76 research outputs found

    Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2

    Get PDF
    In this study we analysed the outcome of the interaction between HPV-16 L2 and E2 on the transactivation and DNA replication functions of E2. When E2 was expressed on its own, it transactivated a number of E2-responsive promoters but co-expression of L2 led to the down-regulation of the transcription transactivation activity of the E2 protein. This repression is not mediated by an increased degradation of the E2 protein. In contrast, the expression of L2 had no effect on the ability of E2 to activate DNA replication in association with the viral replication factor E1. Deletion mutagenesis identified L2 domains responsible for binding to E2 (first 50 N-terminus amino acid residues) and down-regulating its transactivation function (residues 301–400). The results demonstrate that L2 selectively inhibits the transcriptional activation property of E2 and that there is a direct interaction between the two proteins, although this is not sufficient to mediate the transcriptional repression. The consequences of the L2–E2 interaction for the viral life cycle are discussed

    A preliminary validation study of PuO2 incorporation into zirconolite glass-ceramics

    Get PDF
    Zirconolite glass-ceramics are being developed as potential wasteforms for the disposition of Pu wastes in the UK. Previous studies utilised a variety of surrogates whilst this work uses both cold-press and sinter and hot isostatic press methods to validate the wasteform with PuO2. A cold press and sinter sample was fabricated as part of a validation study for plutonium incorporation in hot isostatically pressed (HIPed) wasteforms. The results confirmed the cold-press and sinter, achieved successful waste incorporation and a microstructure and phase assemblage that was in agreement with those expected of a HIPed equivalent. A HIP sample was fabricated of the same composition and characterised by SEM and XRD. Results were in agreement with the sintered sample and achieved complete waste incorporation into the glass-ceramic wasteform. These samples have demonstrated successful incorporation of PuO2 into glass-ceramic HIPed wasteforms proposed for processing Pu-based waste-streams in the UK

    New insights into the genetic etiology of Alzheimer's disease and related dementias.

    Get PDF
    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    New insights into the genetic etiology of Alzheimer's disease and related dementias

    Get PDF
    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    A comparison of the feeding and grazing behaviour of primiparous Holstein-Friesian and Jersey × Holstein-Friesian dairy cows

    Get PDF
    Peer-reviewed articleFood intake and feeding behaviour of Holstein-Friesian (HF) and Jersey × Holstein- Friesian (J × HF) dairy cows (14 primiparous cows of each genotype) were measured during a 54-day confinement period [cows offered a complete diet comprising conserved forage and concentrates; 66:34 dry matter (DM) basis], while herbage intakes and grazing behaviour were measured on three occasions during a 96-day grazing period. Throughout the experiment HF cows had a higher milk yield than J × HF cows (P < 0.05), while fat + protein yield was unaffected by genotype. During the confinement period HF cows had a higher food intake than the J × HF cows (P < 0.01), although DM intake/kg metabolic live weight (live weight0.75) was unaffected by genotype. With the exception of the number of ruminating bouts/day (P < 0.05), and idling time/day (P < 0.05), both of which were highest with the J × HF cows, genotype had no significant effect on any of the feeding behaviours examined during the confinement period. Herbage intake did not differ between genotypes during the grazing period, although when expressed on a kg live weight0.75 basis, intakes were highest with the J × HF cows (P < 0.05). While the smaller J × HF cows had fewer grazing bouts per day (P < 0.01), the mean duration of each grazing bout was longer (P < 0.001), resulting in a longer total grazing time (P < 0.05) and a greater number of grazing bites each day (P < 0.01). The smaller crossbred cows had to ‘work harder’ during the grazing period to achieve the same intakes as the larger HF cows.Department of Agriculture and Rural Development for Northern Ireland (DARD); Agri-Searc

    CsAlSi/sub 5/O/sub 12/: a possible host for /sup 137/Cs immobilization

    No full text
    CsAlSi/sub 5/O/sub 12/ exhibits more acid resistance than pollucite (CsAlSi/sub 2/O/sub 6/). At pH values of 1.02 and 1.40, the extraction of Cs from CsAlSi/sub 5/O/sub 12/ at 25/sup 0/C was approximately proportional to the square root of leach time. The Cs extraction at 25/sup 0/C varied as (H/sup +/)/sup 0/ /sup 36/ over the pH range of 1 to 6. Also, the Cs extraction in various brines at 300/sup 0/C/30 MPa was comparable with that for pollucite. CsAlSi/sub 5/O/sub 12/ can be crystallized at about 1000/sup 0/C from calcines if a small amount of CaO is present, but in the absence of such sintering acids, crystallization temperatures of about 1400/sup 0/C are necessary. Compatibility data were also obtained with respect to several other phases with which CsAlSi/sub 5/O/sub 12/ might be expected to coexist in tailored ceramics designed for high-level defense waste
    corecore