Recent exposure to ultrafine particles in school children alters miR-222 expression in the extracellular fraction of saliva

Background: Ultrafine particles (< 100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children. This study examined whether exposure to fine and ultrafine particulate matter (PM) is associated with changes in the extracellular content of miR-222 and miR-146a of children. Methods: Saliva was collected from 80 children at two different time points, circa 11 weeks apart and stabilized for RNA preservation. The extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We regressed the extracellular miRNA expression against recent exposure to ultrafine and fine particles measured at the school site using mixed models, while accounting for sex, age, BMI, passive smoking, maternal education, hours of television use, time of the day and day of the week. Results: Exposure to ultrafine particles (UFP) at the school site was positively associated with miR-222 expression in the extracellular fraction in saliva. For each IQR increase in particles in the class room (+8504 particles/cm(3)) or playground (+ 28776 particles/cm(3)), miR-222 was, respectively 23.5 % (95 % CI: 3.5 %-41.1 %; p = 0.021) or 29.9 % (95 % CI: 10.6 %-49.1 %; p = 0.0027) higher. No associations were found between miR-146a and recent exposure to fine and ultrafine particles. Conclusions: Our results suggest a possible epigenetic mechanism via which cells respond rapidly to small particles, as exemplified by miR-222 changes in the extracellular fraction of saliva

Maternal exposure to ambient black carbon particles and their presence in maternal and fetal circulation and organs : an analysis of two independent population-based observational studies

Funding European Research Council, Flemish Scientific Research Foundation, Kom op Tegen Kanker, UK Medical Research Council, and EU Horizon 2020. Acknowledgments The ENVIRONAGE birth cohort was initiated by the European Research Council (ERC-2012-StG 310898) and received additional funding from the Flemish Scientific Research Foundation and Kom op Tegen Kanker (KoTK). The detection equipment was funded by the METHUSALEM Program and the INCALO project (ERC-PoC). We acknowledge the Flemish Scientific Research Foundation (FWO; 1150920N to EB and G082317N). The SAFeR study was funded by the UK Medical Research Council (MR/L010011/1 and MR/P011535/1) and the EU's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie project PROTECTED (grant agreement number 722634) and FREIA project (grant agreement number 825100) as well as by NHS Grampian Endowments grants (16/11/056, 17/034, 18/14, 19/029, and 20/031) to PAF. We thank the midwives from the maternity ward of the East-Limburg Hospital in Genk, Belgium, for coordinating and supporting the study at the ward. We thank the Advanced Optical Microscopy Centre for the maintenance of the microscopic instruments. Moreover, we thank our colleagues from the Centre for Environmental Sciences for their hard work in collecting and processing the samples for the ENVIRONAGE birth cohort. Additionally, we thank the NHS Grampian Research Nurses and NHS Grampian R&D for their tireless recruitment work for the SAFeR study. We thank the past and present SAFeR team for their hard work with the fetuses and placentae. Finally, we thank the NHS Grampian Biorepository for their oversight role in SAFeR and assistance in processing and preparation of tissue sections.Peer reviewedPublisher PD

Children’s screen time alters the expression of saliva extracellular miR-222 and miR-146a

An imbalance between energy uptake and energy expenditure is the most important reason for increasing trends in obesity starting from early in life. Extracellular miRNAs are expressed in all bodily fluids and their expression is influenced by a broad range of stimuli. We examined whether screen time, physical activity and BMI are associated with children's salivary extracellular miR-222 and miR-146a expression. In 80 children the extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We studied the association between children's salivary extracellular miRNA expression and screen time, physical activity and BMI using mixed models, while accounting for potential confounders. We found that higher screen time was positively associated with salivary extracellular miR-222 and miR-146a levels. On average, one hour more screen time use per week was associated with a 3.44% higher miR-222 (95% CI: 1.34 to 5.58; p = 0.002) and 1.84% higher miR-146a (95% CI: -0.04 to 3.75; p = 0.055) level in saliva. BMI and physical activity of the child were not significantly associated with either miR-222 or miR-146a. A sedentary behaviour, represented by screen time use in children, is associated with discernible changes in salivary expression of miR-146a and or miR-222. These miRNA targets may emerge attractive candidates to explore the role of these exposures in developmental processes of children's health

Detection and localization of multiple rate changes in Poisson spike trains

Poster presentation from Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011. In statistical spike train analysis, stochastic point process models usually assume stationarity, in particular that the underlying spike train shows a constant firing rate (e.g. [1]). However, such models can lead to misinterpretation of the associated tests if the assumption of rate stationarity is not met (e.g. [2]). Therefore, the analysis of nonstationary data requires that rate changes can be located as precisely as possible. However, present statistical methods focus on rejecting the null hypothesis of stationarity without explicitly locating the change point(s) (e.g. [3]). We propose a test for stationarity of a given spike train that can also be used to estimate the change points in the firing rate. Assuming a Poisson process with piecewise constant firing rate, we propose a Step-Filter-Test (SFT) which can work simultaneously in different time scales, accounting for the high variety of firing patterns in experimental spike trains. Formally, we compare the numbers N1=N1(t,h) and N2=N2(t,h) of spikes in the time intervals (t-h,t] and (h,t+h]. By varying t within a fine time lattice and simultaneously varying the interval length h, we obtain a multivariate statistic D(h,t):=(N1-N2)/V(N1+N2), for which we prove asymptotic multivariate normality under homogeneity. From this a practical, graphical device to spot changes of the firing rate is constructed. Our graphical representation of D(h,t) (Figure 1A) visualizes the changes in the firing rate. For the statistical test, a threshold K is chosen such that under homogeneity, |D(h,t)|<K holds for all investigated h and t with probability 0.95. This threshold can indicate potential change points in order to estimate the inhomogeneous rate profile (Figure 1B). The SFT is applied to a sample data set of spontaneous single unit activity recorded from the substantia nigra of anesthetized mice. In this data set, multiple rate changes are identified which agree closely with visual inspection. In contrast to approaches choosing one fixed kernel width [4], our method has advantages in the flexibility of h

Onset of negative interspike interval correlations in adapting neurons

Negative serial correlations in single spike trains are an effective method to reduce the variability of spike counts. One of the factors contributing to the development of negative correlations between successive interspike intervals is the presence of adaptation currents. In this work, based on a hidden Markov model and a proper statistical description of conditional responses, we obtain analytically these correlations in an adequate dynamical neuron model resembling adaptation. We derive the serial correlation coefficients for arbitrary lags, under a small adaptation scenario. In this case, the behavior of correlations is universal and depends on the first-order statistical description of an exponentially driven time-inhomogeneous stochastic process.Comment: 12 pages (10 pages in the journal version), 6 figures, published in Phys. Rev. E; http://link.aps.org/doi/10.1103/PhysRevE.84.04190

The cord blood insulin and mitochondrial DNA content related methylome

Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone modification, CYP-metabolism, and aging, indicating etiological origins in epigenetic programming. Variation in metabolic hormones at birth, reflected by molecular changes, might via these alterations predispose children to metabolic diseases later in life. The results of this study may provide important markers for following targeted studies

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Aluminum or low pH - which is the bigger enemy of barley? Transcriptome analysis of barley root meristem under Al and low pH stress

Aluminum (Al) toxicity is considered to be the most harmful abiotic stress in acidic soils that today comprise more than 50% of the world’s arable lands. Barley belongs to a group of crops that are most sensitive to Al in low pH soils. We present the RNAseq analysis of root meristems of barley seedlings grown in hydroponics at optimal pH (6.0), low pH (4.0), and low pH with Al (10 mM of bioavailable Al3C ions). Two independent experiments were conducted: with short-term (24 h) and long-term (7 days) Al treatment. In the short-term experiment, more genes were differentially expressed (DEGs) between root meristems grown at pH = 6.0 and pH = 4.0, than between those grown at pH = 4.0 with and without Al treatment. The genes upregulated by low pH were associated mainly with response to oxidative stress, cell wall organization, and iron ion binding. Among genes upregulated by Al, overrepresented were those related to response to stress condition and calcium ion binding. In the long-term experiment, the number of DEGs between hydroponics at pH = 4.0 and 6.0 were lower than in the short-term experiment, which suggests that plants partially adapted to the low pH. Interestingly, 7 days Al treatment caused massive changes in the transcriptome profile. Over 4,000 genes were upregulated and almost 2,000 genes were downregulated by long-term Al stress. These DEGs were related to stress response, cell wall development and metal ion transport. Based on our results we can assume that both, Al3C ions and low pH are harmful to barley plants. Additionally, we phenotyped the root system of barley seedlings grown in the same hydroponic conditions for 7 days at pH = 6.0, pH = 4.0, and pH = 4.0 with Al. The results correspond to transcriptomic data and show that low pH itself is a stress factor that causes a significant reduction of root growth and the addition of aluminum further increases this reduction. It should be noted that in acidic arable lands, plants are exposed simultaneously to both of these stresses. The presented transcriptome analysis may help to find potential targets for breeding barley plants that are more tolerant to such conditions

Traffic Air Pollution and Oxidized LDL

BACKGROUND: Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized that individual exposure to particulate matter (PM) derived from fossil fuel would correlate with plasma concentrations of oxidized low-density lipoprotein (LDL), taken as a marker of atherosclerosis. We tested this hypothesis in patients with diabetes, who are at high risk for atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study of non-smoking adult outpatients with diabetes we assessed individual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputum induction and by determining the distance from the patient's residence to a major road, through geocoding. These exposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogen activator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Each doubling in the distance of residence from major roads was associated with a 0.027 µm(2) decrease (95% confidence interval (CI): -0.048 to -0.0051) in the carbon load of airway macrophages. Independently from other covariates, we found that each increase of 0.25 µm(2) [interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3 to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of -2.9 U/L (95% CI: -5.2 to -0.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residence to major roads, were associated with plasma von Willebrand factor or PAI-1. CONCLUSIONS: The observed positive association, in a susceptible group of the general population, between plasma oxidized LDL levels and either the carbon load of airway macrophages or the proximity of the subject's residence to busy roads suggests a proatherogenic effect of traffic air pollution