571 research outputs found

    Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8

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    Nucleoside triphosphate diphosphohydrolases 1, 2, 3 and 8 (NTPDases 1, 2, 3 and 8) are the dominant ectonucleotidases and thereby expected to play important roles in nucleotide signaling. Distinct biochemical characteristics of individual NTPDases should allow them to regulate P2 receptor activation differentially. Therefore, the biochemical and kinetic properties of these enzymes were compared. NTPDases 1, 2, 3 and 8 efficiently hydrolyzed ATP and UTP with Km values in the micromolar range, indicating that they should terminate the effects exerted by these nucleotide agonists at P2X1- and P2Y2,4,11 receptors. Since NTPDase1 does not allow accumulation of ADP, it should terminate the activation of P2Y1,12,13 receptors far more efficiently than the other NTPDases. In contrast, NTPDases 2, 3 and 8 are expected to promote the activation of ADP specific receptors, because in the presence of ATP they produce a sustained (NTPDase2) or transient (NTPDases 3 and 8) accumulation of ADP. Interestingly, all plasma membrane NTPDases dephosphorylate UTP with a significant accumulation of UDP, favoring P2Y6 receptor activation. NTPDases differ in divalent cation and pH dependence, although all are active in the pH range of 7.0-.5. Various NTPDases may also distinctly affect formation of extracellular adenosine and therefore adenosine receptor-mediated responses, since they generate different amounts of the substrate (AMP) and inhibitor (ADP) of ecto-5-nucleotidase, the rate limiting enzyme in the production of adenosine. Taken together, these data indicate that plasma membrane NTPDases hydrolyze nucleotides in a distinctive manner and may therefore differentially regulate P2 and adenosine receptor signaling

    Compact planar lenses based on a pinhole and an array of single mode metallic slits

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    Plasmonic lenses are based on complex combinations of nanoscale high aspect ratio slits. We show that their design can be greatly simplified, keeping similar performance while releasing technological constraints. The simplified system, called Huygens lens, consists in a central aperture surrounded by several identical single mode slits in a thin gold layer that does not rely anymore on surface plasmons. The focusing behaviour with respect to the position and number of slits is investigated, and we demonstrate the interest of this design to get compact array of lenses

    Large magnetoresistance by Pauli blockade in hydrogenated graphene

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    We report the observation of a giant positive magnetoresistance in millimetre scale hydrogenated graphene with magnetic field oriented in the plane of the graphene sheet. A positive magnetoresistance in excess of 200\% at a temperature of 300 mK was observed in this configuration, reverting to negative magnetoresistance with the magnetic field oriented normal to the graphene plane. We attribute the observed positive, in-plane, magnetoresistance to Pauli-blockade of hopping conduction induced by spin polarization. Our work shows that spin polarization in concert with electron-electron interaction can play a dominant role in magnetotransport within an atomic monolayer.Comment: 6 pages, 3 figures, and supplemental informatio

    Infinite families of superintegrable systems separable in subgroup coordinates

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    A method is presented that makes it possible to embed a subgroup separable superintegrable system into an infinite family of systems that are integrable and exactly-solvable. It is shown that in two dimensional Euclidean or pseudo-Euclidean spaces the method also preserves superintegrability. Two infinite families of classical and quantum superintegrable systems are obtained in two-dimensional pseudo-Euclidean space whose classical trajectories and quantum eigenfunctions are investigated. In particular, the wave-functions are expressed in terms of Laguerre and generalized Bessel polynomials.Comment: 19 pages, 6 figure

    Hearing the voices of older adult patients: processes and findings to inform health services research

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    Background Clinical academic research and service improvement is planned using Patient and Public Involvement and Engagement (PPIE) but older PPIE participants are consulted less often due to the perception that they are vulnerable or hard to engage. Objectives To consult frail older adults about a recently adopted service, discharge to assess (D2A), and to prioritise services improvements and research topics associated with the design and delivery of discharge from hospital. To use successive PPIE processes to enable a permanent PPIE panel to be established. Participants Following guidance from an established hospital PPI panel 27 older adult participants were recruited. Participants from Black, Asian and Minority Ethnic (BAME) communities, affluent and non-affluent areas and varied social circumstances were included. Methods Focus groups and individual interviews were conducted in participants own homes or nearby social venues. Results Priorities for discharge included remaining independent despite often feeling lonely at home; to remain in hospital if needed; and for services to ensure effective communication with families. The main research priority identified was facilitating independence, whilst establishing a permanent PPIE panel involving older adults was viewed favourably. Conclusions Taking a structured approach to PPIE enabled varied older peoples’ voices to express their priorities and concerns into early discharge from hospital, as well as enabling the development of health services research into hospital discharge planning and management. Older people as participants identified research priorities after reflecting on their experiences. Listening and reflection enabled researchers to develop a new “Community PPIE Elders Panel” to create an enduring PPIE infrastructure for frail older housebound people to engage in research design, development and dissemination

    Distribution of Class 1 Integrons with IS26-Mediated Deletions in Their 3′-Conserved Segments in Escherichia coli of Human and Animal Origin

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    Class 1 integrons play a role in the emergence of multi-resistant bacteria by facilitating the recruitment of gene cassettes encoding antibiotic resistance genes. 512 E. coli strains sourced from humans (n = 202), animals (n = 304) and the environment (n = 6) were screened for the presence of the intI1 gene. In 31/79 integron positive E. coli strains, the gene cassette regions could not be PCR amplified using standard primers. DNA sequence analysis of 6 serologically diverse strains revealed atypical integrons harboured the dfrA5 cassette gene and only 24 bp of the integron 3′-conserved segment (CS) remained, due to the insertion of IS26. PCR targeting intI1 and IS26 followed by restriction fragment length polymorphism (RFLP) analysis identified the integron-dfrA5-IS26 element in 27 E. coli strains of bovine origin and 4 strains of human origin. Southern hybridization and transformation studies revealed the integron-dfrA5-IS26 gene arrangement was either chromosomally located or plasmid borne. Plasmid location in 4/9 E. coli strains and PCR linkage of Tn21 transposition genes with the intI1 gene in 20/31 strains, suggests this element is readily disseminated by horizontal transfer
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