102 research outputs found
Accessing elite nurses for research: reflections on the theoretical and practical issues of telephone interviewing
Elite groups are interesting as they frequently are powerful (in terms of position, knowledge and influence) and enjoy considerable authority. It is important, therefore, to involve them in research concerned with understanding social contexts and processes. This is particularly pertinent in healthcare, where considerable strategic development and change are features of everyday practice that may be guided or perceived as being guided, by elites.
This paper evolved from a study investigating the availability and role of nurses whose remit involved leading nursing research and development within acute NHS Trusts in two health regions in Southern England. The study design included telephone interviews with Directors of Nursing Services during which time the researchers engaged in a reflective analysis of their experiences of conducting research with an `elite' group. Important issues identified were the role of gatekeepers, engagement with elites and the use of the telephone interview method in this context. The paper examines these issues and makes a case for involving executive nurses in further research. The paper also offers strategies to help researchers design and implement telephone interview studies successfully to maximise access to the views and experiences of `hard to reach groups', such as elites, while minimising the associated disruption
Characterisation of carbon nanotubes in the context of toxicity studies
Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies
EDS1 complexes are not required for PRR responses and execute TNLâETI from the nucleus in Nicotiana benthamiana
Heterodimeric complexes incorporating the lipase-like proteins EDS1 with PAD4 or SAG101 are central hubs in plant innate immunity. EDS1 functions encompass signal relay from TIR domain-containing intracellular NLR-type immune receptors (TNLs) towards RPW8-type helper NLRs (RNLs) and, in Arabidopsis thaliana, bolstering of signaling and resistance mediated by cell-surface pattern recognition receptors (PRRs). Increasing evidence points to the activation of EDS1 complexes by small molecule binding. We used CRISPR/Cas-generated mutant lines and agroinfiltration-based complementation assays to interrogate functions of EDS1 complexes in Nicotiana benthamiana. We did not detect impaired PRR signaling in N. benthamiana lines deficient in EDS1 complexes or RNLs. Intriguingly, in assays monitoring functions of SlEDS1-NbEDS1 complexes in N. benthamiana, mutations within the SlEDS1 catalytic triad could abolish or enhance TNL immunity. Furthermore, nuclear EDS1 accumulation was sufficient for N. benthamiana TNL (Roq1) immunity. Reinforcing PRR signaling in Arabidopsis might be a derived function of the TNL/EDS1 immune sector. Although Solanaceae EDS1 functionally depends on catalytic triad residues in some contexts, our data do not support binding of a TNL-derived small molecule in the triad environment. Whether and how nuclear EDS1 activity connects to membrane pore-forming RNLs remains unknown
Interaction Analysis between HLA-DRB1 Shared Epitope Alleles and MHC Class II Transactivator CIITA Gene with Regard to Risk of Rheumatoid Arthritis
Abstract HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases. We wanted to explore whether the risk variant rs3087456 in the CIITA gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA. We tested this hypothesis in a case-control study with 11767 individuals from four European Caucasian populations (6649 RA cases and 5118 controls). We found no significant additive interaction for risk alleles among Swedish Caucasians with RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: 20.2-0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA) presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: 20.05-0.6, ACPA negative: n = 2268, AP = 20.2, 95%CI: 21.0-0.6). We further found no significant interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from British, Dutch and Norwegian populations also indicated an absence of significant interaction between genetic variants in CIITA and SE alleles with regard to RA risk. Our data suggest that risk from the CIITA locus is independent of the major risk for RA from HLA-DRB1 SE alleles, given that no significant interaction between rs3087456 and SE alleles was observed. Since a biological link between products of these genes is evident, the genetic contribution from CIITA and class II antigens in the autoimmune process may involve additional unidentified factors
Pathogen effector recognition-dependent association of NRG1 with EDS1 and SAG101 in TNL receptor immunity
Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 âhelperâ NLRs (RNLs) cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). The mechanism of RNL/EDS1 family protein cooperation is not understood. Here, we present genetic and molecular evidence for exclusive EDS1/SAG101/NRG1 and EDS1/PAD4/ADR1 co-functions in TNL immunity. Using immunoprecipitation and mass spectrometry, we show effector recognition-dependent interaction of NRG1 with EDS1 and SAG101, but not PAD4. An EDS1-SAG101 complex interacts with NRG1, and EDS1-PAD4 with ADR1, in an immune-activated state. NRG1 requires an intact nucleotide-binding P-loop motif, and EDS1 a functional EP domain and its partner SAG101, for induced association and immunity. Thus, two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) mediate TNL receptor defence signalling
A comparative genomics study of 23 Aspergillus species from section Flavi
Section Flavi encompasses both harmful and beneficial Aspergillus species, such as Aspergillus oryzae, used in food fermentation and enzyme production, and Aspergillus flavus, food spoiler and mycotoxin producer. Here, we sequence 19 genomes spanning section Flavi and compare 31 fungal genomes including 23 Flavi species. We reassess their phylogenetic relationships and show that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans and identify high genome diversity, especially in sub-telomeric regions. We predict abundant CAZymes (598 per species) and prolific secondary metabolite gene clusters (73 per species) in section Flavi. However, the observed phenotypes (growth characteristics, polysaccharide degradation) do not necessarily correlate with inferences made from the predicted CAZyme content. Our work, including genomic analyses, phenotypic assays, and identification of secondary metabolites, highlights the genetic and metabolic diversity within section Flavi.Peer reviewe
Measurement of antibodies to pneumococcal, meningococcal and haemophilus polysaccharides, and tetanus and diphtheria toxoids using a 19-plexed assay
Interaction Analysis between HLA-DRB1 Shared Epitope Alleles and MHC Class II Transactivator CIITA Gene with Regard to Risk of Rheumatoid Arthritis
HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases
VX-659âTezacaftorâIvacaftor in patients with cystic fibrosis and one or two Phe508del alleles
BACKGROUND: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659âtezacaftorâivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis. METHODS: We evaluated the effects of VX-659âtezacaftorâivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659âtezacaftorâivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508delâMF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508delâPhe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1). RESULTS: VX-659âtezacaftorâivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659âtezacaftorâivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659âtezacaftorâivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P<0.001) of up to 13.3 points in patients with Phe508delâMF genotypes; in patients with the Phe508delâPhe508del genotype already receiving tezacaftorâivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV1. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis QuestionnaireâRevised improved in both patient populations. CONCLUSIONS: Robust in vitro activity of VX-659âtezacaftorâivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508delâMF or Phe508delâPhe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351. opens in new tab and NCT03029455. opens in new tab.
Les terres agricoles face Ă lâurbanisation
La perte de terres agricoles liĂ©es Ă lâurbanisation constitue lâune des facettes de la consommation des terres. CommencĂ© dans les annĂ©es 1970, ce phĂ©nomĂšne â essentiellement dĂ» Ă lâĂ©talement urbain â prend des proportions jusque-lĂ inĂ©galĂ©es. Les consĂ©quences de ces processus dâartificialisation sont multiples et portent Ă la fois sur la production et sur la sĂ©curitĂ© alimentaire ainsi que sur la perte de biodiversitĂ©. Ces processus interrogent aussi les formes de solidaritĂ© territoriale entre les villes et les espaces pĂ©ri-urbains et ruraux. Issu dâune collaboration scientifique lancĂ©e au dĂ©but des annĂ©es 2010 entre lâUniversitĂ© de technologie de Sydney (University of Technology Sydney, UTS) et lâInstitut national de recherche en sciences et technologies pour lâenvironnement et lâagriculture (Irstea), cet ouvrage aborde des points clĂ©s de la problĂ©matique de la consommation des terres en se focalisant sur les terres agricoles en France et en Australie. PlutĂŽt que dâoffrir une analyse comparative approfondie de la planification des terres agricoles pĂ©riurbaines entre les deux pays, il propose une exploration des « boĂźtes Ă outils » de lâingĂ©nierie territoriale dĂ©veloppĂ©es et mobilisĂ©es pour faire face Ă lâenjeu de la perte de terres agricoles liĂ©e Ă lâurbanisation. Il offre Ă©galement un « arrĂȘt sur image » dans un panorama de champs de recherche en pleine Ă©volution, autant du point de vue thĂ©orique que mĂ©thodologique
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