196 research outputs found

    Nanoscale Electronic Order in Iron Pnictides

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    The charge distribution in RFeAs (R=La, Sm) iron pnictides is probed using As NQR. Whereas undoped and optimally-doped/overdoped compounds feature a single charge environment, two charge environments are detected in the underdoped region. Spin- lattice relaxation measurements show their coexistence at the nanoscale. Together with the quantitative variations of the spectra with doping, they point at a local electronic order in the iron layers, where low- and high-doping-like regions would coexist. Implications for the interplay of static magnetism and superconductivity are discussed

    Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

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    Peer reviewedPublisher PD

    Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

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    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

    Movement asymmetries in horses presented for prepurchase or lameness examination

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    Background The increasing popularity of objective gait analysis makes application in prepurchase examinations (PPE) a logical next step. Therefore, there is a need to have more understanding of asymmetry during a PPE in horses described on clinical evaluation as subtly lame.Objectives The objective of this study is to objectively compare asymmetry in horses raising minor vet concerns in a PPE and in horses raising major vet concerns with that found in horses presented with subtle single-limb lameness, and to investigate the effect of age/discipline on the clinicians' interpretation of asymmetry on the classification of minor vet concerns in a PPE.Study Design Clinical case-series.Methods Horses presented for PPE (n = 98) or subjectively evaluated as single limb low-grade (1-2/5) lame (n = 24, 13 forelimb lame, 11 hindlimb lame), from the patient population of a single clinic, were enrolled in the study provided that owners were willing to participate. Horses undergoing PPE were assigned a classification of having minor vet concerns (n = 84) or major vet concerns (n = 14) based on findings during the dynamic-orthopaedic part of the PPE. Lame horses were only included if pain-related lameness was confirmed by an objective improvement after diagnostic analgesia exceeding daily variation determined for equine symmetry parameters using optical motion capture. Clinical evaluation was performed by six different clinicians, each with >= 8 years of equine orthopaedic experience. Vertical movement symmetry was measured using optical motion capture, simultaneously with the orthopaedic examination. Data were analysed using previously described parameters and mixed model analysis and least squares means were used to calculate differences between groups.Results There was no effect of age or discipline on the levels of asymmetry within PPE horses raising minor vet concerns. MinDiff and RUD of the head discriminated between forelimb lame and PPE horses raising minor vet concerns; MinDiff, MaxDiff, RUD of the Pelvis, HHDswing and HHDstance did so for hindlimb lameness. Two lameness patterns differentiated both forelimb and hindlimb lame from PPE horses with minor vet concerns: RUD Poll + MinDiff Withers - RUD Pelvis and RUD Pelvis + RUD Poll - MinDiff Withers. Correcting for vertical range of motion enabled differentiation of PPE horses with minor vet concerns from PPE horses with major vet concerns.Main Limitations Objective data only based on trot on soft surface, limited number of PPE horses with major vet concerns.Conclusions Combinations of kinematic parameters discriminate between PPE horses with minor vet concerns and subtly lame horses, though overlap exists

    Sulphur limitation and early sulphur deficiency responses in poplar: significance of gene expression, metabolites, and plant hormones

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    The influence of sulphur (S) depletion on the expression of genes related to S metabolism, and on metabolite and plant hormone contents was analysed in young and mature leaves, fine roots, xylem sap, and phloem exudates of poplar (Populus tremula×Populus alba) with special focus on early consequences. S depletion was applied by a gradual decrease of sulphate availability. The observed changes were correlated with sulphate contents. Based on the decrease in sulphate contents, two phases of S depletion could be distinguished that were denominated as ‘S limitation’ and ‘early S deficiency’. S limitation was characterized by improved sulphate uptake (enhanced root-specific sulphate transporter PtaSULTR1;2 expression) and reduction capacities (enhanced adenosine 5â€Č-phosphosulphate (APS) reductase expression) and by enhanced remobilization of sulphate from the vacuole (enhanced putative vacuolar sulphate transporter PtaSULTR4;2 expression). During early S deficiency, whole plant distribution of S was impacted, as indicated by increasing expression of the phloem-localized sulphate transporter PtaSULTR1;1 and by decreasing glutathione contents in fine roots, young leaves, mature leaves, and phloem exudates. Furthermore, at ‘early S deficiency’, expression of microRNA395 (miR395), which targets transcripts of PtaATPS3/4 (ATP sulphurylase) for cleavage, increased. Changes in plant hormone contents were observed at ‘early S deficiency’ only. Thus, S depletion affects S and plant hormone metabolism of poplar during ‘S limitation’ and ‘early S deficiency’ in a time series of events. Despite these consequences, the impact of S depletion on growth of poplar plants appears to be less severe than in Brassicaceae such as Arabidopsis thaliana or Brassica sp

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
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