Trace element fractionation between PM10 and PM2.5 in coal mine dust: Implications for occupational respiratory health

This is the final version. Available on open access from Elsevier via the DOI in this recordInvestigations into the respiratory health impacts of coal mine particulate matter (PM) face the challenge of understanding its chemical complexity. This includes highly variable concentrations of trace metals and metalloids such as Fe, Ti, Mn, Zn, Ni, V, Cr, Cu, Pb, Cd, Sb, As and Sn, which may be capable of inducing cell damage. Analysis of PM10 and PM2.5 samples size-separated from deposited coal mine dusts collected on PVC flat surfaces at a height of 1.5-2 m inside the second level in the Velenje lignite mine, Slovenia, demonstrates that some of these metallic elements (in this case Cu, Sb, Sn, Pb, Zn, As, Ni) can be concentrated in PM2.5, the most deeply inhalable and therefore potentially most bioreactive size fraction. These elements are likely to be mainly present in silicates, oxides, and perhaps antimonides and arsenides, rather than in the calcareous, carbonaceous or sulphide components which show no obvious affinity for PM2.5. Whereas in the Velenje lignites concentrations of these metallic elements are low and so do not present any obvious extra health risk to the miners, this is unlikely to be the case in mines where unusually metal-enriched coals are being excavated. We therefore recommend that levels of potentially toxic elements in PM2.5 should be assessed where metal- and metalloid-rich coals are being mined worldwide, especially given uncertainties relating to the efficiency of current dust suppression and respiratory protective equipment for such fine particle sizes.European Commission Research Fund for Coal and Stee

Ultrasonic inspection of flooded mineshafts for stability monitoring

This is the author accepted manuscript.The final version is available from Maney via the DOI in this record.Inspecting abandoned mine shafts is critical in ensuring their safety through early identification of signs of deterioration. Since the common inspection methods of CCTV and LiDAR are not very effective underwater, two modules have been designed for inspecting the linings of flooded, abandoned mine shafts. Using sonar technology, they allow the early stages of degradation to the lining to be detected which – since this could be indicative of imminent collapse – provides protection against the consequential risk to property and human life. Detailed measurements of several shafts’ cross-sections have been recorded using profiling and imaging sonar technology. Although imaging sonar provides very different results in the confined and reverberant environment of a mine shaft, compared to its more common environment of a seabed, it was shown that when combined with the profiling sonar, it allows shafts to be surveyed in a shorter period of time and improves the reliability of the profiling function.European Commissio

Self-reduction of the native TiO2(110) surface during cooling after thermal annealing - in-operando investigations

We investigate the thermal reduction of TiO2 in ultra-high vacuum. Contrary to what is usually assumed, we observe that the maximal surface reduction occurs not during the heating, but during the cooling of the sample back to room temperature. We describe the self-reduction, which occurs as a result of differences in the energies of defect formation in the bulk and surface regions. The findings presented are based on X-ray photoelectron spectroscopy carried out in-operando during the heating and cooling steps. The presented conclusions, concerning the course of redox processes, are especially important when considering oxides for resistive switching and neuromorphic applications and also when describing the mechanisms related to the basics of operation of solid oxide fuel cells

Chemistry and particle size distribution of respirable coal dust in underground mines in Central Eastern Europe

This is the final version. Available on open access from Springer via the DOI in this recordDespite international efforts to limit worker exposure to coal dust, it continues to impact the health of thousands of miners across Europe. Airborne coal dust has been studied to improve risk models and its control to protect workers. Particle size distribution analyses shows that using spraying systems to suppress airborne dusts can reduce particulate matter concentrations and that coals with higher ash yields produce finer dust. There are marked chemical differences between parent coals and relatively coarse deposited dusts (up to 500 µm, DD500). Enrichments in Ca, K, Ba, Se, Pb, Cr, Mo, Ni and especially As, Sn, Cu, Zn and Sb in the finest respirable dust fractions could originate from: (i) mechanical machinery wear; (ii) variations in coal mineralogy; (iii) coal fly ash used in shotcrete, and carbonates used to reduce the risk of explosions. Unusual enrichments in Ca in mine dusts are attributed to the use of such concrete, and elevated K to raised levels of phyllosilicate mineral matter. Sulphur concentrations are higher in the parent coal than in the DD500, probably due to relatively lower levels of organic matter. Mass concentrations of all elements observed in this study remained below occupational exposure limits.European Commission Research Fund for Coal and SteelGeneralitat de Cataluny

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Histone deacetylases (HDACs) regulate the acetylation of histones in the control of gene expression. Many non-histone proteins are also targeted for acetylation, including TGF-ß signalling pathway components such as Smad2, Smad3 and Smad7. Our studies in mouse C3H10T1/2 fibroblasts suggested that a number of TGF-ß-induced genes that regulate matrix turnover are selectively regulated by HDACs. Blockade of HDAC activity with trichostatin A (TSA) abrogated the induction of a disintegrin and metalloproteinase 12 (Adam12) and tissue inhibitor of metalloproteinases-1 (Timp-1) genes by TGF-ß, whereas plasminogen activator inhibitor-1 (Pai-1) expression was unaffected. Analysis of the activation of cell signalling pathways demonstrated that TGF-ß induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-ß induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation without affecting Smad signalling. Analysis of TGF-ß-induced Adam12 and Timp-1 expression and ERK/PI3K signalling in the presence of semi-selective HDAC inhibitors valproic acid, MS-275 and apicidin implicated a role for class I HDACs. Furthermore, depletion of HDAC3 by RNA interference significantly down-regulated TGF-ß-induced Adam12 and Timp-1 expression without modulating Pai-1 expression. Correlating with the effect of HDAC inhibitors, depletion of HDAC3 also blocked the activation of ERK and PI3K by TGF-ß. Collectively, these data confirm that HDACs, and in particular HDAC3, are required for activation of the ERK and PI3K signalling pathways by TGF-ß and for the subsequent gene induction dependent on these signalling pathways

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

The First Detections of the Extragalactic Background Light at 3000, 5500, and 8000A (II): Measurement of Foreground Zodiacal Light

We present a measurement of the absolute surface brightness of the zodiacal light (3900-5100A) toward a fixed extragalactic target at high ecliptic latitude based on moderate resolution (~1.3A per pixel) spectrophotometry obtained with the du Pont 2.5m telescope at Las Campanas Observatory in Chile. This measurement and contemporaneous Hubble Space Telescope data from WFPC2 and FOS comprise a coordinated program to measure the mean flux of the diffuse extragalactic background light (EBL). The zodiacal light at optical wavelengths results from scattering by interplanetary dust, so that the zodiacal light flux toward any extragalactic target varies seasonally with the position of the Earth. This measurement of zodiacal light is therefore relevant to the specific observations (date and target field) under discussion. To obtain this result, we have developed a technique that uses the strength of the zodiacal Fraunhofer lines to identify the absolute flux of the zodiacal light in the multiple-component night sky spectrum. Statistical uncertainties in the result are 0.6% (1 sigma). However, the dominant source of uncertainty is systematic errors, which we estimate to be 1.1% (1 sigma). We discuss the contributions included in this estimate explicitly. The systematic errors in this result contribute 25% in quadrature to the final error in our coordinated EBL measurement, which is presented in the first paper of this series.Comment: Accepted for publication in ApJ, 22 pages using emulateapj.sty, version with higher resolution figures available at http://www.astro.lsa.umich.edu/~rab/publications.html or at http://nedwww.ipac.caltech.edu/level5/Sep01/Bernstein2/frames.htm

A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains

SummaryAlternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide “microexons” display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism