454 research outputs found
Immune dysregulation as a cause of autoinflammation in fragile X premutation carriers: link between FMRI CGG repeat number and decreased cytokine responses.
BackgroundIncreased rates of autoinflammatory and autoimmune disorders have been observed in female premutation carriers of CGG repeat expansion alleles of between 55-200 repeats in the fragile X mental retardation 1 (FMR1) gene. To determine whether an abnormal immune profile was present at a cellular level that may predispose female carriers to autoinflammatory conditions, we investigated dynamic cytokine production following stimulation of blood cells. In addition, splenocyte responses were examined in an FMR1 CGG knock-in mouse model of the fragile X premutation.MethodsHuman monocyte and peripheral blood leukocytes (PBLs) were isolated from the blood of 36 female FMR1 premutation carriers and 15 age-matched controls. Cells were cultured with media alone, LPS or PHA. In the animal model, splenocytes were isolated from 32 CGG knock-in mice and 32 wild type littermates. Splenocytes were cultured with media alone or LPS or PMA/Ionomycin. Concentrations of cytokines (GM-CSF, IL-1β, IL-6, IL-10, IL-13, IL-17, IFNγ, TNFα, and MCP-1) were determined from the supernatants of cellular cultures via Luminex multiplex assay. Additionally, phenotypic cellular markers were assessed on cells isolated from human subjects via flow cytometry.ResultsWe found decreases in cytokine production in human premutation carriers as well as in the FMR1 knock-in mice when compared with controls. Levels of cytokines were found to be associated with CGG repeat length in both human and mouse. Furthermore, T cells from human premutation carriers showed decreases in cell surface markers of activation when compared with controls.ConclusionsIn this study, FMR1 CGG repeat expansions are associated with decreased immune responses and immune dysregulation in both humans and mice. Deficits in immune responses in female premutation carriers may lead to increased susceptibility to autoimmunity and further research is warranted to determine the link between FMR1 CGG repeat lengths and onset of autoinflammatory conditions
Magnesium sulphate at 30 to 34 weeks' gestational age: neuroprotection trial (MAGENTA) -study protocol
Extent: 9 p.BACKGROUND: Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages. The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks’ gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age. METHODS/DESIGN: DESIGN: Randomised, multicentre, placebo controlled trial. INCLUSION CRITERIA: Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks’ gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate. TRIAL ENTRY & RANDOMISATION: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo. TREATMENT GROUPS: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes. PRIMARY STUDY OUTCOME: Death or cerebral palsy measured in children at two years’ corrected age. SAMPLE SIZE: 1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). DISCUSSION: Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks’ gestation is both important and relevant for clinical practice globally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry - ACTRN12611000491965Caroline A. Crowther, Philippa F. Middleton, Dominic Wilkinson, Pat Ashwood and Ross Haslam for the MAGENTA Study Grou
Air Pollution and Lymphocyte Phenotype Proportions in Cord Blood
Effects of air pollution on morbidity and mortality may be mediated by alterations in immune competence. In this study we examined short-term associations of air pollution exposures with lymphocyte immunophenotypes in cord blood among 1,397 deliveries in two districts of the Czech Republic. We measured fine particulate matter < 2.5 μm in diameter (PM(2.5)) and 12 polycyclic aromatic hydrocarbons (PAHs) in 24-hr samples collected by versatile air pollution samplers. Cord blood samples were analyzed using a FACSort flow cytometer to determine phenotypes of CD3(+) T-lymphocytes and their subsets CD4(+) and CD8(+), CD19(+) B-lymphocytes, and natural killer cells. The mothers were interviewed regarding sociodemographic and lifestyle factors, and medical records were abstracted for obstetric, labor and delivery characteristics. During the period 1994 to 1998, the mean daily ambient concentration of PM(2.5) was 24.8 μg/m(3) and that of PAHs was 63.5 ng/m(3). In multiple linear regression models adjusted for temperature, season, and other covariates, average PAH or PM(2.5) levels during the 14 days before birth were associated with decreases in T-lymphocyte phenotype fractions (i.e., CD3(+) CD4(+), and CD8(+)), and a clear increase in the B-lymphocyte (CD19(+)) fraction. For a 100-ng/m(3) increase in PAHs, which represented approximately two standard deviations, the percentage decrease was −3.3% [95% confidence interval (CI), −5.6 to −1.0%] for CD3(+), −3.1% (95% CI, −4.9 to −1.3%) for CD4(+), and −1.0% (95% CI, −1.8 to −0.2%) for CD8(+) cells. The corresponding increase in the CD19(+) cell proportion was 1.7% (95% CI, 0.4 to 3.0%). Associations were similar but slightly weaker for PM(2.5). Ambient air pollution may influence the relative distribution of lymphocyte immunophenotypes of the fetus
Structure of Be probed via secondary beam reactions
The low-lying level structure of the unbound neutron-rich nucleus Be
has been investigated via breakup on a carbon target of secondary beams of
B at 35 MeV/nucleon. The coincident detection of the beam velocity
Be fragments and neutrons permitted the invariant mass of the
Be+ and Be++ systems to be reconstructed. In the case of
the breakup of B, a very narrow structure at threshold was observed in
the Be+ channel. Contrary to earlier stable beam fragmentation
studies which identified this as a strongly interacting -wave virtual state
in Be, analysis here of the Be++ events demonstrated that
this was an artifact resulting from the sequential-decay of the
Be(2) state. Single-proton removal from B was found to
populate a broad low-lying structure some 0.70 MeV above the neutron-decay
threshold in addition to a less prominent feature at around 2.4 MeV. Based on
the selectivity of the reaction and a comparison with (0-3)
shell-model calculations, the low-lying structure is concluded to most probably
arise from closely spaced J=1/2 and 5/2 resonances
(E=0.400.03 and 0.85 MeV), whilst the broad
higher-lying feature is a second 5/2 level (E=2.350.14 MeV). Taken
in conjunction with earlier studies, it would appear that the lowest 1/2
and 1/2 levels lie relatively close together below 1 MeV.Comment: 14 pages, 13 figures, 2 tables. Accepted for publication in Physical
Review
Earthworm records and habitat associations in the British Isles
The National Earthworm Recording Scheme (NERS) is the most comprehensive national database of earthworm species occurrence records for the British Isles, and possibly for any individual country in the world. Utilising the NERS database, we sought to update the current knowledge of earthworm species occurrences in the UK, Ireland and Channel Islands; identify species-specific habitat and microhabitat associations; reveal any biases and complementarities between amateur naturalist and research-related earthworm record collection; and inform how future earthworm sampling can be better focussed to improve our knowledge of earthworm ecology. We found that the most commonly occurring earthworm species were present in farmland and woodland, and recovered via soil pit sampling, the most common habitat-sampling protocol combinations. However, several earthworm species showed specificity to alternative habitats (such as trees, wetlands, and compost), and association with microhabitat (non-soil) sampling. There were clear disparities between scientific researchers and amateur naturalist recorders in terms of habitat types visited and sampling protocols/microhabitats used in the collection of earthworm records. Most importantly, we found that earthworm species currently considered to be nationally ‘rare’ in the British Isles are significantly associated with the most under-represented habitat-protocol/microhabitat combinations (forest deadwood and other microhabitats, in addition to scrubland, wetland and heathland habitats), and thus may not be rare, only under-sampled. We therefore encourage earthworm researchers and recorders to give greater attention to these situations, to gain new insights into these earthworm species' ecologies and distributions. Finally, we would like to promote the establishment of earthworm recording schemes in other countries, to enable national and global collaborative monitoring of earthworm responses to environmental change
Structure of 12Be: intruder d-wave strength at N=8
The breaking of the N=8 shell-model magic number in the 12Be ground state has
been determined to include significant occupancy of the intruder d-wave
orbital. This is in marked contrast with all other N=8 isotones, both more and
less exotic than 12Be. The occupancies of the 0 hbar omega neutron p1/2-orbital
and the 1 hbar omega, neutron d5/2 intruder orbital were deduced from a
measurement of neutron removal from a high-energy 12Be beam leading to bound
and unbound states in 11Be.Comment: 5 pages, 2 figure
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