•Ultrafine particle sources were identified and quantified in four European cities.•Common sources were Photonucleation, different Traffic sources, and Secondary.•Maximum contribution of traffic ...sources ranged 71–94% of total particle number.•Airport emissions contributed to nucleation particles in urban background areas.
Ultrafine particles (UFP) are suspected of having significant impacts on health. However, there have only been a limited number of studies on sources of UFP compared to larger particles. In this work, we identified and quantified the sources and processes contributing to particle number size distributions (PNSD) using Positive Matrix Factorization (PMF) at six monitoring stations (four urban background and two street canyon) from four European cities: Barcelona, Helsinki, London, and Zurich. These cities are characterised by different meteorological conditions and emissions. The common sources across all stations were Photonucleation, traffic emissions (3 sources, from fresh to aged emissions: Traffic nucleation, Fresh traffic – mode diameter between 13 and 37 nm, and Urban – mode diameter between 44 and 81 nm, mainly traffic but influenced by other sources in some cities), and Secondary particles. The Photonucleation factor was only directly identified by PMF for Barcelona, while an additional split of the Nucleation factor (into Photonucleation and Traffic nucleation) by using NOx concentrations as a proxy for traffic emissions was performed for all other stations. The sum of all traffic sources resulted in a maximum relative contributions ranging from 71 to 94% (annual average) thereby being the main contributor at all stations. In London and Zurich, the relative contribution of the sources did not vary significantly between seasons. In contrast, the high levels of solar radiation in Barcelona led to an important contribution of Photonucleation particles (ranging from 14% during the winter period to 35% during summer). Biogenic emissions were a source identified only in Helsinki (both in the urban background and street canyon stations), that contributed importantly during summer (23% in urban background). Airport emissions contributed to Nucleation particles at urban background sites, as the highest concentrations of this source took place when the wind was blowing from the airport direction in all cities.
Treatment with the α-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a ...number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites.
Microbial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely uncultured Bacteroidales family Muribaculaceae and were the same taxonomic unit at two of the three sites. Propionate concentrations in feces were consistently elevated in treated mice, while the concentrations of acetate and butyrate reflected a dependence on study site. Across all samples, Muribaculaceae abundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose.
We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the responses illustrate the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, testing causal roles of SCFAs in the observed effects of acarbose.
Size-fractionated samples of airborne particulate matter have been collected in a number of campaigns at Marylebone Road, London and simultaneously at background sites either in Regents Park or at ...North Kensington. Analysis of these samples has enabled size distributions of total mass and of a number of elements to be determined, and roadside increments attributable to nonexhaust emissions arising from traffic activity have been calculated. Taking a novel approach, the combined use of size distribution information and tracer elements has allowed the separate estimation of the contributions of brake dust, tire dust, and resuspension to particle mass in the range 0.9–11.5 μm aerodynamic diameter and mean contributions (±s.e.) at the Marylebone Road sampling site are estimated as resuspended dust 38.1 ± 9.7%, brake dust 55.3 ± 7.0%, and tire dust 10.7 ± 2.3%, (accounting for a total of 104.1% of coarse particle mass in the traffic increment above background).
Ground-level ozone (O3) levels are usually lower in urban centers than nearby rural sites. To compare trends in O3 levels during the period 1990–2010, we obtained monitoring data from paired urban ...and rural sites from the European Environment Agency and the US Environmental Protection Agency. Ozone peaks decreased at both station types, with no significant differences between urban and rural stations. Ozone annual averages increased at both urban and rural sites, with a faster rate of increase for urban centers. The overall trend was for convergence between urban and rural O3 data. Ozone levels exceeded the criteria established for the protection of human and vegetation health at both urban and rural sites.
•We compared trends over 1990–2010 at paired urban and rural sites from USA and Europe.•Peaks decreased at both station types, with no differences between types.•Annual averages increased at both site types, with a faster rate at urban centers.•The overall trend was for convergence between urban and rural data.•Criteria for protection of people and vegetation were exceeded at both site types.
Ozone annual averages in European and USA cities are increasing more than at rural sites, while peaks are decreasing.
Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength ...between multiple neural populations relates to behaviour. For example, studies have used 'functional connectivity fingerprints' to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits.
Temporal fluctuations in functional Magnetic Resonance Imaging (fMRI) have been profitably used to study brain activity and connectivity for over two decades. Unfortunately, fMRI data also contain ...structured temporal “noise” from a variety of sources, including subject motion, subject physiology, and the MRI equipment. Recently, methods have been developed to automatically and selectively remove spatially specific structured noise from fMRI data using spatial Independent Components Analysis (ICA) and machine learning classifiers. Spatial ICA is particularly effective at removing spatially specific structured noise from high temporal and spatial resolution fMRI data of the type acquired by the Human Connectome Project and similar studies. However, spatial ICA is mathematically, by design, unable to separate spatially widespread “global” structured noise from fMRI data (e.g., blood flow modulations from subject respiration). No methods currently exist to selectively and completely remove global structured noise while retaining the global signal from neural activity. This has left the field in a quandary—to do or not to do global signal regression—given that both choices have substantial downsides. Here we show that temporal ICA can selectively segregate and remove global structured noise while retaining global neural signal in both task-based and resting state fMRI data. We compare the results before and after temporal ICA cleanup to those from global signal regression and show that temporal ICA cleanup removes the global positive biases caused by global physiological noise without inducing the network-specific negative biases of global signal regression. We believe that temporal ICA cleanup provides a “best of both worlds” solution to the global signal and global noise dilemma and that temporal ICA itself unlocks interesting neurobiological insights from fMRI data.
•Temporal ICA separates global noise and global signal allowing each to be measured.•Temporal ICA enables new neurobiological insights into functional networks.•Temporal ICA enables generation of unbiased functional connectivity.•Temporal ICA solves the GSR/no GSR cleanup dilemma.
Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which ...mutations are acquired.
We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells.
The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as "TET2-first patients"), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first ("JAK2-first patients") had a greater likelihood of presenting with polycythemia vera than with essential thrombocythemia, an increased risk of thrombosis, and an increased sensitivity of JAK2-mutant progenitors to ruxolitinib in vitro. Mutation order influenced the proliferative response to JAK2 V617F and the capacity of double-mutant hematopoietic cells and progenitor cells to generate colony-forming cells. Moreover, the hematopoietic stem-and-progenitor-cell compartment was dominated by TET2 single-mutant cells in TET2-first patients but by JAK2-TET2 double-mutant cells in JAK2-first patients. Prior mutation of TET2 altered the transcriptional consequences of JAK2 V617F in a cell-intrinsic manner and prevented JAK2 V617F from up-regulating genes associated with proliferation.
The order in which JAK2 and TET2 mutations were acquired influenced clinical features, the response to targeted therapy, the biology of stem and progenitor cells, and clonal evolution in patients with myeloproliferative neoplasms. (Funded by Leukemia and Lymphoma Research and others.).
Particle number concentration data have been collected on a very busy road in central London (Marylebone Road). Continuous size distributions from 15 nm to 10 μm diameter, collected over 21 days, ...were analyzed using positive matrix factorization which identified 10 factors, five of which were observed to make major contributions (greater than 8%) to either the total number or volume of particulate matter. The sources associated with each factor were identified from the size distribution, directional association, diurnal variation and their relationship to meteorological pollution and traffic volume variables. The factors related to the emissions on Marylebone Road accounted for 40.5% of particle volume and 71.9% of particle number. These comprised nucleation mode exhaust particles (3.6% of total volume and 27.4% of total number), solid mode exhaust particles (18.8% of total volume and 38.0% of total number), brake dust (13.7% of total volume and 1.7% of total number and resuspension (4.4% of total volume and 4.8% of total number). Another six factors were associated with the urban background accounting for 59.5% of total volume and 28.2% of total particle number count. The method is extremely successful at separating the components of on-road emissions including brake wear and resuspension.
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