts of version and variant management are presented in this thesis. In this context, a model comparison and fusion of PSA models is precised. Model comparison provides important feedback to model engineers and model fusion kind of combines the work from different model engineers (concurrent model engineering). Apart from model management, methods to understand the content of PSA models are presented. The methods focus to highlight the dependencies between modules rather than their contents. Dependencies are automatically derived from a model structure. They express relations between model objects (for example a fault tree may have dependencies to basic events). To visualize those dependencies (for example in form of a model cartography) can constitute a crucial aid to model engineers for understanding complex interrelations in PSA models. Within the scope of this thesis, a software named 'Andromeda' has been

Anomalies and modular invariance in string theory

International Nuclear Information System (INIS)

Schellekens, A.N.; Warner, N.P.

1986-01-01

All known anomaly cancellations of heterotic string theories are derived directly from one-loop modular invariance, and are shown to be related to a property of modular functions of weight 2. Using modular invariance infinite classes of anomaly free field theories are constructed in (8m+2) dimensions for any m. A generating function is obtained for the anomalies of string-related field theories in (8m+2) dimensions. (orig.)

Modular Universal Scalable Ion-trap Quantum Computer

Science.gov (United States)

2016-06-02

SECURITY CLASSIFICATION OF: The main goal of the original MUSIQC proposal was to construct and demonstrate a modular and universally- expandable ion...Distribution Unlimited UU UU UU UU 02-06-2016 1-Aug-2010 31-Jan-2016 Final Report: Modular Universal Scalable Ion-trap Quantum Computer The views...P.O. Box 12211 Research Triangle Park, NC 27709-2211 Ion trap quantum computation, scalable modular architectures REPORT DOCUMENTATION PAGE 11

Modular high-temperature gas-cooled reactor

International Nuclear Information System (INIS)

Shepherd, L.R.

1988-01-01

The high financial risk involved in building large nuclear power reactors has been a major factor in halting investment in new plant and in bringing further technical development to a standstill. Increased public concern about the safety of nuclear plant, particularly after Chernobyl, has contributed to this stagnation. Financial and technical risk could be reduced considerably by going to small modular units, which would make it possible to build up power station capacity in small steps. Such modular plant, based on the helium-cooled high temperature reactor (HTR), offers remarkable advantages in terms of inherent safety characteristics, partly because of the relatively small size of the individual modules but more on account of the enormous thermal capacity and high temperature margins of the graphitic reactor assemblies. Assessments indicate that, in the USA, the cost of power from the modular systems would be less than that from conventional single reactor plant, up to about 600 MW(e), and only marginally greater above that level, a margin that should be offset by the shorter time required in bringing the modular units on line to earn revenue. The modular HTR would be particularly appropriate in the UK, because of the considerable British industrial background in gas-cooled reactors, and could be a suitable replacement for Magnox. The modular reactor would be particularly suited to combined heat and power schemes and would offer great potential for the eventual development of gas turbine power conversion and the production of high-temperature process heat. (author)

Antimicrobial biosynthetic potential and genetic diversity of endophytic actinomycetes associated with medicinal plants.

Science.gov (United States)

Gohain, Anwesha; Gogoi, Animesh; Debnath, Rajal; Yadav, Archana; Singh, Bhim P; Gupta, Vijai K; Sharma, Rajeev; Saikia, Ratul

2015-10-01

Endophytic actinomycetes are one of the primary groups that share symbiotic relationships with medicinal plants and are key reservoir of biologically active compounds. In this study, six selective medicinal plants were targeted for the first time for endophytic actinomycetes isolation from Gibbon Wild Life Sanctuary, Assam, India, during winter and summer and 76 isolates were obtained. The isolates were found to be prevalent in roots followed by stem and leaves. 16S rRNA gene sequence analysis revealed 16 genera, including rare genera, Verrucosispora, Isoptericola and Kytococcus, which have never been previously reported as endophytic. The genus Streptomyces (66%) was dominant in both seasons. Shannon's diversity index showed that Azadirachta indica (1.49), Rauwolfia serpentina (1.43) and Emblica officinalis (1.24) were relatively good habitat for endophytic actinomycetes. Antimicrobial strains showed prevalence of polyketide synthase (PKS) type-II (85%) followed by PKS type-I (14%) encoded in the genomes. Expression studies showed 12-fold upregulation of PKSII gene in seventh day of incubation for Streptomyces antibioticus (EAAG90). Our results emphasize that the actinomycetes assemblages within plant tissue exhibited biosynthetic systems encoding for important biologically active compounds. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modularity and its effects on innovation

DEFF Research Database (Denmark)

Boer, Henrike Engele Elisabeth; Hansen, Poul H. Kyvsgård

systematic work and management type of tasks, although it conflicts with the typical characteristics associated with the entrepreneur. If not managed properly, modularization can foster the modularity trap over time. At this stage intrapreneurial activities can help the organization stay ahead of the game...

A simple biosynthetic pathway for large product generation from small substrate amounts

Science.gov (United States)

Djordjevic, Marko; Djordjevic, Magdalena

2012-10-01

A recently emerging discipline of synthetic biology has the aim of constructing new biosynthetic pathways with useful biological functions. A major application of these pathways is generating a large amount of the desired product. However, toxicity due to the possible presence of toxic precursors is one of the main problems for such production. We consider here the problem of generating a large amount of product from a potentially toxic substrate. To address this, we propose a simple biosynthetic pathway, which can be induced in order to produce a large number of the product molecules, by keeping the substrate amount at low levels. Surprisingly, we show that the large product generation crucially depends on fast non-specific degradation of the substrate molecules. We derive an optimal induction strategy, which allows as much as three orders of magnitude increase in the product amount through biologically realistic parameter values. We point to a recently discovered bacterial immune system (CRISPR/Cas in E. coli) as a putative example of the pathway analysed here. We also argue that the scheme proposed here can be used not only as a stand-alone pathway, but also as a strategy to produce a large amount of the desired molecules with small perturbations of endogenous biosynthetic pathways.

A simple biosynthetic pathway for large product generation from small substrate amounts

Energy Technology Data Exchange (ETDEWEB)

Djordjevic, Marko [Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade (Serbia); Djordjevic, Magdalena [Institute of Physics Belgrade, University of Belgrade (Serbia)

2012-10-01

A recently emerging discipline of synthetic biology has the aim of constructing new biosynthetic pathways with useful biological functions. A major application of these pathways is generating a large amount of the desired product. However, toxicity due to the possible presence of toxic precursors is one of the main problems for such production. We consider here the problem of generating a large amount of product from a potentially toxic substrate. To address this, we propose a simple biosynthetic pathway, which can be induced in order to produce a large number of the product molecules, by keeping the substrate amount at low levels. Surprisingly, we show that the large product generation crucially depends on fast non-specific degradation of the substrate molecules. We derive an optimal induction strategy, which allows as much as three orders of magnitude increase in the product amount through biologically realistic parameter values. We point to a recently discovered bacterial immune system (CRISPR/Cas in E. coli) as a putative example of the pathway analysed here. We also argue that the scheme proposed here can be used not only as a stand-alone pathway, but also as a strategy to produce a large amount of the desired molecules with small perturbations of endogenous biosynthetic pathways. (paper)

A simple biosynthetic pathway for large product generation from small substrate amounts

International Nuclear Information System (INIS)

Djordjevic, Marko; Djordjevic, Magdalena

2012-01-01

A recently emerging discipline of synthetic biology has the aim of constructing new biosynthetic pathways with useful biological functions. A major application of these pathways is generating a large amount of the desired product. However, toxicity due to the possible presence of toxic precursors is one of the main problems for such production. We consider here the problem of generating a large amount of product from a potentially toxic substrate. To address this, we propose a simple biosynthetic pathway, which can be induced in order to produce a large number of the product molecules, by keeping the substrate amount at low levels. Surprisingly, we show that the large product generation crucially depends on fast non-specific degradation of the substrate molecules. We derive an optimal induction strategy, which allows as much as three orders of magnitude increase in the product amount through biologically realistic parameter values. We point to a recently discovered bacterial immune system (CRISPR/Cas in E. coli) as a putative example of the pathway analysed here. We also argue that the scheme proposed here can be used not only as a stand-alone pathway, but also as a strategy to produce a large amount of the desired molecules with small perturbations of endogenous biosynthetic pathways. (paper)

Generalized epidemic process on modular networks.

Science.gov (United States)

Chung, Kihong; Baek, Yongjoo; Kim, Daniel; Ha, Meesoon; Jeong, Hawoong

2014-05-01

Social reinforcement and modular structure are two salient features observed in the spreading of behavior through social contacts. In order to investigate the interplay between these two features, we study the generalized epidemic process on modular networks with equal-sized finite communities and adjustable modularity. Using the analytical approach originally applied to clique-based random networks, we show that the system exhibits a bond-percolation type continuous phase transition for weak social reinforcement, whereas a discontinuous phase transition occurs for sufficiently strong social reinforcement. Our findings are numerically verified using the finite-size scaling analysis and the crossings of the bimodality coefficient.

Effects of polyamines and polyamine biosynthetic inhibitors on mitotic activity of Allium cepa root tips.

Science.gov (United States)

Unal, Meral; Palavan-Unsal, Narcin; Tufekci, M A

2008-03-01

The genotoxic and cytotoxic effects of exogenous polyamines (PAs), putrescine (Put), spermidine (Spd), spermine (Spm) and PA biosynthetic inhibitors, alpha-difluoromethylornithine (DFMO), cyclohexilamine (CHA), methylglioxal bis-(guanylhydrazone) (MGBG) were investigated in the root meristems of Allium cepa L. The reduction of mitotic index and the induction of chromosomal aberrations such as bridges, stickiness, c-mitotic anaphases, micronuclei, endoredupliction by PAs and PA biosynthetic inhibitors were observed and these were used as evidence of genotoxicity and cytotoxicity.

Criteria for software modularization

Science.gov (United States)

Card, David N.; Page, Gerald T.; Mcgarry, Frank E.

1985-01-01

A central issue in programming practice involves determining the appropriate size and information content of a software module. This study attempted to determine the effectiveness of two widely used criteria for software modularization, strength and size, in reducing fault rate and development cost. Data from 453 FORTRAN modules developed by professional programmers were analyzed. The results indicated that module strength is a good criterion with respect to fault rate, whereas arbitrary module size limitations inhibit programmer productivity. This analysis is a first step toward defining empirically based standards for software modularization.

Automatic Modeling and Simulation of Modular Robots

Science.gov (United States)

Jiang, C.; Wei, H.; Zhang, Y.

2018-03-01

The ability of reconfiguration makes modular robots have the ability of adaptable, low-cost, self-healing and fault-tolerant. It can also be applied to a variety of mission situations. In this manuscript, a robot platform which relied on the module library was designed, based on the screw theory and module theory. Then, the configuration design method of the modular robot was proposed. And the different configurations of modular robot system have been built, including industrial mechanical arms, the mobile platform, six-legged robot and 3D exoskeleton manipulator. Finally, the simulation and verification of one system among them have been made, using the analyses of screw kinematics and polynomial planning. The results of experiments demonstrate the feasibility and superiority of this modular system.

The modular high temperature gas cooled reactor

International Nuclear Information System (INIS)

Lutz, D.E.; Lipps, A.J.

1984-01-01

Due to relatively high operating temperatures, the gas-cooled reactor has the potential to serve a wide variety of energy applications. This paper discusses the energy applications which can be served by the modular HTGR, the magnitude of the potential markets, and the HTGR product cost incentives relative to fossil fuel competition. Advantages of the HTGR modular systems are presented along with a description of the design features and performance characteristics of the current reference HTGR modular systems

Modular bootstrap in Liouville field theory

International Nuclear Information System (INIS)

Hadasz, Leszek; Jaskolski, Zbigniew; Suchanek, Paulina

2010-01-01

The modular matrix for the generic 1-point conformal blocks on the torus is expressed in terms of the fusion matrix for the 4-point blocks on the sphere. The modular invariance of the toric 1-point functions in the Liouville field theory with DOZZ structure constants is proved.

Modular bootstrap in Liouville field theory

Energy Technology Data Exchange (ETDEWEB)

Hadasz, Leszek, E-mail: hadasz@th.if.uj.edu.p [M. Smoluchowski Institute of Physics, Jagiellonian University, Reymonta 4, 30-059 Krakow (Poland); Jaskolski, Zbigniew, E-mail: jask@ift.uni.wroc.p [Institute of Theoretical Physics, University of Wroclaw, pl. M. Borna, 50-204 Wroclaw (Poland); Suchanek, Paulina, E-mail: paulina@ift.uni.wroc.p [Institute of Theoretical Physics, University of Wroclaw, pl. M. Borna, 50-204 Wroclaw (Poland)

2010-02-22

The modular matrix for the generic 1-point conformal blocks on the torus is expressed in terms of the fusion matrix for the 4-point blocks on the sphere. The modular invariance of the toric 1-point functions in the Liouville field theory with DOZZ structure constants is proved.

Modular bootstrap in Liouville field theory

Science.gov (United States)

Hadasz, Leszek; Jaskólski, Zbigniew; Suchanek, Paulina

2010-02-01

The modular matrix for the generic 1-point conformal blocks on the torus is expressed in terms of the fusion matrix for the 4-point blocks on the sphere. The modular invariance of the toric 1-point functions in the Liouville field theory with DOZZ structure constants is proved.

Modularized Functions of the Fanconi Anemia Core Complex

Directory of Open Access Journals (Sweden)

Yaling Huang

2014-06-01

Full Text Available The Fanconi anemia (FA core complex provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. Of the seven FA gene products forming the core complex, FANCL possesses a RING domain with demonstrated E3 ligase activity. The other six components do not have clearly defined roles. Through epistasis analyses, we identify three functional modules in the FA core complex: a catalytic module consisting of FANCL, FANCB, and FAAP100 is absolutely required for the E3 ligase function, and the FANCA-FANCG-FAAP20 and the FANCC-FANCE-FANCF modules provide nonredundant and ancillary functions that help the catalytic module bind chromatin or sites of DNA damage. Disruption of the catalytic module causes complete loss of the core complex function, whereas loss of any ancillary module component does not. Our work reveals the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex.

cDNA cloning and expression of anthocyanin biosynthetic genes in ...

African Journals Online (AJOL)

GRACE

2006-05-16

May 16, 2006 ... that influence anthocyanin pigments have been isolated from Solanaceae. A few genes of anthocyanin ... Long, 1955), and the purple anthocyanin pigments are primarily derived from the related compound ..... anthocyanin production in tuber skins. this result was similar with carrot (daucus carota l) cell ...

Algebra and Arithmetic of Modular Forms

DEFF Research Database (Denmark)

Rustom, Nadim

In [Rus14b] and [Rus14a], we study graded rings of modular forms over congruence subgroups, with coefficients in subrings A of C, and determine bounds of the weights of modular forms constituting a minimal set of generators, as well as on the degree of the generators of the ideal of relations...... between them. We give an algorithm that computes the structures of these rings, and formulate conjectures on the minimal generating weight for modular forms with coefficients in Z. We discuss questions of finiteness of systems of Hecke eigenvalues modulo pm, for a prime p and an integer m ≥ 2, in analogy...

Hierarchical modularity in human brain functional networks

Directory of Open Access Journals (Sweden)

David Meunier

2009-10-01

Full Text Available The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or “modules-within-modules” decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at the highest level of the hierarchy were medial occipital, lateral occipital, central, parieto-frontal and fronto-temporal systems; occipital modules demonstrated less sub-modular organization than modules comprising regions of multimodal association cortex. Connector nodes and hubs, with a key role in inter-modular connectivity, were also concentrated in association cortical areas. We conclude that methods are available for hierarchical modular decomposition of large numbers of high resolution brain functional networks using computationally expedient algorithms. This could enable future investigations of Simon's original hypothesis that hierarchy or near-decomposability of physical symbol systems is a critical design feature for their fast adaptivity to changing environmental conditions.

Conserved intron positions in FGFR genes reflect the modular structure of FGFR and reveal stepwise addition of domains to an already complex ancestral FGFR.

Science.gov (United States)

Rebscher, Nicole; Deichmann, Christina; Sudhop, Stefanie; Fritzenwanker, Jens Holger; Green, Stephen; Hassel, Monika

2009-10-01

We have analyzed the evolution of fibroblast growth factor receptor (FGFR) tyrosine kinase genes throughout a wide range of animal phyla. No evidence for an FGFR gene was found in Porifera, but we tentatively identified an FGFR gene in the placozoan Trichoplax adhaerens. The gene encodes a protein with three immunoglobulin-like domains, a single-pass transmembrane, and a split tyrosine kinase domain. By superimposing intron positions of 20 FGFR genes from Placozoa, Cnidaria, Protostomia, and Deuterostomia over the respective protein domain structure, we identified ten ancestral introns and three conserved intron groups. Our analysis shows (1) that the position of ancestral introns correlates to the modular structure of FGFRs, (2) that the acidic domain very likely evolved in the last common ancestor of triploblasts, (3) that splicing of IgIII was enabled by a triploblast-specific insertion, and (4) that IgI is subject to substantial loss or duplication particularly in quickly evolving genomes. Moreover, intron positions in the catalytic domain of FGFRs map to the borders of protein subdomains highly conserved in other serine/threonine kinases. Nevertheless, these introns were introduced in metazoan receptor tyrosine kinases exclusively. Our data support the view that protein evolution dating back to the Cambrian explosion took place in such a short time window that only subtle changes in the domain structure are detectable in extant representatives of animal phyla. We propose that the first multidomain FGFR originated in the last common ancestor of Placozoa, Cnidaria, and Bilateria. Additional domains were introduced mainly in the ancestor of triploblasts and in the Ecdysozoa.

Modular invariance, chiral anomalies and contact terms

International Nuclear Information System (INIS)

Kutasov, D.

1988-03-01

The chiral anomaly in heterotic strings with full and partial modular invariance in D=2n+2 dimensions is calculated. The boundary terms which were present in previous calculations are shown to be cancelled in the modular invariant case by contact terms, which can be obtained by an appropriate analytic continuation. The relation to the low energy field theory is explained. In theories with partial modular invariance, an expression for the anomaly is obtained and shown to be non zero in general. (author)

An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae.

Science.gov (United States)

Lin-Wang, Kui; Bolitho, Karen; Grafton, Karryn; Kortstee, Anne; Karunairetnam, Sakuntala; McGhie, Tony K; Espley, Richard V; Hellens, Roger P; Allan, Andrew C

2010-03-21

The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA) are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry). Key identifying amino acid residues were found in both the DNA-binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal-spatial colour change.

An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae

Directory of Open Access Journals (Sweden)

McGhie Tony K

2010-03-01

Full Text Available Abstract Background The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. Results We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry. Key identifying amino acid residues were found in both the DNA-binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. Conclusions This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal-spatial colour change.

Hierarchy of modular graph identities

Energy Technology Data Exchange (ETDEWEB)

D’Hoker, Eric; Kaidi, Justin [Mani L. Bhaumik Institute for Theoretical Physics, Department of Physics and Astronomy,University of California,Los Angeles, CA 90095 (United States)

2016-11-09

The low energy expansion of Type II superstring amplitudes at genus one is organized in terms of modular graph functions associated with Feynman graphs of a conformal scalar field on the torus. In earlier work, surprising identities between two-loop graphs at all weights, and between higher-loop graphs of weights four and five were constructed. In the present paper, these results are generalized in two complementary directions. First, all identities at weight six and all dihedral identities at weight seven are obtained and proven. Whenever the Laurent polynomial at the cusp is available, the form of these identities confirms the pattern by which the vanishing of the Laurent polynomial governs the full modular identity. Second, the family of modular graph functions is extended to include all graphs with derivative couplings and worldsheet fermions. These extended families of modular graph functions are shown to obey a hierarchy of inhomogeneous Laplace eigenvalue equations. The eigenvalues are calculated analytically for the simplest infinite sub-families and obtained by Maple for successively more complicated sub-families. The spectrum is shown to consist solely of eigenvalues s(s−1) for positive integers s bounded by the weight, with multiplicities which exhibit rich representation-theoretic patterns.

Hierarchy of modular graph identities

International Nuclear Information System (INIS)

D’Hoker, Eric; Kaidi, Justin

2016-01-01

The low energy expansion of Type II superstring amplitudes at genus one is organized in terms of modular graph functions associated with Feynman graphs of a conformal scalar field on the torus. In earlier work, surprising identities between two-loop graphs at all weights, and between higher-loop graphs of weights four and five were constructed. In the present paper, these results are generalized in two complementary directions. First, all identities at weight six and all dihedral identities at weight seven are obtained and proven. Whenever the Laurent polynomial at the cusp is available, the form of these identities confirms the pattern by which the vanishing of the Laurent polynomial governs the full modular identity. Second, the family of modular graph functions is extended to include all graphs with derivative couplings and worldsheet fermions. These extended families of modular graph functions are shown to obey a hierarchy of inhomogeneous Laplace eigenvalue equations. The eigenvalues are calculated analytically for the simplest infinite sub-families and obtained by Maple for successively more complicated sub-families. The spectrum is shown to consist solely of eigenvalues s(s−1) for positive integers s bounded by the weight, with multiplicities which exhibit rich representation-theoretic patterns.

Modularity in New Market Formation

DEFF Research Database (Denmark)

Sanchez, Ron; Hang, Chang Chieh

2017-01-01

In this paper we appraise the ways in which use of closed-system proprietary product architectures versus open-system modular product architectures is likely to influence the dynamics and trajectory of new product market formation. We compare the evolutions of new markets in China for gas......-powered two-wheeled vehicles (G2WVs) based (initially) on closed-system proprietary architectures and for electric-powered two-wheeled vehicles (E2WVs) based on open-system modular architectures. We draw on this comparison to suggest ways in which the use of the two different kinds of architectures...... as the basis for new kinds of products may result in very different patterns and speeds of new market formation. We then suggest some key implications of the different dynamics of market formation associated with open-system modular architectures for both the competence-based strategic management (CBSM...

Modular system design and evaluation

CERN Document Server

Levin, Mark Sh

2015-01-01

This book examines seven key combinatorial engineering frameworks (composite schemes consisting of algorithms and/or interactive procedures) for hierarchical modular (composite) systems. These frameworks are based on combinatorial optimization problems (e.g., knapsack problem, multiple choice problem, assignment problem, morphological clique problem), with the author’s version of morphological design approach – Hierarchical Morphological Multicritieria Design (HMMD) – providing a conceptual lens with which to elucidate the examples discussed. This approach is based on ordinal estimates of design alternatives for systems parts/components, however, the book also puts forward an original version of HMMD that is based on new interval multiset estimates for the design alternatives with special attention paid to the aggregation of modular solutions (system versions). The second part of ‘Modular System Design and Evaluation’ provides ten information technology case studies that enriches understanding of th...

Configurable double-sided modular jet impingement assemblies for electronics cooling

Science.gov (United States)

Zhou, Feng; Dede, Ercan Mehmet

2018-05-22

A modular jet impingement assembly includes an inlet tube fluidly coupled to a fluid inlet, an outlet tube fluidly coupled to a fluid outlet, and a modular manifold having a first distribution recess extending into a first side of the modular manifold, a second distribution recess extending into a second side of the modular manifold, a plurality of inlet connection tubes positioned at an inlet end of the modular manifold, and a plurality of outlet connection tubes positioned at an outlet end of the modular manifold. A first manifold insert is removably positioned within the first distribution recess, a second manifold insert is removably positioned within the second distribution recess, and a first and second heat transfer plate each removably coupled to the modular manifold. The first and second heat transfer plates each comprise an impingement surface.

SCREENING OF ANTIMICROBIAL ACTIVITY AND GENES CODING POLYKETIDE SYNTHETASE AND NONRIBOSOMAL PEPTIDE SYNTHETASE OF ACTINOMYCETE ISOLATES

Directory of Open Access Journals (Sweden)

Silvia Kovácsová

2013-12-01

Full Text Available The aim of this study was to observe antimicrobial activity using agar plate diffusion method and screening genes coding polyketide synthetase (PKS-I and nonribosomal peptide synthetase (NRPS from actinomycetes. A total of 105 actinomycete strains were isolated from arable soil. Antimicrobial activity was demonstrated at 54 strains against at least 1 of total 12 indicator organisms. Antifungal properties were recorded more often than antibacterial properties. The presence of PKS-I and NRPS genes were founded at 61 of total 105 strains. The number of strains with mentioned biosynthetic enzyme gene fragments matching the anticipated length were 19 (18% and 50 (47% respectively. Overall, five actinomycete strains carried all the biosynthetical genes, yet no antimicrobial activity was found against any of tested pathogens. On the other hand, twenty-one strains showed antimicrobial activity even though we were not able to amplify any of the PKS or NRPS genes from them. Combination of the two methods showed broad-spectrum antimicrobial activity of actinomycetes isolated from arable soil, which indicate that actinomycetes are valuable reservoirs of novel bioactive compounds.

A modular interpretation of various cubic towers

DEFF Research Database (Denmark)

Anbar Meidl, Nurdagül; Bassa, Alp; Beelen, Peter

2017-01-01

In this article we give a Drinfeld modular interpretation for various towers of function fields meeting Zink's bound.......In this article we give a Drinfeld modular interpretation for various towers of function fields meeting Zink's bound....

Failure of Emperion modular femoral stem with implant analysis

Directory of Open Access Journals (Sweden)

Benjamin M. Stronach, MD, MS

2016-03-01

Full Text Available Modularity in total hip arthroplasty provides multiple benefits to the surgeon in restoring the appropriate alignment and position to a previously damaged hip joint. The vast majority of modern implants incorporate modularity into their design with some implants having multiple modular interfaces. There is the potential for failure at modular junctions because of fretting and crevice corrosion in combination with mechanical loading. This case report details the failure of an Emperion (Smith and Nephew, Memphis, TN femoral stem in a 67-year-old male patient 6 years after total hip replacement. Analysis of the implant revealed mechanically assisted crevice corrosion that likely accelerated fatigue crack initiation in the hip stem. The benefits of modularity come with the potential drawback of a combination of fretting and crevice corrosion at the modular junction, which may accelerate fatigue, crack initiation and ultimately reduce the hip longevity.

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

Science.gov (United States)

Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

2004-03-01

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Towards Versatile Robots Through Open Heterogeneous Modular Robots

DEFF Research Database (Denmark)

Lyder, Andreas

arises, a new robot can be assembled rapidly from the existing modules, in contrast to conventional robots, which require a time consuming and expensive development process. In this thesis we define a modular robot to be a robot consisting of dynamically reconfigurable modules. The goal of this thesis......Robots are important tools in our everyday life. Both in industry and at the consumer level they serve the purpose of increasing our scope and extending our capabilities. Modular robots take the next step, allowing us to easily create and build various robots from a set of modules. If a problem...... is to increase the versatility and practical usability of modular robots by introducing new conceptual designs. Until now modular robots have been based on a pre-specified set of modules, and thus, their functionality is limited. We propose an open heterogeneous design concept, which allows a modular robot...

Genomics-Based Discovery of Plant Genes for Synthetic Biology of Terpenoid Fragrances: A Case Study in Sandalwood oil Biosynthesis.

Science.gov (United States)

Celedon, J M; Bohlmann, J

2016-01-01

Terpenoid fragrances are powerful mediators of ecological interactions in nature and have a long history of traditional and modern industrial applications. Plants produce a great diversity of fragrant terpenoid metabolites, which make them a superb source of biosynthetic genes and enzymes. Advances in fragrance gene discovery have enabled new approaches in synthetic biology of high-value speciality molecules toward applications in the fragrance and flavor, food and beverage, cosmetics, and other industries. Rapid developments in transcriptome and genome sequencing of nonmodel plant species have accelerated the discovery of fragrance biosynthetic pathways. In parallel, advances in metabolic engineering of microbial and plant systems have established platforms for synthetic biology applications of some of the thousands of plant genes that underlie fragrance diversity. While many fragrance molecules (eg, simple monoterpenes) are abundant in readily renewable plant materials, some highly valuable fragrant terpenoids (eg, santalols, ambroxides) are rare in nature and interesting targets for synthetic biology. As a representative example for genomics/transcriptomics enabled gene and enzyme discovery, we describe a strategy used successfully for elucidation of a complete fragrance biosynthetic pathway in sandalwood (Santalum album) and its reconstruction in yeast (Saccharomyces cerevisiae). We address questions related to the discovery of specific genes within large gene families and recovery of rare gene transcripts that are selectively expressed in recalcitrant tissues. To substantiate the validity of the approaches, we describe the combination of methods used in the gene and enzyme discovery of a cytochrome P450 in the fragrant heartwood of tropical sandalwood, responsible for the fragrance defining, final step in the biosynthesis of (Z)-santalols. © 2016 Elsevier Inc. All rights reserved.

Modular supervisory controller for hybrid power systems

Energy Technology Data Exchange (ETDEWEB)

Lemos Pereira, A. de

2000-06-01

The power supply of remote places has been commonly provided by thermal power plants, usually diesel generators. Although hybrid power systems may constitute the most economical solution in many applications their widespread application to the electrification schemes of remote areas still depends on improvements in the issues of design and operation control. The main limitations of the present hybrid power systems technology, which are identified in this work, are related to the control and supervision of the power system. Therefore this thesis focuses on the modularity of supervisory controllers in order to design cost-competitive and reliable hybrid power systems. The modular supervisory controller created in this project is considered an important part of a system design approach that aims to overcome the technical difficulties of the current engineering practice and contribute to open the market of hybrid power systems. The term modular refers to a set of design characteristics that allows the use of basically the same supervisory controller in different projects. The modularization and standardisation of the controller include several issues such as interfacing components, communication protocols, modelling, programming and control strategies. The modularity can reduce the highly specialised system engineering related to the integration of components, operation and control. It can also avoid the high costs for installation, service and maintenance. A modular algorithm for supervisory controllers has been developed (a Matlab program called SuperCon) using an object-oriented design and it has been tested through several simulations using different hybrid system configurations and different control strategies. This thesis presents a complete control system design process which can be used as the basis for the development and implementation of intelligent and autonomous supervisory controllers for hybrid power systems with modular characteristics. (au)

Robustness and modular structure in networks

DEFF Research Database (Denmark)

Bagrow, James P.; Lehmann, Sune; Ahn, Yong-Yeol

2015-01-01

-12]. Many complex systems, from power grids and the Internet to the brain and society [13-15], can be modeled using modular networks comprised of small, densely connected groups of nodes [16, 17]. These modules often overlap, with network elements belonging to multiple modules [18, 19]. Yet existing work...... on robustness has not considered the role of overlapping, modular structure. Here we study the robustness of these systems to the failure of elements. We show analytically and empirically that it is possible for the modules themselves to become uncoupled or non-overlapping well before the network disintegrates....... If overlapping modular organization plays a role in overall functionality, networks may be far more vulnerable than predicted by conventional percolation theory....

Modularization Technology in Power Plant Construction

International Nuclear Information System (INIS)

Kenji Akagi; Kouichi Murayama; Miki Yoshida; Junichi Kawahata

2002-01-01

Since the early 1980's, Hitachi has been developing and applying modularization technology to domestic nuclear power plant construction, and has achieved great rationalization. Modularization is one of the plant construction techniques which enables us to reduce site labor by pre-assembling components like equipment, pipes, valves and platforms in congested areas and installing them using large capacity cranes for cost reduction, better quality, safety improvement and shortening of construction time. In this paper, Hitachi's modularization technologies are described especially from with respect to their sophisticated design capabilities. The application of 3D-CAD at the detailed layout design stage, concurrent design environment achieved by the computer network, module design quantity control and the management system are described. (authors)

Measuring Modularity in Open Source Code Bases

Directory of Open Access Journals (Sweden)

Roberto Milev

2009-03-01

Full Text Available Modularity of an open source software code base has been associated with growth of the software development community, the incentives for voluntary code contribution, and a reduction in the number of users who take code without contributing back to the community. As a theoretical construct, modularity links OSS to other domains of research, including organization theory, the economics of industry structure, and new product development. However, measuring the modularity of an OSS design has proven difficult, especially for large and complex systems. In this article, we describe some preliminary results of recent research at Carleton University that examines the evolving modularity of large-scale software systems. We describe a measurement method and a new modularity metric for comparing code bases of different size, introduce an open source toolkit that implements this method and metric, and provide an analysis of the evolution of the Apache Tomcat application server as an illustrative example of the insights gained from this approach. Although these results are preliminary, they open the door to further cross-discipline research that quantitatively links the concerns of business managers, entrepreneurs, policy-makers, and open source software developers.

Identification of a trichothecene gene cluster and description of the harzianum A biosynthesis pathway in the fungus Trichoderma arundinaceum

Science.gov (United States)

Trichothecenes are sesquiterpenes that act like mycotoxins. Their biosynthesis has been mainly studied in the fungal genera Fusarium, where most of the biosynthetic genes (tri) are grouped in a cluster regulated by ambient conditions and regulatory genes. Unexpectedly, few studies are available abou...

Modularizing development

DEFF Research Database (Denmark)

Müller, Anders Riel; Doucette, Jamie

a deeper and wider understanding of Korea’s development experience with the hope that Korea’s past can offer lessons for developing countries in search of sustainable and broad‐based development" (KSP 2011). To do so, the KSP provides users with a modularized set of policy narratives that represent Korea...

A Modular Approach to Redundant Robot Control

International Nuclear Information System (INIS)

Anderson, R.J.

1997-12-01

This paper describes a modular approach for computing redundant robot kinematics. First some conventional redundant control methods are presented and shown to be 'passive control laws', i.e. they can be represented by a network consisting of passive elements. These networks are then put into modular form by applying scattering operator techniques. Additional subnetwork modules can then be added to further shape the motion. Modules for obstacle detection, joint limit avoidance, proximity sensing, and for imposing nonlinear velocity constraints are presented. The resulting redundant robot control system is modular, flexible and robust

Brain modularity controls the critical behavior of spontaneous activity.

Science.gov (United States)

Russo, R; Herrmann, H J; de Arcangelis, L

2014-03-13

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

Modular invariance and stochastic quantization

International Nuclear Information System (INIS)

Ordonez, C.R.; Rubin, M.A.; Zwanziger, D.

1989-01-01

In Polyakov path integrals and covariant closed-string field theory, integration over Teichmueller parameters must be restricted by hand to a single modular region. This problem has an analog in Yang-Mills gauge theory---namely, the Gribov problem, which can be resolved by the method of stochastic gauge fixing. This method is here employed to quantize a simple modular-invariant system: the Polyakov point particle. In the limit of a large gauge-fixing force, it is shown that suitable choices for the functional form of the gauge-fixing force can lead to a restriction of Teichmueller integration to a single modular region. Modifications which arise when applying stochastic quantization to a system in which the volume of the orbits of the gauge group depends on a dynamical variable, such as a Teichmueller parameter, are pointed out, and the extension to Polyakov strings and covariant closed-string field theory is discussed

Modular assembly of optical nanocircuits

Science.gov (United States)

Shi, Jinwei; Monticone, Francesco; Elias, Sarah; Wu, Yanwen; Ratchford, Daniel; Li, Xiaoqin; Alù, Andrea

2014-05-01

A key element enabling the microelectronic technology advances of the past decades has been the conceptualization of complex circuits with versatile functionalities as being composed of the proper combination of basic ‘lumped’ circuit elements (for example, inductors and capacitors). In contrast, modern nanophotonic systems are still far from a similar level of sophistication, partially because of the lack of modularization of their response in terms of basic building blocks. Here we demonstrate the design, assembly and characterization of relatively complex photonic nanocircuits by accurately positioning a number of metallic and dielectric nanoparticles acting as modular lumped elements. The nanoparticle clusters produce the desired spectral response described by simple circuit rules and are shown to be dynamically reconfigurable by modifying the direction or polarization of impinging signals. Our work represents an important step towards extending the powerful modular design tools of electronic circuits into nanophotonic systems.

What is a gene? From molecules to metaphysics.

Science.gov (United States)

Rolston, Holmes

2006-01-01

Mendelian genes have become molecular genes, with increasing puzzlement about locating them, due to increasing complexity in genomic webworks. Genome science finds modular and conserved units of inheritance, identified as homologous genes. Such genes are cybernetic, transmitting information over generations; this too requires multi-leveled analysis, from DNA transcription to development and reproduction of the whole organism. Genes are conserved; genes are also dynamic and creative in evolutionary speciation-most remarkably producing humans capable of wondering about what genes are.

Buying Modular Systems in Technology-Intensive Markets

NARCIS (Netherlands)

Frambach, R.T.; Stremersch, S.; Weiss, Allen M.; Dellaert, B.

2003-01-01

Technology-intensive markets consist of products that are often interdependent and operate together as a modular system. Although prior research has extensively addressed standardization and network externalities in such markets, it has not addressed the buying of modular systems. The authors

Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar

Directory of Open Access Journals (Sweden)

Bron James E

2008-06-01

Full Text Available Abstract Background There is an increasing drive to replace fish oil (FO in finfish aquaculture diets with vegetable oils (VO, driven by the short supply of FO derived from wild fish stocks. However, little is known of the consequences for fish health after such substitution. The effect of dietary VO on hepatic gene expression, lipid composition and growth was determined in Atlantic salmon (Salmo salar, using a combination of cDNA microarray, lipid, and biochemical analysis. FO was replaced with VO, added to diets as rapeseed (RO, soybean (SO or linseed (LO oils. Results Dietary VO had no major effect on growth of the fish, but increased the whole fish protein contents and tended to decrease whole fish lipid content, thus increasing the protein:lipid ratio. Expression levels of genes of the highly unsaturated fatty acid (HUFA and cholesterol biosynthetic pathways were increased in all vegetable oil diets as was SREBP2, a master transcriptional regulator of these pathways. Other genes whose expression was increased by feeding VO included those of NADPH generation, lipid transport, peroxisomal fatty acid oxidation, a marker of intracellular lipid accumulation, and protein and RNA processing. Consistent with these results, HUFA biosynthesis, hepatic β-oxidation activity and enzymic NADPH production were changed by VO, and there was a trend for increased hepatic lipid in LO and SO diets. Tissue cholesterol levels in VO fed fish were the same as animals fed FO, whereas fatty acid composition of the tissues largely reflected those of the diets and was marked by enrichment of 18 carbon fatty acids and reductions in 20 and 22 carbon HUFA. Conclusion This combined gene expression, compositional and metabolic study demonstrates that major lipid metabolic effects occur after replacing FO with VO in salmon diets. These effects are most likely mediated by SREBP2, which responds to reductions in dietary cholesterol. These changes are sufficient to maintain

Advantages of going modular in HTRs

International Nuclear Information System (INIS)

Reutler, H.; Lohnert, G.H.

1984-01-01

A multitude of problems that are encountered in large HTR power plans, constructively as well as concerning plant safety, can be related to the mere physical size of a large reactor core. In limiting the thermal power of an HTR-module to approximately 200 MW an inherent limitation of the fuel element temperature below critical values can be guaranteed for all possible core heat up accidents. Consequently, a significant failure rate of coated particles can be excluded and, hence, out of physical reasons, no intolerable fission product release from the core will ever have to be considered. The HTR-module is so qualified and very well suited for all possible plant sides which have to be taken into consideration for medium sized plants for the production of process steam and electricity. The cost investigations show considerable cost advantages for modular HTRs. For German conditions it was found that even a four-modular plant (800 MW/thermal) is competitive with a fossile-fueled plant of the same size, the specific plant costs were evaluated to be DM 4700/kW (electric). Moreover the investigations show that the increase of the power of the modular unit yields only small cost advantages, therefore in a modularized power plant it even would be possible to reduce the power of a modular unit below 200 MW without having to cope with severe economic penalties, if the distance from technological or safety limits is felt to be too small. (orig.)

An Incremental Approach to Support Realization of Modularization Benefits

DEFF Research Database (Denmark)

Hansen, Poul H. Kyvsgård; Sun, Hongyi

2010-01-01

In general, the phenomenon of managing modularization is not well known. The cause-effect relationships between modularization and realized benefits are complex and comprehensive. Though a number of research works have contributed to the study of the phenomenon of efficient and effective...... modularization management it is far from clarified. Recognizing the need for further empirical research, we studied 40 modularity cases. Then we develop a research framework with the purpose of uncovering the current state. Furthermore, we formulate a tentative model aiming at guiding the platform management...

Calculation and modular properties of multi-loop superstring amplitudes

International Nuclear Information System (INIS)

Danilov, G S

2012-01-01

Multi-loop superstring amplitude is calculated in the conventional gauge where Grassmann moduli are carried by the 2D gravitino field. Generally, instead of the modular symmetry, the amplitudes hold the symmetry under modular transformations added by relevant transformations of the 2D local supersymmetry. If a number of loops are larger than 3, the integration measures are not modular forms. In this case the expression for the amplitude contains an integral over the bound of the fundamental region of the modular group. (paper)

Metabolic engineering of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway into transgenic plants.

Science.gov (United States)

Ruiz-López, Noemi; Sayanova, Olga; Napier, Johnathan A; Haslam, Richard P

2012-04-01

Omega-3 (ω-3) very long chain polyunsaturated fatty acids (VLC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5 Δ5,8,11,14,17) and docosahexaenoic acid (DHA; 22:6 Δ4,7,10,13,16,19) have been shown to have significant roles in human health. Currently the primary dietary source of these fatty acids are marine fish; however, the increasing demand for fish and fish oil (in particular the expansion of the aquaculture industry) is placing enormous pressure on diminishing marine stocks. Such overfishing and concerns related to pollution in the marine environment have directed research towards the development of a viable alternative sustainable source of VLC-PUFAs. As a result, the last decade has seen many genes encoding the primary VLC-PUFA biosynthetic activities identified and characterized. This has allowed the reconstitution of the VLC-PUFA biosynthetic pathway in oilseed crops, producing transgenic plants engineered to accumulate ω-3 VLC-PUFAs at levels approaching those found in native marine organisms. Moreover, as a result of these engineering activities, knowledge of the fundamental processes surrounding acyl exchange and lipid remodelling has progressed. The application of new technologies, for example lipidomics and next-generation sequencing, is providing a better understanding of seed oil biosynthesis and opportunities for increasing the production of unusual fatty acids. Certainly, it is now possible to modify the composition of plant oils successfully, and, in this review, the most recent developments in this field and the challenges of producing VLC-PUFAs in the seed oil of higher plants will be described.

Modular Lego-Electronics

KAUST Repository

Shaikh, Sohail F.; Ghoneim, Mohamed T.; Bahabry, Rabab R.; Khan, Sherjeel M.; Hussain, Muhammad Mustafa

2017-01-01

. Here, a generic manufacturable method of converting state-of-the-art complementary metal oxide semiconductor-based ICs into modular Lego-electronics is shown with unique geometry that is physically identifiable to ease manufacturing and enhance

Complex modular structure of large-scale brain networks

Science.gov (United States)

Valencia, M.; Pastor, M. A.; Fernández-Seara, M. A.; Artieda, J.; Martinerie, J.; Chavez, M.

2009-06-01

Modular structure is ubiquitous among real-world networks from related proteins to social groups. Here we analyze the modular organization of brain networks at a large scale (voxel level) extracted from functional magnetic resonance imaging signals. By using a random-walk-based method, we unveil the modularity of brain webs and show modules with a spatial distribution that matches anatomical structures with functional significance. The functional role of each node in the network is studied by analyzing its patterns of inter- and intramodular connections. Results suggest that the modular architecture constitutes the structural basis for the coexistence of functional integration of distant and specialized brain areas during normal brain activities at rest.

Modular envelopes, OSFT and nonsymmetric (non-$\\sum$) modular operads

Czech Academy of Sciences Publication Activity Database

Markl, Martin

2016-01-01

Roč. 10, č. 2 (2016), s. 775-809 ISSN 1661-6952 Institutional support: RVO:67985840 Keywords : open string * surface * modular completion Subject RIV: BA - General Mathematics Impact factor: 0.625, year: 2016 http://www.ems-ph.org/journals/show_abstract.php?issn=1661-6952&vol=10&iss=2&rank=12

On Modularity in (V)Shorad Air Defense

NARCIS (Netherlands)

Veen, E.M. van der

2001-01-01

This paper addresses the concept of modularity in the context of (V)Shorads Air Defence. Modularity is a technical concept that provides improved operational flexibility to (V)Shorad systems. Such improved flexibility is specifically relevant to mobile crisis reaction forces. The discussion is

Economics of the modular reactor as new-generation nuclear power

International Nuclear Information System (INIS)

Hattori, Sadao

1987-01-01

This paper lists thirteen advantages which could be effectuated by modular reactors. These advantages are derived basically from the general attributes of modularization, i.e., continuity of production, smallness of size/capacity, ease of standardization, and built-in passive safety. This paper also suggests a general direction in which the development of modular reactors evolve, and a possible nuclear application where modular reactors be effectively utilized. (author)

Bio-based production of fuels and industrial chemicals by repurposing antibiotic-producing type I modular polyketide synthases: opportunities and challenges.

Science.gov (United States)

Yuzawa, Satoshi; Keasling, Jay D; Katz, Leonard

2017-04-01

Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from large enzyme complexes named type I modular polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides of predicted structure. We have repurposed PKSs to produce a number of short-chain mono- and di-carboxylic acids and ketones that could have applications as fuels or industrial chemicals.

Bio-based production of fuels and industrial chemicals by repurposing antibiotic-producing type I modular polyketide synthases: opportunities and challenges

Energy Technology Data Exchange (ETDEWEB)

Yuzawa, Satoshi [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Keasling, Jay D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). QB3 Inst.; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering; Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering; Technical Univ. of Denmark, Horsholm (Denmark). Novo Nordisk Foundation Center for Biosustainability; Katz, Leonard [Univ. of California, Berkeley, CA (United States). QB3 Inst.

2016-11-16

Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from large enzyme complexes named type I modular polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides of predicted structure. Finally, we have repurposed PKSs to produce a number of short-chain mono- and di-carboxylic acids and ketones that could have applications as fuels or industrial chemicals.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

KAUST Repository

Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

2015-01-01

validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation

Modular categories and 3-manifold invariants

International Nuclear Information System (INIS)

Tureav, V.G.

1992-01-01

The aim of this paper is to give a concise introduction to the theory of knot invariants and 3-manifold invariants which generalize the Jones polynomial and which may be considered as a mathematical version of the Witten invariants. Such a theory was introduced by N. Reshetikhin and the author on the ground of the theory of quantum groups. here we use more general algebraic objects, specifically, ribbon and modular categories. Such categories in particular arise as the categories of representations of quantum groups. The notion of modular category, interesting in itself, is closely related to the notion of modular tensor category in the sense of G. Moore and N. Seiberg. For simplicity we restrict ourselves in this paper to the case of closed 3-manifolds

Balancing Modularity and Solution Space Freedom

DEFF Research Database (Denmark)

Vos, Maren A.; Raassens, Néomie; Van der Borgh, Michel

2018-01-01

that modularity reflects knowledge specialisation and solution space freedom reflects knowledge variety. Both of these dimensions affect organisational learning and, in turn, sustainable innovation. Second, we argue that the relationship between customisation and organisational learning is affected by supplier...... theory to provide insights into how TI firms can achieve ‘win-win’ situations where sustainable innovation is increased through customisation. First, we argue that customisation should be viewed two-dimensionally and identify both modularity and solution space freedom as important dimensions. We argue...... characteristics, specifically supplier sophistication. Survey data from 166 managers were used to empirically test the conceptual model and hypotheses. Polynomial response surface analysis confirms that customising by balancing high degrees of both modularity and solution space freedom results in superior...

Overexpression of snapdragon Delila (Del) gene in tobacco enhances anthocyanin accumulation and abiotic stress tolerance.

Science.gov (United States)

Naing, Aung Htay; Park, Kyeung Il; Ai, Trinh Ngoc; Chung, Mi Young; Han, Jeung Sul; Kang, Young-Wha; Lim, Ki Byung; Kim, Chang Kil

2017-03-23

Rosea1 (Ros1) and Delila (Del) co-expression controls anthocyanin accumulation in snapdragon flowers, while their overexpression in tomato strongly induces anthocyanin accumulation. However, little data exist on how Del expression alone influences anthocyanin accumulation. In tobacco (Nicotiana tabacum 'Xanthi'), Del expression enhanced leaf and flower anthocyanin production through regulating NtCHS, NtCHI, NtF3H, NtDFR, and NtANS transcript levels. Transgenic lines displayed different anthocyanin colors (e.g., pale red: T 0 -P, red: T 0 -R, and strong red: T 0 -S), resulting from varying levels of biosynthetic gene transcripts. Under salt stress, the T 2 generation had higher total polyphenol content, radical (DPPH, ABTS) scavenging activities, antioxidant-related gene expression, as well as overall greater salt and drought tolerance than wild type (WT). We propose that Del overexpression elevates transcript levels of anthocyanin biosynthetic and antioxidant-related genes, leading to enhanced anthocyanin production and antioxidant activity. The resultant increase of anthocyanin and antioxidant activity improves abiotic stress tolerance.

Convergent evolution of modularity in metabolic networks through different community structures

Directory of Open Access Journals (Sweden)

Zhou Wanding

2012-09-01

Full Text Available Abstract Background It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. Results In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxomony. Conclusions We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct enzymes in the organism’s metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability. Further, our results

Convergent evolution of modularity in metabolic networks through different community structures.

Science.gov (United States)

Zhou, Wanding; Nakhleh, Luay

2012-09-14

It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxonomy. We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organism's metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network

PCL-HA microscaffolds for in vitro modular bone tissue engineering.

Science.gov (United States)

Totaro, Alessandra; Salerno, Aurelio; Imparato, Giorgia; Domingo, Concepción; Urciuolo, Francesco; Netti, Paolo Antonio

2017-06-01

The evolution of microscaffolds and bone-bioactive surfaces is a pivotal point in modular bone tissue engineering. In this study, the design and fabrication of porous polycaprolactone (PCL) microscaffolds functionalized with hydroxyapatite (HA) nanoparticles by means of a bio-safe and versatile thermally-induced phase separation process is reported. The ability of the as-prepared nanocomposite microscaffolds to support the adhesion, growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in standard and osteogenic media and using dynamic seeding/culture conditions was investigated. The obtained results demonstrated that the PCL-HA nanocomposite microparticles had an enhanced interaction with hMSCs and induced their osteogenic differentiation, even without the exogenous addition of osteogenic factors. In particular, calcium deposition, alizarin red assay, histological analysis, osteogenic gene expression and collagen I secretion were assessed. The results of these tests demonstrated the formation of bone microtissue precursors after 28 days of dynamic culture. These findings suggest that PCL-HA nanocomposite microparticles represent an excellent platform for in vitro modular bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Modular Knowledge Representation and Reasoning in the Semantic Web

Science.gov (United States)

Serafini, Luciano; Homola, Martin

Construction of modular ontologies by combining different modules is becoming a necessity in ontology engineering in order to cope with the increasing complexity of the ontologies and the domains they represent. The modular ontology approach takes inspiration from software engineering, where modularization is a widely acknowledged feature. Distributed reasoning is the other side of the coin of modular ontologies: given an ontology comprising of a set of modules, it is desired to perform reasoning by combination of multiple reasoning processes performed locally on each of the modules. In the last ten years, a number of approaches for combining logics has been developed in order to formalize modular ontologies. In this chapter, we survey and compare the main formalisms for modular ontologies and distributed reasoning in the Semantic Web. We select four formalisms build on formal logical grounds of Description Logics: Distributed Description Logics, ℰ-connections, Package-based Description Logics and Integrated Distributed Description Logics. We concentrate on expressivity and distinctive modeling features of each framework. We also discuss reasoning capabilities of each framework.

Modular nuclear fuel element, modular capsule for a such element and fabrication process for a modular capsule

International Nuclear Information System (INIS)

Chotard, A.

1988-01-01

The nuclear fuel rod is made by a tubular casing closed at both ends and containing a series of modular capsules with little play with the casing and made by a jacket closed by porous plugs at both ends and containing a stack of fuel pellets [fr

Development of modularity in the neural activity of children's brains

International Nuclear Information System (INIS)

Chen, Man; Deem, Michael W

2015-01-01

We study how modularity of the human brain changes as children develop into adults. Theory suggests that modularity can enhance the response function of a networked system subject to changing external stimuli. Thus, greater cognitive performance might be achieved for more modular neural activity, and modularity might likely increase as children develop. The value of modularity calculated from functional magnetic resonance imaging (fMRI) data is observed to increase during childhood development and peak in young adulthood. Head motion is deconvolved from the fMRI data, and it is shown that the dependence of modularity on age is independent of the magnitude of head motion. A model is presented to illustrate how modularity can provide greater cognitive performance at short times, i.e. task switching. A fitness function is extracted from the model. Quasispecies theory is used to predict how the average modularity evolves with age, illustrating the increase of modularity during development from children to adults that arises from selection for rapid cognitive function in young adults. Experiments exploring the effect of modularity on cognitive performance are suggested. Modularity may be a potential biomarker for injury, rehabilitation, or disease. (paper)

Curriculum Development through YTS Modular Credit Accumulation.

Science.gov (United States)

Further Education Unit, London (England).

This document reports the evaluation of the collaborately developed Modular Training Framework (MainFrame), a British curriculum development project, built around a commitment to a competency-based, modular credit accumulation program. The collaborators were three local education authorities (LEAs), those of Bedfordshire, Haringey, and Sheffield,…

Emergent interfaces for feature modularization

CERN Document Server

Ribeiro, Márcio; Brabrand, Claus

2014-01-01

Developers frequently introduce errors into software systems when they fail to recognise module dependencies. Using forty-three software families and Software Product Lines (SPLs), where the majority are commonly used in industrial practice, the authors reports on the feature modularization problem and provides a study of how often it may occur in practice. To solve the problem they present the concept of emergent feature modularization which aims to establish contracts between features to prevent developers from breaking other features when performing a maintenance task.

Modular invariants from simple currents. An explicit proof

International Nuclear Information System (INIS)

Schellekens, A.N.; Yankielowicz, S.

1989-01-01

In a previous paper an orbifold construction was used to demonstrate that the existence of primary fields with simple fusion rules in a conformal field theory implies the existence of non-diagonal modular invariant partition functions. Here we present a direct and explicit proof of modular invariance, which also covers a few cases that could not be obtained with the orbifold method. We also give a very simple general formula for the modular matrix M. (orig.)

Calculation and modular properties of multiloop superstring amplitudes

International Nuclear Information System (INIS)

Danilov, G. S.

2013-01-01

Multiloop superstring amplitudes are calculated within an extensively used gauge where the two-dimensional gravitino field carries Grassmann moduli. In general, the amplitudes possess, instead of modular symmetry, symmetry with respect to modular transformation supplemented with appropriate transformations of two-dimensional local supersymmetry. If the number of loops is larger than three, the integrationmeasures are notmodular forms, while the expression for the amplitude contains integrals along the boundary of the fundamental region of the modular group.

Reliability and diagnostic of modular systems

Directory of Open Access Journals (Sweden)

J. Kohlas

2014-01-01

Full Text Available Reliability and diagnostic are in general two problems discussed separately. Yet the two problems are in fact closely related to each other. Here, this relation is considered in the simple case of modular systems. We show, how the computation of reliability and diagnostic can efficiently be done within the same Bayesian network induced by the modularity of the structure function of the system.

Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli.

Science.gov (United States)

Stahlhut, Steen G; Siedler, Solvej; Malla, Sailesh; Harrison, Scott J; Maury, Jérôme; Neves, Ana Rute; Forster, Jochen

2015-09-01

Plant secondary metabolites are an underutilized pool of bioactive molecules for applications in the food, pharma and nutritional industries. One such molecule is fisetin, which is present in many fruits and vegetables and has several potential health benefits, including anti-cancer, anti-viral and anti-aging activity. Moreover, fisetin has recently been shown to prevent Alzheimer's disease in mice and to prevent complications associated with diabetes type I. Thus far the biosynthetic pathway of fisetin in plants remains elusive. Here, we present the heterologous assembly of a novel fisetin pathway in Escherichia coli. We propose a novel biosynthetic pathway from the amino acid, tyrosine, utilizing nine heterologous enzymes. The pathway proceeds via the synthesis of two flavanones never produced in microorganisms before--garbanzol and resokaempferol. We show for the first time a functional biosynthetic pathway and establish E. coli as a microbial platform strain for the production of fisetin and related flavonols. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Manufacturing Development of the NCSX Modular Coil Windings

International Nuclear Information System (INIS)

Chrzanowski, JH; Fogarty, PJ; Heitzenroeder, PJ; Meighan, T.; Nelson, B.; Raftopoulos, S.; Williamson, D.

2005-01-01

The modular coils on the National Compact Stellarator Experiment (NCSX) present a number of significant engineering challenges due to their complex shapes, requirements for high dimensional accuracy and the high current density required in the modular coils due to space constraints. In order to address these challenges, an R and D program was established to develop the conductor, insulation scheme, manufacturing techniques, and procedures. A prototype winding named Twisted Racetrack Coil (TRC) was of particular importance in dealing with these challenges. The TRC included a complex shaped winding form, conductor, insulation scheme, leads and termination, cooling system and coil clamps typical of the modular coil design. Even though the TRC is smaller in size than a modular coil, its similar complex geometry provided invaluable information in developing the final design, metrology techniques and development of manufacturing procedures. In addition a discussion of the development of the copper rope conductor including ''Keystoning'' concerns; the epoxy impregnation system (VPI) plus the tooling and equipment required to manufacture the modular coils will be presented

Hierarchical functional modularity in the resting-state human brain.

Science.gov (United States)

Ferrarini, Luca; Veer, Ilya M; Baerends, Evelinda; van Tol, Marie-José; Renken, Remco J; van der Wee, Nic J A; Veltman, Dirk J; Aleman, André; Zitman, Frans G; Penninx, Brenda W J H; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, Julien

2009-07-01

Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a more advanced topological property, has been hypothesized to be evolutionary advantageous, contributing to adaptive aspects of anatomical and functional brain connectivity. However, current definitions of modularity for complex networks focus on nonoverlapping clusters, and are seriously limited by disregarding inclusive relationships. Therefore, BFC's modularity has been mainly qualitatively investigated. Here, we introduce a new definition of modularity, based on a recently improved clustering measurement, which overcomes limitations of previous definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy subjects. Results show hierarchical functional modularity in the brain. Copyright 2009 Wiley-Liss, Inc

Capital costs of modular HTR reactors

International Nuclear Information System (INIS)

Kugeler, K.; Froehling, W.

1993-01-01

A decisive factor in the introduction of a reactor line, in addition of its safety, which should exclude releases of radioactivity into the environment, is its economic development and, consequently, its competitiveness. The costs of the pressurized water reactor are used for comparison with the modular HTR reactor. If the measures proposed for evolutionary increases in safety of the PWR are taken, cost increases will have to be expected for that line. The modular HTR can now attain specific construction costs of 3000 deutschmarks per electric kilowatt. Mass production and the introduction of cost-reducing innovations can improve the economy of this line even further. In this way, the modular HTR concept offers the possibility to vendors and operators to set up new economic yardsticks in safety technology. (orig.) [de

Theta function identities associated with Ramanujan's modular ...

Indian Academy of Sciences (India)

In Chapter 20 of his second notebook [6], Ramanujan recorded several theta function identities associated with modular equations of composite degree 15. These identities have previously been proved by Berndt in [3]. But he proved most of these theta function identities using modular equations. These identities can also ...

The modularization construction of piping system installation in AP1000 plant

International Nuclear Information System (INIS)

Lu Song; Wang Yuan; Wei Junming

2012-01-01

Modularization construction is the main technique used in AP1000 plants, the piping Modularization installation will impact directly to the module construction as the important part of the Modularization construction. After the piping system has took the modularization design in AP1000 plants, some installation works of piping system has moved from the site to fabrication shop. With improving the construction quality and minimizing the time frame of project, the critical paths can be optimized. This paper has analyzed the risk and challenge that met during the modularization construction period of piping systems though introducing the characteristic of modularization construction for AP1000 piping systems, and get construction experiences from the First AP1000 plants in the world, then it will be the firmly basics for the wide application of modularization construction in the future. (authors)

Evaluation of modular robot system for maintenance tasks in hot cell

Energy Technology Data Exchange (ETDEWEB)

Pagala, Prithvi Sekhar, E-mail: ps.pagala@upm.es [Centre for Automation and Robotics UPM-CSIC (Spain); Ferre, Manuel, E-mail: m.ferre@upm.es [Centre for Automation and Robotics UPM-CSIC (Spain); Orona, Luis, E-mail: l.orona@gsi.de [GSI Helmholtzzentrum für Schwerionenforschung (Germany)

2014-10-15

Highlights: •Modular robot deployment inside hot cell for remote manipulation evaluated. •Flexible and adaptable system for variety of tasks presented. •Uses in large workspaces and evolving requirements shown. -- Abstract: This work assesses the use of a modular robot system to perform maintenance and inspection tasks such as, remote flexible inspection, manipulation and cooperation with deployed systems inside the hot cell. A flexible modular solution for the inclusion in maintenance operations is presented. The proposed heterogeneous modular robotic system is evaluated using simulations of the prototype across selected robot configuration to perform tasks. Results obtained show the advantages and ability of the modular robot to perform the necessary tasks as well as its ability to adapt and evolve depending on the need. The simulation test case inside hot cell shows modular robot configuration, a two modular arm to perform tele-operation tasks in the workspace and a wheeled platform for inspection collaborating to perform tasks. The advantage of using re-configurable modular robot over conventional robot platforms is shown.

Modular Firewalls for Storage Areas

Science.gov (United States)

Fedor, O. H.; Owens, L. J.

1986-01-01

Giant honeycomb structures assembled in modular units. Flammable materials stored in cells. Walls insulated with firebrick to prevent spread of fire among cells. Portable, modular barrier withstands heat of combustion for limited time and confines combustion products horizontally to prevent fire from spreading. Barrier absorbs heat energy by ablation and not meant to be reused. Designed to keep fires from spreading among segments of solid rocket propellant in storage, barrier erected between storage units of other flammable or explosive materials; tanks of petroleum or liquid natural gas. Barrier adequate for most industrial purposes.

An analytically solvable model for rapid evolution of modular structure.

Directory of Open Access Journals (Sweden)

Nadav Kashtan

2009-04-01

Full Text Available Biological systems often display modularity, in the sense that they can be decomposed into nearly independent subsystems. Recent studies have suggested that modular structure can spontaneously emerge if goals (environments change over time, such that each new goal shares the same set of sub-problems with previous goals. Such modularly varying goals can also dramatically speed up evolution, relative to evolution under a constant goal. These studies were based on simulations of model systems, such as logic circuits and RNA structure, which are generally not easy to treat analytically. We present, here, a simple model for evolution under modularly varying goals that can be solved analytically. This model helps to understand some of the fundamental mechanisms that lead to rapid emergence of modular structure under modularly varying goals. In particular, the model suggests a mechanism for the dramatic speedup in evolution observed under such temporally varying goals.

Design Requirements for Designing Responsive Modular Manufacturing Systems

DEFF Research Database (Denmark)

Jørgensen, Steffen; Madsen, Ole; Nielsen, Kjeld

2011-01-01

Customers demand the newest technologies, newest designs, the ability to customise, high quality, and all this at a low cost. These are trends which challenge the traditional way of operating manufacturing companies, especially in regard to product development and manufacturing. Research...... the needed flexibility and responsiveness, but such systems are not yet fully achieved. From related theory it is known that achieving modular benefits depend on the modular architecture; a modular architecture which must be developed according to the customer needs. This makes production needs a design...... requirement in order to achieve responsiveness and other benefits of modular manufacturing systems (MMS). Due to the complex and interrelated nature of a production system and its surroundings these production needs are complex to identify. This paper presents an analysis framework for identification...

Modular remote radiation monitor

International Nuclear Information System (INIS)

Lacerda, Fabio; Farias, Marcos S.; Aghina, Mauricio A.C.; Oliveira, Mauro V.

2013-01-01

The Modular Remote Radiation Monitor (MRRM) is a novel radiation monitor suitable for monitoring environmental exposure to ionizing radiation. It is a portable compact-size low-power microprocessor-based electronic device which provides its monitoring data to other electronic systems, physically distant from it, by means of an electronic communication channel, which can be wired or wireless according to the requirements of each application. Besides its low-power highly-integrated circuit design, the Modular Remote Radiation Monitor is presented in a modular architecture, which promotes full compliance to the technical requirements of different applications while minimizing cost, size and power consumption. Its communication capability also supports the implementation of a network of multiple radiation monitors connected to a supervisory system, capable of remotely controlling each monitor independently as well as visualizing the radiation levels from all monitors. A prototype of the MRRM, functionally equivalent to the MRA-7027 radiation monitor, was implemented and connected to a wired MODBUS network of MRA-7027 monitors, responsible for monitoring ionizing radiation inside Argonauta reactor room at Instituto de Engenharia Nuclear. Based on the highly positive experimental results obtained, further design is currently underway in order to produce a consumer version of the MRRM. (author)

Modular Cure Provision

DEFF Research Database (Denmark)

Winther-Hansen, Casper; Frandsen, Thomas

facilitate co-creation through open platforms and service modularity. Based on data from two pharmaceuticals we explore issues of governance related to the relative openness of platforms and their completeness. Whereas some pharmaceuticals should cater to sophisticated needs of competent users through open...

Alteration in expression of defence genes in Pisum sativum after exposure to supplementary ultraviolet-B radiation

International Nuclear Information System (INIS)

Strid, A.

1993-01-01

Alterations in the amounts of mRNA for different types of defence genes after exposure of peas to supplementary ultraviolet-B radiation are demonstrated. The expression of the genes which encode the chalcone synthase of the flavonoid biosynthetic pathway and glutathione reductase was induced, while a decrease was found for the chloroplastic radical-scavenging enzyme, superoxide dismutase. (author)

Modular chemiresistive sensor

Energy Technology Data Exchange (ETDEWEB)

Alam, Maksudul M.; Sampathkumaran, Uma

2018-02-20

The present invention relates to a modular chemiresistive sensor. In particular, a modular chemiresistive sensor for hypergolic fuel and oxidizer leak detection, carbon dioxide monitoring and detection of disease biomarkers. The sensor preferably has two gold or platinum electrodes mounted on a silicon substrate where the electrodes are connected to a power source and are separated by a gap of 0.5 to 4.0 .mu.M. A polymer nanowire or carbon nanotube spans the gap between the electrodes and connects the electrodes electrically. The electrodes are further connected to a circuit board having a processor and data storage, where the processor can measure current and voltage values between the electrodes and compare the current and voltage values with current and voltage values stored in the data storage and assigned to particular concentrations of a pre-determined substance such as those listed above or a variety of other substances.

Application and development analysis of nuclear power plant modular construction

International Nuclear Information System (INIS)

Fang Xiaopeng

2015-01-01

Modular Construction is currently one of the major development trends for the nuclear power plant construction technology worldwide. In the first-of-a-kind AP1000 Nuclear Power Project practiced in China, the large-scale structural modules and mechanical modules have been successfully fabricated, assembled and installed. However, in the construction practice of the project, some quality issues are identified with the assembly and installation process of large-scale structural modules in addition to the issue of incomplete supply of mechanical modules, which has failed to fully demonstrate the features and merits of modular construction. This paper collects and consolidates the issues of modular construction of AP1000 first of a kind reactor, providing root cause analysis in the aspects of process design, quality control, site construction logic, interface management in the process of module fabrication, assembly and installation; modular construction feasibility assessment index is proved based on the quantification and qualitative analysis of the impact element. Based on the modular construction feasibility, NPP modular construction improvement suggestions are provided in the aspect of modular assembly optimization definition, tolerance control during the fitting process and the construction logic adjustment. (author)

Kinetics of Nif gene expression in a nitrogen-fixing bacterium.

Science.gov (United States)

Poza-Carrión, César; Jiménez-Vicente, Emilio; Navarro-Rodríguez, Mónica; Echavarri-Erasun, Carlos; Rubio, Luis M

2014-02-01

Nitrogen fixation is a tightly regulated trait. Switching from N2 fixation-repressing conditions to the N2-fixing state is carefully controlled in diazotrophic bacteria mainly because of the high energy demand that it imposes. By using quantitative real-time PCR and quantitative immunoblotting, we show here how nitrogen fixation (nif) gene expression develops in Azotobacter vinelandii upon derepression. Transient expression of the transcriptional activator-encoding gene, nifA, was followed by subsequent, longer-duration waves of expression of the nitrogenase biosynthetic and structural genes. Importantly, expression timing, expression levels, and NifA dependence varied greatly among the nif operons. Moreover, the exact concentrations of Nif proteins and their changes over time were determined for the first time. Nif protein concentrations were exquisitely balanced, with FeMo cofactor biosynthetic proteins accumulating at levels 50- to 100-fold lower than those of the structural proteins. Mutants lacking nitrogenase structural genes or impaired in FeMo cofactor biosynthesis showed overenhanced responses to derepression that were proportional to the degree of nitrogenase activity impairment, consistent with the existence of at least two negative-feedback regulatory mechanisms. The first such mechanism responded to the levels of fixed nitrogen, whereas the second mechanism appeared to respond to the levels of the mature NifDK component. Altogether, these findings provide a framework to engineer N2 fixation in nondiazotrophs.

Modular biometric system

Science.gov (United States)

Hsu, Charles; Viazanko, Michael; O'Looney, Jimmy; Szu, Harold

2009-04-01

Modularity Biometric System (MBS) is an approach to support AiTR of the cooperated and/or non-cooperated standoff biometric in an area persistent surveillance. Advanced active and passive EOIR and RF sensor suite is not considered here. Neither will we consider the ROC, PD vs. FAR, versus the standoff POT in this paper. Our goal is to catch the "most wanted (MW)" two dozens, separately furthermore ad hoc woman MW class from man MW class, given their archrivals sparse front face data basis, by means of various new instantaneous input called probing faces. We present an advanced algorithm: mini-Max classifier, a sparse sample realization of Cramer-Rao Fisher bound of the Maximum Likelihood classifier that minimize the dispersions among the same woman classes and maximize the separation among different man-woman classes, based on the simple feature space of MIT Petland eigen-faces. The original aspect consists of a modular structured design approach at the system-level with multi-level architectures, multiple computing paradigms, and adaptable/evolvable techniques to allow for achieving a scalable structure in terms of biometric algorithms, identification quality, sensors, database complexity, database integration, and component heterogenity. MBS consist of a number of biometric technologies including fingerprints, vein maps, voice and face recognitions with innovative DSP algorithm, and their hardware implementations such as using Field Programmable Gate arrays (FPGAs). Biometric technologies and the composed modularity biometric system are significant for governmental agencies, enterprises, banks and all other organizations to protect people or control access to critical resources.

Investigation of small and modular-sized fast reactor

International Nuclear Information System (INIS)

Kubota, Kenichi; Kawasaki, Nobuchika; Umetsu, Yoichiro; Akatsu, Minoru; Kasai, Shigeo; Konomura, Mamoru; Ichimiya, Masakazu

2000-06-01

In this paper, feasibility of the multipurpose small fast reactor, which could be used for requirements concerned with various utilization of electricity and energy and flexibility of power supply site, is discussed on the basis of examination of literatures of various small reactors. And also, a possibility of economic improvement by learning effect of fabrication cost is discussed for the modular-sized reactor which is expected to be a base load power supply system with lower initial investment. (1) Multipurpose small reactor (a) The small reactor with 10MWe-150MWe has a potential as a power source for large co-generation, a large island, a middle city, desalination and marine use. (b) Highly passive mechanism, long fuel exchange interval, and minimized maintenance activities are required for the multipurpose small reactor design. The reactor has a high potential for the long fuel exchange interval, since it is relatively easy for FR to obtain a long life core. (c) Current designs of small FRs in Japan and USA (NERI Project) are reviewed to obtain design requirements for the multipurpose small reactor. (2) Modular-sized reactor (a) In order that modular-sized reactor could be competitive to 3200MWe twin plant (two large monolithic reactor) with 200kyenWe, the target capital cost of FOAK is estimated to be 260kyen/yenWe for 800MWe modular, 280kyen/yenWe for 400MWe modular and 290kyen/yenWe for 200MWe by taking account of the leaning effect. (b) As the result of the review on the current designs of modular-sized FRs in Japan and USA (S-PRISM) from the viewpoint of economic improvement, since it only be necessary to make further effort for the target capital cost of FOAK, since the modular-sized FRs requires a large amount of material for shielding, vessels and heat exchangers essentially. (author)

Advanced Modular Power Approach to Affordable, Supportable Space Systems

Science.gov (United States)

Oeftering, Richard C.; Kimnach, Greg L.; Fincannon, James; Mckissock,, Barbara I.; Loyselle, Patricia L.; Wong, Edmond

2013-01-01

Recent studies of missions to the Moon, Mars and Near Earth Asteroids (NEA) indicate that these missions often involve several distinct separately launched vehicles that must ultimately be integrated together in-flight and operate as one unit. Therefore, it is important to see these vehicles as elements of a larger segmented spacecraft rather than separate spacecraft flying in formation. The evolution of large multi-vehicle exploration architecture creates the need (and opportunity) to establish a global power architecture that is common across all vehicles. The Advanced Exploration Systems (AES) Modular Power System (AMPS) project managed by NASA Glenn Research Center (GRC) is aimed at establishing the modular power system architecture that will enable power systems to be built from a common set of modular building blocks. The project is developing, demonstrating and evaluating key modular power technologies that are expected to minimize non-recurring development costs, reduce recurring integration costs, as well as, mission operational and support costs. Further, modular power is expected to enhance mission flexibility, vehicle reliability, scalability and overall mission supportability. The AMPS project not only supports multi-vehicle architectures but should enable multi-mission capability as well. The AMPS technology development involves near term demonstrations involving developmental prototype vehicles and field demonstrations. These operational demonstrations not only serve as a means of evaluating modular technology but also provide feedback to developers that assure that they progress toward truly flexible and operationally supportable modular power architecture.

Adaptive Modular Playware

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

2011-01-01

In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user...

The Impact of Product and Service Modularity on Business Performance

DEFF Research Database (Denmark)

Hsuan, Juliana; Frandsen, Thomas; Raja, Jawwad

Modularity has been proposed as a powerful way of managing complexity. The emerging literature points to the importance of modularity of service architecture, with case based studies in logistics and healthcare. Little is known about the relationship between product and service modularity...... and their effects on business performance, both empirically and theoretically. This paper explores the relationship between product and service modularity and their effects on business performance based on a survey of Danish manufacturers. We provide empirical and theoretical insights into the emerging fields...

Music, Language and Modularity Framed in Action

Directory of Open Access Journals (Sweden)

Isabelle Peretz

2009-06-01

Full Text Available Here, I examine to what extend music and speech share processing components by focusing on vocal production, that is, singing and speaking. In shaping my review, the modularity concept has been and continues to play a determinant role. Thus, I will first provide a brief background on the contemporary notion of modularity. Next, I will present evidence that musical abilities depend, in part, on modular processes. The evidence is coming mainly from neuropsychological dissociations. The relevance of findings of overlap in neuroimaging, of interference and domain-transfer effects between music and speech will also be addressed and discussed. Finally, I will contrast the modularity position with the resource-sharing framework proposed by Patel (2003, 2008a. This critical review should be viewed as an invitation to undertake future comparative research between music and language by focusing on the details of the functions that these mechanisms carry out, not only their specificity. Such comparative research is very important not only theoretically but also in practice because of their obvious clinical and educational implications.

HexaMob—A Hybrid Modular Robotic Design for Implementing Biomimetic Structures

Directory of Open Access Journals (Sweden)

Sasanka Sankhar Reddy CH.

2017-10-01

Full Text Available Modular robots are capable of forming primitive shapes such as lattice and chain structures with the additional flexibility of distributed sensing. The biomimetic structures developed using such modular units provides ease of replacement and reconfiguration in co-ordinated structures, transportation etc. in real life scenarios. Though the research in the employment of modular robotic units in formation of biological organisms is in the nascent stage, modular robotic units are already capable of forming such sophisticated structures. The modular robotic designs proposed so far in modular robotics research vary significantly in external structures, sensor-actuator mechanisms interfaces for docking and undocking, techniques for providing mobility, coordinated structures, locomotions etc. and each robotic design attempted to address various challenges faced in the domain of modular robotics by employing different strategies. This paper presents a novel modular wheeled robotic design - HexaMob facilitating four degrees of freedom (2 degrees for mobility and 2 degrees for structural reconfiguration on a single module with minimal usage of sensor-actuator assemblies. The crucial features of modular robotics such as back-driving restriction, docking, and navigation are addressed in the process of HexaMob design. The proposed docking mechanism is enabled using vision sensor, enhancing the capabilities in docking as well as navigation in co-ordinated structures such as humanoid robots.

Harmonic Maass forms and mock modular forms

CERN Document Server

Bringmann, Kathrin; Ono, Ken

2017-01-01

Modular forms and Jacobi forms play a central role in many areas of mathematics. Over the last 10-15 years, this theory has been extended to certain non-holomorphic functions, the so-called "harmonic Maass forms". The first glimpses of this theory appeared in Ramanujan's enigmatic last letter to G. H. Hardy written from his deathbed. Ramanujan discovered functions he called "mock theta functions" which over eighty years later were recognized as pieces of harmonic Maass forms. This book contains the essential features of the theory of harmonic Maass forms and mock modular forms, together with a wide variety of applications to algebraic number theory, combinatorics, elliptic curves, mathematical physics, quantum modular forms, and representation theory.

Non-Archimedean L-functions and arithmetical Siegel modular forms

CERN Document Server

1991-01-01

This book is devoted to the arithmetical theory of Siegel modular forms and their L-functions. The central object are L-functions of classical Siegel modular forms whose special values are studied using the Rankin-Selberg method and the action of certain differential operators on modular forms which have nice arithmetical properties. A new method of p-adic interpolation of these critical values is presented. An important class of p-adic L-functions treated in the present book are p-adic L-functions of Siegel modular forms having logarithmic growth (which were first introduced by Amice, Velu and Vishik in the elliptic modular case when they come from a good supersingular reduction of ellptic curves and abelian varieties). The given construction of these p-adic L-functions uses precise algebraic properties of the arihmetical Shimura differential operator. The book could be very useful for postgraduate students and for non-experts giving a quick access to a rapidly developping domain of algebraic number theory: ...

Local modular Hamiltonians from the quantum null energy condition

Science.gov (United States)

Koeller, Jason; Leichenauer, Stefan; Levine, Adam; Shahbazi-Moghaddam, Arvin

2018-03-01

The vacuum modular Hamiltonian K of the Rindler wedge in any relativistic quantum field theory is given by the boost generator. Here we investigate the modular Hamiltonian for more general half-spaces which are bounded by an arbitrary smooth cut of a null plane. We derive a formula for the second derivative of the modular Hamiltonian with respect to the coordinates of the cut which schematically reads K''=Tv v . This formula can be integrated twice to obtain a simple expression for the modular Hamiltonian. The result naturally generalizes the standard expression for the Rindler modular Hamiltonian to this larger class of regions. Our primary assumptions are the quantum null energy condition—an inequality between the second derivative of the von Neumann entropy of a region and the stress tensor—and its saturation in the vacuum for these regions. We discuss the validity of these assumptions in free theories and holographic theories to all orders in 1 /N .

Modular products: Smartphone design from a circular economy perspective

OpenAIRE

Schischke, Karsten; Proske, Marina; Nissen, Nils F.; Lang, Klaus-Dieter

2016-01-01

Currently a range of modular smartphones is emerging, including the Fairphone 2, Puzzlephone, Google's Project ARA, RePhone, LG's G5 and others. In an industry of perceived short product cycles a modular design concept might become crucial for longer product lifetimes. The paper provides an overview on latest product developments and assesses these against environmental criteria, including longevity, durability, upgradeability, repairability and Design for Recycling and Reuse. Modular product...

Modular, Reconfigurable, High-Energy Technology Development

Science.gov (United States)

Carrington, Connie; Howell, Joe

2006-01-01

The Modular, Reconfigurable High-Energy (MRHE) Technology Demonstrator project was to have been a series of ground-based demonstrations to mature critical technologies needed for in-space assembly of a highpower high-voltage modular spacecraft in low Earth orbit, enabling the development of future modular solar-powered exploration cargo-transport vehicles and infrastructure. MRHE was a project in the High Energy Space Systems (HESS) Program, within NASA's Exploration Systems Research and Technology (ESR&T) Program. NASA participants included Marshall Space Flight Center (MSFC), the Jet Propulsion Laboratory (JPL), and Glenn Research Center (GRC). Contractor participants were the Boeing Phantom Works in Huntsville, AL, Lockheed Martin Advanced Technology Center in Palo Alto, CA, ENTECH, Inc. in Keller, TX, and the University of AL Huntsville (UAH). MRHE's technical objectives were to mature: (a) lightweight, efficient, high-voltage, radiation-resistant solar power generation (SPG) technologies; (b) innovative, lightweight, efficient thermal management systems; (c) efficient, 100kW-class, high-voltage power delivery systems from an SPG to an electric thruster system; (d) autonomous rendezvous and docking technology for in-space assembly of modular, reconfigurable spacecraft; (e) robotic assembly of modular space systems; and (f) modular, reconfigurable distributed avionics technologies. Maturation of these technologies was to be implemented through a series of increasingly-inclusive laboratory demonstrations that would have integrated and demonstrated two systems-of-systems: (a) the autonomous rendezvous and docking of modular spacecraft with deployable structures, robotic assembly, reconfiguration both during assembly and (b) the development and integration of an advanced thermal heat pipe and a high-voltage power delivery system with a representative lightweight high-voltage SPG array. In addition, an integrated simulation testbed would have been developed

Analysis of Advanced Modular Power Systems (AMPS) for Deep Space Exploration

Science.gov (United States)

Oeftering, Richard; Soeder, James F.; Beach, Ray

2014-01-01

The Advanced Modular Power Systems (AMPS) project is developing a modular approach to spacecraft power systems for exploration beyond Earth orbit. AMPS is intended to meet the need of reducing the cost of design development, test and integration and also reducing the operational logistics cost of supporting exploration missions. AMPS seeks to establish modular power building blocks with standardized electrical, mechanical, thermal and data interfaces that can be applied across multiple exploration vehicles. The presentation discusses the results of a cost analysis that compares the cost of the modular approach against a traditional non-modular approach.

Characterization and engineering of thermophilic aldolases : synthesizing nitrogen-heterocycles in biosynthetic routes

NARCIS (Netherlands)

Wolterink-van Loo, S.

2009-01-01

Aldolases are enzymes that catalyze reactions in both degradation and biosynthetic pathways in vivo and have been discovered in all domains of life. they. An interesting property of aldolases is that they can synthesize carbon-carbon bonds, generating a new stereogenic centre. As enzymes are

Modularization of Courses.