Scaled Down Tunnel Testing for Comparison of Surface Support Performance

A number of scaled down tunnels were prepared and tested to understand stress induced failures around underground excavations and surface support performance following violent failure. The experiment results corresponded well with full scale size tunnels. The failure mechanisms were examined and failure induced stress was evaluated as a function of the intact rock strength. Different surface support elements were compared and various surface support schemes were evaluated as an integrated system

Identification, origin and characteristics of bio-bead microplastics from beaches in western Europe.

Primary microplastics have been collected from 17 beaches along the Atlantic, English Channel and southern North Sea coasts of western Europe. Based on visual characteristics, these plastics were differentiated as either relatively smooth, lentil- or disc-shaped pre-production pellets (or nurdles), which were usually a few mm in diameter and were mainly white to off-white, or rougher and more irregular pellets that were slightly larger and usually black. The latter appeared to be bio-beads, or plastics that are specifically manufactured for use as biomedia in certain sewage water treatment (SWT) plants and, possibly, in other industrial wastewater treatment applications. Identification of bio-beads was confirmed following the acquisition of identical samples from a SWT plant in southwest England and a French supplier of bio-beads. Infrared and x-ray fluorescence analysis revealed that bio-beads have, at least historically, been constructed of plasticised polyethylene and, unlike pre-production pellets, contained variable quantities of potentially toxic elements: Br, Cd, Cr, Hg, Pb and Sb; with a distinctive Br to Sb ratio indicative of brominated flame retardants and antimony-based retardant synergists. It is asserted that bio-beads have been manufactured from a heterogeneous mix of recycled polyethylene and end-of-life electrical and electronic plastic, with concentrations of Br, Cd, Cr or Pb in about 50 bio-beads (out of 497 analysed) non-compliant or potentially non-compliant with respect to current regulations on hazardous plastic waste. Concentrations of Br, Cd, Cr, Pb and Sb extracted from individual bio-beads by a simulated avian digestive fluid were variable, with maximum values of about 14, 0.8, 1.3, 20 and 1.4 μg g-1, respectively. The presence and, in many cases, dominance of bio-beads among beached primary microplastics is discussed with regard to the classification of microplastics and potential impacts on wildlife

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates.

Genetic mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). Although mitochondrial dysfunction and stress granule have been crucially implicated in FUS proteinopathy, the molecular basis remains unclear. Here, we show that DHX30, a component of mitochondrial RNA granules required for mitochondrial ribosome assembly, interacts with FUS, and plays a crucial role in ALS-FUS. WT FUS did not affect mitochondrial localization of DHX30, but the mutant FUS lowered the signal of mitochondrial DHX30 and promoted the colocalization of cytosolic FUS aggregates and stress granule markers. The immunohistochemistry of the spinal cord from an ALS-FUS patient also confirmed the colocalization, and the immunoelectron microscope demonstrated decreased mitochondrial DHX30 signal in the spinal motor neurons. Subcellular fractionation by the detergent-solubility and density-gradient ultracentrifugation revealed that mutant FUS also promoted cytosolic mislocalization of DHX30 and aggregate formation. Interestingly, the mutant FUS disrupted the DHX30 conformation with aberrant disulfide formation, leading to impaired mitochondrial translation. Moreover, blue-native gel electrophoresis revealed an OXPHOS assembly defect caused by the FUS mutant, which was similar to that caused by DHX30 knockdown. Collectively, our study proposes DHX30 as a pivotal molecule in which disulfide-mediated conformational change mediates mitochondrial dysfunction and cytosolic aggregate formation in ALS-FUS

DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds

A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)-regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals