22 research outputs found
Biomonitoring of arsenic, cadmium and lead in two artisanal and small-scale gold mining areas in Zimbabwe
People living and working in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to elemental mercury (Hg), which is used for gold extraction. However, additional exposure to other toxic metals such as arsenic (As), cadmium (Cd) and lead (Pb) may result from mining-related activities and could be ingested via dust, water or food. In these areas, only limited biomonitoring data is available for toxic metals other than Hg. In particular, data about the exposure to As, Cd and Pb is unavailable for the Zimbabwean population. Therefore, we conducted a cross-sectional study in two ASGM areas in Zimbabwe to evaluate the internal exposure to these metals. In total, urine and blood samples from 207 people that identified themselves as miners were collected and analysed for As and Cd in urine as well as Pb in blood by GF-AAS. Median levels (interquartile ranges in ÎŒg/l) of As and Pb were 9.7 ÎŒg/l (4.0, 18.5) and 19.7 ÎŒg/l (12.5, 34.5), respectively. The 25th percentile and the median for Cd were below the limit of detection (0.5 ÎŒg/l); the 75th percentile was at 0.9 ÎŒg/l. The results were compared to reference values found for the general population in the USA and Germany, and a significant number of participants exceeded these values (As, 33 %; Cd, 27 %; Pb, 32 %), indicating a relevant exposure to toxic metals. Although not representative for the Zimbabwean population, our results demonstrate that the exposure to toxic metals is relevant for the public health in Zimbabwe and requires further investigation
Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets
Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications. Though global CNS delivery of antibodies can be achieved by intrathecal application, these procedures are invasive. A non-invasive method to bring antibodies into the CNS reliably and reproducibly remains an important unmet need in neurology. In the present study, we show that intranasal application of a mouse monoclonal antibody against the neurite growth-inhibiting and plasticity-restricting membrane protein Nogo-A leads to a rapid transfer of significant amounts of antibody to the brain and spinal cord in intact adult rats. Daily intranasal application for 2 wk of anti-Nogo-A antibody enhanced growth and compensatory sprouting of corticofugal projections and functional recovery in rats after large unilateral cortical strokes. These findings are a starting point for clinical translation for a less invasive route of application of therapeutic antibodies to CNS targets for many neurological indications
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Blood Leukocyte Dna Methylation Predicts Risk of Future Myocardial infarction and Coronary Heart Disease
BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.
METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.
RESULTS: Among 11â461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate
CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD
DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.
BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (nâ=â8863) and trans-ethnic replication in African Americans (nâ=â4111). We found differential methylation at 218 CpG sites to be associated with CRP (Pâ<â1.15âĂâ10-7) in the discovery panel of European ancestry and replicated (Pâ<â2.29âĂâ10-4) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (Pâ<â8.47âĂâ10-5), ten (17%) CpG sites were associated with a nearby genetic variant (Pâ<â2.50âĂâ10-3), and 51 (88%) were also associated with at least one related cardiometabolic entity (Pâ<â9.58âĂâ10-5). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants. CONCLUSION: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation
PEPS DataFlow : Analyse de données pour des capteurs fluidiques à haute précision
International audienc
Le rĂ©seau dâacteurs du tourisme, outil dâinsertion des entreprises dans leur territoire
Une enquĂȘte rĂ©alisĂ©e auprĂšs dâentreprises appartenant Ă trois rĂ©seaux tou -ristiques (Onlylyon, le Voyage Ă Nantes et Vignobles & DĂ©couvertes en Savoie) montre que celles-ci nâattendent pas de retombĂ©es directes du rĂ©seau. Les effets positifs quâelles perçoivent de cette adhĂ©sion concer -nent surtout lâinsertion dans leur territoire (accĂšs Ă lâinformation, actions de promotion âŠ). La prise en compte de lâavis des diffĂ©rentes parties prenantes est en tout cas essentielle pour construire un rĂ©seau solide
Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets
Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications. Though global CNS delivery of antibodies can be achieved by intrathecal application, these procedures are invasive. A non-invasive method to bring antibodies into the CNS reliably and reproducibly remains an important unmet need in neurology. In the present study, we show that intranasal application of a mouse monoclonal antibody against the neurite growth-inhibiting and plasticity-restricting membrane protein Nogo-A leads to a rapid transfer of significant amounts of antibody to the brain and spinal cord in intact adult rats. Daily intranasal application for 2 wk of anti-Nogo-A antibody enhanced growth and compensatory sprouting of corticofugal projections and functional recovery in rats after large unilateral cortical strokes. These findings are a starting point for clinical translation for a less invasive route of application of therapeutic antibodies to CNS targets for many neurological indications.ISSN:0027-8424ISSN:1091-649