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  • 1
    Language: English
    In: Science (New York, N.Y.), 29 June 2012, Vol.336(6089), pp.1704-8
    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 F(2) 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): Genes, Plant ; Multigene Family ; Antineoplastic Agents, Phytogenic -- Biosynthesis ; Noscapine -- Metabolism ; Papaver -- Genetics
    ISSN: 0036-8075
    E-ISSN: 1095-9203
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  • 2
    Language: English
    In: Science (New York, N.Y.), 17 July 2015, Vol.349(6245), pp.309-12
    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): Benzylisoquinolines -- Metabolism ; Cytochrome P-450 Enzyme System -- Metabolism ; Isoquinolines -- Metabolism ; Morphinans -- Metabolism ; Papaver -- Enzymology ; Plant Proteins -- Metabolism ; Quaternary Ammonium Compounds -- Metabolism
    ISSN: 0036-8075
    E-ISSN: 1095-9203
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  • 3
    Article
    Article
    2015
    ISSN: 1354-4187 
    In: British Journal of Learning Disabilities, December 2015, Vol.43(4), pp.246-253
    Description: Accessible summary: More people with learning disabilities are living longer. This is a good news story! But, the bad news is that they do not live as long as the rest of the population. Health and other services need to be better organised to ensure that people with learning disabilities get better healthcare and other services which would help them lead more healthy lives. Most older people with learning disabilities live at home with their Mum or Dad, who are getting older too and find life more difficult. Care and support services need to adapt as families' needs change, but often this does not happen. We need to know more about these problems, which people with learning disabilities and their family carers face as they get older. This article looks at what we know and what more we need to find out to help older people with learning disabilities and their family carers live happier and healthier lives. Abstract: Background: Growing numbers of people with learning disabilities are now living into older age. This study aims to examine the state of knowledge about their lives and the challenges that ageing has for both family carers and policymakers and practitioners. Materials and Methods: The article synthesises existing research in the fields of learning disability, ageing and family and social care with a view to learning lessons from these separate fields, identifying possibilities for collaboration and identifying gaps in knowledge. Results: The article concludes that existing research in the fields of ageing and family and social care can add significantly to an understanding of the impact of ageing on people with learning disabilities and their carers but, to date, there has been little collaboration or sharing of knowledge between the three areas. Conclusion: The article concludes that further research is required to fully understand the impact of ageing on the quality of life of people with learning disabilities and their family carers and to inform the design and delivery of services. A useful and productive way forward would be learn from and to work with researchers in cogniscent fields, notably, but not only, in the fields of social gerontology and family and social care. Special Issue: Aging and People with Learning Disabilities. References
    Subject(s): Family ; Health &Amp; Social Care Policy And Practice ; Learning Intellectual Disabilities ; Research
    ISSN: 1354-4187
    E-ISSN: 1468-3156
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  • 4
    Language: English
    In: Critical Care Medicine, 2012, Vol.40, pp.1-328
    ISSN: 0090-3493
    Source: Wolters Kluwer - Ovid - Lippincott Williams & Wilkins (via CrossRef)
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  • 5
    Language: English
    In: Justice System Journal, 01 May 2010, Vol.31(2), pp.225-241
    Description: This article examines how the presence of judicial elections on the ballot impacts voter participation on direct democracy measures affecting justice. Ballot roll-off occurs on judicial elections and direct democracy measures for similar reasons. We explore the linkage between judicial elections...
    Subject(s): Law
    ISSN: 0098-261X
    E-ISSN: 2327-7556
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  • 6
    Article
    Article
    2012
    ISSN: 0002-5240 
    Language: English
    In: Algebra universalis, 2012, Vol.67(4), pp.347-374
    Description: An algebra with two binary operations · and +  that are commutative, associative, and idempotent is called a bisemilattice. A bisemilattice that satisfies Birkhoff’s equation x · ( x + y ) =  x + ( x · y ) is a Birkhoff system. Each bisemilattice determines, and is determined by, two semilattices, one for the operation +  and one for the operation ·. A bisemilattice for which each of these semilattices is a chain is called a bichain. In this note, we characterize the finite bichains that are weakly projective in the variety of Birkhoff systems as those that do not contain a certain three-element bichain. As subdirectly irreducible weak projectives are splitting, this provides some insight into the fine structure of the lattice of subvarieties of Birkhoff systems.
    Subject(s): Primary: 06A12 ; Secondary: 08B30 ; 03E73
    ISSN: 0002-5240
    E-ISSN: 1420-8911
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  • 7
    Article
    Article
    2018
    ISSN: 0002-5240 
    Language: English
    In: Algebra universalis, 2018, Vol.79(2), pp.1-31
    Description: For L a complete lattice L and $$\mathfrak {X}=(X,(R_i)_I)$$ X = ( X , ( R i ) I ) a relational structure, we introduce the convolution algebra $$L^{\mathfrak {X}}$$ L X . This algebra consists of the lattice $$L^X$$ L X equipped with an additional $$n_i$$ n i -ary operation $$f_i$$ f i for each $$n_i+1$$ n i + 1 -ary relation $$R_i$$ R i of $$\mathfrak {X}$$ X . For $$\alpha _1,\ldots ,\alpha _{n_i}\in L^X$$ α 1 , … , α n i ∈ L X and $$x\in X$$ x ∈ X we set $$f_i(\alpha _1,\ldots ,\alpha _{n_i})(x)=\bigvee \{\alpha _1(x_1)\wedge \cdots \wedge \alpha _{n_i}(x_{n_i}):(x_1,\ldots ,x_{n_i},x)\in R_i\}$$ f i ( α 1 , … , α n i ) ( x ) = ⋁ { α 1 ( x 1 ) ∧ ⋯ ∧ α n i ( x n i ) : ( x 1 , … , x n i , x ) ∈ R i } . For the 2-element lattice 2, $$2^\mathfrak {X}$$ 2 X is the reduct of the familiar complex algebra $$\mathfrak {X}^+$$ X + obtained by removing Boolean complementation from the signature. It is shown that this construction is bifunctorial and behaves well with respect to one-one and onto maps and with respect to products. When L is the reduct of a complete Heyting algebra, the operations of $$L^\mathfrak {X}$$ L X are completely additive in each coordinate and $$L^\mathfrak {X}$$ L X is in the variety generated by $$2^\mathfrak {X}$$ 2 X . Extensions to the construction are made to allow for completely multiplicative operations defined through meets instead of joins, as well as modifications to allow for convolutions of relational structures with partial orderings. Several examples are given.
    Subject(s): Complex algebra ; Heyting algebra ; Boolean algebra with operators ; Kripke frame ; Convolution ; Type-2 truth value algebra ; Relation algebra
    ISSN: 0002-5240
    E-ISSN: 1420-8911
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  • 8
    Article
    Article
    2016
    ISSN: 0884-8173 
    In: International Journal of Intelligent Systems, March 2016, Vol.31(3), pp.257-275
    Description: The algebra of truth values of type‐2 fuzzy sets is the set of maps from the unit interval to itself with convolution ordering. In applications of type‐2 fuzzy sets, the full algebra is seldom used, but rather certain subalgebras that satisfy useful algebraic properties. The algebra of truth values of type‐2 fuzzy sets is not itself a lattice, but the subalgebras considered here are lattices and, in fact, are complete distributive lattices. The subalgebras of special interest are the lattice of convex normal maps, the lattice of convex strongly normal maps, and the lattice of upper semicontinuous convex normal maps. We review and summarize some interesting properties of these subalgebras. A special feature of our treatment is a representation of these algebras as sets of monotone functions with pointwise order, making the operations more intuitive.
    Subject(s): Computer Science;
    ISSN: 0884-8173
    E-ISSN: 1098-111X
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  • 9
    Language: English
    In: Nucleic acids research, May 2014, Vol.42(9), pp.5644-56
    Description: DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3(ATR), Rad26ATRIP, Crb2(53BP1) or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low...
    Subject(s): DNA Breaks, Double-Stranded ; DNA Cleavage ; Genomic Instability ; Recombinational DNA Repair ; Schizosaccharomyces -- Genetics
    ISSN: 0305-1048
    E-ISSN: 1362-4962
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  • 10
    Language: English
    In: Nucleic acids research, 29 February 2016, Vol.44(4), pp.1703-17
    Description: The formation of RNA-DNA hybrids, referred to as R-loops, can promote genome instability and cancer development. Yet the mechanisms by which R-loops compromise genome instability are poorly understood. Here, we establish roles for the evolutionarily conserved Nrl1 protein in pre-mRNA splicing regulation, R-loop suppression and in maintaining genome stability. nrl1Δ mutants exhibit endogenous DNA damage, are sensitive to exogenous DNA damage, and have defects in homologous recombination (HR) repair. Concomitantly, nrl1Δ cells display significant changes in gene expression, similar to those induced by DNA damage in wild-type cells. Further, we find that nrl1Δ cells accumulate high levels of R-loops, which co-localize with HR repair factors and require Rad51 and Rad52 for their formation. Together, our findings support a model in which R-loop accumulation and subsequent DNA damage sequesters HR factors, thereby compromising HR repair at endogenously or exogenously induced DNA damage sites, leading to genome instability.
    Subject(s): Alternative Splicing -- Genetics ; Genomic Instability -- Genetics ; Homologous Recombination -- Genetics ; RNA Precursors -- Genetics ; Schizosaccharomyces Pombe Proteins -- Genetics
    ISSN: 03051048
    E-ISSN: 1362-4962
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