22 research outputs found

    A rapid antibody screening haemagglutination test for predicting immunity to SARS-CoV-2 variants of concern

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    Background: Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. Methods: Firstly, we developed a receptor-binding domain-specific haemagglutination test (HAT) to Wuhan and VOC (alpha, beta, gamma and delta) and compared to pseudotype, microneutralisation and virus neutralisation assays in 835 convalescent sera. Secondly, we investigated the antibody response using the HAT after two doses of mRNA (BNT162b2) vaccination. Sera were collected at baseline, three weeks after the first and second vaccinations from older (80–99 years, n = 89) and younger adults (23–77 years, n = 310) and compared to convalescent sera from naturally infected individuals (1–89 years, n = 307). Results: Here we show that HAT antibodies highly correlated with neutralising antibodies (R = 0.72–0.88) in convalescent sera. Home-dwelling older individuals have significantly lower antibodies to the Wuhan strain after one and two doses of BNT162b2 vaccine than younger adult vaccinees and naturally infected individuals. Moverover, a second vaccine dose boosts and broadens the antibody repertoire to VOC in naïve, not previously infected older and younger adults. Most (72–76%) older adults respond after two vaccinations to alpha and delta, but only 58–62% to beta and gamma, compared to 96–97% of younger vaccinees and 68–76% of infected individuals. Previously infected older individuals have, similarly to younger adults, high antibody titres after one vaccination. Conclusions: Overall, HAT provides a surrogate marker for neutralising antibodies, which can be used as a simple inexpensive, rapid test. HAT can be rapidly adaptable to emerging VOC for large-scale evaluation of potentially decreasing vaccine effectiveness.publishedVersio

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Diurnal patterns of methane emission from a constructed wetland

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    The aim of the study was to investigate if methane emission in a constructed wetland changed in a diurnal pattern correlating to temperature, humidity or light conditions. The gas measurements were carried out with a static chamber technique. The wetland (in Nykvarn outside of Linköping, Sweden) takes care of wastewater to reduce the nitrogen loads. Measurements were carried out at three different occasions in the summer of 1998 on two sites in the wetland. One site was close to the inflow, inhabited by Lemnaceae, and another site was located further downstream inhabited by the emergent macrophyte Typha latifolia. The results showed a variation, but no discernible diurnal pattern. The Typha site had a methane emission rate of 166 mg CH4 m-2d-1 and the Lemnaceae site had an methane emission rate of 712 mg CH4 m-2d-1. In all experiments at the Typha site, the highest methane emission rate was obtained at sunrise

    Cell lysis of competitors and osmotrophy enhance growth of the bloom forming alga Gonyostomum semen

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    Abstract in UndeterminedThe nuisance alga Gonyostomum semen (Raphidophyceae) is known to form dense blooms in many freshwater bodies, and has increased its distribution and abundance. However, information on the mechanisms behind bloom formation and maintenance is scarce. Field observations indicate that G. semen may be favored in humic lakes, In the present study, we performed controlled laboratory experiments on cultures to test whether G. semen growth is enhanced by humic acids. In addition, we tested the mixotrophic capability of G. semen by providing it with Rhodomonas lacustris as prey. G. semen increased its growth rate in the presence of humic substances due to either acquisition of carbon or some unknown growth factor. Moreover, growth rate was enhanced in the presence of R. lacustris, which in turn was negatively influenced when cultured together with G. semen. We found no evidence of phagotrophy, but observed lysis of R. lacustris cells exposed to G. semen pre-grown with R, lacustris. Thus, our experiments suggest that cell lysis (probably via trichocyst action) and osmotrophy could be 2 mechanisms involved in establishing and maintaining dominance of G. semen in humic lakes
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