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  • 1
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2010
    In:  Journal of Integrative Bioinformatics Vol. 7, No. 3 ( 2010-12-1)
    In: Journal of Integrative Bioinformatics, Walter de Gruyter GmbH, Vol. 7, No. 3 ( 2010-12-1)
    Abstract: Drug development is expensive and prone to failure. It is potentially much less risky and expensive to reuse a drug developed for one condition for treating a second disease, than it is to develop an entirely new compound. Systematic approaches to drug repositioning are needed to increase throughput and find candidates more reliably. Here we address this need with an integrated systems biology dataset, developed using the Ondex data integration platform, for the in silico discovery of new drug repositioning candidates. We demonstrate that the information in this dataset allows known repositioning examples to be discovered. We also propose a means of automating the search for new treatment indications of existing compounds.
    Type of Medium: Online Resource
    ISSN: 1613-4516
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2010
    detail.hit.zdb_id: 2147212-9
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  • 2
    In: Microbial Cell Factories, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2022-12)
    Abstract: Geobacillus kaustophilus is a thermophilic Gram-positive bacterium. Methods for its transformation are still under development. Earlier studies have demonstrated that pLS20catΔoriT mobilized the resident mobile plasmids from Bacillus subtilis to G. kaustophilus and transferred long segments of chromosome from one cell to another between B. subtilis . Results In this study, we applied mobilization of the B. subtilis chromosome mediated by pLS20catΔoriT to transform G. kaustophilus . We constructed a gene cassette to be integrated into G. kaustophilus and designed it within the B. subtilis chromosome. The pLS20catΔoriT-mediated conjugation successfully transferred the gene cassette from the B. subtilis chromosome into the G. kaustophilus allowing for the desired genetic transformation. Conclusions This transformation approach described here will provide a new tool to facilitate the flexible genetic manipulation of G. kaustophilus .
    Type of Medium: Online Resource
    ISSN: 1475-2859
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2091377-1
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  • 3
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Applied Microbiology Vol. 1, No. 2 ( 2021-07-16), p. 239-254
    In: Applied Microbiology, MDPI AG, Vol. 1, No. 2 ( 2021-07-16), p. 239-254
    Abstract: Recently, there has been a resurgence of interest in continuous bioprocessing as a cost-optimised production strategy, driven by a rising global requirement for recombinant proteins used as biological drugs. This strategy could provide several benefits over traditional batch processing, including smaller bioreactors, smaller facilities, and overall reduced plant footprints and investment costs. Continuous processes may also offer improved product quality and minimise heterogeneity, both in the culture and in the product. In this paper, a model protein, green fluorescent protein (GFP) mut3*, was used to test the recombinant protein expression in an Escherichia coli strain with industrial relevance grown in chemostat. An important factor in enabling stable productivity in continuous cultures is the carbon source. We have studied the viability and heterogeneity of the chemostat cultures using a chemically defined medium based on glucose or glycerol as the single carbon source. As a by-product of biodiesel production, glycerol is expected to become a sustainable alternative substrate to glucose. We have found that although glycerol gives a higher cell density, it also generates higher heterogeneity in the culture and a less stable recombinant protein production. We suggest that manipulating the balance between different subpopulations to increase the proportion of productive cells may be a possible solution for making glycerol a successful alternative to glucose.
    Type of Medium: Online Resource
    ISSN: 2673-8007
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 3136474-3
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2007
    In:  Bioinformatics Vol. 23, No. 3 ( 2007-02-01), p. 336-343
    In: Bioinformatics, Oxford University Press (OUP), Vol. 23, No. 3 ( 2007-02-01), p. 336-343
    Abstract: Motivation: New developments in post-genomic technology now provide researchers with the data necessary to study regulatory processes in a holistic fashion at multiple levels of biological organization. One of the major challenges for the biologist is to integrate and interpret these vast data resources to gain a greater understanding of the structure and function of the molecular processes that mediate adaptive and cell cycle driven changes in gene expression. In order to achieve this biologists require new tools and techniques to allow pathway related data to be modelled and analysed as network structures, providing valuable insights which can then be validated and investigated in the laboratory. Results: We propose a new technique for constructing and analysing qualitative models of genetic regulatory networks based on the Petri net formalism. We take as our starting point the Boolean network approach of treating genes as binary switches and develop a new Petri net model which uses logic minimization to automate the construction of compact qualitative models. Our approach addresses the shortcomings of Boolean networks by providing access to the wide range of existing Petri net analysis techniques and by using non–determinism to cope with incomplete and inconsistent data. The ideas we present are illustrated by a case study in which the genetic regulatory network controlling sporulation in the bacterium Bacillus subtilis is modelled and analysed. Availability: The Petri net model construction tool and the data files for the B. subtilis sporulation case study are available at Contact:  L.J.Steggles@ncl.ac.uk
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 5
    In: Bioinformatics, Oxford University Press (OUP), Vol. 32, No. 6 ( 2016-03-15), p. 908-917
    Abstract: Motivation: Biological systems are complex and challenging to model and therefore model reuse is highly desirable. To promote model reuse, models should include both information about the specifics of simulations and the underlying biology in the form of metadata. The availability of computationally tractable metadata is especially important for the effective automated interpretation and processing of models. Metadata are typically represented as machine-readable annotations which enhance programmatic access to information about models. Rule-based languages have emerged as a modelling framework to represent the complexity of biological systems. Annotation approaches have been widely used for reaction-based formalisms such as SBML. However, rule-based languages still lack a rich annotation framework to add semantic information, such as machine-readable descriptions, to the components of a model. Results: We present an annotation framework and guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages. We adapt widely adopted annotation approaches to rule-based models. We initially propose a syntax to store machine-readable annotations and describe a mapping between rule-based modelling entities, such as agents and rules, and their annotations. We then describe an ontology to both annotate these models and capture the information contained therein, and demonstrate annotating these models using examples. Finally, we present a proof of concept tool for extracting annotations from a model that can be queried and analyzed in a uniform way. The uniform representation of the annotations can be used to facilitate the creation, analysis, reuse and visualization of rule-based models. Although examples are given, using specific implementations the proposed techniques can be applied to rule-based models in general. Availability and implementation: The annotation ontology for rule-based models can be found at http://purl.org/rbm/rbmo. The krdf tool and associated executable examples are available at http://purl.org/rbm/rbmo/krdf. Contact:  anil.wipat@newcastle.ac.uk   or  vdanos@inf.ed.ac.uk
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 6
    In: Environmental Microbiology, Wiley, Vol. 22, No. 5 ( 2020-05), p. 1784-1800
    Abstract: Sulfur‐oxidizing Sulfurimonas spp. are widespread in sediments, hydrothermal vent fields, aquifers and subsurface environments such as oil reservoirs where they play an important role in the sulfur cycle. We determined the genome sequence of the oil field isolate Sulfurimonas sp. strain CVO and compared its gene expression during nitrate‐dependent sulfide oxidation to the coastal sediment isolate Sulfurimonas denitrificans . Formation of elemental sulfur (S 0 ) and high expression of sulfide quinone oxidoreductase (SQR) genes indicates that sulfide oxidation in both strains is mediated by SQR. Subsequent oxidation of S 0 was achieved by the sulfur oxidation enzyme complex (SOX). In the coastal S. denitrificans , the genes are arranged and expressed as two clusters: soxXY 1 Z 1 AB and soxCDY 2 Z 2 H , and sulfate was the sole metabolic end product. By contrast, the oil field strain CVO has only the soxCDY 2 Z 2 H cluster and not soxXY 1 Z 1 AB . Despite the absence of the soxXY 1 Z 1 AB cluster, strain CVO oxidized S 0 to thiosulfate and sulfate, demonstrating that soxCDY 2 Z 2 H genes alone are sufficient for S 0 oxidation in Sulfurimonas spp. and that thiosulfate is an additional metabolic end product. Screening of publicly available metagenomes revealed that Sulfurimonas spp. with only the soxCDY 2 Z 2 H cluster are widespread suggesting this mechanism of thiosulfate formation is environmentally significant.
    Type of Medium: Online Resource
    ISSN: 1462-2912 , 1462-2920
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2020213-1
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Portland Press Ltd. ; 2017
    In:  Biochemical Society Transactions Vol. 45, No. 3 ( 2017-06-15), p. 781-783
    In: Biochemical Society Transactions, Portland Press Ltd., Vol. 45, No. 3 ( 2017-06-15), p. 781-783
    Abstract: The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties — Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers. The CSBB trains the next generation of scientists through a 1-year MSc in Synthetic Biology.
    Type of Medium: Online Resource
    ISSN: 0300-5127 , 1470-8752
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2017
    SSG: 12
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  • 8
    In: Biochemical Society Transactions, Portland Press Ltd., Vol. 45, No. 3 ( 2017-06-15), p. 793-803
    Abstract: A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications.
    Type of Medium: Online Resource
    ISSN: 0300-5127 , 1470-8752
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2017
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-12-7)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-12-7)
    Abstract: Boosting the production of recombinant therapeutic antibodies is crucial in both academic and industry settings. In this work, we investigated the usage of varying signal peptides by antibody V-genes and their roles in recombinant transient production, systematically comparing myeloma and the native signal peptides of both heavy and light chains in 168 antibody permutation variants. We found that amino acids count and types (essential or non-essential) were important factors in a logistic regression equation model for predicting transient co-transfection protein production rates. Deeper analysis revealed that the culture media were often incomplete and that the supplementation of essential amino acids can improve the recombinant protein yield. While these findings are derived from transient HEK293 expression, they also provide insights to the usage of the large repertoire of antibody signal peptides, where by varying the number of specific amino acids in the signal peptides attached to the variable regions, bottlenecks in amino acid availability can be mitigated.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 10
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2014-09-11)
    Abstract: Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1 , which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2553671-0
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