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  • 1
    Language: English
    In: Science (American Association for the Advancement of Science), 2015-07-17, Vol.349 (6245), p.309-312
    Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
    Subject(s): Biosynthesis ; Enzymes ; Metabolites ; Modules ; Morphine ; Narcotics ; Pathways ; Poppies ; Proteins ; REPORTS
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: Get It Now
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  • 2
    Language: English
    In: Science (American Association for the Advancement of Science), 2018-10-19, Vol.362 (6412), p.343-347
    Description: Morphinan-based painkillers are derived from opium poppy ( L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.
    Subject(s): Addiction ; Analgesics ; Benzylisoquinolines - metabolism ; Biological evolution ; Biosynthesis ; Chemical properties ; Chromosomes ; Clusters ; Divergence ; Drug abuse ; Drug trafficking ; Evolution, Molecular ; Gene Duplication ; Gene Fusion ; Gene Order ; Gene rearrangement ; Genes ; Genetic aspects ; Genome, Plant ; Genomes ; Metabolism ; Morphinans - metabolism ; Multigene Family ; NADPH-Ferrihemoprotein Reductase - genetics ; Narcotics ; Opiates ; Opioids ; Opium poppy ; Oxidoreductase ; Papaver - genetics ; Papaver - metabolism ; Papaver somniferum ; Phthalideisoquinoline ; Plant Proteins - genetics ; Production processes ; Proteins ; Reproduction (copying) ; Synteny
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: Get It Now
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  • 3
    Language: English
    In: Science (American Association for the Advancement of Science), 2012-06-29, Vol.336 (6089), p.1704-1708
    Description: Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F₂ mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.
    Subject(s): Alkaloids ; Anticancer properties ; Antineoplastic Agents, Phytogenic - biosynthesis ; Biological and medical sciences ; Biosynthesis ; Capsules ; Classical genetics, quantitative genetics, hybrids ; Clusters ; Cough ; Enzymes ; Flowers & plants ; Fundamental and applied biological sciences. Psychology ; Gene silencing ; Genes ; Genes, Plant ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; Genomes ; Latex ; Libraries ; Low level ; Molecular Sequence Data ; Morphinans ; Multigene Family ; Narcotics ; Noscapine - metabolism ; Open reading frames ; Papaver - enzymology ; Papaver - genetics ; Papaver - metabolism ; Papaver somniferum ; Pharmaceutical sciences ; Physiological aspects ; Plant biology ; Poppies ; Pteridophyta, spermatophyta ; REPORTS ; Research ; Synthesis ; Vegetals
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: Get It Now
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  • 4
    Language: English
    In: The Plant journal : for cell and molecular biology, 2010-01, Vol.61 (1), p.166-175
    Description: Summary High‐density oligonucleotide arrays are widely used for analysis of gene expression on a genomic scale, but the generated data remain largely inaccessible for comparative analysis purposes. Similarity searches in databases with differentially expressed gene (DEG) lists may be used to assign potential functions to new genes and to identify potential chemical inhibitors/activators and genetic suppressors/enhancers. Although this is a very promising concept, it requires the compatibility and validity of the DEG lists to be significantly improved. Using Arabidopsis and human datasets, we have developed guidelines for the performance of similarity searches against databases that collect microarray data. We found that, in comparison with many other methods, a rank‐product analysis achieves a higher degree of inter‐ and intra‐laboratory consistency of DEG lists, and is advantageous for assessing similarities and differences between them. To support this concept, we developed a tool called MASTA (microarray overlap search tool and analysis), and re‐analyzed over 600 Arabidopsis microarray expression datasets. This revealed that large‐scale searches produce reliable intersections between DEG lists that prove to be useful for genetic analysis, thus aiding in the characterization of cellular and molecular mechanisms. We show that this approach can be used to discover unexpected connections and to illuminate unanticipated interactions between individual genes.
    Subject(s): Analysis ; analysis of microarrays ; Arabidopsis ; Arabidopsis - genetics ; Biological and medical sciences ; Botany ; Chemical inhibitors ; Computational Biology - methods ; Databases ; Databases, Genetic ; differentially expressed genes ; extracellular matrix ; Fundamental and applied biological sciences. Psychology ; Gene expression ; General aspects ; Genomics ; Humans ; Investigations ; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects) ; Oligonucleotide Array Sequence Analysis - methods ; Plant physiology and development ; rank product ; reactive oxygen ; Research methodology ; suppressor/enhancer screen
    ISSN: 0960-7412
    E-ISSN: 1365-313X
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 5
    Language: English
    In: The Plant journal : for cell and molecular biology, 2010-01, Vol.61 (1), p.166-175
    ISSN: 0960-7412
    E-ISSN: 1365-313X
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 6
    Language: English
    In: Science (American Association for the Advancement of Science), 2015-07-17, Vol.349 (6245), p.309-312
    Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
    Subject(s): Base Sequence ; Benzylisoquinolines - chemistry ; Benzylisoquinolines - metabolism ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Genetic Loci ; Isoquinolines - chemistry ; Isoquinolines - metabolism ; Molecular Sequence Data ; Morphinans - chemistry ; Morphinans - metabolism ; Mutation ; Oxidation-Reduction ; Papaver - enzymology ; Papaver - genetics ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Quaternary Ammonium Compounds - chemistry ; Quaternary Ammonium Compounds - metabolism
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: Get It Now
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  • 7
    Language: English
    In: Analele stiintifice ale Universitatii "Al. I. Cuza" din Iasi. Sectiunea II a. Biologie vegetala, 2008-07-01, Vol.54 (2), p.109-109
    Description:   The aerial surfaces of land plants are covered with cuticle that acts as a barrier providing protection against water loss, pathogen invasion and other environmental aggressions. Besides physical and chemical barriers, such as a waxy cuticle, plant defense mechanisms also involve a coordinated activation of cellular responses to limit damage. The eceriferum (cer) mutants of Arabidopsis define multiple genes required for various steps in cuticular wax biosynthesis, transport and regulation of lipid-related pathways. Although the basic biochemistry of wax production has been elucidated, very little is known about its regulation and its contribution to the natural immunity. This review presents recently cloned wax biosynthetic genes and discusses regulatory aspects of wax biosynthesis. [PUBLICATION ABSTRACT]
    Subject(s): Arabidopsis ; Arabidopsis thaliana ; Fatty acids ; Genes ; Metabolism ; Proteins
    ISSN: 1223-6578
    E-ISSN: 2247-2711
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    Description: Morphinan-based painkillers are derived from opium poppy (Papaver somniferum L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ∼7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the STORR gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.
    Source: White Rose Research Repository
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  • 9
    Language: English
    Description: Provider: Deutsche Digitale Bibliothek - Institution: Deutsche Nationalbibliothek - Data provided by Europeana Collections- Köln, Univ., Diss., 2009- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
    Subject(s): Biowissenschaften, Biologie
    Source: Europeana Collections
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  • 10
    Language: English
    In: Medicina (Kaunas, Lithuania), 2020-12-23, Vol.57 (1), p.6
    Description: The combination of immune checkpoint inhibitors and definitive radiotherapy is investigated for the multimodal treatment of cisplatin non-eligible locally advanced head and neck cancers (HNC). In the case of recurrent and metastatic HNC, immunotherapy has shown benefit over the EXTREME protocol, being already considered the standard treatment. One of the biggest challenges of multimodal treatment is to establish the optimal therapy sequence so that the synergistic effect is maximal. Thus, superior results were obtained for the administration of anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of the tumor in case of concurrent administration. The synergistic effect of radiotherapy-immunotherapy (RT-IT) has been demonstrated in clinical practice, with an overall response rate of about 18% for HNC. Given the demonstrated potential of radiotherapy to activate the immune system through already known mechanisms, it is necessary to identify biomarkers that direct the "nonresponders" of immunotherapy towards a synergistic RT-IT stimulation strategy. Stimulation of the immune system by irradiation can convert "nonresponder" to "responder". With the development of modern techniques, re-irradiation is becoming an increasingly common option for patients who have previously been treated with higher doses of radiation. In this context, radiotherapy in combination with immunotherapy, both in the advanced local stage and in recurrent/metastatic of HNC radiotherapy, could evolve from the "first level" of knowledge (i.e., ballistic precision, dose conformity and homogeneity) to "level two" of "biological dose painting" (in which the concept of tumor heterogeneity and radio-resistance supports the need for doses escalation based on biological criteria), and finally to the "third level" ofthe new concept of "immunological dose painting". The peculiarity of this concept is that the radiotherapy target volumes and tumoricidal dose can be completely reevaluated, taking into account the immune-modulatory effect of irradiation. In this case, the tumor target volume can include even the tumor microenvironment or a partial volume of the primary tumor or metastasis, not all the gross and microscopic disease. Tumoricidal biologically equivalent dose (BED) may be completely different from the currently estimated values, radiotherapy treating the tumor in this case indirectly by boosting the immune response. Thus, the clinical target volume (CTV) can be replaced with a new immunological-clinical target volume (ICTV) for patients who benefit from the RT-IT association (Image 1).
    Subject(s): ab-scopal ; Cisplatin ; head and neck cancers ; Head and Neck Neoplasms - radiotherapy ; Humans ; Immunotherapy ; Opinion ; radiotherapy ; Re-Irradiation ; Tumor Burden ; Tumor Microenvironment
    ISSN: 1648-9144
    ISSN: 1010-660X
    E-ISSN: 1648-9144
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Source: ProQuest Central
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